JP2009063310A - Analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an analyzer capable of collectively performing the analysis of a sample and the recording of analyzed data using one disc-like inspection disc and capable of performing analytic processing at a high speed by a compact constitution using fine wells within an arbitrary range among a large number of the fine wells formed to one inspection substrate. <P>SOLUTION: A plurality of the nozzles of a jet head 20 are arranged so as to be superposed on the optical axis position of the object lens 41 of a light head 40, the jet head 20 is moved to a position in a radial direction where microwells W are formed by the irradiation with a laser beam by the light head 40 and the detection of reflected light, and liquid droplets are respectively ejected from a plurality of the nozzles so as to shift timing while detecting the angle of rotation of the inspection disc D on the basis of the output of a rotary encoder to charge a plurality of kinds of liquid agents in one microwell. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an analyzer for testing DNA (deoxyribonucleic acid), for example.

  An analysis method for analyzing a sample using a DNA chip has been known. A DNA chip has a variety of cDNA (complementary DNA) fragments immobilized on the chip, and a solution of mRNA (messenger ribonucleic acid) extracted from a sample is sprinkled onto the DNA chip to give a specific gene to the DNA. It can be analyzed whether or not a sequence is included. That is, mRNA binds only to cDNA having the same sequence and does not bind to other c-DNA. Then, it is possible to evaluate whether or not a specific gene sequence is present in the DNA of the specimen by distinguishing between the bound and unbound mRNA and cDNA using a fluorescent substance. For example, by using a DNA fragment related to canceration of cells in cDNA, it is possible to analyze how much cancer cells are contained in cells taken out from a specimen.

In addition, as a conventional technique related to the invention of the present application, the following technique has been disclosed. For example, Patent Documents 1 and 2 disclose bioassay devices that perform dropping of a DNA solution and fluorescence detection using a disc-shaped bioassay substrate. Patent Document 3 discloses that a signal recording film is formed in a predetermined range on the inner peripheral side of a disc-shaped bioassay substrate, and information relating to the inspection of the bioassay substrate is recorded. Patent Document 4 discloses an apparatus for analyzing a sample by fluorescence detection by ejecting a plurality of chemical solutions from a jet head onto a chip to which a sample of a specimen is attached, reacting with the sample.
JP 2006-133021 A JP 2006-133077 A JP 2005-03450 A JP 2007-113996 A

  The present inventor performs an analysis / analysis multiple times over a long period of time using a single inspection board, and an analysis kit that can collectively collect information on analysis results so far on the same inspection board I thought it would be very convenient. With such an analysis kit, for example, by assigning one test board to one subject, the test and analysis from one past to the present and the analysis data can be stored in one test for one subject. Can be done centrally on the board.

  In order to realize such a configuration, it was considered necessary to provide a large number of fine wells on one inspection substrate so that a plurality of inspections can be performed using arbitrary wells little by little.

  However, in the techniques of the cited references 1 and 2, since a plurality of nozzles for injecting a solution are arranged radially and these are fixed, when many fine wells are provided on the substrate, the number of wells is increased. Correspondingly, a large number of nozzles have to be provided radially, and there is a problem that the configuration for injecting the solution becomes large. In addition, when performing analysis using only a range of wells out of a large number of wells, it is necessary to add the necessary liquid agent to the wells to be used. There was a problem that was difficult.

  Moreover, since the technique of the cited document 3 has a configuration in which the solution is dropped into the well by the dropping head, there is a problem that the volume of the dropped solution is relatively large and it is difficult to correspond to a fine well. . In addition, there is a problem that it is difficult to put a plurality of liquid agents into one well at a high speed.

  The object of the present invention is to apply the technology of optical discs, and to perform integrated analysis of samples and recording of analysis data, etc. using a disk-shaped inspection substrate, and a fine well on one inspection substrate. It is an object of the present invention to provide an analyzer capable of performing a high-speed test with a compact configuration using only a well in an arbitrary range among the many wells.

  In order to achieve the above object, the present invention uses a disc-shaped inspection disk on which a plurality of microwells for reacting a sample and a recording area capable of data recording are formed, and analyzes and analyzes the sample. A spindle mechanism that rotationally drives the inspection disk, a rotary encoder that detects a rotation angle of the inspection disk rotated by the spindle mechanism, and a plurality of liquid agents into fine droplets. And a jet head in which the plurality of nozzles are arranged side by side in the rotation direction of the inspection disk, and an objective lens that irradiates and collects light to the inspection disk. A fluorescence detection unit that irradiates the inspection disk with excitation light and detects the amount of fluorescence emitted therefrom; and a laser to the inspection disk An optical head having a data recording unit that records and reproduces data by irradiating a laser beam, a slide mechanism that moves the jet head and the optical head relative to the inspection disk in a radial direction, and controls each unit. And a control means for performing, the radial position of the inspection disk of the plurality of nozzles is arranged so as to overlap the optical axis position of the objective lens of the optical head, the control means is a laser by the optical head The jet head is moved to the radial position where the microwell is formed by detecting light irradiation and reflected light, and the timing from the plurality of nozzles is detected while detecting the rotation angle of the inspection disk based on the output of the rotary encoder. Injecting multiple types of liquid agent into one microwell by spraying fine droplets by shifting It was formed.

  According to such means, the analysis of the sample and the recording of the analysis data can be comprehensively performed with one inspection disk, and the inspection disk on which many fine wells are formed is arbitrarily selected. It is possible to inspect the sample by introducing the necessary liquid into the wells in the range. In addition, since the jet head for injecting the liquid agent has a configuration in which the liquid agent can be input to all the microwells from one nozzle, the configuration for injecting the liquid agent is compact even if a large number of microwells are formed. I can do it.

  Specifically, the jet head may be configured to eject the liquid agent as fine droplets of 20 picoliters or less.

  Thereby, the size of the microwell formed on the inspection disk can be reduced, and a larger number of microwells can be formed.

  More specifically, the inspection disk has a concentric through hole in the center, and a plurality of microwells each having a concave substrate surface are arranged in a spiral shape within a certain radius range from the center side. A groove having a concave substrate surface is formed so as to connect adjacent microwells along the row of microwells, and a data mark is formed by laser light on the outer peripheral side of the microwell formation region. It is preferable that a data recording region having a recording layer capable of forming the is formed.

  More specifically, the control means adjusts the position of the optical head in the radial direction so that the laser beam is focused on the groove, thereby changing the position of the jet head to the radius where the microwell is formed. It is good to have a configuration that matches the position.

  With such a configuration, it is possible to continuously analyze the sample in a plurality of microwells along the groove by rotating the inspection disk with the Giotto head along the groove. It is also easy to confirm the position of the microwell by detecting the groove and to move the jet head to a predetermined microwell position.

  Preferably, upon receiving an instruction to start a sample analysis process, the control means reads the storage data of the recording area to check the unused area of the microwell; and the microwell of the unused area A step of supplying a liquid agent to the jet head, a step of performing fluorescence detection of the microwell into which the liquid agent has been added, and data relating to the fluorescence detection and data indicating a range of the used microwells in the recording area. It is preferable that the steps are sequentially performed.

  With such a configuration, it is possible to perform a plurality of inspections over a long period of time with a single inspection disk by automatic control, and comprehensively collect the analysis data so far on the same inspection disk. I can go.

  According to the present invention, it is possible to comprehensively perform sample analysis and storage of analysis data with a disk-shaped inspection disk, and to form a large number of fine wells on one inspection disk, There is an effect that high-speed inspection can be performed with a compact configuration using only wells in an arbitrary range.

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

  FIG. 1 is a configuration diagram showing a mechanical configuration and an optical configuration of an analyzer 1 according to an embodiment of the present invention, and FIG. 2 is a block diagram showing a circuit configuration of the analyzer 1 according to the embodiment.

  The analysis apparatus 1 according to this embodiment uses a disc-shaped test disk D to analyze human DNA and record the analysis data. The test disk D is held on a rotating shaft 10a and driven to rotate. A spindle motor 10 that detects the encode mark of the test disk D, and a rotary encoder 12 that detects the rotation angle, and a jet head that puts a blood solution or a drug solution as a specimen into the microwell of the test disk D 20, an optical head 40 having an optical system (41 to 61) that performs fluorescence detection, data recording / reproduction, and the like, a base frame 14 on which the jet head 20 and the optical head 40 are mounted, and the base frame 14 as a nut 17 and 17 and a slide motor 15 that moves in the radial direction of the inspection disk D via a lead screw 15a.

  An optical system mounted on the optical head 40 includes an objective lens 41 that converges light on the inspection disk D and collects reflected light and fluorescence, and a lens actuator that slightly displaces the objective lens 41 in a focus direction and a tracking direction. 42, a dichroic mirror 43 that separates laser light, excitation light, and fluorescence, emitter filters 44a and 44b that transmit red fluorescence and green fluorescence, and a PMT (photomultiplier) 45 that detects the amount of fluorescence light. A light source 49 that emits excitation light, a collimator lens 47 that converts the excitation light into parallel light, an exciter filter 47 that extracts the wavelength of the excitation light, and a filter mirror that reflects the excitation light and transmits laser light for recording and reproduction. 46, a semiconductor laser 53 that emits a laser beam for recording / reproducing, a traveling wave and a reflected wave of the laser beam for recording / reproducing, A quarter-wave plate 50 and a polarizing beam splitter 52 for separation, a collimator lens 51 that makes the recording / reproducing laser beam parallel, and a prism 54 that separates the reflected beam of the recording / reproducing laser beam in three directions. , 57, a slit 55 in which a dot-like or linear gap is formed, a first optical sensor 56 that detects the intensity of light that has passed through the slit 55, and two prisms that are in contact with each other at different angles and fixed. An optical element 58; a second optical sensor 59 that detects light that has passed through the optical element 58 with a plurality of divided detection surfaces; an optical lens 60 such as a cylindrical lens that imparts astigmatism to the reflected beam; and an optical lens. A third optical sensor 61 or the like is provided for detecting light that has passed through 60 on a plurality of divided detection surfaces.

  The jet head 20 is disposed above the inspection disk D held on the rotating shaft 10a. On the other hand, the objective lens 41 of the optical head 40 is disposed below the inspection disk D. The jet head 20 and the objective lens 41 are aligned so that the extension line of the nozzle and the optical axis of the objective lens 41 are positioned at the same length in the radial direction of the inspection disk D.

  The rotary encoder 12 is configured by, for example, a reflective optical sensor.

  Either one of the emitter filters 44a and 44b is moved on the optical axis by a drive device (not shown) so that the passing wavelength of the fluorescence is switched.

  The slit 55 and the first optical sensor 56 are for detecting the amount of deviation between the focal point of the laser beam converged by the objective lens 41 and the reflecting surface by the confocal method. The optical element 58 and the second optical sensor 59 are for detecting the amount of deviation of the focal point of the laser beam by the double knife edge method. The optical lens 60 such as a cylindrical lens and the third optical sensor 61 are for detecting the amount of focus deviation of the laser beam by the astigmatism method. The third optical sensor 61 is also used to generate a reproduction signal when reading data.

  In addition, as shown in FIG. 2, the analysis apparatus 1 according to this embodiment includes arithmetic circuits 65 and 66 that calculate detection signals from the second optical sensor 59 and the third optical sensor 61 and generate focus error signals. Digital sampling circuits 62 to 63, 71 for converting focus error signals obtained from detection outputs of the optical sensors 56, 59, 61 into digital signals; a digital sampling circuit 64 for converting fluorescence detection signals of the PMT 45 into digital signals; A control circuit 70 for controlling the driving of the lens actuator 42, the jet head 20, the slide motor 15, the spindle motor 10 and the like by inputting signals from these optical sensors 45, 56, 59, 61, the rotary encoder 12, and the like, and for data recording A write data processing circuit 69 for performing the signal processing, and the slide motor 15 and the spindle motor. A driver 67, 68 for driving the 10, and a laser driver 73 for driving the semiconductor laser 53.

  The slide motor 15 is composed of a stepping motor or the like, and the control circuit 70 can recognize the position of the optical head 40 and the jet head 20 in the radial direction of the inspection disk D from the amount of rotation.

  FIG. 3 is a plan view showing the configuration of the test disk according to the embodiment of the present invention, FIG. 4 is a diagram schematically showing the overall configuration of the microwell formed in the microassay region, and FIG. 5 is the microwell. FIG. 6 is a sectional view of a part of the inspection disk.

  The inspection disk D has a disk shape equivalent to that of a compact disk, for example, and a concentric through hole D0 held by the rotating shaft 10a is formed at the center thereof. Further, an encode mark M1 for detecting the rotation angle is formed on the lower surface on the inner peripheral side near the through hole D0, and in the range from the encode mark M1 to the middle of the disk radius on the outer peripheral side, a minute micro A microassay region A1 having many wells W on the upper surface of the disk is formed. Further, on the outer peripheral side, a data recording area A2 having a recording layer in which a data mark can be formed by a laser beam in the disc is formed in the same manner as the optical disc.

  As shown in FIGS. 4 and 5, in the microassay region A1, a large number of microwells W each having a disk surface formed in a circular concave shape are formed so as to spiral from the center side to the outside. Note that FIG. 4 schematically shows that the microwells are arranged in a vortex, in fact, two adjacent rows of vortices are arranged closer together, and adjacent microwells along the row The interval of W is also made narrower.

  A thin groove G is formed between two microwells W adjacent to each other along the row so as to connect the two. For example, the microwell has a diameter of about 10 μm and the groove has a diameter of about 0.4 μm. Further, although not particularly limited, as shown in a partially enlarged view of FIG. 3, the microwells W are formed at a predetermined rotation angle from the inner peripheral side to the outer peripheral side. Such processing of the microwell W and the groove G can be created by forming this fine shape on the mold when the disk material is formed by injection molding in the same manner as the process of forming the optical disk. Is.

  In the data recording area A2, a recording layer b1 is formed at a central depth position of the inspection disk, for example, like an optical disk such as a DVD (Digital Versatile Disk). The recording layer b1 includes a dye film, a reflective film, a recording groove, and the like on which a mark is formed by a laser beam, as in the optical disk.

  7 and 8 are a front view and a side view showing the configuration of the jet head 20, respectively.

  As shown in FIG. 7, the jet head 20 has a plurality of independent flow paths 22a to 22d and nozzles 23a to 23d, and ejects the liquid agent as fine droplets from the tips of these nozzles 23a to 23d. is there. FIG. 7 shows an example in which four flow paths 22a to 22d and four nozzles 23a to 23d are formed. However, an enormous number such as 100 or 200 is formed.

  The fine droplet is, for example, a droplet of about 3 pl (picoliter), but if it is a droplet of 20 pl or less, the liquid agent does not jump out of the microwell W by the rotation of the inspection disk D, and the reagent or the like The amount used can be reduced, and the effect of reducing the running cost of the inspection can be obtained. As shown in FIG. 8, the flow paths 22a to 22d and the nozzles 23a to 23d are formed by, for example, etching the surface of the silicon block 25b to form a groove, and bonding the glass 25a or the like to the silicon block 25b. It can be formed between the block 25b and the glass 25a.

  Further, in the middle of the flow paths 22a to 22d, one surface of the piezo elements 24a to 24d is provided so as to cover the flow paths 22a to 22d, and a voltage is applied to the piezo elements 24a to 24d to drive them. The liquid agent in the flow paths 22a to 22d is pressed and fine droplets are ejected from the tips of the nozzles 23a to 23d.

  Pipes 26 are connected to the upper ends of the flow paths 22a to 22d, and liquid agents are supplied from these pipes 26. These configurations are held and fixed by the holder frame 20A. Further, a small tank into which a liquid agent is introduced is provided at the end of the pipe 26, and a liquid medicine or a sample solvent can be introduced into the tank and ejected from the nozzles 23a to 23d.

  As shown in FIG. 7, the plurality of nozzles 23 a to 23 d are assembled so as to be aligned in the rotation direction (circumferential tangential direction) of the inspection disk D held on the rotation shaft 10 a.

  FIG. 9 is a time chart showing an example of the output of the rotary encoder, and FIG. 10 is a time chart explaining an example of the driving operation of the jet head.

  The encode mark M1 is not particularly limited. For example, the encode mark M1 includes a plurality of marks formed at fine angles so that one detection signal is output in an angle range in which one microwell W is formed. It has one mark on a concentric circle formed so that one detection signal is output per rotation. The rotary encoder 12 detects both of these marks independently, so that an encoder output A that outputs one detection pulse every rotation of the inspection disk and an angle range in which one microwell W is present. Encoder output B from which one detection pulse is output.

  As shown in FIG. 10, the control circuit 70 sequentially drives the piezo elements 24a to 24d of the jet head 20 at a predetermined delay interval td0, td, td, td with one detection pulse of the encoder output B as a reference. To do. Thereby, it is possible to inject the liquid agent from a plurality of nozzles 23a to 23d to substantially the same point in one microwell W. The delay td0 from the pulse of the encoder output B to the driving of the first piezo element 24a is the rotation angle from the start point of the encode mark M1 to a predetermined point (for example, the center point) in the microwell W and the inspection disk D. It is the time according to the angular velocity. The delay time td from the drive of one piezo element to the drive of the next adjacent piezo element is determined by the interval between the plurality of nozzles 23a to 23d of the jet head 20 and the velocity (angular velocity) at the liquid injection point of the inspection disk D. X radius to that point). The control circuit 70 obtains the angular velocity of the inspection disk and the radius of the liquid agent injection point, and sequentially drives the piezo elements 24a to 24d of the jet head 20 at the delay intervals td0, td, td, and td calculated from them. By doing so, it is possible to administer a plurality of solutions to a predetermined point in the microwell W.

  Next, the operation of the analysis process using the analyzer 1 having the above configuration will be described.

  In this analyzer 1, various analyzes can be performed by using various samples or drugs as specimens. Here, the DNA of the subject is used as a sample for canceration of the subject's DNA. A process for analyzing whether or not various gene sequences involved are included will be described.

  First, the outline of the analysis principle will be described. In order to perform the analysis process as described above with this analyzer 1, as a liquid agent sprayed from the jet head 20, for example, a blood solvent in which a subject's DNA is dissolved, and a large number of types having a DNA sequence involved in canceration And a solvent for a fluorescent substance that is converted into a structure that emits fluorescence by binding to double-stranded DNA. Then, a plurality of types of cDNA, blood solvent, and fluorescent substance solvent are respectively added to and reacted with a plurality of microwells in a manner that one cDNA corresponds to one microwell.

  Then, if the DNA of the subject's blood solvent has a gene sequence corresponding to cDNA, the mRNA and cDNA related to the subject's DNA are combined to form double-stranded DNA, and the fluorescent material is combined to emit fluorescence. It changes to. On the other hand, if the DNA of the subject's blood solvent does not have a gene sequence corresponding to the cDNA, the mRNA and cDNA associated with the subject's DNA will not bind, and therefore the double-stranded DNA will not be generated and the fluorescent substance will be phosphor. It will not change.

  Therefore, when the liquid agent is put into a plurality of microwells W to react, the microwells W are irradiated with excitation light from below the test disk D, and the amount of fluorescence emitted therefrom is detected by the PMT 45. Then, by confirming the cDNA charged into the microwell W having a fluorescence amount above a certain level, the analysis result that the DNA collected from the subject contains the cDNA gene sequence involved in this canceration is obtained. I can do it.

  Next, the processing procedure of the analysis process by the above-described analyzer 1 will be described.

  FIG. 11 is a perspective view showing a state in which a liquid agent is put into the microwell W, and FIG. 12 shows a state in which the optical axis position is aligned with the groove in the microassay region by the optical head 40 and a state in data recording. FIG. 13 is a graph showing a focus error signal used when focusing on the groove G of the microassay region A1.

  FIG. 14 is a flowchart of the initial process executed by the control circuit 70 when the analysis process is performed for the first time using one inspection disk D, and FIG. 15 is a case where an analysis execution instruction is given. The flowcharts of the microassay process executed by the control circuit 70 are shown respectively.

  When the unused inspection disk D is used for the first time, when the inspection disk D is set in the apparatus, the optical head 40 accesses the data in the data recording area A2, so that it is an unused inspection disk D by the control circuit 70. It is detected. Then, when an unused inspection disk D is detected, the initial process of FIG. 14 is started.

  In the initial process, first, the control circuit 70 causes the information of each microwell W of the test disk D and the cDNA to be inserted therein to be input to the apparatus 1 from the outside in the form of a table (spreadsheet), for example (step S1). ). These data are prepared by the setter. When these data are input, the control circuit 70 moves the optical head 40 to the inner peripheral portion in the data recording area A2 of the inspection disk D (step S2), and writes these data therein (step S3). The control at the time of data writing is the same as that performed on a general optical disk, and the details are omitted.

  Next, in the state where the initial process is completed, when a command for starting the analysis process is input to the analyzer 1, the microassay process of FIG. 15 is started. When the microassay process is started, first, the control circuit 70 moves the optical head 40 to the inner peripheral portion of the data recording area A2, and from there, the table data in which the information on the cDNA to be inserted into each microwell W is recorded. Is read (step S11). Next, the control data in the data recording area A2 is read to check the range of unused microwells W (step S12).

  When the range of unused microwells W is confirmed, a range of the plurality of microwells W used in the current analysis process is designated from the side closer to the inner periphery, and the plurality of microwells W is selected. In addition, a sample (blood solution) serving as a specimen, and a chemical solution and a fluorescent substance based on the above table data are input by driving the jet head 20 (step S13).

  When the liquid agent is put into the designated microwell W, as shown in FIGS. 11 to 12, laser light is emitted from the optical head 40, and this laser light is focused at the position of the groove G in the microassay region A1. Servo-controlled so that In order to realize such servo control, first, three focus error signals as shown in FIG. 13 are input based on the outputs of the first to third optical sensors 56, 59, 61, and based on these, the laser is controlled. The light is focused on the upper surface of the inspection disk D.

  As shown in FIG. 13, the focus error signal obtained by the confocal method can detect a focus shift within a relatively large range by an afocal optical system. On the other hand, the focus error signal obtained by the double knife edge method and the focus error signal obtained by the astigmatism method can detect an accurate focus shift in a relatively medium range and a small range. Therefore, using these three signals, the focus error signal of the confocal method is used in the range where the focus is greatly deviated, and the focus error signal of the double knife edge method and the astigmatism method is used as the focus gradually approaches. Use to focus servo. Thereby, the laser beam is focused on the upper surface of the inspection disk D.

  Next, when the focal point of the laser beam comes to the position of the groove G arranged in a spiral shape, the focus position is shifted to the bottom surface of the groove G, and in the lateral direction of the groove G (radial direction of the inspection disk D). Servo control is also performed so that the focal point of the laser light moves along the groove G. The servo control in the horizontal direction is not shown, but the same configuration as the tracking servo control performed in the recording groove of the optical disk can be applied. That is, the lateral drive control of the lens actuator 42 and the drive control of the slide motor 15 are performed using a three-beam method or the like so that the laser light does not deviate from the groove G. A microwell W is provided in the middle of the groove G, and the groove G disappears in this range. However, since the diameter of the microwell W is about 10 μm, the inspection disk D is rotated at a certain speed so that the laser beam Servo control can be continued so that the focal point does not deviate from the groove G.

  By such servo control, the objective lens 41 of the optical head 40 is brought into a state along the grooves G and the microwells W arranged in a spiral shape, so that the nozzles 23a to 23d. The position is controlled along the grooves G and the microwells W arranged in a spiral shape.

  In this state, from the output of the rotary encoder 12 shown in FIG. 9 and the detection of the rotation amount of the slide motor 15, the control circuit 70 positions the jet head 20 above the microwell W. Find out. When the jet head 20 comes to a position above the designated microwell W, the one corresponding to the liquid agent to be charged is driven among the piezo elements 24a to 24d... Of the jet head 20 at the timing described in FIG. A sample (blood solution), a chemical solution containing cDNA, and a fluorescent substance are added. Then, such a liquid agent is charged into a plurality of types of chemical liquids and a plurality of microwells W designated in succession (step S13).

  When the liquid agent is charged, next, the time for the liquid agent to react is waited (step S14), and then fluorescence detection is performed on the microwell W into which the liquid agent has been charged (step S15). When detecting fluorescence, as described above, first, the focus of the objective lens 41 is adjusted to the spiral groove G or microwell W using laser light, and then excitation light is emitted from the light source 49. Output and digitize the output signal of PMT45. Such fluorescence detection processing is performed once or a plurality of times for each of the plurality of microwells W into which the liquid agent is charged in step S13. Further, the process is performed a plurality of times by switching the emitter filters 44a and 44b of the fluorescence detection unit.

  Next, the microwell W whose fluorescence output has exceeded the threshold value is extracted from the captured output of the PMT 45, and the cDNA of the liquid medicine charged therein is extracted from the table data to generate analysis result data (step S16).

  After the analysis result data is generated, the optical head 40 is moved to the data recording area A2 of the inspection disk D, and the range and analysis of the microwell W used in this analysis process are moved to the sector where no data is written. The result data is written (step S17). By recording the range of the microwells W used in this way, the next time the analysis process is performed using the same test disk D, the used microwells W are excluded and unused. Analysis processing can be performed using the microwell W.

  Next, the fluorescence detection raw data (Raw Data) is also written in the data recording area A2 of the inspection disk D (step S18). By recording the raw data, it becomes possible to analyze and verify the measurement result of fluorescence detection by another method later. When the writing of the raw data is finished, one analysis process is finished.

  As described above, according to the analysis apparatus 1 of this embodiment, it is possible to perform a plurality of analysis of samples and recording of the analysis data using a single inspection disk D. Furthermore, since the designated liquid agent can be injected into an arbitrary microwell W from one nozzle of the jet head 20 by servo control using laser light and detection of the rotation angle of the rotary encoder 12, the jet head 20 Can be made into a minimum and compact configuration. In addition, since the jet head 20 is configured to inject fine droplets of 20 pl or less, the microwell W can be miniaturized to form many microwells W on one inspection disk D. A very large number of analysis processes can be performed on one inspection disk D.

  In addition, since the plurality of microwells W are formed in a spiral shape and the grooves G are formed along the rows, the servo is performed so that the focal point of the laser light does not come off along the grooves G. By applying the control, the position of the jet head 20 can be easily adjusted to the upper position of the microwell W along the groove G. Further, by determining together with the output of the rotary encoder 12, it is possible to determine at which position the jet head 20 is located corresponding to the microwell W.

  The present invention is not limited to the above-described embodiment, and various modifications can be made. For example, in the above-described embodiment, the configuration in which the optical head 40 and the jet head 20 are integrated with the base frame 14 is illustrated. However, these are provided in separate frames, and these two frames are interlocked and equidistant from each other. It may be configured to move. In addition, although the microwells W are provided one by one at the same rotation angle, for example, one microwell W may be provided at equal intervals. In the above embodiment, the example in which the analyzer of the present invention is used for DNA inspection based on the binding of mRNA and cDNA has been shown. However, the analysis content can be applied to various things and used for analysis. Various types of reaction between the sample and the drug to be used can be used.

  In addition, details such as the configuration of the optical system and the encoder mark M1 and the data stored in the data recording area A2 of the inspection disk D can be changed as appropriate without departing from the spirit of the invention.

It is a block diagram which shows the mechanical structure and optical structure of the analyzer 1 of embodiment of this invention. It is a block diagram which shows the circuit structure of the analyzer 1 of embodiment. It is a top view which shows the structure of the test | inspection disk of embodiment of this invention. It is the figure which represented roughly the structure of the microassay area | region. It is a perspective view which shows the detailed structure of a microwell. It is sectional drawing of an inspection disk. It is a front view which shows the structure of a jet head. It is a side view which shows the structure of a jet head. It is a time chart which shows an example of the output of a rotary encoder. It is a time chart explaining an example of the drive operation of a jet head. It is a perspective view which shows the state which has injected | thrown-in the liquid agent to the microwell. It is explanatory drawing showing the state of the fluorescence detection by an optical head, and the state of data recording. It is a wave form diagram which shows the focus error signal used for focus servo control of an optical head. It is a flowchart which shows the process sequence of the initial process with respect to the test | inspection disk performed by a control circuit. It is a flowchart which shows the procedure of the microassay process performed by a control circuit.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Analyzer 10 Spindle motor 12 Rotary encoder 15 Slide motor 15a Lead screw 20 Jet head 23a-23d Nozzle 24a-24d Piezo element 40 Optical head 41 Objective lens 42 Lens actuator 45 PMT
49 Light source of excitation light 53 Semiconductor laser 56, 59, 61 Optical sensor D Inspection disk A1 Micro assay area A2 Data recording area M1 Encoding mark W Microwell G Groove b1 Recording layer

Claims (6)

An analyzer for analyzing a sample and recording analysis data, using a disk-shaped inspection disk in which a plurality of microwells for reacting a sample and a recording area capable of data recording are formed,
A spindle mechanism for rotationally driving the inspection disk;
A rotary encoder for detecting a rotation angle of the inspection disk rotated by the spindle mechanism;
A plurality of nozzles each ejecting a plurality of liquid agents as fine droplets, and a plurality of these nozzles arranged side by side in the rotation direction of the inspection disk;
A fluorescence detection unit that has an objective lens that irradiates and collects light to the inspection disk, irradiates the inspection disk with excitation light, and detects the amount of fluorescence emitted therefrom, and the inspection disk An optical head having a data recording unit for recording and reproducing data by irradiating a laser beam;
A slide mechanism for moving the jet head and the optical head in a radial direction relative to the inspection disk;
Control means for controlling each part;
With
The radial positions of the inspection disks of the plurality of nozzles are arranged so as to overlap the optical axis position of the objective lens of the optical head,
The control means includes
The jet head is moved to a radial position where the microwell is formed by irradiating the optical head with laser light and detecting reflected light.
By detecting the rotation angle of the inspection disk based on the output of the rotary encoder and ejecting fine droplets from the plurality of nozzles at different timings, a plurality of types of liquid agents are injected into one microwell. It is comprised in the analysis apparatus characterized by the above-mentioned.   The analyzer according to claim 1, wherein the jet head is configured to eject the liquid agent as fine droplets of 20 picoliters or less. The inspection disk is
Having a concentric through hole in the center,
A plurality of microwells each having a substrate surface formed in a concave shape are formed in a spiral shape within a certain radius range from the center side, and grooves having a substrate surface formed in a concave shape are formed in the microwell row. Formed to connect adjacent microwells along the
3. The analyzer according to claim 1, wherein a data recording region having a recording layer capable of forming a data mark by a laser beam is formed on an outer peripheral side of the microwell formation region. The control means includes
4. The position of the jet head is adjusted to the radial position where the microwell is formed by adjusting the radial position of the optical head so that the laser beam is focused on the groove. The analyzer described. The control means includes
When you receive an instruction to start the sample analysis process,
Reading stored data in the recording area and checking the unused area of the microwell; and
Charging the liquid agent from the jet head into the microwells of the unused area;
Performing fluorescence detection of the microwells charged with the solution;
Recording data relating to the fluorescence detection and data indicating the range of microwells used in the recording area;
The analyzer according to any one of claims 1 to 4, wherein the analysis is performed sequentially. A plurality of microwells each having a disc shape and having a substrate surface formed in a concave shape in a certain radius range from the center side are formed in a spiral shape, and the groove having a substrate surface formed in a concave shape A data recording region is formed so as to connect adjacent microwells along the row of microwells, and a recording layer having a recording layer capable of forming a data mark by a laser beam is formed on the outer peripheral side of the microwell formation region. An analysis device for analyzing a sample and recording analysis data using an inspection disk,
A spindle mechanism for rotationally driving the inspection disk;
A rotary encoder for detecting a rotation angle of the inspection disk rotated by the spindle mechanism;
A jet head having a plurality of nozzles each ejecting a plurality of liquid agents into fine droplets of 20 picoliters or less, wherein the plurality of nozzles are arranged in the rotation direction of the inspection disk;
A fluorescence detection unit that has an objective lens that irradiates and collects light to the inspection disk, irradiates the inspection disk with excitation light, and detects the amount of fluorescence emitted therefrom, and the inspection disk An optical head having a data recording unit for recording and reproducing data by irradiating a laser beam;
A slide mechanism for moving the jet head and the optical head in a radial direction relative to the inspection disk;
Control means for controlling each part;
With
The radial positions of the inspection disks of the plurality of nozzles are arranged so as to overlap the optical axis position of the objective lens of the optical head,
The control means includes
When you receive an instruction to start the sample analysis process,
Reading stored data in the recording area and checking the unused area of the microwell; and
Charging the liquid agent from the jet head into the microwells of the unused area;
Performing fluorescence detection of the microwells charged with the solution;
Recording data relating to the fluorescence detection and data indicating the range of microwells used in the recording area;
In order,
In the step of introducing the liquid agent,
By adjusting the radial position of the optical head so that the laser beam is focused on the groove, the position of the jet head is moved to the radial position where the microwell is formed,
By detecting the rotation angle of the inspection disk based on the output of the rotary encoder and ejecting fine droplets from the plurality of nozzles at different timings, a plurality of types of liquid agents are injected into one microwell. It is comprised in the analysis apparatus characterized by the above-mentioned.

Images