JP2009062911A - Reaction detecting device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a reaction detecting device for sending a driving liquid at a predetermined flow to a microchip, by correcting a characteristic dispersion in a micropump by a simple method. <P>SOLUTION: This reaction detecting device has a pump for injecting fluid into the microchip, a storage means for storing performance data on the pump, a driving means for driving the pump, and a control means for controlling the driving means, and is characterized in that the control means controls the driving means based on the performance data. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a reaction detection apparatus.

  In recent years, by making full use of micromachine technology and ultrafine processing technology, devices and means (for example, pumps, valves, flow paths, sensors, etc.) for performing chemical analysis, chemical synthesis, etc. are miniaturized and integrated on one chip. Such a system has been developed (see, for example, Patent Document 1).

  This is also called μ-TAS (Micro total Analysis System), bioreactor, lab-on-chip, biochip, medical examination, diagnostic field, environmental measurement field, agricultural production Its application is expected in the manufacturing field. In reality, as seen in genetic testing, automated, faster, and simplified microanalysis systems are costly and necessary when complex processes, skilled techniques, and equipment operations are required. The benefits of enabling time-and-location analysis as well as sample size and time are enormous.

  In the field where various tests such as clinical tests are performed, the quantitativeness of analysis, the accuracy of analysis, and the economy of these test chips that produce results quickly regardless of location are regarded as important. On the other hand, since the inspection chip is severely restricted by its size and form, it is required to establish a highly reliable liquid delivery system with a simple configuration.

  As the micro pump, various types such as a check valve type pump provided with a check valve in the outflow / inflow hole of the valve chamber provided with the actuator can be used. For example, as disclosed in Patent Document 1, It is preferable to use a piezo pump. According to the piezo pump, for example, the liquid feeding direction and the liquid feeding speed can be controlled by changing the driving voltage and frequency of the pump.

  By the way, in a micro total analysis system that inspects a test chip containing a sample and a reagent in a fluid control detection apparatus equipped with the above-described micropump or the like, it is required to reduce the required amount of the sample or reagent as much as possible. ing. In addition to this, it is required to complete an appropriate analysis in a short time.

  In order to respond to such a request, it is necessary to stabilize the feeding of the driving liquid by the micropump. In the micro total analysis system, if the flow rate, the flow rate, etc. are not kept constant, there is a possibility of adversely affecting the analysis result.

However, when driving liquid is supplied from an external micropump into the inspection chip, if the connection with the micropump is not securely established, liquid leakage occurs and the fluid flowing downstream is at a constant speed. In some cases, it did not flow or the flow rate per hour was excessive or insufficient. In order to cope with such a problem, in Patent Document 2, a detection device for obtaining information such as the flow rate of the driving liquid is provided on the upstream side in the flow direction of the driving liquid in the inspection chip body, and based on the detection result. The method of adjusting the flow rate is disclosed.
JP 2001-322099 A JP 2006-275734 A

  However, since the performance of the micropump varies greatly, it has been difficult to stably control the driving fluid at a desired flow rate in the case of a micropump having performance at the upper or lower limit level of variation.

  The present invention has been made in view of the above problems, and provides a reaction detection device that corrects characteristic variations of a micropump by a simple method and sends a driving liquid to a microchip at a predetermined flow rate. Objective.

  In order to solve the above problems, the present invention has the following features.

1.
A pump for injecting fluid into the microchip;
Storage means for storing performance data of the pump;
Drive means for driving the pump;
Control means for controlling the drive means;
Have
The reaction detection apparatus according to claim 1, wherein the control unit controls the driving unit based on the performance data.

2.
The pump is
A first flow path in which the flow path resistance changes according to the differential pressure;
A second flow path in which the ratio of the change in flow path resistance to the change in differential pressure is smaller than the first flow path;
A pressurizing chamber connected to the first flow path and the second flow path;
A piezo actuator for changing the pressure inside the pressurizing chamber;
The reaction detection apparatus according to 1, which comprises:

3.
3. The reaction detection according to claim 1, wherein the performance data is data indicating a relationship between a rise time of a driving voltage waveform generated by the driving means and a flow rate or pressure of the fluid discharged from the pump. apparatus.

4).
4. The reaction detection apparatus according to 3, wherein the control unit controls the flow rate or the pressure by changing a rising time of the drive voltage waveform.

5).
3. The reaction according to claim 1, wherein the performance data is data indicating a relationship between a fall time of a driving voltage waveform generated by the driving unit and a flow rate or pressure of the fluid discharged from the pump. Detection device.

6).
6. The reaction detection apparatus according to 5, wherein the control unit controls the flow rate or the pressure by changing a falling time of the drive voltage waveform.

  According to the present invention, since the driving of the micropump is controlled based on the performance data of each micropump stored in advance in the storage means, a reaction detection device that sends the driving liquid to the microchip at a predetermined flow rate is provided. Can do.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  FIG. 1 is an external view of a reaction detection device 80 according to an embodiment of the present invention.

  The reaction detection device 80 is a device that automatically detects a reaction between a specimen previously injected into the microchip 1 and a reagent and displays the result on the display unit 84. The housing 82 has an insertion port 83, and the microchip 1 is inserted into the insertion port 83 and set inside the housing 82.

  The insertion port 83 is sufficiently higher than the thickness of the microchip 1 so that the microchip 1 does not come into contact with the microchip 1 during insertion. Reference numeral 85 denotes a memory card slot, 86 denotes a print output port, 87 denotes an operation panel, and 88 denotes an input / output terminal.

  The person in charge of inspection inserts the microchip 1 in the direction of the arrow in FIG. 1 and operates the operation panel 87 to start the inspection. Inside the housing 82, a micropump unit 5 (not shown in FIG. 1) injects a liquid such as a driving liquid into the microchip 1 according to a command from the control means, and the reaction in the microchip 1 is automatically inspected. Is called. When the inspection is completed, the result is displayed on the display unit 84 constituted by a liquid crystal panel or the like. The inspection result can be output from the print output port 86 or stored in a memory card inserted into the memory card slot 85 by operating the operation panel 87. Further, data can be stored in the personal computer or the like from the external input / output terminal 88 using, for example, a LAN cable.

  The inspection person takes out the microchip 1 from the insertion port 83 after the inspection is completed.

  Next, an example of the micropump unit 5 according to the embodiment of the present invention will be described with reference to FIG.

  2A is a plan view of the micropump unit 5 according to the present invention, FIG. 2B is a left side view, and FIG. 2C is a right side view. Moreover, FIG.2 (d) is sectional drawing of the part shown by AA in Fig.2 (a).

  As shown in FIG. 2, the micropump unit 5 includes a first substrate 11 and a second substrate 12. In FIG. 2A, the groove provided in the first substrate 11 is indicated by a dotted line.

  The portion indicated by AA in FIG. 2A constitutes one micropump MP, and the liquid sucked from, for example, the input / output port 145 is discharged from the input / output port 146 by a micropump mechanism described later. Alternatively, the liquid sucked from the input / output port 146 in the reverse direction can be discharged from the input / output port 145. In the example of FIG. 2A, eight micro pumps MP are formed on the first substrate 11. Since these micropumps MP have the same structure, the structure will be described below with reference to FIG.

  The first substrate 11 is, for example, a rectangular sheet having a width of 17 mm, a depth of 35 mm, and a thickness of 0.2 mm. As shown in FIG. 2D, each micropump MP formed on the first substrate 11 includes a pump chamber 121, a diaphragm 122, a first throttle channel 123, a first channel 124, and a second throttle channel. 125 and a second flow path 126.

  The first substrate 11 is formed, for example, by processing a silicon wafer into a predetermined shape by a known photolithography process. That is, the patterned silicon substrate is etched to a predetermined depth using an ICP dry etching apparatus.

  After the etching process, dicing is performed to cut out the first substrate 11 from the silicon wafer into a predetermined outer shape. The thickness of the first substrate 11 is about 0.2 mm, for example.

  As shown in FIG. 2D, the piezoelectric element 112 is bonded to the outer surface of the diaphragm 122. Two electrodes for driving the piezoelectric element 112 are drawn to the surfaces on both sides of the piezoelectric element 112 and connected to a flexible wiring (not shown). For the piezoelectric element 112, for example, a piezoelectric actuator is used.

  The second substrate 12 needs to cover the flow path of each micropump MP formed on the first substrate 11 in close contact with the first substrate 11. Therefore, it is desirable that the thermal expansion coefficient of the second substrate 12 is as close as possible to the first substrate 11. In the case where the material of the first substrate 11 is silicon, for example, Pyrex (registered trademark) glass (Pyrex is a registered trademark of Corning Glass Works), Tempax glass (Tempax is a registered trademark of Schott Glasser), or the like is used. These have substantially the same coefficient of thermal expansion as the silicon substrate. The shape of the second substrate 12 is, for example, the same width 17 mm and depth 35 mm as the first substrate 11, and the thickness is 1 mm.

  Next, the input / output port 145 and the input / output port 146 are formed in the second substrate 12 using a method such as ultrasonic processing. After drilling, the second substrate 12 is aligned so that the two sides coincide with the first substrate 11, and bonded by, for example, anodic bonding.

  In this way, the micropump unit 5 can be manufactured. The micro pump unit 5 sucks liquid from one input / output port 145 and discharges liquid from the other input / output port 146 by the operation of the micro pump MP described above. Further, by controlling the driving voltage applied to the piezoelectric element 112, the direction of liquid suction and discharge can be reversed. For the structure of the first substrate 11 itself, reference can be made to Japanese Patent Application Laid-Open No. 2001-322099 described in the section of the prior art.

  Next, the operation principle of the micropump unit 5 will be described.

  The second throttle channel 125 has a low channel resistance when the differential pressure between the inflow side and the outflow side is close to zero, but the channel resistance increases when the differential pressure increases. That is, the pressure dependency is large. The first throttle channel 123 has a larger channel resistance when the differential pressure is close to zero than that of the second throttle channel 125, but has little pressure dependency, and the channel resistance even when the differential pressure increases. Does not change so much, and when the differential pressure is large, the channel resistance becomes smaller than that of the second throttle channel 125.

  Such flow path resistance characteristics allow the liquid (fluid) flowing through the flow path to be turbulent according to the magnitude of the differential pressure, or always to be laminar regardless of the differential pressure. Or can be obtained by Specifically, for example, the second throttle channel 125 is an orifice having a short channel length, and the first throttle channel 123 is a nozzle having the same inner diameter as the second throttle channel 125 and a long channel length. It is possible to realize.

  By utilizing such flow path resistance characteristics of the first throttle flow path 123 and the second throttle flow path 125, pressure is generated in the pump chamber 121, and the rate of change in the pressure is controlled, thereby providing a flow path. It is possible to realize a pump action that discharges a liquid toward a lower resistance.

  That is, if the pressure in the pump chamber 121 is increased and the rate of change is increased, the differential pressure increases and the flow resistance of the second throttle flow path 125 is greater than that of the first throttle flow path 123. It becomes larger than the path resistance, and the liquid in the pump chamber 121 is discharged from the first throttle channel 123 (discharge process). If the pressure in the pump chamber 121 is lowered and the rate of change is reduced, the differential pressure is kept small, and the flow resistance of the first throttle channel 123 is greater than that of the second throttle channel 125. The resistance becomes larger than the resistance, and the liquid flows into the pump chamber 121 from the second throttle channel 125 (suction process).

  On the contrary, if the pressure in the pump chamber 121 is increased and the rate of change is reduced, the differential pressure is maintained smaller, and the flow resistance of the first throttle flow path 123 is greater than that of the second throttle flow path. The flow path resistance of 125 becomes larger, and the liquid in the pump chamber 121 is discharged from the second throttle flow path 125 (discharge process). If the pressure in the pump chamber 121 is lowered and the rate of change is increased, the differential pressure increases, and the flow resistance of the first throttle flow path 123 is greater than that of the second throttle flow path 125. And the liquid flows into the pump chamber 121 from the first throttle channel 123 (suction process).

  Such pressure control of the pump chamber 121 is realized by controlling the drive voltage supplied to the piezoelectric element 112 and controlling the amount and timing of deformation of the diaphragm 122.

  FIG. 3 is an explanatory diagram showing the relationship between the drive voltage E supplied to the piezoelectric element 112 and the flow rate Q. When a high drive voltage is applied to the piezoelectric element 112, the pressure in the pump chamber 121 is increased.

  Since the rise time T1 <fall time T3 in the waveform shown in FIG. 3A-1, the rate of change when the pressure in the pump chamber 121 rises is higher than the rate of change when the pressure in the pump chamber 121 falls. large. Therefore, the liquid in the pump chamber 121 is discharged from the first throttle channel 123 as described above.

  FIG. 3A-2 shows an example of the flow rate Q of the liquid discharged from the flow path 123 in the flow path 124. Since the pressure in the pump chamber 121 suddenly rises during the rise time T1, the flow rate Q flowing through the flow path 124 also suddenly rises. When the pressure in the pump chamber 121 gradually falls during the fall time T3 after the pause period of T2, the liquid mainly flows into the pump chamber 121 from the second throttle flow path 125, and a part of the first throttle flow. It flows into the pump chamber 121 from the passage 123. Therefore, the flow rate Q decreases gently. However, the flow rate Q that decreases during the fall time T3 is less than the flow rate Q that flows during the rise time T1, and the flow rate Q increases from the initial state during the rest period of T4. Thus, the flow rate Q increases by repeating the cycle from T1 to T4.

  On the other hand, since the fall time T7 <rise time T5 in the waveform shown in FIG. 3B-1, the rate of change when the pressure in the pump chamber 121 rises is the change rate when the pressure in the pump chamber 121 falls. Less than a percentage. Therefore, the liquid flows into the pump chamber 121 from the first throttle channel 123 as described above.

  FIG. 3B-2 shows an example of the flow rate Q of the liquid sucked from the flow path 123 in the flow path 124. When the pressure in the pump chamber 121 gradually rises during the rise time T5, the liquid is mainly discharged from the second throttle channel 125 and a part is discharged from the first throttle channel 123. Therefore, the flow rate Q increases gently. On the other hand, when the pressure in the pump chamber 121 suddenly drops during the fall time T7 after the pause period of T6, the liquid flows into the pump chamber 121 from the first throttle channel 123. Therefore, the flow rate Q decreases rapidly. However, the flow rate Q that increases during the period T5 is less than the flow rate Q that is discharged during the fall time T7, and the flow rate Q decreases during the rest period of T8 from the initial state. Thus, the flow rate Q decreases by repeating the cycle from T5 to T8.

  In FIG. 3, the maximum voltage e1 applied to the piezoelectric element 112 is about several volts to several tens of volts, and about 100 volts at the maximum. Times T1 and T7 are about 20 μs, times T2 and T6 are about 0 to several μs, and times T3 and T5 are about 60 μs. Times T4 and T8 may be zero. The frequency of the drive voltage E is about 11 kHz. With the drive voltage E shown in FIGS. 3 (a-1) and 3 (b-1), for example, a flow rate as shown in FIGS. 3 (a-2) and 3 (b-2) is applied to the flow path 23. can get. The flow curves in FIGS. 3 (a-2) and 3 (b-2) schematically show the flow rate obtained by the pump operation, and actually the inertial vibration of the fluid is superimposed. Therefore, a curve obtained by superimposing a vibration component on the flow rate curves shown in these figures indicates the actual flow rate obtained.

  FIG. 4 is an explanatory diagram showing the relationship between the rise time T1, the fall time T2 of the drive voltage waveform supplied to the piezoelectric element 112, the flow rate Q, and the pressure P. FIG. 5 shows the maximum voltage e1 and the flow rate Q supplied to the piezoelectric element 112. It is explanatory drawing which shows the relationship of the pressure P. FIG. The pressure P is a pressure at which liquid is discharged from the input / output port 146.

  First, the characteristic variation of the micropump MP will be described with reference to FIG. The horizontal axis represents the maximum voltage e1 (V) of the drive voltage waveform shown in FIG. 3, and the vertical axis represents the flow rate Q or the pressure P. 5A shows that when the maximum voltage e1 is 40 V, there is a micropump MP with a flow rate Q of 400 nl / s and a micropump MP with 600 nl / s. Thus, since the piezoelectric element 112 such as a piezoelectric actuator has a large variation in characteristics, the maximum voltage e1 at which a predetermined flow rate Q or pressure P can be obtained differs for each micropump MP.

  In the method of changing the maximum voltage e1 for each micropump MP in order to obtain a predetermined flow rate Q or pressure P, it is necessary to provide a power supply circuit capable of setting the maximum voltage e1 for each micropump MP, and the circuit configuration becomes complicated. There is a problem.

  FIG. 4A illustrates one cycle of the waveform of the drive voltage E illustrated in FIG.

FIG. 4B is a graph showing the relationship between the rise time T1 of the drive voltage waveform, which is one of the performance data of the micropump MP, the flow rate Q, and the pressure P. When T2 to T4 are constant, the flow rate Q or the pressure P can be controlled by changing the period of the rising time T1 as shown in FIG. FIG 4 (b) the rise time T1 is the maximum time T1 _0, even beyond T1 _0, also the flow rate be less than T1 ₀ Q, pressure P is reduced.

  The graph of FIG. 4B is obtained by measuring the flow rate Q and the pressure P with the conditions other than the rising time T1 being constant for each micropump. For example, the micropump MP is driven by changing the rising time T1 on the condition that the maximum voltage e1 is 40V, the time T2 is 2 μs, the time T3 is 60 μs, the time T4 is 1 μs, and the frequency of the driving voltage E is 11 kHz, and the flow rate Q, pressure Measure P.

  When the flow rate Q or the pressure P is measured in this way, a graph of performance data as shown in FIG. 4B is obtained. For example, when the predetermined flow rate Q is, for example, 400 nl / s, the value of the rise time T1 at which this flow rate Q is obtained is obtained from the performance data acquired in advance for each micropump MP, and other conditions are obtained when the performance data is acquired. The micropump MP is driven under conditions.

  FIG. 4C is a graph showing the relationship between the falling period T3 of the drive voltage waveform, which is one of the performance data of the micropump MP, the flow rate Q, and the pressure P. Similarly, it is obtained by measuring the flow rate Q and the pressure P by driving the micropump MP while changing the falling time T3 with T1, T3, and T4 as constant conditions. Further, the fall time T3 for obtaining the desired flow rate Q and pressure P can be obtained from the performance data.

  As described above, the flow rate Q and the pressure P can be easily controlled by changing the rising time T1 and the falling time T3 of the drive voltage waveform.

  Note that the relationship between the flow rate Q and the pressure P is similarly measured for the rise time T5 and the fall time T7 of the waveform of the driving voltage E of the micropump MP shown in FIG. 3, and the rise time T5 and the fall time T7 are variable. By doing so, a desired flow rate Q and pressure P can be obtained.

  Next, an example of the microchip 1 according to the embodiment of the present invention will be described with reference to FIG.

  6A and 6B are external views of the microchip 1. FIG. In FIG. 6A, an arrow indicates an insertion direction in which the microchip 1 is inserted into a case 82 to be described later, and FIG. 6A illustrates a surface that becomes the upper surface of the microchip 1 when inserted. FIG. 6B is a side view of the microchip 1.

  The detection unit window 111a and the detection unit flow path 111b in FIG. 6A are provided for optically detecting the reaction between the specimen and the reagent, and are configured of a transparent member such as glass or resin. . Reference numerals 110a, 110b, 110c, 110d, and 110e denote driving liquid injection units that communicate with the internal fine flow paths. The driving liquid injection units 110 inject driving liquids to drive internal reagents and the like. Reference numeral 213 denotes a sample injection unit for injecting the sample into the microchip 1.

  As shown in FIG. 6B, the microchip 1 includes a groove forming substrate 108 and a covering substrate 109 that covers the groove forming substrate 108. Next, materials used for the groove forming substrate 108 and the covering substrate 109 constituting the microchip 1 will be described.

  The microchip 1 is desired to be excellent in processability, non-water absorption, chemical resistance, weather resistance, cost and the like. In consideration of the structure, application, detection method, etc. of the microchip 1, The material of chip 1 is selected. Various known materials can be used as the material, and usually the substrate and the flow path element are formed by appropriately combining one or more materials in accordance with individual material characteristics.

  In particular, it is desirable that a chip intended for a large number of measurement specimens, particularly clinical specimens at risk of contamination and infection, be of a disposable type. Therefore, a plastic resin that can be mass-produced, is lightweight, is strong against impact, and can be easily disposed of by incineration, for example, polystyrene that is excellent in transparency, mechanical properties, and moldability and is easy to be finely processed is preferable. For example, when it is necessary to heat the chip to near 100 ° C. in analysis, it is preferable to use a resin having excellent heat resistance (for example, polycarbonate). In addition, when protein adsorption becomes a problem, it is preferable to use polypropylene. Resin and glass have low thermal conductivity, and by using these materials in the locally heated region of the microchip, heat conduction in the surface direction is suppressed, and only the heated region is selectively heated. Can do.

  In the case where the detection unit 111 optically detects a color reaction product or a fluorescent substance, at least the substrate of this part uses a light-transmitting material (for example, alkali glass, quartz glass, transparent plastics). It is necessary to allow light to pass through. In the present embodiment, the groove forming substrate that forms the window 111a of the detection unit and at least the flow path 111b of the detection unit is made of a light-transmitting material so that light can pass through the detection unit 111. ing.

  In the microchip 1 according to the embodiment of the present invention, a minute groove-like flow path (fine flow path) and a functional component (flow path element) for performing inspection, sample processing, and the like correspond to applications. It is arranged in an appropriate manner. In the present embodiment, an example of a process for performing amplification and detection of a specific gene performed in the microchip 1 by using these microchannels and channel elements will be described with reference to FIG. The application of the present invention is not limited to the example of the microchip 1 described with reference to FIG. 6C, and can be applied to the microchip 1 for various uses.

  FIG. 6C is an explanatory diagram for explaining the functions of the fine flow paths and flow path elements inside the microchip 1.

  The microchannel is provided with, for example, a sample storage unit 221 for storing a sample liquid, a reagent storage unit 220 for storing reagents, and the like, so that the reagent storage unit 220 can be quickly examined regardless of location and time. Necessary reagents, washing solution, denaturing treatment solution and the like are stored in advance. In FIG. 6C, the reagent storage unit 220, the sample storage unit 221 and the flow path element are represented by squares, and the fine flow path therebetween is represented by a solid line and an arrow.

  The microchip 1 includes a groove forming substrate 108 in which a fine flow path is formed and a covering substrate 109 that covers the groove-shaped flow path. The fine channel is formed on the order of micrometers, for example, the width is several μm to several hundred μm, preferably 10 to 200 μm, and the depth is about 25 to 500 μm, preferably 25 to 250 μm.

  At least in the groove forming substrate 108 of the microchip 1, the fine flow path is formed. The coated substrate 109 needs to cover at least the fine flow path of the groove forming substrate in close contact, and may cover the entire surface of the groove forming substrate. Note that the microchannel 1 is provided with a part for controlling liquid feeding, such as a liquid feeding control unit (not shown), a backflow prevention unit (a check valve, an active valve, etc.), and the like. In this case, liquid feeding is performed according to a predetermined procedure.

  The sample injection unit 213 is an injection unit for injecting the sample into the microchip 1, and the driving liquid injection unit 110 is an injection unit for injecting the driving liquid into the microchip 1. Prior to performing the test using the microchip 1, the person in charge of the test injects the sample from the sample injection unit 213 using a syringe or the like. As shown in FIG. 6C, the sample injected from the sample injection unit 213 is stored in the sample storage unit 221 through the communicating fine channel.

  Next, when the driving liquid is injected from the driving liquid injection unit 110 a, the driving liquid pushes out the sample stored in the sample storage unit 221 through the communicating fine flow path, and sends the sample to the amplification unit 222.

  On the other hand, the driving liquid injected from the driving liquid injection section 110b pushes out the reagent a stored in the reagent storage section 220a through the communicating fine channel. The reagent a pushed out from the reagent storage unit 220a is sent to the amplification unit 222 by the driving liquid. Depending on the reaction conditions at this time, it is necessary to set the amplification unit 222 to a predetermined temperature, and as described later, the reaction is performed at a predetermined temperature by heating or absorbing heat inside the housing 82.

  After a predetermined reaction time, a solution containing the sample after reaction sent out from the amplification unit 222 by the driving liquid is injected into the detection unit 111. The injected solution reacts with the reactants carried on the flow path wall of the detection unit 111 and is immobilized on the flow path wall.

  Next, when the driving liquid is injected from the driving liquid injection unit 110c, the driving liquid pushes the reagent b stored in the reagent storage unit 220b through the communicating fine flow path, and injects the reagent b from the fine flow path into the detection unit 111. .

  Similarly, when the driving liquid is injected from the driving liquid injection section 110d, the driving liquid pushes out the reagent stored in the reagent storage section 220c through the communicating fine flow path, and injects it into the detection section 111 from the fine flow path.

  Finally, the driving liquid is injected from the driving liquid injection unit 110e, the cleaning liquid is pushed out from the cleaning liquid storage unit 223, and is injected into the detection unit 111. The unreacted solution 41 remaining in the detection unit 111 is washed with the washing liquid.

  After washing, the detected substance such as the amplified gene is detected by optically measuring the concentration of the reactant adsorbed on the flow path wall of the detection unit 111. Thus, a predetermined process is performed inside the microchip 1 by sequentially injecting the driving liquid from the driving liquid injection unit 110.

  FIG. 7 is a cross-sectional view illustrating an example of an internal configuration of the reaction detection device 80 according to the embodiment. The reaction detection device 80 includes a temperature adjustment unit 152, a light detection unit 150, an intermediate flow path unit 180, a micro pump unit 5, packings 90a and 90b, a driving liquid tank 91, and the like. Hereinafter, the same reference numerals are given to the same components as those described so far, and description thereof will be omitted.

  FIG. 7 shows a state where the upper surface of the microchip 1 is in close contact with the temperature adjustment unit 152 and the micropump unit 5. The microchip 1 is driven by a driving member (not shown) and can move in the vertical direction on the paper.

  In the initial state, the microchip 1 can be inserted / removed in the horizontal direction of FIG. 7, and the person inspecting inserts the microchip 1 from the insertion port 83 until it comes into contact with a regulating member (not shown). When the microchip 1 is inserted to a predetermined position, the chip detection unit 95 using a photo interrupter or the like detects the microchip 1 and is turned on.

  The temperature adjustment unit 152 is a unit that incorporates a Peltier element, a power supply device, a temperature control device, and the like and adjusts the lower surface of the microchip 1 to a predetermined temperature by generating heat or absorbing heat.

  When a control unit (not shown) receives a signal that the chip detection unit 95 is turned on, the microchip 1 is lowered by the driving member, and the lower surface of the microchip 1 is intermediately flowed through the temperature control unit 152 and the packing 92. Press against the road portion 180 to bring it into close contact.

  The driving liquid injection part 110 of the microchip 1 is provided at a position that communicates with a corresponding opening 185 provided in the intermediate flow path part 180 when the microchip 1 and the packing 92 are brought into close contact with each other. The intermediate flow path portion 180 includes a transparent first substrate 184 provided with a groove of the intermediate flow path 182 and a transparent second substrate 183 that covers the first substrate 184, and openings 185 are formed at both ends of the intermediate flow path 182. And an opening 186. The opening 186 communicates with the input / output port 146 of the micro pump unit 5 through the packing 90b.

  A driving liquid tank 91 is connected to the suction side of the micropump unit 5 via a packing 90a, and the driving liquid filled in the driving liquid tank 91 is sucked via the packing 90a. On the other hand, the input / output port 146 provided on the discharge-side end face of the micropump unit 5 communicates with the driving liquid injection unit 110 of the microchip 1 through the intermediate flow path 182, and thus is sent out from the micropump unit 5. The driving liquid thus injected is injected from the driving liquid injection part 110 of the microchip 1 into the flow path 250 formed in the microchip 1. In this way, the driving liquid is injected from the micropump unit 5 into the driving liquid injection unit 110.

  The liquid temperature adjustment unit 195 includes a Peltier element, a power supply device, a temperature control device, and the like, and is a unit that adjusts the driving liquid tank 91 to a predetermined temperature by generating heat or absorbing heat.

  In the example of the micropump unit 5 shown in FIG. 2, eight micropumps MP are provided, but it is not necessary to use all the micropumps MP. In the case of the microchip 1 illustrated in FIG. 6, the driving liquid injection unit 110 may be disposed so that the five micropumps MP communicate with each other.

  In the detection unit 111 of the microchip 1, the specimen and the reagent stored in the microchip 1 react to cause, for example, coloration, light emission, fluorescence, turbidity, and the like. In the present embodiment, as described with reference to FIG. 6, the reaction result of the reagent occurring in the detection unit 111 is optically detected. The light detection unit 150 includes a second light emitting unit 150a and a second light receiving unit 150b, and is arranged so as to be able to detect light transmitted through the detection unit 111 of the microchip 1.

  FIG. 8 is a circuit block diagram of the reaction detection device 80 in the embodiment of the present invention.

  The control unit 99 includes a CPU 98 (central processing unit), a RAM 97 (Random Access Memory), a ROM 96 (Read Only Memory), and the like, and reads a program stored in the ROM 96 as a nonvolatile storage unit to the RAM 97. Each part of the reaction detector 80 is centrally controlled according to the program.

  Hereinafter, functional blocks having the same functions as those described so far are denoted by the same reference numerals, and description thereof is omitted.

  The CPU 98 performs inspections in a predetermined sequence and stores the inspection results in the RAM 97. The inspection result can be stored in the memory card 501 by the operation of the operation unit 87 or printed by the printer 503. The CPU 98 has a pump drive control unit 412.

  The ROM 96 includes a pump performance table 302 in which performance data indicating the relationship between the flow rate Q, the pressure P, and the waveform parameters of the drive voltage E is provided for each micropump MP. The parameter of the waveform of the drive voltage E is either the rise time T1 or the fall time T3 described with reference to FIG.

  The pump drive unit 500 is a drive unit of the present invention that drives the piezoelectric element 112 of each micropump MP. The pump drive control unit 412 controls the pump drive unit 500 so as to inject or suck the drive liquid based on the program.

  Specifically, the pump drive control unit 412 drives the waveform timing (rise time T1 or fall time T3) at which a predetermined flow rate Q or pressure P is obtained based on the pump performance table 302 stored in the ROM 96. Command to unit 500. The pump drive unit 500 receives a command from the pump drive control unit 412 and generates a drive voltage having a waveform as shown in FIG. 3 to drive the micropump MP. Note that the timing of the waveform other than the timing of the waveform that received the command and the maximum voltage e1 are preset in the pump drive unit 500.

  A command from the pump drive control unit 412 is input to the pump drive unit 500 as a control voltage by a D / A converter provided in the control unit 99, for example. The pump driving unit 500 integrates the input control voltage to generate the driving voltage described with reference to FIG.

  The pump drive control unit 412 is control means of the present invention, the ROM 96 is storage means of the present invention, and the pump performance table 302 is performance data of the present invention.

  The chip detector 95 transmits a detection signal to the CPU 98 when the microchip 1 comes into contact with the regulating member. When the CPU 98 receives the detection signal, it instructs the mechanism driving unit 32 to lower or raise the microchip 1 according to a predetermined procedure.

  The CPU 98 performs inspections in a predetermined sequence and stores the inspection results in the RAM 97. The inspection result can be stored in the memory card 501 by the operation of the operation unit 87 or printed by the printer 503.

  FIG. 9 is a flowchart for explaining the inspection procedure by the reaction detection device 80 in the embodiment of the present invention.

  It is assumed that the CPU 98 controls the mechanism driving unit 32 to lower the microchip 1 inserted from the insertion port 83 until the microchip 1 comes into close contact with the packing 92 and the temperature adjustment unit 152 with an appropriate pressure. Further, it is assumed that the temperature adjustment unit 152 is energized when the reaction detector 80 is turned on and has a predetermined temperature.

  S101: This is a step of referring to the pump performance table 302.

  The pump drive control unit 412 obtains parameters for driving at a predetermined flow rate Q or pressure P from the performance data of a predetermined micropump MP stored in the pump performance table 302. The parameter is either a rise time T1 or a fall time T3.

  S102: This is a step for setting parameters.

  The pump drive control unit 412 sets predetermined parameters in the pump drive unit 500. The parameter is either a rise time T1 or a fall time T3.

  S103: This is a step of driving the micropump MP.

  The pump drive control unit 412 instructs the pump drive unit 500 to drive a predetermined micropump MP according to a predetermined sequence parameter, and sequentially injects the drive liquid into the drive liquid injection unit 110 of the microchip 1. The injected driving liquid sends a sample and a reagent in the flow path of the microchip 1 to the detection unit 111 in a predetermined sequence and reacts them.

  S104: This is a step of detecting the reaction result of the detection unit 111.

  After a predetermined reaction time has elapsed, the CPU 98 illuminates the detection unit 111 of the microchip 1 by causing the light emission unit 150a to emit light, and the CPU 98 incorporates an input signal from the light reception unit 150b that has received the transmitted light transmitted through the detection unit 111. A / D converter converts the digital value to a digital value to obtain a photometric value.

  S105: This is a step of displaying the reaction result.

  The CPU 98 calculates from the result of photometry performed by the light detection unit 150 and displays the reaction result on the display unit 84.

  This is the end of the inspection procedure.

  In the present embodiment, the example in which the pump drive control unit 412 sets the rise time T1 or the fall time T3 as parameters has been described, but there is no particular limitation, and the waveforms of the flow rate Q, the pressure P, and the drive voltage E are not limited. These parameters may be the maximum voltage e1, the frequency, the duty ratio of the drive voltage waveform, or the like.

  As described above, according to the present invention, it is possible to provide a reaction detection device that corrects the characteristic variation of the micropump with a simple method and sends the driving liquid to the microchip at a predetermined flow rate or pressure.

It is an external view of the reaction detection apparatus 80 in embodiment of this invention. It is explanatory drawing about an example of the micropump unit 5 concerning embodiment of this invention. 3 is an explanatory diagram showing a relationship between a drive voltage E supplied to a piezoelectric element 112 and a flow rate Q. FIG. 4 is an explanatory diagram showing a relationship between a rise time T1 and a fall time T2 of a drive voltage waveform supplied to a piezoelectric element 112, a flow rate Q, and a pressure P. FIG. 4 is an explanatory diagram showing a relationship between a maximum voltage e1 supplied to a piezoelectric element 112, a flow rate Q, and a pressure P. FIG. It is explanatory drawing about an example of the microchip 1 concerning embodiment of this invention. 4 is a cross-sectional view showing an example of an internal configuration of a reaction detection device 80. FIG. It is a circuit block diagram of the reaction detection apparatus 80 in the embodiment of the present invention. 4 is a flowchart for explaining a procedure of an inspection of a reaction detection device 80.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microchip 4 Drive liquid 5 Micro pump unit 80 Reaction detection apparatus 83 Insertion port 84 Display part 90 Packing 91 Drive liquid tank 110 Drive liquid injection | pouring part 111 Detection part 150 Photodetection part 190 Drive liquid detection means 191 1st light-receiving part 193 1st 1 light emission unit 195 liquid temperature adjustment unit 213 sample injection unit 302 pump performance table 412 pump drive control unit 500 pump drive unit MP micro pump

Claims (6)

A pump for injecting fluid into the microchip;
Storage means for storing performance data of the pump;
Drive means for driving the pump;
Control means for controlling the drive means;
Have
The reaction detection apparatus according to claim 1, wherein the control unit controls the driving unit based on the performance data. The pump is
A first flow path in which the flow path resistance changes according to the differential pressure;
A second flow path in which the ratio of the change in flow path resistance to the change in differential pressure is smaller than the first flow path;
A pressurizing chamber connected to the first flow path and the second flow path;
A piezo actuator for changing the pressure inside the pressurizing chamber;
The reaction detection device according to claim 1, comprising: The said performance data are data which show the relationship between the rise time of the drive voltage waveform which the said drive means generate | occur | produces, and the flow volume or pressure of the said fluid which the pump discharges, The claim 1 or 2 characterized by the above-mentioned. Reaction detector. 4. The reaction detection apparatus according to claim 3, wherein the control unit controls the flow rate or the pressure by changing a rising time of the drive voltage waveform. The said performance data are data which show the relationship between the fall time of the drive voltage waveform which the said drive means generate | occur | produces, and the flow volume or pressure of the said fluid which the said pump discharges, The claim 1 or 2 characterized by the above-mentioned. Reaction detector. 6. The reaction detection apparatus according to claim 5, wherein the control unit controls the flow rate or the pressure by changing a fall time of the drive voltage waveform.

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