JP2006175387A - Liquid feed device and microfluidic device equipped with it - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new liquid feed device for feeding a liquid in a micro channel of a microfluidic device, and the microfluidic device equipped with it. <P>SOLUTION: The liquid feed device comprises a synthetic resin layer and a liquid feed tube embedded in the synthetic resin layer. The liquid feed tube has at least one opening communicating with the air at the embedded part of the synthetic resin layer. The microfluidic device comprises: the liquid feed device comprising the synthetic resin layer, and the liquid feed tube embedded in the synthetic resin layer and having at least one opening communicated with the air at the embedded part of the synthetic resin layer; and a polymer sheet, one side surface of which has the microchannel of a predetermined depth and width, and which has an access port to communicate with the air at the end of the microchannel. The polymer sheet overlies the surface of the synthetic resin layer so that the position of the micro channel is matched with the opening of the liquid feed tube. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a microfluidic device. More specifically, the present invention relates to a microfluidic device including a tube for feeding a liquid to a microchannel or the like.

  Recently, as is known by the names such as Microscale Total Analysis Systems (μTAS) or Lab-on-Chip, a micro that constitutes a microchannel with a predetermined shape in a substrate. Providing a fine structure such as a channel and a port and performing various operations such as chemical reaction, synthesis, purification, extraction, generation and / or analysis of substances within the fine structure has been proposed and partially put into practical use. A structure manufactured for such a purpose and having a fine structure such as a microchannel and a port in a substrate is collectively referred to as a “microfluidic device”.

  Microfluidic devices can be used in a wide range of applications such as genetic analysis, clinical diagnosis, drug screening, and environmental monitoring. Compared with the same type of equipment of common size, microfluidic devices (1) use significantly less sample and reagent, (2) shorter analysis time, (3) higher sensitivity, (4) carry on site, It has the advantages of being able to analyze on the spot and (5) disposable.

  The material and structure of a conventional microfluidic device are proposed in Patent Document 1, for example. As shown in FIGS. 6A and 6B, the conventional microfluidic device 100 includes at least one microchannel (fine microchannel) on a substrate 101 such as a polymer sheet (for example, polydimethylsiloxane (PDMS)). A flow path) 102 is formed, and input / output ports 103 and 104 are formed at both ends of the microchannel 102, and a transparent or opaque material (for example, glass or a synthetic resin film) is formed on the lower surface side of the substrate 101. A facing substrate 105 made of is bonded. Due to the presence of the facing substrate 105, the ports 103 and 104 and the bottom of the microchannel 102 are sealed.

  The main uses of the I / O ports 103 and 104 are (a) injection of chemicals and samples (dispensing), (b) removal of waste liquids and products, and (c) supply of gas pressure (mainly for liquid delivery) Positive pressure and negative pressure), (d) release to the atmosphere (dispersion of internal pressure generated during pumping, release of gas generated by reaction), and (e) sealing (preventing liquid evaporation and deliberately reducing internal pressure) For the purpose of generating).

When liquid is fed into the microchannel, the inner diameter of the microchannel 102 is too thin even if it is attempted to feed only by gravity and capillary force from the opening of the port 103 or 104 by a micropipette (not shown). It was difficult to send the liquid from the port 103 or 104 to the inside of the microchannel 102.
For this reason, as shown in FIG. 7, a tube 107 made of Teflon, silicon or glass is fixed to one or both of the ports 103 and 104 with an adhesive 109 and connected to the other end of the tube 107. In general, a liquid supply source (not shown) is configured to pump liquid into the microchannel 102 by a pressure pump (not shown).

  However, the method of fixing the tube to the port opening has the following drawbacks. (1) Since the liquid feeding part (liquid feeding port 103) of the microfluidic device 100 and the tube fixing position are fixed, the liquid feeding position cannot be changed. (2) Since the tube 107 is inserted into the port 103, the inner diameter of the tube 107 is deformed. (3) The operation of fixing the tube 107 to the port 103 is complicated. (4) The tube 107 cannot be replaced or replaced in principle, and is discarded together with the microfluidic device 100. This discarding not only wastes the tube 107, but also wastes the labor required for the tube fixing operation, which is extremely uneconomical.

  As another method, as shown in FIG. 8, there is a method in which the tube 107 is fixed to a dedicated socket 111 and the socket 111 is detachably installed in the port 103 or 104. This method is advantageous in that an operation for fixing the tube 107 to the port 103 with the adhesive 109 is not necessary, and the tube 107 can be reused, and the tube 107 is not wasted. However, in the case of the detachable socket method, (a) an O-ring (not shown) is used between the port 103 and the socket 111 in order to ensure sealing between the port 103 and the socket 111, The structure is complicated because the socket is formed of a flexible soft material such as rubber. (b) In the case of the detachable socket 111, pumping occurs when the detachable socket 111 is attached / detached from the port 103, and an adverse effect due to unexpected pressurization or pulling on the microchannel 102 may occur.

  There is strong development of a new apparatus for supplying a liquid to the microchannel 102 without fixing the liquid supply tube 107 to the liquid supply port 103 of the microfluidic device 100 with the adhesive 109 or using the socket 111. Although there has been a need, perfect equipment has not been developed.

JP 2001-157855 A

Accordingly, an object of the present invention is to provide a novel liquid delivery apparatus for delivering a liquid into a microchannel of a microfluidic device.
Another object of the present invention is to provide a microfluidic device having a novel liquid delivery device for delivering a liquid into a microchannel.

  The invention according to claim 1 as means for solving the above-mentioned problems comprises a synthetic resin layer and a liquid feeding tube embedded in the synthetic resin layer, and the liquid feeding tube is formed in the synthetic resin layer embedded portion. It is a liquid feeding device characterized by having an opening communicating with at least one atmosphere.

  According to this liquid feeding device, the liquid can be supplied from the opening of the buried liquid feeding tube. Since the tube is embedded in the synthetic resin layer, it is stably held.

  The invention according to claim 2 as means for solving the problem is the liquid feeding device according to claim 1, wherein the synthetic resin layer is supported on a support substrate.

  By supporting the synthetic resin layer on the support substrate, the mechanical strength of the entire liquid feeding device can be increased.

  The invention according to claim 3 as means for solving the problem is the liquid feeding device according to claim 1 or 2, wherein the synthetic resin layer is formed of polydimethylsiloxane (PDMS). .

  When the synthetic resin layer is formed from PDMS, a superior sealing property is obtained due to the self-adsorption property of PDMS, and a preferable function as a liquid feeding device is exhibited.

  The invention according to claim 4 as means for solving the problem comprises a synthetic resin layer and a liquid feeding tube embedded in the synthetic resin layer, and the liquid feeding tube is formed in the synthetic resin layer embedded portion. A polymer sheet having a liquid delivery device having an opening communicating with at least one atmosphere, a microchannel having a predetermined depth and width formed on one surface side, and an access port communicating with the atmosphere at one end of the microchannel The polymer sheet is a microfluidic device in which the microchannel is stacked on the surface of the synthetic resin layer so that the position of the microchannel matches the opening of the liquid feeding tube.

  If the liquid feeding apparatus of this invention is used, a liquid can be supplied to a microchannel, without connecting a tube to the liquid feeding port of a microchannel. Thereby, even after using the microfluidic device, only the liquid delivery device can be reused any number of times, and the economic efficiency is dramatically improved.

  The invention according to claim 5 as means for solving the problem is the microfluidic device according to claim 4, wherein the synthetic resin layer is supported on a support substrate.

  By supporting the synthetic resin layer on the support substrate, not only the liquid feeding device but also the mechanical strength of the entire microfluidic device can be increased.

  The invention according to claim 6 as means for solving the above-mentioned problems is that the synthetic resin layer and the polymer sheet are made of polydimethylsiloxane (PDMS). It is a device.

  When the synthetic resin layer and the polymer sheet are formed from PDMS, a superior microchannel sealing property is obtained due to the self-adsorption property of PDMS, and a preferable function as a microfluidic device is exhibited.

A liquid feeding device and a polymer sheet are formed separately, and a microfluidic device can be formed by stacking both members at the time of use. With this configuration, the alignment position between the liquid feeding tube opening of the liquid feeding device and the microchannel of the polymer sheet can be arbitrarily changed. As a result, the distance between the liquid feeding tube opening of the liquid feeding device and the access port of the microchannel can be appropriately changed according to the application, and the flexibility of analysis work is ensured.
Further, unlike the conventional microfluidic device, if the liquid feeding device of the present invention is used, the troublesome work of joining the liquid feeding tube to the port of the polymer sheet with an adhesive can be omitted. Further, in the conventional microfluidic device, since the liquid feeding tube is inserted into the port and bonded with an adhesive, the inner diameter of the tube is deformed and smooth liquid feeding is difficult. According to this, since the inner diameter of the tube is not deformed at all, smooth liquid feeding is always possible.
Furthermore, in the conventional microfluidic device, since the liquid feeding tube is bonded to the port of the microchannel with an adhesive, the liquid feeding tube must be discarded together with the microfluidic device after using the microfluidic device. . On the other hand, according to the microfluidic device of the present invention, it is only necessary to peel and discard the polymer sheet having the microchannel, and the liquid feeding device itself can be reused any number of times, which is extremely economical. .

  Hereinafter, preferred embodiments of the inspection jig of the present invention will be described with reference to the drawings. FIG. 1 is a partial schematic plan view of an example of the liquid delivery device of the present invention, and FIG. 2 is a sectional view taken along line II-II in FIG. As shown in FIGS. 1 and 2, the liquid feeding device 1 of the present invention includes a synthetic resin layer 5 fixed on the upper surface of a support substrate 3 and a liquid feeding tube 7 embedded in the synthetic resin layer 5. Become. At least one opening 9 is established at an appropriate position of the embedded portion of the liquid feeding tube 7 so as to communicate with the atmosphere. The liquid feeding tube 7 embedded in the synthetic resin layer 5 is not limited to one as illustrated. Further, the liquid feeding tube 7 can also be embedded in any position as long as it is within the synthetic resin layer 5. The liquid feeding tube 7 is not limited to the illustrated lateral direction, but can be embedded in the longitudinal direction. One end of the liquid feeding tube 7 is connected to a liquid feeding pump (not shown), and the other end is connected to a liquid supply source (not shown) or the like, so that excess liquid can be returned to its original state. Alternatively, it can simply be occluded.

  The support substrate 3 is used to support the synthetic resin layer 5 and the embedded liquid feeding tube 7. However, if the synthetic resin layer 5 itself has sufficient mechanical rigidity, the support substrate 3 may not be used. is there. The support substrate 3 can be made of any material such as glass, ceramic, synthetic resin (for example, polydimethylsiloxane (PDMS)) or metal. The thickness of the support substrate 3 should just be the thickness which can exhibit mechanical strength required and sufficient in order to support the synthetic resin layer 5 and the embedded liquid feeding tube 7. FIG. For example, it is about several hundred microns to several millimeters.

  The liquid feeding tube 7 can be formed of any material such as silicon, Teflon, glass, or metal. The outer diameter of the liquid feeding tube 7 can be appropriately determined in consideration of the thickness of the synthetic resin layer 5, the amount of liquid feeding, the diameter of the opening 9, and the like. Generally, the outer diameter of the liquid feeding tube 7 is about several hundred microns to several millimeters.

  The synthetic resin layer 5 is made of a material in which the liquid feeding tube 7 can be embedded. For example, an arbitrary thermoplastic synthetic resin material such as a silicon resin such as polydimethylsiloxane (PDMS), an elastomer resin, a nylon resin, a polyethylene resin, or a polyacryl resin can be used. When the substrate 3 is glass or PDMS, the synthetic resin layer 5 is preferably PDMS. This is because the glass substrate 3 and the PDMS synthetic resin layer 5 can be permanently bonded as they are. The thickness of the synthetic resin layer 5 is determined by the outer diameter of the liquid feeding tube 7 to be used.

  As another embodiment of the present invention, if the synthetic resin layer 5 has a necessary and sufficient mechanical strength, a liquid feeding device 1 that does not use the support substrate 3 is also possible. Therefore, in this embodiment, the liquid feeding device 1 in which the liquid feeding tube 7 is simply embedded in the synthetic resin layer 5 is obtained.

FIG. 3 is a process diagram for explaining an example of a method for producing the liquid delivery device 1 of the present invention. In step (A), the support substrate 3 is prepared. It is preferable to clean the upper surface of the support substrate 3. The cleaning treatment can be performed, for example, by cleaning the upper surface of the support substrate 3 with an aqueous solvent such as pure water or distilled water and / or an organic solvent such as alcohol, or by irradiating oxygen plasma or excimer UV light. . In step (B), the liquid feeding tube 7 is disposed at a predetermined position on the upper surface of the cleaned support substrate 3. If necessary, the liquid feeding tube 7 can be fixed to the upper surface of the support substrate 3 in advance or temporarily fixed. The liquid feeding tube 7 can be fixed or temporarily fixed using an adhesive or the like. In step (C), a molten synthetic resin is cast on the upper surface of the support substrate 3 and cured to embed the liquid feeding tube 7 in the synthetic resin layer 5. Finally, in step (D), an opening 9 is formed by an appropriate means from the uppermost portion of an appropriate portion of the liquid feeding tube 7 embedded in the synthetic resin layer 5. The diameter of the opening 9 is about several hundred microns to several millimeters.
Alternatively, the synthetic resin layer 5 in which the liquid feeding tube 7 is embedded on another suitable production substrate is produced, and this synthetic resin layer 5 is peeled off from the production substrate and adhered to the support substrate 3. Also, the liquid delivery device 1 of the present invention can be manufactured.

  4A is a schematic plan view of an example of the microfluidic device 20 having the liquid delivery device of the present invention, and FIG. 4B is a cross-sectional view taken along line 4B-4B in FIG. 4A. . As shown in FIGS. 4A and 4B, the polymer sheet 13 having the microchannel 11 is stacked on the upper surface of the liquid feeding device 1. At this time, the microchannel 11 of the polymer sheet 13 is aligned with the opening 9 of the liquid feeding tube 7. A port 15 is formed at one end of the microchannel 11. Accordingly, when the liquid is pressurized and fed from the liquid feed tube 7 connecting direction of the liquid feed tube 1 of the liquid feed device 1, it flows into the microchannel 11 of the polymer sheet 13 from the opening 9 of the liquid feed tube 7, and the port 15. The liquid can be taken out from. Such a polymer sheet 13 having the microchannel 11 and the port 15 can be manufactured by a publicly known and commonly used method. When the synthetic resin layer 5 is formed of PDMS, the polymer sheet 13 is preferably made of PDMS. This is because PDMS can easily self-adsorb and high sealing performance can be easily obtained.

  FIG. 5A is a schematic plan view of another example of the microfluidic device 20A having the liquid delivery device of the present invention, and FIG. 5B is a cross-sectional view taken along line 5B-5B in FIG. It is. The microfluidic device 20A shown in FIG. 5A has the same basic structure as the microfluidic device 20 shown in FIG. The difference from the microfluidic device 20 in FIG. 4A is the position of the polymer sheet 13. In the microfluidic device 20A shown in FIG. 5A, the polymer sheet 13 is stacked on the upper surface of the lower liquid delivery device 1 while moving toward the left side. As a result, the channel distance from the opening 9 of the liquid feeding tube 7 of the liquid feeding device 1 to the port 15 of the polymer sheet 13 is shorter than that of the microfluidic device 20 of FIG. Thus, by using the liquid feeding device 1 of the present invention in combination with the polymer sheet 13 having the microchannel 11, the distance to the port 15 can be freely changed, and the analysis flexibility is ensured. Is done.

(1) Production of liquid feeding device A glass supporting substrate having a thickness of 1 mm, a length of 76 cm, and a width of 52 cm was prepared. One surface of the glass support substrate was washed with pure water, then washed with isopropyl alcohol, air-dried, and then cleaned by irradiating the surface with excimer UV light. A silicone tube (length: 20 cm) with an outer diameter of 2 mm and an inner diameter of 1 mm is placed on this clean surface, and then a SYLGARD 184 SILICONE ELASTOMER made by Dow Corning, USA is about 3 mm thick as a PDMS prepolymer mixture. Then, it was deaerated and heated (65 ° C., 4 hours). After 4 hours, it was removed from the oven and a PDMS layer was formed. A hole with a diameter of 1 mm was formed in the silicone tube from the upper surface of the PDMS layer to form an opening.
(2) Production of polymer sheet First, a 4-inch wafer substrate was prepared. In order to obtain process reliability, it is necessary to clean and dry the wafer substrate before using the resist. In this example, after the piranha etching / clean (H ₂ SO ₄ and H ₂ O ₂ ) treatment, Rinse with distilled water. Thereafter, in order to remove the surface oxide film of silicon, it was immersed in BHF (buffered hydrofluoric acid) for 15 minutes and rinsed with distilled water. Then, in order to dehydrate the surface, it was baked at 60 ° C. for about 30 minutes in a convection oven. On this surface-treated wafer, SU-8 negative photoresist was applied at a rotational speed of 1000 rpm for about 25 seconds, the solvent was evaporated, and soft baking was performed at 65 ° C. for 30 minutes (STEP 1). It processed at 95 degreeC for 90 minutes (STEP2). After cooling, this resist film was covered with a mask having a pattern with a channel width of 100 μm, and contact exposure was performed with an exposure apparatus (PEM-800 manufactured by Union Optics). Thereafter, in order to crosslink the exposed portion of the resist film, the film is heated at 65 ° C. for 15 minutes (STEP 1) and at 95 ° C. for 25 minutes (STEP 2). After cooling, development with a 1-methoxy-2-propylacetic acid developer is performed. After development, the substrate was rinsed with isopropyl alcohol (IPA) for a short time. Then, after drying at 65 ° C. for 30 minutes, hard baking was carried out at 150 ° C. for 5 minutes to complete a master having a resist thickness of 200 μm.
The surface of this master was treated with a reactive ion etching system in the presence of fluorocarbon (CHF ₃ ) to form a CHF ₃ release film on the surface. Pour a SYLGARD 184 SILICONE ELASTOMER manufactured by Dow Corning, USA, into the thickness of about 2 mm as a PDMS prepolymer mixture on the surface of the master release film, and then deaerate and heat (65 ° C, 4 hours) )did. After 4 hours, it was removed from the oven and the PDMS polymer sheet was peeled off from the master. A through hole was formed at one end of the microchannel of the obtained PDMS polymer sheet.
(3) Manufacture of microfluidic device The polymer sheet obtained by said (2) was piled up on the upper surface of the liquid feeding apparatus obtained by said (1), and both were made to self-adsorb. At this time, both members were self-adsorbed so that the position of the liquid feeding tube opening on the upper surface of the liquid feeding device was aligned with the position of the microchannel of the polymer sheet.
(4) Liquid-feeding test When a liquid-feeding pump is connected to one end of the liquid-feeding tube of the microfluidic device obtained in the above (3) and the liquid is pumped at a pressure of 5 kPa, the liquid flows into the microchannel from the opening of the liquid-feeding tube. It was able to flow in and take out from the atmosphere communication port at the end of the microchannel.
The same liquid feeding test was performed by changing the self-adsorption position of the polymer sheet and changing the distance between the opening of the liquid feeding tube and the microchannel port. I was able to take it out.

  The liquid feeding device of the present invention can be used in various microfluidic devices that need to feed a liquid to a microchannel or the like.

It is a partial outline top view of an example of the liquid feeding apparatus of this invention. It is sectional drawing along the II-II line in FIG. It is process drawing explaining an example of the manufacturing method of the liquid feeding apparatus of this invention. (A) is an outline top view of an example of a microfluidic device which has a liquid sending device of the present invention, and (B) is a sectional view which met a 4B-4B line in (A). (A) is an outline top view of another example of a microfluidic device which has a liquid sending device of the present invention, and (B) is a sectional view which met a 5B-5B line in (A). (A) is an outline top view of an example of the conventional microfluidic chip, and (B) is an outline sectional view which met a BB line in (A). FIG. 7 is a partial schematic cross-sectional view of an example of a mode in which a liquid feeding tube is connected to a port of the conventional microfluidic chip shown in FIG. 6. FIG. 7 is a partial schematic cross-sectional view of another example of a mode in which a liquid feeding tube is connected to a port of the conventional microfluidic chip shown in FIG. 6.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Liquid supply apparatus of this invention 3 Support substrate 5 Synthetic resin layer 7 Liquid supply tube 9 Opening part 11 Microchannel 13 Microchannel 15 Access port 100 Conventional microfluidic device 101 Polymer sheet 102 Microchannel 103,104 Input / output (access) Port 105 Support substrate 107 Liquid feeding tube 109 Adhesive 111 Socket

Claims (6)

The synthetic resin layer and a liquid feeding tube embedded in the synthetic resin layer, wherein the liquid feeding tube has at least one opening communicating with the atmosphere in the synthetic resin layer embedded portion. Liquid delivery device. The liquid feeding device according to claim 1, wherein the synthetic resin layer is supported on a support substrate. The liquid feeding device according to claim 1, wherein the synthetic resin layer is formed of polydimethylsiloxane (PDMS). A synthetic resin layer and a liquid feeding tube embedded in the synthetic resin layer, the liquid feeding tube having at least one opening communicating with the atmosphere in the synthetic resin layer embedded part; and A microchannel having a predetermined depth and width is formed on one surface side, and a polymer sheet having an access port communicating with the atmosphere at one end of the microchannel, and the microchannel includes the liquid feeding tube. A microfluidic device, wherein the microfluidic device is stacked on the surface of the synthetic resin layer so as to match the position of the opening. The microfluidic device according to claim 4, wherein the synthetic resin layer is supported on a support substrate. 6. The microfluidic device according to claim 4, wherein the synthetic resin layer and the polymer sheet are made of polydimethylsiloxane (PDMS).

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