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(11) | EP 2 977 606 A1 |
| (12) | EUROPEAN PATENT APPLICATION |
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| (54) | Microfluidic device and method of manufacturing thereof |
| (57) A microfluidic device and method of manufacturing thereof are disclosed. In one embodiment,
the microfluidic device includes a fluidic channel encapsulated in a solid container.
Further, one wall of the fluidic channel is formed by an oxide. Furthermore, a surface
of the solid container includes a first recess down to the oxide thereby allowing
optical inspection of a fluid sample in the fluidic channel via the first recess,
through the oxide.
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Field of the Invention
[0001] Embodiments of the present invention relate to microfluidic devices. In particular, embodiments of the present invention relate to the manufacturing of such microfluidic devices.
Background to the Invention
[0002] Micromachining is a technology used to create fluidic channels of microfluidic devices. These microfluidic devices are generally used for lab-on-chip applications having a chemical reaction based detection principle. The fluidic channels are used for parallel analysis of and manipulation of small volumes.
[0003] Generally, a polymer material, e.g. PDMS, may be used for defining the fluidic channels. However, if the detection mechanism is optical (for example, based on fluorescence), the use of the fluidic channels defined in polymer material may become problematic because of their auto-fluorescence and optical properties, such as refractive index, which are difficult to control. Also, the polymer material has limited temperature resistance, poor mechanical properties, poor resistance to certain chemicals and ages with time.
[0004] In fabricating fluidic channels for such lab-on-chip applications, existing techniques provide a substrate having trenches defined in silicon oxide that has lower light absorbance and auto-fluorescence within a wider wavelength range compared to e.g. polymer materials. Further, the existing techniques use anodic bonding of Pyrex (i.e. glass) to seal the topside of the trenches defined in the silicon oxide. However, auto-fluorescence caused by sodium (Na) doping, necessary for this glass. may limit its use for fluorescence based optical detection. Further, the thickness of the top glass wafer must be at least 100 micrometer (µm) to 200µm to prevent breaking.
Summary of the Invention
[0006] According to one aspect of the present invention, the microfluidic device includes a fluidic channel encapsulated in a solid container. Further, one wall of the fluidic channel is formed by an oxide. Furthermore, a surface of the solid container includes a first recess exposing the oxide thereby allowing optical inspection of a fluid sample in the fluidic channel underneath the first recess, through the oxide.
[0007] According to another aspect of the present invention, a first substrate having a first oxide layer is provided. The first substrate may be a silicon substrate. Further, a second substrate is provided. The second substrate may be a silicon substrate. Furthermore, a fluidic structure is etched in the second substrate. Moreover, the first substrate is bonded with the second substrate, wherein the first oxide layer is bonded to the second substrate thereby closing the fluidic structure. Also, the first recess is created in the first substrate down to the first oxide layer. In addition, a second recess may be created in the second substrate down to the fluidic structure for supplying or exiting the fluid sample.
Brief Description of the Drawings
[0008]
FIG 1A to FIG1B illustrate cross-sectional views of an exemplary microfluidic device including a fluidic channel encapsulated in a solid container, according to an embodiment.
FIG 2A to FIG 2C illustrate cross-sectional views of exemplary microfluidic devices depicting various types of fluidic channels, according to different embodiments.
FIG 3A to FIG 3E are schematic illustrations of a method of manufacturing a microfluidic device, according to an embodiment.
FIG 4A to FIG 4E are schematic illustrations of a method of manufacturing a microfluidic device, according to another embodiment.
FIG 5 illustrates a flow chart of an exemplary method of manufacturing a microfluidic device, according to an embodiment.
Description of the Invention
[0009] A microfluidic device and method of manufacturing thereof are disclosed. In the following detailed description of the embodiments of the present invention, references are made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration specific embodiments in which the present invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the present invention, and it is to be understood that other embodiments may be utilized and that changes may be made without departing from the scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present subject matter is defined by the appended claims.
[0010] FIG 1A and FIG 1B illustrate cross-sectional views of an exemplary microfluidic device 100 including a fluidic channel 10 6 encapsulated in a solid container 10 2, according to an embodiment. For example, the fluidic channel 106 is a microfluidic channel or a nanofluidic channel. A cross section of the fluidic channel 106 may be rectangular. Referring now to FIG 1A, one wall of the fluidic channel 10 6 is formed by an oxide 104. Preferably, the oxide 104 is a thermally grown oxide. For example, the thickness of the oxide 104 is in the range of 100 nanometers (nm) to 3 microns (µm). It is an advantage of the invention that the thermally grown oxide is a thin layer which does not disrupt optical signals during inspection of the fluid channel 106 through the thermally grown oxide. It also is an advantage of the invention that the fluidic channel 106 can remain closed during optical inspection.
[0011] As shown in FIG 1A, a surface 108 of the solid container 102 includes a first recess 110 down to the oxide 104 thereby allowing optical inspection of a fluid sample in the fluidic channel 106 via the first recess 110, through the oxide 104. For example, an external optical system can visualize fine details of the fluid sample in the fluidic channel 106 through the thin oxide 104. The thin oxide 104 significantly increases the numerical aperture of the external optical system monitoring the fluid sample.
[0012] Referring now to FIG 1B, the outer surface 10 8 of the solid container 10 2 further includes a second recess 112 down to the fluidic channel 106 for supplying or exiting the fluid sample to and from the fluidic channel.
[0013] Further, the solid container 10 2 is formed by two bonded semiconductor substrates, for example, one semiconductor substrate comprising the fluidic channel 10 6, e.g. formed in the surface of that semiconductor substrate, and the other semiconductor substrate closing the fluidic channel 10 6. This assembly is explained in detail with reference to FIG 2A to 2C.
[0014] FIG 2A to 2C illustrate cross-sectional views of exemplary microfluidic devices depicting various types of fluidic channels, according to different embodiments. Referring now to FIG 2A, the microfluidic device 100 includes a first substrate 202 and a second substrate 204. Particularly, the solid container 102, shown in FIG 1A and FIG 1B, in the microfluidic device 100 is formed by bonding the first substrate 202 to the second substrate 204. In the example shown in FIG 2A, the first substrate 202 comprises a first oxide layer 206 and the second substrate 204 comprises a second oxide layer 208. Preferably, the first substrate 202 and the second substrate 204 are semiconductor substrates. Preferably, the first oxide layer 206 and, optionally, the second oxide layer 208 are thermally grown on such first substrate 202 and such second substrate 204, respectively. A preferred example of such thermally grown oxide is silicon dioxide. Alternatively, the first oxide layer 206 and, optionally, the second oxide layer 208 are deposited on such first substrate 202 and such second substrate 204, respectively
[0015] Furthermore, the second substrate 204 includes the fluidic channel 106. In this embodiment, the fluidic channel 106 is etched in the second oxide layer 208 of the second substrate 204. Further, the first substrate 202 and the second substrate 204 are bonded to each other whereby the first oxide layer 206 closes the fluidic channel 106. This is explained in detail with reference to FIG 3C. Furthermore in this embodiment, all the walls of the fluidic channel 10 6 are formed by an oxide, preferably thermally grown oxide.
[0016] Referring now to FIG 2B, the microfluidic device 100 includes: the first substrate 202 comprising the first oxide layer 206, and the second substrate 204. In this embodiment, the fluidic channel 106 is etched in the second substrate 204. Further, the first substrate 202 and the second substrate 204 are bonded to each other such that the first oxide layer 206 closes the fluidic channel 10 6. This is explained in detail with reference to FIG 4C.
[0017] Referring now to FIG 2C, the first substrate 202 comprises the first oxide layer 206, and the second substrate 204 comprises the second oxide layer 208. In this embodiment, the fluidic channel 106 is etched in the second oxide layer 208 and partly in the underlying second substrate 204. Further, the first substrate 202 and the second substrate 204 are bonded to each other such that the first oxide layer 206 closes the fluidic channel 10 6.
[0018] In the examples shown in FIG 2A to 2C, the first substrate 202 comprises the first recess 110 down to the first oxide layer 206 thereby allowing optical inspection of the fluid sample in the fluidic channel 106 via the first recess 110, through the first oxide layer 206. Further, the first substrate 202 or the second substrate 204 can also comprise a second recess 112 down to the fluidic channel 106 for supplying or exiting the fluid sample.
[0019] FIG 3A to 3E are schematic illustrations of a method of manufacturing a microfluidic device 100, according to an embodiment. Referring now to FIG 3A, the first substrate 202 comprising the first oxide layer 206 is provided. The first oxide layer 206 is a thermally grown oxide, located on at least a part of the top of a surface of the first substrate 202. The thickness of the first oxide layer 206 may be in the range of 100nm to 3 µm. Further, the second substrate 204 is provided. In this embodiment, the second substrate 204 comprises the second oxide layer 208. For example, the second oxide layer 208 may be deposited or thermally grown on a surface of the second substrate 204. When deposited, the second oxide layer 208 may have a thickness between 20-30 µm. When thermally grown, the second oxide layer 208 may have a thickness between 100 nm and 3µm.
[0020] Referring now to FIG 3B, a fluidic structure 210 (i.e., the fluidic channel 106 shown in FIG 1 and FIG 2) is etched in the second substrate 204. In the example shown in FIG 3B, the fluidic structure 210 is etched at least partly into the second oxide layer 208 of the second substrate 204.
[0021] Referring now to FIG 3C, the first substrate 202 and the second substrate 204 are bonded. The first substrate 202 and the second substrate 204 are bonded such that the first oxide layer 206 is bonded to the second substrate 204 thereby closing the fluidic structure 210. In one example, the first substrate 202 and the second substrate 204 are bonded by activating the first oxide layer 206 and the second oxide layer 208. In this case, all the walls of the fluidic structure 210 are formed by the thermally grown oxide. The first and second oxide layers are activated by increasing the number of Si-OH groups on their surface. These groups are highly reactive and when the two surfaces contact each other, permanent Si-O-Si bonds are formed. The activation may comprise an 02, Ar or N2 plasma exposure of the surfaces. The plasma step may be followed by H2O spray on the substrate surface.
[0022] Referring now to FIG 3D, the first recess 110 is created in the first substrate 202 down to the first oxide layer 206. In this embodiment, the first recess 110 is created in a surface of the first substrate 202 opposing the surface of the first substrate 202 comprising the first oxide layer 206. The first recess 110 allows optical inspection of the fluid sample in the fluidic structure 210 through the first oxide layer 206. Referring now to FIG 3E, the second recess 112 is created in the second substrate 204 down to the fluidic structure 210 for supplying or exiting the fluidic sample therefrom. The second recess 112 is created in a surface of the second substrate 204 opposing the surface of the second substrate 204 comprising the second oxide layer 208. Alternatively, the second recess 112 may also be created in the first substrate 202 down to the fluidic structure 210.
[0023] FIG 4A to 4E are schematic illustrations of a method of manufacturing the microfluidic device 100, according to another embodiment. Referring now to FIG 4A, the first substrate 202 comprising the first oxide layer 206 located on at least a part of a surface of the first substrate 202 is provided. Further, the second substrate 204 is provided. Referring now to FIG 4B, the fluidic structure 210 is etched in the second substrate 204.
[0024] Referring now to FIG 4C, the first substrate 202 and the second substrate 204 are bonded. The first substrate 202 and the second substrate 204 are bonded such that the first oxide layer 206 is bonded to the second substrate 204 thereby closing the fluidic structure 210. In one example, the first substrate 202 and the second substrate 204 are bonded by activating both surfaces. For example, the deposited first oxide layer 206 on a first substrate 202 may be activated. A second substrate 204 may have a native oxide layer because of natural oxidation which occurs due to the exposure to air, e.g. exposure of a silicon wafer to air. Thus, that native oxidation layer may also be activated.
[0025] Referring now to FIG 4D, the first recess 110 is created in the first substrate 202 down to the first oxide layer 206. The recess 110 is created in a surface of the first substrate 202 opposing the surface comprising the first oxide layer 206. The first recess 110 allows optical inspection of the fluid sample in the fluidic structure 210 through the first oxide layer 206. The dimensions of the first recess are selected thereby allowing optical inspection through the first recess 110. For example, when an external optical tool is used to perform optical inspection, the dimensions of the first recess 110 are chosen thereby allowing optical inspection using that external optical tool, e.g. a microscope. Referring now to FIG 4E, the second recess 112 is created in the second substrate 204 down to the fluidic structure 210 for supplying or exiting the fluidic sample therefrom.
[0026] FIG 5 illustrates a flow chart 500 of an exemplary CMOS-compatible method of manufacturing a microfluidic device, according to an embodiment.
[0027] At step 502, a first substrate 202 comprising a first oxide layer 206 is provided. In one embodiment, the first oxide layer 206 is a thermally grown oxide. Further, the first oxide layer 206 can have a thickness in the range of 100nm to 3 µm.
[0028] At step 50 4, a second substrate 20 4 is provided. This is explained in detail with reference to FIG 3A to FIG 4A.
[0029] At step 506, a fluidic structure 210 is etched in the second substrate 204. In one embodiment, the second substrate 204 comprises a second oxide layer. The fluidic structure 210 is then at least partly etched into the second oxide layer of the second substrate 204.
[0030] At step 508, the first substrate 202 and the second substrate 204 are bonded. The first substrate 202 is bonded with the second substrate 204 such that the first oxide layer 206 is bonded to the second substrate 204 thereby closing the fluidic structure 210. This is explained in detail with reference to FIG 3C and FIG 4C.
[0031] At step 510, a first recess 110 is created in the first substrate 202 down to the first oxide layer 206.
[0032] At step 512, a second recess 112 is created in the second substrate 204 down to the fluidic structure 210 for supplying or exiting a fluid sample. This is explained in detail with reference to FIG 3E and FIG 4E. This step 512 is optional. The second recess 112 is dimensioned thereby allowing application of a fluid sample in the fluidic structure 210. The size of the second recess 112 may be adapted to allow external tools, e.g. pipetting tools, to provide a fluid sample in the fluidic structure 210.
[0033] Though the FIG 1 through FIG 5 are explained with reference to one fluidic channel, the same embodiments are applicable to a microfluidic device with multiple fluidic channels. Also, the different embodiments of the fluidic channel, explained with reference to FIG 2A to FIG 2C, can be fabricated in any combination in the microfluidic device.
1. A microfluidic device (100) comprising a fluidic channel (106) encapsulated in a solid
container (102), wherein one wall of the fluidic channel (106) is formed by an oxide
(104),
characterized in that:
characterized in that:
a surface (108) of the solid container (102) comprises a first recess (110) down to the oxide (104) thereby allowing optical inspection, through the oxide (104), of a fluid sample in the fluidic channel (106) via the first recess (110).
2. The microfluidic device (100) according to claim 1, wherein the oxide (104) is a thermally
grown oxide.
3. The microfluidic device (100) according to claim 2, wherein all walls of the fluidic
channel (106) are formed by a thermally grown oxide.
4. The microfluidic device (100) according to any of the preceding claims, wherein the
thickness of the oxide (104) is in the range of 100 nanometers (nm) to 3 microns (µm).
5. The microfluidic device (100) according to any of the preceding claims, wherein the
surface (108) of the solid container (102) further comprises a second recess (112)
down to the fluidic channel (106) for supplying or exiting the fluid sample therefrom.
6. The microfluidic device (100) according to any of the preceding claims, wherein the
solid container (102) further comprises a first substrate (202) and a second substrate
(204), wherein the second substrate (204) comprises the fluidic channel (106), wherein
the first substrate (202) closes at least the fluidic channel (106), and wherein the
first substrate (202) and the second substrate (204) are bonded with each other.
7. A method of manufacturing a microfluidic device (100), the method comprising:
- providing a first substrate (202) comprising a first oxide layer (206);
- providing a second substrate (204);
- etching a fluidic structure (210) in the second substrate (204);
- bonding the first substrate (202) and the second substrate (204), wherein the first oxide layer (206) is bonded to the second substrate (204) thereby closing the fluidic structure (210); and
- creating a first recess (110) in the first substrate (202) down to the first oxide layer (206).
8. The method according to claim 7, wherein the first oxide layer (206) is a thermally
grown oxide.
9. The method according to any of claims 7 to 8, wherein the first oxide layer (206)
has a thickness in the range of 100nm to 3 microns (µm).
10. The method according to any of claims 7 to 9, further comprising: creating a second
recess (112) in the second substrate (204) down to the fluidic structure (210) for
supplying or exiting a fluid sample therefrom.
11. The method according to any of claims 7 to 10, wherein the second substrate (204)
comprises a second oxide layer (208), and wherein etching the fluidic structure (210)
in the second substrate (204) comprises at least partly etching into the second oxide
layer (208) of the second substrate (204).
12. The method according to any of claims 7 to 11, wherein the first substrate (202) and
the second substrate (204) are semiconductor substrates.