TWI275562B - Microfluidic device and method for packaging same - Google Patents

Abstract

A microfluidic device and method for packing same are disclosed. The method comprising providing a first substrate, a second substrate and an intermedium layer disposed between the first substrate and second substrate. The first substrate is provided with a plurality of connection openings and the second substrate is provided, correspondingly, with a plurality of connection pins protruding therefrom. The connection pins pass through the connection openings and subsequently are imposed heat and pressure at the top ends of the pins such that the first substrate, second substrate and the intermedium layer are tightly bonded to form a microfluidic configuration.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a microfluidic driving device and an assembly method thereof, and more particularly to a microfluidic driving device assembly for use in, for example, protein detection, screening, nucleic acid hybridization, and the like. method. [Prior Art] Recently, microfluidic driving devices have been used to process, analyze, and inspect biological substances (such as nucleic acids or proteins), which are generally fabricated in small pieces using microelectromechanical techniques (eg, 1〇X 10x3 public). a microfluidic channel, a pump, a valve, a reaction chamber, and the like are fabricated on the carrier. Through these configurations, the known specific biological substance applied to the carrier can be surface-measured, and the result after the contact is further Each _ face or money substance is quantified to determine the object to be tested. The 15-20 microfluidic drive device is constructed of a structurally uniform substrate, so that the combination of the multilayer substrates is involved in the group f. There are known a variety of microfluidic crane device multilayer substrate junctions: methods such as adhesion, screwing, and the like. Most of the adhesives use a viscous layer or a glue as a medium for 2. For example, in U.S. Patent No. 6,548,895, a microfluidic driven interlayer layer is lost between the two substrates to adhere the substrate. However, in the case of using adhesiveness, it is necessary to carefully position the miscellaneous layer to drive the components of the 3 channel and the chamber, etc. In the case of using the transfer assembly, it is also necessary to pay attention to the subsequent σ coating. Turn over the overflow to the ribbed flow channel and chamber. Therefore, conventional methods require careful handling of the assembly of the microfluidic drive, thus allowing the required assembly to be added. In addition, no matter whether the layered silk gel is used to assemble the texture driving device, the heart 5 is cut off 5 (for example, the adhesive layer or the component of the Na is contaminated by the flow channel), and the misjudgment may occur in the future when adding the test. In addition to the increased man-hours required for the non-two-two drive unit, the known adhesion test may affect the test results. Others, such as the technique of screwing a multi-layer substrate, avoid the above-mentioned stickiness, . The assembly time of the shackle screw will be longer than that of the viscous method. In addition, the combination method of the conventional 25 1275562 requires more bonding materials, so it is expensive. Because of the assembly of the multilayer substrate of the conventional microfluidic driving device The method has the above-mentioned defects, so a microfluidic driving device and an assembly method which can quickly assemble a multi-layer substrate, and which are low in cost and do not affect the accuracy of the inspection result are required. SUMMARY OF THE INVENTION An object of the present invention is to provide a microfluidic driving device and The assembly method, the device is suitable for rapid assembly and is not easy to cause defects in assembly and affects the detection capability and correctness of the fluid drive device. The microfluid drive according to the present invention The device includes: first and third substrates that are mutually rich to form a fluid between the first and second substrates, wherein the fluid layout is formed by the first or second substrate a plurality of fluid storage tanks, a reaction zone, and a passage extending from the fluid storage tank to one or more capillary sizes of the reaction zone to restrict fluid flow from the fluid storage tank to the reaction zone; a seal is located in the first An intermediate layer of the interface between the second substrates, wherein the sealing interface formed by the intermediate layer forms the fluid layout and the bonding interface between the first and second substrates, and is included on the first substrate a plurality of engagement holes formed at intervals and spaced apart from the second substrate to form a plurality of engagement pins respectively corresponding to the positions of the engagement holes, in such a manner that when the engagement pins are respectively engaged with the engagement holes, the The first base 2 is fixed by the second substrate such that the intermediate layer is sealed between the first and second substrates. In an embodiment, the lower surface of the first substrate forms at least one set of grooves and recesses, Groove and recess Connecting the upper surface of the second substrate to form at least one set of recesses corresponding to the grooves and recesses on the lower surface of the first substrate; the elastic intermediate layer includes a plurality of through holes corresponding to the grooves and recesses of the first substrate, and the a recess of the second substrate. When the first substrate: the intermediate layer is tightly coupled to the second substrate, the elastic intermediate layer, the first plate, and the corresponding groove in the second substrate The recess and the through hole constitute a fluid structure such as a fluid storage 1255562 groove, a capillary, a pump, a valve, a reaction chamber, and a waste chamber. In another embodiment, the joint layout includes the first substrate and the second substrate. A plurality of corresponding engaging holes are respectively formed at intervals, and a plurality of engaging pins respectively passing through the engaging holes to fix the first substrate and the second substrate together. The present invention also provides an assembly of the microfluidic driving. [Embodiment] The present invention provides a microfluidic driving device formed by combining three or more layers of materials in a heated lamination manner. As shown in Fig. 1, a microfluidic driving device 8 according to an embodiment of the present invention comprises a first substrate 1A, a second substrate 40, and an elastic intermediate layer 3B between the two layers. The bottom surface 12 of the first substrate 10 forms five sets of similar recesses (丨4, 15, 16, 17) and the recesses 18. For the sake of brevity, only one of the sets, that is, the recesses 18 are sequentially connected to separate recesses ( 14, 15, 16, 17), the groove 18 is bent into a braid at the crotch region 22 and terminates at the end point 24. As explained below, when the first substrate 1 and the elastic intermediate layer 3 are joined to the second substrate 40, the recess 14 is formed to correspond to the elastic intermediate layer 3 and the second substrate 4 to form a sample fluid or The storage tank for the reagent, the recesses (15 and 17, 16) and the corresponding positions 32 and 34, 42 of the elastic intermediate layer 30 and the second substrate 40 respectively constitute a valve element and a pump, and the groove 18 and the elastic intermediate layer 3〇 corresponds to the position of the second substrate 4〇 to form a capillary for fluid circulation, and the crotch region 22 constitutes a reaction chamber with a position corresponding to the elastic intermediate layer 3〇 and the second substrate 40. The fluid storage tank, the reaction zone, the capillary size passage, and the like constitute a fluid layout. The elastic intermediate layer 30 has five sets of through-holes penetrating from the top surface (the surface adjacent to the first substrate 10) to the bottom surface (the surface adjacent to the second substrate 40). For the sake of brevity, only one of them is illustrated. Group, that is, through holes (32, 34). The through holes (32, 34) correspond to the recesses (15, 17) of the first substrate 10 to form a valve member after the layers are combined, while the elastic intermediate layer 30 covers the recess 16 of the first substrate 1 to constitute a pump cavity. The elastic intermediate layer 3 has a bead perforation 38 corresponding to the end point 24 of the crotch region 22 of the first substrate 1; and the through hole 36 corresponds to the through hole 19 of the first substrate 1''. 1275562 The first substrate 40 has five sets of similar recesses (42, 44) formed on its top surface 41. For the sake of brevity, only one of the sets, namely the grooves (42, 44), will be described. When the first substrate 1 and the elastic intermediate layer 30 are joined to the second substrate 4, the grooves (42, 44) correspond to the through holes (32, 34) of the elastic intermediate layer 30 and the recesses of the first substrate 1 (15). (7) to form the valve element. The top surface 41 of the second substrate 40 further has a recess 48 which can communicate with the through holes 36 and 38 of the elastic intermediate layer 30. When the elastic intermediate layer 23 is engaged with the second substrate 4, the recess 48 The waste liquid chamber is configured to receive the waste liquid from the reaction chamber 22, and the through holes 36 and 19 provide ventilation. The first substrate 10, the elastic intermediate layer 3〇 and the second substrate 4〇 can be combined to form a liquid to be tested. The analyte is transported, for example, by an external device (not shown), the liquid sample to be tested, the appropriate reagent is input into a specific storage tank through a hole (not drawn) on the first substrate 1 , and then an external actuating device is used ( Not shown) the pump and the valve element are activated, and the liquid sample and the reagent to be tested are flowed through the capillary channel according to a specific sequence, and flow into the reaction chamber, and the biological substance fixed in the reaction chamber may or may not react. Inspection and analysis of the liquid sample to be tested. The operation is described in more detail in the applicant's patent application entitled "Microfluidic Drives", No. 91,224, 431, filed on Sep. 27, 1989. The first and second substrates of the present invention can be used. Suitable thermoplastic plastic materials to produce 'such as polymethyi nethacryiate (pmMA), polystyrene (PS), polycarbonate (p〇iyCarb〇nate, pc), polypropylene (polypropylene) , PP), polyvinyl chloride (p〇iyyinyichi〇r [de, PVC), cyclic olefin copolymer (C0C) and propylene nitrite-butylene-styrene copolymer (ABS). If the reaction chamber needs to transmit light to enhance or detect the reaction, the first substrate may be selected from a transparent thermoplastic plastic material. The elastic intermediate layer has compressible and bendable elasticity to form a liquid-tight, airtight structure with the adjacent substrate. The seal forms a fluid structure such as a capillary channel, a through hole, a reaction chamber, a pump and a valve. The elastic intermediate layer can be formed of a polymer or a rubber material such as latex or silicone elastomer (silicone elas). One of t〇mers), polyethylene vinyl b〇lyyinylchl〇ride, 1275562 PVC) and fluoroelastomer (flu〇r〇eiast〇mers). 5 10 15 20 The grooves, recesses or through holes on the first substrate and the second substrate for forming capillary channels, through holes, reaction chambers, pumps and valves, etc., can be formed by plastic injection molding technology, die casting molding, Hot pressing or cutting is formed. The thickness of the substrate is generally from 丨 cm to 3 cm ' but is not limited thereto. The fluid structure on the intermediate elastic layer can be formed by methods such as die cutting, rotary die cutting, laser cutting, injection molding, or reactive injection molding. One of the features of the present invention is that the three-layer structure can be tightly coupled by a heating lamination method. For this reason, as shown in FIGS. 1 and 2, a plurality of engagement holes 60 are provided around the first substrate 1〇, and the engagement holes are provided. The counterbore 62 and the guiding hole 63 are both formed. The elastic intermediate layer 3 is provided with an opening 64 at the corresponding engaging hole 60. The second substrate 40 is provided with an engaging pin 66 corresponding to the upwardly protruding engaging hole 6〇. In order to place the elastic intermediate layer 3 between the first substrate 10 and the second substrate 40, as shown in FIG. 2, the bonding pin 66 of the second substrate 4 is over the opening of the elastic intermediate layer 3 64. The guiding hole portion 63 of the first substrate 1 is engaged with the guiding hole portion 63 and beyond the length of the counterbore 62, and the length can be deformed and expanded under the subsequent hot pressing procedure to tightly combine the aforementioned three layers, as described below. . Referring to FIG. 4A, the first substrate 1A, the elastic intermediate layer 30 and the second substrate 40 semi-finished product as shown in FIG. 2 are first placed on the lower table 82 of a hot press 8〇, and the cylinder 84 is lowered. The table 82 drives the semi-finished product to rise, and approaches the upper table 81. When the upper table 81 contacts the spring pin 88 (refer to the upper table 81 for the first base (1), the intermediate layer 30, and the second substrate 4 At the same time, the pressure is applied, and at the same time, the heated heating rod % starts to contact the top end of the engaging pin 66. The table 81 and 82_ continue to move upward, and the heating rod 86 presses the top end of the engaging pin 66 to be softened and deformed by the heat until it works. a phantom upper edge hits the lower edge of the limiting block 90, as shown in Fig. 4C. After a period of cold venting, the table 8 is returned to the original position, and the tip of the engaging pin 66 is condensed into a desired shape. 3, the joint 68 is shown. 25 1275562 Point 68 'The joint 68 is larger than the inner diameter of the joint hole 63, so that the first substrate 1 弹性, the elastic intermediate layer 3 〇 and the second substrate 4 〇 are tightly bonded together. The above heating stacking method is suitable for automated assembly without additional bonding materials, so The utility model can save the assembly man-hour and save the consumables cost. The heating stacking method without the adhesive material can also prevent the adhesive material from being blocked in the fluid passage of the substrate. The joint pin of the invention can be manufactured by using a suitable thermoplastic material. For example, polymethyl nethacrylate (PMMA), polystyrene (PS), polycarbonate (PC), polypropylene (PP), polyvinyl chloride (PVC), ring An olefin copolymer (cyclic olefin (7) (10) 5% C0C) and a propylene nitrite-butylene-styrene copolymer (ABS), etc. Further, in order to prevent hot deformation of the joint hole during hot pressing, the melting point of the material forming the joint hole Preferably, the melting point of the material forming the bonding pin is higher. In another embodiment, in order to make the first and second substrates closely fit, the elastic intermediate layer sandwiched between the two functions to provide a better sealing effect. The pair of engaging holes and the engaging pins are disposed not only around the substrate but also in the inner region of the substrate (that is, an area inward from the periphery of the substrate, not shown), close to the fluid reservoir. In the vicinity of the tank, the reaction zone, the waste liquid, the passage, and the like, and the corresponding opening 64 is also disposed in the intermediate layer 30. The joint layout thus constructed can better surround the fluid storage tank, the corresponding area, and the capillary size passage. Of course, the engaging pins in the above embodiments need not necessarily be disposed on the second substrate. For example, they may be reversely disposed on the first substrate and pass through corresponding holes in the intermediate elastic layer and the second substrate. Alternatively, it is also possible to form individual bonding pins by using a thermoplastic material, and to provide through holes and engaging holes and counter holes (not shown) on the respective substrates and the elastic layer, and to pass the bonding pins through the substrates and the elastic layer. The holes are pressed against the substrate and the elastic layer, and then the both ends of the pin are heat-pressed to deform and expand to tightly bond the substrates to the elastic layer. The fluid element structure and the number of the first substrate, the elastic intermediate layer and the second substrate of the present invention are only a non-limiting embodiment, and those skilled in the art can understand the structure and quantity of the fluid components. Selections/changes of design are made as needed, and such changes are considered to be within the scope of the claimed invention. Further, although the embodiment is an assembly of the 1275562 on the substrate, the substrate of the plurality of layers can be understood by those skilled in the art, and the techniques of the present invention can be combined. At the same time, the number and position of the engaging holes and the engaging pins on each of the substrates can also be selected according to actual conditions to achieve a tight and stable joint effect. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an exploded perspective view of a three-layer structure of a microfluidic driving device of the present invention; FIG. 2 is a schematic view of the three-layer structure of the microfluidic driving device of FIG. Figure 2 is a cross-sectional view of the three-layer structure semi-finished product of Figure 2 after hot pressing; Figures 4A-4C show the process of the semi-finished product shown in Figure 2 being placed on a hot press for heating lamination. [Description of Symbol Component Code] 8 Microfluidic Drive 10 First Substrate 12 Bottom Surface 14 Concave (Storage Slot) 15 Recess (Valve) 16 Concave (Gap) 17 Concave (Valve) 18 Groove (Capillary) 19 Through Hole 22 Crotch zone (reaction chamber) 24 End point 30 Elastic intermediate layer 32 Through hole 34 Through hole 36 Through hole 11 1275562 38 Through hole 40 Second substrate 41 Top surface 42 Groove 44 Groove 48 Concave (waste tank) 60 Bonding Hole 62 countersunk hole 63 guide hole

64 opening 66 dowel pin 68 joint 69 pin body 80 hot press 81 upper table 82 lower table 84 cylinder 86 heating pin 88 spring pin

90 Limit JC 12

Claims (1)

1275562 Pickup, patent application scope: 1. A microfluidic driving device comprising: first and second substrates overlapping each other to form a fluid cloth between the first and second substrates Restricting fluid from the fluid storage tank by - or a plurality of fluid storage tanks, a reaction zone, and a channel extending from the fluid storage tank to one or more capillary sizes of the first fresh base substrate Flowing into the reaction zone; sealing an intermediate layer between the first and second substrates, wherein the intermediate layer forms a closed interface to form the fluid layout between the first and second substrates; and a bonding arrangement, comprising: a plurality of bonding holes formed on the first substrate and a plurality of bonding pins spaced apart on the second substrate to respectively correspond to positions of the bonding holes, in this manner When the engaging pins are respectively engaged with the engaging holes, the first substrate is fixed by the second substrate such that the intermediate layer is sealed between the first and second substrates. 2. A microfluidic driving device comprising: 15 first and second substrates overlapping each other to form a fluid layout between the first and second substrates, wherein the fluid layout is located on the first and second substrates Forming one or more fluid storage tanks, a reaction zone, and a passage extending from the fluid storage tank to one or more capillary sizes of the reaction zone to restrict fluid flow from the fluid storage tank to the reaction zone; An intermediate layer located at an interface between the first and second substrates, wherein the sealed interface formed by the intermediate layer 20 forms a fluid layout between the first and second substrates; and a bonding layout included in the a plurality of corresponding engaging holes formed on the first substrate and the second substrate, and a plurality of engaging pins respectively passing through the engaging holes to fix the first substrate and the second substrate together So that the intermediate layer is sealed between the first and the second substrate. The microfluidic drive device of claim 1 or 2, wherein the intermediate layer is a compressible elastic layer formed of a polymer or a rubber material. 4. The microfluidic driving device of claim 3, wherein the polymer or rubber material is a latex 13 1275562 gel, a silicone elastomer, a polyethylene gas, or a fluoroelastomer. The microfluidic driving device of claim 1 or 2, wherein the first substrate and the second substrate are made of a thermoplastic material. The microfluidic driving device according to the fifth item of claim, wherein the thermoplastic plastic material is polymethyl propylene S stellite g, polystyrene, polycarbonate, polypropylene, polyethylene oxide, cycloolefin copolymer Or a propylene nitrite-butadiene-styrene copolymer. The microfluidic driving device of claim 1 or 2, wherein each of the engaging pins has an elongated pin body slidably into the engaging hole, respectively, and one of the pin bodies extends to engage the same The enlarged joints of the individual joint holes are such that the first substrate is fixed to the second substrate. 1. The microfluidic driving device of claim 7, wherein each of the engaging holes comprises a guiding hole portion and a countersunk hole portion extending coaxially, wherein a diameter of the guiding hole portion of the engaging hole is larger The countersunk portion is small so that the engaging pin can be slidably inserted into the engaging hole, respectively, so that the engaging pin is blocked by the guiding hole portion of the engaging hole, and the engaging point of the engaging pin can be engaged with the engaging hole The counterbore portion is partially engaged to closely engage the second substrate with the first substrate. I5 9. The microfluidic driving device of the seventh aspect of the printing track, wherein each of the engaging pins is composed of a deformable material such that the open end of the engaging pin slides into the engaging hole after the engaging pin respectively slides A deformation can be caused such that the open end becomes large to form a joint. 1A. The fluid drive device of claim 9, wherein the joint pin is made of a thermoplastic material. 2〇11·such as the Shenqing range 苐ίο item of the microfluidic drive device, wherein the thermoplastic plastic material is polymethyl methacrylate vinegar, polystyrene, polycarbonate, polypropylene, polyethylene, oxime A smoke copolymer, or a propylene nitrite-butadiene-styrene copolymer. 12. The microfluidic drive device of claim 7, wherein the material forming each of the joint holes has a melting point higher than a melting point of each of the materials forming the joint pin. 25 13 . The microfluidic driving device of claim 8 wherein each of the engaging pins is composed of a deformable material such that the open end of the engaging pin can slide into the engaging hole after the engaging pin is respectively slid The deformation causes the open end to become large to form a joint. </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; So that the first substrate and the second substrate are in close contact. The microfluidic driving device of claim 8, wherein the engaging holes are formed at intervals around and inside the first substrate, and the corresponding engaging pins are respectively engaged by the engaging holes, so that the The first substrate is in close contact with the second substrate. The microfluidic driving device of claim 13, wherein the engaging holes are formed at intervals around and inside the first substrate, and the corresponding engaging pins are respectively engaged by the engaging holes, so that the first The substrate is intimately bonded to the second substrate. 7. The microfluidic driving device of claim 14, wherein the intermediate layer further comprises a ruth or a plurality of openings formed around and inside the spacer so that the engaging pin can slide through the intermediate layer The opening is embedded in the joint hole to positively place the intermediate layer between the first substrate and the second substrate. The microfluidic drive device of claim 15, wherein the intermediate layer further comprises one or more openings formed around the interior and the interior thereof such that the engagement pin is slidably inserted through the opening of the intermediate layer The bonding hole is configured to positively place the intermediate layer between the first substrate and the second substrate. The microfluidic driving device of claim 16, wherein the intermediate layer further comprises a 1-2 〇 or a plurality of openings formed around and inside the spacer so that the engaging pin can slide through the intermediate layer The opening is embedded in the joint hole to positively place the intermediate layer between the first substrate and the second substrate. 2. A method of assembling a microfluidic driving device comprising a first substrate, a second substrate, and an intermediate layer sealed at an interface between the first and second substrates to form a fluid layout therein, comprising the steps of: 25 (λ) provides a first substrate having a plurality of through-holes; (b) providing a second substrate having a plurality of protrusions from the upper surface of the second substrate and respectively and the first substrate The plurality of engaging holes correspond to the engaging pins; 15 1275562 (6) sliding the engaging pins into the engaging holes to overlap the first and second substrates, wherein the intermediate layer is located on the first and second substrates Forming a hermetic interface to form a fluid layout between the first and second substrates; and (Φ causing the open end of each of the bonding pins to deform to form an enlarged joint to the first 5 and second substrates The assembly is carried out in an overlapping manner, and the intermediate layer is sealed between the first and second substrates. 21. The method of claim 20, wherein the step (9) further comprises using the heat to cause the one or more of the engagement pins The The method of claim 20, wherein the method of claim 20, wherein each of the engaging holes comprises a guiding hole portion and a countersunk portion extending coaxially The diameter of the guiding hole portion of the hole is smaller than that of the countersunk hole portion, so that the bonding pin can be used for the financial person to block the receiving pin so that the receiving pin is blocked by the guiding hole portion of the engaging hole and the engaging pin The bonding point can be engaged with the countersunk hole portion of the connector hole to make the second and first substrate tight. The method of claim 21, wherein each of the bonding includes a coaxial extension The diameter of the hole portion and the counterbore portion of the engaging hole are smaller than the counterbore portion so that the engaging pin can be slidably inserted into the individual engaging hole so that the engaging pin The miscellaneous miscellaneous joints of the joint hole can be bitten with the countersunk hole portion of the joint hole, so that the second and the first substrate are closely connected. 24. The method according to 2G, wherein the bonding hole is on the circumference of the second substrate and the internal interval Forming, and the engagement lock is extended from the circumference and the interior of the second substrate such that the engagement pins are respectively engaged by the engagement holes to tightly engage the first substrate and the second substrate. The method of claim 2, wherein the joint hole is formed around the first substrate and the inner side of the first substrate, and the closed portion of the second substrate of the joint lock region is extended and extended. So that the engaging pin can be engaged by the engaging hole, and the first substrate and the second substrate are tightly joined. 26. If the method of riding the 23rd riding method is applied, the _ _ _ s fresh-substrate week! 275562 Surrounding the internal ship, and the miscellaneous surface is extended from the circumference (10) of the two substrates so that the engaging pins can be bitten by the engaging holes, respectively, so that the first substrate and the second substrate are tightly bonded . 27. The method of claim 24, further comprising, prior to step (6), one or more openings formed in the compartment of the intermediate layer and internally spaced to allow the engagement pin to be slidably passed The opening of the intermediate layer is immersed in the joint hole to place the intermediate layer between the first substrate and the second substrate. 28. The method of claim 25, further comprising, prior to step (c), one or more openings formed around and within the intermediate layer such that the engagement pins are slidable The opening is embedded in the opening through the opening of the intermediate layer to place the intermediate layer between the __ substrate and the second substrate. The method of claim 26, further comprising, prior to step (c), an opening formed around and within the intermediate layer to allow the engaging pin to slide through the intermediate layer The opening is embedded in the joint hole to place the intermediate layer between the first substrate and the second substrate. 17