[0001] The present invention relates to micro-fluidic device and methods to fill or "de-gas"
a micro-fluidic device.
[0002] Micro-fluidic devices nowadays are becoming more important, in particular in the
biotechnological field. A micro-fluidic device may be used, for example, in biotechnological
and pharmaceutical applications and in microchannel cooling systems in microelectronics
applications.
[0003] A micro-fluidic device comprises components and one or more micro-fluidic channels,
which are filled with a fluid, often a gas, used during the production process of
the micro-fluidic device. In order to make the micro-fluidic device ready for use,
the micro-fluidic device, more particular the components and micro-fluidic channels,
are to be filled with a fluid which is often a buffered aqueous solution.
[0004] One of the major issues when developing micro-fluidic devices (such as those required
for lab-on-a-chip applications) is to ensure that micro-fluidic channels are not blocked
by the presence of gas bubbles. One of the known approaches is to make use of micro-fluidic
channels based upon a semi-permeable material such as polydimethylsiloxane (PDMS).
PDMS is gas permeable and therefore if there are any gas bubbles they can be removed
by applying pressure for a prolonged period of time until degassing occurs. Gas bubbles
are eliminated after a period of sustained pressure. Such an approach has been confirmed
as being very effective.
[0005] A disadvantage of this approach is that the micro-fluidic device has to be sufficiently
transparent to allow visual inspection, and that the device has to be repeatedly visually
inspected to see if all trapped gas has been removed. This is obviously not desirable
as it requires a technician to repeatedly inspect the device and will therefore result
in a costly assay.
[0006] Another disadvantage of a visual check is that it also excludes some applications
where cartridges comprising the micro-fluidic device is enclosed within a non-transparent
reader device and visual access is impaired.
[0007] An attempt to automate the detection of defects, such as gas bubbles, is disclosed
in
US7161356B1. After filling or degassing of the micro-fluidic device, the resistance of the fluid
present in the micro-fluidic channels is measured by measuring of the voltage over
different fluidic openings, and compare the measured voltage with target voltages.
In case of defects, such as gas bubbles present in a micro-fluidic channel, the measured
and target voltages may differ.
[0008] A disadvantage of this test is that one can only check the status of the process
after the process has been completed. A further disadvantage is that gas bubbles which
are present in the micro-fluidic channel, but which are not present along the path
between the two fluidic openings, might not be detected.
[0009] It is an object of embodiments of the present invention to provide a good micro-fluidic
device. An advantage of this device can be that filling or degassing of the device
can be monitored. It is an advantage of some embodiments of the present invention
that the filling or degassing operation can be performed swiftly and in a short time.
According to some embodiments, the degassing or filling of the micro-fluidic device
may be performed, with reduced risk or even without the risk of damaging or rupturing
of the micro-fluidic device. It is an advantage of some embodiments of the present
invention that the filling or degassing operation can be monitored in real time. According
to some embodiments, the filling or degassing operation can optionally be stopped
or interrupted upon measurement of too large defects, too many defects, the observation
that defects are no longer present, measurement of overpressures and the like. According
to some embodiments of the present invention, the filling or degassing of the micro-fluidic
device may be controlled by a control signal provided by a controller being separate
from or being part of the micro-fluidic device. This control signal may be used to
e.g. interrupt or activate fluid pumping means, or e.g. to control the flow rate of
the fluid pumping means. Microfluidic pumps are known. It is an advantage of some
embodiments of the present invention that visual inspection of the progress of the
degassing or filling process may be avoided.
[0010] The above objective is accomplished by a method and device according to the present
invention.
[0011] Particular and preferred aspects of the invention are set out in the accompanying
independent and dependent claims. Features from the dependent claims may be combined
with features of the independent claims and with features of other dependent claims
as appropriate and not merely as explicitly set out in the claims.
[0012] According to a first aspect of the present invention, an arrangement of a micro-fluidic
device and a controller is provided. The microfluidic device comprises at least one
micro-fluidic channel for holding a fluid, the micro-fluidic channel having an interior
channel wall. The micro-fluidic device comprises a plurality of electrodes present
at the interior channel wall. The controller is adapted for measuring the value of
an electrical property of the fluid between at least two electrodes of the plurality
of electrodes and for generating an output signal dependent on the measured value
of the electrical property indicating whether a gas volume is present between the
at least two electrodes.
[0013] According to some embodiments of the present invention, at least part of the interior
channel wall, hence at least part of the device, may be made from semi-permeable material.
The part of the interior channel wall made from semi-permeable material enables gas
to pass through the interior channel wall, hence enables to evacuate gas from the
channel, e.g. by means of an overpressure created in the channel.
[0014] The micro-fluidic device may comprise a structure in which the at least one micro-fluidic
channel is provided. The structure may comprise a base structure, e.g. a glass or
plastic substrate, onto which electrodes are placed, such as e.g. by a lithographical
process. The part of the wall oriented in a direction extending from this base structure,
such as e.g. about perpendicular, and providing the so-called vertical walls is provided
by a second, vertical, structure, e.g. formed from e.g. PDMS. A top substrate, e.g.
a PDMS layer which is connected to the base structures via the vertical walls, e.g.
PDMS walls. The term channel wall hence is to be understood as any of the walls of
the channel, which are provided by different structures together providing the channel.
[0015] An advantage of the arrangement according to the present invention is obtained during
degassing of the micro-fluidic device, i.e. during provision of a fluid, such as a
buffer fluid, usually a liquid, in the micro-fluidic channel of the micro-fluidic
device.
[0016] As the plurality of electrodes, i.e. two electrodes or more, is present at the inner
wall of the micro-fluidic channel, the values measured between pairs of the electrodes
are dependent on the presence of the buffer fluid between these electrodes. If no
buffer fluid is present, the electrical property of the gas present in the micro-fluidic
channel is measured. When the micro-fluidic channel is completely filled with buffer
fluid between the electrodes, the electric property of the buffer fluid will be measured.
In case the buffer fluid holds a gas bubble between the electrodes (hence the micro-fluidic
device is not yet completely degassed), the value of the electric property measured
between the two electrodes will not be equal to the electric property of the buffer
fluid itself.
[0017] Thus by comparing the measured value of the electric property (e.g. by adapting the
controller in the appropriate way), measured between the electrodes, and comparing
this measured value with a predetermined value of this electric property of the buffer
fluid property (e.g. by adapting the controller in the appropriate way), a decision
with regard to the presence of defects, such as gas bubbles, and degree of filling
of the micro-fluidic channel between the electrodes can be made property (e.g. by
adapting the controller in the appropriate way).
[0018] As such, upon measuring preset values for the electric property between the electrodes,
the controller can be adapted to give a signal indicating the completeness of the
filling or degassing operation. This signal may be used to control, e.g. interrupt
pumping devices providing the buffer fluid to the micro-fluidic device.
[0019] The electric property measured may be an impedance between the electrodes. For example,
the capacitance or resistance between two electrodes may be measured and the controller
may be adapted accordingly.
[0020] It is understood that the type of buffer fluid and the dimensions of the micro-fluidic
channel at the section of the micro-fluidic channel encompassing the two electrodes
may influence the preset value of the electric property, which is to be measured between
two electrodes when the micro-fluidic channel is completely filled with buffer fluid.
Hence, the controller may comprise a look-up table, comprising for each pair of electrodes
the preset value to be measured, optionally in function of the buffer fluid.
[0021] In case a plurality of electrodes is distributed along the micro-fluidic channel,
the sequence of measured values between pairs of electrodes along the inner wall of
the micro-fluidic channel represents the progress of the degassing or "filling". Hence
the filling can be monitored. The last pair of electrodes for which a value equal
to the predetermined electric property of the buffer fluid is measured, is an indication
of where the buffer liquid has reached in the micro-fluidic channel. The pairs of
electrode being upstream of this last pair of electrodes for which a value equal to
the electric property of the buffer fluid is measured, may optionally provide a measured
value different from the value equal to the electric property of the buffer fluid.
At the location of these upstream pairs of electrodes, the buffer fluid may comprise
gas bubbles.
[0022] The electrodes are provided along the inner channel wall of the micro-fluidic channel.
Optionally the plurality of electrodes may be substantially equally distributed along
the inner wall of the micro-fluidic channel. The electrodes may be located on the
channel wall, providing zones on the micro-fluidic channel, or they may be partially
or completely sunken in the channel wall. In the later case, the surface of the electrode
used to contact the buffer fluid may be coplanar with the inner channel wall.
[0023] A plurality of electrodes may be provided along the complete longitudinal length
of the micro-fluidic channel or micro-fluidic channels. The centre-to-centre distance
between adjacent electrodes is optionally in the range of 10µm to 1000µm. So optionally
50 electrodes per millimetre along the longitudinal direction of the micro-fluidic
channel may be provided. The electrodes themselves may have any suitable shape, such
as being substantially rectangular or circular. The electrodes may have a with of
e.g. 1µm to 1000µm and a thickness of e.g. 10nm to 1000nm.
[0024] The controller may be adapted to monitor automatically the progress of the degassing
or filling of the micro-fluidic channel of the micro-fluidic device. The controller
may optionally be adapted to generate a signal indicative for the progress of the
filling or degassing, dependent upon the sequence of measured values, measured between
electrodes. This signal may be used to set the flow rate, the volume and/or pressure
of the buffer fluid provided to the micro-fluidic device by means of e.g. pumps. As
an example the flow rate can be set high at start of the filling or degassing procedure,
and be gradually or stepwise reduced to a relatively low flow rate when the filling
or degassing process reaches its end point.
[0025] It is also an advantage that, since the progress of filling or degassing, the controller
may give a fault signal, indicating than the filling or degassing process has not
correctly proceeded at that moment. The defect signal may be used to interrupt the
filling or degassing process. Because the micro-fluidic device may comprise "buffer
fluid sensitive" components, i.e. components which cannot be reused once they have
been in contact with buffer fluid, an early interruption of the filling or degassing
process may be advantageous in case the micro-fluidic device can still be emptied
and refilled, without the buffer fluid sensitive components having been in contact
with buffer fluid. As an example a hybridisation spot for DNA detection, being buffer
fluid sensitive components, may form part of the micro-fluidic device.
[0026] The micro-fluidic device may comprise more than one micro-fluidic channel, which
micro-fluidic channels may be linked one to the other for defining a complex labyrinth
of micro-fluidic channels. Optionally each of the micro-fluidic channels may be provided
with a plurality of electrodes, such that for each micro-fluidic channel, the progress
of the filling or degassing in this particular micro-fluidic channel may be monitored
and controlled. The micro-fluidic device may also comprise one or more components
having a particular function when the micro-fluidic device is used as e.g. a biosensor
device. Such components may be mixing chambers, reagent inlet openings, and alike.
The cross-flow geometries of channels may be designed or provided for exerting force
on a cell to flow through the channel. The device may be a device for performing RT(PCR),
a matrix device for quantifying multiple individual cells, a device with electrodes
for classifying cells via their electrical properties and alike.
[0027] The micro-fluidic device further comprises one or more fluidic openings. It is understood
that the plurality of electrodes are located within the micro-fluidic channel present
between these fluid openings.
[0028] The device according to the present invention has the advantage that there is no
longer a need for visual inspection of the degassing or filling rate, hence the filling
or degassing may be automated, even without the necessity of the presence of inspection
windows in the micro-fluidic device. The micro-fluidic device may be mounted in cartridges
that impair visual access as the present invention removes the need for visual access.
[0029] The semi-permeable material may be used to provide the base structure of the device.
As an example, the base structure may be made from polymethylsiloxane (PDMS). Alternatively
any other gas permeable and liquid impermeable material such as various fine porous
gels or polyethylene may be used.
[0030] Semi-permeable material is to be understood as being permeable for gasses, but impermeable
for liquids, in particular the buffer liquids to be used.
[0031] During the filling or degassing of the micro-fluidic device, gas bubbles may be formed
in one or more of the micro-fluidic channels. These defects may be found by the measured
values of the electric properties over the plurality of electrodes. As it is known
that maintaining a given fluid pressure will cause the gas to dissipate though the
semi-permeable material. Hence the controller, obtaining the measured values and comparing
these with the predetermined values, the controller may provide a control signal to
maintain the fluid pressure until e.g. the measured values meet the predetermined
values and/or for preset period in time.
[0032] According to some embodiments of the present invention, the plurality of electrodes
may comprise a plurality of electrode pairs, the controller being adapted for measuring
the electric property between the electrodes of each pair of electrodes.
[0033] Each pair may comprise a reference electrode and a probe electrode.
[0034] The perimeter of the micro-fluidic channel has a longitudinal direction (which is
identical to the flow direction of the fluid in the micro-fluidic channel) and may
have any suitable cross sectional shape in radial cross section, such as circular,
oval, rectangular or square or similar. The plurality of electrodes may be provided
at identical or different, even opposite positions relative to a radial cross section
of the micro-fluidic channel.
[0035] A radial cross section at a given position in longitudinal direction is to be understood
as a section according to a plane being perpendicular to the longitudinal direction
of the micro-fluidic channel at that given position along the longitudinal direction.
[0036] According to some embodiments of the present invention, the at least one micro-fluidic
channel may have a substantially rectangular radial cross section having two pairs
of mutually opposite sides, the plurality of electrodes baing present along the same
side of the radial cross sections.
[0037] It is understood that the radial cross sections of the micro-fluidic channel or micro-fluidic
channels along their longitudinal direction must not be identical all along the longitudinal
direction.
[0038] The electrodes may be provided using a large area electronics substrate, such as
a low temperature poly silicon substrate (LTPS).
[0039] According to some embodiments of the present invention, the micro-fluidic device
further may comprise an overpressure measuring device.
[0040] According to some embodiments of the present invention, the overpressure measuring
device may comprise at least one expansion chamber being separated from the at least
one micro-fluidic channel by means of a membrane , which membrane cooperates with
a sensor for generating a signal when the pressure over the membrane becomes larger
than a given threshold pressure.
[0041] As an example, two electrodes, e.g. 10µm wide electrodes are provided, and the impedance
between them is measured. The two electrodes may be coupled to a resistance meter.
Alternatively a transistor, such as an ISFET e.g. provided using LTPS technology could
be used. The resistance transistor channel may be measured and will change when the
gate comes into contact with the liquid, optionally a conductive solution. The pressure
of deformation should be less than the pressure required for device failure.
[0042] According to some embodiments of the present invention, the membrane may be adapted
to rupture when said threshold pressure is reached.
[0043] The sensor may be located within the expansion chamber. Upon rupture of the membrane,
the buffer fluid will contact the sensor, which contact may cause the signal of the
sensor to be generated.
[0044] According to some embodiments of the present invention, the membrane and sensor may
be in contact with each other when a fluid pressure less than the threshold pressure
is applied to the membrane, the contact between the membrane and sensor being interrupted
when a fluid pressure less than the threshold pressure is applied to the membrane
or vice versa.
[0045] The interruption of the contact may cause the signal of the sensor to be generated.
[0046] Upon receipt of the signal from the sensor by the controller, the filling or degassing
processes may be interrupted. The controller may further evaluate the measured values
of the plurality of electrodes to evaluate if the filling or degassing process is
completed, or if the overpressure at the sensor was caused by accidental pressure
build up during the process. In the later case, the controller may provide a signal
indicating an incomplete, incorrect filling or degassing process.
[0047] It is understood that in case the micro-fluidic device comprises more than one micro-fluidic
channel, optionally coupled to each other, a plurality of such overpressure measuring
devices may be provided, such as at least one per micro-fluidic channel of the micro-fluidic
device.
[0048] According to some embodiments of the present invention, the at least one micro-fluidic
channel may be provided using a substrate. The micro-fluidic device further may comprise
at least one of a valve or a pump, the at least one of a valve or a pump being integrated
in the substrate.
[0049] According to a second aspect of the present invention, a method for degassing a micro-fluidic
device is provided. The micro-fluidic device comprises at least one micro-fluidic
channel for holding a fluid.. The method comprises:
- providing a buffer fluid to the at least one micro-fluidic channel of the micro-fluidic
device;
- measuring a value of an electrical property of the fluid in the micro-fluidic channel;
- generating an output signal dependent on the measured value of the electrical property
indicating when a gas volume is present in the microfluidic channel.
[0050] The micro-fluidic channel may have an interior channel wall, at least part of the
interior channel wall, hence at least part of the micro-fluidic device, being made
from semi-permeable material. The at least part of the interior channel wall which
is made from semi-permeable material, enables gas to be removed or evacuated from
the channel by passing the gas through the semi-permeable material.
[0051] According to some embodiments of the present invention, the micro-fluidic channel
may have an interior channel wall. The micro-fluidic device may comprise a plurality
of electrodes present at the interior channel wall, the measuring step including measuring
between at least two of the plurality of electrodes.
[0052] According to some embodiments of the present invention, the output signal may be
used to determine the end of a degassing of the micro-fluidic device.
[0053] According to some embodiments of the present invention, the buffer fluid may be provided
to the micro-fluidic device by means of a pump (1910), the output signal being used
to control the pump.
[0054] According to some embodiments of the present invention, the output signal may be
used to control the flow rate of buffer fluid provided by the pump.
[0055] According to a third aspect of the present invention, a controller for controlling
a micro-fluidic device is provided. The micro-fluidic device comprises at least one
micro-fluidic channel for holding a fluid. The controller comprises:
- means for controlling provision of a buffer fluid to the at least one micro-fluidic
channel of the micro-fluidic device;
- means for measuring a value of an electrical property of the fluid in the micro-fluidic
channel;
- means for generating an output signal dependent on the measured value of the electrical
property indicating when a bubble is present between the at least two electrodes.
[0056] The micro-fluidic channel may have an interior channel wall, at least part of the
interior channel wall, hence at least part of the micro-fluidic device being made
from semi-permeable material. The at least part of the interior channel wall which
is made from semi-permeable material enables gas to be removed or evacuated from the
channel by passing the gas through the semi-permeable material.
[0057] A micro-fluidic device according to embodiments of the present invention may be used
in biotechnological or biomedical applications such as biosensors, rapid DNA separation
and sizing, cell manipulation and sorting, or in pharmaceutical applications, in particular
high-throughput combinatorial testing. A micro-fluidic device according to embodiments
of the present invention may also be used in microchannel cooling systems in microelectronics
applications.
[0058] The above and other characteristics, features and advantages of the present invention
will become apparent from the following detailed description, taken in conjunction
with the accompanying drawings, which illustrate, by way of example, the principles
of the invention. This description is given for the sake of example only, without
limiting the scope of the invention. The reference figures quoted below refer to the
attached drawings.
Fig. 1 is a schematical view of a part of a micro-fluidic device according to a first
embodiment of the present invention.
Fig. 2 shows a detail of the micro-fluidic device of Figure 1.
Fig. 3, Fig. 4 and Fig. 5 are radial and a longitudinal cross-sections of micro-fluidic
channels of part of a micro-fluidic device according to the first embodiment of the
present invention.
Fig. 6 is a schematical view of a circuitry in accordance with an embodiment of the
present invention for the detection of the gas bubble using the micro-fluidic device
as shown in Figure 2.
Fig. 7a and Fig. 7b shows a schematic view of a micro-fluidic device according to
the first embodiment of the present invention, comprising an overpressure measuring
device.
Fig. 8a and Fig. 8b shows a schematic view of an alternative micro-fluidic device
according to the first embodiment of the present invention, comprising an overpressure
measuring device.
Fig 9a, Fig 9b, Fig 9c, Fig 9d and Fig 9e show schematic views of a micro-fluidic
device during a degassing and filling process according to a second embodiment of
the present invention.
[0059] In the different figures, the same reference signs refer to the same or analogous
elements.
[0060] The present invention will be described with respect to particular embodiments and
with reference to certain drawings but the invention is not limited thereto but only
by the claims. Any reference signs in the claims shall not be construed as limiting
the scope. The drawings described are only schematic and are non-limiting. In the
drawings, the size of some of the elements may be exaggerated and not drawn on scale
for illustrative purposes.
[0061] Where the term "comprising" is used in the present description and claims, it does
not exclude other elements or steps. Where an indefinite or definite article is used
when referring to a singular noun e.g. "a" or "an", "the", this includes a plural
of that noun unless something else is specifically stated.
[0062] Furthermore, the terms first, second, third and the like in the description and in
the claims, are used for distinguishing between similar elements and not necessarily
for describing a sequence, either temporally, spatially, in ranking or in any other
manner. It is to be understood that the terms so used are interchangeable under appropriate
circumstances and that the embodiments of the invention described herein are capable
of operation in other sequences than described or illustrated herein.
[0063] Moreover, the terms top, bottom, over, under and the like in the description and
the claims are used for descriptive purposes and not necessarily for describing relative
positions. It is to be understood that the terms so used are interchangeable under
appropriate circumstances and that the embodiments of the invention described herein
are capable of operation in other orientations than described or illustrated herein.
[0064] Reference throughout this specification to "one embodiment" or "an embodiment" means
that a particular feature, structure or characteristic described in connection with
the embodiment is included in at least one embodiment of the present invention. Thus,
appearances of the phrases "in one embodiment" or "in an embodiment" in various places
throughout this specification are not necessarily all referring to the same embodiment,
but may. Furthermore, the particular features, structures or characteristics may be
combined in any suitable manner, as would be apparent to one of ordinary skill in
the art from this disclosure, in one or more embodiments.
[0065] Similarly it should be appreciated that in the description of exemplary embodiments
of the invention, various features of the invention are sometimes grouped together
in a single embodiment, figure, or description thereof for the purpose of streamlining
the disclosure and aiding in the understanding of one or more of the various inventive
aspects. This method of disclosure, however, is not to be interpreted as reflecting
an intention that the claimed invention requires more features than are expressly
recited in each claim. Rather, as the following claims reflect, inventive aspects
lie in less than all features of a single foregoing disclosed embodiment. Thus, the
claims following the detailed description are hereby expressly incorporated into this
detailed description, with each claim standing on its own as a separate embodiment
of this invention.
[0066] Furthermore, while some embodiments described herein include some but not other features
included in other embodiments, combinations of features of different embodiments are
meant to be within the scope of the invention, and form different embodiments, as
would be understood by those in the art. For example, in the following claims, any
of the claimed embodiments can be used in any combination.
[0067] Furthermore, some of the embodiments are described herein as a method or combination
of elements of a method that can be implemented by a processor of a computer system
or by other means of carrying out the function. Thus, a processor with the necessary
instructions for carrying out such a method or element of a method forms a means for
carrying out the method or element of a method. Furthermore, an element described
herein of an apparatus embodiment is an example of a means for carrying out the function
performed by the element for the purpose of carrying out the invention.
[0068] In the description provided herein, numerous specific details are set forth. However,
it is understood that embodiments of the invention may be practiced without these
specific details. In other instances, well-known methods, structures and techniques
have not been shown in detail in order not to obscure an understanding of this description.
[0069] The following terms or definitions are provided solely to aid in the understanding
of the invention.
[0070] Semi-permeable material is to be understood as a liquid permeable and gas impermeable
material, i.e. being permeable for gasses, but impermeable for liquids, in particular
the buffer liquids to be used.
[0071] Substantially planar is to be understood as lying in the same plane, within deviations,
which are in typical tolerances applicable for the related technical field.
[0072] Similarly, the term substantially rectangular or circular is to be understood as
being rectangular or circular, within deviations, which are in typical tolerances
applicable for the related technical field.
[0073] Also substantially equal distances is to be understood as distances being equal,
plus or minus deviations which are in typical tolerances applicable for the related
technical field. Typical deviations may be less than or equal to 30µm, even less than
or equal to 20µm, even less than 10µm such as in the range of 5µm to 10µm.
[0074] A micro-fluidic device 100 according to a first embodiment of the present invention
is shown schematically in Figure 1. The micro-fluidic device 100 comprises a structure
110. The structure comprises at least one, and in this particular case a plurality
of micro-fluidic channels 120 for holding and/or transporting a fluid, e.g. a gas
or a liquid. The micro-fluidic device 100 further comprises a plurality of fluidic
openings 130, of which two are shown in Figure 1. The micro-fluidic channels 120 visible
in Figure 1 show two gas volumes or gas bubbles 200. The micro-fluidic device is further
filled with a buffer liquid 210.
[0075] The device 100 with the plurality of fluidic openings 130 in figure 1 is purely given
as an example of a micro fluidic device.
[0076] This buffer fluid is typically a buffer liquid. The liquid can be either an aqueous
liquid or an oily liquid, e.g. an oil. If aqueous then it may be a buffered saline
solution. These include PBS (phosphate buffered saline), SSC (sodium chloride and
sodium citrate), and zwitterionic buffers, such as HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic
acid), HEPPS (3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid), Bis-Tris
(1,3-bis(tris(hydroxymethyl)methylamino)propane), MOPS (3-N-(morpholino)-propanesulfonic
acid), and electrophoresis Tris (tris(hydroxymethyl)-aminomethane) buffers, such as
Tris acetate EDTA (ethylenediamine tetraacetic acid), TBE (Tris base, boric acid,
EDTA), TT-SDS (tris tricine-sodium dodecyl sulfate) or TG-SDS (tris glycine-sodium
dodecyl sulfate).
[0077] The aqueous solution may also contain e.g. BCS (Bovine Calf Serum), BSA protein,
(growth factors such as VEGF).
[0078] A detail "A" of the micro-fluidic device 100 of Figure 1 is shown in Figure 2. The
micro-fluidic channel 120, in which one of the gas bubbles 200 is present, is shown
in detail in Figure 2. The micro-fluidic channel 120 has an interior channel wall
121. The micro-fluidic device 100 comprises a plurality of electrodes 300, present
at the interior channel wall 121. The micro-fluidic device 100 further comprises a
controller 400 for measuring the value of an electrical property of the fluid 500,
being either the gas 200 or the buffer liquid 210, between at least two electrodes
of the plurality of electrodes 300 and for generating an output signal dependent on
the measured value of the electrical property. The controller can be a separate item
from the micro-fluidic device or may be incorporated in it.
[0079] The channel with its channel wall may be provided by the additional of several layers
constituting the structure 110. As an example, a base structure, e.g. a glass or plastic
substrate is provided, onto which electrodes are provided. The vertical structures
that may be formed from e.g. PDMS, may provide the vertical walls of the channel.
A top substrate, e.g. a PDMS layer which is connected to the base structures via the
vertical walls, e.g. PDMS walls. The term channel wall hence is to be understood as
any of the walls of the channel, which may be provided by different structure parts
together providing the structure 110.
[0080] As an example, the base structure may be made from polymethylsiloxane (PDMS).
[0081] As shown in Figure 2, the plurality of electrodes 300 comprises a plurality of electrode
pairs 310, each pair comprising a reference electrode 311 and a probe electrode 312.
The controller 400 is adapted to measure an electrical property of the fluid 500,
which is present between the reference electrode 311 and the probe electrode 312.
[0082] The controller 400 is adapted to monitor e.g. the impedance between the electrodes
311 and 312 of each pair of electrodes 310 within the micro-fluidic device 100. Depending
on the frequency of the probe signal the impedance can be dominated by either a capacitive
contribution or a resistive contribution. The controller may include means or may
control means for measuring impedance between the electrodes 311 and 312. By measuring
the impedance between alternate electrodes the presence (or absence) of trapped gas
can be sensed, as gas, e.g. air, has typically a higher resistance than the buffer
fluid, e.g. saline water.
[0083] In the situation as shown in Figure 2, the resistance R
G measured over electrode pair 313 will be relatively high, since the resistance is
determined by the electrical resistance of the gas 200. The resistance R
L measured over electrode pair 314 will be low because the resistance is determined
by the fluid 210, e.g. a liquid that can be an electrolyte. Alternatively, the large
difference in capacitance between gas (e.g. air : ε = 1) and buffer fluid (e.g. water
: ε = 80) could also be exploited to determine the presence of the gas bubble 200,
e.g. by measuring the capacitance between the electrodes.
[0084] The controller 400 can be adapted to compare the impedances, e.g. resistances or
capacitances measured at each of the pairs of electrodes with a preset or predetermined
value indicating the presence of buffer fluid between the reference electrode 311
and probe electrode 312. In response to the comparison the controller 400 can be adapted
to monitor where gas is present along the longitudinal direction 122 of the micro-fluidic
channel 120.
[0085] The controller 400 can also be adapted to determine how much gas 200 remains in the
micro-fluidic device, and therefore how much additional fluid 210 is required to just
fill the micro-fluidic device and hence complete the degassing. This can be achieved
by summing all the locations where gas has been detected, i.e. the controller may
include a means for summing all the locations where measurements between the electrode
pairs indicate gas and not liquid. With this information, pumping devices coupled
to one of the fluidic openings 130 can be programmed to only deliver the required
amount of additional fluid, hence reducing the chances of rupturing the micro-fluidic
channels 120. The controller 400 may be adapted to control the pumping devices to
only deliver the required amount of additional fluid.
[0086] An embodiment of the present invention for realizing the plurality of electrodes
in the micro-fluidic channels and monitoring the impedance between the electrodes
is to use a large area electronics substrate with electrodes positioned in the branches,
for example use of low temperature polysilicon (LTPS) substrates, large area amorphous
silicon substrates, microcrystalline substrates with electrodes positioned in the
branches. In embodiments of the present invention monocrystalline substrates need
not be used.
[0087] As an example, the micro-fluidic channels 120 of the micro-fluidic device 100 may
have an average radial cross section area in the range of e.g. 90µm height and 150µm
width, or e.g. 10µm height and 10µm width, or e.g. up to 300µm height and up to e.g.
1000 µm width. The centre-to-centre distance D between adjacent electrodes is optionally
in the range of 10 µm to 1000µm, such as e.g. 20µm. So optionally 50 electrodes per
millimetre along the longitudinal direction of the micro-fluidic channel may be provided.
The electrodes themselves may have any suitable shape, such as being substantially
rectangular or circular. The width W of the electrodes may be e.g. 1 µm to 1000µm,
e.g. 10µm.
[0088] The plurality of electrodes 300 as shown in Figure 2 are located on the inner channel
wall 121, so they provide zones on the inner channel wall 121 having a minor thickness,
e.g. of about 100 nm to 200 nm thickness. Optionally the electrodes may be situated
on the top and bottom of the wall. The channel with its channel wall may be provided
by the additional of several layers. As an example, a base structure, e.g. a glass
or plastic substrate is provided, onto which electrodes are placed. The vertical structures
that may be formed from e.g. PDMS, may provide the vertical walls of the channel.
A top substrate, e.g. a PDMS layer which is connected to the base structures via the
vertical walls, e.g. PDMS walls. The term channel wall hence is to be understood as
any of the walls of the channel, which may be provided by different structures together
providing the channel. The PDMS wall and/or the PDMS layer can be a semi-permeable
material, hence providing at least a part of the interior channel wall being provided
from semi-permeable material.
[0089] Other alternative examples of setups of a distribution of the plurality of electrodes
along the longitudinal direction of the micro-fluidic channel are shown in Figure
3, Figure 4 and Figure 5.
[0090] In Figure 3, the reference electrodes 311 and the probe electrodes 312 of the pairs
of electrodes 310 are sunk into the wall 121 of the micro-fluidic channel. The micro-fluidic
channel 120, in this particular example has a perimeter having a substantially rectangular
radial cross section. The electrodes 311 may extend along the full width of the channel
120, as shown in Figure 3. The electrodes 311 and 312 have their surface 320 substantially
coplanar with the inner channel wall 121. The electrodes are positioned at identical
positions relative to the radial cross section. The rectangular cross section has
two pairs of mutually opposed sides, being a first pair of mutually opposed sides
710 and 711, and a second pair of mutually opposed sides 720 and 721. The electrodes
311 and 312 are all located at the same side, in this embodiment side 711.
[0091] In Figure 4, the reference electrodes 311 and the probe electrodes 312 of the pairs
of electrodes 310 are sunk into the wall 121 of the micro-fluidic channel. The micro-fluidic
channel 120, in this particular example, has a perimeter having a substantially rectangular
radial cross section. The electrodes 311 and 312 have their surface 320 substantially
coplanar with the inner channel wall 121. The electrodes are positioned at opposite
positions relative to the radial cross section, at opposite sides of the rectangular
perimeter. The reference electrode 311 and the probe electrode 312 of each pair of
electrodes 310 are mounted face to face along the longitudinal direction 122 of the
micro-fluidic channel 120.
[0092] In Figure 5, the reference electrodes 311 and the probe electrodes 312 of the pairs
of electrodes 310 are mounted on the wall 121 of the micro-fluidic channel. The micro-fluidic
channel 120, in this particular example, has a perimeter having a substantially circular
radial cross section. The electrodes are positioned at different positions relative
to the radial cross section. The adjacent electrodes are provided at a distance D
in longitudinal direction.
[0093] It is understood that there are many alternative setups for electrode distribution
included within the scope of the present invention. As an example, the micro-fluidic
channel may be provided with N reference electrodes, distributed along the channel
wall, and a M probe electrodes, M being larger than N. Each probe electrode may form
a pair with one of the N reference electrodes or more. In particular one common reference
electrode may exist at e.g. the liquid inlet where it is always in contact with the
liquid. The resistance of every other probe electrode could be measured with respect
to this common reference.
[0094] An exemplary circuitry for the detection of a gas bubble using several electrodes
as used in Figure 2 is shown in detail in Figure 6. The circuit relies upon the fact
that the resistance between two neighbouring electrodes of a pair of electrodes 310,
being a reference electrode 311 and a probe electrode 312, is higher if the bubble
is situated between those electrodes i.e. it changes from R
F (low resistance fluid) to R
G (high resistance gas).
[0095] Figure 6 shows a example of such circuitry. A voltage +V is applied to a reference
electrode 311. The probe electrode 312 is connected to a voltage -V via a resistor
R, chosen between R
F (low resistance fluid) and R
G (high resistance). The fluid resistance R
F and resistor R determine the voltage at the probe electrode 312. If the probe electrode
312 is surrounded by fluid, the probe electrode will be at around +V. If the probe
electrode 312 is surrounded by gas, the probe electrode will be at around -V.
[0096] The voltage of the probe electrode 312 forms the input for a comparator 330, which
determines whether the probe electrode is surrounded by gas or fluid. The comparator
330 will provide an output value Vx which will be used by the controller 400 to determine
if buffer fluid or gas is present at the position of the pair of electrodes 310.
[0097] The comparator can easily be constructed using standard techniques. A technique that
can be used in LTPS circuitry is to use an inverter, as is also shown in figure 6.
[0098] As shown in Figure 7a and Figure 7b, each of the micro-fluidic channels 120 of the
micro-fluidic device 100 may be provided with an overpressure measuring device 600.
The overpressure measuring device 600 can comprise at least one expansion chamber
610 being separated from the at least one micro-fluidic channel by means of a membrane
620. The membrane 620, which can be in the form of a thin flexible section of PDMS
wall, cooperates with a sensor 630 for generating a signal when the pressure of the
fluid 500, such as the buffer fluid 210, over the membrane 620 becomes larger than
a given threshold pressure.
[0099] For the embodiment shown in Figure 7a and Figure 7b, the membrane 620 will rupture
when subjected to pressures more than the threshold pressure. In Figure 7a, the pressure
over the membrane 620 is less than the threshold pressure. The membrane 620 remains
uninterrupted. When the fluid pressure rises above the threshold pressure, the membrane
620 ruptures, as shown in Figure 7b. The sensor 630, which is now in contact with
the fluid, e.g. the buffer fluid 210, may generate a signal, which is provided to
the controller 400. The controller, obtaining the signal of sensor 630, may provide
an output signal for e.g. deactivating the pumping device providing buffer fluid to
the micro-fluidic device 100.
[0100] An alternative is shown in Figure 8a and Figure 8b, the membrane 620 will expand
when subjected to pressures more than the threshold pressure. In Figure 8a, the pressure
over the membrane 620 is less than the threshold pressure. The membrane 620 remains
in contact with the sensor 630. When the fluid pressure rises above the threshold
pressure, the contact between the sensor 630 and the membrane 620 is interrupted,
as shown in Figure 8b. The sensor 630, which is now no longer in contact with the
membrane 620 but which is completely covered with fluid 210, generates a signal, which
is provided to the controller 400. The controller, obtaining the signal of sensor
630, may provide an output signal for e.g. deactivating the pumping device providing
buffer fluid to the micro-fluidic device 100. Alternatively, the membrane 620 is in
its rest position not in contact with the sensor 630. When the fluid pressure rises
above the threshold pressure, the contact between the sensor 630 and the membrane
620 is made and the sensor provides a signal indicative of an overpressure.
[0101] A further advantage is that some part of the fluid may enter into the expansion chamber,
thereby again reducing the fluid pressure in the micro-fluidic channel, whereby other
components of the micro-fluidic device is protected from further over pressure.
[0102] As an example, the membrane may be a piece of flexible wall, e.g. flexible PDMS wall,
covering a sensor chamber. The strength of the membrane may be tuned by changing or
selecting its thickness, since making the membrane thinner weakens the membrane. It
is also possible to photolithographically create a small metal area under a section
of wall. This results in a decrease in the adherence of the PDMS at this point and
allows it to be pushed back via pressure. This is in particular useful for providing
a reversible sensor. The membrane does not have to make a good seal as there is no
vent in the chamber containing the sensor. The liquid cannot enter the chamber unless
the pressure is sufficient to compress the gas.
[0103] The sensor may e.g. be two electrodes of e.g. 10µm width. The volume behind the membrane
is dry but when the pressure increases the membrane deforms and allows liquid to flow
over the sensor. By measuring the impedance between the sensor electrodes the presence
of liquid and hence over pressure is detected.
[0104] Volume of sensor chamber may be e.g. 50 by 50 by 50 µm but may be tuned depending
on time needed to switch off the liquid flow. A large volume with a plurality of sensors
may provide a larger expansion volume. The sensitivity to overflow remains, but the
larger expansion volume provides more time to switch off the liquid displacement means
such as a pump.
[0105] Turning now to a second embodiment of the present invention, a method to fill or
degas a micro-fluidic device is provided.
[0106] In a first step, a micro-fluidic device 1000 is provided. The micro-fluidic device
1000 comprises a structure 1110, in this embodiment comprising a base structure being
a PDMS semi-permeable base structure, having at least one micro-fluidic channel 1120
for holding a fluid. The micro-fluidic channel 1120 has an interior channel wall 1121.
The micro-fluidic device comprises a plurality of electrodes 1300 present at the interior
channel wall 1121. The micro-fluidic device comprises a controller 1400 for measuring
the value of an electrical property of the fluid 1500 between at least two electrodes
1300 of the plurality of electrodes and for generating an output signal dependent
on the measured value of the electrical property. The controller may be separate from
or integrated in the micro-fluidic device.
[0107] As an example shown in Figure 9a, the micro-fluidic device 1000 comprises two fluidic
openings, one opening 1131 being the opening via which buffer fluid 1210 is provided
to the micro-fluidic channel 1120. The other opening 1132 is the fluid outlet. The
buffer fluid 1210, preferably a degassed liquid, is provided to the micro-fluidic
channel 1120 by means of a pump 1910. Prior to the filling and degassing process,
the micro-fluidic channel 1120 is filled with gas 1200. Similar to what is shown in
Figure 2, the plurality of electrodes comprises a plurality of electrode pairs 1310.
Each pair of electrodes 1310 comprises a reference electrode 1311 and a probe electrode
1312, between which an electrical property of the fluid 1500 is measured, e.g. an
impedance such as the electrical resistance or capacitance, using a comparator 1330.
The comparators provide a measured value for the electric property to the controller
1400. The micro-fluidic channel 1120 further comprises an overpressure measuring device
1600. The overpressure measuring device 1600 can comprise at least one expansion chamber
1610 being separated from the at least one micro-fluidic channel by means of a membrane
1620. The membrane 1620 cooperates with a sensor 1630 for generating a signal when
the pressure of the fluid 1500, such as the buffer fluid 1210, over the membrane 1620
becomes larger than a given threshold pressure.
[0108] As shown in Figure 9a, the micro-fluidic channel 1120 is filled with gas and is to
be filled or "degassed".
[0109] In a further step, as shown in Figure 9b, a buffer fluid 1210 is provided to the
micro-fluidic channel 1120 of the micro-fluidic device 1000. This is done by activating
a fluid displacement means, e.g. the pump 1910. As the fluid leading edge 1224 moves
along the micro-fluidic channel 1120 in longitudinal direction, some pairs 1381 of
electrodes will generate and communicate a measured value, i.e. an impedance such
as a resistance or a capacitance, to the controller 1400, which matches a predetermined
value indicating the electrodes to be contacted by buffer fluid 1210. Other pairs
1382 of electrodes will generate and communicate a measured value, i.e. a resistance,
to the controller 1400, which does not match the predetermined value indicating the
electrodes to be contacted by buffer fluid 1210. The controller is able to identify
the progress of the filling of the micro-fluidic channel 1120, as the fluid leading
edge is situated between the last pair 1381 of electrodes measuring the predetermined
value and the first pair 1382 of electrodes not measuring the predetermined value.
[0110] In case, during filling, a gas bubble 1201 develops, as shown in Figure 9c, at least
one of the pairs of electrodes, here referred to as pair 1383, will provide a measured
value for the electric property to the controller 1400, which does not or does no
longer match the predetermined value, whereas downstream in the micro-fluidic channel
1120, there are pairs 1381 which when measured provide the predetermined value. The
controller 1400 may thus determine the presence of a gas bubble 1201, and by determining
the size of the measured value, e.g. comparing with one of a number of reference values,
it may determine a value relating to the dimension of the bubble 1201 as well. As
the progress of the filling or degassing operation is monitored, the flow into the
micro-fluidic device 1000 can be either increased or released accordingly in response
to the monitoring, e.g. by using a control signal of the controller 1400 to adjust
the flow of the fluid displacement means or pumping device, such as pump 1910. Due
to the real time measurement of the impedance such as the resistance, it becomes possible
to vary the flow rate during the filling procedure, i.e. the controller may be adapted
to control pumping devices such that the flow rate can be high in the beginning of
the procedure and slow when filling is almost complete.
[0111] When, as shown in Figure 9d, the last pair 1384 of electrodes measures the predetermined
value relating to the expected property when liquid is present, the controller may
switch off the pump 1910, or in case there are electrodes, such as pair of electrodes
1383, measuring a value not matching the predetermined value, the controller may reduce
the flow of the pump 1910.
[0112] In the later case, the pressure of the fluid may be kept substantially constant as
long as there are gas bubbles 1201 present and detected. The gas of the gas bubble
1201 will gradually dissipate through the semi-permeable basic structure 1110.
[0113] When the gas bubble has dissipated, the fluid pressure may suddenly raise, since
there is no gas volume anymore, which can be compressed. This pressure pulse may be
sufficient to cause the overpressure measuring device 1600 to generate a signal by
means of the sensor 1630, as shown in Figure 9e. Upon receiving this signal from the
overpressure measuring device 1600, the controller 1400 can be adapted to switch off
the pump 1910 immediately. Because all pairs of electrodes now provide the predetermined
value, the controller may generate a control signal indicating that the micro-fluidic
device 1000 is filled and degassed completely according to the required procedure.
[0114] According to an alternative setups for electrode distribution included within the
scope of the present invention, the micro-fluidic channel may be provided with one
reference electrode located at the entrance of the channel, and a plurality of probe
electrodes along the channel. Each probe electrode may form a pair with the reference
electrode. The resistance of every other probe electrode could be measured with respect
to this common reference. By gradually filling the channel with fluid, the measured
electrical property, such as the resistance, between the reference electrode and each
of the probe electrodes, may be monitored. Depending on the measured values, the controller
may identify the progress of the filling, and the presence of gas volumes or gas bubbles,
similar as described in relation to the previous example.
[0115] It is understood that, in case the controller 1400 measures the predetermined value
at each pair of electrodes, without the overpressure measuring device giving an overpressure
signal, the controller may be adapted to stop the pump 1910, and indicate that the
process has been completed without defects. It is also understood that, after the
overpressure measuring device 1600 gave a signal, and the controller still obtains
measured values from one or more pairs of electrodes that do not match the predetermined
value, the controller 1400 may give a control signal indicating then an incorrect
filling and degassing process has been performed.
[0116] It is further understood that the controller may comprise a look-up table with predetermined
values for each pair of electrodes. The predetermined values may differ from each
other, e.g. due to the geometrical dimensions of the micro-fluidic channel at the
location of the pair of electrodes.
[0117] It is also understood that similar methods to those described above also fall under
the scope of the present invention, that use other electrode setups, different from
the setup using pairs of electrodes as described above with respect to the second
embodiment of the present invention.
[0118] It is understood that the micro-fluidic device may further comprise numerous components,
such as electrodes for heating the liquid, either uniformly for PCR reactions or for
not uniformally for creating flows, electrodes for creating flow via, electrothermal,
electroosmosis, magnetohydrodynamic or any other electrokinetic principle, integrated
photodiodes or other optical detectors, electrode geometries for bio particle manipulation,
e.g. electrophoresis, cell lysis, DNA extraction cell separation, bacteria separation.
Also functional microfluidics for particle separation via flow separation or mechanical
cell lysis may be provided.
[0119] The provision of one or more of such components may render the micro-fluidic device
suitable for its particular use as e.g. biosensors, in rapid DNA separation and sizing,
cell manipulation and sorting, or in pharmaceutical applications, in particular high-throughput
combinatorial testing where local mixing is essential. By providing appropriate components,
such as multiple parallel channels, the micro-fluidic device according to embodiments
of the present invention may also be used in microchannel cooling systems in microelectronics
applications.
[0120] Other arrangements for accomplishing the objectives of the micro-fluidic device embodying
the invention will be obvious for those skilled in the art.
[0121] In a further aspect, the present invention also provides the controller 1400 for
use in micro-fluidic device 1000 for measuring the value of an electrical property
of the fluid 1500 between at least two electrodes 1300 of the plurality of electrodes
and for generating an output signal dependent on the measured value of the electrical
property and optionally for controlled driving of the fluid in the micro-fluidic device
1000 according to embodiments of the present invention.
[0122] The controller as described above may include a computing device, e.g. microprocessor,
for instance it may be a micro-controller. In particular, it may include a programmable
controller, for instance a programmable digital logic device such as a Programmable
Array Logic (PAL), a Programmable Logic Array, a Programmable Gate Array, especially
a Field Programmable Gate Array (FPGA). The use of an FPGA allows subsequent programming
of the microfluidic system, e.g. by downloading the required settings of the FPGA.
The controller may be operated in accordance with settable parameters, such as driving
parameters, for example, threshold values of impedance when a bubble is present or
liquid is present.
[0123] The processing system in the controller may include at least one customisable or
programmable processor coupled to a memory subsystem that includes at least one form
of memory, e.g., RAM, ROM, and so forth. It is to be noted that the processor or processors
may be a general purpose, or a special purpose processor, and may be for inclusion
in a device, e.g., a chip that has other components that perform other functions.
Thus, one or more aspects of the methods according to embodiments of the present invention
can be implemented in digital electronic circuitry, or in computer hardware, firmware,
software, or in combinations of them. The processing system may include a storage
subsystem that has at least one solid state memory, or disk drive and/or CD-ROM drive
and/or DVD drive. In some implementations, a display system, a keyboard, and a pointing
device may be included as part of a user interface subsystem to provide for a user
to manually input information, such as parameter values. Ports for inputting and outputting
data, e.g. desired or obtained flow rate, also may be included. More elements such
as network connections, interfaces to various devices, and so forth, may be included.
The various elements of the processing system may be coupled in various ways, including
via a bus subsystem for simplicity as a single bus, but will be understood to those
in the art to include a system of at least one bus. The memory of the memory subsystem
may at some time hold part or all of a set of instructions that when executed on the
processing system implement the steps of the method embodiments described herein.
[0124] The present invention also includes a computer program product which provides the
functionality of any of the methods according to the present invention when executed
on a computing device. Such computer program product can be tangibly embodied in a
carrier medium carrying machine-readable code for execution by a programmable processor.
The present invention thus relates to a carrier medium carrying a computer program
product that, when executed on computing means, provides instructions for executing
any of the methods as described above. The term "carrier medium" refers to any medium
that participates in providing instructions to a processor for execution. Such a medium
may take many forms, including but not limited to, non-volatile media, and transmission
media. Non-volatile media includes, for example, optical or magnetic disks, such as
a storage device which is part of mass storage. Common forms of computer readable
media include, a CD-ROM, a DVD, a flexible disk or floppy disk, a tape, a memory chip
or cartridge or any other medium from which a computer can read. Various forms of
computer readable media may be involved in carrying one or more sequences of one or
more instructions to a processor for execution. The computer program product can also
be transmitted via a carrier wave in a network, such as a LAN, a WAN or the Internet.
Transmission media can take the form of acoustic or light waves, such as those generated
during radio wave and infrared data communications. Transmission media include coaxial
cables, copper wire and fibre optics, including the wires that comprise a bus within
a computer.
[0125] It is to be understood that although preferred embodiments, specific constructions
and configurations, as well as materials, have been discussed herein for devices according
to the present invention, various changes or modifications in form and detail may
be made without departing from the scope of this invention as defined by the appended
claims.
1. An arrangement of a micro-fluidic device (100, 1000) and a controller (400, 1400),
the microfluidic device comprising at least one micro-fluidic channel (120, 1120)
for holding a fluid (500, 1500), the micro-fluidic channel having an interior channel
wall (121, 1121), at least part of the interior channel wall being made from semi-permeable
material, the micro-fluidic device comprising a plurality of electrodes (300, 1300)
present at the interior channel wall, the controller (400, 1400) being adapted for
measuring the value of an electrical property of the fluid between at least two electrodes
of the plurality of electrodes and for generating an output signal dependent on the
measured value of the electrical property indicating whether a gas volume is present
between the at least two electrodes.
2. The arrangement according to claim 1, characterised in that the plurality of electrodes comprises a plurality of electrode pairs (310, 313, 314,
1381, 1382, 1383, 1384), the controller being adapted for measuring the electric property
between the electrodes (311, 312, 1311, 1312) of each pair of electrodes.
3. The arrangement according to any previous claim, wherein the at least one micro-fluidic
channel has a substantially rectangular radial cross section having two pairs of mutually
opposite sides (710, 711, 720, 721), the plurality of electrodes are present along
the same side of the radial cross sections.
4. The arrangement according to any previous claim, wherein the micro-fluidic device
further comprises an overpressure measuring device (600, 1600).
5. The arrangement according to claim 4, wherein the overpressure measuring device comprises
at least one expansion chamber (610, 1610) being separated from the at least one micro-fluidic
channel by means of a membrane (620, 1620), the membrane cooperating with a sensor
(630, 1630) for generating a signal when the pressure over the membrane becomes larger
than a given threshold pressure.
6. The arrangement according to claim 5, wherein the membrane is adapted to rupture when
said threshold pressure is reached.
7. The arrangement according to claim 5, wherein the membrane and sensor are in contact
with each other when a fluid pressure less than the threshold pressure is applied
to the membrane, the contact between the membrane and sensor being interrupted when
a fluid pressure less than the threshold pressure is applied to the membrane or vice
versa.
8. The arrangement according to any one of the claims 1 to 7, wherein the at least one
micro-fluidic channel is provided in a substrate (110, 1110), the micro-fluidic device
further comprising at least one of a valve or a pump, the at least one of a valve
or a pump being integrated in the substrate.
9. A method for degassing a micro-fluidic device (100, 1000) comprising at least one
micro-fluidic channel (120, 1120) for holding a fluid (500, 1500), the micro-fluidic
channel having an interior channel wall (121, 1121), at least part of the interior
channel wall being made from semi-permeable material, the method comprising:
- providing a buffer fluid to the at least one micro-fluidic channel of the micro-fluidic
device;
- measuring a value of an electrical property of the fluid in the micro-fluidic channel;
- generating an output signal dependent on the measured value of the electrical property
indicating when a gas volume is present in the microfluidic channel.
10. The method according to claim 9, wherein the micro-fluidic device comprises a plurality
of electrodes (300, 1300) present at the interior channel wall, the measuring step
including measuring between at least two of the plurality of electrodes.
11. A method according to claim 9 or 10, wherein the output signal is used to determine
the end of a degassing of the micro-fluidic device.
12. A method according to any of the claims 9 to 11, wherein the buffer fluid is provided
to the micro-fluidic device by means of a pump (1910), the output signal being used
to control the pump.
13. A method according to claim 12, wherein the output signal is used to control the flow
rate of buffer fluid provided by the pump.
14. A controller for controlling a micro-fluidic device (100, 1000) comprising at least
one micro-fluidic channel (120, 1120) for holding a fluid (500, 1500), the micro-fluidic
channel having an interior channel wall (121, 1121) at least part of the interior
channel wall being made from semi-permeable material, the controller comprising:
means for controlling provision of a buffer fluid to the at least one micro-fluidic
channel of the micro-fluidic device;
means for measuring a value of an electrical property of the fluid in the micro-fluidic
channel;
means for generating an output signal dependent on the measured value of the electrical
property indicating when a bubble is present between the at least two electrodes.