JP2010085181A - Sample preparation device, cell analyzer, and cell discrimination device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sample preparation device capable of discriminating a cell having a prescribed size, and improving easily filtration treatment speed. <P>SOLUTION: This sample preparation device 4 is equipped with: cell discrimination parts 416 (417, 418) including a plurality of plate members 416a (417a, 418a) provided at prescribed intervals s1 (s2, s3) for passing cells having a prescribed size in a biosample, and for blocking cells which are larger than the cell having the prescribed size; and a sample preparation part 42 for preparing a measuring sample from a prescribed reagent and at least either of cells passing the intervals between the plurality of plate members 416a (417a, 418a) and cells captured by the plurality of plate members 416a (417a, 418a) which are separated by passing of the biosample through the intervals between the plurality of plate members 416a (417a, 418a). <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a sample preparation device, a cell analysis device, and a cell discrimination device.

  Conventionally, a cell analyzer for analyzing cells contained in a biological sample is known (see, for example, Patent Document 1).

  Patent Document 1 discloses a cell analyzer that uses epithelial cells in a biological sample as a measurement target. Since the biological sample collected from the subject includes cells other than the measurement target cell and foreign substances other than the cell other than the measurement target cell, a predetermined cell is used as in the cell analyzer of Patent Document 1 described above. In a cell analyzer to be measured, if a biological sample is used as it is as a measurement sample, the cell to be measured cannot be analyzed accurately. For this reason, conventionally, a cell discriminating apparatus that discriminates predetermined cells is desired. Conventionally, a microorganism collection kit (discrimination device) is known as a means for discriminating microorganisms having a cell level (see, for example, Patent Document 2).

  Patent Document 2 discloses a microorganism collection kit (discrimination device) including a metal foreign matter removal filter and a microorganism collection filter. Each of these foreign matter removal filter and microorganism collection filter has a plurality of pores with cell sizes of 5 μm to 20 μm and 0.2 μm to 0.8 μm in diameter. By passing through the pores, it is possible to discriminate microorganisms having a cell level size.

WO2006 / 103920 publication JP 2005-291940 A

  However, in the microorganism collection kit (discrimination device) of Patent Document 2 described above, it is possible to discriminate microorganisms having a cell level size. On the other hand, since a filter having a plurality of pores is used, the aperture ratio of the filter (= There is an inconvenience that it is difficult to increase the opening area by the pores / the surface area of the filter. That is, when a plurality of pores having a cell level size are provided in a filter, it is known that it is difficult to manufacture an aperture ratio of 30% or more even if an electrocasting method that easily increases the aperture ratio is used. ing. For this reason, since it is difficult to increase the amount of the biological sample passing through the filter within a predetermined time, there is a problem that it is difficult to improve the filtration processing speed.

  The present invention has been made to solve the above-described problems. One object of the present invention is to discriminate cells of a predetermined size and to easily improve the filtration processing speed. The present invention provides a sample preparation device, a cell analysis device, and a cell discrimination device that can be used.

Means for Solving the Problems and Effects of the Invention

  In order to achieve the above object, the sample preparation device according to the first aspect of the present invention allows a cell having a predetermined size in a biological sample to pass therethrough and does not pass a cell larger than a cell having a predetermined size. A cell discriminating portion including a plurality of plate-like portions provided at intervals, a cell through which a biological sample passes through the gap between the plurality of plate-like portions by passing through the gap between the plurality of plate-like portions, and And a sample preparation unit for preparing a measurement sample from at least one of the cells captured by the plurality of plate-like parts and a predetermined reagent.

  In the sample preparation device according to the first aspect of the present invention, as described above, cells of a predetermined size in a biological sample are allowed to pass, and cells larger than cells of a predetermined size are not passed at predetermined intervals. By providing the cell discriminating portion including a plurality of plate-like portions provided in a predetermined manner, it is possible to discriminate between cells having a predetermined size and cells larger than cells having a predetermined size. Further, by providing a plurality of plate-like portions arranged at predetermined intervals in the cell discriminating portion, compared with the case of providing pores in the cell discriminating portion, a member (plate-like portion) between the openings is manufactured. ) Can be easily reduced, so that the aperture ratio can be easily increased. Thereby, since the quantity of the biological sample which passes the cell discrimination part within predetermined time can be increased easily, the processing speed of filtration can be improved easily. Further, by filtering using a plurality of plate-like portions, the thickness (length) in the flow direction of the biological sample can be easily increased as compared with the case where a filter having a small thickness in the flow direction of the biological sample is used. Therefore, the mechanical strength of the cell discriminating part in the flow direction of the biological sample can be easily increased.

  In the sample preparation device according to the first aspect described above, preferably, the cell having a predetermined size is a first cell including at least one selected from red blood cells, white blood cells, and bacteria, and is more than a cell having a predetermined size. A large cell is a second cell containing epithelial cells, and the plurality of plate-like portions are formed by the biological sample passing through the gaps between the plurality of plate-like portions, so that the first cell becomes a gap between the plurality of plate-like portions. And the second cells are captured by the plurality of plate-like portions. If comprised in this way, the 1st cell containing at least 1 selected from a red blood cell, a white blood cell, and bacteria and the 2nd cell containing an epithelial cell can be discriminated. If such a sample preparation device capable of discriminating between the first cell and the second cell is applied to a cell analysis device for measuring epithelial cells, red blood cells, white blood cells, bacteria, and the like that are not the measurement target are removed from the measurement sample. Therefore, the measurement object can be measured with high accuracy.

  In the sample preparation device according to the first aspect, preferably, the cell having a predetermined size is a third cell including a single cell of an epithelial cell, and the cell larger than the cell having a predetermined size is an epithelial cell. Is a fourth cell containing aggregated cells, and the plurality of plate-like portions pass through the gaps between the plurality of plate-like portions so that the third cells pass through the gaps between the plurality of plate-like portions. The fourth cell is configured to pass through and be captured by the plurality of plate-like portions. If comprised in this way, the 3rd cell containing the single cell of an epithelial cell and the 4th cell containing the aggregated cell which the epithelial cell aggregated can be discriminated. If such a sample preparation device capable of discriminating between the third cell and the fourth cell is applied to a cell analysis device for measuring epithelial cells, a single cell of epithelial cells is to be measured, or Since it is possible to select whether to measure both single cells and aggregated cells of epithelial cells, the degree of freedom of measurement can be improved.

  In the sample preparation device according to the first aspect, preferably, the cell having a predetermined size is a fifth cell including an aggregated cell in which three or less epithelial cells are aggregated, and is larger than the cell having a predetermined size. The cell is a sixth cell including an aggregated cell in which four or more epithelial cells are aggregated, and the plurality of plate-like parts are formed by passing the biological sample through the gaps between the plurality of plate-like parts. The sixth cell is configured to pass through the gaps between the plurality of plate-like portions and be captured by the plurality of plate-like portions. If comprised in this way, the 5th cell containing the aggregated cell which three or less epithelial cells aggregated and the 6th cell containing the aggregated cell which four or more epithelial cells aggregated can be discriminated. If such a sample preparation device capable of discriminating between the fifth cell and the sixth cell is applied to a cell analysis device for measuring epithelial cells, aggregated cells in which four or more epithelial cells are aggregated from the measurement sample can be obtained. Since it can be removed, the measurement object can be measured with high accuracy using aggregated cells in which three or less epithelial cells are aggregated.

  In the sample preparation device according to the first aspect described above, preferably, a plurality of second plate-like portions that are arranged on the upstream side of the flow of the biological sample from the cell discriminating portion and are provided with a wider interval than a predetermined interval are provided. A second cell discriminating unit is further included. If comprised in this way, after distinguishing a comparatively big cell by the 2nd plate-shaped part, since the cell discrimination part can discriminate | determine the cell of a predetermined | prescribed magnitude | size further, a cell is discriminated accurately. be able to.

  In this case, the predetermined size cell is preferably a first cell including at least one selected from red blood cells, white blood cells, and bacteria, and a cell larger than the predetermined size cell is a single epithelial cell. A plurality of plate-like portions of the cell discriminating portion, wherein the biological sample passes through the gaps between the plurality of plate-like portions, so that the first cell becomes a gap between the plurality of plate-like portions. And the third cells are captured by the plurality of plate-like portions, and the plurality of second plate-like portions of the second cell discriminating portion allow the third cells to pass through and the epithelial cells aggregate. The fourth cell including the aggregated cells is provided at an interval that does not allow passage of the fourth cell, and the biological sample passes through the gap between the plurality of second plate-like portions, so that the third cell is between the plurality of second plate-like portions. Configured to pass through the gap and be captured by the plurality of second plates. That. If comprised in this way, while being able to discriminate | determine the 3rd cell containing the single cell of an epithelial cell and the 4th cell containing the aggregated cell which the epithelial cell aggregated by the 2nd cell discrimination part, a cell discrimination part By this, the first cell containing at least one selected from erythrocytes, leukocytes and bacteria can be discriminated from the third cell containing a single cell of epithelial cells. 4 cells, a third cell containing a single cell of epithelial cells, and a first cell containing at least one selected from red blood cells, white blood cells and bacteria can be discriminated.

  In the configuration including the second cell discriminating portion, preferably, the plurality of second plate-like portions of the second cell discriminating portion include aggregated cells that allow the third cells to pass therethrough and aggregate three or less epithelial cells. The sample preparation device is further provided with a third cell discriminating unit disposed at an upstream side of the flow of the biological sample from the second cell discriminating unit. A plurality of third plate-like portions provided at intervals that prevent passage of foreign cells larger than the sixth cells and the fifth cells through which the fifth cells pass and the four or more epithelial cells aggregate. And the biological sample passes through the gaps between the plurality of third plate-like parts, so that the fifth cells pass through the gaps between the plurality of third plate-like parts, and the sixth cells and foreign substances are in the plurality of third plates. It is comprised so that it may be caught by the shape part. If comprised in this way, the 5th cell containing the aggregated cell which three or less epithelial cells aggregated by the 3rd cell discrimination part, and the 6th cell containing the aggregated cell which four or more epithelial cells aggregated, and 5th Since foreign substances larger than cells can be further discriminated, foreign substances larger than the sixth cells and fifth cells including aggregated cells in which four or more epithelial cells are aggregated and three or less epithelial cells aggregated A fifth cell containing an aggregated cell, a third cell containing a single epithelial cell, and a first cell containing at least one selected from red blood cells, white blood cells, and bacteria can be discriminated.

  In the sample preparation device according to the first aspect described above, preferably, a sample supply unit that supplies a biological sample to a gap between a plurality of plate-like portions of the cell discriminating unit, and cells captured by the plurality of plate-like portions And a cell recovery unit for recovery. If comprised in this way, the cell in the biological sample supplied from a sample supply part can be discriminated by a cell discriminating part, and the discriminated cell can be collect | recovered by a cell collection | recovery part.

  In this case, preferably, the cell recovery unit supplies the recovery liquid in a direction intersecting the flow direction of the biological sample in the storage container and the cell discrimination unit, so that the cells and the recovery liquid captured by the plurality of plate-shaped parts And a cell transfer section for transferring the sample to the storage container. If comprised in this way, since a collection | recovery liquid can be supplied so that a shear force may be applied with respect to a cell discrimination part, the discriminated cell can be easily separated from a cell discrimination part, As a result, Easily discriminated cells can be transferred together with the recovery liquid to the storage container.

  In the configuration provided with the cell transfer section, preferably, the apparatus further includes a cell discrimination apparatus including a cell discrimination section, and the cell discrimination apparatus receives the biological sample supplied to the sample supply section, and receives the biological sample in the cell discrimination section. A sample introduction unit for introduction, a sample reception unit arranged in the flow direction of the biological sample, for receiving the biological sample that has passed through the gaps between the plurality of plate-like parts, and for taking it out of the cell discrimination device, and cell transfer The recovery liquid supplied by the section is received, and the recovery liquid introduction section for introducing the recovery liquid in a direction crossing the flow direction of the biological sample is disposed in the flow direction of the recovery liquid, and is captured by a plurality of plate-shaped sections. And a collection liquid receiving section for receiving the collected cells and the collection liquid introduced into the collection liquid introduction section and taking them out of the cell discrimination device.

  In the configuration provided with the cell transfer unit, preferably, the sample supply unit supplies the biological sample to the cell discriminating unit together with the storage solution for storing the biological sample, and the cell transfer unit prepares the measurement sample as a recovery solution. It is comprised so that the liquid for sample preparation used for may be supplied. If comprised in this way, a preservation | save liquid can be diluted with the liquid for sample preparation, conveying the discriminated cell to a storage container. Moreover, since the discriminated cell and the sample preparation liquid can be transferred to the container, solution replacement between the storage solution and the sample preparation liquid can be performed.

  The sample preparation device according to the first aspect preferably further includes a cleaning unit that cleans the cell discrimination unit by supplying a cleaning liquid in a direction that intersects the flow direction of the biological sample in the cell discrimination unit. If comprised in this way, since a washing | cleaning liquid can be supplied so that a shear force may be applied with respect to a cell discrimination part, a cell and a foreign material can be easily separated from a cell discrimination part, As a result, it is easy. The cell discrimination part can be washed.

  In the sample preparation device according to the first aspect, preferably, the length of the plate-like portion in the flow direction of the biological sample in the cell discriminating portion is twice or more the interval between the plurality of plate-like portions. If comprised in this way, the mechanical strength in the flow direction of the biological sample of a some plate-shaped part can be raised easily.

  In the sample preparation device according to the first aspect described above, preferably, the plurality of plate-like portions are formed in substantially the same shape, and the plate-like portions are arranged substantially parallel to each other. If comprised in this way, since the magnitude | size of the clearance gap between several plate-shaped parts can be made substantially constant with respect to the flow direction of a biological sample, a cell can be discriminated accurately.

  In the sample preparation device according to the first aspect described above, preferably, the cell discriminating unit is manufactured by forming a plurality of gaps with a predetermined interval on the silicon wafer using dry etching. If comprised in this way, the several plate-shaped part of a cell discrimination part can be manufactured easily and accurately.

  The cell analyzer according to the second aspect of the present invention is a plurality of cells provided at predetermined intervals that allow cells of a predetermined size in a biological sample to pass therethrough and prevent cells larger than the cells of a predetermined size from passing through. The cell discriminating portion including the plate-like portion, and the biological sample passing through the gaps between the plurality of plate-like portions, and captured by the cells passing through the gaps between the plurality of plate-like portions and the plurality of plate-like portions. Detection unit for detecting information on at least one of a predetermined size cell and a cell larger than a predetermined size cell from a measurement sample prepared from at least one of the generated cells and a predetermined reagent And analysis means for analyzing at least one of a cell having a predetermined size and a cell larger than the cell having a predetermined size based on a detection result of the detection unit.

  In the cell analyzer according to the second aspect of the present invention, as described above, cells of a predetermined size in the biological sample are allowed to pass, and cells larger than the cells of the predetermined size are not passed at predetermined intervals. By providing the cell discriminating portion including a plurality of plate-like portions provided in a predetermined manner, it is possible to discriminate between cells having a predetermined size and cells larger than cells having a predetermined size. Further, by providing a plurality of plate-like portions arranged at predetermined intervals in the cell discriminating portion, compared with the case of providing pores in the cell discriminating portion, a member (plate-like portion) between the openings is manufactured. ) Can be easily reduced, so that the aperture ratio can be easily increased. Thereby, since the quantity of the biological sample which passes the cell discrimination part within predetermined time can be increased easily, the processing speed of filtration can be improved easily. Further, by filtering using a plurality of plate-like portions, the thickness (length) in the flow direction of the biological sample can be easily increased as compared with the case where a filter having a small thickness in the flow direction of the biological sample is used. Therefore, the mechanical strength of the cell discriminating part in the flow direction of the biological sample can be easily increased.

  The cell discriminating apparatus according to the third aspect of the present invention is a plurality of cells provided at predetermined intervals that allow cells of a predetermined size in a biological sample to pass therethrough and prevent cells larger than the cells of a predetermined size from passing therethrough. The biological sample passes through the gap between the plurality of plate-like parts, so that the cells of a predetermined size pass through the gaps between the plurality of plate-like parts, and the cells of the predetermined size A cell discriminator configured to capture larger cells in a plurality of plate-like portions.

  In the cell discriminating apparatus according to the third aspect of the present invention, as described above, cells of a predetermined size in the biological sample are allowed to pass, and cells larger than the cells of the predetermined size are not passed at predetermined intervals. By providing the cell discriminating portion including a plurality of plate-like portions provided in a predetermined manner, it is possible to discriminate between cells having a predetermined size and cells larger than cells having a predetermined size. Further, by providing a plurality of plate-like portions arranged at predetermined intervals in the cell discriminating portion, compared with the case of providing pores in the cell discriminating portion, a member (plate-like portion) between the openings is manufactured. ) Can be easily reduced, so that the aperture ratio can be easily increased. Thereby, since the quantity of the biological sample which passes the cell discrimination part within predetermined time can be increased easily, the processing speed of filtration can be improved easily. Further, by filtering using a plurality of plate-like portions, the thickness (length) in the flow direction of the biological sample can be easily increased as compared with the case where a filter having a small thickness in the flow direction of the biological sample is used. Therefore, the mechanical strength of the cell discriminating part in the flow direction of the biological sample can be easily increased.

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

(First embodiment)
FIG. 1 is a perspective view showing a usage state of the cell analyzer according to the first embodiment of the present invention. 2-14 is a figure for demonstrating the structure of the cell analyzer by 1st Embodiment shown in FIG. First, with reference to FIGS. 1-14, the structure of the cell analyzer 1 by 1st Embodiment of this invention is demonstrated.

  As shown in FIG. 1, the cell analyzer 1 according to the first embodiment of the present invention analyzes a measurement device 2 having a function of measuring a cell and measurement data output from the measurement device 2 to obtain an analysis result. The data processing device 3 to be obtained and the sample preparation device 4 for preparing the measurement sample are configured. Further, the cell analyzer 1 uses cervical epithelial cells in a biological sample as an analysis target, and is used for screening cervical cancer. The measuring device 2 is configured to measure epithelial cells of the cervix by flow cytometry. The flow cytometry method is a method of forming a sample flow including a measurement sample and irradiating the sample flow with laser light to generate forward scattered light, side scattered light, and side light emitted from particles in the measurement sample. This is a method for measuring particles that detect fluorescence.

  As shown in FIG. 2, the measurement device 2 controls a detection unit 21 for measuring a measurement sample, an analog processing unit 22 for the output of the detection unit 21, a display / operation unit 23, and the measurement device 2. And a microcomputer unit 24.

  As shown in FIG. 3, the detector 21 emits laser light, a light emitting part 21a, an irradiation lens unit 21b, a sheath flow cell 21c irradiated with the laser light, and the laser light emitted from the light emitting part 21a travels. The condensing lens 21d, the pinhole 21e and the PD (photodiode) 21f arranged on the extension line of the direction, and the condensing lens arranged in a direction intersecting the direction in which the laser light emitted from the light emitting portion 21a travels 21g, a dichroic mirror 21h, an optical filter 21i, a pinhole 21j, an APD (avalanche photodiode) 21k, and a PD 21l disposed on the side of the dichroic mirror 21h.

  The light emitting unit 21a is provided to emit light to the sample flow including the measurement sample passing through the inside of the sheath flow cell 21c. The irradiation lens unit 21b is provided for condensing the light emitted from the light emitting unit 21a onto the measurement sample flowing through the sheath flow cell 21c. Specifically, as shown in FIG. 4, the irradiation lens unit 21b is provided with a collimator lens 211, a plano-convex cylinder lens 212, a biconvex cylinder lens 213, and condenser lenses 214 and 215 in this order from the light emitting unit 21a side. ing. The PD 21f is provided to receive forward scattered light emitted from the sheath flow cell 21c. Note that it is possible to obtain information on the size of the particles in the measurement sample from the forward scattered light emitted from the sheath flow cell 21c.

  The dichroic mirror 21h is provided to separate the side scattered light and the side fluorescence emitted from the sheath flow cell 21c. Specifically, the dichroic mirror 21h is provided to allow the side scattered light emitted from the sheath flow cell 21c to be incident on the PD 21l and to cause the side fluorescence emitted from the sheath flow cell 21c to be incident on the APD 21k. The PD 21l is provided to receive side scattered light. In addition, it is possible to obtain internal information such as the size of the nuclei of the particles in the measurement sample by the side scattered light emitted from the sheath flow cell 21c. The APD 21k is provided for receiving side fluorescence. Information on the degree of staining of particles in the measurement sample can be obtained from the side fluorescence emitted from the sheath flow cell 21c. Each of the PDs 21f and 21l and the APD 21k has a function of converting the received optical signal into an electric signal.

  As shown in FIG. 3, the analog processing unit 22 includes amplifiers 22a, 22b, and 22c. The amplifiers 22a, 22b and 22c are provided for amplifying and waveform processing the electric signals output from the PDs 21f, 21l and APD 21k, respectively.

  As shown in FIG. 2, the microcomputer unit 24 includes a control unit 241 having a control processor and a memory for operating the control processor, and an A / A for converting a signal output from the analog processing unit 22 into a digital signal. A D conversion unit 242 and a calculation unit 243 for performing predetermined processing on the digital signal output from the A / D conversion unit 242 are included.

  The control unit 241 has a function of controlling the detection unit 21 via the bus 244a and the interface 245a. The control unit 241 is connected to the display / operation unit 23 via the bus 244a and the interface 245b, and is connected to the data processing device 3 via the bus 244b and the interface 245c. The calculation unit 243 has a function of outputting a calculation result to the control unit 241 via the interface 245d and the bus 244a. The control unit 241 has a function of transmitting a calculation result (measurement data) to the data processing device 3.

  As shown in FIG. 1, the data processing device 3 is composed of a personal computer (PC) or the like, and has a function of analyzing the measurement data of the measuring device 2 and displaying the analysis result. The data processing device 3 includes a control unit 31, a display unit 32, and an input device 33 as shown in FIG.

  The control unit 31 has a function of transmitting a measurement start signal including measurement mode information and a shutdown signal to the measurement device 2. As shown in FIG. 5, the control unit 31 includes a CPU 31a, a ROM 31b, a RAM 31c, a hard disk 31d, a reading device 31e, an input / output interface 31f, an image output interface 31g, and a communication interface 31i. Has been. The CPU 31a, ROM 31b, RAM 31c, hard disk 31d, reading device 31e, input / output interface 31f, image output interface 31g, and communication interface 31i are connected by a bus 31h.

  The CPU 31a is provided for executing computer programs stored in the ROM 31b and computer programs loaded in the RAM 31c. The ROM 31b is configured by a mask ROM, PROM, EPROM, EEPROM, or the like, and stores a computer program executed by the CPU 31a, data used for the same, and the like.

  The RAM 31c is configured by SRAM, DRAM, or the like. The RAM 31c is used to read out computer programs recorded in the ROM 31b and the hard disk 31d. Further, when these computer programs are executed, they are used as a work area of the CPU 31a.

  The hard disk 31d is installed with various computer programs to be executed by the CPU 31a, such as an operating system and application programs, and data used for executing the computer programs. An application program 34a described later is also installed in the hard disk 31d.

  The reading device 31e is configured by a flexible disk drive, a CD-ROM drive, a DVD-ROM drive, or the like, and can read a computer program or data recorded on the portable recording medium 34. In addition, the portable recording medium 34 stores an application program 34a for causing a computer to realize a predetermined function. The computer as the data processing device 3 is configured to read the application program 34a from the portable recording medium 34 and install the application program 34a in the hard disk 31d.

  The application program 34a is not only provided by the portable recording medium 34, but also from an external device that is communicably connected to the data processing device 3 through an electric communication line (whether wired or wireless). It can also be provided through a communication line. For example, the application program 34a is stored in the hard disk of a server computer on the Internet. The data processing apparatus 3 accesses the server computer to download the application program 34a and install it on the hard disk 31d. Is also possible.

  The hard disk 31d is installed with an operating system that provides a graphical user interface environment such as Windows (registered trademark) manufactured and sold by Microsoft Corporation. In the following description, the application program 34a according to the first embodiment is assumed to operate on the operating system.

  The input / output interface 31f includes, for example, a serial interface such as USB, IEEE1394, RS-232C, a parallel interface such as SCSI, IDE, IEEE1284, and an analog interface including a D / A converter, an A / D converter, and the like. Has been. An input device 33 including a keyboard and a mouse is connected to the input / output interface 31f, and the user can input data to the data processing device 3 by using the input device 33.

  The image output interface 31g is connected to a display unit 32 composed of an LCD or a CRT, and outputs a video signal corresponding to the image data given from the CPU 31a to the display unit 32. The display unit 32 is configured to display an image (screen) according to the input video signal.

  The communication interface 31 i is connected to the measurement device 2 and has a function for receiving measurement data of the measurement device 2. Further, the communication interface 31 i has a function for transmitting a command from the CPU 31 a to the measuring device 2.

  The sample preparation device 4 is provided for preparing a measurement sample used in the detection unit 21 of the measurement device 2. Specifically, the sample preparation device 4 is configured to prepare a measurement sample from a cervical epithelial cell in a biological sample which is a measurement target of the measurement device 2 and a predetermined reagent.

  As shown in FIG. 6, the sample preparation device 4 includes a discrimination unit 41, a sample preparation unit 42 (see FIG. 7), a sample supply unit 43, a first cell recovery unit 44, and a second cell recovery unit 45. The cleaning liquid supply unit 46, the replacement liquid supply unit 47, and the sample setting unit 48 are included. Furthermore, the sample preparation device 4 includes a measurement sample supply unit 49 and a control unit 50 as shown in FIG. Further, the sample preparation device 4 is configured to transfer each liquid in the device using the negative pressure and the positive pressure supplied from the negative pressure source 51 and the positive pressure source 52 of a pneumatic device (not shown). Yes.

  Here, in 1st Embodiment, the discrimination part 41 is provided in order to discriminate | determine the foreign material, such as dust larger than the measurement object cell, other cells, and the measurement object cell other than a cell. As shown in FIGS. 6 and 9, the discriminating unit 41 includes a sample supply unit 411, a biological sample basin unit 412, and a biological sample discharge unit 413. The discriminating unit 41 includes a first liquid supply unit 414a, a second liquid supply unit 414b, a third liquid supply unit 414c, a first liquid recovery unit 415a, a second liquid recovery unit 415b, and a third liquid recovery unit 415c. The first cell discriminating unit 416, the second cell discriminating unit 417, and the third cell discriminating unit 418 are further included.

  The sample supply unit 411 is configured to function as a biological sample inlet when supplying the biological sample to the discrimination unit 41. Further, as shown in FIG. 9, the sample supply unit 411 is formed with a depth D2 (about 800 μm) so as to extend in the flow direction of the biological sample (in the direction of the arrow X1) as seen in a plan view. The sample supply unit 411 is provided at the end of the basin unit 412 on the arrow X2 direction side.

  The basin portion 412 is a region where the biological sample introduced from the sample supply portion 411 flows toward the discharge portion 413. The basin section 412 is connected to the sample supply section 411 as shown in FIG. The basin portion 412 is formed so that the width gradually increases from the end of the sample supply portion 411 on the arrow X1 direction side toward the arrow X1 direction, and the largest width is W1 (about 20 mm). It is formed as follows. Further, the basin portion 412 is formed so that a portion having a width of W1 extends in the directions of the arrows X1 and X2 by a length D1 (about 10 mm). Moreover, the arrow X1 direction side of the basin portion 412 is formed so that the width gradually decreases from W1 in the arrow X1 direction so as to be symmetrical with the arrow X2 direction side. The end of the basin portion 412 on the arrow X1 direction side is connected to the discharge portion 413. Further, the basin part 412 has the same depth D2 (about 800 μm) as the sample supply part 411.

  The discharge unit 413 is configured to function as an outlet for discharging the biological sample from which the epithelial cells have been filtered from the discrimination unit 41. Further, as shown in FIG. 9, the discharge unit 413 extends in the biological sample flow direction (arrow X1 direction) from the end on the arrow X1 direction side of the basin portion 412 as viewed in a plan view. And the same depth D2 (about 800 μm). In addition, a positive pressure source 52 is connected to the discharge unit 413 through an electromagnetic valve 52a, and a drain unit 53 to be described later is connected through an electromagnetic valve 52b.

  The first liquid supply unit 414a, the second liquid supply unit 414b, and the third liquid supply unit 414c each have a basin portion for a cleaning liquid supplied from the cleaning liquid supply unit 46 and a replacement liquid supplied from a replacement liquid supply unit 47 described later. 412 is configured to function as an inlet for supplying to 412. In addition, the cleaning liquid and the replacement liquid supplied from the first liquid supply unit 414a, the second liquid supply unit 414b, and the third liquid supply unit 414c are respectively substantially orthogonal to the flow direction of the biological sample (the direction of the arrow X1) ( In the direction of arrow Y1). Further, as shown in FIG. 9, the first liquid supply unit 414a, the second liquid supply unit 414b, and the third liquid supply unit 414c are respectively side surfaces on the arrow Y2 direction side of the portion having the width W1 of the basin portion 412. It is connected to the. The first liquid supply unit 414a, the second liquid supply unit 414b, and the third liquid supply unit 414c are each in a direction (arrow Y2 direction) orthogonal to the flow direction of the biological sample (arrow X1 direction) when seen in a plan view. ) At the same depth D2 (about 800 μm) as the basin part 412 so as to extend outward from the basin part 412. Further, as shown in FIG. 6, a cleaning liquid supply unit 46 is connected to the first liquid supply unit 414a, the second liquid supply unit 414b, and the third liquid supply unit 414c via electromagnetic valves 46a, 46b, and 46c, respectively. Has been. Further, the replacement liquid supply unit 47 is connected to the first liquid supply unit 414a, the second liquid supply unit 414b, and the third liquid supply unit 414c via electromagnetic valves 47a, 47b, and 47c, respectively.

  The first liquid recovery unit 415a, the second liquid recovery unit 415b, and the third liquid recovery unit 415c flow into the basin unit 412 from the first liquid supply unit 414a, the second liquid supply unit 414b, and the third liquid supply unit 414c, respectively. The washing liquid and the replacement liquid are configured to function as an outlet for allowing the biological sample to flow out from the discrimination unit 41. Further, as shown in FIG. 9, the first liquid recovery part 415a, the second liquid recovery part 415b, and the third liquid recovery part 415c are respectively side surfaces on the arrow Y1 direction side of the portion having the width W1 of the basin part 412. It is connected to the. The first liquid recovery unit 415a, the second liquid recovery unit 415b, and the third liquid recovery unit 415c are each in a direction (arrow Y1 direction) orthogonal to the flow direction of the biological sample (arrow X1 direction) when seen in a plan view. ) At the same depth D2 (about 800 μm) as the basin part 412 so as to extend outward from the basin part 412. Further, as shown in FIG. 6, a drainage unit 53 is connected to the first liquid recovery unit 415a, the second liquid recovery unit 415b, and the third liquid recovery unit 415c via electromagnetic valves 53a, 53b, and 53c, respectively. Has been.

  As shown in FIGS. 9 and 10, the first cell discriminating section 416 has a plurality of plate-like members 416a made of silicon having excellent chemical resistance. The plurality of plate-like members 416a are formed in substantially the same shape and are arranged substantially parallel to each other. Specifically, as shown in FIG. 10, each of the plurality of plate-like members 416a has t1 (about 15 μm) in a direction (arrows Y1 and Y2 directions) orthogonal to the flow direction of the biological sample (arrow X1 direction). It has a thickness. The plurality of plate-like members 416a have the same height h1 (about 800 μm) as the depth D2 of the basin portion 412 in the directions of arrows Z1 and Z2, respectively, and in the biological sample flow direction (arrow X1 direction). It has a length of L1 (about 1000 μm) that is twice or more the interval s1 of a plate-like member 416a described later. Further, the plurality of plate-like members 416a are arranged so that the opening ratio of the first cell discriminating portion 416 is substantially 50%. Specifically, the plurality of plate-like members 416a allow microcells 60 such as red blood cells, white blood cells, and bacteria to pass through in a direction (arrow Y1 and Y2 directions) orthogonal to the flow direction of the biological sample (arrow X1 direction). The cervical epithelial cells are arranged at an interval s1 (about 15 μm) that does not allow the single cell 61 to pass through. Thus, the first cell discriminating unit 416 has a function of discriminating between the micro cell 60 and the single cell 61 when the biological sample is passed. The plurality of plate-like members 416a made of silicon are manufactured by forming the gap s1 in the silicon wafer using dry etching. Accordingly, the thickness t1 of the plate-like member 416a can be easily reduced as compared with the case where the pores are provided by using an electroforming method or the like, and thus the aperture ratio can be easily increased. . The plurality of plate-like members 416a are arranged such that the surface on the arrow X2 direction side is flush with the side surface on the arrow X1 direction side of the first liquid supply unit 414a.

  As shown in FIGS. 9 and 10, the second cell discriminating unit 417 is arranged on the upstream side (arrow X2 direction side) of the flow of the biological sample from the first cell discriminating unit 416. Further, the second cell discriminating portion 417 has a plurality of plate-like members 417a made of silicon having excellent chemical resistance. The plurality of plate-like members 417a are formed in substantially the same shape and are arranged substantially parallel to each other. Specifically, as shown in FIG. 10, each of the plurality of plate-like members 417a has t2 (about 80 μm) in a direction (arrow Y1 and Y2 directions) orthogonal to the flow direction of the biological sample (arrow X1 direction). It has a thickness. The plurality of plate-like members 417a have the same height h2 (about 800 μm) as the depth D2 of the basin portion 412 in the directions of arrows Z1 and Z2, respectively, and in the biological sample flow direction (arrow X1 direction). It has a length of L2 (about 1000 μm) that is at least twice as large as the interval s2 of the plate-like member 417a described later. In addition, the plurality of plate-like members 417a are arranged so that the opening ratio of the second cell discriminating portion 417 is substantially 50%. Specifically, the plurality of plate-like members 417a pass through the single cell 61 of the cervical epithelial cell in a direction (arrow Y1 and Y2 direction) orthogonal to the flow direction of the biological sample (arrow X1 direction). In addition, two or three cervical epithelial cells are arranged at an interval s2 (about 80 μm) that prevents the aggregated first aggregated cells 62 from passing therethrough. Accordingly, the second cell discriminating unit 417 has a function of discriminating between the single cells 61 and the first aggregated cells 62 when the biological sample is passed. The plurality of plate-like members 417a made of silicon are manufactured by forming the gap s2 in the silicon wafer using dry etching. As a result, the thickness t2 of the plate-like member 417a can be easily reduced as compared with the case where the pores are provided by using an electroforming method or the like, so that the aperture ratio can be easily increased. . The plurality of plate-like members 417a are arranged such that the surface on the arrow X2 direction side is flush with the side surface on the arrow X1 direction side of the second liquid supply unit 414b.

  As shown in FIGS. 9 and 10, the third cell discriminating unit 418 is arranged on the upstream side (arrow X2 direction side) of the flow of the biological sample from the second cell discriminating unit 417. Further, the third cell discriminating portion 418 has a plurality of plate-like members 418a made of silicon having excellent chemical resistance. The plurality of plate-like members 418a are formed in substantially the same shape and are arranged substantially parallel to each other. Specifically, as shown in FIG. 10, each of the plurality of plate-like members 418a has t3 (about 120 μm) in a direction (arrows Y1 and Y2 directions) orthogonal to the flow direction of the biological sample (arrow X1 direction). It has a thickness. The plurality of plate-like members 418a have the same height h3 (about 800 μm) as the depth D2 of the basin portion 412 in the directions of arrows Z1 and Z2, respectively, and in the biological sample flow direction (arrow X1 direction). It has a length of L3 (about 1000 μm) that is twice or more the interval s3 of a plate-like member 418a described later. Further, the plurality of plate-like members 418a are arranged so that the opening ratio of the third cell discriminating portion 418 is substantially 50%. Specifically, the plurality of plate-like members 418a aggregate two or three cervical epithelial cells in a direction (arrows Y1 and Y2) orthogonal to the flow direction of the biological sample (arrow X1 direction). The first aggregated cells 62 are allowed to pass through, and the second aggregated cells 63 in which four or more cervical epithelial cells have aggregated and the foreign matter 64 other than the cells are arranged at an interval s3 (about 120 μm). . Thus, the third cell discriminating unit 418 has a function of discriminating the first aggregated cells 62 from the second aggregated cells 63 and the foreign matter 64 other than the cells when the biological sample is passed. The plurality of plate-like members 418a made of silicon are manufactured by forming the gap s3 in the silicon wafer using dry etching. As a result, the thickness t3 of the plate-like member 418a can be easily reduced as compared with the case where pores are provided by using an electroforming method or the like, so that the aperture ratio can be easily increased. . The plurality of plate-like members 418a are arranged such that the surface on the arrow X2 direction side is flush with the side surface on the arrow X1 direction side of the third liquid supply unit 414c.

  As shown in FIGS. 9 and 11, the discriminating unit 41 includes a sample supply unit 411, a biological sample basin unit 412, a biological sample discharge unit 413, liquid supply units 414a to 414c, and liquid recovery units 415a to 415c. An upper glass plate 419a (see FIG. 11) and a lower glass plate 419b are arranged so as to close the whole from the vertical direction (arrow Z1 and Z2 direction side). The plurality of plate-like members 416a to 418a are supported so as to be sandwiched between the upper glass plate 419a and the lower glass plate 419b from the vertical direction (arrow Z1 and Z2 directions), respectively.

  With the above configuration, as shown in FIG. 9, the discriminating unit 41 captures the second aggregated cells 63 and the foreign matter 64 other than the cells in the region on the arrow X2 direction side of the third cell discriminating unit 418 of the basin unit 412. It is possible. In addition, the discriminating unit 41 can capture the first aggregated cells 62 in a region between the third cell discriminating unit 418 and the second cell discriminating unit 417 of the basin unit 412. Further, the discriminating unit 41 can capture the single cell 61 of the cervical epithelial cell in a region between the second cell discriminating unit 417 and the first cell discriminating unit 416 of the basin unit 412.

  The sample preparation unit 42 is provided to supply each of a staining solution for staining DNA and an RNase for performing RNA treatment on cells to a concentrated solution in which cells to be measured are concentrated. Specifically, as shown in FIG. 7, the sample preparation unit 42 sets the staining liquid quantified by the syringe pump 422 from the staining tank 421 installed in the sample preparation device 4 in the sample setting unit 48. It is configured to be supplied via a pipette 423 to a cuvette 70 that contains the concentrated liquid after filtration. In addition, the sample preparation unit 42 supplies the RNase quantified by the syringe pump 425 from the RNase tank 424 installed in the sample preparation device 4 to the cuvette 70 that stores the concentrated liquid after the filtration process through the pipette 423. It is configured. The staining liquid tank 421 and the syringe pump 422 are connected via an electromagnetic valve 426, and the RNase tank 424 and the syringe pump 425 are connected via an electromagnetic valve 427. Moreover, the syringe pump 422 and the syringe pump 425 are each configured to be driven by a stepping motor.

  The sample supply unit 43 is configured to hold the biological sample before being filtered by the discrimination unit 41 and to supply the biological sample before the filtration process to the discrimination unit 41. Further, as shown in FIG. 6, the sample supply unit 43 includes a sample holding unit 431 that stores a biological sample before filtration, and the sample holding unit 431 is a sample of the discriminating unit 41 via an electromagnetic valve 432. It is connected to the supply unit 411. Further, the sample holder 431 is connected to a drainage unit 53 described later via an electromagnetic valve 433. The sample holding unit 431 is connected to the cleaning liquid supply unit 46 via the electromagnetic valve 434 and is connected to the replacement liquid supply unit 47 via the electromagnetic valve 435. Further, the sample holder 431 is connected to the negative pressure source 51 via the electromagnetic valve 436 and is connected to the positive pressure source 52 via the electromagnetic valve 437. The sample holder 431 is connected to the sample pipette 483 via the electromagnetic valve 438. Further, the biological sample in the sample supply unit 43 is accommodated together with a storage solution made of methanol as described later, and the biological sample is transferred from the sample holding unit 431 to the sample supply unit 411 of the discrimination unit 41 together with the storage solution. The

  The first cell recovery unit 44 captures the single cell 61 of the cervical epithelial cell captured in the region between the second cell discrimination unit 417 and the first cell discrimination unit 416 of the basin unit 412 of the discrimination unit 41. It is provided for recovery. As shown in FIG. 6, the first cell collection unit 44 includes a first storage container 441, a first collection pipette 442, and a syringe pump 443. The first container 441 is connected to the first liquid recovery unit 415a of the discrimination unit 41 via the electromagnetic valve 444. Further, the first storage container 441 is connected to the cleaning liquid supply unit 46 via the electromagnetic valve 445 and is connected to the drainage unit 53 via the electromagnetic valve 446. The first container 441 accommodates a single cell 61 of epithelial cells of the cervix together with a replacement liquid described later. The first container 441 is open to the atmosphere. Further, the first recovery pipette 442 has a function of sucking the replacement liquid stored in the first storage container 441 and the single cell 61 of the cervix epithelial cells by the liquid amount determined by the syringe pump 443. ing. The first recovery pipette 442 is configured to discharge the sample sucked from the first storage container 441 to the cuvette 70 set in the sample setting unit 48. Further, the first recovery pipette 442 is configured to be moved from the suction position in the first storage container 441 to the discharge position to the cuvette 70 by the first recovery pipette driving unit 447 shown in FIG. The syringe pump 443 is connected to the cleaning liquid supply unit 46 via an electromagnetic valve 448 and is configured to be driven by a stepping motor.

  The second cell collection unit 45 has two or three cervical epithelial cells captured in a region between the third cell discrimination unit 418 and the second cell discrimination unit 417 of the basin unit 412 of the discrimination unit 41. It is provided for collecting the aggregated first aggregated cells 62. As shown in FIG. 6, the second cell collection unit 45 includes a second storage container 451, a second collection pipette 452, and a syringe pump 453. The second storage container 451 stores the first aggregated cells 62 together with a replacement liquid described later. Moreover, since the 2nd cell collection | recovery part 45 is the same as that of the structure of the above-mentioned 1st cell collection | recovery part 44, description is abbreviate | omitted. The second storage container 451, the second recovery pipette 452, and the syringe pump 453 of the second cell recovery unit 45 are the first storage container 441, the first recovery pipette 442, and the syringe pump 443 of the first cell recovery unit 44, respectively. It corresponds to. In addition, the electromagnetic valve 454, the electromagnetic valve 455, the electromagnetic valve 456, the second recovery pipette driving unit 457, and the electromagnetic valve 458 of the second cell recovery unit 45 are the electromagnetic valve 444 and the electromagnetic valve 445 of the first cell recovery unit 44, respectively. , Corresponding to the electromagnetic valve 446, the first recovery pipette drive unit 447 and the electromagnetic valve 448.

  The cleaning liquid supply unit 46 has a function of supplying the cleaning liquid to each part of the sample preparation device 4. Further, as shown in FIG. 12, the cleaning liquid supply unit 46 has a cleaning liquid tank 461 for storing a cleaning liquid made of hypochlorous acid or the like, and the cleaning liquid tank 461 is connected to each part of the sample preparation device 4 via an electromagnetic valve. It is connected. The cleaning liquid tank 461 is connected to the negative pressure source 51 via the electromagnetic valve 462 and is connected to the positive pressure source 52 via the electromagnetic valve 463. The cleaning liquid tank 461 is connected to a cleaning liquid storage tank outside the apparatus via an electromagnetic valve 464.

  The replacement liquid supply unit 47 includes a first liquid supply unit 414a, a second liquid supply unit 414b, and a third liquid supply unit 414c of the discrimination unit 41. The replacement liquid includes a pH adjuster, a DNase deactivator, and a surfactant. It has the function to supply. Further, as shown in FIG. 13, the replacement liquid supply unit 47 includes a replacement liquid tank 471, and the replacement liquid tank 471 is connected to each part of the sample preparation device 4 through each electromagnetic valve. The replacement liquid tank 471 is connected to the negative pressure source 51 via the electromagnetic valve 472 and is connected to the positive pressure source 52 via the electromagnetic valve 473. The replacement liquid tank 471 is connected to a replacement liquid storage tank outside the apparatus via an electromagnetic valve 474.

  As shown in FIG. 1, the specimen setting unit 48 holds a cuvette 70 and a biological container 71 that stores a biological sample before the filtration process, and also sucks the biological sample before the filtration process from the biological container 71 to provide a sample holding unit. 431 has a function of transferring to 431. Specifically, the sample setting unit 48 includes a rotary table 481 that holds the cuvette 70 and the biological container 71, a stepping motor 482 (see FIGS. 6 and 8) for rotating the rotary table 481, and a sample pipette 483. (See FIG. 6). The rotary table 481 has a function of heating the liquid in the cuvette 70 and the biological container 71 to be held at about 40 ° C. The sample pipette 483 is configured to be movable in the vertical direction by the sample pipette driving unit 484, and the sample setting unit 48 uses the sample pipette 483 to aspirate a biological sample before filtration from the biological container 71. It is configured to be transferred to the holding unit 431. The specimen setting unit 48 further includes a cell dispersion unit (not shown), and is configured to disperse cells by stirring a biological sample to which a storage solution made of methanol is added in the biological container 71 by the cell dispersion unit. ing.

  As shown in FIG. 8, the measurement sample supply unit 49 has a function of transferring the measurement sample that has been subjected to DNA staining and RNA processing by the sample preparation unit 42 to the detection unit 21 of the measurement apparatus 2.

  As shown in FIG. 8, the control unit 50 is connected to the interface 245a of the measurement apparatus 2 through the interface 50a, and also the sample preparation apparatus 4 through the I / O (Input / Output) unit 50b and each circuit. Connected to each part of

  As shown in FIG. 14, the drainage unit 53 is provided to discharge the liquid transferred from each unit of the sample preparation device 4 to the outside of the device. The drainage unit 53 includes a drainage tank 531 that stores liquid transferred from each unit of the sample preparation device 4, and the drainage tank 531 discharges the liquid to the outside of the sample preparation device 4 via the electromagnetic valve 532. Is configured to do. The drain tank 531 is connected to the negative pressure source 51 via the electromagnetic valve 533 and is connected to the positive pressure source 52 via the electromagnetic valve 534.

  FIG. 15 is a flowchart for explaining the analysis processing operation of the cell analyzer according to the first embodiment shown in FIG. Next, with reference to FIG. 6 and FIG. 15, an analysis processing operation of the cell analyzer according to the first embodiment of the present invention will be described.

  First, in step S1 of FIG. 15, the data processing device 3 is initialized, and in step S2, a menu screen (not shown) for accepting a measurement start instruction is displayed on the display unit 32. In step S3, the CPU 31a determines whether or not a measurement start instruction has been accepted. If not, the process proceeds to step S8. On the other hand, when a measurement start instruction is accepted, a signal for starting measurement is transmitted to the measurement apparatus 2 in step S4.

  In the measuring apparatus 2, after initialization is performed in step S <b> 11, in step S <b> 12, the control unit 241 determines whether a signal for starting measurement is received from the data processing apparatus 3. If no measurement start signal is received, the process proceeds to step S17. If a measurement start signal is received, a signal for preparing a measurement sample is transmitted to the sample preparation device 4 in step S13. .

  In the sample preparation device 4, after initialization is performed in step S <b> 21, in step S <b> 22, the control unit 50 determines whether a signal for preparing a measurement sample is received from the measurement device 2. When the measurement sample preparation signal is not received, the process proceeds to step S31. When the measurement sample preparation signal is received, the cells in the biological container 71 are dispersed in step S23. Specifically, after the preservation solution is added to the biological sample before the filtration treatment in the biological container 71 set on the rotary table 481 of the specimen setting unit 48, the cell dispersion unit (not shown) stores the biological sample in the biological sample. Cells are dispersed. Thereafter, in step S 24, the biological sample stored in the biological container 71 is aspirated by the sample pipette 483 and transferred to the sample holding unit 431. In step S25, discrimination / replacement processing is performed.

  FIG. 16 is a flowchart for explaining the discrimination / replacement processing operation in step S25 of the analysis processing operation shown in FIG. Here, the discrimination / replacement processing operation in step S25 of the analysis processing operation shown in FIG. 15 will be described with reference to FIGS.

  First, in step S251 of FIG. 16, the biological sample is sent to the discriminating unit 41 together with the storage solution. Specifically, the sample holding unit 411 is opened by opening the electromagnetic valve 432 between the sample supply unit 411 and the sample holding unit 431 and the electromagnetic valve 437 between the sample holding unit 431 and the positive pressure source 52 as shown in FIG. The biological sample stored in the unit 431 is transferred to the sample supply unit 411 of the discrimination unit 41 together with the storage solution. Then, the biological sample passes through the third cell discriminating unit 418, the second cell discriminating unit 417, and the first cell discriminating unit 416 sequentially from the upstream side in the direction of the arrow X1. As a result, the third cell discriminating unit 418 captures the second aggregated cells 63 in which four or more cervical epithelial cells aggregate and the foreign substance 64 other than the cells, and the second cell discriminating unit 417 captures two or The first aggregated cells 62 obtained by aggregating three cervical epithelial cells are captured. In the first cell discriminating unit 416, a single cell 61 of the cervical epithelial cell is captured.

  In step S252, the control unit 50 sets n = 1. Here, n is a real number starting from 1. Thereafter, in step S253, the electromagnetic valve 52a between the discharge unit 413 and the positive pressure source 52, the electromagnetic valve 432 between the sample supply unit 411 and the sample holding unit 431, and the sample holding unit 431 and the negative pressure source 51 When the electromagnetic valve 436 is opened, a positive pressure is instantaneously applied (about 0.1 second) from the downstream side to the upstream side of the biological sample flow (toward the arrow X2 direction). . As a result, the cells and foreign matter sandwiched between the gaps of the first cell discriminating unit 416, the second cell discriminating unit 417, and the third cell discriminating unit 418 are pushed back to the upstream side of each cell discriminating unit. By the supply operation of the replacement liquid, the trapped cells and foreign substances are easily flowed in the direction (arrow Y1 direction) perpendicular to the flow direction of the biological sample (arrow X1 direction).

  Next, in step S254, the replacement liquid is supplied in a direction (arrow Y1 direction) orthogonal to the flow direction of the biological sample (arrow X1 direction). Specifically, the electromagnetic valve 47c between the replacement liquid supply part 47 and the third liquid supply part 414c, the electromagnetic valve 53c between the third liquid recovery part 415c and the drainage part 53, and the replacement liquid shown in FIG. By opening the electromagnetic valve 473 between the tank 471 and the positive pressure source 52, the replacement liquid is supplied to the third liquid supply unit 414c. Then, the supplied replacement liquid flows in the arrow Y1 direction through the region on the arrow X2 direction side of the third cell discriminating part 418 in the flow area part 412 of the discriminating part 41. Thereby, the second aggregated cells 63 and the foreign matter 64 other than the cells captured by the third cell discriminating unit 418 are pushed away by the replacement liquid and transferred to the drainage unit 53.

  Further, the electromagnetic valve 47b between the replacement liquid supply part 47 and the second liquid supply part 414b, the electromagnetic valve 454 between the second liquid recovery part 415b and the second storage container 451, and the replacement liquid tank 471 shown in FIG. When the electromagnetic valve 473 between the positive pressure source 52 and the positive pressure source 52 is opened, the replacement liquid is supplied to the second liquid supply unit 414b. Then, the supplied replacement liquid flows in the direction of the arrow Y1 through the region between the second cell discriminating part 417 and the third cell discriminating part 418 in the flow area 412 of the discriminating part 41. Thereby, the first aggregated cells 62 captured by the second cell discriminating unit 417 are pushed away by the replacement liquid and transferred to the second storage container 451. At this time, the preservation solution supplied together with the biological sample is diluted to a predetermined concentration with the replacement solution. That is, by supplying the replacement liquid, it is possible to transfer the captured first aggregated cells 62 to the second storage container 451 while diluting the storage liquid to a predetermined concentration. Further, since the captured first aggregated cells 62 and the replacement solution can be transferred to the second storage container 451, solution replacement between the storage solution and the replacement solution can be performed.

  Further, the electromagnetic valve 47a between the replacement liquid supply part 47 and the first liquid supply part 414a, the electromagnetic valve 444 between the first liquid recovery part 415a and the first storage container 441, and the replacement liquid tank 471 shown in FIG. When the electromagnetic valve 473 between the positive pressure source 52 and the positive pressure source 52 is opened, the replacement liquid is supplied to the first liquid supply unit 414a. Then, the supplied replacement liquid flows in the direction of the arrow Y1 through the region between the first cell discriminating unit 416 and the second cell discriminating unit 417 in the flow area 412 of the discriminating unit 41. Thereby, the single cell 61 of the epithelial cell of the cervix captured by the first cell discriminating unit 416 is pushed away by the replacement liquid and transferred to the first storage container 441. At this time, the preservation solution supplied together with the biological sample is diluted to a predetermined concentration with the replacement solution. That is, by supplying the replacement liquid, it is possible to transfer the captured single cells 61 of the cervical epithelial cells to the first storage container 441 while diluting the preservation liquid to a predetermined concentration. In addition, since the captured single cells 61 of the epithelial cells and the replacement solution can be transferred to the first container 441, solution replacement between the storage solution and the replacement solution can be performed.

  In step S255, the control unit 50 determines whether or not n is larger than 1. If it is larger, the discrimination / replacement processing operation is terminated as it is. On the other hand, if n is not larger than 1, in step S256, the controller 50 sets n = n + 1 (1 is incremented by n), and the operations in steps S253 to 255 are executed again.

  After the discrimination / replacement processing operation in step S25 of FIG. 15 is executed, in step S26, the single cells 61 of the cervical epithelial cells stored in the first storage container 441 shown in FIG. Aspirated by pipette 442. Then, the aspirated concentrated liquid is discharged to the cuvette 70 held on the rotary table 481 of the sample setting unit 48. Also in the second cell recovery unit 45, the concentrated solution of the first aggregated cells 62 in which two or three cervical epithelial cells stored in the second storage container 451 are aggregated by the second recovery pipette 452. Sucked. Then, the aspirated concentrated liquid is discharged to the cuvette 70 held on the rotary table 481 of the sample setting unit 48. Thereafter, in step S27, a cleaning process is performed.

  FIG. 17 is a flowchart for explaining the cleaning processing operation in step S27 of the analysis processing operation shown in FIG. Here, the cleaning processing operation in step S27 of the analysis processing operation shown in FIG. 15 will be described with reference to FIG. 6, FIG. 12, and FIG.

  First, in step S271 in FIG. 17, the controller 50 sets n = 1. Here, n is a real number starting from 1. Thereafter, in step S272, the electromagnetic valve 52a between the discharge unit 413 and the positive pressure source 52, the electromagnetic valve 432 between the sample supply unit 411 and the sample holding unit 431, and the negative pressure with the sample holding unit 431 shown in FIG. By opening the electromagnetic valve 436 to and from the source 51, the positive pressure is instantaneous (about 0.1 second) from the downstream side to the upstream side of the biological sample flow (in the direction of the arrow X2). To be applied. As a result, the cells and foreign matter sandwiched between the gaps of the first cell discriminating unit 416, the second cell discriminating unit 417, and the third cell discriminating unit 418 are pushed back to the upstream side of each cell discriminating unit. By the operation of supplying the cleaning liquid, the trapped cells and foreign substances are easily flowed in the direction (arrow Y1 direction) orthogonal to the flow direction of the biological sample (arrow X1 direction).

  Next, in step S273, the cleaning liquid is supplied in a direction (arrow Y1 direction) orthogonal to the flow direction of the biological sample (arrow X1 direction). Specifically, the electromagnetic valve 46c between the cleaning liquid supply unit 46 and the third liquid supply unit 414c, the electromagnetic valve 53c between the third liquid recovery unit 415c and the drainage unit 53, and the cleaning liquid tank 461 shown in FIG. When the electromagnetic valve 463 between the positive pressure source 52 and the positive pressure source 52 is opened, the cleaning liquid is supplied to the third liquid supply unit 414c. Then, the supplied cleaning liquid flows in the arrow Y1 direction through the region on the arrow X2 direction side of the third cell discriminating part 418 in the flow area part 412 of the discriminating part 41. Thereby, the second aggregated cells 63 and the foreign matter 64 other than the cells remaining in the region on the arrow X2 direction side of the third cell discriminating portion 418 in the basin portion 412 are pushed away by the cleaning liquid and transferred to the drainage portion 53. .

  Further, the electromagnetic valve 46b between the cleaning liquid supply unit 46 and the second liquid supply unit 414b, the electromagnetic valve 53b between the second liquid recovery unit 415b and the drainage unit 53, and the cleaning liquid tank 461 shown in FIG. By opening the electromagnetic valve 463 to and from the source 52, the cleaning liquid is supplied to the second liquid supply unit 414b. And the supplied washing | cleaning liquid flows through the area | region between the 2nd cell discrimination part 417 and the 3rd cell discrimination part 418 in the flow area part 412 of the discrimination part 41, and flows into the arrow Y1 direction. As a result, the first aggregated cells 62 remaining in the region between the second cell discriminating portion 417 and the third cell discriminating portion 418 in the basin portion 412 are pushed away by the washing liquid and transferred to the drainage portion 53.

  Further, the electromagnetic valve 46a between the cleaning liquid supply section 46 and the first liquid supply section 414a, the electromagnetic valve 53a between the first liquid recovery section 415a and the drainage section 53, and the cleaning liquid tank 461 shown in FIG. By opening the electromagnetic valve 463 with the source 52, the cleaning liquid is supplied to the first liquid supply unit 414a. And the supplied washing | cleaning liquid flows through the area | region between the 1st cell discrimination part 416 and the 2nd cell discrimination part 417 in the flow area part 412 of the discrimination part 41, and flows into the arrow Y1 direction. Thereby, the single cells 61 of the cervical epithelial cells remaining in the region between the first cell discriminating part 416 and the second cell discriminating part 417 in the basin part 412 are washed away by the washing liquid, and the drainage part 53 It is transferred to.

  As described above, the discriminating unit 41 and each flow path are cleaned by the supply operation of the cleaning liquid, so that biological samples collected from different subjects are prevented from being mixed with each other.

  In step S274, the control unit 50 determines whether n is larger than 1. If it is larger, the cleaning processing operation is terminated as it is. On the other hand, if n is not greater than 1, in step S275, the controller 50 sets n = n + 1 (increments 1 to n), and the operations in steps S272 to 274 are executed again.

  After the washing process operation in step S27 of FIG. 15 is executed, in step S28, the sample preparation unit 42 supplies the staining solution and the RNase to the cuvette 70 that stores the concentrated solution. In step S29, heating is performed for a predetermined time by the rotary table 481, and DNA staining and RNA processing are performed. Thereafter, in step S30, the measurement sample that has been subjected to DNA staining and RNA processing is sent to the detection unit 21 of the measurement apparatus 2 by the measurement sample supply unit 49.

  In the measuring apparatus 2, it is determined whether or not the measurement sample is supplied in step S14, and this determination is repeated until it is supplied. When the measurement sample is supplied, measurement is performed in step S15, and measurement data is transmitted to the data processing device 3 via the interface 245c in step S16.

  In step S5, the data processing device 3 determines whether or not measurement data has been received, and this determination is repeated until it is received. When the measurement data is received, the analysis is performed based on the measurement data in step S6, and the analysis result is displayed on the display unit 32 in step S7. Then, in step S8, it is determined whether or not there is a shutdown instruction. If there is no instruction, the process proceeds to step S3. If there is a shutdown instruction, a shutdown instruction signal is transmitted to the measuring apparatus 2 in step S9, and the analysis processing operation in the data processing apparatus 3 is terminated.

  In step S17, the measuring apparatus 2 determines whether or not a shutdown instruction signal is received from the data processing apparatus 3. If there is no shutdown instruction, the process proceeds to step S12. On the other hand, when a shutdown instruction is received, a shutdown instruction signal is transmitted to the sample preparation device 4 in step S18. In step S19, the shutdown is executed, and the analysis processing operation in the measuring device 2 is ended.

  In step S31, the sample preparation apparatus 4 determines whether or not a shutdown instruction signal is received from the measurement apparatus 2. If there is no shutdown instruction, the process proceeds to step S22. On the other hand, when the shutdown instruction is received, the shutdown is executed in step S32, and the analysis processing operation in the sample preparation device 4 is ended.

  In the first embodiment, as described above, the cell discriminating units 416 to 418 are provided with a plurality of plate-like members 416a to 418a arranged at predetermined intervals s1 to s3 in the cell discriminating units 416 to 418. Compared with the case where pores are provided, the thickness of the members (plate-like members 416a to 418a) between the openings can be easily reduced in manufacturing, so that the aperture ratio can be easily increased. Thereby, since the quantity of the biological sample which passes the cell discrimination part 416-418 within predetermined time can be increased easily, the processing speed of filtration can be improved easily. In addition, by filtering using a plurality of plate-like members 416a to 418a, the thickness (length) L1 to L3 in the flow direction of the biological sample is reduced as compared with the case where a filter having a small thickness in the flow direction of the biological sample is used. Since it can be enlarged easily, the mechanical strength of the cell discriminators 416 to 418 in the flow direction of the biological sample can be easily increased.

  Further, in the first embodiment, the first cell discriminating unit 416 that allows microcells 60 such as red blood cells, white blood cells, and bacteria to pass therethrough but does not pass the single cell 61 of the cervical epithelial cells, and the cervical epithelial cells. A second cell discriminator 417 that passes a single cell 61 but does not pass a first aggregated cell 62 in which two or three cervical epithelial cells have aggregated; and two or three cervical epithelial cells By providing a second aggregated cell 63 in which four or more cervical epithelial cells have aggregated and a third cell discriminator 418 that does not allow the passage of foreign substances 64 other than the cells. A second aggregated cell 63 in which four or more cervical epithelial cells aggregate and a foreign substance 64 other than the cells; a first aggregated cell 62 in which two or three cervical epithelial cells aggregate; and the cervix Of epithelial cells It can be discriminated as one cell 61, red blood cells, and a micro cell 60, such as white blood cells and bacteria.

  Further, in the first embodiment, the replacement liquid is supplied in a direction (arrow Y1 direction) that intersects with the storage containers 441 and 451 and the flow direction of the biological sample (arrow X1 direction). The first cell discriminating unit is provided by providing the replacement liquid supply unit 47 that transfers the replacement liquid and at least one of the size cells and the cells larger than the predetermined size cell to the storage containers 441 and 451. 416 and the second cell discriminating portion 417 can be supplied with a replacement liquid so as to apply a shearing force, so that the discriminated cells can be easily separated from the plurality of plate-like members 416a to 418a, As a result, easily discriminated cells can be transferred to the storage containers 441 and 451 together with the replacement liquid.

  In the first embodiment, the biological sample is supplied to the discriminating unit 41 together with the storage solution for storing the biological sample, and the replacement liquid used for the preparation of the measurement sample is supplied as the recovery liquid. While the discriminated cells are transferred to the storage containers 441 and 451, the preservation solution can be diluted with a replacement solution. Moreover, since the discriminated cell and the replacement solution can be transferred to the storage containers 441 and 451, solution replacement between the storage solution and the replacement solution can be performed.

  Moreover, in 1st Embodiment, by providing the washing | cleaning liquid supply part 46 which wash | cleans the discrimination part 41 by supplying a washing | cleaning liquid in the direction which cross | intersects the flow direction of a biological sample, with respect to the cell discrimination parts 416-418. Since the cleaning liquid can be supplied so as to apply a shearing force, the cells and foreign matters can be easily separated from the plurality of plate-like members 416a to 418a, and as a result, the discriminating portion 41 can be easily cleaned. Can do.

  In the first embodiment, the lengths L1 to L3 of the plate members 416a to 418a in the flow direction of the biological sample (arrow X1 direction) are set to be twice or more the intervals s1 to s3 between the plurality of plate portions. Thus, the mechanical strength in the flow direction of the biological sample of the plurality of plate-like members 416a to 418a can be easily increased.

  Moreover, in 1st Embodiment, since the plate-shaped members 416a-418a of the cell discrimination parts 416-418 are formed using the silicon | silicone which is excellent in chemical resistance, the choice of a washing | cleaning liquid can be expanded. Therefore, it is possible to use a cleaning solution having a strong cleaning power, and it is possible to more effectively prevent biological samples collected from different subjects from being mixed with each other.

(Second Embodiment)
FIG. 18 is a perspective view showing a discriminator of the cell analyzer according to the second embodiment of the present invention. 19-21 is a figure for demonstrating the structure of the discrimination part of the cell analyzer by 2nd Embodiment shown in FIG. Next, referring to FIG. 18 to FIG. 21, in the second embodiment, unlike the first embodiment, the second cell discriminating part 417 and the third cell discriminating part 418 are not provided, but the first cell discrimination is performed. The configuration of the discriminator 141 provided with only the part 416b will be described.

  The discriminating unit 141 according to the second embodiment is provided to discriminate between the measurement target cell and other cells. As shown in FIGS. 18 to 20, the discrimination unit 141 includes a sample supply unit 411a, a biological sample basin unit 412a (see FIGS. 19 and 20), and a biological sample discharge unit 413a. Yes. The discrimination unit 141 further includes a first liquid recovery unit 415d and a first cell discrimination unit 416b.

  The sample supply unit 411a is configured to function as an input port for the biological sample when supplying the biological sample to the discrimination unit 141. Moreover, the sample supply part 411a is formed so that it may penetrate the upper side glass plate 419c to a perpendicular direction (arrow Z1 and Z2 direction), as shown in FIGS. Further, as shown in FIG. 19, the sample supply unit 411a is provided on the upper glass plate 419c at the end on the arrow Y4 direction side on the arrow X4 direction side of the basin portion 412a as seen in a plan view. In addition, a sample holding unit 431 is connected to the sample supply unit 411a via an electromagnetic valve 432.

  The basin portion 412a is formed on each of the upper glass plate 419c and the lower glass plate 419d. In addition, the basin portion 412a is a region where the biological sample flowing in from the sample supply portion 411a flows toward the discharge portion 413a or the first liquid recovery portion 415d. Further, the basin portion 412a in the upper glass plate 419c is connected to each of the sample supply portion 411a and the first liquid recovery portion 415d. Specifically, the basin portion 412a of the upper glass plate 419c has a U shape in plan view, and is connected to the sample supply portion 411a and the first liquid recovery portion 415d at both ends thereof. Yes. Further, the flow area 412a of the upper glass plate 419c has a width W2 (about 800 μm) in the narrowest portion in the directions of the arrows X3 and X4. Further, the flow area 412a of the upper glass plate 419c is formed with a depth D4 (about 500 μm) over the distance D3 (about 20 mm) in the directions of the arrows Y3 and Y4.

  Moreover, the basin part 412a in the lower glass plate 419d is connected to the discharge part 413a. Specifically, the basin portion 412a of the lower glass plate 419d has an inverted L shape when seen in a plan view, and is connected to the discharge portion 413a at the terminal portion. Further, the flow area 412a of the lower glass plate 419d has a width W3 (about 800 μm) in the narrowest portion in the directions of the arrows X3 and X4. Further, the flow area 412a of the lower glass plate 419d is formed with a depth D6 (about 500 μm) over the distance D5 (about 20 mm) in the directions of the arrows Y3 and Y4.

  The discharge part 413a is configured to function as an outlet for discharging the biological sample from which the epithelial cells have been filtered from the discrimination part 141. Moreover, the discharge part 413a is formed so that it may penetrate the lower glass plate 419d in the vertical direction (arrow Z1 and Z2 directions) as shown in FIGS. Further, as shown in FIG. 19, the discharge portion 413a is provided at the end on the arrow Y4 direction side on the arrow X4 direction side of the basin portion 412a in the lower glass plate 419d as viewed in a plan view. Further, a positive pressure source 52 is connected to the discharge part 413a via an electromagnetic valve 52a, and a drain part 53 is connected via an electromagnetic valve 53d.

  The first liquid recovery unit 415d is configured to function as an outlet for allowing the cleaning liquid, the replacement liquid, and the biological sample flowing into the flow area 412a from the sample supply unit 411a to flow out of the discrimination unit 141. Further, as shown in FIGS. 18 to 20, the first liquid recovery part 415d is formed so as to penetrate the upper glass plate 419c in the vertical direction (arrow Z1 and Z2 directions). Further, as shown in FIG. 19, the first liquid recovery unit 415d is provided at the end on the arrow Y3 direction side on the arrow X4 direction side of the basin portion 412a in the upper glass plate 419c as viewed in a plan view. . In addition, a drainage unit 53 is connected to the first liquid recovery unit 415d through an electromagnetic valve 53a, and a first container 441 is connected through an electromagnetic valve 444.

  As shown in FIGS. 19 and 20, the first cell discriminating portion 416b has a plurality of plate-like members 416c made of silicon having excellent chemical resistance. As shown in FIG. 20, each of the plurality of plate-like members 416c is t4 (about 15 μm) in a direction (arrow Y3 and Y4 direction) perpendicular to the flow direction of the biological sample (arrow Z2 direction) in the first cell discriminating part 416b. ). Further, as shown in FIG. 19, the plurality of plate-like members 416c are formed with the same length h4 (about 800 μm) as the widths W2 and W3 of the basin portion 412a in the directions of the arrows X3 and X4, respectively. In addition, as shown in FIG. 20, the plurality of plate-like members 416c are L4 (about 1000 μm) larger than twice the interval s4 of the plate-like members 416c described later in the biological sample flow direction (arrow Z2 direction). Has a length of Further, the plurality of plate-like members 416c are arranged so that the opening ratio of the first cell discriminating portion 416b is substantially 50%. Specifically, the plurality of plate-like members 416c have red blood cells, white blood cells, bacteria, etc. in directions (arrows Y3 and Y4) orthogonal to the flow direction of the biological sample (arrow Z2 direction) in the first cell discriminating part 416b. Of the cervical epithelial cells, the first aggregated cells 62 larger than the single cells 61, the second aggregated cells 63, and the foreign substance 64 other than the cells s4 ( About 15 μm). Thereby, the first cell discriminating unit 416b discriminates the micro cell 60 from the single cell 61, the first aggregated cell 62, the second aggregated cell 63, and the foreign substance 64 other than the cell when the biological sample is passed. It has a function to do. The plurality of plate-like members 416c are formed by dry etching. As a result, the thickness t4 of the plate-like member 416c can be easily reduced as compared with the case where the pores are provided by using an electroforming method or the like, so that the aperture ratio can be easily increased. .

  Next, the discrimination / substitution process in the discrimination unit 141 according to the second embodiment will be described. In the discriminating part 141, as shown in FIG. 21, the electromagnetic valve 432 between the sample supply part 411a and the sample holding part 431 and the electromagnetic valve 53d between the discharge part 413a and the drainage part 53 are opened. Thus, the biological sample is supplied to the sample supply unit 411a together with the storage solution. Then, the biological sample passes through the first cell discriminating part 416b in the direction of the arrow Z2, whereby the single cells 61, 2 or 3 of the cervical epithelial cells aggregated. The first aggregated cells 62, the second aggregated cells 63 obtained by aggregating four or more cervical epithelial cells, and the foreign matter 64 other than the cells are captured. In addition, microcells 60 such as red blood cells, white blood cells, and bacteria that have passed through the gaps of the first cell discriminating unit 416b are transferred to the drainage unit 53 via the discharge unit 413a. Thereby, a measurement object cell such as a single cell 61 of an epithelial cell and a micro cell 60 such as red blood cell, white blood cell, and bacteria are discriminated.

  Thereafter, an electromagnetic valve 52a between the discharge unit 413a and the positive pressure source 52, an electromagnetic valve 432 between the sample supply unit 411a and the sample holding unit 431, and an electromagnetic valve between the sample holding unit 431 and the negative pressure source 51 By opening 436, a positive pressure is instantaneously applied (about 0.1 second) from the downstream side of the flow of the biological sample toward the upstream side (toward the arrow Z1 direction side). As a result, the cells and foreign matter sandwiched between the gaps of the first cell discriminating portion 416b are pushed back to the upstream side of the first cell discriminating portion 416b. It becomes easy to flow in the direction (arrow Y3 direction) orthogonal to the flow direction of the biological sample (arrow Z2 direction).

  Next, an electromagnetic valve 435 between the replacement liquid supply unit 47 and the sample holding unit 431, an electromagnetic valve 432 between the sample supply unit 411a and the sample holding unit 431, the first liquid recovery unit 415d and the first storage container 441 are provided. And the electromagnetic valve 473 between the replacement liquid tank 471 and the positive pressure source 52 shown in FIG. 13 are opened, whereby the replacement liquid is supplied to the sample supply unit 411a. The supplied replacement liquid flows in the direction of the arrow Y3 through the region on the arrow Z1 direction side of the first cell discriminating portion 416b of the basin portion 412a. Thereby, the single cells 61 of the cervical epithelial cells captured by the first cell discriminating unit 416b are pushed away by the replacement liquid and transferred to the first storage container 441 via the first liquid recovery unit 415d. The At this time, the preservation solution supplied together with the biological sample is diluted to a predetermined concentration with the replacement solution. That is, by supplying the replacement liquid, it is possible to transfer the captured single cells 61 of the cervical epithelial cells to the first storage container 441 while diluting the preservation liquid to a predetermined concentration. . In addition, since the replacement liquid can be transferred to the first container 441 and the single cells 61 of the captured epithelial cells, solution replacement between the storage liquid and the replacement liquid can be performed.

  The remaining structure of the second embodiment is the same as that of the first embodiment.

  In the second embodiment, as described above, by providing only the first cell discriminating unit 416b without providing the second cell discriminating unit 417 and the third cell discriminating unit 418, an increase in the number of parts is suppressed. However, it is possible to discriminate between measurement target cells such as single cells 61 of epithelial cells and microcells 60 such as red blood cells, white blood cells, and bacteria.

  The remaining effects of the second embodiment are similar to those of the aforementioned first embodiment.

  The embodiment disclosed this time should be considered as illustrative in all points and not restrictive. The scope of the present invention is shown not by the above description of the embodiments but by the scope of claims for patent, and further includes all modifications within the meaning and scope equivalent to the scope of claims for patent.

  For example, in the first embodiment and the second embodiment, the example in which the positive pressure is always applied from the downstream side to the upstream side before the replacement liquid is supplied has been described. Not limited to this, the positive pressure may not be applied before supplying the replacement liquid for the first time, and the positive pressure may be applied only before supplying the replacement liquid for the second time. Moreover, it is not necessary to apply any positive pressure from the downstream side toward the upstream side before supplying the replacement liquid.

  Moreover, in the said 1st Embodiment, although the example which provides the discrimination part which has three cell discrimination parts, a 1st cell discrimination part, a 2nd cell discrimination part, and a 3rd cell discrimination part was shown, this invention is not limited to this. Alternatively, a configuration may be provided in which a discriminating unit having any one cell discriminating unit among the first cell discriminating unit, the second cell discriminating unit, and the third cell discriminating unit is provided. In addition, by connecting in series the discriminator having only the first cell discriminator, the discriminator having only the second cell discriminator and the discriminator having only the third cell discriminator, respectively, with the first embodiment A similar effect can be obtained.

  In the first embodiment, each plate member of the first cell discriminating part, the second cell discriminating part, and the third cell discriminating part has the same height (about 800 μm) as the depth D2 of the basin part. However, the present invention is not limited to this, and each plate-like member of the first cell discriminating part, the second cell discriminating part, and the third cell discriminating part may have a height different from the depth of the basin part. Good. For example, the depth of the basin is about 1000 μm, the height of the plate-like member of the first cell discriminating part is about 750 μm, the height of the plate-like member of the second cell discriminating part is about 800 μm, The height of the plate member may be about 900 μm.

  Moreover, although the example which provides the discrimination part which has only a 1st cell discrimination part was shown in the said 2nd Embodiment, this invention is not restricted to this, The space | interval between plate-shaped members is the same structure as 2nd Embodiment. By changing the above, it is possible to provide a discriminator having only the second cell discriminator or a discriminator having only the third cell discriminator. Further, in this case, a configuration in which the discriminator having only the first cell discriminator, the discriminator having only the second cell discriminator and the discriminator having only the third cell discriminator may be connected in series, respectively. . In this case, it is possible to obtain the same effect as in the first embodiment. Moreover, in the said 2nd Embodiment, you may provide the discrimination part containing three, a 1st cell discrimination part, a 2nd cell discrimination part, and a 3rd cell discrimination part. Also in this case, the same effect as the first embodiment can be obtained.

  In the first and second embodiments, the microcells 60 such as red blood cells, white blood cells, and bacteria that have passed through the cell discriminating unit are discarded. However, the present invention is not limited to this, and the microcells 60 are prepared from the microcells 60. The measured measurement sample may be measured.

It is the perspective view which showed the use condition of the cell analyzer by 1st Embodiment of this invention. It is the block diagram which showed the structure of the measuring apparatus of the cell analyzer by 1st Embodiment shown in FIG. It is a perspective view for demonstrating the structure of the measuring apparatus of the cell analyzer by 1st Embodiment shown in FIG. It is a figure for demonstrating the structure of the measuring apparatus of the cell analyzer by 1st Embodiment shown in FIG. It is the block diagram which showed the structure of the data processor of the cell analyzer by 1st Embodiment shown in FIG. FIG. 2 is a flow chart for explaining the configuration of the sample preparation device of the cell analyzer according to the first embodiment shown in FIG. 1. It is a figure for demonstrating the structure of the sample preparation apparatus of the cell analyzer by 1st Embodiment shown in FIG. It is a block diagram for demonstrating the structure of the sample preparation apparatus of the cell analyzer by 1st Embodiment shown in FIG. It is a perspective view for demonstrating the structure of the discrimination part of the cell analyzer by 1st Embodiment shown in FIG. It is a perspective view for demonstrating the structure of the discrimination part of the cell analyzer by 1st Embodiment shown in FIG. FIG. 10 is a cross-sectional view taken along line 100-100 in FIG. 9. It is a perspective view for demonstrating the structure of the sample preparation apparatus of the cell analyzer by 1st Embodiment shown in FIG. It is a perspective view for demonstrating the structure of the sample preparation apparatus of the cell analyzer by 1st Embodiment shown in FIG. It is a perspective view for demonstrating the structure of the sample preparation apparatus of the cell analyzer by 1st Embodiment shown in FIG. 3 is a flowchart for explaining an analysis processing operation of the cell analyzer according to the first embodiment shown in FIG. 1. 16 is a flowchart for explaining a discrimination / substitution processing operation in step S25 of the analysis processing operation shown in FIG. 15; It is a flowchart for demonstrating the washing | cleaning processing operation in step S27 of the analysis processing operation | movement shown in FIG. It is the perspective view which showed the discrimination part of the cell analyzer by 2nd Embodiment of this invention. It is a disassembled perspective view for demonstrating the structure of the discrimination part of the cell analyzer by 2nd Embodiment shown in FIG. It is sectional drawing for demonstrating the structure of the discrimination part of the cell analyzer by 2nd Embodiment shown in FIG. FIG. 19 is a flow chart for explaining a configuration of a discrimination unit of the cell analyzer according to the second embodiment shown in FIG. 18.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Cell analyzer 3 Data processor 4 Sample preparation apparatus 21 Detection part 41 Discrimination part 42 Sample preparation part 43 Sample supply part 46 Washing liquid supply part 47 Replacement liquid supply part 60 Micro cell 61 Single cell 62 First aggregation cell 63 Second Aggregated cell 64 Foreign body 416, 416b First cell discriminating part 416a, 416c Plate member 417 Second cell discriminating part 417a Plate member 418 Third cell discriminating part 418a Plate member 441 First container 451 Second container s1, s2, s3 interval

Claims (17)

A cell discriminating unit including a plurality of plate-like portions provided at predetermined intervals that allow cells of a predetermined size in a biological sample to pass therethrough and prevent cells larger than the cells of the predetermined size from passing through;
When the biological sample passes through the gaps between the plurality of plate-like parts, at least of the cells that have passed through the gaps between the plurality of plate-like parts, and the cells captured by the plurality of plate-like parts A sample preparation device comprising one and a sample preparation unit for preparing a measurement sample from a predetermined reagent. The cell of the predetermined size is a first cell including at least one selected from red blood cells, white blood cells, and bacteria;
A cell larger than the cell of the predetermined size is a second cell containing an epithelial cell,
In the plurality of plate-like parts, the biological sample passes through the gaps between the plurality of plate-like parts, so that the first cells pass through the gaps between the plurality of plate-like parts, and the second cells The sample preparation device according to claim 1, wherein the sample preparation device is configured to be captured by the plurality of plate-like portions. The cell of the predetermined size is a third cell including a single cell of an epithelial cell;
A cell larger than the cell of the predetermined size is a fourth cell including an aggregated cell in which the epithelial cells are aggregated,
In the plurality of plate-like portions, when the biological sample passes through the gaps between the plurality of plate-like portions, the third cells pass through the gaps between the plurality of plate-like portions, and the fourth cells The sample preparation device according to claim 1, wherein the sample preparation device is configured to be captured by the plurality of plate-like portions. The cell having the predetermined size is a fifth cell including an aggregated cell in which three or less epithelial cells are aggregated;
A cell larger than the cell of the predetermined size is a sixth cell including an aggregated cell in which four or more epithelial cells are aggregated,
In the plurality of plate-like portions, when the biological sample passes through the gaps between the plurality of plate-like portions, the fifth cells pass through the gaps between the plurality of plate-like portions, and the sixth cells The sample preparation device according to claim 1, wherein the sample preparation device is configured to be captured by the plurality of plate-like portions.   The apparatus further comprises a second cell discriminating unit that is disposed upstream of the flow of the biological sample from the cell discriminating unit and includes a plurality of second plate-like parts provided at intervals wider than the predetermined interval. Item 2. The sample preparation device according to Item 1. The cell of the predetermined size is a first cell including at least one selected from red blood cells, white blood cells, and bacteria;
A cell larger than the cell of the predetermined size is a third cell including a single cell of an epithelial cell;
The plurality of plate-like portions of the cell discriminating unit is configured such that the biological sample passes through the gaps between the plurality of plate-like portions, so that the first cells pass through the gaps between the plurality of plate-like portions, The third cell is configured to be captured by the plurality of plate-like portions,
The plurality of second plate-like portions of the second cell discriminating portion are provided at an interval that allows the third cells to pass therethrough and does not allow the fourth cells including the aggregated cells in which the epithelial cells have aggregated to pass through. When the sample passes through the gaps between the plurality of second plate-like portions, the third cells pass through the gaps between the plurality of second plate-like portions, and the fourth cells pass through the plurality of second plate-like portions. The sample preparation device according to claim 5, wherein the sample preparation device is configured to be captured by a shape portion. The plurality of second plate-like portions of the second cell discriminating portion are provided at an interval that allows the third cells to pass therethrough and does not allow passage of fifth cells including aggregated cells in which three or less epithelial cells are aggregated. And
The sample preparation device further includes a third cell discriminating unit arranged on the upstream side of the flow of the biological sample from the second cell discriminating unit,
The third cell discriminating unit is provided with an interval at which the fifth cell passes and the sixth cell including the aggregated cells in which four or more epithelial cells are aggregated and a foreign substance larger than the fifth cell are not allowed to pass. A plurality of third plate-like parts formed, and the biological sample passes through the gaps between the plurality of third plate-like parts, so that the fifth cell has a gap between the plurality of third plate-like parts. The sample preparation device according to claim 6, wherein the sample preparation device is configured to pass through and the sixth cells and the foreign substances are captured by the plurality of third plate-like portions. A sample supply unit for supplying the biological sample to the gap between the plurality of plate-like portions of the cell discrimination unit;
The sample preparation device according to any one of claims 1 to 7, further comprising a cell collection unit that collects cells captured by the plurality of plate-like units. The cell recovery unit is
A containment vessel;
A cell transfer unit for transferring the cells captured by the plurality of plate-like parts and the recovery liquid to the storage container by supplying the recovery liquid in a direction intersecting the flow direction of the biological sample in the cell discrimination unit. The sample preparation device according to claim 8, comprising: A cell discrimination device including the cell discriminator;
The cell discrimination device includes:
A sample introduction unit for receiving the biological sample supplied to the sample supply unit and introducing the biological sample into the cell discrimination unit;
A sample receiving unit arranged in the flow direction of the biological sample, for receiving the biological sample that has passed through the gap between the plurality of plate-like units and taking it out of the cell discrimination device;
A recovery liquid introduction unit for receiving the recovery liquid supplied by the cell transfer unit and introducing the recovery liquid in a direction crossing the flow direction of the biological sample;
A recovery liquid that is arranged in the flow direction of the recovery liquid and receives the cells captured by the plurality of plate-like parts and the recovery liquid introduced into the recovery liquid introduction part and outputs them to the outside of the cell discrimination device The sample preparation device according to claim 9, further comprising a receiving unit. The sample supply unit supplies the biological sample together with a storage solution for storing the biological sample to the cell discrimination unit,
The sample preparation apparatus according to claim 9 or 10, wherein the cell transfer unit is configured to supply a sample preparation liquid used for preparing the measurement sample as the recovery liquid.   The washing | cleaning part which wash | cleans the said cell discrimination part by supplying a washing | cleaning liquid in the direction which cross | intersects the flow direction of the said biological sample in the said cell discrimination part is further provided of any one of Claims 1-11. Sample preparation device.   The length of the plate-like part in the flow direction of the biological sample in the cell discriminating part is at least twice as long as the interval between the plurality of plate-like parts. Sample preparation device.   The sample according to any one of claims 1 to 13, wherein each of the plurality of plate-like portions is formed in substantially the same shape, and each of the plate-like portions is arranged substantially parallel to each other. Preparation equipment.   The sample preparation device according to any one of claims 1 to 14, wherein the cell discriminating unit is manufactured by forming a plurality of gaps with the predetermined interval on a silicon wafer using dry etching. A cell discriminating unit including a plurality of plate-like portions provided at predetermined intervals that allow cells of a predetermined size in a biological sample to pass therethrough and prevent cells larger than the cells of the predetermined size from passing through;
When the biological sample passes through the gaps between the plurality of plate-like parts, at least of the cells that have passed through the gaps between the plurality of plate-like parts, and the cells captured by the plurality of plate-like parts A detection unit for detecting information on at least one of the cells of the predetermined size and the cells larger than the cells of the predetermined size from a measurement sample prepared from one and a predetermined reagent;
A cell analyzer comprising: analysis means for analyzing at least one of the predetermined size cell and the larger cell than the predetermined size cell based on the detection result of the detection unit.   A plurality of plate-like portions provided at predetermined intervals that allow cells of a predetermined size in the biological sample to pass therethrough and prevent cells larger than the cells of the predetermined size from passing, wherein the biological sample is By passing through the gaps between the plurality of plate-like parts, the cells of the predetermined size pass through the gaps between the plurality of plate-like parts, and cells larger than the cells of the predetermined size are A cell discrimination device comprising a cell discriminator configured to be captured by a plate-like part.

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