JP2009019962A - Fluorescence detection unit, reaction detection device, and microchip inspection system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a small-sized fluorescence detection unit, a reaction detection device and a microchip inspection system capable of receiving only the fluorescence, using a simple constitution. <P>SOLUTION: This fluorescence detection unit has a light-emitting part for irradiating an exciting light to a fluorescent material, an exciting light cut filter for blocking the exciting light and allowing transmission of fluorescence emitted from the fluorescent material, and a light-receiving part for receiving the fluorescence transmitted through the exciting light cut filter and converting it into an electrical signal. The light-emitting part is constituted so that the exciting light is irradiated from an angle, at which the exciting light regularly reflected by the fluorescent material does not enter the light-receiving part. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a fluorescence detection unit, a reaction detection device, and a microchip inspection system.

  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 conventional sample preparation, chemical analysis, chemical synthesis, etc. have been miniaturized. A system integrated on a chip 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 / diagnosis field, environmental measurement field, Its application is expected in the field of agricultural production. 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. It can be said that not only the amount of sample and the time required, but also the benefits of enabling analysis at any time and place are great.

In addition, the present applicant encloses a reagent or the like in the microchannel of the microchip, injects a liquid into the microchannel by a micropump, moves the reagent, and flows it to the reaction unit and then the detection unit, A reaction detection device capable of measuring a reaction result with a specimen such as blood has been proposed (for example, see Patent Document 2). In such a reaction detection device, excitation light is emitted from the light emission part of the fluorescence detection unit to the detection part of the microchip, and the very weak fluorescence emitted by the fluorescent substance contained in the reagent is detected by the light reception part of the fluorescence detection unit. Is configured to do.
JP 2004-28589 A JP 2006-149379 A

  An example of a conventional fluorescence detection unit is shown in FIG.

  Reference numeral 1 denotes a microchip, and the detection unit 19 measures the reaction result between the reagent and the sample. Excitation light emitted from the light emitting unit 160 enters the lens 158 via the slit 157, and the excitation light condensed by the lens 158 is reflected by the dichroic mirror 159 and irradiates the detection unit 19. The fluorescence generated by the detection unit 19 passes through the dichroic mirror 159 and enters the lens 155, and the light collected by the lens 155 enters the light receiving unit 161 via the excitation light cut filter 156.

  Thus, conventionally, excitation light and fluorescence have been optically coaxially arranged. For this reason, since the light transmitted through the dichroic mirror 159 contains a lot of excitation light, the excitation light is cut by the excitation light cut filter 156 so that only the fluorescence is incident on the light receiving unit 161.

  However, the difference between the excitation light for exciting the fluorescent material and the wavelength of the fluorescence is very small, from several nm to several tens of nm. Therefore, the excitation light cut filter 156 needs to have a steep cutoff characteristic in order to separate excitation light and fluorescence. Since such a filter is difficult to manufacture, it is large and expensive, and it is difficult to completely remove the excitation light incident on the light receiving unit 161.

  Further, the fluorescence detection unit is required to have a small optical system so that a plurality of detection units 19 of the microchip can be measured. However, since the dichroic mirror 159 is used, it is difficult to reduce the size.

  The present invention has been made in view of the above problems, and an object thereof is to provide a small fluorescence detection unit, a reaction detection device, and a microchip inspection system that can receive only fluorescence with a simple configuration. .

  The object of the present invention can be achieved by the following constitution.

1.
A light emitting unit for irradiating the fluorescent material with excitation light;
A light receiving unit that receives the fluorescence emitted by the fluorescent material and converts it into an electrical signal;
In a fluorescence detection unit having
The fluorescence detecting unit, wherein the light emitting unit is configured to irradiate the excitation light from an angle at which the excitation light regularly reflected by the fluorescent material does not enter the light receiving unit.

2.
Having the fluorescence detection unit according to 1;
A reaction detection apparatus characterized by irradiating a fluorescent substance with excitation light by the fluorescence detection unit and measuring an electrical signal obtained by converting the received fluorescence.

3.
A microchip having a detection unit capable of optically detecting a specimen reacted with a reagent containing a fluorescent substance;
The reaction detection device according to 2, and
A microchip inspection system comprising:

4).
The microchip has a plurality of the detection units,
The reaction detection device includes:
Driving means for driving the fluorescence detection unit to a predetermined position;
Position control means for controlling the driving means;
Have
The position control means controls the drive means so that the fluorescence detection unit sequentially moves to a position where one of the plurality of detection units can receive the excitation light and receive fluorescence of the fluorescent substance. 4. The microchip inspection system according to 3.

5).
5. The microchip inspection system according to 3 or 4, further comprising a fluorescent reflector that reflects the fluorescent light and enters the light receiving unit.

6).
The fluorescent reflector is
A first fluorescent reflector disposed in the vicinity of the periphery of the detection unit so that an end surface thereof is in contact with or substantially in contact with the surface of the microchip 1;
A second fluorescent reflector disposed in parallel to face the first fluorescent reflector at a position that does not block excitation light emitted from the light emitting unit;
6. The microchip inspection system according to 5, wherein

  According to the present invention, the light emitting unit emits the excitation light from an angle at which the excitation light specularly reflected by the fluorescent material does not enter the light receiving unit, so that only the fluorescence can be received with a simple configuration.

  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 of the reaction detection device 80 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 as not to contact the insertion port 83 when the microchip 1 is inserted. 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 reaction detector 80, the reaction in the microchip 1 is automatically inspected, and 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 microchip 1 according to the embodiment of the present invention will be described with reference to FIG.

  2A and 2B are external views of the microchip 1. FIG. In FIG. 2A, an arrow indicates an insertion direction in which the microchip 1 is inserted into a reaction detection device 80 described later, and FIG. 2A illustrates a surface that becomes the lower surface of the microchip 1 when inserted. FIG. 2B is a side view of the microchip 1.

  The window 111 in FIG. 2A is provided for optically detecting the reaction between the specimen and the reagent containing the fluorescent substance performed by the detection unit 19 inside the microchip 1, and is a transparent member such as glass or resin. It consists of 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 113 denotes a sample injection unit for injecting a sample into the microchip 1.

  As shown in FIG. 2B, the microchip 1 includes a groove forming substrate 108 and a covering substrate 109 that covers the groove forming substrate 108.

  The 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 present embodiment, since the detection unit 19 optically detects the fluorescent substance, at least the substrate of this part uses a light transmissive material (for example, alkali glass, quartz glass, transparent plastics), and transmits light. It is necessary to do so. In the present embodiment, the window 111 of the detection unit is made of a light transmissive material so that light can pass through the window 111.

  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. 2C, but can be applied to the microchip 1 for various uses.

  FIG. 2C is an explanatory diagram for explaining the functions of the fine flow path and flow path element inside the microchip 1.

  The fine channel is provided with, for example, a sample storage unit 121 that stores a sample liquid, a reagent storage unit 120 that stores reagents, and the like, so that the reagent storage unit 120 can be quickly tested regardless of location and time. Necessary reagents, washing solution, denaturing treatment solution and the like are stored in advance. In FIG. 2C, the reagent storage unit 120, the sample storage unit 121, 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 113 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 11 into the microchip 1. Prior to performing the test using the microchip 1, the tester injects the sample from the sample injection unit 113 using a syringe or the like. As shown in FIG. 2C, the sample injected from the sample injection unit 113 is stored in the sample storage unit 121 through the communicating fine channel.

  Next, when the driving liquid 11 is injected from the driving liquid injection unit 110 a, the driving liquid 11 pushes the sample stored in the sample storage unit 121 through the communicating fine flow path, and sends the sample to the amplification unit 122.

  On the other hand, the driving liquid 11 injected from the driving liquid injection unit 110b pushes out the reagent containing the fluorescent substance stored in the reagent storage unit 120a through the communicating fine channel. The reagent containing the fluorescent material pushed out from the reagent storage unit 120 a is sent to the amplification unit 122 by the driving liquid 11. Depending on the reaction conditions at this time, it is necessary to set the amplifying unit 122 to a predetermined temperature, and as described later, the reaction is heated or absorbed in the reaction detector 80 and reacted at the predetermined temperature.

  After a predetermined reaction time, a solution containing the sample after reaction sent out from the amplification unit 122 by the driving liquid 11 is injected into the detection unit 19. When the detection unit 19 is irradiated with excitation light from the window 111, the reagent that has reacted with the specimen emits fluorescence, so that the reaction result can be measured by measuring the amount of fluorescence.

  FIG. 3 is a perspective view showing an example of the internal configuration of the reaction detection device 80 in the embodiment of the present invention, and FIG. 4 is a cross-sectional view showing an example of the internal configuration of the reaction detection device 80 in the embodiment of the present invention. .

  The reaction detection device 80 includes a temperature adjustment unit 152, a fluorescence detection unit 15, a driving liquid pump 92, a packing 90, a driving liquid tank 91, a feed screw 301, a joint 302, a motor 300, and the like. 3 and 4 show a state in which the microchip 1 is in close contact with the temperature adjustment unit 152 and the packing 90b. Hereinafter, the embodiment will be described with reference to FIGS. 3 and 4.

  The temperature adjustment unit 152 and the microchip 1 are driven by a driving member (not shown) and can move in the vertical direction on the paper surface. In the initial state, the temperature adjustment unit 152 is raised from the state of FIG. 3 by the thickness of the microchip 1 by the driving member. Then, the microchip 1 can be inserted / removed in the direction of the arrow A in FIG. 3, 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 surface of the microchip 1 to a predetermined temperature by generating heat or absorbing heat.

  Next, the temperature adjustment unit 152 and the microchip 1 are lowered by the driving member, and the microchip 1 is brought into close contact with the temperature adjustment unit 152 and the packing 90b.

  In the detection unit 19 of the microchip 1, the sample and the reagent containing the fluorescent substance stored in the microchip 1 react and emit fluorescence when irradiated with excitation light. In this embodiment, the reaction result of the reagent that occurs in the detection unit 19 is optically detected from the window 111.

  The microchip 1 shown in FIG. 3 is an example in which four detection units 19 that measure the reaction result of the reagent are provided inside the microchip 1.

  The four detection units 19a, 19b, 19c, and 19d are arranged along a straight line F shown in FIG. Windows 111a, 111b, 111c, 111d (not shown) of the detectors 19a, 19b, 19c, 19d are provided on the surface of the coated substrate 109, respectively, and the reaction results are optically transmitted through the windows 111a, 111b, 111c, 111d. Can be detected.

  The fluorescence detection unit 15 has a threaded portion that is screwed with the feed screw 301, and moves in the direction of arrow B in FIG. The feed screw 301 is arranged in parallel with the straight line F. When the fluorescence detection unit 15 is moved by the feed screw 301, the fluorescence detection unit 15 is illustrated at the center of each of the detection units 19a, 19b, 19c, and 19d. The light receiving unit 161 is arranged so that the optical axes thereof coincide with each other. After moving to a predetermined position, the fluorescence detection unit 15 sequentially irradiates the detection units 19a, 19b, 19c, and 19d with excitation light, receives fluorescence emitted from the fluorescent material, and outputs an electrical signal.

  The feed screw 301 is driven by a motor 300 via a joint 302. The motor 300 is a pulse motor, for example, and rotates by a predetermined amount by a pulse. The motor 300 is the driving means of the present invention.

  The fluorescence detection unit 15 is provided with a guide hole 173 (not shown in FIG. 3) for preventing rotation, and moves along a guide rod that passes through the guide hole 173. The guide bar is disposed in parallel with the feed screw 301.

  In the present embodiment, the case where four detection units 19 are provided has been described. However, the number of detection units 19 may be any number as long as it is one or more. When the number of detection units 19 is one, there is no need to move the fluorescence detection unit 15, and therefore the feed screw 301, the motor 300, and the like are unnecessary.

  As shown in FIG. 4, a packing 90 c is connected to the suction side of the driving fluid pump 92 so that the driving fluid filled in the driving fluid tank 91 is sucked. On the other hand, a packing 90b is connected to the discharge side of the driving liquid pump 92, and the driving liquid sucked from the packing 90c is formed in the microchip 1 from the driving liquid injection part 110 of the microchip 1 through the packing 90b. Into the fine flow path 6. The packing 90b is sandwiched between the driving liquid pump 92 and the microchip 1, and the driving liquid outlet of the driving liquid pump 92, the opening of the packing 90b, and the driving liquid injection section 110 communicate with each other. In this manner, the driving liquid is injected from the driving liquid injection section 110 from the driving liquid pump 92 through the packing 90b that is in communication.

  FIG. 5 is an explanatory diagram showing an optical system of the fluorescence detection unit 15 in the embodiment of the present invention.

  The difference from the conventional example described with reference to FIG. 10 is that the dichroic mirror 159 is not used and the detection unit 19 is irradiated with excitation light from an oblique direction with respect to the optical axis L of the detection unit 19.

  As shown in FIG. 5, a lens 155 that collects fluorescence, an excitation light cut filter 156 that blocks excitation light and transmits fluorescence emitted from the fluorescent material, and a light receiving unit 161 that converts fluorescence into an electrical signal are the microchip 1. The optical axis L is arranged along the vertical axis. A photodiode or the like is used for the light receiving unit 161.

  On the other hand, the light emitting unit 160 that emits the excitation light, the slit 157 that restricts the light beam of the excitation light, and the lens 158 that collects the excitation light are arranged along the optical axis M. Excitation light emitted from the light emitting unit 160 enters the lens 158 via the slit 157, and the excitation light collected by the lens 158 irradiates the detection unit 19 from an oblique angle. Although the fluorescent material of the detection unit 19 emits fluorescence by excitation light, a part of the excitation light specularly reflected by the fluorescent material goes in the direction of arrow R in FIG. The angle at which the excitation light is irradiated may be an angle at which the excitation light specularly reflected by the fluorescent material of the detection unit 19 does not enter the light receiving unit 161. The excitation light cut filter 156 used in this embodiment is provided to remove weak excitation light reflected at an angle other than regular reflection. If the optical filter has a general performance, the excitation light is sufficiently removed. Can do.

  Conventionally, since the optical axis L of the light receiving unit 161 and the optical axis M of the light emitting unit 160 coincide with each other, strong excitation light regularly reflected by the fluorescent material enters the light receiving unit 161 and is difficult to be removed by the excitation light cut filter 156. It was. In the present invention, since the specularly reflected excitation light does not enter the light receiving portion 161, only fluorescence can be received with a simple configuration.

  FIG. 6 is a cross-sectional view for explaining an example of a lens barrel of the fluorescence detection unit 15 in the embodiment of the present invention.

  The first lens barrel 170 holds a lens 155, an excitation light cut filter 156, and a light receiving unit 161. Reference numeral 172 denotes a screw hole, which is screwed with the feed screw 301. Reference numeral 173 denotes a guide hole through which a guide rod (not shown) provided in parallel with the feed screw 301 passes. The second lens barrel 171 holds a lens 158, a slit 157, and a light emitting unit 160. The second lens barrel 171 is attached to and integrated with the first lens barrel 170.

  The optical axis M of the second lens barrel 171 is inclined with respect to the optical axis L of the first lens barrel 170, and is arranged in the detector 19 so that the optical axis M and the optical axis L intersect.

  FIG. 7 is a cross-sectional view for explaining a reaction detection device 80 provided with a fluorescent reflector in an embodiment of the present invention.

  The fluorescence emitted from the detection unit 19 is emitted not only in the direction of the optical axis L of the light receiving unit 161 but also over approximately 180 degrees. In the optical system shown in FIG. 7, paying attention to such points, the first fluorescent reflection plate 301 and the second fluorescent reflection plate 302 are provided, and the fluorescence reflected in the direction of the optical axis L and incident on the light receiving unit 161 is reflected. It is to increase.

  FIGS. 7A and 7B are explanatory diagrams for explaining the first fluorescent reflector 301 and the second fluorescent reflector 302. FIG.

  As shown in FIG. 7A, the first fluorescent reflector 301 and the second fluorescent reflector 302 are arranged in parallel with the optical axis L in between, and the first fluorescent reflector 301 and the second fluorescent reflector 302 are opposed to each other. The surface to be used is a reflector that reflects fluorescence.

  The first fluorescent reflector 301 is disposed along the vicinity of the detection portions 19a, 19b, 19c, and 19d so that the end surfaces thereof are in contact with the surface of the microchip 1 or slightly parallel to each other. . As shown in FIG. 7A, the second fluorescent reflector 302 is disposed in parallel to face the first fluorescent reflector 301 at a position that does not block the excitation light emitted from the light emitting unit 160 of the second lens barrel 171. Yes.

  In this way, a part of the light flux that could not be collected by the lens 155 out of the fluorescence emitted from the detector 19 is reflected by the first fluorescent reflector 301 or the second fluorescent reflector 302 and guided to the light receiver 161. Can do.

  The case where the fluorescence detection unit 15 is moved and the detection units 19a, 19b, 19c, and 19d are measured respectively will be described with reference to FIG. In FIG. 7B, the second fluorescent reflector 302 and the second lens barrel 171 are not shown.

  FIG. 7B shows a state in which the fluorescence detection unit 15 is moved to a position where the optical axis L of the fluorescence detection unit 15 substantially coincides with the center of the detection unit 19a. In the figure, the optical axes L corresponding to the detectors 19a, 19b, 19c, and 19d are illustrated and distinguished from La, Lb, Lc, and Ld. When the measurement of the detector 19a is completed, the fluorescence detection unit 15 is moved to the position Lb and measurement is performed. In this way, the four detectors 19 are sequentially measured.

  Since the first fluorescent reflection plate 301 and the second fluorescent reflection plate 302 are provided in parallel with the moving direction of the fluorescence detection unit 15, the optical axis L is large in any measurement of the detection units 19a, 19b, 19c, and 19d. Fluorescence emanating in different directions can be directed to the lens 155.

  The stopper 303 is a detection member for detecting the initial position, and has a built-in switch that is turned on when the fluorescence detection unit 15 contacts.

  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 which is 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 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 pump drive unit 500 is a drive unit that drives the piezoelectric element of each micropump. Based on the program, the pump drive control unit 412 controls the pump drive unit 500 to inject or suck a predetermined amount of drive fluid. The pump drive unit 500 receives the command from the pump drive control unit 412 and drives the piezoelectric element.

  The CPU 98 performs inspections in a predetermined sequence and stores the inspection results in the RAM 97. The detection position control unit 411 rotates the motor 300 by a predetermined amount to move the fluorescence detection unit 15 to a position where the predetermined detection unit 19 is inspected. The light amount calculation unit 410 calculates the light amount of the fluorescence from the electrical signal output from the light receiving unit 161 and uses it as the inspection result. The detection position control unit 411 is position control means of the present invention.

  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 temperature adjustment unit 152 is energized when the reaction detector 80 is turned on and has a predetermined temperature. Further, it is assumed that the driving liquid 11 is filled up to the upper end of the packing 90b prior to the inspection.

  The person in charge of the inspection first inserts the microchip 1 from the insertion port 83 until it abuts against a regulating member (not shown). Then, the CPU 98 detects a detection signal from the chip detection unit 95 and controls the mechanism driving unit 32, so that the packing 90b and the temperature adjustment unit 152 are in close contact with the microchip 1 as shown in FIGS. In this embodiment, from this state, the pump drive control unit 412 injects the driving liquid from each driving liquid injection unit 110 according to a predetermined procedure, performs a predetermined reaction in the flow path inside the microchip 1, It is assumed that the reacted specimen is injected into the detection unit 19.

  A procedure performed by the CPU 98 for inspection from this state will be described. In the present embodiment, it is assumed that a plurality of detectors 19 are arranged in a line as in the microchip 1 shown in FIGS.

  S101: The number of measurements is set to n = 0.

  The CPU 98 sets the number of measurements to n = 0.

  S102: This is a step of initializing the position of the fluorescence detection unit 15.

  The detection position control unit 411 detects the state of the stopper 303 while rotating the motor 300 so that the fluorescence detection unit 15 moves in the direction opposite to the arrow B in FIG. When the fluorescence detection unit 15 comes into contact with the stopper 303 and the switch provided in the stopper 303 is turned on, the detection position control unit 411 stops the rotation of the motor 300.

  S103: The fluorescence detection unit 15 is moved by a predetermined amount.

  The detection position control unit 411 applies a predetermined pulse to the motor 300 to move it until the optical axis L of the first lens barrel 170 moves to a position that substantially coincides with the center of the detection unit 19 to be measured. For example, when measuring the detector 19a, a predetermined pulse is applied so as to move from the initial position in the direction of arrow B in FIG. 7B, and the motor 300 is rotated to stop at the position shown in FIG. 7B. .

  S104: This is a step of measuring the amount of light.

  The light amount calculation unit 410 instructs the light emitting unit 160 to emit light, and temporarily stores in the RAM 97 electrical signal data proportional to the light amount output from the light receiving unit 161.

  S105: n = n + 1.

  The CPU 98 sets the number of measurements to n = n + 1.

  S106: This is a step of determining whether or not n = N.

  The CPU 98 determines whether or not the number of measurements is a predetermined number N. For example, when the number of detection units 19 is four, N = 4.

  If n = N is not satisfied (step S208; No), the process returns to step S103.

  If n = N (step S208; Yes), the process ends.

  This is the end of the procedure for measuring the light amount of each detector 19.

  The CPU 98 outputs the inspection result to the printer 503 and the external output 502 based on the light amount data measured in step S104.

  As described above, according to the present invention, it is possible to provide a small fluorescence detection unit, reaction detection device, and microchip inspection system that can receive only fluorescence with a simple configuration.

It is an external view of the reaction detection apparatus 80 in embodiment of this invention. It is explanatory drawing of the microchip 1 concerning embodiment of this invention. It is a perspective view which shows an example of the internal structure of the reaction detection apparatus 80 in embodiment of this invention. It is sectional drawing which shows an example of the internal structure of the reaction detection apparatus 80 in embodiment of this invention. It is explanatory drawing which shows the optical system of the fluorescence detection unit 15 in embodiment of this invention. It is sectional drawing for demonstrating the lens barrel of the fluorescence detection unit 15 in embodiment of this invention. It is sectional drawing for demonstrating the reaction detection apparatus 80 which provided the fluorescence reflecting plate in embodiment of this invention. It is a circuit block diagram of the reaction detection apparatus 80 in the embodiment of the present invention. 5 is a flowchart illustrating a procedure for an inspection by a reaction detection device 80 in the embodiment of the present invention. It is explanatory drawing explaining the example of the optical system of the conventional fluorescence detection unit.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microchip 6 Packing 15 Fluorescence detection unit 19 Detection part 35 Air pump 37 Electromagnetic valve 62 Micro pump 80 Reaction detection device 82 Case 83 Insertion port 84 Display part 91 Drive liquid tank 92 Pump 110 Drive liquid injection part 152 Temperature control unit 160 Light emission Part 161 light receiving part 300 motor 301 feed screw 302 joint 303 stopper

Claims (6)

A light emitting unit for irradiating the fluorescent material with excitation light;
A light receiving unit that receives the fluorescence emitted by the fluorescent material and converts it into an electrical signal;
In a fluorescence detection unit having
The fluorescence detecting unit, wherein the light emitting unit is configured to irradiate the excitation light from an angle at which the excitation light regularly reflected by the fluorescent material does not enter the light receiving unit. The fluorescence detection unit according to claim 1,
A reaction detection apparatus characterized by irradiating a fluorescent substance with excitation light by the fluorescence detection unit and measuring an electrical signal obtained by converting the received fluorescence. A microchip having a detection unit capable of optically detecting a specimen reacted with a reagent containing a fluorescent substance;
A reaction detection device according to claim 2;
A microchip inspection system comprising: The microchip has a plurality of the detection units,
The reaction detection device includes:
Driving means for driving the fluorescence detection unit to a predetermined position;
Position control means for controlling the driving means;
Have
The position control means controls the drive means so that the fluorescence detection unit sequentially moves to a position where one of the plurality of detection units can receive the excitation light and receive fluorescence of the fluorescent substance. The microchip inspection system according to claim 3. 5. The microchip inspection system according to claim 3, further comprising a fluorescent reflector that reflects the fluorescent light and enters the light receiving unit. The fluorescent reflector is
A first fluorescent reflector disposed in the vicinity of the periphery of the detection unit so that an end surface thereof is in contact with or substantially in contact with the surface of the microchip 1;
A second fluorescent reflector disposed in parallel to face the first fluorescent reflector at a position that does not block excitation light emitted from the light emitting unit;
The microchip inspection system according to claim 5, comprising:

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