JP2007010676A - Micro chemical chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To make a chip compact, improve analysis accuracy for samples, enable a sample having no charge to be analyzed, and make a channel multiple easily. <P>SOLUTION: A micro chemical chip 10A is equipped with: a plate-like substrate 12; and one channel 14 which is formed on the surface of the substrate 12 and in which fluid flows. A fluid reservoir section 16 in which the fluid is stored, is formed at the start edge of the channel 14 so as to be in communication with the channel 14, and a fluid discharge section 18 is formed at the termination edge of the channel so as to be in communication with the channel 14. Furthermore, a pump section 22 of a push type is formed integrally with the substrate 12 in the channel 14 and near the fluid reservoir section 16. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a microchemical chip having one or more channels through which a fluid flows in a substrate.

  Recently, research and development of a microchemical chip that conducts a chemical experiment using a chip of a palm size (several centimeters square) is underway (see, for example, Patent Documents 1 and 2).

  This microchemical chip is constructed by forming a minute channel on the surface of a substrate made of glass, quartz, or the like. By supplying the sample to the channel and moving it downstream, the components of the sample are separated and reacted. Biochemistry experiments such as purification and gene analysis can be performed on the chip.

  As a measurement principle using this microchemical chip, methods such as electrophoresis and flow cytometry are known.

  By using this microchemical chip, there is an advantage that a result can be obtained in a short time with a very small amount of sample as compared with a conventional experimental apparatus.

Special table 2000-508058 gazette JP 11-347392 A

  By the way, in a conventional microchemical chip, when a sample is moved into a channel formed on the surface of the substrate, a large pump is installed outside the substrate, and the sample is pushed or pulled by the large pump. Alternatively, it is performed by an electroosmotic flow generated in the sample solvent by applying a voltage between the electrodes arranged at the entrance and exit of the channel.

  When a large pump is used, the analyzer including the microchemical chip becomes large, resulting in an increase in cost. In addition, a large pump can only roughly adjust the moving speed of the sample, leading to deterioration in analysis accuracy and use efficiency of expensive samples.

  When using electroosmotic flow, it is usually necessary to apply a very high electric field of about several hundred volts / cm between the electrodes, resulting in a large size and high price of the device and careful handling for safety. is there. In addition, since the entire sample solution flows toward the cathode using Coulomb force, it is good when performing an electrophoretic test or the like, when the sample (solute) to be inspected is a negatively charged substance (DNA or protein), etc. However, in the case of a substance having a positive charge or a substance having no charge (such as a cell), there is a problem that it is difficult to make a difference in mobility of an inspection target and the resolution of the inspection deteriorates.

  Furthermore, the moving speed of the sample solution is generally several hundred to several thousand picoliters / second in the case of a channel having a cross-sectional area of several hundred to several thousand square microns, which is sufficiently satisfactory for high-speed inspection. It's not going.

  Moreover, in a conventional microchemical chip, in order to supply a sample into the channel from the outside, it is dispensed into an injection port having an opening of about several millimeters to several centimeters φ using a commercially available micropipette. The amount of one-time dispensing is limited to a small amount of about several hundred to several thousand nanoliters, and a more miniaturized injection method is also expected.

  The present invention has been made in consideration of such problems, and enables miniaturization of a chip, improvement of analysis accuracy for a sample, analysis of a sample independent of charge with high accuracy, and greatly shortening an inspection time. An object of the present invention is to provide a microchemical chip that can be easily multi-channeled.

  In addition to the above, another object of the present invention is to enable a micro-sample to be supplied from the outside, further improving the use efficiency of the sample, the accuracy of analysis, and the speed of analysis. To provide a chip.

  The present invention relates to a microchemical chip having one or more channels through which a fluid flows in a base, and has a pump part upstream and / or downstream of the channel, and the pump part is integrated with the base. It is characterized by being formed.

  Since the pump part is formed integrally with the base body, the pump part can realize the pushing of the fluid into the channel or the drawing of the fluid from the channel, and a large pump outside the base body. No need to install. As a result, it is possible to reduce the size of the chip.

  In addition, a large pump can only roughly adjust the amount of fluid movement. However, if the pump unit is formed integrally with the base, an adjustable unit flow rate (resolution) is the amount of fluid flowing through the channel. Therefore, the amount of fluid movement can be adjusted with high accuracy. The moving speed of the fluid can be freely changed by a drive signal to the pump, and several picoliters / second to several microliters / second can be realized. Furthermore, it is not necessary to apply a very high electric field of about several hundred volts / cm for the movement of the fluid, so that an increase in size and cost of the apparatus can be avoided, and safety handling becomes easy.

  In addition, since the fluid can be moved by the pump unit, it is possible to move the fluid having no electric charge, and in the electrophoretic inspection, the inspection accuracy depends on the component of the sample (solute) and the state of the electric charge. There is no inconvenience such as being influenced.

  And in the said structure, it has a valve part at least upstream of the said channel, and the said valve part may be integrally formed in the said base | substrate. As a result, when a valuable or expensive fluid is handled, the supply amount of the valuable or expensive fluid to the channel can be arbitrarily adjusted by the valve unit, which contributes to an improvement in use efficiency of the sample and a reduction in cost. Can be made.

  Moreover, in the said structure, you may make it form the electrode for the electrophoresis of a fluid in the upstream and / or downstream of the said channel. This is preferably employed when performing an electrophoretic test in which the test accuracy is not affected by the sample (solute) component and the state of charge. For example, when the sample (solute) to be inspected is a negatively charged DNA or protein, the amount of fluid movement relative to the sample is further controlled by reversing the direction of electrophoresis from the direction of movement by the pump unit. And the inspection accuracy can be improved. That is, by making the electrode in the direction of fluid movement by the pump part negative, the sample itself exerts a force attracted in the direction opposite to the flow (positive electrode), and the separation ability is improved.

  In addition, when the fluid itself has a polarity, by adjusting the strength of the electric field applied between the electrodes, in addition to the movement of the fluid by the pump, the movement by the electroosmotic flow occurs, and the fluid can be more effectively and at high speed. Movement and analysis are completed.

  When the sample (solute) to be inspected is positively charged, the force of the sample itself being drawn in the direction opposite to the flow (negative electrode) works by making the electrode in the direction of fluid movement by the pump part positive. Sufficient separation ability is ensured.

  In the above configuration, the channel may have one or more sample channels through which one or more samples to be inspected flow. As a result, channel multiplexing can be easily realized.

  Further, in the above configuration, the one or more sample channels may be configured to allow a corresponding sample and a transport fluid to circulate, respectively. This leads to the saving of valuable or expensive samples, which is advantageous in terms of cost while improving the efficiency of the experiment. In addition, by adjusting the sample supply timing, the sample supplied to the channel and the sample supplied from another channel can be mixed.

  In the above configuration, a sample supply unit may be provided for supplying a corresponding sample to each of the one or more sample channels. As a result, the supply timing and supply amount of a small amount of sample (picoliter level) to the channel can be set arbitrarily and accurately. This is because fine control such as biochemical reaction in the channel can be performed. It will be possible to improve the accuracy of experiment, inspection and analysis, reduce the inspection time and reduce the cost.

  Further, in the above configuration, the channel may include a merge channel in which one or more samples from the one or more sample channels merge. Reaction, analysis, and the like as a result of joining a large number of samples can be easily performed.

  Further, in the above configuration, the channel includes one or more sample channels through which one or more samples to be inspected flow, and one transport channel through which a transport fluid for transporting the sample flows. You may do it.

  In this case, the channel is a merge channel in which one or more samples from the one or more sample channels and a transfer fluid from the one transfer channel merge, or one from the one or more sample channels. You may make it have a confluence | merging channel where the fluid with which the above sample was mixed and the fluid for conveyance from said one conveyance channel merge. By forming the sample channel and the transport channel separately, it is possible to select the optimal shape, material, etc. for the physical properties of each fluid, more effectively moving and merging saving valuable or expensive samples. This increases the efficiency of the experiment and is advantageous in terms of cost.

  In the above configuration, each of the one or more sample channels may have a valve portion in front of the merging channel. Thereby, the movement of the valuable or expensive fluid to the merging portion can be arbitrarily and reliably adjusted by the valve portion. Moreover, you may make it have a vibration generation part in a junction part. The merging efficiency of one or more samples at the merging portion can be increased, and the mixing speed, biochemical reaction speed, inspection speed, etc. can be improved, while mixing and biochemical reaction can be performed more reliably. Note that the vibration generating portion may be formed on any of the upper surface, the flat surface, the side surface, and the entire surrounding surface as long as it is at least part of the wall surface of the channel at the merge portion.

  The one or more sample channels may cross each other, the one or more sample channels and the one transport channel cross each other, or a merge channel of the one or more sample channels. And the one transport channel may cross each other. In this way, each channel has a pump, and the pump drive timing, pump suction, and pushing force can be controlled and combined for each channel. Sample mixing, or movement from one channel to the other. In this case, each of the one or more sample channels may have a valve portion at the front stage of the crossing portion. Accordingly, the movement of the valuable or expensive fluid to the crossing portion can be arbitrarily and reliably adjusted by the valve portion, and the movement of the sample from one channel to the other channel is more reliably performed. Moreover, you may make it have a vibration generation part in a crossing part. In this case, the mixing efficiency of one or more samples at the crossing portion can be increased, and the biochemical reaction and inspection speed can be improved. It should be noted that the vibration generating portion may be formed on any of the upper surface, the flat surface, the side surface, and the entire surrounding surface as long as it is at least a part of the wall surface of the channel at the intersection.

  And in the said structure, you may make it the said valve part have a heater which heats with respect to a part of said channel. This utilizes a change in flow path resistance due to a change in viscosity of the fluid due to heat. When the heater is energized and the portion of the channel corresponding to the heater is heated, the heat generally reduces the viscosity of the fluid and the fluid flows through the channel. On the other hand, when the energization to the heater is stopped and the valve portion is in a cooled state, the viscosity of the fluid increases, and as a result, the flow path resistance increases and the fluid flow stops. That is, the flow of the fluid can be controlled by energizing the heater and stopping the energization, and functions as a valve portion.

  The valve unit may include a vibration generating unit that applies vibration to a part of the channel. This utilizes a change in flow path resistance due to vibration. When vibration is applied to a part of the channel, the flow resistance is increased, so that the fluid flow stops. In addition, as long as the formation location of a vibration generation part is at least one part of the wall surface of a channel, any of an upper surface, a plane, a side surface, and the surrounding whole surface may be sufficient.

  The valve portion may include a cavity communicating with the channel and an actuator portion that makes the volume of the cavity variable. With such a configuration, the operation timing of the actuator of the pump unit and the valve unit is synchronized, that is, when the volume of the cavity is reduced by the operation of the actuator unit when the fluid in the channel is moved by the pump unit. , By operating the actuator at the timing when the force that causes the flow in the reverse direction (the direction opposite to the flow direction of the fluid by the pump) is applied to the fluid in the cavity, the flow of the fluid is stopped in the valve portion as a result. be able to.

  Constructing the valve part with the above-mentioned heater, vibration generating part, or actuator part can realize a reliable operation with a simple and inexpensive structure as compared with a conventional mechanical valve, but also has excellent durability. .

  The pump unit and the sample supply unit may include a nozzle, a cavity that communicates with the channel, and a pump actuator unit that makes the volume of the cavity variable. In this case, when the capacity of the cavity is reduced by the operation of the actuator unit, the fluid in the cavity is forced to flow downstream, and when the capacity of the cavity expands or returns, the upstream fluid is drawn into the cavity. Become. By repeating these operations sequentially, the upstream fluid is sequentially pushed downstream.

  A valve portion may be provided between the channel and the cavity of the pump portion. In this case, the valve portion includes a valve body disposed in a communication portion between the channel and the cavity, and a valve actuator portion that operates the valve body to selectively open and close the communication portion. Can be configured. This makes the movement of the fluid by the pump easier and in particular makes it easier to fill the empty channel.

  As described above, according to the microchemical chip of the present invention, the chip can be downsized, the analysis accuracy of the sample can be improved, the analysis of the sample without charge can be performed, and the number of channels can be easily increased.

  Further, by combining electrophoresis, it is possible to further improve the analysis accuracy and speed up the analysis.

  Embodiments of a microchemical chip according to the present invention will be described below with reference to FIGS.

  First, as shown in FIG. 1, the microchemical chip 10A according to the first embodiment is formed on a plate-like substrate 12 and the surface of the substrate 12, and the upper surface is closed by a transparent glass plate. It has one channel 14 through which fluid is circulated. A fluid reservoir 16 for storing fluid is formed at the start end of the channel 14 so as to communicate with the channel 14, and a fluid discharge portion 18 is formed at the end of the channel 14 so as to communicate with the channel 14.

  Examples of the fluid include only a solution in which a sample (solute) to be inspected is dissolved or dispersed, or a combination of a sample solution to be inspected and a transport fluid. By using the transport fluid in addition to the sample, it is possible to save an expensive sample.

  Examples of the sample that can be used include nucleic acids, proteins, saccharides, cells, and complexes thereof. Nucleic acids are DNA and / or fragments or amplified thereof, cDNA and / or fragments or amplified thereof, RNA or antisense RNA and / or fragments or amplified thereof, chemically synthesized DNA or amplified Or chemically synthesized RNA or amplified. Examples of the protein include an antigen, an antibody, a lectin, an adhesin, a receptor for a physiologically active substance, or a peptide.

  In the channel 14, for example, a heat generation unit, a heating unit, a cooling unit, a pH adjustment unit, a laser irradiation unit, a radiation irradiation unit, an inspection unit, and the like used for chemical analysis such as chromatography are installed. In the example of FIG. 1, the case where three types of heat generation parts 20a-20c are installed is shown.

  Examples of the constituent material of the base 12 include glass, plastic, silicon (quartz), ceramics, and glass ceramics. Among these materials, for example, a glass material is preferable in view of the case where an electrophoresis method is used and has an electrical insulating property, and in consideration of chemical durability and transparency. The channel 14 can be formed on the surface of the substrate 12 by using an etching method such as photolithography.

  In addition to the viewpoint that the glass material is easy to form the channel 14, the glass material is resistant to weak acids and weak alkalis, wettability, water repellency, surface tension, elution of glass components, glass surface polarity, surface groups, etc. The selection is preferably made in consideration of factors that affect the fluid.

  As a glass material, for example, many glasses such as La-based, Zr-based, and Ti-based materials including borosilicate based materials such as a white plate (BK7) can be used.

  And in this 1st Embodiment, the extrusion type pump part 22 is integrally formed in the base | substrate 12 in the vicinity of the fluid storage part 16 among the channels 14 in the upstream of the channel 14, FIG. .

  Here, an example of the extrusion type pump unit 22 will be described. As this pump part 22, the 1st and 2nd pump parts 22A and 22B can be used, for example. Hereinafter, the first and second pump units 22A and 22B will be described.

  The details of the first pump unit 22A are as described in Japanese Patent Application Laid-Open No. 2000-314381, but here, the first pump unit 22A will be briefly described as shown in FIG. A casing 30 made of, for example, ceramic, to which fluid is supplied, one input valve 32 provided to face one surface of the casing 30, one pump 34, and one output valve 36 are provided. Each of the input valve 32, the pump 34, and the output valve 36 has an actuator unit 38.

  The casing 30 is formed by laminating a plurality of zirconia ceramic green sheets and integrally firing them, and a partition plate 40 provided in contact with the surface of the base 12, and a first plate provided opposite to the partition plate 40. 2 base bodies 42, and a support member 44 provided between the partition plate 40 and the second base body 42.

  The first pump unit 22A selectively forms a flow path on the back surface of the casing 30 through selective movement of the input valve 32, the pump 34, and the output valve 36 in the approaching / separating direction, thereby allowing fluid flow. To control.

  Further, the partition plate 40 is formed with an introduction hole 46 for supplying a fluid and a discharge hole 48 for discharging the fluid, and the input valve 32 and the pump 34 are provided between the introduction hole 46 and the discharge hole 48. And the output valve 36 is arranged in the horizontal direction.

  Inside the second base 42, there are provided voids 50 for forming vibrating portions at positions corresponding to the input valve 32, the pump 34 and the output valve 36. Each space 50 communicates with the outside through a through-hole 52 having a small diameter provided on the end surface of the second base 42.

  Of the second base body 42, the portion where the void 50 is formed is thin, and the other portion is thick. The thin portion functions as the vibration portion 54 with a structure that is susceptible to vibration with respect to external stress, and the portion other than the void 50 functions as a fixing portion 56 that supports the vibration portion 54.

  Further, between the partition plate 40 and the second base 42, a plurality of support columns (not shown) are interposed in the vicinity of the actuator portion 38 to maintain rigidity. In this example, rigidity is also maintained in the support member 44 of the casing 30.

  Each actuator unit 38 includes a vibrating part 54 and a fixed part 56, a shape holding layer 60 such as a piezoelectric / electrostrictive layer and an antiferroelectric layer formed on the vibrating part 54, and the shape holding layer 60. An operating part 66 having an upper electrode 62 and a lower electrode 64 formed on the lower surface is provided.

  Further, the first pump unit 22A has a displacement transmission unit 68. The displacement transmission unit 68 is formed on each actuator unit 38 and transmits the displacement of each actuator unit 38 in the direction of the back surface of the casing 30.

  When the fluid upstream of the first pump part 22A is sent to the downstream side of the first pump part 22A, the actuator part 38 of the input valve 32 is driven, and the input of the displacement transmission part 68 is input. By separating the end surface corresponding to the valve 32 from the partition plate 40 and then driving the actuator portion 38 of the pump 34 to separate the end surface corresponding to the pump 34 of the displacement transmitting portion 68 from the partition plate 40, The upstream fluid flows through the input valve 32 toward the pump 34.

  Thereafter, the actuator portion 38 of the input valve 32 is driven, the end face corresponding to the input valve 32 of the displacement transmitting portion 68 is brought into contact with the partition plate 40, and then the actuator portion 38 of the output valve 36 is driven, Of the displacement transmitting unit 68, the end surface corresponding to the output valve 36 is separated from the partition plate 40, and the actuator unit 38 of the pump 34 is driven to partition the end surface corresponding to the pump 34 of the displacement transmitting unit 68. By contacting the plate 40, the fluid flows toward the output valve 36.

  Thereafter, the actuator portion 38 of the output valve 36 is driven, and the end face corresponding to the output valve 36 of the displacement transmitting portion 68 is brought into contact with the partition plate 40, so that the fluid flows downstream of the channel 14 through the discharge hole 48. Will flow.

  By sequentially repeating the above-described operation, the fluid that has been on the upstream side of the first pump unit 22A (in this case, the fluid storage unit 16) is moved downstream of the first pump unit 22A, that is, on the downstream side of the channel 14. It will flow sequentially.

  Next, as shown in FIG. 3, the second pump part 22B includes a partition plate 70 provided in contact with the surface of the base 12, a diaphragm 72 provided opposite to the partition plate 70, and these And a support member 74 provided between the partition plate 70 and the diaphragm 72. The partition plate 70, the diaphragm 72, and the support member 74 can be configured by stacking a plurality of zirconia ceramic green sheets and firing them together.

  An operating portion 76 is formed on the upper surface of the diaphragm 72. Similar to the first pump portion 22A described above, the operating portion 76 includes a shape retaining layer 78 such as a piezoelectric / electrostrictive layer or an antiferroelectric layer, and upper portions formed on the upper and lower surfaces of the shape retaining layer 78. An electrode 80 and a lower electrode 82 are included. The diaphragm 72 and the operating part 76 constitute an actuator part 84.

  A cavity 86 for allowing fluid to enter is formed in a portion corresponding to the operating portion 76 in the lower portion of the diaphragm 72. That is, the cavity 86 is partitioned by the partition plate 70, the vibration plate 72, and the support member 74, and communicates with the introduction hole 88 and the discharge hole 90 provided in the partition plate 70.

  On the other hand, in the channel 14 of the base 12, an input valve 92 and an output valve 94 are provided at portions corresponding to the introduction hole 88 and the discharge hole 90.

  The input valve 92 includes an actuator unit 96 and a conical displacement transmission unit 98 provided on the actuator unit 96. The actuator unit 96 includes a space 100 formed in the base body 12, a vibration unit 102 and a fixing unit 104 configured by forming the space 100, and an operation unit 106 formed on the vibration unit 102. It is configured. Similarly, the output valve 94 includes an actuator unit 108 and a conical displacement transmission unit 110 provided on the actuator unit 108.

  Then, the displacement transmitting portion 98 in the input valve 92 closes and opens the introduction hole 88 due to the vertical displacement operation of the actuator portion 96 in the input valve 92, and the vertical displacement of the actuator portion 108 in the output valve 94. By the operation, the displacement transmission unit 110 in the output valve 94 closes and opens the discharge hole 90.

  Therefore, the fluid on the upstream side of the second pump part 22B is guided into the cavity 86 through the input valve 92 and the introduction hole 88, and the volume of the cavity 86 is changed by the drive of the actuator part 84. The fluid flows through the discharge hole 90 and the output valve 94 to the downstream side.

  In the microchemical chip 10A according to the first embodiment, the pump portion 22 is formed integrally with the base 12 on the upstream side of the channel 14, so that it has the same size as the conventional microchemical chip. The fluid was pushed into the channel 14 and moved. In addition, the viscosity of the fluid can be moved to a high viscosity fluid of about 100,000 centipoise, and the moving speed can be realized from 10 picoliter / second to a maximum of 10 microliter / second.

  Next, as shown in FIG. 4, the microchemical chip 10B according to the second embodiment has substantially the same configuration as the microchemical chip 10A according to the first embodiment described above. The downstream side, FIG. 4, is different in that a suction type pump unit 22 is formed integrally with the base 12 in the vicinity of the fluid discharge unit 18 in the channel 14.

  As the pump unit 22, in addition to the first and second pump units 22A and 22B described above, the following third and fourth pump units 22C and 22D can also be used.

  The details of the third pump unit 22C are as described in, for example, Japanese Patent Application Laid-Open No. 2001-124789, but here briefly, the third pump unit 22C is configured as shown in FIG. Further, a partition plate 120 provided in contact with the surface of the base 12, a diaphragm 122 provided to face the partition plate 120, and a support member provided between the partition plate 120 and the diaphragm 122. 124. The partition plate 120, the diaphragm 122, and the support member 124 can be configured by laminating a plurality of zirconia ceramic green sheets and integrally firing them.

  An operating portion 126 is formed on the upper surface of the diaphragm 122. Similar to the first pump portion 22A described above, the operating portion 126 includes a shape retention layer 128 such as a piezoelectric / electrostrictive layer or an antiferroelectric layer, and upper portions formed on the upper and lower surfaces of the shape retention layer 128. An electrode 130 and a lower electrode 132 are included. The diaphragm 122 and the operating part 126 constitute an actuator part 134.

  A cavity 136 for allowing fluid to enter is formed in a portion corresponding to the operating portion 126 in the lower portion of the diaphragm 122. That is, the cavity 136 is partitioned by the partition plate 120, the vibration plate 122, and the support member 124, and communicates with the introduction hole 138 and the discharge hole 139 provided in the partition plate 120.

  When the fluid on the upstream side of the third pump part 22C is sent to the downstream side of the third pump part 22C, the actuator part 134 is driven to reduce the capacity of the cavity 136, thereby reducing the cavity 136. When the fluid inside is pushed away downstream and the actuator unit 134 is driven to expand or restore the capacity of the cavity 136, the fluid on the upstream side is guided into the cavity 136. By repeating these operations in sequence, the upstream fluid flows sequentially downstream.

  Next, as shown in FIG. 6, the fourth pump portion 22D includes a partition plate 140 provided in contact with the surface of the base 12, an upper plate 142 provided opposite to the partition plate 140, and these A side wall 144 is provided between the partition plate 140 and the upper plate 142.

  The side wall 144 is composed of a piezoelectric / electrostrictive body or an antiferroelectric body. Although not shown, an electrode film is formed on the side wall 144. By applying a voltage to the electrode film and applying an electric field to the side wall, the side wall 144 expands and contracts in the vertical direction according to the strength of the electric field. To do.

  A portion surrounded by the partition plate 140, the side wall 144, and the upper plate 142 is formed as a cavity 146 for allowing fluid to enter, and communicates with the introduction hole 148 and the discharge hole 150 provided in the partition plate 140. Yes.

  The diameter of the introduction hole 148 is set smaller toward the cavity 146, and the opening diameter on the channel 14 side is set larger than the opening diameter on the cavity 146 side. Similarly, the diameter of the discharge hole 150 is set larger toward the cavity 146, and the opening diameter on the channel 14 side is set smaller than the opening diameter on the cavity 146 side. That is, the introduction hole 148 has a structure in which the upstream fluid easily enters the cavity 146 through the introduction hole 148, and the fluid in the cavity 146 does not easily exit through the introduction hole 148, and the discharge hole 150 has the fluid in the cavity 146. Is easy to exit to the downstream side through the discharge hole 150, and the downstream fluid is difficult to enter the cavity 146 through the discharge hole 150.

  When the fluid upstream of the fourth pump part 22D is sent to the downstream side of the fourth pump part 22D, the cavity 144 is contracted by applying a positive electric field to the side wall 144 to contract the side wall 144, for example. By reducing the volume of the cavity 146, the fluid in the cavity 146 is forced to flow downstream, and for example, by applying a negative electric field to the side wall 144 and extending the side wall 144, the capacity of the cavity 146 is expanded or restored. The upstream fluid is drawn into the cavity 146. By repeating these operations in sequence, the upstream fluid flows sequentially downstream.

  In the microchemical chip 10B according to the second embodiment, as well as the microchemical chip 10A according to the first embodiment described above, the miniaturization can be realized and the pump unit 22 has a valve structure. Therefore, the microchemical chip 10B that can be simply and inexpensively configured and has improved durability can be realized. In addition, since the pump unit 22 in the microchemical chip 10B according to the second embodiment does not have a valve structure, it cannot push out the fluid, and the downstream side of the fluid is the atmosphere as in the embodiment, Operates as a suction pump with the upstream side filled with fluid. The movable fluid was a fluid having a viscosity up to about 1000 centipoise, and the moving speed could be realized from 1 picoliter / second to a maximum of 10 microliter / second. Then, when experiments and analyzes were performed using the microchemical chips 10A and 10B according to the first and second embodiments, it was possible to improve analysis accuracy for fluids and to perform biochemical analysis of fluids without charge I was able to.

  Next, a microchemical chip 10C according to a third embodiment will be described with reference to FIG.

  The microchemical chip 10C according to the third embodiment has substantially the same configuration as the microchemical chip 10B according to the second embodiment described above, but a sample supply unit for supplying a sample to the channel 14 The difference is that 160 is provided.

  In the sample supply unit 160, a part of the channel 14 has an opening on the upper surface, a supply unit main body 162 formed thereon, a sample storage unit 164 formed on the surface of the base 12, and the sample storage unit A sample channel 166 for guiding a sample from the unit 164 to the supply unit main body 162.

  As shown in FIG. 8, the supply unit main body 162 includes a ceramic casing 170 formed on the surface of the base 12. The casing 170 is formed by stacking a plurality of zirconia ceramic green sheets and integrally firing them. The first and second cavities 172 and 174 that temporarily store the sample from the sample channel 166, the communication hole 176 that communicates between the first and second cavities 172 and 174, and the channel 14 And a sample discharge hole 178 formed toward the opening.

  The supply unit main body 162 includes an actuator unit 177 that vibrates the casing 170 and changes the volume of the second cavity 174. The second cavity 174 includes a lower plate 180 in which a sample discharge hole 178 and a communication hole 176 are formed, an upper plate 184 (vibration plate) positioned on the second cavity 174, and between the lower plate 180 and the upper plate 184. It is divided by the arranged side plate 182. The actuator portion 177 is formed on the surface of the upper plate 184.

  According to the supply unit body 162 configured as described above, when the volume of the second cavity 174 is reduced by driving the actuator unit 177, the sample in the second cavity 174 is discharged from the sample discharge hole 178 at a predetermined speed. And supplied to the channel 14. When the actuator unit 177 is driven to expand or restore the capacity of the second cavity 174, the sample in the first cavity 172 is guided into the second cavity 174 through the communication hole 176, and The sample in the sample reservoir 164 is introduced into the first cavity 172 through the sample channel 166. By sequentially repeating these operations, the sample in the sample supply unit 160 is sequentially supplied to the channel 14.

  The size of the supply unit main body 162 is selected depending on the overall size of the microchemical chip, the type of sample to be handled, and the like, but the size of the second cavity 174 is 3 mm in length, 0.3 mm in width, When the thickness is 0.3 mm and the diameter of the sample discharge hole 178 and the communication hole 176 is 0.07 mm, 100 picoliters of sample is supplied by one driving when the viscosity of the sample is 2 centipoise.

  In the microchemical chip 10C according to the third embodiment, the sample supply unit 160 can arbitrarily set the supply timing and supply amount of the sample to the channel 14 in picoliter units. Thus, the microchemical chip 10C capable of further improving the use efficiency of the sample, analysis accuracy, and speeding up the analysis can be provided at a reduced cost.

  In the case of the microchemical chip 10C, the pump unit 22 is not always necessary, and the movement of the fluid in the channel 14 may use a conventional external pump or electroosmotic flow.

  Next, a microchemical chip 10D according to a fourth embodiment will be described with reference to FIG.

  As shown in FIG. 9, the microchemical chip 10D according to the fourth embodiment has substantially the same configuration as the microchemical chip 10A according to the first embodiment described above, but includes two fluid reservoirs. The difference is that the pump unit 22 is formed in the vicinity of each of the fluid storage units 16A and 16B and the point having the (first and second fluid storage units 16A and 16B). As the pump unit 22, the first and second pump units 22A and 22B shown in FIGS. 2 and 3 can be used.

  That is, in the microchemical chip 10D according to the fourth embodiment, as shown in FIG. 9, the first channel 14a for sending the fluid in the first fluid storage section 16A to the downstream side, and the second fluid storage It has the 2nd channel 14b which sends the fluid of the part 16B downstream, and the confluence | merging channel 14 where two types of fluids sent through the 1st and 2nd channels 14a and 14b merge.

  For example, when a sample to be inspected is supplied to the first fluid reservoir 16A, another sample to be inspected may be supplied to the second fluid reservoir 16B. In this case, biochemical analysis or the like as a result of merging (reaction) of two kinds of samples can be easily performed. Of course, you may make it supply the fluid for conveyance to the 2nd fluid storage part 16B. In that case, by moving the sample to the confluence with the pump unit 22 installed in the first channel 14a, by continuing to supply the transport fluid in the pump unit 22 installed in the second channel 14b, Only the sample that has moved to the merging point can be efficiently used for separation, reaction, analysis, and the like.

  Moreover, like the microchemical chip 10Da according to the modification shown in FIG. 10, for example, three fluid storage portions 16A to 16C are provided on the surface of the base 12, and further, the first to third channels 14a to 14c and the merging channel are provided. By providing 14, if different samples are supplied to the first and second channels 14 a and 14 b and a transport fluid is supplied to the third channel 14 c, it is possible to save valuable or expensive samples. While planning, the result after merging of different samples can be easily inspected. Of course, four or more channels and one or more merging channels may be provided.

  Next, as shown in FIG. 11, the microchemical chip 10E according to the fifth embodiment has substantially the same configuration as the microchemical chip 10D according to the fourth embodiment described above. The difference is that the vibration generator 190 is provided. For example, as shown in FIG. 12, the vibration generating unit 190 is provided on the upper part of the joining portion of the channel 14, and the vibration unit 192 and the operation unit 194 formed on the vibration plate 192 (the shape retaining layer 196, the upper electrode 198). And the lower electrode 199). By applying an alternating voltage to the upper electrode 198 and the lower electrode 200, vibrations can be easily generated in the merged portion. The diaphragm 192 is necessary for forming the operating portion 194 by integrally firing, but is not necessary when the operating portion 194 is formed by forming an electrode on a bulk piezoelectric body, for example. The part 194 may be directly attached to the channel 14. Further, the vibration generating unit 190 may be installed on the side surface, the bottom surface, or the like in addition to being installed on the channel 14. In particular, when the substrate 12 is made of zirconia ceramics, the vibration generating unit 190 may be formed integrally with the pump unit 22 described above.

  Also in the microchemical chip 10E according to the fifth embodiment, by applying vibration to the joining part, the joining and mixing efficiency of two kinds of samples at the joining part can be increased, and the reaction and inspection speed are improved. I was able to.

  Next, a microchemical chip 10F according to a sixth embodiment will be described with reference to FIG.

  The microchemical chip 10F according to the sixth embodiment has substantially the same configuration as the microchemical chip 10B according to the second embodiment described above, as shown in FIG. The difference is that the first and second fluid reservoirs 16A and 16B are provided, and the check valve 210 is formed in the vicinity of each fluid reservoir 16A and 16B. As the pump unit 22, any one of the first to fourth pump units 22A to 22D shown in FIGS. 2 and 3 and FIGS. 5 and 6 can be used.

  The microchemical chip 10F according to the sixth embodiment also sends the first channel 14a that sends the fluid in the first fluid reservoir 16A downstream and the fluid in the second fluid reservoir 16B downstream. It has the 2nd channel 14b and the confluence | merging channel 14 where two types of fluids sent through the 1st and 2nd channels 14a and 14b merge.

  As the check valve 210, the first check valve 210A shown in FIG. 14 or the second check valve 210B shown in FIG. 15 can be used. The description of the check valve 210 will be made on the assumption that the cover plate 212 that covers at least the channels 14 a and 14 b is covered on the base 12.

  As shown in FIG. 14, the first check valve 210 </ b> A has a valve body 214 provided in the channels 14 a and 14 b of the base 12.

  The valve main body 214 includes an upper plate 216, a side wall 218 provided between the base 12 and the upper plate 216, and a conical displacement transmission unit 220 provided on the upper plate 216. In addition, a conical recess 222 is formed in a portion of the cover plate 212 corresponding to the displacement transmission unit 220.

  The side wall 218 is composed of a piezoelectric / electrostrictive body or an antiferroelectric body. Although not shown, an electrode film is formed on the side wall 218. By applying a voltage to the electrode film and applying an electric field to the side wall 218, the side wall 218 is vertically moved according to the strength of the electric field. It expands and contracts.

  Then, for example, by applying a negative electric field to the side wall 218 and extending the side wall 218, the displacement transmitting unit 220 is brought into contact with the inner surface of the recess 222, thereby stopping the flow of the fluid. By contracting the side wall 218, the displacement transmitting portion 220 is separated from the concave portion 222, so that the fluid flows in the channel 14a (14b).

  On the other hand, the second check valve 210B has a valve body 230 provided in the channels 14a and 14b of the base 12 as shown in FIG.

  The valve body 230 includes an actuator part 232 and a conical displacement transmission part 234 provided on the actuator part 232. The actuator unit 232 includes a space 236 formed in the base body 12, a vibration unit 238 and a fixing unit 240 configured by forming the space 236, and an operation unit 242 formed on the vibration unit 238. It is configured.

  Then, the displacement transmitting portion 234 comes into contact with or separates from the concave portion 222 due to the vertical displacement operation of the actuator portion 232 in the valve main body 230, and the flow of the fluid stops or advances.

  Then, as shown in FIG. 13, for example, a sample to be inspected and a transport fluid are supplied to the first fluid reservoir 16A, and another sample to be inspected and a transport fluid are supplied to the second fluid reservoir 16B. May be supplied. In this case, biochemical analysis or the like as a result of merging (reaction) of two kinds of samples can be easily performed. Each check valve 210 can arbitrarily adjust the supply amount of the sample to each channel 14a and 14b, which is advantageous in improving the accuracy of analysis and reducing the cost.

  Further, for example, a sample to be inspected may be supplied to the first fluid storage unit 16A, and a transport fluid may be supplied to the second fluid storage unit 16B. Also in this case, the check valve 210 can arbitrarily adjust the supply amount of the sample and the transport fluid to the channels 14a and 14b.

  Next, a microchemical chip 10G according to a seventh embodiment will be described with reference to FIG.

  As shown in FIG. 16, the microchemical chip 10G according to the seventh embodiment has substantially the same configuration as the microchemical chip 10B according to the second embodiment described above, but the upstream side of the channel 14 And the point that electrodes 250 and 252 are formed on the downstream side.

  Specifically, in the channel 14, one electrode 250 is formed in the vicinity of the fluid storage unit 16, and the other electrode 252 is formed in the vicinity of the upstream side of the pump unit 22. When the sample to be inspected is a solute having a charge and has a negative charge, for example, one electrode 250 is used as an anode (electrode having a high potential), and the other electrode 252 is used as a cathode. Electrophoresis is performed in a direction opposite to the moving direction by the pump unit 22.

  Thus, also in the microchemical chip 10G according to the seventh embodiment, the sample itself is drawn in the direction opposite to the flow (positive electrode) by reversing the direction of electrophoresis with the direction of movement by the pump unit 22. The separation force of electrophoretic analysis was improved.

  In addition, when the fluid itself has a polarity, by adjusting the strength of the electric field applied between the electrodes, in addition to the movement of the fluid by the pump, the movement by the electroosmotic flow occurs, and the movement of the fluid is more effective and faster. The analysis was completed.

  Furthermore, when the sample (solute) to be inspected is positively charged, the sample itself is drawn in the direction opposite to the flow (negative electrode) by making the electrode in the fluid moving direction by the pump unit 22 positive. Power worked and sufficient separation ability was secured.

  Next, a microchemical chip 10H according to an eighth embodiment will be described with reference to FIG.

  As shown in FIG. 17, the microchemical chip 10H according to the eighth embodiment has substantially the same configuration as the microchemical chip 10B according to the second embodiment described above, but crosses the channel 14. The difference is that another channel 260 is formed and electrodes 250 and 252 are formed upstream and downstream of the other channel 260.

  Specifically, in the other channel 260, one electrode 250 is formed in the vicinity of the fluid storage part 262, and the other electrode 252 is formed in the vicinity of the fluid discharge part 264. When the sample to be inspected is a fluid having a charge and has a negative charge, for example, one of the electrodes 250 is a cathode (an electrode having a low potential) and the other electrode 252 is an anode, thereby discharging the fluid. An electroosmotic flow is generated in the direction of the portion 264.

  Accordingly, a sample having an electric charge or not is supplied to one channel 14, and a sample having an electric charge is supplied to the other channel 260, so that these samples are mixed at the crossover portion. By flowing the mixed fluid downstream of the channel 14 through the channel 14, biochemical analysis can be performed on the mixed fluid.

  Of course, by forming the vibration generating portion 190 (see FIG. 11) at the crossing portion, the mixing and reaction efficiency of two types of samples at the crossing portion can be increased, and the experiment and inspection speed can be improved.

  In the microchemical chip 10H according to the eighth embodiment, the sample is supplied from the fluid reservoir 262 to the crossing portion by the electroosmotic flow described above, and then pumped from the fluid reservoir 16 through the channel 14. When the sample is separated and moved by the carrier fluid supplied to the crossing part by the part 22, the voltage applied to the electrodes is reversed while the pump part 22 is operating, so that the sample other than the sample supplied to the crossing part is reversed. The sample can be prevented from flowing into the channel 14.

  Next, a microchemical chip 10I according to a ninth embodiment will be described with reference to FIG.

  As shown in FIG. 18, the microchemical chip 10I according to the ninth embodiment has substantially the same configuration as the microchemical chip 10F according to the sixth embodiment described above. The difference is that a valve portion 300 is formed in the first channel 14a that flows. That is, the valve part 300 is not formed in the second channel 14b through which the transport fluid flows, but the valve part 300 is formed only in the first channel 14a to which a valuable or expensive sample is supplied.

  As this valve part 300, the 1st valve part 300A shown in FIG. 19, the 2nd valve part 300B shown in FIG. 20, or the 3rd valve part 300C shown in FIG. 21, for example can be used.

  As shown in FIG. 19, the first valve unit 300 </ b> A includes, for example, a ceramic channel resistor 302 and a heater 304 embedded in the channel resistor 302.

  The first valve portion 300A utilizes a change in flow path resistance due to a change in fluid viscosity due to heat. When the heater 304 is energized and the portion of the first channel 14a corresponding to the flow path resistor 302 is heated, the heat lowers the viscosity of the fluid, and the fluid is the first channel 14a. Flow through the channel 14a. On the other hand, when the energization to the heater 304 is stopped and the portion corresponding to the flow path resistor 302 is cooled, the viscosity of the fluid increases, and as a result, the flow path resistance increases and the flow of the fluid stops. Become. That is, the flow of the fluid can be controlled by energizing the heater 304 and stopping energization, and the valve unit 300 functions.

  As shown in FIG. 20, the second valve unit 300B includes a vibration generating unit 310 that applies vibration to a part of the first channel 14a. The vibration generating unit 310 includes a vibration plate 312 provided on the first channel 14a and an operation unit 314 (shape holding layer 316, upper electrode 318, and lower electrode 320) formed on the vibration plate 312. be able to. By applying an alternating voltage to the upper electrode 318 and the lower electrode 320, vibration can be easily generated in the first channel 14a.

  The second valve unit 300B utilizes a change in flow path resistance due to vibration. When vibration is applied to a part of the first channel 14a, the flow resistance is increased, so that the fluid flow stops.

  As shown in FIG. 21, the third valve unit 300 </ b> C includes a casing 332 provided on a cover plate 330 that is covered so as to close at least the first channel 14 a. A cavity 338 communicating with the first channel 14 a through the introduction hole 334 and the discharge hole 336 is formed in the casing 332.

  On the casing 332, an operation unit 340 (a shape retaining layer 342, an upper electrode 344 and a lower electrode 346) is formed, and functions as an actuator unit 350 together with the upper part (the diaphragm 348) of the casing 332.

  Contrary to the case of the pump unit shown in FIG. 6, the diameter of the introduction hole 334 is set larger toward the cavity 338, and the opening diameter on the first channel 14 a side is set smaller than the opening diameter on the cavity 338 side. Has been. Similarly, the diameter of the discharge hole 336 is set smaller toward the cavity 338, and the opening diameter on the first channel 14a side is set larger than the opening diameter on the cavity 338 side. In other words, the introduction hole 334 has a structure in which the fluid in the cavity 338 can easily apply pressure to the upstream fluid through the introduction hole 334, and the discharge hole 336 has a structure in which the downstream fluid passes through the discharge hole 336. It is structured to easily apply pressure to the fluid inside.

  Then, when the volume of the cavity 338 is reduced by driving the actuator unit 350 while the sample is moving in the first channel 14a by the pump unit 22 shown in FIG. A force that causes a flow in a direction opposite to the direction of fluid flow by the pump unit 22 works, and as a result, the flow of fluid can be stopped in the third valve unit 300C.

  In the above example, an example in which two channels or three channels are merged or an example in which two channels are crossed is shown. Of course, when four or more channels are merged, three or more channels are merged. It can also be applied when the channels are crossed.

  The microchemical chip according to the present invention is not limited to the above-described embodiment, but can of course have various configurations without departing from the gist of the present invention. For example, the base 12 may be formed of zirconia ceramics having low reactivity with the actuator material from the viewpoint of integration with the pump unit 22 and the sample supply unit 160, or only the plate material that closes the channel 14 on the upper surface is made of glass. It may consist of a composite with zirconia ceramics.

1 is a perspective view showing a microchemical chip according to a first embodiment. It is sectional drawing which shows a 1st pump part. It is sectional drawing which shows a 2nd pump part. It is a perspective view which shows the microchemical chip which concerns on 2nd Embodiment. It is sectional drawing which shows a 3rd pump part. It is sectional drawing which shows a 4th pump part. It is a perspective view which shows the microchemical chip concerning a 3rd embodiment. It is sectional drawing which shows the structure of the supply part main body of a sample supply part. It is a perspective view which shows the microchemical chip which concerns on 4th Embodiment. It is a perspective view which shows the modification of the microchemical chip concerning 4th Embodiment. It is a perspective view which shows the microchemical chip concerning a 5th embodiment. It is sectional drawing which shows the structure of a vibration generation part. It is a perspective view which shows the microchemical chip concerning a 6th embodiment. It is sectional drawing which shows a 1st non-return valve. It is sectional drawing which shows a 2nd non-return valve. It is a perspective view which shows the microchemical chip concerning a 7th embodiment. It is a perspective view which shows the microchemical chip based on 8th Embodiment. It is a perspective view which shows the microchemical chip concerning a 9th embodiment. It is sectional drawing which shows a 1st valve part. It is sectional drawing which shows a 2nd valve part. It is sectional drawing which shows a 3rd valve part.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10A-10I ... Micro chemical chip 12 ... Base | substrate 14 ... Channel 14a ... 1st channel 14b ... 2nd channel 16 ... Fluid storage part 16A, 16B ... 1st, 2nd fluid storage part 18 ... Fluid discharge part 22 ... Pump part 22A-22D ... 1st-4th pump part 160 ... Sample supply part 162 ... Supply part main body 190 ... Vibration generating part 210 ... Check valve 210A, 210B ... 1st, 2nd check valve 250,252 ... Electrode 260 ... Another channel 300 ... Valve part 300A to 300C ... First to third valve parts

Claims (22)

In a microchemical chip having one or more channels through which a fluid flows in a substrate,
Having a pump section upstream and / or downstream of the channel;
The microchemical chip, wherein the pump unit is formed integrally with the base. The microchemical chip according to claim 1, wherein
Having a valve portion at least upstream of the channel;
The microchemical chip, wherein the valve portion is formed integrally with the base body. The microchemical chip according to claim 1 or 2,
A microchemical chip, wherein an electrode for electrophoresis of fluid is formed on the upstream side and / or the downstream side of the channel. The microchemical chip according to claim 1, wherein
The microchemical chip characterized in that the channel has one or more sample channels through which one or more samples to be inspected circulate. The microchemical chip according to claim 4,
The microchemical chip according to claim 1, wherein the one or more sample channels each have a corresponding sample and a transport fluid flowing therethrough. The microchemical chip according to claim 4 or 5,
A microchemical chip, wherein a sample supply section for supplying a corresponding sample to each of the one or more sample channels is provided. The microchemical chip according to claim 6,
The microchemical chip according to claim 1, wherein the channel has a merge channel in which one or more samples from the one or more sample channels merge. The microchemical chip according to claim 1, wherein
The channel has one or more sample channels through which one or more samples to be inspected flow, and one transport channel through which a transport fluid for transporting the sample flows. Chemical chip. The microchemical chip according to claim 8,
The channel is a merging channel in which one or more samples from the one or more sample channels merge with a transport fluid from the one transport channel, or one or more samples from the one or more sample channels. A microchemical chip comprising a merging channel where a fluid mixed with a fluid for transportation from the one transportation channel merges. The microchemical chip according to claim 7 or 9,
The one or more sample channels each have a valve portion in front of the confluence channel. The microchemical chip according to claim 7, 9 or 10,
A microchemical chip comprising a vibration generating portion at the joining portion. The microchemical chip according to claim 6,
The microchemical chip, wherein the one or more sample channels intersect each other. The microchemical chip according to claim 8,
The one or more sample channels and the one transport channel intersect each other, or the merge channel of the one or more sample channels and the one transport channel intersect each other. Micro chemical chip. The microchemical chip according to claim 12 or 13,
The one or more sample channels each have a valve portion in front of the crossing portion. The microchemical chip according to any one of claims 12 to 14,
A microchemical chip comprising a vibration generating portion at the crossing portion. The microchemical chip according to claim 2, 10 or 14,
The microchemical chip, wherein the valve portion includes a heater that applies heat to a part of the channel. The microchemical chip according to claim 2, 10 or 14,
The microchemical chip, wherein the valve unit includes a vibration generating unit that applies vibration to a part of the channel. The microchemical chip according to claim 2, 10, 14 or 17,
2. The microchemical chip according to claim 1, wherein the valve portion includes a cavity communicating with the channel and an actuator portion that makes the volume of the cavity variable. The microchemical chip according to claim 1, wherein
The microchemical chip, wherein the pump unit includes a cavity communicating with the channel and a pump actuator unit that makes the volume of the cavity variable. The microchemical chip according to claim 6,
The sample supply section includes a nozzle and a cavity communicating with the channel;
A microchemical chip comprising: a pump actuator section that makes the volume of the cavity variable. The microchemical chip according to claim 19, 20,
A microchemical chip comprising a valve portion between the channel and the cavity. The microchemical chip according to claim 21,
The valve portion includes a valve body disposed in a communication portion between the channel and the cavity, and a valve actuator portion that operates the valve body to selectively open and close the communication portion. Micro chemical chip to do.

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