Microfluidic system or device and method of manufacturing a microfluidic system or device

Abstract

A method of manufacturing a microfluidic system or microfluidic device having at least one channel includes providing a base sheet, providing a deformable intermediate layer, providing a cover film, and laminating the base sheet, the intermediate layer and the cover film so that a back surface of the intermediate layer is attached to a front surface of the base sheet and a back surface of the cover film is attached to a front surface of the intermediate layer opposite to the back surface thereof, thereby forming a laminate comprising the base sheet, the intermediate layer and the cover film. Further, the method includes applying pressure to the front surface of the intermediate layer through the cover film so as to deform the intermediate layer, thereby forming the at least one channel. The invention also relates to a microfluidic system or microfluidic device) manufactured by this method.

Claims

1. A method of manufacturing a microfluidic device having at least one channel, wherein the method comprises: providing a base sheet; providing a deformable intermediate layer; providing a cover film; laminating the base sheet, the intermediate layer and the cover film so that a back surface of the intermediate layer is attached to a front surface of the base sheet and a back surface of the cover film is attached to a front surface of the intermediate layer opposite to the back surface of the intermediate layer, thereby forming a laminate comprising the base sheet, the intermediate layer and the cover film; and applying pressure to the front surface of the intermediate layer by a pressure application means, the pressure applied by the pressure application means pressing the intermediate layer through the cover film so as to deform the intermediate layer, thereby forming the at least one channel, the method further including removing the pressure application means from the entire laminate, including the base sheet, the intermediate layer and the cover film, wherein a thickness of the intermediate layer where the at least one channel is formed is smaller than a thickness of the intermediate layer where the channel is not formed, and the intermediate layer is curable by an external stimulus.

2. The method according to claim 1, wherein the cover film is expandable and the method further comprises expanding the cover film.

3. The method according to claim 2, wherein the cover film is expanded when the pressure is applied to the front surface of the intermediate layer through the cover film.

4. The method according to claim 1, further comprising applying the external stimulus to the intermediate layer so as to cure the intermediate layer, after forming the at least one channel.

5. The method according to claim 1, wherein the base sheet, the intermediate layer and the cover film are laminated first, thereby forming the laminate comprising the base sheet, the intermediate layer and the cover film, and subsequently pressure is applied to the front surface of the intermediate layer through the cover film so as to deform the intermediate layer, thereby forming the at least one channel.

6. The method according to claim 1, wherein the at least one channel has a width in the range of 5 to 800 μm and/or a depth in the range of 5 to 200 μm and/or a length in the range of 0.5 to 100 mm.

7. The method according to claim 1, wherein the microfluidic device has a plurality of channels, and the pressure is applied to the front surface of the intermediate layer through the cover film so as to deform the intermediate layer, thereby forming the plurality of channels.

8. The method according to claim 7, wherein at least two of the plurality of channels are connected to each other.

9. The method according to claim 1, wherein the pressure is applied to the front surface of the intermediate layer through the cover film by a stamp, a mold or a die.

10. The method according to claim 1, wherein the base sheet is made of a rigid material.

11. The method according to claim 1, wherein the base sheet has a thickness in the range of 200 to 1500 μm.

12. The method according to claim 1, wherein the intermediate layer is formed of a resin, an adhesive or a gel.

13. The method according to claim 1, wherein the intermediate layer has a thickness in the range of 20 to 1000 μm.

14. The method according to claim 1, wherein the cover film is made of a polymer material.

15. The method according to claim 1, wherein the cover film has a thickness in the range of 5 to 200 μm.

16. A microfluidic device having at least one channel, wherein the microfluidic device comprises: a laminate comprising a base sheet, an intermediate layer and a cover film; wherein a back surface of the intermediate layer is attached to a front surface of the base sheet and a back surface of the cover film is attached to a front surface of the intermediate layer opposite to the back surface of the intermediate layer, and the at least one channel is formed in the intermediate layer of the laminate so that the entire at least one channel is exposed along a front surface of the cover film opposite to the back surface of the cover film, a thickness of the intermediate layer where the at least one channel is formed is smaller than a thickness of the intermediate layer where the channel is not formed, and the intermediate layer is curable or cured by an external stimulus.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Hereinafter, non-limiting examples of the invention are explained with reference to the drawings, in which:

(2) FIG. 1 is a perspective view showing a first embodiment of a pressure application means to be used for the manufacturing method of the present invention;

(3) FIG. 2 is a perspective view showing a second embodiment of a pressure application means to be used for the manufacturing method of the present invention;

(4) FIG. 3 is a schematic cross-sectional view of the pressure application means shown in FIG. 2;

(5) FIG. 4 is a cross-sectional view illustrating a step of attaching a cover film to the pressure application means shown in FIG. 2 in a manufacturing method according to an embodiment of the present invention;

(6) FIG. 5 is a cross-sectional view showing the outcome of the attachment step illustrated in FIG. 4;

(7) FIG. 6 is a cross-sectional view illustrating a step of pressing the pressure application means, having the cover film attached thereto, against an intermediate layer in the manufacturing method according to the embodiment of the present invention;

(8) FIG. 7 is a cross-sectional view showing the outcome of the pressure application step illustrated in FIG. 6;

(9) FIG. 8 is a cross-sectional view illustrating a step of curing the intermediate layer in the manufacturing method according to the embodiment of the present invention;

(10) FIG. 9 is a cross-sectional view illustrating a step of removing the pressure application means from a laminate, comprising a base sheet, the intermediate layer and the cover film, in the manufacturing method according to the embodiment of the present invention;

(11) FIG. 10 is a cross-sectional view illustrating a step of cutting the laminate in the manufacturing method according to the embodiment of the present invention;

(12) FIG. 11 is a top view showing a microfluidic system or device obtained by the cutting step illustrated in FIG. 10;

(13) FIG. 12 is a cross-sectional view of the microfluidic system or device shown in FIG. 11;

(14) FIG. 13 is an enlarged view of the encircled area in FIG. 12; and

(15) FIG. 14 is a cross-sectional view of a laminate, comprising a base sheet, an intermediate layer and a cover film, for use in a manufacturing method according to another embodiment of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

(16) Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. The preferred embodiments relate to methods of manufacturing microfluidic systems or microfluidic devices and to microfluidic systems or microfluidic devices manufactured by these methods.

(17) FIG. 1 is a perspective view showing a first embodiment of a pressure application means 2 which can be used for the manufacturing method of the present invention. The pressure application means 2 is in the form of a mold or a die.

(18) The pressure application means 2 has a base 3, i.e., a base substrate, and a plurality of projections 5 protruding from the base 3, i.e., protruding from a plane surface of the base 3. The projections 5 are formed on a front side 3a of the base 3.

(19) The base 3 has a circular shape in a top view thereon. All of the projections 5 are identical to each other in shape, substantially exhibiting a Y-shape in a top view on the pressure application means 2 (see FIG. 1). Further, all of the projections 5 have the same dimensions, i.e., the same length, width and height.

(20) The base 3 and the projections 5 are made of the same material. The material of the base 3 and the projections 5 is a rigid, hard material, such as a metal, a plastic, a ceramic or a semiconductor, e.g., Si.

(21) The projections 5 may be formed on the front side 3a of the base 3 by a cutting process, such as mechanical cutting, e.g., using a blade or a saw, or laser cutting, as has been detailed above.

(22) FIG. 2 is a perspective view showing a second embodiment of a pressure application means 2 which can be used for the manufacturing method of the present invention. Also the pressure application means 2 of the second embodiment is in the form of a mold or a die.

(23) The pressure application means 2 according to the second embodiment differs from the pressure application means 2 according to the first embodiment in the shape of the base and the configuration of the projections. In the description of the second embodiment of the pressure application means 2, the elements which are substantially identical or similar to those of the first embodiment are denoted by the same reference signs and a repeated detailed description thereof is omitted.

(24) As is shown in FIG. 2, the base 3 of the pressure application means 2 according to the second embodiment has a rectangular shape in a top view thereon. Two different types of projections 5a, 5b are formed on a front side 3a of the base 3. The first projections 5a are identical to each other in shape, substantially exhibiting a Y-shape in a top view on the pressure application means 2. The second projections 5b are identical to each other in shape, exhibiting an undulating shape with a branched end portion in a top view on the pressure application means 2 (see FIG. 2). Further, all of the first projections 5a have the same dimensions, and all of the second projections 5b have the same dimensions.

(25) Due to the provision of the two different types of projections 5a, 5b on the front side 3a of the base 3, the pressure application means 2 shown in FIG. 2 can be used to manufacture a plurality of different microfluidic systems or devices, having different types of channels, in a single process, as will be further detailed below. Hence, this pressure application means 2 can be particularly advantageously used for the mass production of such systems and devices.

(26) The shape of the base 3 is not particularly limited and can be, for example, a circular shape (see FIG. 1), an oval shape or a polygonal shape, such as a rectangular shape (see FIG. 2) or a square shape.

(27) The shapes and dimensions of the projections 5, 5a, 5b are chosen dependent on the desired shapes and dimensions of the channel or channels to be formed. The shapes and dimensions of the channel or channels to be formed will be substantially identical to those of the projections 5, 5a, 5b, allowing for the channel or channels to be formed with a high degree of accuracy.

(28) FIG. 3 is a schematic cross-sectional view of the pressure application means 2 shown in FIG. 2. Specifically, FIG. 3 shows a cross-section along the long side of the rectangular base 3 and through the portion of the base 3 where the second projections 5b are arranged. It is to be noted that, for the sake of simplicity and better presentability, only ten portions of the projections 5b are shown in the cross-sectional view of FIG. 3. As is further shown in FIG. 3, the base 3 has a back side 3b opposite to its front side 3a.

(29) In the following, a method of manufacturing a microfluidic system or microfluidic device according to an embodiment of the present invention, using the pressure application means 2 shown in FIG. 2, will be described with reference to FIGS. 4 to 13.

(30) First, a cover film 4 is provided (see FIG. 4). The cover film 4 has a front surface 4a and a back surface 4b. The cover film 4 may be made of a polymer material, such as polyvinyl chloride (PVC), polyolefin (PO) or ethylene vinyl acetate (EVA). For example, the cover film may be a “Saran” wrap-like material.

(31) The cover film 4 may have a thickness in the range of 5 to 200 μm, preferably 8 to 100 μm, more preferably 10 to 80 μm and even more preferably 12 to 50 μm.

(32) The cover film 4 is flexible and pliable, so that it can be particularly reliably ensured that the cover film 4 conforms to the contours of the projections 5a, 5b. Particularly preferably, the cover film 4 is expandable, e.g., expandable to twice its original size or more, three times its original size or more, or four times its original size or more.

(33) An adhesive layer 9 is applied to the front surface 4a of the cover film 4. The adhesive layer 9 may have a thickness in the range of 5 to 200 μm, preferably 10 to 150 μm and even more preferably 20 to 100 μm.

(34) The adhesive layer 9 is provided only in a peripheral area of the cover film 4, as is shown in FIG. 4. For example, the adhesive layer 9 may have an annular shape. The adhesive layer 9 serves to attach the cover film 4 to a frame 10, such as an annular frame. By attaching the cover film 4 to the frame 10 in this manner (see FIG. 4), handling of the cover film 4 in subsequent process steps is facilitated. However, the use of a frame, such as the frame 10, for handling the cover film 4 is purely optional. Further, the adhesive layer 9 serves to attach the cover film 4 to the front side 3a of the base 3, as will be detailed below with reference to FIG. 5.

(35) The adhesive of the adhesive layer 9 may be curable by an external stimulus, such as heat, UV radiation, an electric field and/or a chemical agent. In this way, the pressure applications means 2 can be particularly easily removed after forming the plurality of channels. The external stimulus may be applied to the adhesive so as to lower the adhesive force thereof, thus allowing for an easy removal of the pressure applications means 2.

(36) After attaching the cover film 4 to the frame 10 by means of the adhesive layer 9, the cover film 4 is attached to the front side 3a of the base 3 of the pressure application means 2 shown in FIG. 2, as is indicated by an arrow in FIG. 4. Before attaching the cover film 4 to the front side 3a of the base 3, the pressure application means 2 is placed on a chuck table 12, e.g., in a vacuum chamber, in a state in which the back side 3b of the base 3 is in contact with an upper surface of the chuck table 12 and the front side 3a of the base 3, from which the projections 5a, 5b protrude, is oriented upward (see FIG. 4).

(37) As has been indicated above, the step of attaching the cover film 4 to the front side 3a of the base 3 may be carried out in a vacuum chamber. In particular, the cover film 4 may be attached to the front side 3a of the base 3 by using a vacuum laminator, e.g., in the manner detailed above. If the cover film 4 is expandable, it is expanded when being attached to the front side 3a of the base 3.

(38) The outcome of the attachment step illustrated in FIG. 4 is shown in FIG. 5. As is shown in this latter drawing, the cover film 4 is attached to the front side 3a of the base 3 so as to closely follow the contours of the projections 5a, 5b. Hence, at a subsequent stage of the manufacturing method of the present embodiment, channels can be formed with a particularly high degree of accuracy.

(39) The cover film 4 is attached to the front side 3a of the base 3 by means of the adhesive layer 9. As is also shown in FIG. 5, the adhesive layer 9 is provided only in a peripheral area of the front side 3a. Thus, it can be particularly reliably ensured that no residues of the adhesive layer 9 remain in the region of the front side 3a where the projections 5a, 5b are formed after removal of the pressure applications means 2. Also, any adhesive residues in the channels to be formed by the pressure applications means 2 are avoided.

(40) Further, by providing the adhesive layer 9 only in the peripheral area of the front side 3a, the area in which cover film 4 and pressure applications means 2 are attached to each other via the adhesive is significantly reduced. Thus, the pressure applications means 2 can be removed more easily after forming the channels.

(41) In addition or as an alternative to attaching the cover film 4 to the front side 3a of the base 3 by means of the adhesive layer 9, the cover film 4 may be attached to the front side 3a by heating the cover film 4 during and/or after applying the cover film 4 to the front side 3a. Further, the cover film 4 can be softened by such a heating process, thus particularly reliably ensuring that the cover film 4 conforms to the topography of the front side 3a.

(42) An attachment force between cover film 4 and base 3 may be generated through the heating process, as has been detailed above. The attachment of the cover film 4 to the base 3 may be caused in the heating process itself and/or in a subsequent process of allowing the cover film 4 to cool down. For example, the cover film 4 may be softened by the heating process. Upon cooling down, e.g., to its initial temperature, the cover film 4 may reharden, e.g., so as to create a form fit and/or a material bond to the base 3.

(43) The cover film 4 may be heat resistant up to a temperature of 180° C. or more, preferably up to a temperature of 220° C. or more, and more preferably up to a temperature of 250° C. or more. In the heating process, the cover film 4 may be heated to a temperature in the range of 60° C. to 150° C., preferably 70° C. to 140° C., more preferably 80° C. to 130° C. and even more preferably 90° C. to 120° C. Particularly preferably, the cover film 4 is heated to a temperature of approximately 100° c.

(44) In the heating process, the cover film 4 may be heated over a duration in the range of 30 sec to 10 min, preferably 1 min to 8 min, more preferably 1 min to 6 min, even more preferably 1 min to 4 min and yet more preferably 1 min to 3 min, during and/or after applying the cover film 4 to the front side 3a of the base 3.

(45) The cover film 4 may be directly and/or indirectly heated, as has been detailed above. For example, the cover film 4 may be indirectly heated by heating the pressure application means 2 before and/or during and/or after applying the cover film 4 to the front side 3a of the base 3. The pressure application means 2 may be heated by heating the chuck table 12 (see FIG. 4).

(46) Alternatively, the cover film 4 may be attached to the front side 3a of the base 3 in a different manner, other than heating the cover film 4 and/or using the adhesive layer 9. In particular, the cover film 4 may be attached to the front side 3a of the base 3 without the use of an adhesive.

(47) Further, a base sheet 7 and a deformable intermediate layer 13 are provided (see FIG. 6).

(48) The material of the base sheet 7 is not particularly limited. Preferably, the base sheet 7 is made of a rigid material, such as polyethylene terephthalate (PET) and/or silicon and/or glass and/or stainless steel. The base sheet 7 may have a thickness in the range of 200 to 1500 μm, preferably 400 to 1200 μm and more preferably 500 to 1000 μm.

(49) The intermediate layer 13 may be formed of a resin, an adhesive, a gel or the like. The intermediate layer 13 may have a thickness in the range of 20 to 1000 μm, preferably 50 to 800 μm, more preferably 100 to 600 μm, even more preferably 150 to 500 μm, and yet even more preferably 200 to 400 μm.

(50) The intermediate layer 13 is curable by an external stimulus, such as UV radiation, heat, an electric field and/or a chemical agent. Thus, the intermediate layer 13 hardens, at least to some degree, upon application of the external stimulus thereto. The intermediate layer 13 may be configured so as to reach a rigid, hard state after curing. Preferred examples of UV curable resins for use as the intermediate layer 13 are ResiFlat by the DISCO Corporation and TEMPLOC by DENKA.

(51) The base sheet 7 and the intermediate layer 13 are laminated so that a back surface of the intermediate layer 13 is attached to a front surface of the base sheet 7. A back surface 7b of the base sheet 7 opposite to its front surface (see FIG. 8) is arranged on an upper surface of a support 14, such as a chuck table (see FIG. 6). A front surface 13a of the intermediate layer 13 opposite to its back surface is arranged so as to face upwards.

(52) Subsequently, the pressure application means 2, having the cover film 4 attached thereto, is pressed against the front surface 13a of the intermediate layer 13, as is illustrated by an arrow in FIG. 6. In this way, pressure is applied to the front surface 13a of the intermediate layer 13 through the cover film 4 so as to deform the intermediate layer 13, thereby forming a plurality of channels 20 (see FIG. 9). Specifically, the projections 5a, 5b are pressed into the intermediate layer 13, with the cover film 4 arranged therebetween, so as to deform the intermediate layer 13.

(53) Further, by pressing the pressure application means 2, having the cover film 4 attached thereto, against the front surface 13a of the intermediate layer 13, the back surface 4b of the cover film 4 is attached to the front surface 13a of the intermediate layer 13, thereby forming a laminate comprising the base sheet 7, the intermediate layer 13 and the cover film 4. Hence, in the method of the present embodiment, the channels 20 are formed during, i.e., at the same time as, forming the laminate comprising the base sheet 7, the intermediate layer 13 and the cover film 4.

(54) FIG. 7 is a cross-sectional view showing the outcome of the pressure application step illustrated in FIG. 6. The back surface 7b of the base sheet 7 is parallel to the back side 3b of the base 3 of the pressure application means 2, as is indicated by dashed arrows in FIG. 7. Thus, the channels 20 are formed in a particularly precise and homogeneous manner.

(55) Subsequently, the external stimulus, such as UV radiation, heat, an electric field and/or a chemical agent, is applied to the intermediate layer 13, as is indicated by arrows in FIG. 8, so as to cure the intermediate layer 13.

(56) Specifically, the intermediate layer 13 is cured by applying the external stimulus thereto while the projections 5a, 5b are pressed into the intermediate layer 13. By curing the intermediate layer 13, the attachment between cover film 4 and intermediate layer 13 may be further enhanced.

(57) If the base sheet 7 is made of PET or glass and the intermediate layer 13 is curable by radiation, the intermediate layer 13 may be cured with radiation that is transmittable through PET or glass, for instance UV radiation. In this case, the radiation may be applied from the side of the back surface 7b of the base sheet 7 (see FIG. 8). For example, ResiFlat by the DISCO Corporation and TEMPLOC by DENKA may be used as UV curable resins for the intermediate layer 13.

(58) After curing the intermediate layer 13, the pressure application means 2 is removed from the laminate, as is indicated by an arrow in FIG. 9.

(59) If the adhesive of the adhesive layer 9 is curable by an external stimulus, such as heat, UV radiation, an electric field and/or a chemical agent, this stimulus may be applied to the adhesive so as to lower the adhesive force thereof, thus allowing for a particularly easy removal of the pressure applications means 2 from the laminate.

(60) As is further shown in FIG. 9, the laminate comprises a plurality of channels 20 formed therein by the pressure applications means 2. The channels 20 are formed in the laminate so as to be open to the side of the cover film 4.

(61) After removing the pressure applications means 2 from the laminate, the laminate is cut along its thickness direction, as is indicated by dashed vertical lines in FIG. 10. In this way, a plurality of microfluidic systems and/or microfluidic devices 30 (see FIG. 11) are obtained.

(62) Further, by this cutting process, the microfluidic systems and/or microfluidic devices 30 are separated from the adhesive layer 9 and the frame 10.

(63) FIG. 11 is a top view showing a microfluidic system or device 30 obtained by the cutting step illustrated in FIG. 10. The microfluidic system or device 30 is a microfluidic system or device according to an embodiment of the present invention.

(64) The microfluidic system or device 30 has a channel 20, the shape and dimensions of which are substantially identical to those of the second projections 5b. Specifically, the channel 20 has an undulating shape with a branched end portion in a top view on the microfluidic system or device 30. Hence, the channel 20 effectively consists of two channels which are connected to each other, the first channel consisting of the undulating portion of the channel 20 and one straight branch of the branched end portion and the second channel consisting of the other straight branch of the branched end portion. The branched end portion of the channel 20 may be used, e.g., for separating and/or mixing a fluid or fluids, in particular, small amounts of a fluid or fluids, e.g., on the order of microliters.

(65) The channel 20 is configured to receive and transport test materials and specimens to be treated and/or analysed. The channel 20 is a microfluidic channel.

(66) The channel 20 may have a width in the range of 5 to 800 μm, preferably 10 to 600 μm, more preferably 20 to 400 μm and even more preferably 50 to 200 μm. The channel 20 may have a depth in the range of 5 to 200 μm, preferably 10 to 150 μm and more preferably 20 to 100 μm. The channel 20 may have a length in the range of 0.5 to 100 mm, preferably 1 to 80 mm, more preferably 2 to 60 mm and even more preferably 5 to 50 mm.

(67) FIG. 12 is a cross-sectional view of the microfluidic system or device 30 taken along the dashed line in FIG. 11. FIG. 13 is an enlarged view of the encircled area in FIG. 12. As is shown in FIG. 13, the channel 20 does not extend along the entire thickness of the intermediate layer 13.

(68) According to another embodiment of the manufacturing method of the present invention, the base sheet 7, the intermediate layer 13 and the cover film 4 may be laminated first, thereby forming the laminate comprising the base sheet 7, the intermediate layer 13 and the cover film 4. Such a laminate is shown in FIG. 14. Optionally, an adhesive layer 9 may be applied to the front surface 4a of the cover film 4 substantially in the same manner as detailed above. The adhesive layer 9 may serve to attach the cover film 4 to a frame, such as the frame 10, in order to facilitate handling of the laminate in subsequent process steps. However, the adhesive layer 9 may also be omitted.

(69) Subsequently, after forming the laminate, pressure may be applied to the front surface 13a of the intermediate layer 13 through the cover film 4 so as to deform the intermediate layer 13, thereby forming the channels 20 in the laminate.

(70) The process of applying pressure to the front surface 13a of the intermediate layer 13 may be performed substantially in the same manner as detailed above, i.e., by using the pressure application means 2. The approach of the present embodiment mainly differs from that described above with reference to FIGS. 4 to 13 in that the cover film 4 is attached to the intermediate layer 13 rather than the pressure application means 2 when the pressure application means 2 is pressed against the intermediate layer 13.

(71) If the cover film 4 is expandable, it is expanded when the pressure is applied to the front surface 13a of the intermediate layer 13 through the cover film 4.

(72) Subsequent steps of curing the intermediate layer 13, removing the pressure application means 2 from the laminate and cutting the laminate may be performed in the same manner as described above with reference to FIGS. 8 to 10.