JP3895525B2 - Microfluidic system - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a microfluidic system that is used in fields such as medical treatment, chemistry, and biochemistry, and that performs separation, mixing, synthesis, analysis, and the like using a small amount of sample in a small apparatus.
[0002]
[Prior art]
In conventional microfluidic systems, multiple glass substrates and silicon substrates with processed mixing chambers and flow paths are firmly bonded using an anodic bonding method, or multiple unsintered ceramic layers are stacked. And then sintering to produce an integrated integrated microfluidic system.
[0003]
[Problems to be solved by the invention]
There are several problems with conventional fluid systems that combine micropumps and microvalves. For example, in the case of an integrated microfluidic system in which the layers are firmly joined, the volume, shape, combination, etc. of the valve portion, pumping portion, flow path portion, mixing chamber portion, etc. could not be changed. For this reason, when performing different work, it was necessary to exchange the whole, and the versatility was very low. At the same time, it was necessary to change the design of the power supply and control system for driving the actuator.
[0004]
In addition, when a failure occurs partially or when foreign matter is mixed inside, there is a problem that the cost is increased because the whole must be replaced.
[0005]
An object of the present invention is to solve the above problems, to provide a microfluidic system which is rich in versatility, realizes cost reduction, and is easy to handle.
[0006]
[Means for Solving the Problems]
The fluid system of the present invention has a structure in which an actuator substrate for deforming a diaphragm by an actuator and a cover substrate having a valve portion, a pumping portion, a flow path portion, and the like are brought into close contact with each other and fixed. For this reason, it is possible to freely attach and detach the substrate, and when changing the volume, shape, and combination of the valve portion and the pumping portion, it is only necessary to replace the cover substrate, and the actuator substrate is used in common. It became possible. In addition, when foreign matter is mixed, it is possible to easily clean the inside by removing the actuator substrate and the cover substrate.
[0007]
The actuator substrate is pre-arranged in the form of a matrix with diaphragms, actuators, heaters, coolers, sensors, etc. All elements necessary for microfluidic systems such as micropumps, microvalves, flow paths, and mixing chambers It can be determined only by the design of the cover substrate. For this reason, even when constructing different fluid systems, the actuator substrate is always the same, and by replacing only the cover substrate, the actuator's electrical wiring and control system can always be the same. The structure.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of the present invention will be described below with reference to the drawings.
[Embodiment 1]
In this embodiment, an example of a fluid system in which the actuator substrate has a 3 × 3 matrix diaphragm and the cover substrate has four valve portions and one pumping portion will be described.
[0009]
First, the function of the valve unit used in the fluid system will be described. 2 and 3 are explanatory diagrams thereof. An exploded view of only the valve portion is shown in FIG. 2, and a cross-sectional view is shown in FIG. In this embodiment, a silicon substrate is used as the actuator substrate, and a silicone resin is used as the cover substrate.
[0010]
The cover substrate 2 has a recess, and the recess is separated by a separator 3. A through hole is formed in the recess, and functions as a fluid inlet / outlet 4 through which fluid enters and exits from the outside. The cover substrate 2 can be formed in any shape by a method in which a resist mold is prepared using a photolithographic technique, an uncured silicone resin is poured into the cover substrate, and then cured.
[0011]
The actuator substrate 1 is made of a silicon substrate and has a diaphragm 5 made by etching with an aqueous potassium hydroxide solution. A piezoelectric element 6 is bonded to the back surface, and a unimorph structure of the diaphragm 5 and the piezoelectric element 6 is formed. Therefore, when a voltage is applied to the piezoelectric element 6, the diaphragm bends in a direction perpendicular to the actuator substrate. In the present embodiment, a piezoelectric element is used as a method for deforming the diaphragm. However, it is also possible to perform deformation using other methods such as electrostatic force, magnetic force, air pressure, and shape memory alloy. Further, although the concave shape of the cover substrate and the diaphragm shape of the actuator substrate are rectangular, the shape is not limited to this.
[0012]
The cover substrate 2 and the actuator substrate 1 are such that the surface of the cover substrate 2 on the side where the concave portion exists and the surface opposite to the surface on which the piezoelectric element is bonded on the actuator substrate 1 are in contact with each other except for the concave portion. Can be brought into close contact. At this time, the two substrates are positioned such that the center of the separator in the cover substrate 1 and the center of the diaphragm 5 in the actuator substrate 1 coincide. If a silicone resin having high adhesiveness such as PDMS (polydimethylsiloxane) is used for the cover substrate 2 and a silicon substrate having a high surface flatness is used for the actuator substrate 1, a high adhesion can be obtained between the two. . In this case, even if a pressure of about several kilopascals is applied from the fluid inlet / outlet 4, no fluid leaks from between the actuator substrate 1 and the cover substrate 2. The two substrates are in close contact with each other due to the adhesiveness of the cover substrate, and are not bonded. For this reason, the cover substrate can be easily peeled off from the actuator substrate using tweezers or the like.
[0013]
Further, when used under high pressure, there is a method of fixing by sandwiching the actuator substrate 1 and the cover substrate 2 using a holder 37 as shown in FIG. The holder 37 is fixed by screws 39 via spacers 38. The pressure-bonding force between the actuator side substrate 1 and the cover substrate 2 can be adjusted by the thickness of the spacer 38. In this case, since both the substrates are constantly pressed by the holder 37, fluid leakage does not occur between the substrates even when used under high pressure. Further, if the conduit 40 is formed integrally with the holder on the cover substrate 2 side, high adhesion can be obtained between the holder 37 and the cover substrate 2 as well, thereby realizing a leak-free conduit. become able to.
[0014]
The materials of the cover substrate 2 and the actuator substrate 1 are not limited to silicone resin and silicon substrate, respectively. Any material may be used as long as both materials have good adhesion and are detachable. Further, even when the cover substrate 2 and the actuator substrate 1 are both made of a material that does not have adhesiveness, at least one of the contact surfaces of the cover substrate 1 and the actuator substrate 2 is adhesive. By forming a thin film, a structure in which both can be detached and high adhesion can be obtained. Further, a thermoplastic adhesive layer can be used between the two substrates, and the two substrates can be attached and detached by heating / cooling.
[0015]
Next, the operation of the valve unit composed of the two substrates will be described. When the actuator substrate 1 and the cover substrate 2 are in close contact, the separator 3 and the diaphragm 5 are also in close contact. Therefore, if no voltage is applied to the piezoelectric element, the two fluid inlets / outlets 4 are completely blocked by the separator 3, and the flow is blocked between the two fluid inlets / outlets, so that the valve is closed. Is preserved. On the other hand, when a voltage is applied to the piezoelectric element 6, the diaphragm 5 is bent by the unimorph structure of the piezoelectric element 6 and the diaphragm 5, and a gap is generated between the diaphragm 5 and the separator 3. As the fluid moves through this gap, the valve is opened (FIG. 4). In this way, the valve unit opens by applying a voltage and closes by stopping the application of voltage. Further, by reversing the direction of the voltage applied to the piezoelectric element, an operation of pressing the diaphragm against the separator and closing the valve more firmly is also possible. Note that the fluid inlet / outlet does not need to be a through hole, and may have a structure in which fluid enters and exits from the outside through the flow path 7 as shown in FIG.
[0016]
Next, the pumping unit will be described. The pumping portion is formed by bringing a cover substrate having a concave portion like the valve portion into close contact with an actuator substrate having a diaphragm to which a piezoelectric element is bonded. However, unlike the valve portion, the cover substrate does not have a separator. Therefore, when the diaphragm is deformed by the piezoelectric element, the fluid is sucked and discharged through the fluid inlet / outlet due to the volume change between the cover substrate and the diaphragm.
[0017]
An example of a fluid system in which these valve unit and pump unit are combined is shown in FIG. This fluid system is a combination of four valve sections and one pump section. The actuator substrate 1 has nine diaphragms 5 arranged in a 3 × 3 matrix, and has a unimorph structure by bonding a piezoelectric element 6 to each of them. Moreover, the size and thickness of each diaphragm are the same, and the same piezoelectric element is used. By unifying the actuators in this way, the entire system including the control system can be simplified. Further, as described in the explanation of the structure of the valve portion, the cover substrate and the actuator substrate can be freely attached and detached.
[0018]
On the other hand, the cover substrate 2 is formed with four valve portions of the first valve 13, the second valve 14, the third valve 15, and the fourth valve 16 and the pumping portion 12. These valve parts are connected to the pumping part 12 by flow paths 7, respectively, and fluid inlets / outlets 7 for moving fluid to the outside are formed in each valve part.
[0019]
The actuator substrate 1 and the cover substrate 2 are brought into close contact with each other, and the position of the valve portion and the pumping portion formed on the cover substrate 2 and the position of the diaphragm 5 formed on the actuator substrate 1 are determined by two substrates. It arrange | positions so that it may correspond, when making it closely_contact | adhere. However, the total number of valve portions and pumping portions on the cover substrate and the total number of diaphragms on the actuator substrate do not necessarily need to match. In the case of this embodiment, the total number of valve portions and pumping portions in the cover substrate is five, but the total number of diaphragms in the actuator substrate is nine. In this case, the four diaphragms that do not correspond to the valve portion or the pumping portion of the cover substrate are not driven.
[0020]
Next, an example of the operation of this fluid system will be described. Here, separate reagent tanks were connected to the first valve unit 13, the second valve unit 14, and the third valve unit 15, respectively. Reagents were sucked into the pumping unit 12 at a constant rate in order from each valve, and after synthesis and mixing, the reagent was discharged from the fourth valve unit 16. By operating the fluid system in this way, a fluid system as shown in FIG. 7 could be realized. The amount of reagent sucked from each valve can be controlled by the amount of diaphragm displacement in the pumping unit 12.
[0021]
Further, the arrangement of elements such as the pumping unit and the valve unit of the fluid system is determined by the cover substrate, and the actuators are arranged in advance in a 3 × 3 matrix on the actuator substrate. For this reason, it is possible to construct an arbitrary fluid system having a maximum of nine elements by simply replacing the cover substrate using the actuator substrate in common.
[0022]
In the present embodiment, a fluid system using an actuator substrate having a 3 × 3 matrix diaphragm has been described. Of course, the number of diaphragms is not limited. For example, when an actuator substrate having a 10 × 10 matrix diaphragm is used, a maximum of 100 valve parts or pumping parts can be arranged, and thus a complicated fluid system can be realized. Furthermore, to facilitate control of the entire system, the shape, size, thickness, and actuator performance of all diaphragms are unified.
[0023]
In this fluid system, the arrangement of components such as a valve unit, a pumping unit, and a flow path is all determined by a cover substrate, and actuators are arranged in a matrix on the actuator substrate. In addition, since the actuator substrate and the cover substrate can be attached and detached, if one actuator substrate and its control system are prepared, a different fluid system can be easily constructed simply by replacing the cover substrate. It has a very high versatility. In addition, it is possible to use the same electrical wiring and control system for the actuator, and it is only necessary to replace the cover substrate, so that the cost can be reduced.
[0024]
Furthermore, components such as the valve section, pumping section, and flow path are integrally formed on the cover substrate, so there is no need to connect each element via a connector, and problems such as leakage and assembly errors are solved. ing.
[0025]
Even when particles are mixed in the fluid system, it is possible to remove the cover substrate and easily clean the inside. When the cover substrate is deteriorated, it can be replaced, and the actuator substrate can be used as it is. Since partial replacement is possible in this way, the life of the entire fluid system could be extended.
[Embodiment 2]
In the present embodiment, an example of a fluid system that realizes an efficient mixing action by using the actuator substrate having the 3 × 3 diaphragm described in the first embodiment and changing the cover substrate will be described.
[0026]
FIG. 8 is an exploded view of the present system. The cover substrate has two pumping parts, a first pumping part 17 and a second pumping part 18, in the middle of the two valve parts 11.
[0027]
For example, in the case of the fluid system described in the first embodiment, it is impossible to drive the pumping unit because fluid cannot be moved to the outside when all four valves are closed. Therefore, it has been difficult to perform efficient mixing in the pumping section.
[0028]
However, when two pumping parts are installed as in the system shown in FIG. 8, the two valve parts are closed after the fluid is sucked, and the pump parts are further closed in FIG. 9 (9-a, 9-b). By driving symmetrically as shown, it is possible to achieve efficient mixing without changing the total volume of the pumping section.
[0029]
Thus, in the fluid system according to the present invention, an efficient mixing device can be realized by installing two pumping diaphragms in the middle of the two valve portions. In this embodiment, an example in which two pumping diaphragms are installed is described. However, the same effect can be obtained even if the number of pumping diaphragms is two or more. Further, the arrangement of the pumping diaphragm is not particularly limited, and the same effect can be obtained as long as a plurality of pumping diaphragms are positioned between the two valve portions.
[Embodiment 3]
In the present embodiment, an example will be described in which the actuator substrate having the 3 × 3 diaphragm described in the first embodiment is used, and a plurality of actuators correspond to one concave portion of the cover substrate.
[0030]
FIG. 10 shows an example in which four diaphragms 5 correspond to one pumping unit 12. By bringing the two substrates into close contact, the four diaphragms 5 are all covered with the pumping unit 12.
[0031]
In the case of such a structure, by efficiently displacing the four diaphragms two by two, efficient mixing can be performed as in the configuration described in the second embodiment.
[0032]
In addition, by simultaneously displacing the four diaphragms in the same direction, the amount of fluid movement in one pumping operation can be increased fourfold. Of course, the number of diaphragms corresponding to one pump unit is not limited to four.
[0033]
Thus, by making a plurality of diaphragms correspond to one pump unit, it is possible not only to perform efficient mixing work but also to increase the amount of fluid movement by one pumping.
[Embodiment 4]
In this embodiment, the actuator substrate having the 3 × 3 diaphragm described in the first embodiment is used, and a plurality of reagents can be mixed any number of times by changing the cover substrate. The system which is is demonstrated. FIG. 1 is an exploded view of the entire system. A first valve 13, a second valve 14, and a third valve 15 are connected to the pumping unit 12 by a flow path 7. A first cleaning valve 19 and a second cleaning valve 20 for cleaning the inside of the pumping unit 12 are also connected to the pumping unit 12 through the flow path 7. FIG. 11 shows a schematic diagram showing how the fluid moves in the present embodiment.
[0034]
The fluid sucked from the first valve 13 and the second valve 14 is mixed in the pumping unit 12 and discharged from the third valve 15. The mixing ratio can be arbitrarily set by controlling the amount of displacement of the pumping unit 12 when the fluid is sucked from the first valve 13 and the second valve 14, respectively. In order to continue the operation of mixing at another ratio, the first cleaning valve 19 to the second cleaning valve are first closed with all the first valve 13, the second valve 14, and the third valve 15 closed. The cleaning liquid is fed toward 20 to clean the inside of the pumping unit 12, and then the mixing from the first valve 13 and the second valve 14 is performed again.
[0035]
[Embodiment 5]
In the present embodiment, a fluid system in which not only an actuator unit using a piezoelectric element but also a heating unit and a cooling unit are installed on a diaphragm formed on an actuator substrate will be described.
[0036]
The fluid system described in the present embodiment is composed of a detachable actuator substrate and a cover substrate in the same manner as described in the first embodiment. Here, a silicon substrate is used as the actuator substrate, and a diaphragm is formed on the silicon substrate by etching with an aqueous potassium hydroxide solution. If a piezoelectric element is bonded to this diaphragm, it can be used as an actuator unit that performs valve operation or pumping operation.However, if a heater is bonded instead of the piezoelectric element, a heating unit that heats only the diaphragm part is used as a Peltier element. If it adhere | attaches, the cooling part which cools a diaphragm part is realizable. In particular, since the diaphragm portion is thinner than other portions of the actuator substrate, it is possible to realize temperature control with good responsiveness.
[0037]
FIG. 12 is a top view of the actuator substrate. The actuator substrate is etched from the back side on the paper surface. Piezoelectric elements, heaters, and Peltier elements are bonded to the etched parts, respectively, and arranged in a 4x4 matrix as the actuator part, heating part, and cooling part. It is. Each of these elements is connected to the controller and can be operated independently. For example, when a cover substrate as shown in FIG. 13 is brought into close contact with such an actuator substrate, a fluid system as shown in FIG. 14 is constructed.
[0038]
Each element such as an actuator unit, a heating unit, and a cooling unit is arranged in advance on a matrix on an actuator substrate, and all elements to be used are determined by the design of the cover substrate. Therefore, it is possible to construct an arbitrary fluid system by exchanging the cover substrate. In this embodiment, the actuator, heater, and cooler are used as the elements to be arranged on the actuator substrate, but various sensors such as a pressure sensor, a temperature sensor, a pH sensor, and a glucose sensor are similarly arranged in a matrix. Of course it is also possible to do.
[0039]
In addition, the actuator board is not provided with a pump part or valve part, but only a heater, cooler, various sensors, etc. are installed, and all of the fluid is transferred by external pressure application or high voltage application electrophoresis. Of course it is possible.
[0040]
The fluid system described in the present embodiment has a structure in which the actuator substrate and the cover substrate can be attached and detached. Therefore, if one actuator substrate and its control system are prepared, the cover substrate is replaced. It has the feature that a different fluid system can be easily constructed only by itself. Moreover, since it is possible to use a common thing about the electrical wiring and control system of an actuator, versatility is also high and cost reduction is also realizable. In the case of this fluid system, since each component is integrally formed on the cover substrate, there is no need to connect each component via a connector, and problems such as leakage and positioning are solved.
[0041]
Furthermore, there is an advantage that the cover substrate can be removed when particles are mixed in the fluid system, and the inside can be easily cleaned. When the cover substrate is deteriorated, it can be replaced, and the actuator substrate can be used as it is. Since partial replacement is possible in this way, the life of the fluid system as a whole could be extended.
[0042]
【The invention's effect】
The fluid system of the present invention comprises an actuator substrate having elements such as a plurality of actuator parts, sensor parts, heater parts, and cooler parts, and a cover substrate that connects these elements, and has a detachable structure. Yes. For this reason, it is possible to easily realize a fluid system having different functions by preparing a plurality of cover substrates and replacing them as necessary. In this case, only the cover substrate needs to be replaced, and the actuator substrate can be used in common, so that the cost can be reduced. Moreover, since it is possible to use the same electrical wiring and control system for the actuator, versatility has also increased. Further, when foreign matter is mixed in the fluid system, the inside of the fluid system can be cleaned by removing both of them.
[Brief description of the drawings]
FIG. 1 is an exploded view showing an example of a fluid system of the present invention.
FIG. 2 is an exploded view showing a structure of a valve portion.
FIG. 3 is a cross-sectional view showing a structure of a valve portion.
FIG. 4 shows a state where a valve portion is opened.
FIG. 5 is an example of a cover substrate in a valve portion.
FIG. 6 is a fluid system having four valve parts and one pump part.
7 shows the flow in the system of FIG.
FIG. 8 is a fluid system having two pump parts and capable of highly efficient mixing in this part.
FIG. 9 shows a state in which fluid is mixed in two pump units.
FIG. 10 is a fluid system in which four actuators correspond to one pump unit.
FIG. 11 shows the flow in the system of FIG.
FIG. 12 is an actuator substrate in which an actuator unit, a heating unit, and a cooling unit are arranged in a matrix.
13 is an example in which a fluid system is constructed by bringing a cover substrate into close contact with the actuator substrate in FIG.
14 shows a flow in the system of FIG.
FIG. 15 shows a state where an actuator substrate and a cover substrate are fixed by a holder.
[Explanation of symbols]
1. 1. Actuator substrate 2. Cover substrate Separator 4. 4. Fluid inlet / outlet Diaphragm 6. Piezoelectric element 7. Channel 11. Valve part 12. Pumping unit 13. First valve 14. Second valve 15. Third valve 16. Fourth valve 17. First pumping unit 18. Second pumping unit 19. First cleaning valve 20. Second cleaning valve 31. Actuator section 32. Heating unit 33. Cooling unit 34. First inlet valve 35. Second inlet valve 36. Outlet valve 37. Holder 38. Spacer 39. Screw 40. Pipeline

Claims (14)

Substrate A having at least two fluid inlets and at least one recess connected to the fluid inlet;
The substrate B having at least one active element acting on the fluid in the recess, at least one passive element for detecting the state of the fluid in the recess, or both the active element and the passive element;
When the substrate A and the substrate B are in close contact , a closed space is formed between the recess and the substrate B ,
A microfluidic system in which a fluid moves in the closed space by the action of the active element ,
A microfluidic system according to claim 1, wherein a plurality of the substrates A are prepared according to applications, the substrate B is shared, and the substrate A is replaced to cope with a plurality of applications. At least two fluid ports;
A substrate A having at least one recess connected to the fluid inlet / outlet;
It is composed of a substrate B having at least one passive element that detects the state of the fluid,
The substrate A and the substrate B are in close contact with each other, and a closed space is formed between the recess and the substrate B. At least two fluid ports;
A substrate A having at least one recess connected to the fluid inlet / outlet;
A substrate B having at least one active element acting on the fluid in the recess and at least one passive element for detecting the state of the fluid in the recess;
The substrate A and the substrate B are in close contact with each other, and a closed space is formed between the recess and the substrate B. The microfluidic system according to claim 2 or 3, wherein at least one of the passive elements is any one of a pressure sensor, a temperature sensor, a pH sensor, and a glucose sensor. The microfluidic system according to claim 2 or 3, wherein the passive elements are arranged in a grid pattern on the substrate B. The microfluidic system according to claim 2 or 3, wherein all the passive elements arranged on the substrate B have the same size. 4. The microfluidic system according to claim 3, wherein at least one of the active elements includes a diaphragm formed on the substrate B and an actuator for deforming the diaphragm. 5. 4. The microfluidic system according to claim 3, wherein at least one of the active elements is a heater for heating a fluid or a cooler for cooling the fluid. The microfluidic system according to claim 3, wherein the active element and the passive element are arranged in a lattice pattern on the substrate B. The microfluidic system according to claim 3, wherein the active element and the passive element arranged on the substrate B are all the same size. The substrate A and the substrate B have means for repeatedly attaching and detaching, and when the substrate A and the substrate B are in close contact, fluid does not leak from the contact surface of the substrate A and the substrate B. The microfluidic system according to claim 10. The fluid system according to claim 11, wherein the means for repeatedly attaching and detaching the substrate A and the substrate B is that at least one of the contact surfaces of the substrate A and the substrate B has adhesiveness. In the adhesive structure, either the substrate A or the substrate B is made of an adhesive material, or at least one of the substrate A or the substrate B is a multilayer structure, The microfluidic system according to claim 12, wherein at least one layer is made of an adhesive material. The means for repeatedly attaching and detaching the substrate A and the substrate B is the base. The microfluidic system according to claim 11, wherein the microfluidic system is mechanically coupled by a detachable holder installed outside the plate A and the substrate B.

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