Field of technology
[0001] The present invention relates to a disposable cartridge that can be used in or on
digital microfluidics systems for manipulating samples in liquid droplets. The digital
microfluidics systems comprise an electrode array supported by a substrate, and a
central control unit for controlling the selection of individual electrodes of this
electrode array and for providing them with individual voltage pulses for manipulating
liquid droplets by electrowetting. The invention also relates to a digital microfluidics
system for facilitating droplet actuated molecular techniques and to an alternative
method for manipulating samples in liquid droplets digital in a microfluidics system
or device.
Related prior art
[0002] Automated liquid handling systems are generally well known in the art. An example
is the Freedom EVO
® robotic workstation from the present applicant (Tecan Schweiz AG, Seestrasse 103,
CH-8708 Männedorf, Switzerland). This device enables automated liquid handling in
a stand-alone instrument or in automated connection with an analytical system. These
automated systems typically require larger volumes of liquids (microliter to milliliter)
to process. They are also larger systems that are not designed to be portable.
[0003] Many approaches to deal with the automated processing of biological samples originate
from the field of microfluidics. This technical field generally relates to the control
and manipulation of liquids in a small volume, usually in the micro- or nanoscale
format. Liquid movement in a channel system is known
per se as, e.g. being controlled by micro pumps in stationary devices or centripetal forces
in rotating labware. In digital microfluidics, a defined voltage is applied to electrodes
of an electrode array, so that individual droplets are addressed (electrowetting).
[0004] For a general overview of the electrowetting method, please see
Washizu, IEEE Transactions on Industry Applications, Volume 34, No. 4, 1998, and
Pollack et al., Lab chip, 2002, Volume 2, 96-101. Briefly, electrowetting refers to a method to move liquid droplets using arrays
of microelectrodes, preferably covered by a hydrophobic layer. By applying a defined
voltage to electrodes of the electrode array, a change of the surface tension of the
liquid droplet, which is present on the addressed electrodes, is induced. This results
in a remarkable change of the contact angle of the droplet on the addressed electrode,
hence in a movement of the droplet. For such electrowetting procedures, two principle
ways to arrange the electrodes are known: using one single surface with an electrode
array for inducing the movement of droplets or adding a second surface that is opposite
a similar electrode array and that provides at lest one ground electrode. A major
advantage of the electrowetting technology is that only a small volume of liquid is
required, e.g. a single droplet. Thus, liquid processing can be carried out within
considerably shorter time. Furthermore the control of the liquid movement can be completely
under electronic control resulting in automated processing of samples.
[0005] A device for liquid droplet manipulation by electrowetting using one single surface
with an electrode array (a monoplanar arrangement of electrodes) is known from the
US patent No. 5,486,337. All electrodes are placed on a surface of a carrier substrate, lowered into the
substrate, or covered by a non-wettable surface. A voltage source is connected to
the electrodes. The droplet is moved by applying a voltage to subsequent electrodes,
thus guiding the movement of the liquid droplet above the electrodes according to
the sequence of voltage application to the electrodes.
[0006] An electrowetting device for microscale control of liquid droplet movements, using
an electrode array with an opposing surface with at least one ground electrode is
known from
US 6,565,727 (a biplanar arrangement of electrodes). Each surface of this device may comprise
a plurality of electrodes. The drive electrodes of the electrode array are preferably
arranged in an interdigitated relationship with each other by projections located
at the edges of each single electrode. The two opposing arrays form a gap. The surfaces
of the electrode arrays directed towards the gap are preferably covered by an electrically
insulating, hydrophobic layer. The liquid droplet is positioned in the gap and moved
within a non-polar filler fluid by consecutively applying a plurality of electric
fields to a plurality of electrodes positioned on the opposite sites of the gap.
[0007] Containers with a polymer film for manipulating samples in liquid droplets thereon
are known from
WO 2010/069977 A1: A biological sample processing system comprises a container for large volume processing
and a flat polymer film with a lower surface and a hydrophobic upper surface. The
flat polymer film is kept at a distance to a base side of the container by protrusions.
This distance defines at least one gap when the container is positioned on the film.
A liquid droplet manipulation instrument comprises at least one electrode array for
inducing liquid droplet movements. A substrate supporting the at least one electrode
array is also disclosed as well as a control unit for the liquid droplet manipulation
instrument. The container and the film are reversibly attached to the liquid droplet
manipulation instrument. The system thus enables displacement of at least one liquid
droplet from the at least one well through the channel of the container onto the hydrophobic
upper surface of the flat polymer film and above the at least one electrode array.
The liquid droplet man ipulation instrument is accomplished to control a guided movement
of said liquid droplet on the hydrophobic upper surface of the flat polymer film by
electrowetting a nd to process there the biological sample.
[0008] The use of such an electrowetting device for manipulating liquid droplets in the
context of the processing of biological samples is also known from the international
patent application published as
WO 2011/002957 A2. There, it is disclosed that a droplet actuator typically includes a bottom substrate
with the control electrodes (electrowetting electrodes) insulated by a dielectric,
a conductive top substrate, and a hydrophobic coating on the bottom and top substrates.
Also disclosed are droplet actuator devices for replacing one or more components of
a droplet actuator, i.e. disposable components that may be readily replaced (such
as movable films, reversibly attachable top and bottom substrates, and self-contained
replaceable cartridges).
[0009] From the international application published as
WO 2011/002957 A2, droplet actuators with a fixed bottom substrate (e.g. of a PCB), with electrowetting
electrodes, and with a removable or replaceable top substrate are known. A self-containing
cartridge may e.g. include buffers, reagents, and filler fluid. Pouches in the cartridge
may be used as fluid reservoirs and may be punctured to release fluid (e.g. a reagent
or oil) into a cartridge gap. The cartridge may include a ground electrode, which
may be replaced by a hydrophobic layer, and an opening for loading samples into the
gap of the cartridge. Interface material (e.g. a liquid, glue or grease) may provide
adhesion of the cartridge to the electrode array.
[0010] Disposable cartridges for microfluidic processing and analysis in an automated system
for carrying out molecular diagnostic analysis are disclosed in
WO 2006/125767 A1 (see
US 2009/ 0298059 A1 for an English translation). The cartridge is configured as a flat chamber device
(with about the size of a check card) and can be inserted into the system. A sample
can be pipetted into the cartridge through a port.
[0011] Droplet actuator structures are known from the international patent application
WO 2008/106678. This document particularly refers to various wiring configurations for electrode
arrays of droplet actuators, and additionally discloses a two-layered embodiment of
such a droplet actuator which comprises a first substrate with a reference electrode
array separated by a gap from a second substrate comprising control electrodes. The
two substrates are arranged in parallel, thereby forming the gap. The height of the
gap may be established by spacer. A hydrophobic coating is in each case disposed on
the surfaces which face the gap. The first and second substrate may take the form
of a cartridge, eventually comprising the electrode array.
Objects and summary of the, present invention
[0012] It is an object of the present invention to suggest an alternative disposable cartridge
for use in or on digital microfluidics systems or digital microfluidics devices which
are configured to accommodate one or more disposable cartridges for manipulating samples
in liquid droplets.
[0013] This object is achieved in that a first alternative disposable cartridge is provided.
The first alternative disposable cartridge of the present invention comprises:
- (a) a body with at least one compartment configured to hold therein processing liquids,
reagents or samples, at least one of said compartments comprising a through hole for
delivering at least some of its content;
- (b) a bottom layer with a first hydrophobic surface that is impermeable to liquids
and that is configured as a working film for manipulating samples in liquid droplets
thereon utilizing an electrode array of a digital microfluidics system when the bottom
layer of the disposable cartridge is placed over said electrode array;
- (c) a top layer with a second hydrophobic surface that is attached to a lower surface
of the body of the disposable cartridge; and
- (d) a gap that is located between the first hydrophobic surface of the bottom layer
and the second hydrophobic surface of the top layer.
[0014] Optionally, the second hydrophobic surface provided by the top layer may be or may
be not impermeable to liquids, it is preferred however that the second hydrophobic
surface or the top layer respectively is at least permeable to ions.
[0015] The first alternative disposable cartridge of the present invention is characterized
in that the bottom layer is configured as a flexible film that is sealingly attached
to the top layer along a circumference of the flexible bottom layer, the disposable
cartridge thus being devoid of a spacer that is located between the flexible bottom
layer and the top layer for defining a particular distance between said first hydrophobic
surface a nd said second hydrophobic surface. The first alternative disposable cartridge
of the present invention is further characterized in that the top layer is configured
to provide a seal between a lower end of at least one compartment and the gap, the
top layer comprising loading sites for transferring processing liquids, reagents or
samples into the gap.
[0016] This object is achieved in that a second alternative disposable cartridge is provided.
The second alternative disposable cartridge of the present invention comprises:
- (a) a body with a lower surface, an upper surface, and at least one through hole;
- (b) a bottom layer with a first hydrophobic surface that is impermeable to liquids
and that is configured as a working film for manipulating samples in liquid droplets
thereon utilizing an electrode array of a digital microfluidics system when the bottom
layer of the disposable cartridge is placed over said electrode array;
- (c) an electrically conductive material attached to the lower surface of the body,
the electrically conductive material being configured to provide the lower surface
of the body with a second hydrophobic surface; and
- (d) a gap that is located between the first hydrophobic surface of the bottom layer
and the second hydrophobic surface of the electrically conductive material.
[0017] Optionally, the electrically conductive material that provides the body with the
second hydrophobic surface may be or may be not impermeable to liquids, it is preferred
however that the electrically conductive material that provides the second hydrophobic
surface is at least permeable to ions.
[0018] The second alternative disposable cartridge of the present invention is characterized
in that the bottom layer is configured as a flexible film that is sealingly attached
to the electrically conductive material of the disposable cartridge along a circumference
of the flexible bottom layer, the disposable cartridge thus being devoid of a spacer
that is located between the flexible bottom layer and the electrically conductive
material for defining a particular distance between said first hydrophobic surface
and said second hydrophobic surface. The second alternative disposable cartridge of
the present invention is further characterized in that the at least one through hole
of the body is configured as a loading site for transferring processing liquids, reagents
or samples into the gap.
[0019] It is a further object of the present invention to suggest a microfluidics system
or device into or onto which one or more such disposable cartridges for manipulating
samples in liquid droplets therein can be placed. This object is achieved in that
a first and second alternative digital microfluidics system is provided. The first
and second digital microfluidics system for manipulating samples in liquid droplets
within a gap between a first hydrophobic surface of a bottom layer and a second hydrophobic
surface of at least one disposable cartridge of the present invention comprises:
- (a) a base unit with at least one cartridge accommodation site that is configured
for taking up one disposable cartridge;
- (b) an electrode array located at said at least one cartridge accommodation site of
the base unit, the electrode array being supported by a bottom substrate and substantially
extending in a first plane and comprising a number of individual electrodes;
- (c) a central control unit for controlling the selection of the individual electrodes
of said electrode array and for providing these electrodes with individual voltage
pulses for manipulating liquid droplets within the gap of said cartridge by electrowetting;
- (d) a number of suction holes that penetrate the electrode array and/or the bottom
substrate and that are located at the at least one cartridge accommodation site of
the base unit;
- (e) a vacuum source for establishing an underpressure in an evacuation space; and
- (f) a number of vacuum lines that link the suction holes to the vacuum source.
[0020] The first digital microfluidics system of the present invention is further characterized
in that a gasket, when a disposable cartridge is located at the at least one cartridge
accommodation site, seals in said cartridge accommodation site the evacuation space,
which is defined by a flexible bottom layer of a disposable cartridge, an uppermost
surface of the cartridge accommodation site, and the gasket. The digital microfluidics
system of the present invention is further characterized in that the underpressure
in the evacuation space causes the flexible bottom layer of the disposable cartridge
that is placed at the cartridge accommodation site to be attracted and spread over
the uppermost surface of the cartridge accommodation site of the digital microfluidics
system without the use of a spacer that is located in the gap between the first hydrophobic
surface of the flexible bottom layer and the second hydrophobic surface of the at
least one disposable cartridge.
[0021] The second alternative digital microfluidics system of the present invention is characterized
in that the digital microfluidics system comprises a spacer for defining a particular
distance between said first hydrophobic surface and said second hydrophobic surface
and a frame for centering a disposable cartridge at said cartridge accommodation site,
for holding down the disposable cartridge to the spacer, and for sealing an evacuation
space by first and second seals of the frame. The microfluidics system further comprises
an evacuation space, which is defined by a flexible bottom layer of a disposable cartridge,
an uppermost surface of the cartridge accommodation site, and the frame with the seals.
The digital microfluidics system of the present invention is further characterized
in that the underpressure in the evacuation space causes the flexible bottom layer
that is placed at the cartridge accommodation site to be attracted to and spread over
the uppermost surface of the cartridge accommodation site of the digital microfluidics
system.
[0022] Preferably, the seals are of two different types, comprising i.e. a different material
and/or cross section. A number of first type seals being of a very compliant material
or being configured as a lip seal. The first type seals preferably are capable to
be largely deformed allowing the seal bearing parts to be firmly pressed against respective
counter parts. Preferred materials for this compliant seal are e.g. O-rings of natural
rubber or of a DuPont Elastomer such as Neoprene
®. A second seal type preferably is of a material that is less compliant and stiff
enough to undergo only a minimal compression and thus combining the task of effectively
sealing the evacuation space and of pressing the disposable cartridge firmly against
the spacer. Preferred materials for this stiff seal are e.g. O-rings of a DuPont Performance
Elastomer such as Viton
®.
[0023] It is yet a further object of the present invention to suggest an alternative method
for manipulating samples in liquid droplets digital in a digital microfluidics system
or device. This further object is achieved in that a first alternative method for
manipulating samples in liquid droplets that adhere to a hydrophobic surface of a
working film is proposed. The first alternative method according to the present invention
comprises the steps of:
- (a) providing a disposable cartridge with a first hydrophobic surface of a bottom
layer, with a second hydrophobic surface of a top layer, and with a gap between the
first and second hydrophobic surfaces, the disposable cartridge further comprising
a body with at least one compartment to therein hold processing liquids, reagents
or samples, said compartment comprising a through hole for delivering at least some
of its content to the gap;
- (b) providing a digital microfluidics system with an electrode array that substantially
extends in a first plane and that comprises a number of individual electrodes supported
by a bottom substrate and connected to a central control unit of the digital microfluidics
system for controlling the selection of individual electrodes of said electrode array
and for providing these electrodes with individual voltage pulses for manipulating
said liquid droplets on said first hydrophobic surface by electrowetting; and
- (c) defining the gap so that the hydrophobic surface of the top layer extends substantially
parallel to and in a distance to said first hydrophobic surface of the bottom layer.
[0024] The first alternative method for manipulating samples in liquid droplets of the present
invention is characterized in that the method further comprises the steps of:
(d) providing the bottom layer as a flexible film that is sealingly attached to the
top layer along a circumference of the flexible bottom layer, the disposable cartridge
thus being devoid of a spacer that is located between the flexible bottom layer and
the top layer for defining a particular distance between said first hydrophobic surface
and said second hydrophobic surface;
(e) placing the disposable cartridge on a cartridge accommodation site of a base unit
of the digital microfluidics system, the top layer being configured to provide a seal
between a lower end of at least one compartment and the gap, and the top layer comprising
loading sites for transferring processing liquids, reagents or samples into the gap;
(f) sealing in the cartridge accommodation site an evacuation space by a gasket located
around a circumference of the cartridge accommodation site, the evacuation space being
defined by the flexible bottom layer, the electrode array, the bottom substrate, and
the gasket; and
(g) creating in the evacuation space an underpressure, which causes the flexible bottom
layer of the disposable cartridge that is placed on the cartridge accommodation site
to be attracted and spread over the electrode array and bottom substrate.
[0025] This further object is achieved in that a second alternative method for manipulating
samples in liquid droplets that adhere to a hydrophobic surface of a working film
is proposed. The second alternative method according to the present invention comprises
the steps of:
- (a) providing a disposable cartridge with a body comprising a lower surface, an upper
surface, at least one through hole, and a bottom layer with a first hydrophobic surface;
an electrically conductive material being attached to the lower surface of the body,
the electrically conductive material at least being permeable to ions and configured
to provide the lower surface of the body with a second hydrophobic surface; a gap
being provided between the first and second hydrophobic surfaces;
- (b) providing a digital microfluidics system with an electrode array that substantially
extends in a first plane and that comprises a number of individual electrodes supported
by a bottom substrate and connected to a central control unit of the digital microfluidics
system for controlling the selection of individual electrodes of said electrode array
and for providing these electrodes with individual voltage pulses for manipulating
said liquid droplets on said first hydrophobic surface by electrowetting; and
- (c) defining the gap so that the first and second hydrophobic surfaces extend substantially
parallel and in a distance to each other; the at least one through hole of the body
being configured as a loading site for transferring processing liquids, reagents or
samples into the gap.
[0026] The second alternative method for manipulating samples in liquid droplets of the
present invention is characterized in that the method further comprises the steps
of:
(d) providing the bottom layer as a flexible film that is sealingly attached to the
electrically conductive material along a circumference of the flexible bottom layer,
the disposable cartridge thus being devoid of a spacer that is located between the
first and second hydrophobic surfaces for defining a particular distance between said
first hydrophobic surface and said second hydrophobic surface;
(e) placing the disposable cartridge on a cartridge accommodation site of a base unit
of the digital microfluidics system;
(f) sealing in the cartridge accommodation site an evacuation space by a gasket located
around a circumference of the cartridge accommodation site, the evacuation space being
defined by the flexible bottom layer, the electrode array, the bottom substrate, and
the gasket; and
(g) creating in the evacuation space an underpressure, which causes the flexible bottom
layer of the disposable cartridge that is placed on the cartridge accommodation site
to be attracted and spread over the electrode array and bottom substrate.
[0027] This further object is achieved in that a third and fourth alternative method for
manipulating samples in liquid droplets that adhere to a hydrophobic surface of a
working film is proposed. The third alternative method according to the present invention
comprises the steps of:
- (a) providing a disposable cartridge with a first hydrophobic surface of a bottom
layer, with a second hydrophobic surface, and with a gap between the first and second
hydrophobic surfaces, the disposable cartridge further comprising a body and/or a
plane rigid cover plate, and at least one through hole for delivering processing liquids,
reagents or samples to the gap;
- (b) providing a digital microfluidics system with at least one electrode array that
substantially extends in a first plane and that comprises a number of individual electrodes
supported by a bottom substrate and connected to a central control unit of the digital
microfluidics system for controlling the selection of individual electrodes of said
electrode array and for providing these electrodes with individual voltage pulses
for manipulating said liquid droplets on said first hydrophobic surface by electrowetting;
and
- (c) defining the gap so that the hydrophobic surface extends substantially parallel
to and in a distance to said first hydrophobic surface of the bottom layer.
[0028] The third alternative method for manipulating samples in liquid droplets of the present
invention is characterized in that the method further comprises the steps of:
(d) providing the bottom layer as a flexible film that is sealingly attached to the
body or the plane rigid cover plate of the disposable cartridge along a circumference
of the flexible bottom layer, the disposable cartridge thus being devoid of a spacer
that is located in the gap for defining a particular distance between said first hydrophobic
surface and said second hydrophobic surface;
(e) placing the disposable cartridge at a cartridge accommodation site of a base unit
of the digital microfluidics system;
(f) sealing in the cartridge accommodation site an evacuation space by a gasket, the
evacuation space being defined by the flexible bottom layer of the disposable cartridge,
the uppermost surface of the cartridge accommodation site and the gasket; and
(g) creating in the evacuation space an underpressure, which causes the flexible bottom
layer of the disposable cartridge that is placed on the cartridge accommodation site
to be attracted and spread over the uppermost surface of the cartridge accommodation
site.
[0029] The fourth alternative method for manipulating samples in liquid droplets of the
present invention is characterized in that the method further comprises the steps
of:
(d) providing the bottom layer as a flexible film that is sealingly attached to the
plane rigid cover plate of the disposable cartridge along a circumference of the flexible
bottom layer, the disposable cartridge thus being devoid of a spacer that is located
in the gap for defining a particular distance between said first hydrophobic surface
and said second hydrophobic surface;
(e) placing the disposable cartridge within a centering frame at a cartridge accommodation
site and on a spacer of a base unit of the digital microfluidics system;
(f) applying pressure on the disposable cartridge in the cartridge accommodation site
and sealing an evacuation space by first and second seals of the frame, the evacuation
space being defined by the flexible bottom layer of the disposable cartridge, the
uppermost surface of the cartridge accommodation site, and the frame with the seals;
and
(g) creating in the evacuation space an underpressure, which causes the flexible bottom
layer of the disposable cartridge that is placed on the cartridge accommodation site
to be attracted and spread over the uppermost surface of the cartridge accommodation
site.
[0030] Additional and inventive features and preferred embodiments and variants of the digital
microfluidics system, the disposable cartridge, and the method for manipulating samples
in liquid droplets derive from the respective dependent claims.
[0031] Advantages of the present invention comprise:
- According to one embodiment, a gasket between the cartridge and the PCB of the digital
microfluidics system together with the geometry of the cartridge, the flexible bottom
layer and an underpressure applied to the underside of this flexible bottom layer
is sufficient to define the gap between the two films that enclose the gap.
- According to another embodiment, a spacer between the cartridge and the PCB of the
digital microfluidics system together with the geometry of the cartridge, the flexible
bottom layer, a frame with seals and an underpressure applied to the underside of
this flexible bottom layer is sufficient to define the gap between the two films that
enclose the gap.
- The disposable cartridge of the present invention does not need a spacer between the
two surfaces that enclose the gap where the electrowetting takes place.
- The gasket can be a part of the disposable cartridge or can be fixed to the surface
of the PCB.
- The spacer preferably is a part of the PCB.
Brief introduction of the drawings
[0032] The self-contained disposable cartridge, the digital microfluidics system, and the
method for manipulating samples according to the present invention are explained with
the help of the attached schematic drawings that show selected and exemplary embodiments
of the present invention without narrowing the scope and gist of this invention. It
is shown in:
- Fig. 1
- an overview over a digital microfluidics system that is equipped with a central control
unit and a base unit, with four cartridge accommodation sites that each comprise an
electrode array, and a movable cover plate;
- Fig. 2
- a section view of one cartridge accommodation site with a disposable cartridge according
to a first embodiment accommodated therein;
- Fig. 3
- a section view of one cartridge accommodation site with a disposable cartridge according
to a second embodiment accommodated therein;
- Fig. 4
- section views of one cartridge accommodation site with a disposable cartridge according
to a third embodiment accommodated therein, wherein:
Fig. 4A shows the cushion-like cartridge as laid into a cartridge accommodation site
with a partly closed cover, and
Fig. 4B shows the cushion-like cartridge as pressed into operation shape inside the
cartridge accommodation site by the entirely closed cover;
- Fig. 5
- a section view of one cartridge accommodation site with a disposable cartridge according
to a fourth embodiment accommodated therein;
- Fig. 6
- a section view of one cartridge accommodation site with a disposable cartridge according
to a fifth embodiment accommodated therein;
- Fig. 7
- an overview over a digital microfluidics system that is equipped with a central control
unit and a base unit, with twelve cartridge accommodation sites that each comprise
an electrode array and a fixed cover plate;
- Fig. 8
- section views of one cartridge accommodation site with a disposable cartridge according
to a sixth embodiment accommodated therein, wherein:
Fig. 8A shows a top-entry cartridge inserted into a substantially vertical cartridge
accommodation site with a substantially vertical electrode array and cover plate,
and
Fig. 8B shows the top-entry cartridge as viewed from the section plane B indicated
in Fig. 8A;
- Fig. 9
- a section view of one disposable cartridge before reaching its accommodation site,
the disposable cartridge being configured according to a seventh embodiment;
- Fig. 10
- a section view of the disposable cartridge of Fig. 9 after reaching its accommodation
site, the disposable cartridge being configured according to a seventh embodiment
and being hold in place by a clamp;
- Fig. 11
- a section view of a disposable cartridge after reaching its accommodation site, the
disposable cartridge being configured according to an eighth embodiment and being
hold in place by a clamp;
- Fig. 12
- a section view of a disposable cartridge after reaching its accommodation site, the
disposable cartridge being configured according to a ninth embodiment and being hold
in place without a clamp;
- Fig. 13
- a section view of one disposable cartridge before reaching its accommodation site,
the disposable cartridge being configured according to a tenth embodiment and to be
hold at the cartridge accommodation site with or without a clamp;
- Fig. 14
- a section view of one disposable cartridge before reaching its accommodation site,
the disposable cartridge being configured according to an eleventh embodiment and
to be hold in place at the cartridge accommodation site with or without a clamp;
- Fig. 15
- a partial section view of one disposable cartridge in its accommodation site, the
disposable cartridge being configured according to a twelfth embodiment, centered
in the cartridge accommodation site by a frame and pressed on a spacer of the PCB
with a screwed plate;
- Fig. 16
- a partial section view of one disposable cartridge in its accommodation site, the
disposable cartridge configured according to the twelfth embodiment being centered
in the cartridge accommodation site and pressed on a spacer by a screwed frame profile;
- Fig. 17
- a partial section view of one disposable cartridge in its accommodation site, the
disposable cartridge being configured according to the twelfth embodiment, centered
in the cartridge accommodation site by a screwed frame and pressed on a spacer of
the PCB with a pressing plate.
Detailed description of the present invention
[0033] The Figure 1 shows an overview over an exemplary digital microfluidics system 1 that
is equipped with a central control unit 14 and a base unit 7, with four cartridge
accommodation sites 8 that each comprise an electrode array 9, and a cover plate 12.
The digital microfluidics system 1 is configured for manipulating samples in liquid
droplets 23 within disposable cartridges 2 that contain a bottom layer 3, a top layer
4, and eventually a spacer 5 that defines a gap 6 between the bottom and top layers
3,4. Accordingly, the samples in liquid droplets 23 are manipulated in the gap 6 of
the disposable cartridge 2.
[0034] A typical digital microfluidics system 1 comprises a base unit 7 with at least one
cartridge accommodation site 8 that is configured for taking up a disposable cartridge
2. The digital microfluidics system 1 can be a stand alone and immobile unit, on which
a number of operators is working with cartridges 2 that they bring along. The digital
microfluidics system 1 thus may comprise a number of cartridge accommodation sites
8 and a number of electrode arrays 9, so that a number of cartridges 2 can be worked
on simultaneously and/or parallel. The number of cartridge accommodation sites 8,
electrode arrays 9, and cartridges 2 may be 1 or any number between e.g. 1 and 100
or even more; this number e.g. being limited by the working capacity of the central
control unit 14.
[0035] It may be preferred to integrate the digital microfluidics system 1 into a liquid
handling workstation or into a Freedom EVO
® robotic workstation, so that a pipetting robot can be utilized to transfer liquid
portions and/or sample containing liquids to and from the cartridges 2.
[0036] Alternatively, the system 1 can be can be configured as a hand held unit which only
comprises and is able to work with a low number, e.g. a single disposable cartridge
2. Every person of skill will understand that intermediate solutions that are situated
in-between the two extremes just mentioned will also operate and work.
[0037] A typical digital microfluidics system 1 also comprises at least one electrode array
9 that substantially extends in a first plane and that comprises a number of individual
electrodes 10. Such an electrode array 9 is located at each one of said cartridge
accommodation sites 8 of the base unit 7. Preferably each electrode array 9 is supported
by a bottom substrate 11, which bottom substrate 11 is fixed to the base unit 7. It
is noted that the expressions "electrode array", "electrode layout", and "printed
circuit board (PCB)" are utilized herein as synonyms.
[0038] A typical digital microfluidics system 1 also comprises at least one cover plate
12 with a top substrate 13. In each case, at least one cover plate 12 is located at
said cartridge accommodation sites 8. The top substrate 13 of the cover plate 12 and
the bottom substrate 11 with the electrode array 9 or PCB define a space or cartridge
accommodation site 8 respectively. In a first variant (see the two cartridge accommodation
sites 8 in the middle of the base unit 7), the cartridge accommodation sites 8 are
configured for receiving a slidingly inserted disposable cartridge 2 that is movable
in a direction substantially parallel with respect to the electrode array 9 of the
respective cartridge accommodating site 8. Such front- or top-loading can be supported
by a drawing-in automatism that, following a partial insertion of a disposable cartridge
2, transports the cartridge 2 to its final destination within the cartridge accommodation
site 8, where the cartridge 2 is precisely seated. Preferably, these cartridge accommodation
sites 8 do not comprise a movable cover plate 12. After carrying out all intended
manipulations to the samples in liquid droplets, the used cartridges 2 can be ejected
by the drawing-in automatism and transported to an analysis station or discarded.
[0039] In a second variant (see the two cartridge accommodation sites 8 on the right and
left of the base unit 7), the cartridge accommodation sites 8 comprise a cover plate
12 that is configured to be movable with respect to the electrode array 9 of the respective
cartridge accommodating site 8. The cover plate 12 preferably is configured to be
movable about one or more hinges 16 and/or in a direction that is substantially normal
to the electrode array 9.
[0040] A typical digital microfluidics system 1 also comprises a central control unit 14
for controlling the selection of the individual electrodes 10 of said at least one
electrode array 9 and for providing these electrodes 10 with individual voltage pulses
for manipulating liquid droplets within said cartridges 2 by electrowetting. As partly
indicated in Fig. 1, every single individual electrode 10 is operatively connected
to the central control unit 14 and therefore can be independently addressed by this
central control unit 14, which also comprises the appropriate sources for creating
and providing the necessary electrical potentials in a way known in the art.
[0041] The at least one cover plate 12 further comprises an electrically conductive material
15 that extends in a second plane and substantially parallel to the electrode array
9 of the cartridge accommodation site 8 the at least one cover plate 12 is assigned
to. This electrically conductive material 15 of the cover plate 12 preferably is configured
to be connected to a source of an electrical ground potential. This conductive material
15 contributes to the electrowetting movements of the liquid droplets manipulated
in the digital microfluidics system 1.
[0042] The applicants surprisingly found that the conductive material 15 also contributes
to the electrowetting movements of the liquid droplets manipulated in the digital
microfluidics system 1, if there is no connection between the conductive material
15 of the cover plate 12 and any source of a certain electrical (e.g. ground) potential.
Thus, the cover plate 12 can be configured to be movable in any arbitrary direction
and no electrical contacts have to be taken in into consideration when selecting a
particularly preferred movement of the cover plate 12. Thus, the cover plate 12 may
be configured to be also movable in a direction substantially parallel to the electrode
array 9 and for carrying out a linear, circular or any arbitrary movement with respect
to the respective electrode array 9 of the base unit 7.
[0043] The Figure 2 shows a section view of one exemplary cartridge accommodation site 8
with a disposable cartridge 2 according to a first embodiment accommodated therein.
The cover plate 12 is mechanically connected with the base unit 7 of the digital microfluidics
system 1 via a hinge 16; thus, the cover plate 12 can swing open and a disposable
cartridge 2 can be placed on the cartridge accommodation site 8 via top-entry loading
(see Fig. 1). The electrically conductive material 15 of the cover plate 12 is configured
as a thin metal plate or metal foil that is attached to the top substrate 13.
[0044] Alternatively, the electrically conductive material 15 of the cover plate 12 is configu
red as a metal layer that is deposited onto the top substrate 13. Such deposition
of the conductive material 15 may be carried out by chemical or physical vapor deposition
techniques as they are known per se.
[0045] The cover plate 12 is configured to apply a force to a disposable cartridge 2 that
is accommodated at the cartridge accommodation site 8 of the base unit 7. This force
urges the disposable cartridge 2 against the electrode array 9 in order to position
the bottom layer 3 of the cartridge as close as possible to the surface of the electrode
array 9. This force also urges the disposable cartridge 2 into the perfect position
on the electrode array 9 with respect to a piercing facility 18 of the cover plate
12. This piercing facility 18 is configured for introducing sample droplets into the
gap 6 of the cartridge 2. The piercing facility 18 is configured as a through hole
19 that leads across the entire cover plate 12 and that enables a piercing pipette
tip 20 to be pushed through and pierce the top layer 4 of the cartridge 2. The piercing
pipette tip 20 may be a part of a handheld pipette (not shown) or of a pipetting robot
(not shown).
[0046] In this case, the electrode array 9 is covered by a dielectric layer 24. The electrode
array 9 is fixed to a bottom substrate 11 and every individual electrode 10 is electrically
and operationally connected with the central control unit 14 (only three connections
of the ten electrodes 10 are drawn here). The digital microfluidics system 1 is configured
for manipulating samples in liquid droplets 23 within disposable cartridges 2 that
contain a gap 6. Accordingly, the samples in liquid droplets 23 are manipulated in
the gap 6 of the disposable cartridge 2.
[0047] The disposable cartridge 2 comprises a bottom layer 3, a top layer 4, and a spacer
5 that defines a gap 6 between the bottom and top layers 3,4 for manipulating samples
in liquid droplets 23 in this gap 6. The bottom layer 3 and the top layer 4 comprise
a hydrophobic surface 17 that is exposed to the gap 6 of the cartridge 2. The bottom
layer 3 and the top layer 4 of the cartridge 2 are entirely hydrophobic films or at
least comprise a hydrophobic surface that is exposed to the gap 6 of the cartridge
2. It is clear from this Fig. 2, that the cartridge 2 does not have a conductive layer.
The spacer 5 of the cartridge 2 here at least partially is configured as a body that
includes compartments 21 for reagents needed in an assay that is applied to the sample
droplets in the gap 6.
[0048] The Figure 3 shows a section view of one exemplary cartridge accommodation site 8
with a disposable cartridge 2 according to a second embodiment accommodated therein.
Different to the previous embodiment, the cover plate 12 is mechanically connected
with the base unit 7 of the digital microfluidics system 1 and immovably fixed therewith.
The electrically conductive material 15 of the cover plate 12 is configured as a thick
metal plate that is attached to the top substrate 13. Here, the cover plate 12 is
not configured to apply a force to the disposable cartridge 2 that is accommodated
at the cartridge accommodation site 8 of the base unit 7; thus, the cover plate 12
stays in place and a disposable cartridge 2 can be placed on the cartridge accommodation
site 8 via front-entry loading. Such front-entry loading usually includes a movement
of the disposable cartridge 2 in a direction that is parallel to the electrode array
9 (see Fig. 1). In order to enable proper drawing-in of the disposable cartridge 2
and to neatly position the cartridge at the accommodation site 8, the base unit 7
preferably is equipped with insertion guides 25. These insertion guides 25 preferably
are from a self-lubricating plastic material, such as tetrafluorethylene and preferably
leave a space between them that is just sufficient for slidingly inserting the disposable
cartridge 2. Alternatively the electrically conductive material 15 of the cover plate
12 is configured as a metal plate, a metal foil, or a metal layer that is sandwiched
between materials of the top substrate 13 (see Fig. 8A).
[0049] The disposable cartridge 2 of Fig. 3 comprises a bottom layer 3, a top layer 4, and
a spacer 5 that defines a gap 6 between the bottom and top layers 3,4 for manipulating
samples in liquid droplets 23 in this gap 6. The bottom layer 3 and the top layer
4 comprise a hydrophobic surface 17 that is exposed to the gap 6 of the cartridge
2. The bottom layer 3 and the top layer 4 of the cartridge 2 are entirely hydrophobic
films or at least comprise a hydrophobic surface that is exposed to the gap 6 of the
cartridge 2. As a difference to the one depicted in Fig. 2, this cartridge 2 has dielectric
layer 24 that is attached to or forms a part of the bottom layer 3. Thus, the bottom
layer 3 is covered by a dielectric layer 24 or the bottom layer 3 itself is made from
a dielectric material. In consequence, the electrode array 9 does not need to have
such a dielectric layer 24. The spacer 5 of the cartridge 2 here at least partially
is configured as a body that includes compartments 21 for reagents needed in an assay
that is applied to the sample droplets in the gap 6. In this case, the electrode array
9 is covered by a dielectric layer 24.
[0050] The electrode array 9 is fixed to a bottom substrate 11 and every individual electrode
10 is electrically and operationally connected with the central control unit 14 (only
three connections of the ten electrodes 10 are drawn here). The digital microfluidics
system 1 is configured for manipulating samples in liquid droplets 23 within disposable
cartridges 2 that contain a gap 6. Accordingly, the samples in liquid droplets 23
are manipulated in the gap 6 of the disposable cartridge 2.
[0051] The cover plate 12 also includes a piercing facility 18 that is configured for introducing
sample droplets into the gap 6 of the cartridge 2. The piercing facility 18 is conffgured
as a through hole 19 that leads across the entire cover plate 12 and that enables
a piercing pipette tip 20 to be pushed through and pierce the top layer 4 of the cartridge
2. The piercing pipette tip 20 may be a part of a handheld pipette (not shown) or
of a pipetting robot (not shown). The cover plate 12 here comprises additional piercing
facilities 22 for a piercing pipette tip 20 to be pushed through a through hole 19
that penetrates the cover plate 12, to pierce the top layer 4 of the cartridge 2 and
to withdraw reagent portions from the compartments 21 and for introducing said reagent
portions into the gap 6 of the cartridge 2. Here, the compartment 21 is configured
as a cutout in the body of the spacer 5, the cutout being closed by the bottom layer
3 and top layer 4.
[0052] The Figure 4 shows section views of one exemplary cartridge accommodation site 8
with a disposable cartridge 2 according to a third embodiment accommodated therein.
The electrode array 9 is fixed to a bottom substrate 11 and every individual electrode
10 is electrically and operationally connected with the central control unit 14 (only
three connections of the ten electrodes 10 are drawn here). The digital microfluidics
system 1 is configured for manipulating samples in liquid droplets 23 within disposable
cartridges 2 that contain a gap 6. Accordingly, the samples in liquid droplets 23
are manipulated in the gap 6 of the disposable cartridge 2.
[0053] The cover plate 12 is mechanically connected with the base unit 7 of the digital
microfluidics system 1 via a hinge 16; thus, the cover plate 12 can swing open and
a disposable cartridge 2 can be placed on the cartridge accommodation site 8 via top-entry
loading (see Fig. 1). Here, the electrically conductive material 15 of the cover plate
12 is made of metallic conductive material and comprises both the top substrate 13
and the electrically conductive material 15 as a single integrated part. Alternatively,
the electrically conductive material 15 of the cover plate 12 is configured as compound,
such as titanium indium oxide (TIO) or a plastic material with electrically conductive
filler materials that is attached or integrated into the top substrate 13 (not shown).
In both cases, it may be preferred that the electrically conductive material 15 is
covered by a plastic layer (not shown); the material of this plastic layer preferably
being selected from a group comprising polypropylene (PP) and polyamide (PA). Automatic
opening and closing of the cover plate 12 may be achieved by a closing means 30.
[0054] The cover plate 12 also includes a piercing facility 18 that is configured for introducing
sample droplets into the gap 6 of the cartridge 2. The piercing facility 18 is configured
as a through hole 19 that leads across the entire cover plate 12 and that ena bles
a piercing pipette tip 20 to be pushed through and pierce the top layer 4 of the cartridge
2 (see Fig. 4B). The piercing pipette tip 20 may be a part of a handheld pipette (not
shown) or of a pipetting robot (not shown). The cover plate 12 here comprises additional
piercing facilities 22 for a piercing pipette tip 20 to be pushed through a through
hole 19 that penetrates the cover plate 12, to pierce the top layer 4 of the cartridge
2 and to withdraw e.g. silicon oil from the gap 6 of the cartridge 2 (see Fig. 4B).
[0055] Fig. 4A shows the cushion-like cartridge 2 as laid into a cartridge accommodation
site 8 of a base unit 7 of digital microfluidics system 1 a with a partly closed cover
plate 12. This disposable cartridge 2 comprises a bottom layer 3 and a top layer 4,
but no spacer that would define a gap 6 between the bottom and top layers 3,4 for
manipulating samples in liquid droplets 23 in this gap 6. The bottom layer 3 and the
top layer 4 comprise a hydrophobic surface 17',17" that is exposed to the gap 6 of
the cartridge 2. The bottom layer 3 and the top layer 4 of the cartridge 2 are entirely
hydrophobic films or at least comprise a hydrophobic surface that is exposed to the
gap 6 of the cartridge 2. Like the one depicted in Fig. 2, this cartridge 2 has no
dielectric layer attached to or forms a part of the bottom layer 3. In consequence,
the electrode array 9 does need to have such a dielectric layer 24. This cartridge
2 without spacer is configured as a sack or pillow that preferably is filled with
silicon oil, other oils or another chemically substantially inert material that is
not miscible with water, such as hexadecane.
[0056] Fig. 4B shows the cushion-like cartridge 2 as pressed into operation shape inside
the cartridge accommodation site 8 by the entirely closed cover plate 12. As long
as the cover plate 12 at least partially is open (see Fig. 4A), the cushion-like or
sack-like cartridge 2 may take a shape that is mainly due to the forces that the preferred
oil filling is exerting to the membrane bag or sack of the cartridge 2. Handling (inserting
into and taking out from the accommodation site 8) the cartridge 2 preferably is performed
with a robotized suction device (not shown). When pressed into operation shape however
(se Fig. 4B), the cushion-like or sack-like cartridge 2 is urged into a shape that
conforms to the inner space of the cartridge accommodation site 8 of the base unit
7. Thus, without any need for providing a spacer, the top layer 4 is orientated substantially
parallel and in a defined distance to the bottom layer 3 and to the electrode array
9 below the latter.
[0057] In order to avoid leakage or spilling of oil during or after piercing the pillow-like
cartridge 2, the top layer 4 of the cartridge 2 may be configured as a self-sealing
pierceable membrane. Alternatively or in combination with a self-sealing pierceable
top layer 4, the cover plate 12 may be equipped with a self-sealing pierceable membrane
at least in the region of the piercing facilities 18,22. Such a self-sealing pierceable
membrane at least in the region of the piercing facilities 18,22 (not shown) preferably
is placed onto the surface of the cover plate 12 that is contacting the cartridge
2.
[0058] The Figure 5 shows a section view of one exemplary cartridge accommodation site 8
with a disposable cartridge 2 according to a fourth embodiment accommodated therein.
The cover plate 12 is mechanically connected with the base unit 7 of the digital microfluidics
system 1 via a hinge 16; thus, the cover plate 12 can swing open and a disposable
cartridge 2 can be placed on the cartridge accommodation site 8 via top-entry loading
(see Fig. 1). Here, the electrically conductive material 15 of the cover plate 12
is made of metallic conductive material and comprises both the top substrate 13 and
the electrically conductive material 15 as a single integrated part. Alternatively,
the electrically conductive material 15 of the cover plate 12 is configured as compound,
such as titanium indium oxide (TIO) or a plastic material with electrically conductive
filler materials that is attached or integrated into the top substrate 13 (not shown).
In both cases, it may be preferred that the electrically conductive material 15 is
covered by a plastic layer (not shown); the material of this plastic layer preferably
being selected from a group comprising polypropylene (PP) and polyamide (PA).
[0059] Also here, the cover plate 12 is configured to apply a force to a disposable cartridge
2 that is accommodated at the cartridge accommodation site 8 of the base unit 7. This
force urges the disposable cartridge 2 against the electrode array 9 in order to position
the bottom layer 3 of the cartridge as close as possible to the surface of the electrode
array 9. This force also urges the disposable cartridge 2 into a defined position
on the electrode array 9. In addition, a piercing facility 18 is provided: The disposable
cartridge 2 according to this third embodiment comprises a piercing pin 27 that is
located in the gap 6 of the cartridge 2 and that is configured for piercing the top
layer 4 when the top layer 4 is displaced in a direction against the bottom layer
3. Preferably, the piercing pin 27 is attached to a pin plate 28, which pin plate
28 is connecting the piercing pin 27 with a part of the spacer 5 of the disposable
cartridge 2. The cover plate 12 further comprises a through hole 19 that leads across
the entire cover plate 12 and that is located in register with the piercing pin 27
of a properly positioned disposable cartridge 2 seated at the cartridge accommodation
site 8. The cover plate 12 further comprises a displacement portion 29, which protrudes
from the cover plate 12 for displacing the top layer 4 in a direction against the
bottom layer 3. This displacement portion 29 is configured to cooperate with the piercing
pin 27 when piercing the top layer 4. Thus, by utilization of this piercing facility
18, sample droplets and/or reagent portions may be introduced into the gap 6 of the
cartridge 2. A portion of the through hole 19 preferably is widened such that a disposable
pipette tip 26 may be used for pipetting sample droplets and/or reagent portions to
the gap 6 of the disposable cartridge 2. The disposable pipette tip 26 may be a part
of a handheld pipette (not shown) or of a pipetting robot (not shown).
[0060] In this case, the electrode array 9 is covered by a dielectric layer 24. The electrode
array 9 is fixed to a bottom substrate 11 and every individual electrode 10 is electrically
and operationally connected with the central control unit 14 (only three connections
of the ten electrodes 10 are drawn here). The digital microfluidics system 1 is configured
for manipulating samples in liquid droplets 23 within disposable cartridges 2 that
contain a gap 6. Accordingly, the samples in liquid droplets 23 are manipulated in
the gap 6 of the disposable cartridge 2.
[0061] Like in the already introduced first and second embodiments, the disposable cartridge
2 comprises a bottom layer 3, a top layer 4, and a spacer 5 that defines a gap 6 between
the bottom and top layers 3,4 for manipulating samples in liquid droplets 23 in this
gap 6. The bottom layer 3 and the top layer 4 comprise a hydrophobic surface 17 that
is exposed to the gap 6 of the cartridge 2. The 1
st hydrophobic surface 17' is located on the inside of the bottom layer 3, and the 2
nd hydrophobic surface 17" is located on the inside of the top layer 4. The bottom layer
3 and the top layer 4 of the cartridge 2 are entirely hydrophobic films or at least
comprise a hydrophobic surface that is exposed to the gap 6 of the cartridge 2. It
is clear from this Fig. 2, that the cartridge 2 does not have a conductive layer.
The spacer 5 of the cartridge 2 here does not deed to be configured as a body that
includes compartments 21 for reagents needed in an assay that is applied to the sample
droplets in the gap 6, because these reagents could be added to the gap 6 by conventional
pipetting with a handheld pipette or with a pipetting robot (see above).
[0062] The Figure 6 shows a section view of one exemplary cartridge accommodation site 8
with a disposable cartridge 2 according to a fifth embodiment accommodated therein.
Similar to the previous embodiment, the cover plate 12 is mechanically connected with
the base unit 7 of the digital microfluidics system 1 by a hinge 16. In order to enable
proper top-loading of the disposable cartridge 2 and to neatly position the cartridge
at the accommodation site 8, the base unit 7 preferably is equipped with insertion
guides 25. These insertion guides 25 preferably are from a self-lubricating plastic
material, such as tetrafluorethylene (PTFE) and preferably leave a space between them
that is just sufficient for slidingly inserting the disposable cartridge 2. Also similar
to the previous embodiment and as a first alternative solution, the electrically conductive
material 15 of the cover plate 12 is made of metallic conductive material and comprises
both the top substrate 13 and the electrically conductive material 15 as a single
integrated part. Alternatively, the electrically conductive material 15 of the cover
plate 12 is configured as compound, such as titanium indium oxide (TIO) or a plastic
material with electrically conductive filler materials that is attached or integrated
into the top substrate 13 (not shown). In both cases, it may be preferred that the
electrically conductive material 15 is covered by a plastic layer (not shown); the
material of this plastic layer preferably being selected from a group comprising polypropylene
and polyamide.
[0063] Also here, the cover plate 12 is configured to apply a force to a disposable cartridge
2 that is accommodated at the cartridge accommodation site 8 of the base unit 7. This
force urges the disposable cartridge 2 against the electrode array 9 in order to position
the bottom layer 3 of the cartridge as close as possible to the surface of the electrode
array 9. This force also urges the disposable cartridge 2 into a defined position
on the electrode array 9. In addition, a piercing facility 18 is provided: The disposable
cartridge 2 according to this third embodiment comprises a piercing pin 27 that is
located in the gap 6 of the cartridge 2 and that is configured for piercing the top
layer 4 when the top layer 4 is displaced in a direction against the bottom layer
3. Preferably, the piercing pin 27 is attached to a pin plate 28, which pin plate
28 is connecting the piercing pin 27 with a part of the spacer 5 of the disposable
cartridge 2. The cover plate 12 further comprises a through hole 19 that leads across
the entire cover plate 12 and that is located in register with the piercing pin 27
of a properly positioned disposable cartridge 2 seated at the cartridge accommodation
site 8. The cover plate 12 further comprises a displacement portion 29, which protrudes
from the cover plate 12 for displacing the top layer 4 in a direction against the
bottom layer 3. This displacement portion 29 is configured to cooperate with the piercing
pin 27 when piercing the top layer 4. Thus, by utilization of this piercing facility
18, sample droplets and/or reagent portions may be introduced into the gap 6 of the
cartridge 2. A portion of the through hole 19 preferably is widened such that a disposable
pipette tip 26 may be used for pipetting sample droplets and/or reagent portions to
the gap 6 of the disposable cartridge 2. The disposable pipette tip 26 may be a part
of a handheld pipette (not shown) or of a pipetting robot (not shown). In this case,
the electrode array 9 is covered by a dielectric layer 24. The electrode array 9 is
fixed to a bottom substrate 11 and every individual electrode 10 is electrically and
operationally connected with the central control unit 14 (only three connections of
the ten electrodes 10 are drawn here). The digital microfluidics system 1 is configured
for manipulating samples in liquid droplets 23 within disposable cartridges 2 that
contain a gap 6. Accordingly, the samples in liquid droplets 23 are manipulated in
the gap 6 of the disposable cartridge 2.
[0064] Like in the already introduced first, second, and fourth embodiment, the disposable
cartridge 2 comprises a bottom layer 3, a top layer 4, and a spacer 5 that defines
a gap 6 between the bottom and top layers 3,4 for manipulating samples in liquid droplets
23 in this gap 6. The bottom layer 3 and the top layer 4 comprise a hydrophobic surface
17 that is exposed to the gap 6 of the cartridge 2. The 1
st hydrophobic surface 17' is located on the inside of the bottom layer 3, and the 2
nd hydrophobic surface 17" is located on the inside of the top layer 4. The bottom layer
3 and the top layer 4 of the cartridge 2 are entirely hydrophobic films or at least
comprise a hydrophobic surface that is exposed to the gap 6 of the cartridge 2. It
is clear from this Fig. 2, that the cartridge 2 does not have a conductive layer.
The spacer 5 of the cartridge 2 here does not deed to be configured as a body that
includes compartments 21 for reagents needed in an assay that is applied to the sample
droplets in the gap 6, because these reagents could be added to the gap 6 by conventional
pipetting with a handheld pipette or with a pipetting robot (see above).
[0065] It is noted that the piercing pin 27 of the fourth embodiment (see Fig. 5) of the
disposable cartridge 2 is placed with its back on the 1
st hydrophobic surface of the bottom layer 3. Thus, the bottom substrate 11 and the
electrode array 9 provide stability to the piercing pin 27 when the top layer 4 is
displaced by the displacement portion 29 of the cover plate 12. In consequence, the
pin plate 28 can be very thin. Alternatively, the pin plate 28 is omitted and the
piercing pin 27 is glued to the 1
st hydrophobic surface of the bottom layer 3. Only gluing such a small piercing pin
27 to the inner surface of the bottom layer 3 has the advantage that more of the individual
electrodes 10 can be used for electrowetting. Another advantage is that the position
of the piercing pin 27 (and also of the through hole 19 in the cover plate 12 of course)
can be arbitrarily chosen in any distance to the spacer 5. However, exact positioning
of the piercing pin 27 may be somewhat cumbersome during mass production of the disposable
cartridges 2.
[0066] In contrast, the piercing pin 27 of the fifth embodiment of the disposable cartridge
2 (see Fig. 6) is placed much closer to the spacer 5 with which it is connected by
a self-supporting pin plate 28. Thus, the spacer 6 provides stability to the piercing
pin 27 when the top layer 4 is displaced by the displacement portion 29 of the cover
plate 12. Advantageously, the electrode array 9 is not involved or affected by the
piercing process and all of the individual electrodes 10 can be used for electrowetting.
It is preferred to add a so-called weather groove to the lower part of the piecing
pin 27 (see Fig. 6) if draining the pipetted liquid down to the 1
st hydrophobic surface 17' along the self-supporting pin plate 28 should be avoided.
If such draining down however is preferred, adding of such a weather groove can be
omitted.
[0067] The Figure 7 shows an overview over a digital microfluidics system 1 that is equipped
with a central control unit 14 and a base unit 7, with twelve cartridge accommodation
sites 8 that each comprise an electrode array 9 and a fixed cover plate 12. This base
unit 7 is particularly suited for taking up cartridges 2 according to a sixth embodiment
and loading these cartridges into substantially vertical cartridge accommodation sites
8 with a substantially vertical electrode array 9 and cover plate 12 (see Fig. 8).
Such loading preferably is carried out by a robotized gripping device of a liquid
handling workstation (not shown).
[0068] The Figure 8 shows section views of one exemplary cartridge accommodation site 8
of a base unit 7 of digital microfluidics system 1 with a disposable cartridge 2 according
to a sixth embodiment accommodated therein. It is immediately clear from the Fig 8A,
that a top-entry cartridge 2 is inserted into a substantially vertical cartridge accommodation
site 8 with a substantially vertical electrode array 9 and cover plate 12. This disposable
cartridge 2 comprises a bottom layer 3 and a top layer 4, and a spacer 5 that defines
a gap 6 between the bottom and top layers 3,4 for manipulating samples in liquid droplets
23 in this gap 6. The bottom layer 3 and the top layer 4 comprise a hydrophobic surface
17',17" that is exposed to the gap 6 of the cartridge 2. The bottom layer 3 and the
top layer 4 of the cartridge 2 are entirely hydrophobic films or at least comprise
a hydrophobic surface that is exposed to the gap 6 of the cartridge 2. Like the one
depicted in Fig. 2, this cartridge 2 has no dielectric layer attached to or forms
a part of the bottom layer 3. In consequence, the electrode array 9 does need to have
such a dielectric layer 24. This cartridge 2 preferably is filled with silicon oil.
[0069] The electrode array 9 is fixed to a bottom substrate 11 and every individual electrode
10 is electrically and operationally connected with the central control unit 14 (only
four connections of the fourteen electrodes 10 are drawn here). The digital microfluidics
system 1 is configured for manipulating samples in liquid droplets 23 within disposable
cartridges 2 that contain a gap 6. Accordingly, the samples in liquid droplets 23
are manipulated in the gap 6 of the disposable cartridge 2.
[0070] The cover plate 12 is mechanically connected with or entirely integrated into the
base unit 7 of the digital microfluidics system 1 and is not movable. Thus, a disposable
cartridge 2 can be inserted into the cartridge accommodation site 8 via top-entry
loading (see Fig. 7). Here, the electrically conductive material 15 of the cover plate
12 is made of metallic conductive material and is sandwiched between material of the
top substrate 13. Alternatively, the electrically conductive material 15 of the cover
plate 12 may be covered by a plastic layer instead or additional to the material of
the top substrate 13 (not shown).
[0071] The spacer 5 also includes a piercing facility 18 that is configured for introducing
sample droplets into the gap 6 of the cartridge 2. The piercing facility 18 is configured
as an enlarged portion of the spacer 5. This enlarged spacer portion preferably is
equipped with a pierceable, self-sealing membrane 31 that enables a piercing pipette
tip 20 to be pushed through. The piercing pipette tip 20 may be a part of a handheld
pipette (not shown) or of a pipetting robot (not shown). Automated delivery of liquids
to or withdrawal of liquids from the gap 6 of the cartridge 2 is simplified by the
relatively large piercing area provided by this enlarged spacer portion of the cartridge
2. Assuming a gap width of about 1-3 mm, the width of this piercing area preferably
is about 5-10 mm and therefore has about the size of a well of 96-well microplate,
which easily can be reached by an automated pipettor of a liquid handling system or
of a liquid handling workstation. The same time as providing space for compartments
21 (see also Fig. 8B), the enlarged spacer portion of the cartridge 2 also provides
gripping surfaces for being gripped by an automated robot gripper (not shown) that
is preferably utilized for handling the cartridges outside of the digital microfluidics
system 1 and for inserting and withdrawal of the cartridges 2 from their accommodation
sites 8. In addition, the enlarged spacer portion of the cartridge 2 provides an abutting
surface that abuts the surface of the base unit 7 when the cartridge 2 is correctly
accommodated in the accommodation site 8.
[0072] It is preferred that the electrode array 9 extends to the foremost position with
respect to the surface of the base unit 7 in order to be able to move liquid droplets
23 from a compartment 21 to a distinct position on the printed circuit board (PCB)
or electrode array 9. Also moving liquid droplets 23 in the opposite direction from
a reaction site on the electrode array 9 to a compartment 21 is greatly preferred,
especially in the case if a reaction product shall be analyzed outside of the digital
microfluidics system 1 and also outside of the cartridge 2.
[0073] Fig. 8B shows the top-entry cartridge 2 of Fig. 8A as viewed from the section plane
B indicated in Fig. 8A. The section runs through the gap 6 and between the bottom
layer 3 and the top layer 4 of the self-containing, disposable cartridge 2. The section
also crosses the spacer 5, of which a U-shaped part is located between the bottom
and top layers 3,4 and an enlarged spacer portion is provided around the U-shaped
part and the bottom and top layers 3,4. Preferably, the U-shaped part of the spacer
5 is of plastic material (preferably injection molded) and glued or fused to the bottom
and top layers 3,4. It is preferred that the enlarged spacer portion also is prod
uced by injection molding; this enables the provision of separating bars 32 that on
the one hand create the compartments 21 below the pierceable membrane 31, and that
on the other hand stabilize the pierceable membrane 31. Such stabilization preferably
is provided by back-injection molding the separating bars 32 and the enlarged spacer
portion to the pierceable membrane 31. Preferably, the enlarged spacer portion then
is imposed on the U-shaped part of the spacer 5 with the bottom and top layers 3,4.
[0074] As already pointed out, the spacer 5 also includes a piercing facility 18 that is
configured as an enlarged portion of the spacer 5. This enlarged spacer portion preferably
is equipped with a pierceable self-sealing membrane 31 that enables a piercing pipette
tip 20 to be pushed through. The piercing pipette tip 20 may be a part of a handheld
pipette (not shown) or of a pipetting robot (not shown). The spacer 2 here comprises
additional piercing facilities 22 for a piercing pipette tip 20 to be pushed through
the self-sealing membrane 31 and to withdraw e.g. silicon oil from the gap 6 of the
cartridge 2. In the cartridge 2 of this Fig. 8B, a liquid droplet 23 (e.g. a sample)
was introduced by the piercing pipette tip 20 at the piercing facility 18 and then
moved on the hydrophobic surface 17' of the bottom layer 3 to the actual position.
Simultaneously with introducing the liquid droplet 23 into the compartment 21 and
into the gap 6, a similar amount of silicon oil (or any other chemically inert liquid
that will not mix with the liquid droplet 23) is withdrawn from the respective compartment
21 at the additional piercing facility 22. Alternative to such simultaneous balancing
of liquids in the gap 6, removing of the expected quantity of oil or inert liquid
can be carried out shortly before or after the insertion of the liquid droplet 23.
The compartments 21 also may serve as reservoirs for storing more liquid than necessary
for producing a movable liquid droplet 23 from this liquid; in consequence, a number
of such droplets 23 may be produced from a single liquid volume once introduced into
at least one of the compartments 21. It is advisable however, to set aside one compartment
21, for withdrawal of oil or inert liquid, and to set aside another compartment 21
for withdrawal of reagent products.
[0075] According to an alternative and very simple embodiment (not shown), a disposable
cartridge 2 that comprises a bottom layer 3 and top layer 4 with hydrophobic surfaces
17',17" that in each case are directed to the gap 6, can be mounted on a PCB for electrowetting.
Instead of utilizing a cover plate 12 that is equipped with an electrically conductive
material 15, an electrically conductive film (e.g. an aluminum foil) can be attached
to the outer surface of the top layer 4. It turned out that such a conductive film
enables electrowetting even when this conductive film in not grounded. Instead of
attaching an un-grounded conductive film to the cartridge, the top layer 4 can have
a thin film coating on its outer surface; the thin film coating can be of any metal
and deposited by chemical or physical evaporation techniques. This thin conductive
film on the outer surface of the top layer 4 can even by of conductive paint. It is
thus proposed to provide an electrically conductive material 15 that extends in a
second plane and substantially parallel to the electrode array 9, said electrically
conductive material 15 being situated on the top layer 4 of the cartridge 2 and being
not connected to a source of a distinct electrical potential during manipulating samples
in liquid droplets 23.
[0076] A method for manipulating samples in liquid droplets 23 that adhere to a hydrophobic
surface 17 is characterized that the method comprising the steps of providing a first
hydrophobic surface 17' on a bottom layer 3 of a disposable cartridge 2. This bottom
layer 3 is located substantially parallel above an electrode array 9 of a digital
microfluidics system 1. Said electrode array 9 substantially extends in a first plane
and comprises a number of individual electrodes 10 that are supported by a bottom
substrate 11 of a base unit 7 of the digital microfluidics system 1. Said electrode
array 9 is connected to a central control unit 14 of the digital microfluidics system
1 for controlling the selection of individual electrodes 10 of said electrode array
9 and for providing these electrodes 10 with individual voltage pulses for manipulating
said liquid droplets 23 on said first hydrophobic surface 17' by electrowetting.
[0077] The method also comprises the step of providing a second hydrophobic surface 17"
substantially parallel to and in a distance to said first hydrophobic surface 17'.
In this way, a gap 6 between the first and second hydrophobic surfaces 17',17" is
formed. Preferably, such a gap 6 is defined by a spacer 5, to which the a bottom layer
3 that comprises the first hydrophobic surface 17' and a top layer 4 that comprises
the second hydrophobic surface 17" are attached.
[0078] The method further comprises providing a cover plate 12 with a top substrate 13.
The cover plate 12 also comprises an electrically conductive material 15 that extends
in a second plane and substantially parallel to the electrode array 9. It is especially
preferred that the electrically conductive material 15 of the cover plate 12 is not
connected to a source of a distinct electrical potential during manipulating samples
in liquid droplets 23.
[0079] In all embodiments shown or discussed, it is preferred that the gap 6 of the disposable
cartridge 2 is substantially filled with silicon oil. It is also always preferred
that the bottom layer 3 and the top layer 4 of the cartridge 2 are entirely hydrophobic
films or comprise a hydrophobic surface 17',17" that is exposed to the gap 6 of the
cartridge 2. Following electrowetting and manipulating at least one liquid droplet
23 with the gap 6 of a disposable cartridge 2, the result of the manipulation or of
the assay can be evaluated while the disposable cartridge 2 still is at the cartridge
accommodation site 8, i.e. utilizing an analysis system of the digital microfluidics
system 1 or of a workstation, the digital microfluidics system 1 is integrated into.
Alternately, the disposable cartridges 2 can be taken out of the base unit 7 of the
digital microfluidics system 1 and analyzed elsewhere.
[0080] After analysis, the disposable cartridges 2 can be disposed and the electrode array
9 can be reused. Because the components of the digital microfluidics system 1 never
come into contact with any samples or reagents when working with the first or second
embodiment of the cartridge 2, such re-usage with other disposable cartridges 2 can
be immediately and without any intermediate cleaning. Because the through hole 19
of the cover plate 12 of the digital microfluidics system 1 may come into contact
with samples and reagents when working with the third or fourth embodiment of the
cartridge 2, such re-usage with other disposable cartridges 2 can be carried out after
some intermediate cleaning or after replacement of the cover plates 12.
[0081] It is an aim of the present invention to provide removable and disposable cartridges
with working films that separate the liquid droplets 23 from the electrode array 9
during manipulation of the liquid droplets 23 by electrowetting. As shown in the eight
different embodiments of the self-containing disposable cartridge 2 presented in the
above specification, the removable and disposable films preferably are provided as
a bottom layer 3 and a top layer 4 of a cartridge 2.
[0082] In a preferred embodiment, the bottom layer 3 of the cartridge 2 is attracted to
the PCB by vacuum. Small evacuation holes in the PCB are connected to a vacuum pump
for this purpose. Applying such vacuum attraction to the bottom layer 3 enables avoiding
the use of any liquids or adhesives for better contacting the bottom layer 3 of the
cartridge 2 to the surface of the electrode array 9.
[0083] In the attached Figures 9, 10, and 11, especially preferred embodiments of a disposable
cartridge according to a seventh and eighth embodiment are shown. In each case, the
disposable cartridge 2 comprises a body 47 with at least one compartment 21 that is
configured to hold therein processing liquids, reagents or samples. At least one of
said compartments 21 comprises a through hole 19 for delivering at least some of its
content to a gap 6 below. The disposable cartridge 2 also comprises a bottom layer
3 with a first hydrophobic surface 17' that is impermeable to liquids and that is
configured as a working film for manipulating samples in liquid droplets 23 thereon
utilizing an electrode array 9 of a digital microfluidics system 1 when the bottom
layer 3 of the disposable cartridge 2 is placed over said electrode array 9. The disposable
cartridge 2 further comprises a top layer 4 with a second hydrophobic surface 17"
that at least is permeable to ions and that is attached to a lower surface 48 of the
body 47 of the disposable cartridge 2. Moreover, the disposable cartridge 2 comprises
a gap 6 that is located between the first hydrophobic surface 17' of the bottom layer
3 and the second hydrophobic surface 17" of the top layer 4. The bottom layer 3 of
the inventive cartridge 2 is configured as a flexible film that is sealingly attached
to the top layer 4 along a circumference 40 of the flexible bottom layer 3. Thus,
the disposable cartridge 2 is devoid of any spacer 5 that is located between the flexible
bottom layer 3 and the top layer 4 for defining a particular distance between said
first hydrophobic surface 17' and said second hydrophobic surface 17". The top layer
4 is configured to provide a seal between a lower end of at least one compartment
21 and the gap 6. In addition, the top layer 4 comprises loading sites 41 for transferring
processing liquids, reagents or samples into the gap 6.
[0084] In Fig. 9, a section view of one disposable cartridge 2 before reaching its accommodation
site 8 is presented. The flexible bottom layer 3 is seen as it is only attached to
the top layer 4 around its circumference 40, the majority of the bottom layer 3 being
loosely suspended from its circumference 40 and being not in contact with the top
layer 4. Accordingly, before correctly placing the disposable cartridge 2 in or on
the cartridge accommodation site 8, the gap 6 is enclosed but not defined in its width
and parallel orientation. The body 47 of the disposable cartridge 2 here comp rises
an essentially flat lower surface 48 and is configured as a frame structure with a
central opening 43 that penetrates the entire frame structure.
[0085] In Fig. 10, a section view of the disposable cartridge 2 of Fig. 9 is depicted after
the disposable cartridge 2 reaching its cartridge accommodation site 8 on the electrode
array of a digital microfluidics system 1. The disposable cartridge 2 is configured
according to the seventh embodiment and is hold in place by a clamp 37. On one side,
the clamp 37 preferably is attached to the substrate 11 of the base unit 7 of the
digital microfluidics system 1 by a hinge 16. On the other side, the clamp 37 may
be attached to the substrate 11 of the base unit 7 of the digital microfluidics system
1 by e.g. a clip, a snap-lock, or a screw (not shown).
[0086] In the seventh embodiment of Figs. 9 and 10, the disposable cartridge 2 further comprises
a plane rigid cover plate 12 that is attached to the lower surface 48 of the body
47 of the disposable cartridge 2. The top layer 4 is attached to said rigid cover
plate 12, which rigid cover plate 12 comprises through holes 19 that are located at
the loading sites 41 (here at the piercing site 41' and at the capillary orifice 41")
of the top layer 4. The rigid cover plate 12 here provides for a straight attachment
surface for the top layer 4 and also comprises the through hole 19. The cover plate
may be manufactured from a rigid material like clear Mylar® (trademark of DuPont Teijin;
a film from polyethylene terephthalate, PET). The rigid cover may be coated (preferably
on the lower side) with an electrically conductive material 15, e.g. from titanium
indium oxide (TIO) or from a plastic material with electrically conductive filler
materials in order to achieve the function of the cover plate 12 as described before.
As indicated with darker lines, the cover plate 12 is attached to the lower surface
48 of the body 47 of the disposable cartridge 2. This attachment may be achieved by
the use of an adhesive tape or a glue strip that preferably is from a chemically inert
material just like the Mylar. Depending on the material of the body 4-7 of the cartridge
2, also welding methods can be applied for attaching the cover plate 12 to the cartridge
2. As indicated with darker lines, the top layer 4 here is sealingly attached to the
lower surface 48 of cover plate 12. This attachment of the top layer 4 can be carried
out by using an adhesive tape or a glue strip, or by welding (e.g. by laser welding).
The flexible bottom layer 3 is sealingly attached to the top layer 4 along the circumference
40 of the flexible bottom layer 3 by using an adhesive tape or a glue strip, or by
applying a welding technique.
[0087] In Fig. 9, a pipetting orifice 41"' is depicted as well. Such pipetting orifices
41"' that are located in the central opening 43 of the disposable cartridge 2 and
that are configured to be accessible by a pipette tip can thus be used for pipetting
of processing liquids, reagents or samples directly into the gap 6. Of course, the
pipetting orifice 41'" comprises an opening in the cover plate 12 (if present) and
a through hole in the top layer 4. Such pipetting orifices 41'" can be used in addition
to or instead of one or more piecing orifices 41', which in each case are located
below a compartment 21.
[0088] This disposable cartridge 2 comprises at least one plunger 42 that in each case is
configured to be movable within a compartment 21 manually or by an actuating element
38 (see Fig. 10) for pressing the content of the respective compartment 21 against
a respective loading site 41 of the top layer 4. The plunger 42 comprises a piercing
pin 27 that is configured for piercing the top layer 4 at the respective loading site
41 of the compartment 21. Thus, the plunger 42 is configured for pressing some of
the content of the compartment 21 through the piercing site 41' of the top layer 4
and into the gap 6. Alternatively, the plunger 42 is configured for pressing some
of the content of the compartment 21 through a capillary orifice 41" of the top layer
4 and into the gap 6. This capillary orifice 41" preferably is sized to exhibit capillary
forces that prevent flowing though of aqueous liquids without a pressure being applied
with the plunger 42 (see Fig. 11, left side). Thus, the loading sites 41 preferably
are selected from a group comprising piercing sites 41', capillary orifices 41", and
pipetting orifices 41"'.
[0089] In Fig. 11, a section view of a disposable cartridge 2 after reaching its cartridge
accommodation site 8 on the electrode array 9 of a digital microfluidics system 1
is shown. The disposable cartridge 2 is configured according to an eighth embodiment
and is hold in place by a clamp 37.
[0090] In the Fig. 11, the plunger 42 is configured to sealing the compartment 21 against
an upper surface 49 of the body 47 of the disposable cartridge 2. Preferably, this
sealing is achieved with an O-ring seal 39 around the plunger 42. Alternatively, as
shown in the Figs. 9 and 10, to an upper surface 49 of the body 47 of the disposable
cartridge 2 is sealingly applied an elastic layer 44 that is configured to seal at
least one of the compartments 21 against said upper surface 49. Preferably, the plunger
42 is attached to the elastic layer 44 with its backside, so without applying any
pressure to the outside of the elastic layer (manually or with an actuating element
38, see Fig. 10), the plunger 42 is held in place close to the upper surface 49 of
the body 47 (see Fig. 9).
[0091] If however, the plunger 42 is pressed down (see Fig. 10 and Fig. 11, on the right),
the piercing pin 27 penetrates the through hole 19 in the cover layer 12 or body 47
and pierces the top layer 4. Concurrently, a portion of the content of the compartment
21, be it a processing liquid, a reagent or a sample (in a solution or suspension),
is pressed by the plunger into the gap 6. As a result, on the first hydrophobic surface
17' of the bottom layer 3, a droplet 23 is built up and can be manipulated in the
gap between this first hydrophobic surface 17' of the bottom layer 3 and the second
hydrophobic surface 17" of the top layer 4. Manipulating the droplet 23 is effected
by the electrode array 9 of the digital microfluidics system 1 the disposable cartridge
2 is accommodated on.
[0092] Alternatively, pressing down the plunger 42 shall force a portion of the contents
of the compartment 21, be it a processing liquid, a reagent or a sample (in a solution
or suspension), to be moved through the capillary orifice 41" and into the gap 6 (see
Fig. 11, left side, where the plunger 42 is ready to move). As a result, on the first
hydrophobic surface 17' of the bottom layer 3, a droplet 23 will be built up and can
be manipulated in the gap between this first hydrophobic surface 17' of the bottom
layer 3 and the second hydrophobic surface 17" of the top layer 4. Again, manipulating
the droplet 23 will be effected by the electrode array 9 of the digital microfluidics
system 1 the disposable cartridge 2 is accommodated on.
[0093] According to the eighth embodiment of Fig. 11, the body 47 of the disposable cartridge
2 is configured as a plate-like structure with an essentially flat lower surface 4-8,
in each case the compartments 21 leading to said lower surface 48 with a through hole
19 at the piercing sites 41' or capillary orifices 41".
[0094] In the seventh and eighth embodiment of the disposable cartridge 2 of the present
invention, it is one preferred alternative that the flexible bottom layer 3 is configured
as a monolayer or single layer, respectively of a hydrophobic material. According
to a second preferred alternative, the flexible bottom layer 3 is configured as a
monolayer or single layer, respectively of electrically non-conductive material, the
upper surface 17 of the flexible bottom layer 3 being treated to be hydrophobic. According
to a third preferred alternative, the flexible bottom layer 3 is configured as a laminate
comprising a lower layer and a hydrophobic upper layer, the lower layer being electrically
conductive or non-conductive. According to another preferred embodiment of the disposable
cartridge 2 of the present invention, a dielectric layer 24 is laminated onto the
lower surface of the bottom layer 3 (see e.g. Fig. 11).
[0095] According to one variant of the seventh and eighth embodiment of the disposable cartridge
of the present invention, the disposable cartridge 2 further comprises a gasket 36
that is attached to a lower surface and along a circumference 40 of the flexible bottom
layer 3. The gasket 36 thus defining a particular distance between said first hydrophobic
surface 17' and said second hydrophobic surface 17", when the disposable cartridge
2 is placed over an electrode array 9 of a digital microfluidics system 1. This is
the case, if said digital microfluidics system 1 is equipped with suction holes 35
in the electrode array 9, and if the flexible bottom layer 3 is aspirated by said
suction holes 35.
[0096] Figure 12 shows a section view of a disposable cartridge 2 after reaching its accommodation
site 8, the disposable cartridge 2 being configured according to a ninth embodiment
and being hold in place without a clamp. Actually, two different variants of the ninth
embodiment are shown:
- on the left side, the body 47 is configured as plate structure;
- on the right side, the body 47 is configured as frame structure;
with the lower surface 48 of the body 47 of the disposable cartridge 2 in both cases
being essentially flat. Thus, the disposable cartridge 2 configured according to the
ninth embodiment comprises a body 47 with a lower surface 48, an upper surface 49,
and at least one through hole 19. The at least one through hole 19 is designed as
a pipetting orifice 41"' that is configured to be accessible by a pipette tip 26.
The through hole 19 and thus allows pipetting of processing liquids, reagents or samples
into the gap 6.
[0097] In addition to the body 47, the disposable cartridge 2 comprises a bottom layer 3
with a first hydrophobic surface 17' that is impermeable to liquids and that is configured
as a working film for manipulating samples in liquid droplets 23 thereon. Such manipulating
is performed utilizing an electrode array 9 of a digital microfluidics system 1 when
the bottom layer 3 of the disposable cartridge 2 is placed over said electrode array
9. Preferably, the flexible bottom layer 3 is sealingly attached to an electrically
conductive material 15 along a circumference 40 of the flexible bottom layer 3 by
an adhesive tape or a glue strip, or alternatively by welding.
[0098] The disposable cartridge 2 further comprises an electrically conductive material
15 attached to the lower surface 48 of the body 47. The electrically conductive material
15 is at least permeable to ions and is configured to provide the lower surface 48
of the body 47 with a second hydrophobic surface 17". The bottom layer 3 is configured
as a flexible film that is sealingly attached to the electrically conductive material
15 of the disposable cartridge 2 along a circumference 40 of the flexible bottom layer
3, the disposable cartridge 2 thus being devoid of a spacer 5 (cv. Figs. 2, 6, and
8-10) that is located between the flexible bottom layer 3 and the electrically conductive
material 15 for defining a particular distance between said first hydrophobic surface
17' and said second hydrophobic surface 17".
[0099] The disposable cartridge 2 further comprises a gap 6 that is located between the
first hydrophobic surface 17' of the bottom layer 3 and the second hydrophobic surface
17" of the electrically conductive material 15. The at least one through hole 19 of
the body 47 is configured as a loading site 41 for transferring processing liquids,
reagents or samples into the gap 6.
[0100] The disposable cartridge 2 further comprises something like a compartment 21, which
is configured as one or more container-like depressions in the body 47 located around
one or more loading sites 41. However, these compartments 21 are not meant to store
liquids over a long period of time or even during shipping, they are merely configured
to allow a pipette tip 26 (disposable or not) to reach near the pipetting orifices
41'" located at the loading sites 41. Preferably, these "compartments 21" comprise
a central depression around the loading sites 41, which central depress ion allows
some liquid to be deposited temporarily prior to the transfer of the liquid into the
gap 6.
[0101] The Figure 13 shows a section view of one disposable cartridge 2 before reaching
its accommodation site 8 of the digital microfluidics system 1. The disposable cartridge
depicted here is configured according to a tenth embodiment and to be hold at the
cartridge accommodation site with or without a clamp. Despite some similarities when
compared with the disposable cartridge according to the seventh embodiment (see above
and Fig. 9), this tenth embodiment is characterized in that it is devoid of compartments
21. In consequence, this tenth embodiment of a disposable cartridge 2 according to
the present invention comprises at least one through hole 19 that is configured as
a loading site 41 for transferring processing liquids, reagents or samples into the
gap 6.
[0102] This disposable cartridge 2 is configured for insertion into a cartridge accommodation
site 8 of a digital microfluidics system 1 and comprises a rigid cover plate 12 with
a lower surface 48'. The rigid cover plate 12 depicted is relatively thin (e.g. having
a thickness of about 0.5 to 2 mm) and for better stabilization is attached to a lower
surface 48 of a frame-like body 47. This disposable cartridge 2 also comprises at
least one through hole 19 located at a loading site 41 of the cover plate 12 and a
second hydrophobic surface 17" that may be or may be not impermeable to liquids, the
second hydrophobic surface 17" at least being permeable to ions. This disposable cartridge
2 further comprises a bottom layer 3 with a first hydrophobic surface 17' that is
impermeable to liquids and that is configured as a working film for manipulating samples
in liquid droplets 23 thereon utilizing an electrode array 9 of the digital microfluidics
system 1 when the bottom layer 3 of the disposable cartridge 2 is placed over said
electrode array 9. This disposable cartridge 2 in addition comprises a gap 6 that
is located between the first hydrophobic surface 17' of the bottom layer 3 and the
second hydrophobic surface 17" of the rigid cover plate 12.
[0103] This disposable cartridge 2 according to a tenth embodiment is characterized in that
the bottom layer 3 is configured as a flexible film that is sealingly attached to
the lower surface 48' of the rigid cover plate 12 along a circumference 40 of the
flexible bottom layer 3. The flexible bottom layer 3 is configured to be attracted
and spread over the uppermost surface 52 of a cartridge accommodation site 8 of the
digital microfluidics system 1 by the underpressure in the evacuation space 46 of
the digital microfluidics system 1. Thus, the disposable cartridge 2 is devoid of
a spacer 5 that is located in the gap 6 between the flexible bottom layer 3 and the
second hydrophobic surface 17" of the rigid cover plate 12 for defining a particular
distance between said first hydrophobic surface 17' and said second hydrophobic surface
17" of the rigid cover plate 12.
[0104] Preferably, this disposable cartridge 2 comprises an electrically conductive material
15 that is attached to the lower surface 48' of the rigid cover plate 12. According
to a preferred variant embodiment as shown, the electrically conductive material 15
is configured to provide the lower surface 48' of the rigid cover plate 12 with the
second hydrophobic surface 17". Alternatively however, a top layer 4 that comprises
the second hydrophobic surface 17" may be attached directly to the lower surface 48'
of the rigid cover plate 12 or the lower surface 48' of the rigid cover plate 12 may
be treated to be hydrophobic and thus, the rigid cover plate 12 itself providing the
second hydrophobic surface 17" (both not shown).
[0105] The Figure 14 shows a section view of one disposable cartridge 2 before reaching
its accommodation site 8, the disposable cartridge 2 being configured according to
an eleventh embodiment and to be hold in place at the cartridge accommodation site
8 with or without a clamp. The depicted disposable cartridge 2 comprises a minimized
number of elements in order to simplify the production costs for the disposable cartridge
2.
[0106] The disposable cartridge 2 according to this eleventh embodiment is configured for
insertion into a cartridge accommodation site 8 of a digital microfluidics system
1 as herein disclosed. This disposable cartridge 2 comprises:
- (a) a plane rigid cover plate 12 comprising a lower surface 48', at least one through
hole 19 located at a loading site 41 and a second hydrophobic surface 17" that at
least is permeable to ions;
- (b) a bottom layer 3 with a first hydrophobic surface 17' that is impermeable to liquids
and that is configured as a working film for manipulating samples in liquid droplets
23 thereon utilizing an electrode array 9 of the digital microfluidics system 1 when
the bottom layer 3 of the disposable cartridge 2 is placed over said electrode array
9; and
- (c) a gap 6 that is located between the first hydrophobic surface 17' of the bottom
layer 3 and the second hydrophobic surface 17" of the rigid cover plate 12.
[0107] The disposable cartridge 2 according to this eleventh embodiment is characterized
in that the bottom layer 3 is configured as a flexible film that is sealingly attached
to the lower surface 48' of the rigid cover plate 12 along a circumference 40 of the
flexible bottom layer 3, the flexible bottom layer 3 being configured to be attracted
a nd spread over the uppermost surface 52 of a cartridge accommodation site 8 of the
digital microfluidics system 1 by the underpressure in the evacuation space 46 of
the digital microfluidics system 1, the disposable cartridge 2 thus being devoid of
a spacer 5 that is located in the gap 6 between the flexible bottom layer 3 and the
second hydrophobic surface 17" of the rigid cover plate 12 for defining a particular
distance between said first hydrophobic surface 17' and said second hydrophobic surface
17" of the rigid cover plate 12. This disposable cartridge 2 being further characterized
in that the at least one through hole 19 of the rigid cover plate 12 is configured
as a loading site 41 for transferring processing liquids, reagents or samples into
the gap 6.
[0108] Preferably, the lower surface 48' of the cover plate 12 is configured as the second
hydrophobic surface 17". It alternatively may be preferred that the cartridge 2 comprises
a top layer 4 that provides the second hydrophobic surface 17" and that is attached
to the lower surface 48' of the rigid cover plate 12 of the disposable cartridge 2.
It may be preferred as a second alternative that the cartridge 2 comprises an electrically
conductive material 15 that is attached to the lower surface 48' the rigid cover plate
12, the electrically conductive material 15 being configured to provide the lower
surface 48' of the rigid cover plate 12 with the second hydrophobic surface 17".
[0109] The digital microfluidics system 1 that is shown in the Figs. 13 and 14 has a similar
construction like the digital microfluidics system 1 shown in the Figures 1-12. However,
the particular embodiments that are depicted in the Figures 9-12 all comprise a number
of suction holes 35, which are located at the cartridge accommodation site 8 of the
base unit 7, and which simply penetrate the electrode array 9 and the bottom substrate
11 that carries the electrode array 9. Those embodiments of the Figures 9-12 comprise
a number of vacuum lines 34 that directly lead to these suction holes 35 and that
link these suction holes 35 to the vacuum source 33. In order to practically evenly
distribute the underpressure within the evacuation space 46, in those embodiments
as shown in the Figs. 9-12, the suction holes 35 need to be practically evenly distributed
over the area of the electrode array 9 and cartridge accommodation site 8.
[0110] The digital microfluidics system 1 as shown in the Figs. 9-14 is suited for manipulating
samples in liquid droplets within a gap 6 between a first hydrophobic surface 17'
of a bottom layer 3 and a second hydrophobic surface 17" of at least one disposable
cartridge 2 as shown in the Figs. 9-14.
[0111] However, the digital microfluidics system 1 shown in the Figs. 13 and 14 comprises
a number of suction holes 35 that penetrate the bottom substrate 11, but not the electrode
array 9. These suction holes 35 are preferably distributed in the cartridge accommodation
site 8 around the area of the electrode array 9. In order to practically evenly distribute
the underpressure within the evacuation space 46, the suction holes 35 are configured
to mouth into suction channels 51, which suction channels 51 are arranged in the uppermost
surface 52 of the cartridge accommodation site 8 of the digital microfluidics system
1. In the embodiment shown in the Figs. 13 and 14, the uppermost surface 52 of the
cartridge accommodation site 8 is provided by the dielectric layer 24 that is attached
to the upper surface of the electrode array 9 and the bottom substrate 11. In consequence,
the suction channels 51 are configured as grooves that are countersunk in the surface
of the dielectric layer 24. The pattern of these suction channels 51 or grooves may
comprise branched or un-branched straight lines, branched or un-branched meandering
lines any combinations thereof. As shown, the suction channels 51 or grooves may reach
over a part of the electrode array 11 and/or over a part of the bottom substrate 11.
Deviating from the straight suction holes 35 as shown in the Figs. 13 and 14, the
suction holes 35 can penetrate the bottom substrate 11 in any arbitrary direction
as best suited, e.g. the suction holes 35 can be configured to penetrate the bottom
substrate 11 at an oblique angle or stepwise. Especially in a case where the bottom
substrate 11 is configured to comprise two separate plates that are sandwiched on
top of each other (not shown), stepwise and/or branched configuration of the suction
holes 35 may be preferred in order to reduce complexity of the suction channels 51
or grooves in the surface of the dielectric layer 24.
[0112] In any case, it is preferred to arrange the suction channels 51 or grooves such that
an even underpressure can be established in the evacuation space 46. As soon as the
disposable cartridge 2 is located at the cartridge accommodation site 8, the gasket
36 seals in the cartridge accommodation site 8 the evacuation space 46, which is defined
by the flexible bottom layer 3 of the disposable cartridge 2, the uppermost surface
52 of the cartridge accommodation site 8, and the gasket 36.
[0113] The suction holes 35 can be directly linked to the vacuum source 33 of the digital
microfluidics system 1 by an appropriate number of vacuum lines 34 (see Figs. 9-12).
Alternatively, the suction holes 35 may be configured to mouth into a vacuum space
50, which vacuum space 50 is arranged at the at least one cartridge accommodation
site 8 and under the electrode array 9 and/or the bottom substrate 11. Preferably,
the vacuum space 50 is connected to the vacuum source 33 of the digital microfluidics
system 1 by at least one vacuum line 34 (see Figs. 13 and 14).
[0114] As in all other embodiments previously shown, the flexible bottom layer 3 preferably
is configured as a monolayer or single layer, respectively of a hydrophobic material.
According to a first preferred alternative variant, the flexible bottom layer 3 is
configured as a monolayer or single layer, respectively of electrically non-conductive
material, an upper surface of the flexible bottom layer 3 being treated to be a hydrophobic
surface 17. According to a second preferred alternative variant, the flexible bottom
layer 3 is configured as a laminate comprising a lower layer and a hydrophobic upper
layer, the lower layer being electrically conductive or non-conductive.
[0115] In another alternative embodiment, the disposable cartridge 2 further comprises a
gasket 36 that is attached to a lower surface and along a circumference 40 of the
flexible bottom layer 3. The gasket 36 thus defining a particular distance between
said first hydrophobic surface 17' and said second hydrophobic surface 17", when the
disposable cartridge 2 is placed over an electrode array 9 of a digital microfluidics
system 1, if said digital microfluidics system 1 is equipped with suction holes 35
in the electrode array 9, and if the flexible bottom layer 3 is aspirated by said
suction holes 35.
[0116] In the Fig. 12, the gasket 36 is attached to the bottom substrate 11 that supports
the individual electrodes 10 of the electrode array 9. Here, a dielectric layer 24
is attached to the surface of the electrode array 9, protecting the individual electrodes
from oxidation, mechanical impact and other influences like contamination. The dielectric
layer 24 also covers the gasket 36 that is configured as a closed ring that extends
around the accommodation site 8 for the disposable cartridge 2. The dielectric layer
24 further covers at least a part of the insertion guide 25 and reaches over a part
(see left side) or beyond the entire height of the disposable cartridge 2 (see right
side).
[0117] According to the seventh, eighth, and ninth embodiment of the of the disposable cartridge
2 of the present invention described so far, it is also proposed an alternative digital
microfluidics system that is configured to take up at least one of these inventive
disposable cartridges 2 in its cartridge accommodation sites 8 located on the electrode
array 9 of the base unit 7. Such a digital microfluidics system 1 for manipulating
samples in liquid droplets within the gap 6 between the flexible bottom layer 3 and
the top layer 4 of at least one such disposable cartridge 2 preferably comprises:
- (a) a base unit 7 with at least one cartridge accommodation site 8 that is configured
for taking up the disposable cartridge 2;
- (b) an electrode array 9 located at said cartridge accommodation site 8 of the base
unit 7, the electrode array 9 being supported by a bottom substrate 11 and substantially
extending in a first plane and comprising a number of individual electrodes 10; and
- (c) a central control unit 14 for controlling the selection of the individual electrodes
10 of said electrode array 9 and for providing these electrodes 10 with individual
voltage pulses for manipulating liquid droplets within the gap 6 of said cartridge
2 by electrowetting.
[0118] The inventive digital microfluidics system 1 further comprises:
(d) a number of suction holes 35 that penetrate the electrode array 9 and that are
distributed over the cartridge accommodation site 8 of the base unit 7;
(e) a vacuum source 33 for establishing an underpressure in an evacuation space 46;
and
(f) a number of vacuum lines 34 that link the suction holes 35 to the vacuum source
33.
[0119] The inventive digital microfluidics system 1 is characterized in that a gasket 36,
when located around a circumference 45 of the cartridge accommodation site 8, seals
in the cartridge accommodation site 8 the evacuation space 46, which is defined by
the flexible bottom layer 3 of the disposable cartridge 2, the electrode array 9 and
the bottom substrate 11 of the digital microfluidics system 1, and the gasket 36.
[0120] The inventive digital microfluidics system 1 is further characterized in that the
underpressure in the evacuation space 46 causes the flexible bottom layer 3 of the
disposable cartridge 2 that is placed on the cartridge accommodation site 8 to be
attracted and spread over the electrode array 9 and bottom substrate 11 of the digital
microfluidics system 1. It is expressly noted that the gap 6 defined by this spreading
the flexible bottom layer 3 of the disposable cartridge 2 is enabled without the use
of a spacer 5 located between the flexible bottom layer 3 and the top layer 4 of the
disposable cartridge 2.
[0121] According to another variant of the seventh and eighth embodiment of the disposable
cartridge 2 of the present invention, the disposable cartridge 2 does not comprise
a gasket 36. Instead, the gasket 36 is permanently fixed to the bottom substrate 11
of the base unit 7 of the digital microfluidics system 1, or the gasket 36 is fixed
to a dielectric layer 24 that permanently covers the electrode array 9 and the bottom
substrate 11. Of course in this case, the dielectric layer 24 has holes at the sites
of the suction holes 35 of the base unit 7 in order to enable formation of the underpressure
in the evacuation space 46, which causes the flexible bottom layer 3 of the disposable
cartridge 2 that is placed on the cartridge accommodation site 8 to be attracted and
spread over the electrode array 9 and bottom substrate 11 of the digital microfluidics
system 1.
[0122] According to a further variant of the seventh and eighth embodiment of the disposable
cartridge 2 of the present invention, the gasket 36 is permanently attached to a lower
surface and along a circumference 40 of the flexible bottom layer 3 of a disposable
cartridge 2 to be placed on the cartridge accommodation site 8 of the base unit 7.
[0123] The inventive digital microfluidics system 1 preferably is equipped with a base unit
7, which comprises an insertion guide 25 that is configured as a frame, which is sized
to accommodate a disposable cartridge 2 therein. It is especially preferred that the
base unit 7 comprises a clamp 37 that is configured to fix this disposable cartridge
2 at a desired position on the cartridge accommodation site 8 of the base unit 7.
As demonstrated in connection with the ninth embodiment (see Fig. 12), there is no
absolute need for using such a clamp 37. Here, the layers are all sealed well and
the vacuum in the evacuation space 46 on the bottom surface holds the disposable cartridge
2 safely in place and within the cartridge accommodation site 8 of the digital microfluidics
system 1.
[0124] It is further preferred that the base unit 7 comprises actuating elements 38 that
are configured for actuating plungers 42 that in each case are configured to be movable
within a compartment 21 of a disposable cartridge 2 that is placed on the cartridge
accommodation site 8. Thus, the plungers 42 in each case are configured for pressing
the content of the respective compartment 21 into the gap 6 of the disposable cartridge
2 that is located on the cartridge accommodation site 8 of the base unit 7. Preferably,
the actuating elements 38 are configured to be motor driven and controlled by the
central control unit 14 of the digital microfluidics system 1. The insertion guide
25 preferably is manufactured from aluminum, from another light metal or light alloy,
or from stainless steel. The following materials and dimensions are especially preferred
for manufacturing a disposable cartridge 2 of the present invention:
Table 1
Part |
No. |
Material |
Dimensions and Shape |
Bottom layer |
3 |
Fluorinated ethylene propylene (FEP), Cyclo olefin polymer (COP) |
Foil: 8-50 µm |
Top layer |
4 |
Al foil |
Foil: 20-100 µm |
Gap |
6 |
--- |
Height: 0.2-2.0 mm; preferably 0.5 mm |
Electrodes |
10 |
Al; Cu; Au; Pt |
Plating: 1.5 x 1.5 mm |
Cover plate |
12 |
Mylar®; acrylic |
Foil, plate: 0.15-1.8 mm; preferably 1.5 mm |
Electrically conductive material |
15 |
Au, Pt, TIO, PP, PA |
Layer: 20-100 µm; preferably 50 µm |
1st hydrophobic surface |
17' |
COP, FEP |
Foil: 8-50 µm |
2nd hydrophob. surface |
17" |
Teflon® |
Spin coating: 5-500 nm; preferably 20 nm |
Liquid droplet |
23 |
--- |
Volume: 0.1-5 µl |
Dielectric layer |
24 |
Fluorinated ethylene propylene, FEP |
Foil or casting: 20-100 µm |
Insertion guide |
25 |
Al; Al/Mg; steel; PTFE |
Frame: 5-30 mm |
Gasket |
36 |
Synthetic or natural rubber |
Frame: 0.2-2.0 mm; preferably 0.5 mm |
Seal, 1st type, compliant seal |
39 |
Natural rubber or Neoprene® |
O-ring: 5-10 mm; preferably 7 mm |
Seal, 2nd type, stiff seal |
39' |
Viton® |
O-ring: 3-8 mm; preferably 4 mm |
Capillary orifice |
41" |
--- |
Diameter: 0.1-0.5 mm |
Pipetting orifice |
41"' |
--- |
Diameter: 0.3-3.0 mm |
Elastic layer |
44 |
Synthetic or natural rubber |
Foil: 0.5-2.0 mm |
Body |
47 |
Polypropylene, PP |
65 x 85 mm; 6-25 mm |
[0125] The inventive disposable cartridge 2 and the inventive digital microfluidics system
1 enable an alternative method for manipulating samples in liquid droplets 23 that
adhere to a hydrophobic surface 17 to be carried out. This method comprising the steps
of:
- (a) providing a disposable cartridge 2 with a first hydrophobic surface 17' of a bottom
layer 3, with a second hydrophobic surface 17" of a top layer 4, and with a gap 6
between the first and second hydrophobic surfaces 17',17", the disposable cartridge
2 further comprising a body 47 with at least one compartment 21 to therein hold processing
liquids, reagents or samples, said compartment 21 comprising a through hole 19 for
delivering at least some of its content to the gap 6;
- (b) providing a digital microfluidics system 1 with an electrode array 9 that substantially
extends in a first plane and that comprises a number of individual electrodes 10 supported
by a bottom substrate 11 and connected to a central control unit 14 of the digital
microfluidics system 1 for controlling the selection of individual electrodes 10 of
said electrode array 9 and for providing these electrodes 10 with individual voltage
pulses for manipulating said liquid droplets 23 on said first hydrophobic surface
17' by electrowetting; and
- (c) defining the gap 6 so that the hydrophobic surface 17" of the top layer 4 extends
substantially parallel to and in a distance to said first hydrophobic surface 17'
of the bottom layer 3.
[0126] This method is characterized in that it comprises the steps of:
(d) providing the bottom layer 3 as a flexible film that is sealingly attached to
the top layer 4 along a circumference 40 of the flexible bottom layer 3, the disposable
cartridge 2 thus being devoid of a spacer 5 that is located between the flexible bottom
layer 3 and the top layer 4 for defining a particular distance between said first
hydrophobic surface 17' and said second hydrophobic surface 17";
(e) placing the disposable cartridge 2 on a cartridge accommodation site 8 of a base
unit 7 of the digital microfluidics system 1, the top layer 4 being configured to
provide a seal between a lower end of at least one compartment 21 and the gap 6, and
the top layer 4 comprising loading sites 41 for transferring processing liquids, reagents
or samples into the gap 6;
(f) sealing in the cartridge accommodation site 8 an evacuation space 46 by a gasket
36 located around a circumference 45 of the cartridge accommodation site 8, the evacuation
space 46 being defined by the flexible bottom layer 3, the electrode array 9, the
bottom substrate 11, and the gasket 36; and
(g) creating in the evacuation space 46 an underpressure, which causes the flexible
bottom layer 3 of the disposable cartridge 2 that is placed on the cartridge accommodation
site 8 to be attracted and spread over the electrode.
[0127] When applying this method, preferably the underpressure in the evacuation space 46
is created by a vacuum source 33, which is controlled by the central control unit
14 of the digital microfluidics system 1, and which is linked by a number of vacuum
lines 34 to suction holes 35 that penetrate the electrode array 9 and that are distributed
over the cartridge accommodation site 8 of the base unit 7. It is further preferred
that a plunger 42 contained in a compartment 21 of the disposable cartridge 2 is moved
manually or by an actuating element 38 and the content of the respective compartment
21 is pressed against a respective loading site 41 of the top layer 4. It is also
preferred that with a piercing pin 27 of the plunger 42, the top layer 4 is pierced
at a respective piercing site 41' of the compartment 21 and some of the content of
the compartment 21 is pressed through a hole punched into this piercing site 41' of
the top layer 4 and into the gap 6. Alternatively or additionally, it is also preferred
that some of the content of the compartment 21 is pressed with the plunger 42 through
a respective capillary orifice 41" of the top layer 4 and into the gap 6, the capillary
orifice 41" being sized to exhibit capillary forces that prevent flowing though of
aqueous liquids without a pressure being applied with the plunger 42.
[0128] In the attached Figures 15 to 17, especially preferred embodiments of a disposable
cartridge according to a twelfth embodiment are shown in partial sections. In each
case, the disposable cartridge 2 is located at its accommodation site 8 of the digital
microfluidics system 1. The disposable cartridge 2 in each case comprises
- (a) a bottom layer 3 with a first hydrophobic surface 17' that is impermeable to liquids
and that is configured as a working film for manipulating samples in liquid droplets
23 thereon utilizing an electrode array 9 of a digital microfluidics system 1 when
the bottom layer 3 of the disposable cartridge 2 is placed over said electrode array
9;
- (b) a rigid cover plate 12 with a lower, second hydrophobic surface 17", an upper
surface 58, and at least one through hole 19; and
- (c) a gap 6 that is located between the first hydrophobic surface 17' of the bottom
layer 3 and the second hydrophobic surface 17" of the rigid cover plate 12.
[0129] The bottom layer 3 in each case is configured as a flexible film that is sealingly
attached to the lower, second hydrophobic surface 17" of the rigid cover plate 12.
Thus, the disposable cartridge is devoid of a spacer located between the flexible
bottom layer 3 and the rigid cover plate 12 for defining a particular distance between
the first hydrophobic surface 17' and the second hydrophobic surface 17". Preferably,
the flexible bottom layer 3 is sealingly attached around its circumference 40 to the
lower surface 17' of the rigid cover plate 12. Preferably, the gap 6 is at least partially
filled with oil 53 when manipulating droplets 23 on the bottom layer 3.
[0130] Preferably, the upper surface 58 of the rigid cover plate 12 is at least partially
covered with a peel-off protection film 54 or with a pierceable membrane 31 that also
functions as a protection film which is hindering contamination of the through holes
19 form the outside and hindering contamination of the surroundings by the content
of the gap 6 of the disposable cartridge 2.
[0131] The digital microfluidics system 1 for manipulating samples in liquid droplets 23
within the gap 6 between the first hydrophobic surface 17' of the bottom layer 3 and
the second hydrophobic surface 17" of the rigid cover plate 12 of the disposable cartridge
depicted in the Figs. 15 to 17 comprises:
- (a) a base unit 7 with at least one cartridge accommodation site 8 that is configured
for taking up one disposable cartridge 2;
- (b) an electrode array 9 located at said at least one cartridge accommodation site
8 of the base unit 7, the electrode array 9 being supported by a bottom substrate
11 and substantially extending in a first plane and comprising a number of individual
electrodes 10;
- (c) a central control unit 14 for controlling the selection of the individual electrodes
10 of said electrode array 9 and for providing these electrodes 10 with individual
voltage pulses for manipulating liquid droplets 23 within the gap 6 of said cartridge
2 by electrowetting;
- (d) a number of suction holes 35 in the electrode array 9, the suction holes 35 mouthing
into a vacuum space 50 of the bottom substrate 11;
- (e) a vacuum source 33 for establishing an underpressure in an evacuation space 46;
and
- (f) a number of vacuum lines 34 (i.e. one or more vacuum lines 34) that link the vacuum
space 50 to the vacuum source 33.
[0132] The digital microfluidics system 1 depicted in the Figs. 15 to 17 comprises a rigid
spacer 5 for defining a particular distance between said first hydrophobic surface
17' and said second hydrophobic surface 17" independently of the level of screwing
or clamping and thereby pressing the cartridge onto the rigid spacer 5. The digital
microfluidics system 1 depicted in the Figs. 15 to 17 further comprises an insertion
guide 25 configured as a frame for centering a disposable cartridge 2 at said cartridge
accommodation site 8, for holding down the disposable cartridge 2 to the rigid spacer
5, and for sealing an evacuation space 46 by first and second seals 39,39' of the
frame. With respect to an inserted cartridge 2, the frame 25 leaves open a small cleft
around the circumference 45 of the cartridge accommodation site 8. The digital microfluidics
system 1 further comprises an evacuation space 46, which is defined by the flexible
bottom layer 3 of the disposable cartridge 2, an uppermost surface 52 of the cartridge
accommodation site 8, and the frame 25 with the seals 39,39'. As in the other embodiments
of the digital microfluidics system 1 shown before, the underpressure in the evacuation
space 46 causes the flexible bottom layer 3 that is placed at the cartridge accommodation
site 8 to be attracted to and spread over the uppermost surface 52 of the cartridge
accommodation site 8 of the digital microfluidics system 1.
[0133] Preferably in the embodiment as shown in the Figs. 15 to 17, the electrode array
or PCB 9 is not covered by a dielectric layer 24 like in the Figs. 11 and 12, but
unlike the embodiments of the Figs. 2-6, 8-10, and 13-14. Thus, the electrodes 10
of the PCB 9 are bare metal and in consequence, the flexible bottom layer 3 or working
film of the disposable cartridge comprises a dielectric layer with a hydrophobic surface
17' or a laminate of a dielectric layer and a hydrophobic layer on top. Alternatively,
the flexible bottom layer 3 is configured as a monolayer or single layer, respectively
of electrically non-conductive material, the upper surface 17' of the flexible bottom
layer 3 being treated to be hydrophobic.
[0134] Preferably, at least some of the suction holes 35 in the electrode array 9 are configured
as conductive through-holes that penetrate the PCB 9 for contacting at least some
of the individual electrodes 10 to the central control unit 14. These conductive through-holes
or vacuum vias in the PCB 9 may be made conductive by electroplating or by lining
with a tube or rivet.
[0135] Preferably to effectively seal the evacuation space 46, seals 39,39' are of two different
types, comprising i.e. a different material and/or cross section. A number of first
type seals 39 (drawn larger in the Figs. 15 to 17) are of a very compliant material
that is largely deformed, in consequence, the seal bearing parts (e.g. the frame 25
and the bottom structure 11) are firmly pressed against the respective counter part
(i.e. the top and bottom side of the PCB 9). Preferred materials for this compliant
seals 39 are O-rings of natural rubber or of a DuPont Elastomer such as Neoprene
®. Alternatively (not shown), the first type seals 39 may be configured as a lip seal.
[0136] Preferably, a second type of a seal 39' is of a material that is less compliant and
stiff enough to undergo only a minimal compression and thus combining the task of
sealing the evacuation space 46 and of pressing the disposable cartridge 2 firmly
against the rigid spacer 5. Preferred materials for this stiff seal 39' are e.g. O-rings
of a DuPont Performance Elastomer such as Viton
®.
[0137] In Figure 15, the disposable cartridge 2 is centered in the cartridge accommodation
site 8 by a frame 25 and pressed on a rigid spacer 5 of the PCB 9 with a closing means
30 that is configured as a pressing plate. The reference numbers 57 point to the screw
holes in the bottom structure 11, PCB 9, Frame 25, and pressing plate 30. Between
the pressing plate 30 and the frame 25 another first type compliant seal 39 is located
for safely sealing the evacuation space 46. If required, at least one through hole
19 in the rigid cover plate 12 can be utilized as a loading site 41 for samples. The
digital microfluidics system 1 may be equipped with an optical detection device 55
and the PCB 9 can be additionally supported by support posts 56, thus allowing optical
analysis of samples inside of the gap 6 of the disposable cartridge 2.
[0138] In Figure 16, the disposable cartridge 2 is centered in the cartridge accommodation
site 8 and pressed on a rigid spacer 5 of the PCB 9 by a frame profile that acts the
same time as an insertion guide 25 and as a closing means 30. Here, the frame profile
is screwed to the PCB 9 and to the bottom structure 11 of the digital microfluidics
system 1. The reference numbers 57 point to the screw holes in the bottom structure
11, PCB 9, and frame profile 25,30. Alternatively (not shown), the frame profile may
be pressed down to the PCB 9 and to the bottom structure 11 of the digital microfluidics
system 1 by a clamp 37 (comparable to Fig. 17). If required, at least one through
holes 19 in the rigid cover plate 12 can be utilized as a pipetting orifice 41"' for
filling samples into the gap 6 or for withdrawing samples from the gap 6 with a piercing
pipette tip 20 or with a disposable pipette tip 26, thus allowing analysis of samples
outside of the gap 6 of the disposable cartridge 2 and in an separate analysis system.
[0139] In Figure 17, the disposable cartridge 2 is centered in the cartridge accommodation
site 8 by a screwed frame 25 and pressed on a rigid spacer 5 of the PCB 9 with a closing
means 30 that is configured as a pressing plate. The reference numbers 57 point to
the screw holes in the bottom structure 11, PCB 9, and Frame 25. Between the pressing
plate 30 and the frame 25 another first type compliant seal 39 is located for safely
sealing the evacuation space 46. The pressing plate 30 may be pressed down to the
frame 25 and to the inserted cartridge 2 by a clamp 37. If required, at least one
through hole 19 in the rigid cover plate 12 can be utilized as a loading site 41 for
samples. The digital microfluidics system 1 may be equipped with an optical detection
device 55 and the PCB 9 can be additionally supported by support posts 56, thus allowing
optical analysis of samples inside of the gap 6 of the disposable cartridge 2.
[0140] In each case it is preferred that after manipulating liquid droplets 23 on said first
hydrophobic surface 17' by electrowetting and/or analyzing the sample in some of these
liquid droplets 23, the disposable cartridge 2 is taken from the cartridge accommodation
site 8 of the base unit 7 of the digital microfluidics system 1 and discarded.
Reference numbers:
1 |
digital microfluidics system |
32 |
separating bar |
2 |
disposable cartridge |
33 |
vacuum source |
3 |
flexible bottom layer |
34 |
vacuum line |
4 |
top layer |
35 |
suction hole |
5 |
spacer, rigid spacer |
36 |
gasket |
6 |
gap, gap between 3 and 4 |
37 |
clamp |
7 |
base unit |
38 |
actuating element |
8 |
cartridge accommodation site |
39 |
seal, 1st type, compliant seal |
9 |
electrode array, PCB |
39' |
seal, 2nd type, stiff seal |
10 |
individual electrode |
40 |
circumference of 3 |
11 |
bottom substrate |
41 |
loading site |
12 |
cover plate; rigid cover plate |
41' |
piercing site |
13 |
top substrate |
41" |
capillary orifice |
14 |
central control unit |
41"' |
pipetting orifice |
15 |
electrically conductive material |
42 |
plunger |
16 |
hinge |
43 |
central opening |
17 |
hydrophobic surface |
44 |
elastic layer |
17' |
1st hydrophobic surface |
45 |
circumference of 8 |
17" |
2nd hydrophobic surface |
46 |
evacuation space |
18 |
piercing facility |
47 |
body |
19 |
through hole |
48 |
lower surface of 47 |
20 |
piercing pipette tip |
48' |
lower surface of 12 |
21 |
compartment |
49 |
upper surface of 47 |
22 |
additional piercing facility |
50 |
vacuum space |
23 |
liquid droplet |
51 |
suction channels |
24 |
dielectric layer |
52 |
uppermost surface of 8 |
25 |
insertion guide, frame |
53 |
oil |
26 |
disposable pipette tip, pipette tip |
54 |
peel-off protection film |
27 |
piercing pin |
55 |
optical detection device |
28 |
pin plate |
56 |
support post |
29 |
displacement portion |
57 |
screw holes |
30 |
closing means, pressing plate |
58 |
upper surface of 12 |
31 |
pierceable membrane |
|
|
1. A digital microfluidics system (1) for manipulating samples in liquid droplets within
a gap (6) between a first hydrophobic surface (17') of a bottom layer (3) and a second
hydrophobic surface (17") of at least one disposable cartridge (2), the digital microfluidics
system (1) comprising:
(a) a base unit (7) with at least one cartridge accommodation site (8) that is configured
for taking up one disposable cartridge (2);
(b) an electrode array (9) located at said at least one cartridge accommodation site
(8) of the base unit (7), the electrode array (9) being supported by a bottom substrate
(11), substantially extending in a first plane and comprising a number of individual
electrodes (10); and
(c) a central control unit (14) for controlling the selection of the individual electrodes
(10) of said electrode array (9) and for providing these electrodes (10) with individual
voltage pulses for manipulating liquid droplets (23) within the gap (6) of said cartridge
(2) by electrowetting,
wherein the digital microfluidics system (1) further comprises:
(d) a number of suction holes (35) that penetrate the electrode array (9) and/or the
bottom substrate (11) and that are located at the at least one cartridge accommodation
site (8) of the base unit (7);
(e) a vacuum source (33) for establishing an underpressure in at least one of an evacuation
space (46) and a vacuum space (50); and
(f) a number of vacuum lines (34) that link the suction holes (35) and/or vacuum space
(50) to the vacuum source (33);
characterized in that a gasket (36) or a number of seals (39,39'), when a disposable cartridge (2) is located
at the at least one cartridge accommodation site (8), seal in said cartridge accommodation
site (8) the evacuation space (46), which is defined by a flexible bottom layer (3)
of a disposable cartridge (2), an uppermost surface (52) of the cartridge accommodation
site (8), and the gasket (36) or the seals (39,39') which are supported by an insertion
guide and closing means (25,30);
and in that the underpressure in the evacuation space (46) causes the flexible bottom layer (3)
of the disposable cartridge (2) that is placed at the cartridge accommodation site
(8) to be attracted and spread over the uppermost surface (52) of the cartridge accommodation
site (8) of the digital microfluidics system (1).
2. The digital microfluidics system (1) of Claim 1, characterized in that the gasket (36) is dimensioned to define a height of the gap (6) between the first
hydrophobic surface (17') of the bottom layer (3) and the second hydrophobic surface
(17") of a disposable cartridge (2).
3. The digital microfluidics system (1) of Claim 1, characterized in that the electrode array (9) of the digital microfluidics system (1) comprises a rigid
spacer (5) that is dimensioned to define a height of the gap (6) between the first
hydrophobic surface (17') of the bottom layer (3) and the second hydrophobic surface
(17") of a disposable cartridge (2).
4. The digital microfluidics system (1) of one of the Claims 1 to 3, characterized in that the suction holes (35) are configured to mouth into suction channels (51), said suction
channels (51) being arranged in the uppermost surface (52) of the cartridge accommodation
site (8) of the digital microfluidics system (1).
5. The digital microfluidics system (1) of one of the Claims 1 to 3, characterized in that the suction holes (35) are configured to mouth into a vacuum space (50), said vacuum
space (50) being arranged at the cartridge accommodation site (8) and under the electrode
array (9) in the bottom substrate (11), said vacuum space (50) being connected to
the vacuum source (33) of the digital microfluidics system (1) by at least one of
the vacuum lines (34).
6. The digital microfluidics system (1) of one of the preceding Claims, characterized in that the uppermost surface (52) of the cartridge accommodation site (8) comprises a dielectric
layer (24) that covers the electrode array (9), the dielectric layer (24) having holes
at the sites of the of suction holes (35) of the base unit (7).
7. The digital microfluidics system (1) of the Claims 1 or 2, characterized in that the gasket (36) is permanently fixed to the electrode array (9) of a cartridge accommodation
site (8) of the base unit (7) of the digital microfluidics system (1).
8. The digital microfluidics system (1) of Claim 6, characterized in that the gasket (36) is fixed to the dielectric layer (24) that permanently covers the
electrode array (9) of a cartridge accommodation site (8) of the digital microfluidics
system (1).
9. The digital microfluidics system (1) of Claim 6, characterized in that the gasket (36) is permanently fixed to the bottom substrate (11) that supports the
electrode array (9); the dielectric layer (24) permanently covering the bottom substrate
(11), the electrode array (9), and the gasket (36).
10. The digital microfluidics system (1) of one of the preceding Claims, characterized in that the base unit (7) comprises an insertion guide (25) that is configured as a frame,
which is sized to accommodate a disposable cartridge (2) therein.
11. The digital microfluidics system (1) of one of the Claims 3 to 10, characterized in that the base unit (7) comprises a closing means (30) that is configured as a pressing
plate for pressing a disposable cartridge (2) to the rigid spacer (5) of the electrode
array (9) of the digital microfluidics system (1).
12. The digital microfluidics system (1) of one of the preceding Claims, characterized in that the base unit (7) comprises a clamp (37) that is configured to fix a disposable cartridge
(2) at a desired position of a cartridge accommodation site (8) of the base unit (7).
13. A disposable cartridge (2) that is configured for insertion into a cartridge accommodation
site (8) of a digital microfluidics system (1) according to Claim 1, the disposable
cartridge (2) comprising:
(a) a body (47) with at least one compartment (21) configured to hold therein processing
liquids, reagents or samples, at least one of said compartments (21) comprising a
through hole (19) for delivering at least some of its content;
(b) a bottom layer (3) with a first hydrophobic surface (17') that is impermeable
to liquids and that is configured as a working film for manipulating samples in liquid
droplets (23) thereon utilizing an electrode array (9) of the digital microfluidics
system (1) when the bottom layer (3) of the disposable cartridge (2) is placed over
said electrode array (9);
(c) a top layer (4) with a second hydrophobic surface (17") that is attached to a
lower surface (48) of the body (47) of the disposable cartridge (2) and that at least
is permeable to ions; and
(d) a gap (6) that is located between the first hydrophobic surface (17') of the bottom
layer (3) and the second hydrophobic surface (17") of the top layer (4),
characterized in that the bottom layer (3) is configured as a flexible film that is sealingly attached
to the top layer (4) or to the body (47) along a circumference (40) of the flexible
bottom layer (3), the flexible bottom layer (3) being configured to be attracted and
spread over the uppermost surface (52) of a cartridge accommodation site (8) of the
digital microfluidics system (1) by the underpressure in the evacuation space (46)
of the digital microfluidics system (1), the disposable cartridge (2) thus being devoid
of a spacer (5) that is located in the gap (6) between the flexible bottom layer (3)
and the top layer (4) for defining a particular distance between said first hydrophobic
surface (17') and said second hydrophobic surface (17").
14. The disposable cartridge (2) of Claim 13, characterized in that the top layer (4) is configured to provide a seal between a lower end of at least
one compartment (21) and the gap (6), the top layer (4) comprising loading sites (41)
for transferring processing liquids, reagents or samples into the gap (6).
15. The disposable cartridge (2) of Claim 14, characterized in that the disposable cartridge (2) comprises at least one plunger (42) that in each case
is configured to be movable within a compartment (21) manually or by an actuating
element (38) for pressing the content of the respective compartment (21) against a
respective loading site (41) of the top layer (4).
16. The disposable cartridge (2) of Claim 14, characterized in that to an upper surface (49) of the body (47) of the disposable cartridge (2) is sealingly
applied an elastic layer (44) that is configured to seal at least one of the compartments
(21) against said upper surface (49).
17. The disposable cartridge (2) of Claim 14, characterized in that the disposable cartridge (2) further comprises a plane rigid cover plate (12) that
is attached to the lower surface (48) of the body (47) of the disposable cartridge
(2), the top layer (4) being attached to said rigid cover plate (12), which rigid
cover plate (12) comprising through holes (19) located at loading sites (41) of the
top layer (4).
18. The disposable cartridge (2) of Claim 14, characterized in that the disposable cartridge (2) is configured as a plate-like structure with a lower
surface (48), in each case the compartments (21) leading to said lower surface (48)
with a through hole (19) at piercing sites (41') or capillary orifices (41").
19. A disposable cartridge (2) that is configured for insertion into a cartridge accommodation
site (8) of a digital microfluidics system (1) according to Claim 1, the disposable
cartridge (2) comprising:
(a) a body (47) with a lower surface (48), an upper surface (49), and at least one
through hole (19);
(b) a bottom layer (3) with a first hydrophobic surface (17') that is impermeable
to liquids and that is configured as a working film for manipulating samples in liquid
droplets (23) thereon utilizing an electrode array (9) of the digital microfluidics
system (1) when the bottom layer (3) of the disposable cartridge (2) is placed over
said electrode array (9);
(c) an electrically conductive material (15) attached to the lower surface (48) of
the body (47), the electrically conductive material (15) being configured to provide
the lower surface (48) of the body (47) with a second hydrophobic surface (17"); and
(d) a gap (6) that is located between the first hydrophobic surface (17') of the bottom
layer (3) and the second hydrophobic surface (17") of the electrically conductive
material (15),
characterized in that the bottom layer (3) is configured as a flexible film that is sealingly attached
to the lower surface (48) of the body (47) along a circumference (40) of the flexible
bottom layer (3), the flexible bottom layer (3) being configured to be attracted and
spread over the uppermost surface (52) of a cartridge accommodation site (8) of the
digital microfluidics system (1) by the underpressure in the evacuation space (46)
of the digital microfluidics system (1), the disposable cartridge (2) thus being devoid
of a spacer (5) that is located in the gap (6) between the flexible bottom layer (3)
and the body (47) for defining a particular distance between said first hydrophobic
surface (17') and said second hydrophobic surface (17").
20. A disposable cartridge (2) that is configured for insertion into a cartridge accommodation
site (8) of a digital microfluidics system (1) according to Claim 1, the disposable
cartridge (2) comprising:
(a) a plane rigid cover plate (12) comprising a lower surface (48'), at least one
through hole (19) located at a loading site (41) and a second hydrophobic surface
(17");
(b) a bottom layer (3) with a first hydrophobic surface (17') that is impermeable
to liquids and that is configured as a working film for manipulating samples in liquid
droplets (23) thereon utilizing an electrode array (9) of the digital microfluidics
system (1) when the bottom layer (3) of the disposable cartridge (2) is placed over
said electrode array (9); and
(c) a gap (6) that is located between the first hydrophobic surface (17') of the bottom
layer (3) and the second hydrophobic surface (17") of the rigid cover plate (12),
characterized in that the bottom layer (3) is configured as a flexible film that is sealingly attached
to the lower surface (48') of the rigid cover plate (12) along a circumference (40)
of the flexible bottom layer (3), the flexible bottom layer (3) being configured to
be attracted and spread over the uppermost surface (52) of a cartridge accommodation
site (8) of the digital microfluidics system (1) by the underpressure in the evacuation
space (46) of the digital microfluidics system (1), the disposable cartridge (2) thus
being devoid of a spacer (5) that is located in the gap (6) between the flexible bottom
layer (3) and the second hydrophobic surface (17") of the rigid cover plate (12) for
defining a particular distance between said first hydrophobic surface (17') and said
second hydrophobic surface (17") of the rigid cover plate (12).
21. The disposable cartridge (2) of Claim 19 or 20, characterized in that the at least one through hole (19) of the body (47) or of the rigid cover plate (12)
is configured as a loading site (41) for transferring processing liquids, reagents
or samples into the gap (6).
22. The disposable cartridge (2) of Claim 19 or 20, characterized in that the cartridge (2) comprises a top layer (4) that provides the second hydrophobic
surface (17") and that is attached to the lower surface (48') of the rigid cover plate
(12) of the disposable cartridge (2).
23. The disposable cartridge (2) of Claim 19, characterized in that the cartridge (2) comprises an electrically conductive material (15) that is attached
to the lower surface (48') of the rigid cover plate (12), the electrically conductive
material (15) being configured to provide the lower surface (48') of the rigid cover
plate (12) with the second hydrophobic surface (17").
24. The disposable cartridge (2) of one of the Claims 13, 19 or 20, characterized in that the cartridge (2) further comprises a gasket (36) that is attached to the lower surface
(48) of the body (47) or to the lower surface (48') of the rigid cover plate (12),
and along a circumference (40) of the flexible bottom layer (3), the gasket (36) defining
a particular distance between said first hydrophobic surface (17') and said second
hydrophobic surface (17"), when the disposable cartridge (2) is placed over an electrode
array (9) of a cartridge accommodation site (8) of the digital microfluidics system
(1), if said digital microfluidics system (1) is equipped with suction holes (35)
in the electrode array (9), and if the flexible bottom layer (3) is aspirated by said
suction holes (35).
25. The disposable cartridge (2) of one of the Claims 13, 19 or 20, characterized in that the loading sites (41) are selected from a group comprising piercing sites (41'),
capillary orifices (41"), and pipetting orifices (41"').
26. The disposable cartridge (2) of Claim 19 or 20, characterized in that the lower surface (48') of the cover plate (12) is configured as the second hydrophobic
surface (17") that at least is permeable to ions.
27. The disposable cartridge (2) of one of the Claims 13, 19 or 20, characterized in that the flexible bottom layer (3) is configured as a single layer of a hydrophobic material.
28. The disposable cartridge (2) of one of the Claims 13, 19 or 20, characterized in that the flexible bottom layer (3) is configured as a single layer of electrically non-conductive
material, an upper surface of the flexible bottom layer (3) being treated to be a
hydrophobic surface (17).
29. The disposable cartridge (2) of one of the Claims 13, 19 or 20, characterized in that the flexible bottom layer (3) is configured as a laminate comprising a lower layer
and a hydrophobic upper layer, the lower layer being electrically non-conductive.
30. A method for manipulating samples in liquid droplets (23) that adhere to a hydrophobic
surface (17) of a working film, the method comprising the steps of:
(a) providing a disposable cartridge (2) with a first hydrophobic surface (17') of
a bottom layer (3), with a second hydrophobic surface (17"), and with a gap (6) between
the first and second hydrophobic surfaces (17',17"), the disposable cartridge (2)
further comprising a body (47) and/or a plane rigid cover plate (12), and at least
one through hole (19) for delivering processing liquids, reagents or samples to the
gap (6);
(b) providing a digital microfluidics system (1) with at least one electrode array
(9) that substantially extends in a first plane and that comprises a number of individual
electrodes (10) supported by a bottom substrate (11) and connected to a central control
unit (14) of the digital microfluidics system (1) for controlling the selection of
individual electrodes (10) of said electrode array (9) and for providing these electrodes
(10) with individual voltage pulses for manipulating said liquid droplets (23) on
said first hydrophobic surface (17') by electrowetting; and
(c) defining the gap (6) so that the hydrophobic surface (17") extends substantially
parallel to and in a distance to said first hydrophobic surface (17') of the bottom
layer (3),
characterized in that the method comprises the steps of:
(d) providing the bottom layer (3) as a flexible film that is sealingly attached to
the body (47) or to the plane rigid cover plate (12) of the disposable cartridge (2)
along a circumference (40) of the flexible bottom layer (3), the disposable cartridge
(2) thus being devoid of a spacer (5) that is located in the gap (6) for defining
a particular distance between said first hydrophobic surface (17') and said second
hydrophobic surface (17");
(e) placing the disposable cartridge (2) at a cartridge accommodation site (8) of
the base unit (7) of the digital microfluidics system (1);
(f) sealing in the cartridge accommodation site (8) an evacuation space (46) by a
gasket (36) or a number of seals (39,39') which are supported by an insertion guide
and closing means (25,30), the evacuation space (46) being defined by the flexible
bottom layer (3) of the disposable cartridge (8), the uppermost surface (52) of the
cartridge accommodation site (8) and the gasket (36) or the number of seals (39,39')
with the insertion guide and closing means (25,30); and
(g) creating in the evacuation space (46) an underpressure, which causes the flexible
bottom layer (3) of the disposable cartridge (2) that is placed on the cartridge accommodation
site (8) to be attracted and spread over the uppermost surface (52) of the cartridge
accommodation site (8).
31. The method of Claim 30, characterized in that defining the gap (6) is carried out by a gasket (36) that is dimensioned to define
a height of the gap (6) between the first hydrophobic surface (17') of the bottom
layer (3) and the second hydrophobic surface (17") of a disposable cartridge (2).
32. The method of Claim 30, characterized in that defining the gap (6) is carried out by a rigid spacer (5) on the electrode array
(9) of the digital microfluidics system (1) that is dimensioned to define a height
of the gap (6) between the first hydrophobic surface (17') of the bottom layer (3)
and the second hydrophobic surface (17") of a disposable cartridge (2).
33. The method of Claim 30, characterized in that the underpressure in the evacuation space (46) is created by a vacuum source (33),
which is controlled by the central control unit (14) of the digital microfluidics
system (1), and which is linked by a number of vacuum lines (34) to suction holes
(35) and/or and a vacuum space (50) for attraction of the flexible bottom layer (3)
of the disposable cartridge (2).
34. The method of Claim 30, characterized in that after manipulating liquid droplets (23) on said first hydrophobic surface (17') by
electrowetting and/or analyzing the sample in some of these liquid droplets (23),
the disposable cartridge (2) is taken from the cartridge accommodation site (8) of
the base unit (7) of the digital microfluidics system (1) and discarded.
1. Ein digitales Mikrofluidik-System (1) zum Manipulieren von Proben in Flüssigkeitströpfchen
in einem Spalt (6) zwischen einer ersten hydrophoben Oberfläche (17') einer unteren
Schicht (3) und einer zweiten hydrophoben Oberfläche (17") von zumindest einer Einweg-Kartusche
(2), wobei das digitale Mikrofluidik-System umfasst:
(a) eine Basiseinheit (7) mit mindestens einer Kartuschen-Aufnahme (8), die zur Aufnahme
einer Einweg-Kartusche (2) ausgebildet ist;
(b) ein Elektroden-Array (9), der an der mindestens einen Kartuschen-Aufnahme (8)
der Basiseinheit (7) angebracht ist, wobei der Elektroden-Array (9) gestützt ist durch
ein unteres Substrat (11), sich im Wesentlichen in einer ersten Ebene erstreckt und
eine Anzahl individueller Elektroden (10) umfasst; und
(c) eine zentrale Steuereinheit (14) zum Steuern der Auswahl der individuellen Elektroden
des Elektroden-Arrays (9) und zum Versorgen dieser Elektroden (10) mit individuellen
Spannungs-Impulsen zum Manipulieren von Flüssigkeitströpfchen (23) innerhalb des Spalts
(6) der Kartusche (2) durch Elektrowetting,
wobei das digitale Mikrofluidik-System (1) weiter umfasst:
(d) eine Anzahl von Sauglöchern (35), welche das Elektroden-Array (9) und/oder das
untere Substrat (11) durchdringen und die an der mindestens einen Kartuschen-Aufnahme
(8) der Basiseinheit (7) angeordnet sind;
(e) eine Vakuum-Quelle (33) zum Aufbauen eines Unterdrucks in mindestens einem Evakuierungsraum
(46) und/oder einem Vakuumraum (50); und
(f) eine Anzahl von Vakuumleitungen (34), welche die Sauglöcher (35) und/oder den
Vakuumraum (50) mit der Vakuum-Quelle (33) verbinden;
dadurch gekennzeichnet, dass
ein Dichtungsring (36) oder eine Anzahl von Dichtungen (39, 39') in der Kartuschen-Aufnahme
(8) den Evakuierungsraum (46) abdichten, wenn eine Einweg-Kartusche (2) in der mindestens
einen Kartuschen-Aufnahme (8) angeordnet ist, wobei der Evakuierungsraum definiert
ist durch eine flexible untere Schicht (3) einer Einweg-Kartusche (2), einer obersten
Oberfläche (52) der Kartuschen-Aufnahme (8) und den Dichtungsring (36) oder die Dichtungen
(39, 39'), die durch eine Einschubführung und Schliessmittel (25, 30) gestützt sind;
und dass
Der Unterdruck in dem Evakuierungsraum (46) bewirkt, dass die flexible untere Schicht
(3) der Einweg-Kartusche (2), die in der Kartuschen-Aufnahme (8) angeordnet ist, angezogen
und über die oberste Oberfläche (52) der Kartuschen-Aufnahme (8) des digitalen Mikrofluidik-Systems
(1) ausgebreitet wird.
2. Das digitale Mikrofluidik-System (1) nach Anspruch 1, dadurch gekennzeichnet, dass der Dichtungsring (36) dafür dimensioniert ist, eine Höhe des Spalts (6) zwischen
der ersten hydrophoben Oberfläche (17') der unteren Schicht (3) und der zweiten hydrophoben
Oberfläche (17") einer Einweg-Kartusche (2) festzulegen.
3. Das digitale Mikrofluidik-System (1) nach Anspruch 1, dadurch gekennzeichnet, dass das Elektroden-Array (9) des digitalen Mikrofluidik-Systems (1) ein starres Distanzstück
(5) umfasst, welches dafür dimensioniert ist, eine Höhe des Spalts (6) zwischen der
ersten hydrophoben Oberfläche (17') der unteren Schicht (3) und der zweiten hydrophoben
Oberfläche (17") einer Einweg-Kartusche (2) festzulegen.
4. Das digitale Mikrofluidik-System (1) nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass die Sauglöcher (35) so ausgelegt sind, dass sie in Saugkanäle (51) münden, wobei
die Saugkanäle (51) in der obersten Oberfläche (52) der Kartuschen-Aufnahme (8) des
digitalen Mikrofluidik-Systems (1) angeordnet sind.
5. Das digitale Mikrofluidik-System (1) nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass die Sauglöcher (35) so ausgelegt sind, dass sie in einen Vakuum-Raum (50) münden,
der an der Kartuschen-Aufnahme (8) und unter dem Elektroden-Array (9) im unteren Substrat
(11) angeordnet ist, wobei der Vakuum-Raum (50) mit der Vakuum-Quelle (33) des digitalen
Mikrofluidik-Systems (1) durch mindestens eine der Vakuum-Leitungen (34) verbunden
ist.
6. Das digitale Mikrofluidik-System (1) nach einem der vorangehenden Ansprüche, dadurch gekennzeichnet, dass die oberste Oberfläche (52) der Kartuschen-Aufnahme (8) eine dielektrische Schicht
(24) umfasst, welche das Elektroden-Array (9) bedeckt, wobei die dielektrische Schicht
(24) an den Orten der Sauglöcher (35) der Basiseinheit (7) Löcher hat.
7. Das digitale Mikrofluidik-System (1) nach einem der Ansprüche 1 oder 2, dadurch gekennzeichnet, dass der Dichtungsring (36) dauerhaft an dem Elektroden-Array (9) einer Kartuschen-Aufnahme
(8) der Basiseinheit (7) des digitalen Mikrofluidik-Systems (1) befestigt ist.
8. Das digitale Mikrofluidik-System (1) nach Anspruch 6, dadurch gekennzeichnet, dass der Dichtungsring (36) dauerhaft an der dielektrischen Schicht (24) befestigt ist,
welche dauerhaft das Elektroden-Array (9) einer Kartuschen-Aufnahme (8) des digitalen
Mikrofluidik-Systems (1) bedeckt.
9. Das digitale Mikrofluidik-System (1) nach Anspruch 6, dadurch gekennzeichnet, dass der Dichtungsring (36) dauerhaft am unteren Substrat (11) befestigt ist, welches
das Elektroden-Array (9) trägt, wobei die dielektrische Schicht (24) dauerhaft das
untere Substrat (11), das Elektroden-Array (9) und den Dichtungsring (36) bedeckt.
10. Das digitale Mikrofluidik-System (1) nach einem der vorangehenden Ansprüche, dadurch gekennzeichnet, dass die Basiseinheit (7) eine Einschubführung (25) umfasst, die als Rahmen ausgeführt
ist, welcher dafür bemessen ist, eine Einweg-Kartusche (2) darin aufzunehmen.
11. Das digitale Mikrofluidik-System (1) nach einem der Ansprüche 3 bis 10, dadurch gekennzeichnet, dass die Basiseinheit (7) ein Schliessmittel (30) umfasst, welches als eine Druckplatte
ausgebildet ist für das Anpressen einer Einweg-Kartusche (2) an das starre Distanzstück
(5) des Elektroden-Arrays (9) des digitalen Mikrofluidik-Systems (1).
12. Das digitale Mikrofluidik-System (1) nach einem der vorangehenden Ansprüche, dadurch gekennzeichnet, dass die Basiseinheit (7) eine Klemme (37) umfasst, welche dazu ausgebildet ist eine Einweg-Kartusche
(2) an einer gewünschten Position einer Kartuschen-Aufnahme (8) der Basiseinheit (7)
festzuhalten.
13. Eine Einweg-Kartusche (2), welche für das Einsetzen in eine Kartuschen-Aufnahme (8)
eines digitalen Mikrofluidik-Systems (1) nach Anspruch 1 ausgebildet ist, wobei die
Einweg-Kartusche (2) umfasst:
(a) einen Körper (47) mit mindestens einer Kammer (21), dafür ausgebildet darin Prozess-Flüssigkeiten,
Reagenzien oder Proben zu halten, wobei mindestens eine der Kammern (21) ein Durchgangsloch
(19) umfasst, um zumindest etwas von ihrem Inhalt auszugeben;
(b) eine untere Schicht (3) mit einer ersten hydrophoben Oberfläche (17') die für
Flüssigkeiten undurchlässig ist und die als Arbeitsfilm für das Manipulieren von Proben
in Flüssigkeitströpfchen (23) gestaltet ist, auf die ein Elektroden-Array (9) des
digitalen Mikrofluidik-Systems (1) angewendet wird, wenn die untere Schicht (3) der
Einweg-Kartusche (2) über dem Elektroden-Array (9) platziert ist;
(c) eine obere Schicht (4) mit einer zweiten hydrophoben Oberfläche (17"), die an
einer unteren Oberfläche (48) des Körpers (47) der Einweg-Kartusche (2) angebracht
ist und die zumindest für Ionen durchlässig ist; und
(d) ein Spalt (6) der sich zwischen der ersten hydrophoben Oberfläche (17') der unteren
Schicht (3) und der zweiten hydrophoben Oberfläche (17") der oberen Schicht (4) befindet,
dadurch gekennzeichnet, dass
die untere Schicht (3) als flexibler Film ausgebildet ist, der dichtend an der oberen
Schicht (4) oder am Körper (47) entlang einem Umfang (40) der flexiblen unteren Schicht
(3) angebracht ist, wobei die flexible untere Schicht (3) dazu ausgebildet ist, durch
den Unterdruck im Evakuations-Raum (46) des digitalen Mikrofluidik-Systems (1) angezogen
und über die oberste Oberfläche (52) einer Kartuschen-Aufnahme (8) des digitalen Mikrofluidik-Systems
(1) ausgebreitet zu werden, wodurch die Einweg-Kartusche (2) frei von einem Distanzstück
(5) ist, das sich in dem Spalt (6) zwischen der flexiblen unteren Schicht (3) und
der oberen Schicht (4) befindet zum Festlegen einer bestimmten Distanz zwischen der
ersten hydrophoben Oberfläche (17') und der zweiten hydrophoben Oberfläche (17").
14. Die Einweg-Kartusche (2) nach Anspruch 13, dadurch gekennzeichnet, dass die obere Schicht (4) dazu ausgebildet ist, eine Abdichtung zwischen einem unteren
Ende von zumindest einer Kammer (21) und dem Spalt (6) vorzusehen, wobei die obere
Schicht (4) Beladestellen (41) zum Übertragen von Prozess-Flüssigkeiten, Reagenzien
oder Proben in den Spalt (6) umfasst.
15. Die Einweg-Kartusche (2) nach Anspruch 14, dadurch gekennzeichnet, dass die Einweg-Kartusche (2) mindestens einen Kolben (42) umfasst, der in jedem Fall
so konfiguriert ist, dass er innerhalb einer Kammer (21) manuell oder durch ein Betätigungselement
(38) beweglich ist, um den Inhalt der entsprechenden Kammer (21) gegen eine entsprechende
Beladstelle (41) der oberen Schicht (4) zu drücken.
16. Die Einweg-Kartusche (2) nach Anspruch 14, dadurch gekennzeichnet, dass eine elastische Schicht (44) dichtend an einer oberen Oberfläche (49) des Körpers
(47) der Einweg-Kartusche (2) angebracht ist, wobei die elastische Schicht ausgebildet
ist mindestens eine der Kammern (21) gegen die obere Oberfläche (49) abzudichten.
17. Die Einweg-Kartusche (2) nach Anspruch 14, dadurch gekennzeichnet, dass die Einweg-Kartusche (2) weiter eine ebene, starre Deckplatte (12) umfasst, die an
der unteren Oberfläche (48) des Körpers (47) der Einweg-Kartusche (2) angebracht ist,
wobei die obere Schicht (4) an der starren Deckplatte (12) angebracht ist, wobei die
starre Deckplatte (12) an Beladestellen (41) der oberen Schicht (4) angeordnete Durchgangslöcher
(19) umfasst.
18. Die Einweg-Kartusche (2) nach Anspruch 14, dadurch gekennzeichnet, dass die Einweg-Kartusche (2) als plattenähnliche Struktur mit einer unteren Oberfläche
(48) gestaltet ist, wobei in jedem Fall die Kammern (21) mit einem Durchgangsloch
(19) an Durchstichstellen (41') oder kapillaren Öffnungen (41") zu der unteren Oberfläche
(48) führen.
19. Eine Einweg-Kartusche (2), die für das Einsetzen in eine Kartuschen-Aufnahme (8) eines
digitalen Mikrofluidik-Systems (1) nach Anspruch 1 ausgebildet ist, wobei die Einweg-Kartusche
(2) umfasst:
(a) einen Körper (47) mit einer unteren Oberfläche (48), einer oberen Oberfläche (49)
und mindestens einem Durchgangsloch (19);
(b) eine untere Schicht (3) mit einer ersten hydrophoben Oberfläche (17'), die undurchlässig
ist für Flüssigkeiten und die als Arbeitsfilm für das Manipulieren von Proben in Flüssigkeitströpfchen
(23) gestaltet ist, auf die ein Elektroden-Array (9) des digitalen Mikrofluidik-Systems
(1) angewendet wird, wenn die untere Schicht (3) der Einweg-Kartusche (2) über dem
Elektroden-Array (9) platziert ist;
(c) ein elektrisch leitendes Material (15), das an der unteren Oberfläche (48) des
Körpers (47) angebracht ist wobei das elektrisch leitendes Material (15) dazu ausgelegt
ist, die untere Oberfläche (48) des Körpers (47) mit einer zweiten hydrophoben Oberfläche
(17") zu versehen; und
(d) ein Spalt (6), der sich zwischen der ersten hydrophoben Oberfläche (17') der unteren
Schicht (3) und der zweiten hydrophoben Oberfläche (17") des elektrisch leitenden
Materials (15) befindet,
dadurch gekennzeichnet, dass
die untere Schicht (3) als flexibler Film ausgebildet ist, der dichtend an der unteren
Oberfläche (48) des Körpers (47) entlang einem Umfang der flexiblen unteren Schicht
(3) angebracht ist, wobei die flexible untere Schicht (3) dazu ausgelegt ist, durch
den Unterdruck in dem Evakuations-Raum (46) des digitalen Mikrofluidik-Systems angezogen
zu werden und über die oberste Oberfläche (52) der Kartuschen-Aufnahme (8) des digitalen
Mikrofluidik-Systems (1) ausgebreitet zu werden, wodurch die Einweg-Kartusche (2)
frei von einem Distanzstück (5) ist, das sich in dem Spalt (6) zwischen der flexiblen
unteren Schicht (3) und dem Körper (47) befindet zur Festlegung einer bestimmten Distanz
zwischen der ersten hydrophoben Oberfläche (17') und der zweiten hydrophoben Oberfläche
(17").
20. Eine Einweg-Kartusche (2), die für das Einsetzen in eine Kartuschen-Aufnahme (8) eines
digitalen Mikrofluidik-Systems (1) nach Anspruch 1 ausgelegt ist, wobei die Einweg-Kartusche
umfasst:
(a) eine ebene, starre Deckplatte (12) umfassend eine untere Oberfläche (48'), mindestens
ein Durchgangsloch (19), das sich an einer Beladestelle (41) befindet, und eine zweite
hydrophobe Oberfläche (17");
(b) eine untere Schicht (3) mit einer ersten hydrophoben Oberfläche (17'), die undurchlässig
ist für Flüssigkeiten und die als Arbeitsfilm für das Manipulieren von Proben in Flüssigkeitströpfchen
(23) gestaltet ist, auf die ein Elektroden-Array (9) des digitalen Mikrofluidik-Systems
(1) angewendet wird, wenn die untere Schicht (3) der Einweg-Kartusche (2) über dem
Elektroden-Array (9) platziert ist; und
(c) ein Spalt (6), der sich zwischen der ersten hydrophoben Oberfläche (17') der unteren
Schicht (3) und der zweiten hydrophoben Oberfläche (17") der starren Deckplatte (12)
befindet,
dadurch gekennzeichnet, dass
dass die untere Schicht (3) als flexibler Film ausgebildet ist, der dichtend an der
untere Oberfläche (48') der starren Deckplatte (12) entlang einem Umfang (40) der
flexiblen unteren Schicht (3) befestigt ist, wobei die flexible untere Schicht (3)
dazu ausgelegt ist, angezogen zu werden und über die unterste Oberfläche (52) einer
Kartuschen-Aufnahme (8) des digitalen Mikrofluidik-Systems (1) ausgebreitet zu werden
durch den Unterdruck im Evakuations-Raum (46) des digitalen Mikrofluidik-Systems,
wodurch die Einweg-Kartusche (2) frei von einem Distanzstück (5) ist, welches sich
in dem Spalt (6) zwischen der flexiblem unteren Schicht (3) und der zweiten hydrophoben
Oberfläche (17") der starren Deckplatte (12) befindet zur Festlegung einer bestimmten
Distanz zwischen der ersten hydrophoben Oberfläche (17') und der zweiten hydrophoben
Oberfläche (17") der starren Deckplatte (12).
21. Die Einweg-Kartusche (2) nach Anspruch 19 oder 20, dadurch gekennzeichnet, dass das mindestens eine Durchgangsloch (19) des Körpers (47) oder der starren Deckplatte
(12) als Beladestelle (41) für das Übertragen von Prozess-Flüssigkeiten, Reagenzien
oder Proben in den Spalt (6) gestaltet ist.
22. Die Einweg-Kartusche (2) nach Anspruch 19 oder 20, dadurch gekennzeichnet, dass die Kartusche (2) eine obere Schicht (4) umfasst, welche die zweite hydrophobe Schicht
(17") zur Verfügung stellt und welche an der unteren Oberfläche (48') der starren
Deckplatte (12) der Einweg-Kartusche (2) angebracht ist.
23. Die Einweg-Kartusche (2) nach Anspruch 19, dadurch gekennzeichnet, dass die Kartusche (2) ein elektrisch leitendes Material (15) umfasst, das an der unteren
Oberfläche (48') der starren Deckplatte (12) angebracht ist, wobei das elektrisch
leitende Material (15) dazu ausgelegt ist, die untere Oberfläche (48') der starren
Deckplatte (12) mit der zweiten hydrophoben Oberfläche (17") zu versehen.
24. Die Einweg-Kartusche (2) nach einem der Ansprüche 13, 19 oder 20, dadurch gekennzeichnet, dass die Kartusche (2) weiter einen Dichtungsring (36) umfasst, der an der unteren Oberfläche
(48) des Körpers (47) oder an der unteren Oberfläche (48') der starren Deckplatte
(12) entlang einem Umfang (40) der flexiblen unteren Schicht (3) angebracht ist, wobei
der Dichtungsring (36) eine bestimmte Distanz zwischen der ersten hydrophoben Schicht
(17') und der zweiten hydrophoben Schicht (17") festlegt, wenn die Einweg-Kartusche
(2) über einem Elektroden-Array (9) einer Kartuschen-Aufnahme (8) des digitalen Mikrofluidik-Systems
(1) platziert wird, falls das digitale Mikrofluidik-System (1) mit Sauglöchern (37)
im Elektroden-Array (9) ausgerüstet ist, und falls die flexible untere Schicht (3)
durch die Sauglöcher angesaugt wird.
25. Die Einweg-Kartusche (2) nach einem der Ansprüche 13, 19 oder 20, dadurch gekennzeichnet, dass die Beladestellen (41) aus einer Gruppe ausgewählt sind, welche Durchstichstellen
(41'), kapillare Öffnungen (41") und Pipettier-Öffnungen (41"') umfasst.
26. Die Einweg-Kartusche (2) nach Anspruch 19 oder 20, dadurch gekennzeichnet, dass die untere Oberfläche (48') der Deckplatte (12) als die zweite hydrophobe Oberfläche
(17") ausgebildet ist, die zumindest für Ionen durchlässig ist.
27. Die Einweg-Kartusche (2) nach einem der Ansprüche 13, 19 oder 20, dadurch gekennzeichnet, dass die flexible untere Schicht (3) als eine einzelne Schicht eines hydrophoben Materials
ausgebildet ist.
28. Die Einweg-Kartusche (2) nach einem der Ansprüche 13, 19 oder 20, dadurch gekennzeichnet, dass die flexible untere Schicht (3) als eine einzelne Schicht eines elektrisch nicht-leitenden
Materials ausgebildet ist, wobei eine obere Oberfläche der flexiblen unteren Schicht
(3) dahingehend behandelt ist eine hydrophobe Oberfläche (17) zu sein.
29. Die Einweg-Kartusche (2) nach einem der Ansprüche 13, 19 oder 20, dadurch gekennzeichnet, dass die flexible untere Schicht (3) als Laminat, umfassend eine untere Schicht und eine
hydrophobe obere Schicht, ausgebildet ist, wobei die untere Schicht elektrisch nicht-leitend
ist.
30. Ein Verfahren zur Manipulation von Proben in Flüssigkeitströpfchen (23), welche an
einer hydrophoben Oberfläche (17) eines Arbeitsfilms anhaften, wobei das Verfahren
die Schritte umfasst:
(a) Bereitstellen einer Einweg-Kartusche (2) mit einer ersten hydrophoben Oberfläche
(17') einer unteren Schicht (3), mit einer zweiten hydrophoben Oberfläche (17") und
mit einem Spalt (6) zwischen der ersten und der zweiten hydrophoben Oberfläche (17',
17"), wobei die Einweg-Kartusche (2) weiter einen Körper (47) und/oder eine ebene,
starre Deckplatte (12) umfasst, und zumindest ein Durchgangsloch (19) für das Abgeben
von Prozess-Flüssigkeiten, Reagenzien oder Proben an den Spalt (6);
(b) Bereitstellen eines digitalen Mikrofluidik-Systems (1) mit mindestens einem Elektroden-Array
(9), das sich im Wesentlichen in einer ersten Ebene ausdehnt und das eine Anzahl von
einzelnen, von einem unteren Substrat (11) gestützten Elektroden (10) umfasst und
das mit einer zentralen Steuereinheit (14) des digitalen Mikrofluidik-Systems (1)
verbunden ist zur Steuerung der Auswahl einzelner Elektroden (10) des Elektroden-Arrays
(9) und zur Versorgung dieser Elektroden (10) mit individuellen Spannungs-Impulsen
zur Manipulation der Flüssigkeitströpfchen (23) auf der ersten hydrophoben Oberfläche
(17') durch Elektrowetting; und
(c) Festlegen des Spalts (6), so dass die hydrophobe Oberfläche (17") sich im Wesentlichen
parallel zu und in einem Abstand von der ersten hydrophoben Oberfläche (17') der unteren
Schicht (3) erstreckt,
dadurch gekennzeichnet, dass das Verfahren die Schritte umfasst:
(d) Bereitstellen der unteren Schicht (3) als einen flexiblen Film, der dichtend am
Körper (47) oder der ebenen, starren Deckplatte (12) der Einweg-Kartusche (2) entlang
einem Umfang (40) der flexiblen unteren Schicht (3) angebracht ist, wodurch die Einweg-Kartusche
(2) frei von einem Distanzstück (5) ist, das sich in dem Spalt (6) befindet zur Festlegung
einer bestimmten Distanz zwischen der ersten hydrophoben Oberfläche (17') und der
zweiten hydrophoben Oberfläche (17");
(e) Platzieren der Einweg-Kartusche (2) an einer Kartuschen-Aufnahme (8) der Basiseinheit
(7) des digitalen Mikrofluidik-Systems (1);
(f) Abdichten eines Evakuations-Raums (46) in der Kartuschen-Aufnahme (8) durch einen
Dichtungsring (36) oder eine Anzahl von Dichtungen (39, 39'), welche durch eine Einschub-Führung
und Schliessmitteln (25, 30) getragen sind, wobei der Evakuationsraum (46) durch eine
flexible untere Schicht (3) der Einweg-Kartusche (2), die oberste Oberfläche (52)
der Kartuschen-Aufnahme (8) und den Dichtungsring (36) oder die Anzahl Dichtungen
(39, 39') mit Einschub-Führung und Schliessmitteln (25, 36) festgelegt ist; und
(g) im Evakuations-Raum (46) Erzeugen eines Unterdrucks, der bewirkt, dass die flexible
untere Schicht (3) der Einweg-Kartusche (2), die auf der Kartuschen-Aufnahme (8) platziert
ist, angezogen und über die oberste Oberfläche (52) der Kartuschen-Aufnahme (8) ausgebreitet
wird.
31. Das Verfahren nach Anspruch 30, dadurch gekennzeichnet, dass das Festlegen des Spalts (6) durch einen Dichtungsring (36) ausgeführt wird, der
dimensioniert ist eine Höhe des Spalts (6) zwischen der ersten hydrophoben Oberfläche
(17') der unteren Schicht (3) und der zweiten hydrophoben Oberfläche (17") einer Einweg-Kartusche
(2) festzulegen.
32. Das Verfahren nach Anspruch 30, dadurch gekennzeichnet, dass das Festlegen des Spalts (6) durch ein starres Distanzstück (5) auf dem Elektroden-Array
(9) des digitalen Mikrofluidik-Systems (1) ausgeführt wird, das dimensioniert ist
eine Höhe des Spalts (6) zwischen der ersten hydrophoben Oberfläche (17') der unteren
Schicht (3) und der zweiten hydrophoben Oberfläche (17") einer Einweg-Kartusche (2)
festzulegen.
33. Das Verfahren nach Anspruch 30, dadurch gekennzeichnet, dass der Unterdruck im Evakuations-Raum (46) durch eine Vakuum-Quelle (33) erzeugt wird,
welche durch die zentrale Steuereinheit (14) des digitalen Mikrofluidik-Systems (1)
gesteuert wird, und welche durch eine Anzahl von Vakuum-Leitungen (34) mit Sauglöchern
(35) und/oder einem Vakuum-Raum (50) verbunden ist zum Anziehen der flexiblen unteren
Schicht (3) der Einweg-Kartusche (2).
34. Das Verfahren nach Anspruch 30, dadurch gekennzeichnet, dass nach Manipulieren von Flüssigkeitströpfchen (23) auf der ersten hydrophoben Oberfläche
(17') durch Elektrowetting und/oder Analysieren der Probe in einigen dieser Flüssigkeitströpfchen
(23), die Einweg-Kartusche (2) aus der Kartuschen-Aufnahme (8) der Basiseinheit (7)
des digitalen Mikrofluidik-Systems (1) entnommen und weggeworfen wird.
1. Système microfluidique numérique (1) permettant de manipuler des échantillons dans
des gouttelettes de liquide à l'intérieur d'un vide (6) entre une première surface
hydrophobe (17') d'une couche inférieure (3) et une deuxième surface hydrophobe (17")
d'au moins une cartouche jetable (2), le système microfluidique numérique (1) comprenant
:
a) une unité de base (7) avec au moins un site de réception de cartouche (8) qui est
configuré pour recevoir une cartouche jetable (2) ;
b) un réseau d'électrodes (9) situé au niveau du au moins un site de réception de
cartouche (8) de l'unité de base (7), le réseau d'électrodes (9) étant soutenu par
un substrat inférieur (11), s'étendant essentiellement dans un premier plan et comprenant
un certain nombre d'électrodes individuelles (10) ; et
c) une unité de commande centrale (14) permettant de commander la sélection des électrodes
individuelles (10) dudit réseau d'électrodes (9) et permettant d'alimenter ces électrodes
(10) avec des impulsions de tension individuelles pour manipuler les gouttelettes
de liquide (23) à l'intérieur du vide (6) de ladite cartouche (2) par électro-mouillage,
le système microfluidique numérique (1) comprenant en outre :
(d) un certain nombre de trous d'aspiration (35) qui pénètrent dans le réseau d'électrodes
(9) et/ou dans le substrat inférieur (11) et qui sont situés au niveau du au moins
un site de réception de cartouche (8) de l'unité de base (7) ;
(e) une source de vide (33) pour établir une dépression dans au moins un espace d'évacuation
(46) et espace de vide (50) ; et
(f) un certain nombre de lignes de vide (34) qui raccordent les trous d'aspiration
(35) et/ou l'espace de vide (50) à la source de vide (33) ;
caractérisé en ce qu'un joint d'étanchéité (36) ou un certain nombre de joints (39, 39'), lorsqu'une cartouche
jetable (2) est située au niveau du au moins un site de réception de cartouche (8),
assurent l'étanchéité dans ledit site de réception de cartouche (8) de l'espace d'évacuation
(46), lequel est défini par une couche inférieure flexible (3) d'une cartouche jetable
(2), une surface supérieure (52) du site de réception de cartouche (8) et le joint
d'étanchéité (36) ou les joints (39, 39') qui sont soutenus par un guide d'insertion
et des moyens de fermeture (25, 30) ;
et
en ce que la dépression dans l'espace d'évacuation (46) oblige la couche inférieure flexible
(3) de la cartouche jetable (2) qui est placée au niveau du site de réception de cartouche
(8) à être attirée et à venir se coller sur la surface supérieure (52) du site de
réception de cartouche (8) du système microfluidique numérique (1).
2. Système microfluidique numérique (1) selon la revendication 1, caractérisé en ce que le joint d'étanchéité (36) est dimensionné pour définir une hauteur du vide (6) entre
la première surface hydrophobe (17') de la couche inférieure (3) et la deuxième surface
hydrophobe (17") d'une cartouche jetable (2).
3. Système microfluidique numérique (1) selon la revendication 1, caractérisé en ce que le réseau d'électrodes (9) du système microfluidique numérique (1) comprend un écarteur
rigide (5) qui est dimensionné pour définir une hauteur du vide (6) entre la première
surface hydrophobe (17') de la couche inférieure (3) et la deuxième surface hydrophobe
(17") d'une cartouche jetable (2).
4. Système microfluidique numérique (1) selon l'une des revendications 1 à 3, caractérisé en ce que les trous d'aspiration (35) sont configurés pour déboucher dans des canaux d'aspiration
(51), lesdits canaux d'aspiration (51) étant disposés dans la surface supérieure (52)
du site de réception de cartouche (8) du système microfluidique numérique (1).
5. Système microfluidique numérique (1) selon l'une des revendications 1 à 3, caractérisé en ce que les trous d'aspiration (35) sont configurés pour déboucher dans un espace de vide
(50), ledit espace de vide (50) étant agencé au niveau du site de réception de cartouche
(8) et sous le réseau d'électrodes (9) dans le substrat inférieur (11), ledit espace
de vide (50) étant raccordé à la source de vide (33) du système microfluidique numérique
(1) par au moins une des lignes de vide (34).
6. Système microfluidique numérique (1) selon l'une des revendications précédentes, caractérisé en ce que la surface supérieure (52) du site de réception de cartouche (8) comprend une couche
diélectrique (24) qui couvre le réseau d'électrodes (9), la couche diélectrique (24)
présentant des trous au niveau des emplacements des trous d'aspiration (35) de l'unité
de base (7).
7. Système microfluidique numérique (1) selon l'une des revendications 1 ou 2, caractérisé en ce que le joint d'étanchéité (36) est fixé de façon permanente au réseau d'électrodes (9)
d'un site de réception de cartouche (8) de l'unité de base (7) du système microfluidique
numérique (1).
8. Système microfluidique numérique (1) selon la revendication 6, caractérisé en ce que le joint d'étanchéité (36) est fixé à la couche diélectrique (24) qui couvre de façon
permanente le réseau d'électrodes (9) d'un site de réception de cartouche (8) du système
microfluidique numérique (1).
9. Système microfluidique numérique (1) selon la revendication 6, caractérisé en ce que le joint d'étanchéité (36) est fixé de façon permanente au substrat inférieur (11)
qui soutient le réseau d'électrodes (9), la couche diélectrique (24) couvrant en permanence
le substrat inférieur (11), le réseau d'électrodes (9) et le joint d'étanchéité (36).
10. Système microfluidique numérique (1) selon l'une des revendications précédentes, caractérisé en ce que l'unité de base (7) comprend un guide d'insertion (25) qui est configuré comme un
cadre qui est dimensionné pour y réceptionner une cartouche jetable (2).
11. Système microfluidique numérique (1) selon l'une des revendications 3 à 10, caractérisé en ce que l'unité de base (7) comprend un moyen de fermeture (30) qui est configuré comme une
plaque de pressage pour presser une cartouche jetable (2) contre l'écarteur rigide
(5) du réseau d'électrodes (9) du système microfluidique numérique (1).
12. Système microfluidique numérique (1) selon l'une des revendications précédentes, caractérisé en ce que l'unité de base (7) comprend un dispositif de serrage (37) qui est configuré pour
fixer une cartouche jetable (2) à une position souhaitée d'un site de réception de
cartouche (8) de l'unité de base (7).
13. Cartouche jetable (2) qui est configurée pour être insérée dans un site de réception
de cartouche (8) d'un système microfluidique numérique (1) selon la revendication
1, la cartouche jetable (2) comprenant :
(a) un corps (47) avec au moins un compartiment (21) configuré pour contenir à l'intérieur
des liquides de traitement, des réactifs ou des échantillons, au moins l'un desdits
compartiments (21) comprenant un orifice (19) pour délivrer au moins un peu de son
contenu ;
(b) une couche inférieure (3) avec une première surface hydrophobe (17') qui est imperméable
aux liquides et qui est configurée comme un film de travail pour manipuler des échantillons
dans des gouttelettes de liquide (23) à l'aide d'un réseau d'électrodes (9) du système
microfluidique numérique (1) lorsque la couche inférieure (3) de la cartouche jetable
(2) est placée sur ledit réseau d'électrodes (9) ;
(c) une couche supérieure (4) avec une deuxième surface hydrophobe (17") qui est fixée
à une surface inférieure (48) du corps (47) de la cartouche jetable (2) et qui est
au moins perméable aux ions ; et
(d) un vide (6) qui est situé entre la première surface hydrophobe (17') de la couche
inférieure (3) et la deuxième surface hydrophobe (17") de la couche supérieure (4),
caractérisé en ce que la couche inférieure (3) est configurée sous la forme d'un film flexible qui est
fixé hermétiquement à la couche supérieure (4) ou au corps (47) le long d'une circonférence
(40) de la couche inférieure flexible (3), la couche inférieure flexible (3) étant
configurée pour être attirée et venir se coller sur la surface supérieure (52) d'un
site de réception de cartouche (8) du système microfluidique numérique (1) par la
dépression créée dans l'espace d'évacuation (46) du système microfluidique numérique
(1), la cartouche jetable (2) étant de ce fait dépourvue d'un écarteur (5) qui est
situé dans le vide (6) entre la couche inférieure flexible (3) et la couche supérieure
(4) pour définir une distance particulière entre ladite première surface hydrophobe
(17') et ladite deuxième surface hydrophobe (17").
14. Cartouche jetable (2) selon la revendication 13, caractérisée en ce que la couche supérieure (4) est configurée pour assurer l'étanchéité entre une extrémité
inférieure d'au moins un compartiment (21) et le vide (6), la couche supérieure (4)
comprenant des sites de chargement (41) pour transférer les liquides de traitement,
les réactifs ou les échantillons dans le vide (6).
15. Cartouche jetable (2) selon la revendication 14, caractérisée en ce que la cartouche jetable (2) comprend au moins un piston (42) qui est configuré dans
chaque cas pour être déplacé dans un compartiment (21) manuellement ou par le biais
d'un élément d'actionnement (38) pour presser le contenu du compartiment respectif
(21) contre un site de chargement respectif (41) de la couche supérieure (4).
16. Cartouche jetable (2) selon la revendication 14, caractérisée en ce qu'une surface supérieure (49) du corps (47) de la cartouche jetable (2) est appliquée
de façon étanche sur une couche élastique (44) qui est configurée pour étanchéifier
au moins un des compartiments (21) contre ladite surface supérieure (49).
17. Cartouche jetable (2) selon la revendication 14, caractérisée en ce que la cartouche jetable (2) comprend en outre une plaque de protection rigide plane
(12) qui est fixée à la surface inférieure (48) du corps (47) de la cartouche jetable
(2), la couche supérieure (4) étant fixée à ladite plaque de protection rigide (12),
laquelle plaque de protection rigide (12) comprenant des orifices (19) situés au niveau
des sites de chargement (41) de la couche supérieure (4).
18. Cartouche jetable (2) selon la revendication 14, caractérisée en ce que la cartouche jetable (2) est configurée sous la forme d'une structure de type plaque
avec une surface inférieure (48), dans chaque cas les compartiments (21) conduisant
à ladite surface inférieure (48) avec un orifice (19) au niveau de sites de perçage
(41') ou d'orifices capillaires (41").
19. Cartouche jetable (2) qui est configurée pour être insérée dans un site de réception
de cartouche (8) d'un système microfluidique numérique (1) selon la revendication
1, la cartouche jetable (2) comprenant :
(a) un corps (47) avec une surface inférieure (48), une surface supérieure (49) et
au moins un orifice (19) ;
(b) une couche inférieure (3) avec une première surface hydrophobe (17') qui est imperméable
aux liquides et qui est configurée comme un film de travail pour y manipuler dessus
des échantillons dans des gouttelettes de liquide (23) à l'aide d'un réseau d'électrodes
(9) du système microfluidique numérique (1) lorsque la couche inférieure (3) de la
cartouche jetable (2) est placée sur ledit réseau d'électrodes (9) ;
(c) un matériau électroconducteur (15) fixé à la surface inférieure (48) du corps
(47), le matériau électroconducteur (15) étant configuré pour fournir à la surface
inférieure (48) du corps (47) une deuxième surface hydrophobe (17") ; et
(d) un vide (6) qui est situé entre la première surface hydrophobe (17') de la couche
inférieure (3) et la deuxième surface hydrophobe (17") du matériau électroconducteur
(15),
caractérisée en ce que la couche inférieure (3) est configurée sous la forme d'un film flexible qui est
fixé de façon hermétique à la surface inférieure (48) du corps (47) le long d'une
circonférence (40) de la couche inférieure flexible (3), la couche inférieure flexible
(3) étant configurée pour être attirée et venir se coller sur la surface supérieure
(52) d'un site de réception de cartouche (8) d'un système microfluidique numérique
(1) par la dépression dans l'espace d'évacuation (46) du système microfluidique numérique
(1), la cartouche jetable (2) étant de ce fait dépourvue d'un écarteur (5) qui est
situé dans le vide (6) entre la couche inférieure flexible (3) et le corps (47) pour
définir une distance particulière entre ladite première surface hydrophobe (17') et
ladite deuxième surface hydrophobe (17").
20. Cartouche jetable (2) qui est configurée pour être insérée dans un site de réception
de cartouche (8) d'un système microfluidique numérique (1) selon la revendication
1, la cartouche jetable (2) comprenant :
(a) une plaque de protection rigide plane (12) comprenant une surface inférieure (48'),
au moins un orifice (19) situé au niveau d'un site de chargement (41) et une deuxième
surface hydrophobe (17") ;
(b) une couche inférieure (3) avec une première surface hydrophobe (17') qui est imperméable
aux liquides et qui est configurée sous la forme d'un film de travail pour manipuler
dessus des échantillons dans des gouttelettes de liquide (23) à l'aide d'un réseau
d'électrodes (9) du système microfluidique numérique (1) lorsque la couche inférieure
(3) de la cartouche jetable (2) est placée sur ledit réseau d'électrodes (9) ; et
(c) un vide (6) qui est situé entre la première surface hydrophobe (17') de la couche
inférieure (3) et la deuxième surface hydrophobe (17") de la plaque de protection
rigide (12),
caractérisée en ce que la couche inférieure (3) est configurée sous la forme d'un film flexible qui est
fixé de façon hermétique à la surface inférieure (48') de la plaque de protection
rigide (12) le long d'une circonférence (40) de la couche inférieure flexible (3),
la couche inférieure flexible (3) étant configurée pour être attirée et venir se coller
sur la surface supérieure (52) d'un site de réception de cartouche (8) du système
microfluidique numérique (1) par la dépression dans l'espace d'évacuation (46) du
système microfluidique numérique (1), la cartouche jetable (2) étant de ce fait dépourvue
d'un écarteur (5) qui est situé dans le vide (6) entre la couche inférieure flexible
(3) et la deuxième surface hydrophobe (17") de la plaque de protection rigide (12)
pour définir une distance particulière entre ladite première surface hydrophobe (17')
et ladite deuxième surface hydrophobe (17") de la plaque de protection rigide (12).
21. Cartouche jetable (2) selon la revendication 19 ou 20, caractérisée en ce que le au moins un orifice (19) du corps (47) ou de la plaque de protection rigide (12)
est configuré sous la forme d'un site de chargement (41) pour transférer les liquides
de traitement, les réactifs ou les échantillons dans le vide (6).
22. Cartouche jetable (2) selon la revendication 19 ou 20, caractérisée en ce que la cartouche (2) comprend une couche supérieure (4) qui fournit la deuxième surface
hydrophobe (17") et qui est fixée à la surface inférieure (48') de la plaque de protection
rigide (12) de la cartouche jetable (2).
23. Cartouche jetable (2) selon la revendication 19, caractérisée en ce que la cartouche (2) comprend un matériau électroconducteur (15) qui est fixé à la surface
inférieure (48') de la plaque de protection rigide (12), le matériau électroconducteur
(15) étant configuré pour fournir à la surface inférieure (48') de la plaque de protection
rigide (12) la deuxième surface hydrophobe (17").
24. Cartouche jetable (2) selon l'une des revendications 13, 19 ou 20, caractérisée en ce que la cartouche (2) comprend en outre un joint d'étanchéité (36) qui est fixé à la surface
inférieure (48) du corps (47) ou à la surface inférieure (48') de la plaque de protection
rigide (12), et le long d'une circonférence (40) de la couche inférieure flexible
(3), le joint d'étanchéité (36) définissant une distance particulière entre ladite
première surface hydrophobe (17') et ladite deuxième surface hydrophobe (17"), lorsque
la cartouche jetable (2) est placée sur un réseau d'électrodes (9) d'un site de réception
de cartouche (8) du système microfluidique numérique (1), si ledit système microfluidique
numérique (1) est équipé de trous d'aspiration (35) dans le réseau d'électrodes (9)
et si la couche inférieure flexible (3) est aspirée par lesdits trous d'aspiration
(35).
25. Cartouche jetable (2) selon l'une des revendications 13, 19 ou 20, caractérisée en ce que les sites de chargement (41) sont sélectionnés parmi un groupe comprenant des sites
de perçage (41'), des orifices capillaires (41") et des orifices de pipetage (41"').
26. Cartouche jetable (2) selon la revendication 19 ou 20, caractérisée en ce que la surface inférieure (48') de la plaque de protection (12) est configurée comme
la deuxième surface hydrophobe (17") qui est au moins perméable aux ions.
27. Cartouche jetable (2) selon l'une des revendications 13, 19 ou 20, caractérisée en ce que la couche inférieure flexible (3) est configurée comme une couche unique de matériau
hydrophobe.
28. Cartouche jetable (2) selon l'une des revendications 13, 19 ou 20, caractérisée en ce que la couche inférieure flexible (3) est configurée comme une couche unique de matériau
électriquement non conducteur, une surface supérieure de la couche inférieure flexible
(3) étant traitée pour être une surface hydrophobe (17).
29. Cartouche jetable (2) selon l'une des revendications 13, 19 ou 20, caractérisée en ce que la couche inférieure flexible (3) est configurée sous la forme d'un stratifié comprenant
une couche inférieure et une couche supérieure hydrophobe, la couche inférieure étant
électriquement non conductrice.
30. Procédé pour manipuler des échantillons dans des gouttelettes de liquide (23) qui
collent à une surface hydrophobe (17) d'un film de travail, le procédé comprenant
les étapes consistant à :
(a) fournir une cartouche jetable (2) avec une première surface hydrophobe (17') d'une
couche inférieure (3), une deuxième surface hydrophobe (17") et un vide (6) entre
ladite première et ladite deuxième surfaces hydrophobes (17', 17"), la cartouche jetable
(2) comprenant en outre un corps (47) et/ou une plaque de protection rigide (12),
et au moins un orifice (19) pour amener les liquides de traitement, les réactifs ou
les échantillons dans le vide (6) ;
(b) fournir un système microfluidique numérique (1) avec au moins un réseau d'électrodes
(9) qui s'étend essentiellement dans un premier plan et qui comprend un certain nombre
d'électrodes individuelles (10) soutenues par un substrat inférieur (11) et raccordées
à une unité de commande centrale (14) du système microfluidique numérique (1) pour
commander la sélection d'électrodes individuelles (10) dudit réseau d'électrodes (9)
et pour alimenter ces électrodes (10) avec des impulsions de tension individuelles
pour manipuler lesdites gouttelettes de liquide (23) sur ladite première surface hydrophobe
(17') par électro-mouillage ; et
(c) définir le vide (6) de sorte que la surface hydrophobe (17") s'étende de façon
essentiellement parallèle et à distance de ladite première surface hydrophobe (17')
de la couche inférieure (3),
caractérisé en ce que le procédé comprend les étapes consistant à :
(d) fournir la couche inférieure (3) sous la forme d'un film flexible qui est fixé
de façon hermétique au corps (47) ou à la plaque de protection rigide plane (12) de
la cartouche jetable (2) le long d'une circonférence (40) de la couche inférieure
flexible (3), la cartouche jetable (2) étant de ce fait dépourvue d'un écarteur (5)
qui est situé dans le vide (6) pour définir une distance particulière entre ladite
première surface hydrophobe (17') et ladite deuxième surface hydrophobe (17") ;
(e) placer la cartouche jetable (2) sur un site de réception de cartouche (8) de l'unité
de base (7) du système microfluidique numérique (1) ;
(f) étanchéifier dans le site de réception de cartouche (8) un espace d'évacuation
(46) par un joint d'étanchéité (36) ou par un certain nombre de joints (39, 39') qui
sont soutenus par un guide d'insertion et des moyens de fermeture (25, 30), l'espace
d'évacuation (46) étant défini par la couche inférieure flexible (3) de la cartouche
jetable (2), la surface supérieure (52) du site de réception de cartouche (8) et le
joint d'étanchéité (36) ou le nombre de joints (39, 39') avec le guide d'insertion
et les moyens de fermeture (25, 30) ; et
(g) créer dans l'espace d'évacuation (46) une dépression qui oblige la couche inférieure
flexible (3) de la cartouche jetable (2) qui est placée sur le site de réception de
cartouche (8) à être attirée et à venir se coller sur la surface supérieure (52) du
site de réception de cartouche (8).
31. Procédé selon la revendication 30, caractérisé en ce que la définition du vide (6) s'effectue par un joint d'étanchéité (36) qui est dimensionné
pour définir une hauteur du vide (6) entre la première surface hydrophobe (17') de
la couche inférieure (3) et la deuxième surface hydrophobe (17") d'une cartouche jetable
(2).
32. Procédé selon la revendication 30, caractérisé en ce que la définition du vide (6) s'effectue par un écarteur rigide (5) sur le réseau d'électrodes
(9) du système microfluidique numérique (1) qui est dimensionné pour définir une hauteur
du vide (6) entre la première surface hydrophobe (17') de la couche inférieure (3)
et la deuxième surface hydrophobe (17") d'une cartouche jetable (2).
33. Procédé selon la revendication 30, caractérisé en ce que la dépression dans l'espace d'évacuation (46) est créée par une source de vide (33)
qui est commandée par l'unité de commande centrale (14) du système microfluidique
numérique (1) et qui est raccordée par un certain nombre de lignes de vide (34) aux
trous d'aspiration (35) et/ou un espace de vide (50) pour attirer la couche inférieure
flexible (3) de la cartouche jetable (2).
34. Procédé selon la revendication 30, caractérisé en ce qu'après avoir manipulé les gouttelettes de liquide (23) sur ladite première surface
hydrophobe (17') par électro-mouillage et/ou après avoir analysé l'échantillon dans
certaines de ces gouttelettes de liquide (23), la cartouche jetable (2) est retirée
du site de réception de cartouche (8) de l'unité de base (7) du système microfluidique
numérique (1) et est jetée.