METHOD OF MANUFACTURING MICROFLUIDIC CHIP AND A MICROFLUIDIC CHIP MADE THEREBY

Abstract

A method of manufacturing a microfluidic chip includes: providing an upper mold having multiple upper ribs extending along a second direction, and a lower mold having multiple lower ribs extending along a first direction different from the second direction; forming a forming material in a filling space defined by the upper and lower molds to provide a channeled plate having multiple upper microfluidic channels complementary in shape to the upper ribs, lower microfluidic channels complementary in shape to the lower ribs, and multiple thin film valves formed at intersections where the upper microfluidic channels intersect the lower microfluidic channels; separating the upper and lower molds; and covering the lower and upper microfluidic channels.

Claims

1. A microfluidic chip comprising: a carrier plate; a channeled plate disposed on said carrier plate and having an upper surface, a lower surface opposite to said upper surface, a gaseous fluid channel unit having an array of upper microfluidic channels indented from said upper surface, said upper microfluidic channels being intercommunicated, spaced apart along a first direction and extending along a second direction different from the first direction, a liquid fluid channel unit having an array of lower microfluidic channels indented from said lower surface and discommunicated from said upper microfluidic channels, said lower microfluidic channels being intercommunicated, spaced apart along the second direction, extending along the first direction, and intersecting said upper microfluidic channels at a plurality of intersections, and an array of thin film valves formed at the intersections; and an upper cover attached to said upper surface and sealing said upper microfluidic channels.

2. The microfluidic chip as claimed in claim 1, wherein the first direction is transverse to the second direction.

3. The microfluidic chip as claimed in claim 1, wherein said gaseous fluid channel unit further has a confluence channel that is indented from said upper surface and that intercommunicates said upper microfluidic channels.

4. The microfluidic chip as claimed in claim 3, wherein said upper cover has an opening that is in spatial communication with said confluence channel of said gaseous fluid channel unit.

5. The microfluidic chip as claimed in claim 1, wherein said liquid fluid channel unit further has a plurality of bending channels that are indented from said lower surface, that are discommunicated from said upper microfluidic channels, and that intercommunicate said lower microfluidic channels.

6. The microfluidic chip as claimed in claim 5, wherein said bending channels are arranged in two rows to intercommunicate adjacent two of said lower microfluidic channels.

7. The microfluidic chip as claimed in claim 6, wherein said two rows of said bending channels are arranged along the second direction.

8. The microfluidic chip as claimed in claim 1, wherein said liquid fluid channel unit further has an array of reaction slots that are indented from said lower surface, that are discommunicated from said upper microfluidic channels, and that are in spatial communication with said lower microfluidic channels.

9. The microfluidic chip as claimed in claim 8, wherein said array of reaction slots is arranged in multiple rows arranged along the second direction.

10. The microfluidic chip as claimed in claim 1, wherein said liquid fluid channel unit further has a first entrance channel, a second entrance channel, a mixing channel that is spatially communicated between said first and second entrance channels and one of said lower microfluidic channels.

11. The microfluidic chip as claimed in claim 10, wherein: said channeled plate further has two side surfaces that are opposite to each other and that each interconnect said upper and lower surfaces; each of said first and second entrance channels has a starting section that is formed in one of said side surfaces, and an ending section that spatially communicates said starting section and said mixing channel.

12. The microfluidic chip as claimed in claim 11, wherein said liquid fluid channel unit further has an exiting channel that has a first exiting section that is formed in the other one of said side surfaces, and a second exiting section that is spatially communicated with said first exiting section and an end of another one of said lower microfluidic channels opposite to said one of said lower microfluidic channels spatially communicated with said mixing channel.

13. The microfluidic chip as claimed in claim 1, wherein: each of said upper microfluidic channels has a width (W1) measured in the first direction; each of said lower microfluidic channels has a width (W2) measured in the second direction; said upper microfluidic channels are spaced apart from said lower microfluidic channels by a distance (T);
2W1/T25; and
2W2/T25.

14. The microfluidic chip as claimed in claim 1, wherein said channeled plate is made of at least one of polysiloxane, polydimethylsiloxane or polyurethane.

15. The microfluidic chip as claimed in claim 1, wherein said channeled plate is made of a thermoplastic material.

16. The microfluidic chip as claimed in claim 15, wherein said channeled plate is made of styrenic thermoplastic elastomer.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Other features and advantages of the disclosure will become apparent in the following detailed description of the exemplary embodiments with reference to the accompanying drawings, of which:

[0014] FIG. 1 shows a manufacturing method of a microfluidic device according to U.S. Pat. No. 6,951,632 B2;

[0015] FIG. 2 shows operation of the microfluidic device;

[0016] FIG. 3 is a flow chart of a first embodiment of a method of manufacturing a microfluidic chip according to the present disclosure;

[0017] FIG. 4 is a schematic view of a metal mold assembly used in the first embodiment;

[0018] FIG. 5 is a fragmentary cross-sectional view of the metal mold assembly taken along line V-V of FIG. 4;

[0019] FIG. 6 shows consecutive steps of the first embodiment;

[0020] FIG. 7 is a flow chart of an electroforming step of the first embodiment;

[0021] FIG. 8 shows consecutive steps of the electroforming step of the first embodiment;

[0022] FIG. 9 is a schematic view of the microfluidic chip made by the first embodiment;

[0023] FIG. 10 is a fragmentary cross-sectional view of the microfluidic chip taken along line X-X of FIG. 9;

[0024] FIG. 11 is a fragmentary cross-sectional view of the microfluidic chip taken along line XI-XI of FIG. 9; and

[0025] FIG. 12 shows consecutive steps of a second embodiment of the method of manufacturing the microfluidic chip according to the present disclosure.

DETAILED DESCRIPTION

[0026] Before the disclosure is described in greater detail, it should be noted that where considered appropriate, reference numerals or terminal portions of reference numerals have been repeated among the figures to indicate corresponding or analogous elements, which may optionally have similar characteristics.

[0027] Referring to FIG. 3, a first embodiment of a method of manufacturing a microfluidic chip according to the present disclosure includes an electroforming step (S1), a providing step (S2), a disposing step (S3), a forming step (S4), a demoulding step (S5), and a packaging step (S6).

[0028] It is noted that the electroforming step (S1) will be described in detail hereinafter.

[0029] Referring further to FIGS. 4 to 6, in the providing step (S2), a metal mold assembly 5 is provided. The metal mold assembly 5 includes an upper mold 51 and a lower mold 52. The upper mold 51 has an array of upper ribs 511 extending toward the lower mold 52, and an array of upper trenches 512, each of the which is defined by two adjacent ones of the upper ribs 511. The lower mold 52 has an array of lower ribs 521 extending toward the upper mold 51, and an array of lower trenches 522, each of which is defined by two adjacent ones of the lower ribs 521. The upper ribs 511 are spaced apart along a first direction (Y) and extend along a second direction (X) different from the first direction (Y). In this embodiment, the first direction (Y) is transverse to the second direction (X). The lower ribs 521 are spaced apart along the second direction (X), extend along the first direction (Y), and intersect the upper ribs 511 at a plurality of intersections. A lower end of the upper ribs 511 and an upper end of the lower ribs 521 cooperatively define a plurality of gaps (G) that are respectively located at the intersections. The upper trenches 512, the lower trenches 522 and the gaps (G) are spatially interconnected and cooperatively define a filling space 50.

[0030] In the disposing step (S3), a forming material 30 is placed onto the lower ribs 521 of the lower mold 52 before the upper and lower molds 51, 52 are closed. The forming material 30 may be in a form of solid or gel. In certain embodiments, the forming material 30 is made of polysiloxane, such as solid or liquid silicone resin. In certain embodiments, the forming material 30 is made of either polydimethylsiloxane or polyurethane.

[0031] In the forming step (S4), the forming material 30 is formed in the filling space 50 by hot press-molding technique to provide a channeled plate 3. The channeled plate 3 has an array of upper microfluidic channels 311 that is complementary in shape to the array of the upper ribs 511 of the upper mold 51, an array of lower microfluidic channels 321 that is complementary in shape to the array of the lower ribs 521 of the lower mold 52, and an array of thin film valves 331. The thin film valves 331 are complementary in shape to the gaps (G). In certain embodiments, in the forming step (S4), the upper and lower molds 51, 52 are preheated, and the forming material 30 is placed on the lower ribs 521 of the preheated lower mold 52, followed by closing the upper and lower molds 51, 52 to shape the forming material 30 into the channeled plate 3. In certain embodiments, in forming step (S4) (i.e., during the forming of the forming material 30 in the filling space 50), at least one of the upper and lower molds 51, 52 is moved toward the other one of the upper and lower molds 51, 52 to provide a clamping force (F) (see FIG. 6, which shows an alternative manner where the upper and lower molds 51, 52 are moved toward each other) to press the forming material 30 between the upper and lower molds 51, 52. A heater 6 schematically shown in FIG. 6 is used to heat the upper and lower molds 51, 52. In certain embodiments, the upper and lower molds 51, 52 are heated to a temperature ranging from 80 C. to 200 C. The pressed forming material 30 in the filling space 50 is cross-linked and hardened upon heating.

[0032] In the demoulding step (S5), the upper and lower molds 51, 52 are separated from the channeled plate 3.

[0033] In the packaging step (S6), the array of the lower microfluidic channels 321 and the array of the upper microfluidic channels 311 are covered. In certain embodiments, a carrier plate 2 made of glass is used for covering the lower microfluidic channels 321, and an upper cover 4 made of glass, silica gel, or plastic is used for covering the upper microfluidic channels 311. Detailed structure of the channeled plate 3 will be described hereinafter.

[0034] It should be noted that the thin film valves 331 are deformable by the pressurized gas in the upper microfluidic channels 311. Referring to FIGS. 4 to 6, each of the upper ribs 511 of the upper mold 51 has a width (W1) measured in the first direction (Y), each of the lower ribs 521 of the lower mold 52 has a width (W2) measured in the second direction (X), and each of the gaps (G) has a height (T) measured between the lower end of the upper ribs (511) and the upper end of the lower ribs (521). In certain embodiments, the upper and lower molds 51, 52 satisfy the following relationships: 2W1/T25; and 2W2/T25. In certain embodiments, the height (T) of each of the gaps (G) satisfies 10 mT500 m.

[0035] Referring to FIGS. 3, 5, 7, and 8, detailed description of the electroforming step (S1) is provided. An electroforming technique is used for manufacturing the metal mold assembly 5, and includes a photoresist forming step (S11), a metal deposition step (S12), a thickening step (S13), and a removing step (S14).

[0036] The photoresist forming step (S11) is conducted by a photolithography technique, in which a first patterned photoresist layer 721 complementary in shape to the upper ribs 511 and the upper trenches 512 of the upper mold 51 is formed on a first carrier plate 711, and a second patterned photoresist layer 722 complementary in shape to the lower ribs 521 and the lower trenches 522 of the lower mold 52 is formed on a second carrier plate 712.

[0037] The metal deposition step (S12) is conducted by a sputtering technique, in which a first metal layer 731 is deposited on the first carrier plate 711 and the first photoresist layer 721, and a second metal layer 732 is deposited on the second carrier plate 712 and the second photoresist layer 722.

[0038] In the thickening step (S13), the first metal layer 731 and the second metal layer 732 are thickened by electroforming to form the upper and lower molds 51, 52.

[0039] In the removing step (S14), the first and second carrier plates 711, 712, and the first and second photoresist layers 721, 722 are removed from the upper and lower molds 51, 52.

[0040] Referring to FIGS. 9 to 11, the microfluidic chip manufactured by the first embodiment of the method according to the present disclosure includes the carrier plate 2, the channeled plate 3, and the upper cover 4.

[0041] The channeled plate 3 has an upper surface 301, a lower surface 302 opposite to the upper surface 301, a gaseous fluid channel unit 31, a liquid fluid channel unit 32, and the array of the thin film valves 331.

[0042] The gaseous fluid channel unit 31 has the array of the upper microfluidic channels 311 and a confluence channel 312. The upper microfluidic channels 311 are indented from the upper surface 301, are intercommunicated by the confluence channel 312 indented from the upper surface 301, are spaced apart along the first direction (Y), and extend along the second direction (X) transverse to the first direction (Y).

[0043] The liquid fluid channel unit 32 has the array of the lower microfluidic channels 321, a plurality of bending channels 322, an array of reaction slots 323, a first entrance channel 324, a second entrance channel 325, a mixing channel 326, and an exiting channel 327 that are indented from the lower surface 302 and are discommunicated from the upper microfluidic channels 311. The lower microfluidic channels 321 are spaced apart along the second direction (X), extend along the first direction (Y), and are intercommunicated by the bending channels 322 that are arranged in two rows along the second direction (X) to intercommunicate adjacent two of the lower microfluidic channels 321 (see FIG. 9). The array of reaction slots 323 is arranged to be in spatial communication with the lower microfluidic channels 321 (see FIG. 9). The lower microfluidic channels 321 intersect the upper microfluidic channels 311 at a plurality of intersections.

[0044] Each of the first and second entrance channels 324, 325 has a starting section 3241, 3251 that is formed in a side surface 303 of the channeled plate 3 that interconnects the upper surface 301 and the lower surface 302, and an ending section 3242, 3252 spatially communicated to the starting section 3241, 3251. The mixing channel 326 is spatially intercommunicated between the ending sections 3242, 3252 of the first and second entrance channels 324, 325 and an end of one of the lower microfluidic channels 321. The exiting channel 327 has a first exiting section 3271 that is formed in a side surface 304 of the channeled plate 3 opposite to the side surface 303, and a second exiting section 3272 that is spatially intercommunicated the first exiting section 3271 and an end of another one of the lower microfluidic channels 321.

[0045] In certain embodiments, a test sample of deoxyribonucleic acid may be introduced into the microfluidic chip through the starting section 3241 of the first entrance channel 324, and a reagent may be introduced into the microfluidic chip through the starting section 3251 of the second entrance channel 325. The test sample and the reagent may be mixed in the mixing channel 326 to undergo a polymerase chain reaction.

[0046] The array of the thin film valves 331 is formed at the intersections where the upper microfluidic channels 311 intersect the lower microfluidic channels 321.

[0047] The upper cover 4 is attached to the upper surface 301 of the channeled plate 3, seals the upper microfluidic channels 311, and has an opening 40 that is in spatial communication with the confluence channel 312 of the gaseous fluid channel unit 31.

[0048] Referring to FIGS. 3 and 12, a second embodiment of the method of manufacturing the microfluidic chip according to the present disclosure has process steps similar to those of the first embodiment, with differences described below.

[0049] In the disposing step (S3), the forming material 30 is in a gel form, is evenly mixed in a feeding system (not shown), and is injected into the filling space 50 through an injection port (not shown) of the metal mold assembly 5.

[0050] In the forming step (S4), the upper and lower molds 51, 52 are heated, and the forming material 30 is hardened to form the channeled plate 3.

[0051] In certain embodiments, the upper and lower molds 51, 52 are closed and heated by the heater 6 to a pre-determined temperature, followed by injecting the forming material 30 into the filling space 50 through the injection port to allow the forming material 30 to be hardened to form the channeled plate 3.

[0052] In certain embodiments, the forming material 30 is made of liquid silicone rubber and is formed into the channeled plate 3 by injection molding technique. In certain embodiments, the forming material 30 may be made of a thermoplastic material, such as styrenic thermoplastic elastomer, and may be hardened by cooling instead of heating.

[0053] To sum up, in this disclosure, the array of the upper ribs 511 of the upper mold 51, the array of the lower ribs 521 of the lower mold 52, and the gaps (G) formed between the upper and lower molds 51, 52 to ensure that the upper microfluidic channels 311, the lower microfluidic channels 321, and the thin film valves 331 of the channeled plate 3 are precisely arranged with respect to each other according to desired lay out, thereby ensuring normal function of the microfluidic chip made by the method of this disclosure.

[0054] In the description above, for the purposes of explanation, numerous specific details have been set forth in order to provide a thorough understanding of the embodiments. It will be apparent, however, to one skilled in the art, that one or more other embodiments may be practiced without some of these specific details. It should also be appreciated that reference throughout this specification to one embodiment, an embodiment, an embodiment with an indication of an ordinal number and so forth means that a particular feature, structure, or characteristic may be included in the practice of the disclosure. It should be further appreciated that in the description, various features 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 various inventive aspects.

[0055] While the disclosure has been described in connection with what are considered the exemplary embodiments, it is understood that this disclosure is not limited to the disclosed embodiments but is intended to cover various arrangements included within the spirit and scope of the broadest interpretation so as to encompass all such modifications and equivalent arrangements.