JP2012173181A - Trace substance detecting apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a trace substance detecting apparatus that allows operations from reaction between a trace substance and a marker substance to detection and quantification to be automated, and that can be integrally molded by using, for example, resin or the like.SOLUTION: A trace substance detecting apparatus comprises: a tube; a mixing and reaction unit for mixing a test substance containing a detection target substance, magnetic beads, a marker substance, and a buffer solution, and causing reaction and bonding of the detection target substance, the magnetic beads, and the marker substance to make a sample solution; a measuring unit, which includes 2 or more electrodes and into which the sample solution is introduced, for measuring the detection target substance to which the marker substance is bonded; a magnetic force controlling unit for adsorbing and retaining the detection target substance bonded with the magnetic beads by using magnetic force provided in the mixing and reaction unit and the measuring unit; suction and pressurizing means for sucking and pressurizing inside the tube and moving the sample solution inside the tube; a plurality of valves provided at suitable places in the tube; and a controlling device for controlling the magnetic force controlling unit, the suction and pressurizing means, and the plurality of valves. The tube and the measuring unit are integrally molded by using resin.

Description

  The present invention relates to a trace substance detection apparatus for detecting a trace substance such as DNA (deoxyribonucleic acid) as a target substance to be detected, and in particular, by measuring a labeled substance bound to the target substance to be detected. In what is configured to measure the presence or amount of a substance, devise so that the work from the binding of a magnetic bead and a labeled substance to the target substance to be detected to the detection of the target substance can be automated, for example, Further, the present invention relates to a device in which a flow path and a measurement unit are devised so as to be integrally formed of resin.

For example, when performing detection or quantification using a trace substance such as DNA as a detection target substance, complicated operations such as isolation and purification of the detection target substance and binding of a labeling substance to the detection target substance are required.
That is, in the case of DNA, for example, as disclosed in Patent Document 1, an immunoreactive agent that is a labeling substance is bound to DNA that is a substance to be detected. Next, the DNA to which the immunoreactive agent is bound is captured by a support to which the DNA and the complementary DNA are bound, and a fluorescent substance that specifically binds to the immunoreactive agent by an immune reaction is targeted. To join. Then, by measuring the fluorescence, DNA as a detection target substance is detected and quantified.

In the case of a protein, for example, as shown in Patent Document 2, a labeling substance is bound to a protein to be detected using an immune reaction, and the bound labeling substance is measured. Detects and quantifies target substances to be detected.
Incidentally, such work for detection and quantification of the target substance to be detected is performed manually.

  Patent Documents 3 and 4 disclose apparatuses for detecting and measuring DNA.

Japanese Patent Laid-Open No. 10-504962 JP-A-10-276786 JP-A-5-199898 JP-A-2-23898

The conventional configuration has the following problems.
First, as described above, there is no device that automates all operations from the binding of the target substance to be detected and the labeling substance to the detection and quantification of the target substance to be detected. All of this work was done manually. Therefore, it takes a long time and a lot of labor for detection, and there is a problem that skill of the operator is required for accurate detection.

  The present invention has been made on the basis of such points, and the object thereof is to automatically perform operations from reaction between a trace substance such as DNA and a labeled substance to detection and quantification, and For example, an object of the present invention is to provide a trace substance detection device in which a flow path, a measurement unit, and the like can be integrally formed of resin.

In order to achieve the above object, a trace substance detection device according to claim 1 of the present invention comprises a tube, a sample provided in the tube, containing a target substance to be detected, a magnetic bead, a labeling substance, and a buffer solution. A mixing / reaction unit that reacts and binds the target substance, the magnetic beads, and the labeling substance to form a sample solution; and at least two or more electrodes provided in the tube so that the sample solution is introduced and the labeling is performed. A measuring unit that measures the target substance to which the substance is bound, a magnetic force control unit that is provided in the mixing / reaction unit and the measuring unit and that adsorbs and holds the target substance that is bound to the magnetic beads by magnetic force; An aspirating / pressurizing means connected to the tube to move the sample solution in the tube by aspirating / pressurizing the tube; and the tube A plurality of valves provided at appropriate positions; the magnetic force control unit; the suction / pressurization means; and a control device for controlling the plurality of valves; and the tube and the measurement unit are made of resin. It is characterized by that.
Further, the trace substance detection apparatus according to claim 2 is the trace substance detection apparatus according to claim 2, wherein the resin is mainly composed of flexible vinyl chloride, polypropylene (PP), polyethylene (PE), or silicon. It is characterized by being.
According to a third aspect of the present invention, there is provided the trace substance detection apparatus according to the second aspect, wherein the flow path is formed by a blow molding method.
According to a fourth aspect of the present invention, there is provided the trace substance detection apparatus according to the second aspect, wherein the flow path is formed by bonding a sheet-like resin or the like.
According to a fifth aspect of the present invention, there is provided the trace substance detection apparatus according to any one of the first to fourth aspects, wherein the substance to be detected is DNA.

As described above, according to the trace substance detection apparatus according to claim 1 of the present invention, the tube, the specimen containing the target substance to be detected, the magnetic beads, the labeling substance, and the buffer solution provided in the tube are mixed. A mixing / reaction unit that reacts and binds the target substance, the magnetic beads, and the labeling substance to form a sample solution; and at least two or more electrodes provided in the tube so that the sample solution is introduced and the labeling is performed. A measuring unit that measures the target substance to which the substance is bound, a magnetic force control unit that is provided in the mixing / reaction unit and the measuring unit and that adsorbs and holds the target substance that is bound to the magnetic beads by magnetic force; An aspirating / pressurizing means connected to the tube to move the sample solution in the tube by aspirating / pressurizing the tube; and the tube A plurality of valves provided at appropriate positions; the magnetic force control unit; the suction / pressurization means; and a control device for controlling the plurality of valves; and the tube and the measurement unit are made of resin. Therefore, a series of operations from the binding of magnetic beads and labeling substances to the target substance to be detected, purification of the target substance to be detected, and detection of the target substance to be detected can be easily automated. The labor required can be reduced and the time required for the work can be shortened. In addition, since the tube and the measurement unit are made of resin, a simple and low-cost apparatus can be provided.
Further, the trace substance detection apparatus according to claim 2 is the trace substance detection apparatus according to claim 2, wherein the resin is mainly composed of flexible vinyl chloride, polypropylene (PP), polyethylene (PE), or silicon. Since there exists, the said effect can be made more reliable.
According to a third aspect of the present invention, the trace substance detection apparatus according to the second aspect is the trace substance detection apparatus according to the second aspect, wherein the flow path is formed by a blow molding method.
According to a fourth aspect of the present invention, there is provided the trace substance detection apparatus according to the second aspect, wherein the flow path is formed by laminating a sheet-like resin or the like. It can be.
A trace substance detection apparatus according to claim 5 is the trace substance detection apparatus according to any one of claims 1 to 4, wherein the substance to be detected is DNA. Also, a simple and low-cost device can be provided.

It is a figure which shows one Embodiment of this invention, and is a systematic diagram which shows the trace amount substance detection apparatus by this Embodiment. It is a figure which shows one Embodiment of this invention, and is a schematic diagram showing a mode that the magnetic bead and the oxidoreductase were couple | bonded with DNA which is a to-be-detected target substance, in order to detect with the trace amount substance detection apparatus by this Embodiment. is there. It is a figure which shows one Embodiment of this invention, and is a circuit diagram which shows the structure of the measurement part and measurement circuit of the trace amount substance detection apparatus by this Embodiment. It is a figure which shows one Embodiment of this invention, and is a schematic diagram for demonstrating the mode of reaction in a measurement chamber. It is a figure which shows one embodiment of this invention, and is a top view of the trace substance detection apparatus which shows the state which integrally formed the tube and the measurement part with resin. It is a figure which shows one embodiment of this invention, and is VI-VI sectional drawing of FIG. It is a figure which shows one embodiment of this invention, and is sectional drawing which expands and shows the VII part of FIG. It is a figure which shows one embodiment of this invention, and is sectional drawing which shows the structure of a fluid connector.

  Hereinafter, an embodiment of the present invention will be described with reference to FIGS. FIG. 1 is a system diagram schematically showing the configuration of a trace substance detection apparatus according to this embodiment. First, there is a tube 1. A sample injection section 3 is provided at one end side (left end in FIG. 1) of the tube 1, and a sample injector 5 is detachably inserted into the sample injection section 3. The sample injector 5 is filled with a sample 7 containing DNA as a substance to be detected. Further, a buffer liquid injection section 9 is installed in the tube 1 in the vicinity of the specimen injection section 3, and the buffer liquid injection section 9 is filled with a buffer liquid 11. The buffer solution 11 is a solution in which a redox substance and an electron mediator are dissolved in a buffer solution. As the buffer solution, for example, an aqueous solution of a mixture of dipotassium hydrogen phosphate and potassium dihydrogen phosphate is used. The electron mediator is a substance for moving electrons.

  The buffer solution injection part 9 is connected to the tube 1 via a branch tube 13, and a first pushing valve 15 is attached to the branch tube 13. The first pushing valve 15 presses the branch tube 13 to prevent liquid from going back and forth, thereby controlling the inflow of the buffer liquid 11 from the buffer liquid injection part 9 into the tube 1. is doing.

  A first reagent injection part 17 and a second reagent injection part 19 are connected to the tube 1 via branch tubes 21 and 23, respectively. The first reagent injection part 17 is filled with a first reagent 25 (a reagent containing magnetic beads). The second reagent injection part 19 is filled with a second reagent 27 (a reagent containing an oxidoreductase as a labeling substance). A second pushing valve 29 is attached to the branch tube 21 and a third pushing valve 31 is also attached to the branch tube 23. Similar to the first pressing valve 15, the second pressing valve 29 and the third pressing valve 31 also flow in the first reagent 25 from the first reagent injection part 17 into the tube 1, and The flow of the second reagent 27 from the second reagent injection part 19 into the tube 1 is controlled.

  A portion where one end side of the tube 1 is connected to the buffer solution injection unit 9, the first reagent injection unit 17, and the second reagent injection unit 19 is a mixing unit 33. The tube 1 is provided with a reaction part 35 adjacent to the mixing part 33. A fourth pushing valve 37 is provided at the boundary between the reaction unit 35 and the mixing unit 33. The mixing portion 33 and the reaction portion 35 are portions corresponding to the mixing / reaction portion in claim 1.

  The reaction unit 35 is provided with a temperature control heater 39 as temperature control means and an ultrasonic vibration device 41 as stirring means. The temperature control heater 39 has a temperature suitable for a reaction in which the DNA contained in the specimen 7, the magnetic beads in the first reagent 25, and the oxidoreductase in the second reagent are bound in the reaction unit 35. It is for controlling. The ultrasonic vibration device 41 is for stirring the inside of the reaction part 35 so as to efficiently combine the DNA with the magnetic beads and the oxidoreductase. A first magnetic force control unit 43 is provided on the other end side (right side in FIG. 1) of the reaction unit 35 with respect to the temperature control heater 39 and the ultrasonic vibration device 41. The first magnetic force control unit 43 adsorbs and holds DNA bound to the magnetic beads in the reaction unit 35.

On the other end side of the tube 1, a measurement chamber 45 as a measurement unit is provided. The measurement chamber 45 is provided with an ion exchange membrane 47, and a pair of chambers 49 and 51 are defined and formed by the ion exchange membrane 47. In these chambers 49 and 51, electrodes 53 and 55 are installed as measurement electrodes. In the case of the present embodiment, measurement is performed while controlling the voltage between the two electrodes 53 and 55 to be substantially “0”. The measurement chamber 45 can be vibrated by an ultrasonic vibration device 41 installed in the reaction unit 35 or by an ultrasonic vibration device provided separately from the ultrasonic vibration device 41.
Although the ion exchange membrane 47 is used in the present embodiment, an ion permeable membrane may be used instead.

  A branch tube 57 is connected between the first magnetic force control unit 43 and the measurement chamber 45 in the reaction unit 35. A branch tube 59 is connected to the chamber 49 on the reaction part 35 side of the measurement chamber 45. The branch tube 57 is provided with a fifth pushing valve 61. A sixth valve 63 is provided at the boundary between the measurement chamber 45 and the reaction unit 35. The branch tube 59 is provided with a seventh pushing valve 65. The branch tube 57 and the branch tube 59 are assembled, and a pump 67 as suction / pressurization means is connected thereto. The measurement chamber 45 is provided with a second magnetic force control unit 69. The second magnetic force control unit 69 adsorbs and holds DNA bound to the magnetic beads in the measurement chamber 45.

  In addition, a control device 71 is installed, and a measurement circuit 73 is provided in the control device 71. Various devices already described, the first pushing valve 15, the second pushing valve 29, the third pushing valve 31, the fourth pushing valve 37, the fifth pushing valve 61, the sixth pushing valve 63, the seventh pushing valve. The pushing valve 65, the temperature control heater 39, the ultrasonic vibration device 41, the first magnetic control unit 43, the pump 67, and the second magnetic control unit 69 are all controlled by the control device 71. Further, the current measurement or the like via the electrodes 53 and 55 is controlled by the measurement circuit 73 of the control device 71.

  The measurement circuit 73 is configured as shown in FIG. First, there is an operational amplifier 75, and an A / D converter 77 is connected to the operational amplifier 75. Output signals from the electrodes 53 and 55 are input to the operational amplifier 75. The signal amplified by the operational amplifier 75 is analog / digital converted by the A / D converter 77 and input to the microcomputer 79. The microcomputer 79 is connected with an I / O 81 and a memory 83. An input means 85 and a closing sensor 87 are connected to the I / O 81. Further, another line comes out from the electrode 53, and a resistor 76 is inserted there, and is branched and connected between the operational amplifier 75 and the A / D converter 77. Further, a ground wire 78 extends from the electrode 55.

  The operation will be described based on the above configuration. First, the first pushing valve 15, the fourth pushing valve 37, and the fifth pushing valve 61 are opened, and the pump 67 is driven. As a result, a negative pressure is generated in the tube 1, and the buffer solution 11 in the buffer solution injection part 9 is sucked and filled in the tube 1. In this state, the sample 7 is injected from the sample injector 5 through the sample injection unit 3.

  Next, the second pressing valve 29, the third pressing valve 31, the fourth pressing valve 37, and the fifth pressing valve 61 are opened, and the first reagent injection unit 17, A small amount of the first reagent 25 and the second reagent 27 are drawn from the two-reagent injection unit 19. At the same time, the first pushing valve 15 is opened and the buffer solution 11 is drawn from the buffer solution injection part 9. As a result, the sample 7, the buffer solution 11, the first reagent 25, and the second reagent 27 are mixed in the mixing unit 33 and led to the reaction unit 35.

Next, the fourth pushing valve 37 and the fifth pushing valve 61 are closed to cause the sample 7 to react with the first reagent 25 and the second reagent 27. At that time, temperature adjustment is performed by the temperature control heater 39 and ultrasonic vibration is applied by the ultrasonic vibration device 41. As a result, a temperature environment suitable for the reaction is provided, and a stirring / mixing action works. By the reaction of the sample 7 with the first reagent 25 and the second reagent 27, the magnetic beads are bound to one end of the DNA as the detection target substance, and the oxidoreductase is bound to the other end. This is shown in FIG. FIG. 2 is a diagram showing a state where a magnetic bead 91 is bound to one end of DNA 89 and an oxidoreductase 93 is bound to the other end.
The magnetic beads 91 and the oxidoreductase 93 are treated so as to specifically bind to the DNA 89.

  Next, the first magnetic force controller 43 is turned on to open the first pushing valve 15, the fourth pushing valve 37, and the fifth pushing valve 61, and the temperature is adjusted by the temperature control heater 39. In addition, while the ultrasonic vibration device 41 applies ultrasonic vibration, the buffer liquid 11 is kept flowing. As a result, only the DNA 89 bound to the magnetic beads 91 is adsorbed and held by the first magnetic force control unit 43, and the others are washed away. Therefore, the DNA 89 that is the detection target substance is purified.

Next, the first magnetic force control unit 43 is turned off, and the second magnetic force control unit 69 is turned on. Thereafter, the first pushing valve 15, the sixth pushing valve 63, and the seventh pushing valve 65 are opened and sucked by the negative pressure of the pump 67, so that they are attracted and held by the first magnetic force control unit 43. The DNA 89 bound to the magnetic beads 91 is guided into the measurement chamber 45 and is attracted and held by the second magnetic force control unit 69. Then, the sixth pushing valve 63 and the seventh pushing valve 65 are closed to perform measurement.

In the case of the present embodiment, detection / quantification of the detection target substance is performed by measuring the current between the electrode 53 and the electrode 55. As shown in FIG. 2, the oxidoreductase 93 is bound to the DNA 89 as a labeling substance. The oxidoreductase 93 oxidizes or reduces the redox substance contained in the buffer solution 11, and the electron mediator contained in the buffer solution 11 receives electrons by the redox reaction or electrons to the redox material. Is charged to “positive” or “negative”. Then, the “positive” or “negative” charged electron mediator moves to the electrode 53 or the electrode 55. This is measured by the measurement circuit 73 as a current, and the DNA 89 that is the detection target substance can be detected and quantified based on the current value.

  Here, with reference to FIG. 4, a chemical reaction in the measurement chamber 45 when an oxidase (for example, glucose oxidase) is used as the oxidoreductase 93 will be specifically described. An oxidase 95 bound to the DNA 89 is present in the chamber 49 above the measurement chamber 45 (upper in FIG. 4). Further, the substance to be oxidized 97 and the electron mediator 99 added to the buffer solution are also present in the measurement chamber 45. The oxidizable substance 97 is oxidized by the oxidase 95 and releases electrons 101 and cations 103. The electrons 101 are captured by the electron mediator 99, and as a result, the electron mediator 99 is negatively charged. The electron mediator 99 charged “negatively” moves to the electrode 53 side having a relatively “positive” potential. On the other hand, the cation 103 passes through the ion exchange membrane 47, is installed on the chamber 51 side, moves to the electrode 55 side having a relatively “negative” potential, and receives the electrons 101. As a result, a potential difference is generated between the chamber 49 and the chamber 51 across the ion exchange membrane, and a current flows between the electrode 53 and the electrode 55. The DNA 89 is detected and quantified by measuring this current.

Further, the present invention is not limited to the above example, and it is conceivable to use a reductase instead of the oxidase 95 as the oxidoreductase 93. In this case, a substance to be reduced is used instead of the substance to be oxidized 97, and electrons are transferred from the electrode 53 to the reductase through the electron mediator to cause a reduction reaction. For this reason, the electrode 53 that receives electrons from the outside serves as a “positive” pole, and the electrode 55 that emits electrons to the outside serves as a “negative” pole.
The measurement of the substance to be detected can also be performed by measuring the voltage between the electrodes 53 and 55.

  After the measurement, the first pressing valve 15 and the seventh pressing valve 65 are opened, and the measured sample 7 and the like are sucked and washed away by the negative pressure by the pump 67. As a result, the pump 67 itself is also cleaned.

In the case of the present embodiment, a part of the trace substance detection apparatus already described, specifically, the tube 1 portion, the branch tubes 13, 21, and 23, the branch tubes 57 and 59, A portion of the measurement chamber 45 as a measurement unit is integrally molded by bonding a resin film. The configuration is shown in FIG. As the resin, flexible vinyl chloride, polypropylene (PP), polyethylene (PE), or silicon is mainly used. A known liquid connector is used for connection with an external component.
In FIG. 5, the same parts as those shown in FIG.

  FIG. 6 is a cross-sectional view taken along line VI-VI in FIG. 5, and FIG. 7 is an enlarged view of the VII portion in FIG. As shown in FIGS. 5 to 7, the resin upper film 101 and the resin lower film 103 are bonded to each other, so that the tube 1, the branch tubes 13, 21 and 23, the branch tubes 57 and 59, and the measurement are performed. A measurement chamber 45 as a part is formed. That is, as shown in FIGS. 6 and 7, the resin upper film 101 and the resin lower film 103 are opposed to each other and compressed with a mold (not shown) in a state where air is supplied in a predetermined region between them ( If necessary, heat, for example). As a result, the tube 1, the branch tubes 13, 21, 23, the branch tubes 57, 59, and the measurement chamber 45 as a measurement unit are integrally molded.

That is, the tube 1 is molded with the flow path 1a, and the branch tubes 13, 21, 23 and the branch tubes 57, 59 are also provided with the flow path. Molded. The measurement chamber 45 is also molded in a state of being sandwiched between the resin upper film 101 and the resin lower film 103, and electrodes 53 and 55 are provided in the molded space 45a. A coating portion 105 is provided on the surface of the electrode 55.

  The liquid connector has a structure as shown in FIG. FIG. 8 is a diagram showing a configuration of a connection portion between the branch tube 13 and a buffer liquid supply portion side (not shown). First, the said branch tube 13 is formed in the state pinched | interposed by the said resin upper film 101 and the resin lower film 103, and the flow path 13a is formed in the inside. The distal end portion of the branch tube 13 is expanded, and a liquid connector 109 is detachably inserted therein. A buffer liquid flow path 111 is formed in the liquid connector 109. As the liquid connector 109, for example, use of “clean click connector” manufactured by Showa Marutsutsu Co., Ltd. is assumed. In addition, such a liquid connector is described in, for example, Patent Document 5 and the like.

JP-T-2002-517292

  FIG. 8 shows only the branch tube 13, but the other connecting parts have the same configuration.

As described above, according to the present embodiment, the following effects can be obtained.
First, according to the trace substance detection apparatus according to the present embodiment, a series of steps from binding of magnetic beads 91 to a target substance to be detected DNA 89 and oxidoreductase 93 as a labeling substance, purification of DNA 89, and detection / quantification of DNA 89. This process can be automatically performed with an apparatus having a relatively simple configuration, so that labor for detecting trace substances can be greatly reduced and the time required for the work can be greatly shortened. This was purified from the first to seventh push-type valves 15, 29, 31, 37, 61, 63, 65, the mixing unit 33 for mixing the sample solution, the reaction unit 35 for reacting the sample solution, and the sample solution. A measurement chamber 45 or the like for measuring the target substance to be detected is continuously provided in the tube 1, a pump 67 for generating a negative pressure for moving the sample solution, and a target substance to be detected coupled to the magnetic beads 91. First and second magnetic force control units 43 and 69 for adsorption and holding, a temperature control heater 39 for controlling the temperature of the reaction unit, and an ultrasonic vibration device 41 for stirring the reaction unit are provided. The pressing type valves 15, 29, 31, 37, 61, 63, 65, the pump 67, the first and second magnetic force control units 43, 69, the temperature control heater 39, and the ultrasonic vibration device 41 are controlled by the control device 71. Configure to It is told.
In addition, since the above-described series of operations can be performed automatically, even a non-expert can accurately and quickly detect and quantify trace substances.
In addition, since the magnetic beads 91 and the DNA 89 to be detected are bonded, the movement of the DNA 89 in the tube 1 using the first and second magnetic force control units 43 and 69 and the pump 67 is controlled. And purification becomes easy.
In addition, since the temperature control heater 39 and the ultrasonic vibration device 41 are installed in the reaction unit 35, the binding of the magnetic beads 91 and the oxidoreductase 93 to the DNA 89 that is the detection target substance is efficiently performed. Can be done well.
In addition, since the first to seventh push-type valves 15, 29, 31, 37, 61, 63, 65 are used, trace substance detection that can be automatically controlled without requiring a complicated mechanical configuration. An apparatus can be realized.
In addition, since the target substance to be detected is detected and quantified by measuring the current and voltage, the measurement can be performed with an inexpensive and simple apparatus. In particular, since the configuration does not use a radioisotope or the like, it is possible to perform measurement safely without worrying about exposure.
In the case of the present embodiment, the portion of the tube 1, the portions of the branch tubes 13, 21, and 23, the portions of the branch tubes 57 and 59, and the portion of the measurement chamber 45 as the measurement portion are replaced with the upper resin film 101 And the resin lower film 103 are compressed and bonded together with a mold in a state where air is supplied between them, so that they are integrally molded. A substance detection device can be obtained.

The present invention is not limited to the one embodiment.
For example, as a labeling substance, it is conceivable to use a fluorescent protein, a radioisotope, or the like in addition to the oxidoreductase.
Further, the measurement method is not limited to the measurement of current and voltage, and the case of measuring fluorescence and radiation can be considered.
Further, the target substance to be detected is not limited to DNA, and various kinds of substances such as nucleic acids and proteins can be considered.
In addition to the pushing type, for example, it is conceivable to use a valve such as a gate valve.
In addition, it is conceivable that various types of buffer solutions used for the buffer solution are used depending on the type of the detection target substance and the labeling substance.
Further, in the case of the above-described embodiment, the measurement chamber has been described as an example of a type having both a room in which a reaction is performed and a room in which a reaction is not performed. However, the measurement chamber is not limited thereto. is not. For example, a chamber in which a reaction is performed and an electrode is provided, and a chamber having the characteristics of an ion exchange membrane or an ion permeable membrane that is directly or indirectly covered with a resin or a membrane and that has an electrode. It may be a measurement chamber having an arrangement.
The direct means that the resin of the ion exchange membrane or the ion permeable membrane is directly applied to the electrode, and the indirect means that the water-containing resin or the like is between the electrode and the resin of the ion exchange membrane or the ion permeable membrane. This means a configuration that intervenes.
In the case of the above embodiment, the case where the electron mediator is placed in the buffer liquid has been described as an example. For example, a third reagent injection part is provided next to the second reagent injection part. An electronic mediator may be placed therein, and the pushing valve may be opened to inject as appropriate.
In the above-described embodiment, an example in which a resinous film is integrally molded by compressing and bonding with a mold in a state where air is supplied to the inside is described. Blow molding using a blow molding machine You may make it integrally mold by the method.
In addition, the illustrated configuration is merely an example.

  For example, the present invention relates to a trace substance detection apparatus for detecting trace substances such as DNA (deoxyribonucleic acid) as a substance to be detected, and in particular, to measure a labeled substance bound to the substance to be detected. In addition to measuring the presence / absence and amount of trace substances, the work from the binding of magnetic beads and labeled substances to the target substance to the detection of the target substance can be automated. As a whole, for example, it is suitable for a detection device for DNA (deoxyribonucleic acid), for example, which is devised so that it can be integrally molded with a resin or the like.

DESCRIPTION OF SYMBOLS 1 Tube 7 Specimen 11 Buffer solution 15 1st pushing valve 25 1st reagent 27 2nd reagent 29 2nd pushing valve 31 3rd pushing valve 33 Mixing part 35 Reaction part 37 4th pushing valve 39 Heater for temperature control DESCRIPTION OF SYMBOLS 41 Ultrasonic vibration device 43 1st magnetic force control part 45 Measurement part 47 Ion exchange membrane 61 5th pushing valve 63 6th pushing valve 65 7th pushing valve 67 Pump 69 2nd magnetic force control part 71 Controller 93 Redox Enzyme 95 Oxidase 97 Oxidized substance 99 Electron mediator 101 Resin upper film 103 Resin lower film

Claims (5)

Tubes,
A sample provided in the tube containing a target substance to be detected, a magnetic bead, a labeling substance, and a buffer solution are mixed, and the target substance to be detected, the magnetic bead and the labeling substance are reacted and combined to form a sample solution.・ Reaction part,
A measuring unit that is provided in the tube and includes at least two or more electrodes, measures the target substance to which the sample solution is introduced and the labeling substance is bound;
A magnetic force control unit that is provided in the mixing / reaction unit and the measurement unit and that adsorbs and holds a target substance to be detected that is bound to the magnetic beads by magnetic force;
Suction / pressurization means connected to the tube and moving the sample solution in the tube by aspirating / pressurizing the tube;
A plurality of valves provided at appropriate positions of the tube;
A controller for controlling the magnetic force control unit, the suction / pressurization means, and the plurality of valves;
A trace substance detection apparatus characterized in that the tube and the measurement part are integrally formed of resin. The trace substance detection device according to claim 2,
A trace substance detection device, wherein the resin is mainly composed of flexible vinyl chloride, polypropylene (PP), polyethylene (PE), or silicon. The trace substance detection device according to claim 2,
A trace substance detection device characterized in that a flow path is formed by a blow molding method. The trace substance detection device according to claim 2,
A trace substance detection device characterized in that a flow path is formed by bonding a sheet-like resin or the like. In the trace substance detection apparatus according to any one of claims 1 to 4,
The trace substance detection apparatus, wherein the substance to be detected is DNA.

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