JP6221276B2 - Screening method and screening apparatus - Google Patents

Description

The present invention relates to a screening how Ho及 beauty screening device.

  For example, as a well plate used for fluorescence measurement of biomolecules, a plate in which a plurality of wells are partitioned by providing a lattice-like frame member via a sealing material on a plate-like plate is known (for example, See Patent Document 1 below).

JP 2005-513457 A

  However, in the technique as described above, a problem that cannot be efficiently dealt with when the number of measurement objects different from the number of wells (for example, one) is measured with respect to the number of wells formed on the plate. was there. For example, when only a part of a plurality of wells is used for measurement, many wells (unused wells) are wasted because all the wells are formed on the same plate.

According to a first aspect of the present invention, a substrate, formed on a first surface of the substrate, and the methods of screening using biochip having a target and capable of specifically reacting biomolecules contained in the sample condition a is a dispensing process for dispensing the specimen into the reaction vessel, in which the second surface is a surface opposite adsorbed and held by the suction holding means and the first surface of the substrate in the biochip Then, a reaction process for immersing the biochip in the sample dispensed in the reaction container to react the target and the biomolecule, a cleaning process for cleaning the biochip after the reaction process , a drying treatment you drying the biochip after the washing process, the drying the after treatment using a biochip, a detection process for detecting the affinity between the target and the biomolecule-containing steaming cleaning method Provided That.

According to the second aspect of the present invention, a dispensing unit that dispenses a specimen containing a target into a reaction container, a substrate, a first surface of the substrate, and capable of specifically reacting with the target An adsorption holding unit for adsorbing and holding a biochip having various biomolecules, a drive unit for moving the adsorption holding unit, a cleaning unit for washing the biochip, a drying unit for drying the biochip, and the bio A support for supporting the chip; an imaging unit for imaging the biomolecule of the biochip; a dispensing process for dispensing the sample into the reaction container by the dispensing unit; and the substrate of the biochip. The driving unit is configured to immerse the biochip in the specimen dispensed in the reaction container in a state where the second surface, which is the surface opposite to the first surface, is adsorbed and held by the adsorption holding unit. Move the suction holding part A reaction process for reacting the target with the biomolecule, and the cleaning of the biochip after the reaction process in a state in which the second surface of the substrate of the biochip is adsorbed and held by the adsorption holding unit. A transfer process for transferring to the part, a cleaning process for cleaning the biochip after the transfer process in the cleaning part, and a state in which the second surface of the substrate in the biochip is suction-held by the suction-holding part. A second transfer process for transferring the biochip after the cleaning process to the drying unit; a drying process for drying the biochip after the second transfer process to the drying unit; and the substrate in the biochip. A third transfer process for transferring the biochip after the drying process to the support part in a state where the second surface is adsorbed and held by the adsorption holding part, and the third transfer process An imaging process for causing the imaging unit to image the biomolecule of the biochip in a state where the biochip is supported by the support unit, and the target and the biomolecule based on a result obtained by the imaging process And a control unit that controls to execute the detection process for detecting the affinity with the screening apparatus .

It is a figure which shows embodiment of this invention, Comprising: The schematic block diagram of the screening apparatus SC. 1 is a schematic configuration diagram of a preassay unit PA according to a first embodiment. FIG. The schematic block diagram of the 2nd box which concerns on 1st Embodiment. The schematic block diagram of the array box which concerns on 1st Embodiment. The schematic block diagram of the array box which concerns on 1st Embodiment. The schematic block diagram of the delivery part which concerns on 1st Embodiment. The schematic block diagram of the marking part which concerns on 1st Embodiment. FIG. 3 is a schematic configuration diagram of a reading unit according to the first embodiment. The schematic block diagram of the delivery part which concerns on 1st Embodiment. The schematic block diagram of the washing | cleaning part which concerns on 1st Embodiment. The schematic block diagram of the reaction part which concerns on 1st Embodiment. The schematic block diagram of the drying part which concerns on 1st Embodiment. The schematic block diagram of the measurement part which concerns on 1st Embodiment. The schematic block diagram of the measurement part which concerns on 1st Embodiment. Process drawing of the screening method which concerns on 1st Embodiment. Process drawing of the screening method which concerns on 2nd Embodiment. The schematic block diagram of the array box which concerns on 2nd Embodiment. Process drawing which fixes the biochip which concerns on 2nd Embodiment to an adapter. Process drawing which fixes the biochip which concerns on 2nd Embodiment to an adapter. Process drawing which fixes the biochip which concerns on 2nd Embodiment to an adapter. Process drawing of the screening method which concerns on 2nd Embodiment. Process drawing of the screening method which concerns on 2nd Embodiment. Process drawing of the screening method which concerns on 2nd Embodiment. The schematic block diagram of the array box for the shipment of the biochip which concerns on 2nd Embodiment. The figure by which the biochip which concerns on 2nd Embodiment was supported by the support container. The figure by which the biochip which concerns on 2nd Embodiment was supported by the washing | cleaning container. The figure by which the biochip which concerns on 2nd Embodiment was supported by the reaction container. The figure by which the biochip which concerns on 2nd Embodiment was supported by the support stand. The schematic block diagram of the reaction part which concerns on 3rd Embodiment. The schematic block diagram of the measurement part which concerns on 3rd Embodiment. The schematic block diagram of the screening apparatus which concerns on 4th Embodiment. The schematic block diagram of the delivery part 3 which concerns on 5th Embodiment. The schematic block diagram of the washing | cleaning part 7 which concerns on 5th Embodiment. The schematic block diagram of the reaction part 6 which concerns on 5th Embodiment. The schematic block diagram of the drying part 8 which concerns on 5th Embodiment. The schematic block diagram of measurement part MS which concerns on 5th Embodiment. The schematic block diagram of the delivery part 9 which concerns on 6th Embodiment, and the washing | cleaning part 7. FIG. The schematic block diagram of the delivery part 9 which concerns on 6th Embodiment, and the washing | cleaning part 7. FIG. The schematic block diagram of the washing | cleaning part 7 and the reaction part 6 which concern on 6th Embodiment. The schematic block diagram of the washing | cleaning part 7 and the reaction part 6 which concern on 6th Embodiment. The schematic block diagram of the reaction part 6 and the drying part 8 which concern on 6th Embodiment. The schematic block diagram of the reaction part 6 and the drying part 8 which concern on 6th Embodiment. The schematic block diagram of the measurement part MS which concerns on another form. The schematic block diagram of the measurement part MS which concerns on another form.

  Embodiments of a biomolecule array processing method, biomolecule array screening method, biomolecule array housing, bioassay device, and screening device according to the present invention will be described below with reference to FIGS.

[First embodiment]
FIG. 1 is a schematic configuration diagram of a biomolecule screening apparatus SC using a biochip (biomolecule array). The screening device SC includes a pre-assay unit PA, an assay unit (bioassay device) AS, a measurement unit (detection device) MS, and delivery units TR1 and TR2.

  Note that the pre-assay unit PA may be configured to be installed in a place (separate processing unit) different from the processing unit having the assay unit AS and the measurement unit MS. In the case of this configuration, the biochip that has been processed by the pre-assay unit PA is supplied to the assay unit AS. In this embodiment, the biochip is automatically processed in series by the pre-assay unit PA, the assay unit AS, and the measurement unit MS described above.

  The pre-assay unit PA includes a mounting unit 1, a marking unit 2, and a delivery unit 3. FIG. 2 is a schematic configuration diagram of the preassay unit PA. The mounting unit 1 mounts a biochip (biomolecule array) 50 on an array box (biomolecule array housing) 20, and includes a manipulator (for example, a mechanical arm that can be automatically driven by computer control) 11, A robot apparatus 13 including an arm 12.

  The biochip 50 includes a biomolecule 51 that can specifically react with a target contained in a specimen, which will be described later, on one side of the substrate 52 (upper side in FIG. 1; hereinafter referred to as the biomolecule side). The biochip 50 is formed by, for example, a large number of probes (spots) formed by laminating a plurality of biomolecules on a 1 to 10 mm square substrate. The biochip 50 is formed, for example, by forming spots on a silicon wafer and then dicing the silicon wafer into individual pieces. The probe repeats, for example, a step of arranging a predetermined biomolecule forming material on a silicon wafer and an exposure step of selectively irradiating the biomolecule forming material with light of a predetermined wavelength through a mask. Thus, it is formed by stacking a plurality of biomolecules. The biomolecule formed in this manner binds to the specimen by a specific reaction with the fluorescently labeled specimen to be measured, and generates predetermined fluorescence by illumination with predetermined light (excitation light).

  The array box 20 includes a first box 30 capable of supporting the biochip 50 from the biomolecule side, and a second box 40 capable of supporting the biochip 50 from the other side of the substrate 52 (hereinafter referred to as the substrate side). ing.

  The first box 30 includes an opening on the side facing the second box 40, for example, a box main body 31 formed in a rectangular frame shape (bottomed rectangular tube shape) and a side wall 31 a of the box main body 31. The supporting wall portion 32 is provided. The support wall 32 includes a plurality of support recesses 33 having a shape in which the surface 32 a facing the second box 40 is omitted. Each support recess 33 includes a first recess 33a that opens to the facing surface 32a and a bottomed second recess 33b that opens to the first recess 33a. The first recess 33a is formed in a size and shape that is shallower than the thickness of the substrate 52 and that can hold the substrate 52 from the outer peripheral side. When the biochip 50 is inserted into the first recess 33a, the second recess 33b is formed in such a size and shape that the peripheral portion of the biochip 50 can be engaged with the bottom 33c of the first recess 33a. The depth of the second recess 33b is such that the biomolecule 51 (probe) does not contact the bottom when the peripheral edge of the biochip 50 is engaged with the bottom 33c of the first recess 33a, and the support recess 33 is When the peripheral portion of the biochip 50 is engaged with the bottom 33c of the first recess 33a and a predetermined amount of sample is injected (dispensed) into the second recess 33b in the state of opening upward, the biomolecule 51 is converted into the sample. Set to contact with.

  The second box 40 includes a box body 41 that opens on the side facing the first box 30, and a support wall portion 42 provided in the box body 41. The box main body 41 includes a side wall 41 a that fits with the outer peripheral surface of the side wall 31 a of the box main body 31. The support wall portion 42 includes a plurality of support recesses 43 having a shape in which the surface 42 a facing the first box 30 is omitted. The support recess 43 seals the biochip 50 in cooperation with the support recess 33 when the first box 30 and the second box 40 are fitted in the side walls 31a and 41a and the opposing surfaces 32a and 42a come into contact with each other. A holding space for holding in a state is formed (see FIG. 4), and is formed with a depth substantially equal to the thickness of the biochip 50. The support recess 43 is formed in a size and shape that can hold the substrate 52 from the outer peripheral side. The side surface of the support recess 43 is formed in a tapered shape that gradually increases in diameter as it goes from the bottom toward the opening.

  A driving device 14 and a suction device 15 are connected to the manipulator 11. The drive device 14 is configured by, for example, a three-dimensional robot device or the like, and the manipulator 11 is controlled by the control device CONT, for example, in a direction along the horizontal plane and in a vertical direction while maintaining a posture extending in the vertical direction. Move to. The suction device 15 is configured by, for example, a negative pressure suction device, and controls the control device CONT to control negative pressure suction from the detachable nozzle 16 provided at the tip (eg, lower end) of the manipulator 11 (eg, operation and operation). By switching between the suction and the stop, the suction holding of the biochip 50 in the nozzle 16 and the suction holding release are switched.

  The robot device 13 includes an arm 12 that can move in two axial directions along a horizontal plane, one axial direction parallel to the vertical direction, and a rotational direction around each of these three axes under the control of the control device CONT. Yes. The arm 12 includes a pair of arm pieces 12a whose holding width can be adjusted under the control of the control device CONT.

  As shown in FIG. 7, the marking unit 2 includes information on the biomolecules 51 on the substrate-side surface (eg, substrate surface, lower surface) of the biochip 50 or the side surface of the biochip 50, information on the manufacturer, information on the laboratory, etc. The identification information is formed using characters, numbers, symbols, figures, barcodes, etc. as appropriate, and includes a marking device 21 such as a laser marker, the manipulator 11, the driving device 14, and a suction device. The transfer apparatus 22 (refer FIG. 1) provided with the structure similar to 15 is provided. The marking unit 2 in the present embodiment is a biochip that is supported by the support recess 33 in a state where the first box 30 described in FIG. 1 is placed so that the support recess 33 faces upward and the substrate 52 is exposed. 50 is configured to form identification information.

  The delivery unit 3 performs the delivery process of the biochip 50 between the mounting unit 1 and the marking unit 2. For example, like the marking unit 2 shown in FIG. The first box 30 is placed so as to face.

  Returning to FIG. 1, the assay unit (bioassay device) AS includes a reading unit 4, a dispensing device (dispensing unit) 5, a reaction unit 6, a washing unit 7, a drying unit 8, and a delivery unit 9. The reading unit 4 includes an imaging device 23 shown in FIG. 8 and a transfer device 24 (see FIG. 1) having the same configuration as the transfer device 22 of the preassay unit PA. The imaging device 24 is a device that images and reads the identification information of the biochip 50 formed on the surface of the biochip 50 on the substrate side, and is configured by a CCD camera, for example. An identification information signal is generated by imaging the identification information using the imaging device 24, and the identification information signal is output to the control device CONT. The imaging device 24 according to the present embodiment places the first box 30 described in FIG. 1 with the support recess 33 facing upward, and the biochip supported by the support recess 33 with the substrate 52 exposed. 50 is configured to image identification information.

  For example, as shown in FIG. 11 showing the reaction container 25 into which the sample 53 has been dispensed, the dispensing device 5 uses the manipulator 11 to identify the biomolecule 51 and the specific reaction container 25 arranged in the reaction unit 6. In this case, a dispensing process for injecting (dispensing) a specimen 53 containing a target that can be reacted is performed.

  The reaction unit 6 performs a reaction process for reacting the biomolecule 51 of the biochip 50 with the target contained in the specimen under a predetermined temperature condition. For example, as shown in FIG. 25 and a manipulator 11 having the above-described removable nozzle 16, a suction holding device (suction holding unit) 26 having the same configuration as the driving device 14 and the suction device 15. 11, only the manipulator 11 is illustrated, and the driving device 14 and the suction device 15 are not illustrated (the same applies to the suction holding device 26 illustrated in FIGS. 10 and 12). Is). The reaction vessel 25 may have a configuration having a plurality of wells. Moreover, although the nozzle 16 in this embodiment is directly contacting and adsorbing to the biochip 50, the biochip 50 may be indirectly adsorbed via a film such as an adsorption protective layer. Further, the nozzle 16 in the present embodiment may be provided with an elastic member for adsorption at the tip, or the tip may be constituted by the elastic body. Note that the nozzle 16 or the elastic member at the tip of the nozzle 16 in the present embodiment may have a wide suction port according to the area of the suction surface of the biochip 50.

  The cleaning unit 7 performs a cleaning process for cleaning the biochip 50, and includes a cleaning container 27 in which a cleaning liquid 28 is stored, as shown in FIG.

  The drying unit 8 performs a drying process on the washed biochip 50, and includes a drying device 28 that ejects, for example, a drying gas as shown in FIG.

  The delivery unit 9 performs a delivery process of the biochip 50 between the reading unit 4 and the reaction unit 6. For example, like the marking unit 2 shown in FIG. The first box 30 placed so as to face is used (see FIG. 9).

  Next, as shown in FIGS. 13 and 14, the measuring unit MS includes a measurement stage ST, an imaging device 60, and a suction holding device (suction holding unit) 29. The suction holding device (suction holding unit) 29 has the same configuration as the suction holding device 26 described above. The measurement stage ST is movable along the XY plane under the control of the control device CONT. The measurement stage ST includes a support base (array holder) 61 that supports the peripheral portion of the biochip 50 on the biomolecule side from below. The support base 61 is formed with a through-hole 61a penetrating in the vertical direction so as to open toward the biomolecule 51 to be measured when the biochip 50 is supported.

  The imaging device 60 includes, for example, a light source, an optical system having an objective lens, a CCD camera, and the like, and is disposed below the through hole 61 a of the support base (array holder) 61. The identification information signal generated by the imaging device 60 is output to the control device CONT.

  Subsequently, the delivery unit TR1 of FIG. 1 performs a delivery process of the biochip 50 between the marking unit 2 and the reading unit 4. In the delivery process, for example, the first box 30 placed so that the support recess 33 faces upward is used similarly to the marking unit 2 shown in FIG. 7 (see FIG. 9).

  The delivery part TR2 in FIG. 1 is a part where the delivery process of the biochip 50 is performed between the reaction part 6 and the measurement part MS. For example, like the marking part 2 shown in FIG. The first box 30 placed so that is directed upward is used.

Next, a method of screening the biochip 50 including the biomolecule array processing method using the screening apparatus SC will be described with reference to the process diagram of FIG.
In the present embodiment, for example, mounting processing, marking processing, reading processing, dispensing processing, reaction processing, cleaning processing, drying processing, measurement processing (detection) are performed as related processing related to measurement of the biochip 50 having the biomolecule 51. Process) and a transfer process for transferring the biochip 50 between these processes is appropriately performed. Hereinafter, these processes will be sequentially described.

  In the following description, the manipulator 11 is moved by the control device CONT controlling the operation of the drive device 14. Further, adsorption holding and holding release of the biochip 50 in the nozzle 16 are performed by the controller CONT controlling the operation of the adsorption device 15. Description of control by these control devices CONT is omitted as appropriate. Similarly, the movement of the arm 12 and the adjustment of the holding width of the pair of arm pieces 12a in the robot apparatus 13 are controlled by the control device CONT, but the description of the control by the control device CONT is also omitted as appropriate.

  First, in the mounting process, as shown in FIG. 2, the biochip 50 is sucked and held by the manipulator 11 and transferred to the support recess 43 of the box body 41 in the second box 40. For example, with respect to a biochip 50 that is singulated by dicing a wafer (biomolecule wafer) W on which a plurality of biochips 50 are collectively formed, first, the manipulator 11 is placed on the biomolecule side of the biochip 50. The biochip 50 is adsorbed and held by the nozzle 16 by the operation of the adsorption device 15. Next, after the manipulator 11 is moved to a position facing the support recess 43 of the box body 41, the biochip 50 is transferred to the support recess 43 as shown in FIG. By releasing, the biochip 50 is mounted on the second box 40 in a state where the substrate 52 is supported by the support wall 42 from below and the biomolecules 51 are exposed upward (step S101).

  After the predetermined number (for example, three) of biochips 50 are mounted on the second box 40, the first box 30 that is spaced apart from the second box 40 is attached to the second box 40 by the robot device 13. Transport to the vicinity. After the conveyance, the robot apparatus 13 fits the second box 40 and the first box 30 together. For example, as shown in FIG. 2, the robot apparatus 13 moves the first box 30 to a position facing the second box 40 in a state where the box body 31 of the first box 30 is sandwiched from above by the arm 12. Thereafter, the robot apparatus 13 moves the first box 30 downward, so that the side wall 31a of the first box 30 is fitted to the inner peripheral side of the side wall 41a of the second box 40 as shown in FIG. Position alignment of the main body 31 and the box main body 41 is performed (step S102). Then, after the first box 30 is moved until the opposing surfaces 32a and 42a come into contact with each other, the holding by the arm 12 is released, so that the biochip 50 is a sealed holding space formed by the support recesses 33 and 43. Held in.

  Next, as shown in FIG. 5, the robot apparatus 13 rotates (i.e., reverses) the first box 30 and the second box 40 by 180 degrees around an axis parallel to the horizontal direction while being sandwiched by the arm 12 from the vertical direction. ). Thereby, the biochip 50 moves by its own weight from the support recess 43 of the second box 40 to the support recess 33 of the first box 30 (step S103). In step S103, the biochip 50 is mounted on the first box 30 with the peripheral edge portion supported by the bottom 33c of the support recess 33.

  After step S103, the second box 40 is removed from the first box 30 by the robot apparatus 13 (arm 12). Then, the arm 12 moves while holding the box body 31 in the horizontal direction, and transfers the first box 30 to the delivery unit 3.

  After the first box 30 on which the biochip 50 is mounted is transferred to the delivery unit 3, the marking process is performed on the biochip 50. As shown in FIG. 7, the marking device 21 forms identification information on the surface exposed on the substrate side of the biochip 50 (substrate 52) (step S104). Thereby, the marking process is completed.

  As described above, when the pre-assay part PA is installed in a place (separate processing unit) different from the assay part AS and the measurement part MS, after the marking process to the biochip 50 is completed, the first box The second box 40 is attached to 30 and transported and shipped in a state in which the sealing property of the holding space of the biochip 50 is ensured (step S105).

  On the other hand, in this embodiment, the biochip 50 supported by the first box 30 of the marking unit 2 is transferred to the manipulator 11 of the transfer device 22 in order to continuously perform a plurality of processes on the biochip 50 that has been subjected to the marking process. It is used for suction holding and transferred to the first box 30 placed on the delivery part TR1. The biochip 50 transferred to the first box 30 in the delivery unit TR1 is adsorbed and held by the manipulator 11 of the transfer device 24 in the reading unit 4, and the first box arranged in the reading unit 4 as shown in FIG. It is transferred to 30 support recesses 33.

  After all or a predetermined number of biochips 50 are transferred to the first box 30, the identification information reading process is performed (step S106). As an example, the imaging device 23 in the reading unit 4 captures and reads the identification information formed on the substrate side of the biochip 50. The control device CONT determines from the identification information signal generated by the imaging device 23 whether or not the biochip 50 is used for processing in the assay unit AS. The control device CONT shifts to the next process when it is a proper biochip 50, and executes a process for generating an error when it is not a proper biochip 50, for example.

  When the biochip 50 is appropriate, the biochip 50 is transferred to the first box 30 placed on the delivery unit 9.

  The biochip 50 is transferred to the first box 30 arranged in the delivery unit 9, and a dispensing process (step S107) and a washing process are performed in the assay unit AS (step S108). As an example, a sample 53 (for example, a sample labeled with a fluorescent dye) containing a target that can specifically react with the biomolecule 51 is injected into the reaction container 25 arranged in the reaction unit 6 by the dispensing device 5. (Dispensing) (see FIG. 11). And the biochip 50 is moved to the washing | cleaning part 7 in the state which adsorbed and hold | maintained the biochip 50 using the manipulator 11 of the adsorption holding device 26 provided in the reaction part 6, and the washing | cleaning part 7 is shown in FIG. Then, the biochip 50 is immersed in the cleaning liquid 28 stored in the cleaning container 27 of the cleaning unit 7 for cleaning. This makes it possible to remove foreign matter even if foreign matter adheres to the biochip 50 before the reaction between the specimen and the biomolecule is performed. In the cleaning of the biochip 50 in the cleaning unit 7, at least a part of the biochip 50 and the nozzle 16 is immersed in the cleaning liquid 28 in the cleaning container 27. However, the manipulator 11 other than the nozzle 16 has the cleaning liquid 28 from the viewpoint of efficiency and cost. Not soaked in.

  The dispensing process is preferably performed in parallel with the identification information reading process of the biochip 50 or the cleaning process from the viewpoint of improving the inspection efficiency.

  After the cleaning process for the biochip 50 is completed, the biochip 50 is transferred into the reaction container 25 into which the specimen 53 is dispensed in a state where the biochip 50 is adsorbed and held by the nozzle 16 of the manipulator 11 ( First transfer process). In the reaction container 25, the biochip 50 is immersed in the specimen 53 in a state where the biochip 50 is adsorbed and held by the nozzle 16, whereby a reaction process between the biomolecule 51 and the target contained in the specimen 53 is performed ( Step S109). For example, when the manipulator 11 is rotated about an axis parallel to the vertical axis, the specimen 53 is agitated in the reaction vessel 25, and the reaction process between the biochip 50 and the target is efficiently performed. In the above-described reaction process, at least a part of the biochip 50 and the adsorption holding unit 26 (in this case, the nozzle 16) is immersed in the specimen 53 in the reaction container 25, but other than the nozzle 16 from the viewpoint of efficiency and cost. The manipulator 11 is not immersed in the specimen 53. For example, when a reaction process between a biomolecule 51 of another biochip 50 and a target contained in another specimen 53 is performed after the above-described reaction process, the manipulator 11 removes the nozzle 16 and creates a new clean nozzle. By attaching 16, the manipulator 11 and the nozzle 16 need not be washed each time the specimen 53 to be examined changes. As a result, the efficiency in the reaction process is improved and the cost in the process is reduced.

  After the reaction process is completed, the biochip 50 is transferred to the cleaning unit 7 while being adsorbed and held by the manipulator 11, and the cleaning process is performed again on the biochip 50 after the reaction. And the biochip 50 after reaction is transferred to the position facing the drying apparatus 28 of the drying part 8, and a drying process is performed (step S110). The biochip 50 that has been dried is transferred to the first box 30 placed on the delivery unit TR2 (see FIG. 1) in a state where the biochip 50 is sucked and held by the manipulator 11 of the suction holding device 26. In the above-described embodiment, the first box 30 disposed in the delivery unit TR1 or the delivery unit TR2 may be the first box 30 used in the previous processing step, or a newly prepared first box 30. But it ’s okay.

  The biochip 50 transferred to the first box 30 in the delivery unit TR2 is adsorbed and held by the manipulator 11 of the adsorption holding device 29 in the measurement unit MS, and as shown in FIG. 13, the predetermined measurement for measurement arranged on the measurement stage ST. It is transferred to the support base 61 which is the position (second transfer process). Thereafter, measurement processing (detection processing) of the biochip 50 is performed (step S111).

  Next, an example of measurement processing (detection processing) of the biochip 50 will be described with reference to FIG. First, by measuring an index mark (not shown) provided on the biomolecule side of the substrate 52 through the through hole 61a by the imaging device 60, measurement alignment (position) for the biochip 50 arranged on the support base 61 is performed. Adjustment) is performed. After the alignment of the biochip 50 is completed, focusing of the imaging device 60 and imaging of the biomolecule 51 are sequentially performed. Further, when the field of view of the imaging device 60 is narrower than the arrangement region of the plurality of biomolecules 51, the control device CONT can regularly move the plurality of stages ST and move the plurality of arrangement regions of the plurality of biomolecules 51. The imaging of the arrangement region of the biomolecule 51 is performed a plurality of times as a series of operations. The control device CONT generates a measurement result by synthesizing a plurality of imaging results obtained by this series of operations, and based on the measurement result, the affinity between the biomolecule 51 and the target (for example, fluorescence generation) The reactivity or binding based on the presence or absence of fluorescence or the intensity of fluorescence.

  As described above, in this embodiment, the biochip 50 is individually adsorbed and held by the manipulator 11 and various related processes related to the measurement of the biomolecule 51 are performed, so that a plate having a plurality of wells is used. Thus, as in the case of performing measurement, efficient measurement and detection can be performed without causing a problem that a well that is wasted without being used for measurement is generated. In the present embodiment, since the sample 53 is agitated by the manipulator 11 in the reaction container 25, it is not necessary to prepare a separate agitating device, and the apparatus can be reduced in size and cost. Furthermore, in this embodiment, since the nozzle in the manipulator 11 adsorbs and transfers the surface of the biochip 50 on the substrate side, it is possible to avoid adversely affecting the biomolecule 51 during adsorption holding.

  In the present embodiment, since the identification information of the biochip 50 is read before the related processing is performed, it is possible to easily determine that the transferred biochip 50 is a processing target, It becomes possible to improve the nature. Furthermore, in this embodiment, since the identification information is marked in the pre-assay part PA on which the biochip 50 separated from the biomolecule wafer W is mounted, the reliability can be further improved.

[Second Embodiment]
Next, a second embodiment of the biomolecule array processing method and the biochip 50 screening method will be described with reference to FIGS.
In these drawings, the same components as those of the first embodiment shown in FIGS. 1 to 15 are denoted by the same reference numerals, and the description thereof is omitted.

  In the first embodiment, the array box 20 directly supports the biochip 50, and the manipulator 11 directly adsorbs and holds the biochip 50. However, in this embodiment, the biochip 50 is held by an adapter, The array box 20 is configured to support the adapter.

In FIG. 17, an adapter (holding unit) 70 that holds the biochip 50 is supported by the array box (biomolecule array housing) 120.
The adapter 70 includes a shaft portion 71 and a flange portion 72. The biochip 50 is fixed and held at the tip of the shaft portion 71 by an adhesive. The flange portion 72 is formed to have a larger diameter than the diameter of the shaft portion 71. The flange portion 72 is provided at the proximal end portion of the shaft portion 71.

The array box 120 includes a first box 130 that can hold the shaft portion 71 and a second box 140 that can support the flange portion 72 from below.
The first box 130 has an opening on the side facing the second box 140, for example, a box body 131 formed in a rectangular frame shape (bottomed rectangular tube shape) and a support erected between the side wall 131a of the box body 131. Wall part 132. When the flange portion 72 is engaged with the surface 132 a facing the second box 140, the biochip 50 held by the shaft portion 71 does not contact the bottom wall 134 of the box body 131. In position. The support wall portion 132 includes a hole 133 that holds the outer peripheral surface of the shaft portion 71. The hole 133 is formed through the support wall 132 and has a tapered shape that gradually increases in diameter toward the side facing the second box 140.

  The second box 140 includes a box body 141 that opens on the side facing the first box 130, and a support recess 142 provided in the box body 141. The box main body 141 includes a side wall 141 a that fits with the inner peripheral surface of the side wall 131 a of the box main body 131. The height of the side wall 141a is such that when the side wall 141a abuts on the support wall 132 of the first box 130 with the flange 72 supported from below, the tip of the shaft 71 is fitted and held in the hole 133. Set to the value to be In addition, the height of the side wall 141 a is set to a value that fits with the inner peripheral surface of the side wall 131 a of the box body 131 before the shaft portion 71 is fitted into the hole 133.

  A plurality of support recesses 142 (three in FIG. 17) are provided according to the number of adapters 70 to be installed. The support recess 142 includes an alignment portion (not shown) to which the adapter 70 is aligned and fixed when the adapter 70 is inserted.

  Next, referring to the process diagram shown in FIG. 16 and the like for a method of screening the biochip 50 including the biomolecule array processing method using the screening apparatus SC, the adapter 70, and the array box 120 described in the above configuration. I will explain. First, as shown in FIGS. 16 and 18, the flange portion 72 of the adapter 70 is inserted into the support concave portion 142 of the second box 140 placed so that the opening portion faces upward, and the adapter 70 is inserted into the second box 140. Are aligned and fixed (step S201).

  Next, as shown in FIGS. 16 and 19, an adhesive 73 is provided on the distal end surface of the shaft portion 71 of the aligned adapter 70 (step S202). The adhesive 73 is an adhesive or a double-sided tape.

  Next, as in the first embodiment, the biochip 50 diced by the biomolecule wafer W (see FIG. 2) is adsorbed and held by the nozzle 16 of the manipulator 11, and FIG. As shown in FIG. 20, it is placed on the tip surface of the shaft portion 71. Thereby, the biochip 50 is bonded and fixed to the distal end surface of the shaft portion 71 (step S203).

  Next, as shown in FIG. 17, the first box 130 is sandwiched and moved using the arm 12 (see FIG. 2) described in the first embodiment, and the first box is moved as shown in FIG. 130 is attached to the second box 140. At this time, the first box 130 and the second box 140 are aligned by fitting the side walls 131a and 141a before the shaft portion 71 is inserted into the hole 133, and the shaft portion 71 has a tapered shape in which the diameter is increased. Is smoothly inserted and held in the hole 133 having

  As shown in FIGS. 16 and 21, after the first box 130 and the second box 140 are combined, the first box 130 and the second box 130 are secondly moved by the arm 12 in a state where the fixing of the adapter 70 by the alignment unit is released. The vertical relationship with the box 140 is reversed. Thereby, the tip adapter 70 moves to a position where the flange portion 72 is engaged with and supported by the surface 132a of the support wall portion 132 by its own weight while the shaft portion 71 is held in the hole 133 (step S204). .

  Thereafter, the second box 140 is removed from the first box 130. As shown in FIGS. 16 and 22, the flange portion 72 is exposed on the upper side, and the identification information of the biochip 50 is marked on the exposed surface (step S205).

  As shown in FIGS. 16 and 23, when continuous processing is performed on the biochip 50, after the flange portion 72 is exposed, the adsorption region for the biochip 50 is larger than the nozzle 16 of the manipulator 11 described above. The exposed surface of the flange 72 is adsorbed and held by the manipulator 111 having the wide nozzle 116, and the biochip 50 is transferred to a predetermined position via the adapter 70 (step S206).

  On the other hand, when the biochip 50 is shipped without being continuously processed for the biochip 50, the second box 140 is contacted with the exposed surface of the flange portion 72 as shown in FIGS. A fixed lid 150 having an elastic member 151 in contact therewith is attached to the first box 130. Thus, the biochip 50 is packed and shipped (step S207).

  After step S206, as shown in FIGS. 16 and 25, the adapter 70 sucked and held by the nozzle 116 of the manipulator 111 has an accommodation space 80a of the shaft portion 71 and an engagement surface 80b with which the flange portion 72 is engaged. It is transferred to the supporting container 80 provided. After the flange portion 72 is engaged with the engagement surface 80b, the suction and holding of the manipulator 111 with respect to the flange portion 72 by the nozzle 116 is released. Then, for example, the identification information about the biochip 50 is imaged and read by the imaging device 23 shown in FIG. 8 (step S208).

  Next, after the reading and confirmation of the identification information of the biochip 50 is completed, as shown in FIGS. 16 and 26, the manipulator 111 sucks and holds the flange portion 72, and similarly to the support container 80, the shaft portion The adapter 70 and the biochip 50 are transferred to a cleaning container 81 having a cleaning space 81a in which 71 is accommodated and an engaging surface 81b with which the flange portion 72 is engaged. Since the cleaning liquid 28 is stored in the cleaning space 81a in the cleaning container 81, the manipulator 111 performs the cleaning process by immersing the biochip 50 in the cleaning liquid 28, similarly to the cleaning process in the cleaning unit 7 described above ( Step S209).

  After the cleaning process of the biochip 50 is completed, as shown in FIGS. 16 and 27, the manipulator 111 sucks and holds the flange portion 72 and, like the cleaning container 81, the reaction space in which the shaft portion 71 is accommodated. The adapter 70 and the biochip 50 are transferred to the reaction vessel 82 having 82a and an engagement surface 82b with which the flange portion 72 engages. Since the specimen 53 is stored in the reaction space 82 a in the reaction vessel 82, the manipulator 111 immerses the biochip 50 in the specimen 53 via the adapter 70 and performs the reaction process similarly to the reaction process in the reaction unit 6 described above. Implement (step S210).

  In addition, after the reaction processing of the biochip 50 is completed, the manipulator 111 sucks and holds the flange portion 72 and transfers the biochip 50 to the cleaning container 81 again to perform the cleaning processing. Then, after the cleaning process is performed, the manipulator 111 uses the drying device 28 in the drying unit 8 in the state where the flange portion 72 is sucked and held, similarly to the first embodiment shown in FIG. 50 is dried (step S211).

  After the drying process is completed, as shown in FIGS. 16 and 28, the manipulator 111 transfers the adapter 70 sucked and held to the support base 161 which is a predetermined position for measurement arranged on the measurement stage ST. The support base 161 includes a hole 161 a that holds the shaft portion 71 of the adapter 70, and an engagement surface 161 b that engages with the flange portion 72. Further, after the shaft portion 71 is inserted into the hole portion 161a and the flange portion 72 is engaged with the engagement surface 161b, the manipulator 111 releases the suction and holding with respect to the adapter 70. After the adapter 70 is supported on the support base 161, the imaging device 60 images the index mark (not shown) provided on the biomolecule side of the substrate 52 as in the first embodiment, whereby the biochip 50 ( The alignment (positioning) with respect to the biomolecule 51) is performed, the focusing of the imaging device 60, and the imaging / measurement processing of the biomolecule 51 are performed (step S212). For example, the affinity between the biomolecule 51 and the above target (for example, reactivity or binding based on the presence / absence of fluorescence generation or the intensity of fluorescence) is detected based on the measurement result.

  As described above, in this embodiment, in addition to obtaining the same operation and effect as the first embodiment, the manipulator 111 indirectly transfers the biochip 50 via the adapter 70 including the flange portion 72. Since the treatment is performed, the adapter 70 (and thus the biochip 50) can be adsorbed in a larger area compared to the case where the substrate side of the biochip 50 is directly adsorbed. Therefore, in the present embodiment, the manipulator 111 transfers the biochip 50 to a predetermined position or reacts the biochip 50 at a predetermined position while holding the biochip 50 firmly and stably with a large adsorption force. It is possible to perform processing. Further, in the present embodiment, since the processing is performed with the flange portion 72 engaged, the biochip 50 being processed falls when the adsorption to the adapter 70 is stopped due to an unexpected situation. Thus, damage to the biomolecule 51 can be reduced.

[Third embodiment]
Next, a third embodiment of the biochip 50 screening method including the biomolecule array processing method using the above-described screening apparatus SC will be described with reference to FIGS. 29 to 30.
In these drawings, the same components as those of the first embodiment shown in FIGS. 1 to 15 are denoted by the same reference numerals, and the description thereof is omitted.

Since 3rd Embodiment differs in the form of the reaction process and the measurement process compared with 1st Embodiment, these differences are demonstrated.
FIG. 29 is a diagram in which the first box 30 is provided in the reaction unit 6 as a reaction vessel.
The first box 30 in the reaction unit 6 is arranged such that the support recess 33 opens upward. The specimen 53 that can specifically react with the biomolecule 51 is dispensed by the dispensing device 5 into the second concave portion 33 b on the bottom side of the support concave portion 33. For example, in a state where the biochip 50 is engaged with the bottom 33c, an amount of the sample 53 that can come into contact with the biomolecule 51 of the biochip 50 is dispensed into the second recess 33b.

  In the above configuration, the manipulator 11 in the adsorption holding device 26 transfers the biochip 50 to the support recess 33 in the first box 30 while adsorbing and holding the substrate side of the biochip 50. As a result, the substrate 52 engages with the bottom 33 c and the biomolecule 51 comes into contact with the sample 53, whereby the reaction process between the target contained in the sample 53 and the biomolecule 51 is performed.

  Then, the biochip 50 that has been subjected to the reaction process, the washing process, and the drying process is adsorbed and held on the substrate side by the manipulator 11 in the adsorption holding device 29 and provided on the biomolecule side of the substrate 52 as shown in FIG. The index mark (not shown) is imaged by the imaging device 60, whereby alignment (positioning) with respect to the biochip 50 (biomolecule 51) is performed. This alignment can be performed by moving the manipulator 11 with respect to the imaging device 60 or by moving the imaging device 60 with respect to the manipulator 11 or the biochip 50. Next, focusing processing of the imaging device 60 and imaging / measurement processing of the biomolecule 51 are performed. For example, the affinity between the biomolecule 51 and the above target (for example, reactivity or binding based on the presence / absence of fluorescence generation or the intensity of fluorescence) is detected based on the measurement result. Further, when the field of view of the imaging device 60 is narrower than the arrangement region of the biomolecules 51, the control device CONT moves the manipulator 11 so that the entire arrangement region of the biomolecules 51 can be comprehensively measured, and the plurality of times. The imaging is performed and the respective imaging results are combined. In addition, the measurement unit MS in the present embodiment performs alignment and measurement processing of the biomolecule 51 (for example, detection of the affinity between the target and the biomolecule) in a state where the biochip 50 is adsorbed and held by the manipulator 11. Is possible.

  Thus, in this embodiment, in addition to obtaining the same operation and effect as in the first embodiment, the first box 30 can be used in the reaction unit 6 for general purposes. Moreover, in this embodiment, in the measurement part MS, a measurement process can be implemented with the manipulator 11, and it can contribute to size reduction and price reduction of an apparatus.

[Fourth embodiment]
Next, a fourth embodiment of the screening method for the biochip 50 including the biomolecule array processing method using the screening apparatus SC will be described with reference to FIG.
In these drawings, the same components as those of the first embodiment shown in FIGS. 1 to 15 are denoted by the same reference numerals, and the description thereof is omitted.

  In the first to third embodiments, the screening device SC described above includes, for example, the marking unit 2, the reading unit 4, the dispensing device 5, the reaction unit 6, the cleaning unit 7, the drying unit 8, and the measuring unit MS. The related processing unit includes an adsorption holding device including the manipulator 11, and the biochip 50 is transferred through a delivery unit disposed between the units. In the present embodiment, as shown in FIG. 31, the case where the biochip 50 is transferred and the processing in each related processing unit is performed using the adsorption holding device 80 including one manipulator is described. To do.

  As shown in FIG. 31, the screening device SC of the present embodiment has a marking unit 2 and a reading unit 4 with a suction holding unit 80 having the same configuration as the manipulator 11, the driving device 14, and the suction device 15 described above. The related processing units of the dispensing device 5, the reaction unit 6, the cleaning unit 7, the drying unit 8, and the measurement unit MS are sequentially arranged in an annular shape so as to surround the suction holding unit 80.

  The adsorption holding unit 80 adsorbs and transfers the biochip 50 that has been processed in the previous process to each related processing unit, transfers the biochip 50, and causes the related processing unit to perform processing in the adsorbed and held state. After the processing in the related processing unit is completed, the adsorption holding unit 80 transfers the biochip 50 to the related processing unit that performs the next processing in a state where the biochip 50 is adsorbed and held, and the biochip 50 is adsorbed and held. The process in the related processing unit is repeated.

As described above, in the present embodiment, since the related processing can be completed in a state where the biochip 50 is adsorbed and held by the single adsorbing and holding unit 80, the apparatus can be significantly reduced in size and cost. .
In the present embodiment, the suction holding unit 80 transfers the biochip 50 to each related processing unit without performing the above-described delivery unit between the suction holding unit 80 and each related processing unit. By carrying out this, it is possible to further reduce the size and cost of the apparatus. For example, when the reaction process of the biomolecule 51 of another biochip 50 and the target contained in another specimen 53 is performed after the above-described reaction process, the manipulator 11 removes the nozzle 16 and performs a new clean. By attaching the appropriate nozzle 16, it becomes unnecessary to clean the manipulator 11 and the nozzle 16 every time the specimen 53 to be examined changes. As a result, the efficiency in the reaction process is improved and the cost in the process is reduced.

  As described above, a procedure for transferring the biochip 50 via a delivery unit provided between the related processing units, or a procedure for transferring the biochip 50 directly to each related processing unit by the adsorption holding unit 80. In addition, the robot apparatus 13 including the arm 12 provided between the related processing units having the first box 30 to which the biochip 50 subjected to the related processing in each related processing unit has been transferred has the biochip 50. A procedure for transferring the first box 30 may be used. By adopting this configuration, the moving distance of the suction holding unit (manipulator 11) provided in each related processing unit can be shortened, which can contribute to downsizing of the suction holding unit.

[Fifth Embodiment]
Next, a fifth embodiment of the screening method for the biochip 50 including the biomolecule array processing method using the screening apparatus SC will be described with reference to FIGS. 32 to 36.
In these drawings, the same components as those of the first embodiment shown in FIGS. 1 to 15 are denoted by the same reference numerals, and the description thereof is omitted.

  In the first embodiment, the procedure in which the biochips 50 are transferred one by one by the manipulator 11 and the related processing is performed is illustrated. However, in this embodiment, a plurality (three in this case) of biochips 50 are included in the manipulator 11. An example in which the related processing is performed by being transferred collectively and collectively as described above will be described.

FIG. 32 is a diagram illustrating, as an example, the first box 30 disposed in the delivery unit 3 and the transfer device 22 that transfers the biochip 50 to the first box 30.
The transfer device 22 includes a plurality of (in this case) three manipulators 11 arranged in correspondence with the arrangement pitch of the support recesses 33. Each of the three manipulators 11 includes a detachable nozzle 16 and is fixed together (or integrally) by a rigid suspension 18 extending in the horizontal direction.

  FIG. 33 is a diagram showing a plurality (here, three) of cleaning containers 27 that are disposed in the cleaning unit 7 and store the cleaning liquid 28, respectively, and the suction holding device 26 as an example. The suction holding device 26 includes a plurality (three here) of manipulators 11 arranged in correspondence with the arrangement pitch of the cleaning containers 27, and a suspension 18 that extends in the horizontal direction and fixes the three manipulators 11 collectively. And.

  FIG. 34 is a diagram showing, as an example, a plurality (three in this case) of reaction containers 25 that are arranged in the reaction unit 6 and store specimens 53, respectively, and the adsorption holding device 26 described above. The arrangement pitch of the reaction vessels 25 corresponds to the arrangement pitch of the three manipulators 11.

  FIG. 35 is a diagram illustrating a plurality of (here, three) drying devices 28 arranged in the drying unit 8 and the suction holding device 26 as an example. The arrangement pitch of the drying device 28 corresponds to the arrangement pitch of the three manipulators 11.

  FIG. 36 is a diagram illustrating the measurement stage ST, the suction holding device 29, and the imaging device 60 arranged in the measurement unit MS as an example. The measurement stage ST includes a plurality of support bases 61 that support the peripheral portion on the biomolecule side of a plurality (three in this case) of biochips 50 from below. The support base 61 is formed with a plurality (three in this case) of through-holes 61a penetrating in the vertical direction so as to open toward the biomolecule 51 to be measured when the biochip 50 is supported. . The adsorption holding device 29 includes a plurality of (three in this case) manipulators 11 arranged in correspondence with the arrangement pitch of the support portion of the biochip 50 and the through holes 61a, and the three manipulators 11 extending in the horizontal direction. And a suspension portion 18 to be fixed. Note that a plurality of imaging devices 60 illustrated in FIG. 36 may be arranged according to the number of biochips 50 to be detected.

In the screening device SC configured as described above, the transfer of the biochip 50 to and from the first box 30 by the transfer device 22 in the delivery unit 3, and the transfer of the biochip 50 to the cleaning container 27 by the adsorption holding device 26 in the cleaning unit 7. And the cleaning process, the transfer of the biochip 50 to the reaction vessel 25 by the adsorption holding device 26 in the reaction unit 6 and the reaction process, the transfer of the biochip 50 to the processing position of the drying device 28 by the adsorption holding device 26 in the drying unit 8 and The drying process, the transfer of the biochip 50 to the support base 61 by the adsorption holding device 29 in the measurement unit MS, and the measurement of the biochip 50 are collectively performed on a plurality (three in this case) of biochips 50. The
Therefore, in this embodiment, it is possible to perform the screening process for a large number of biochips 50 in a short time.

[Sixth Embodiment]
Next, a sixth embodiment of the screening method for the biochip 50 including the biomolecule array processing method using the screening apparatus SC will be described with reference to FIGS. 37 to 42.
In these drawings, the same components as those of the first embodiment shown in FIGS. 1 to 15 are denoted by the same reference numerals, and the description thereof is omitted.

  In the present embodiment, a case will be described in which three biochips 50A to 50C are sequentially screened using a pipeline method. In the present embodiment, a screening process using a pipeline system is described across the delivery unit 9, the reaction unit 6, the cleaning unit 7, the drying unit 8, and the measurement unit MS. In addition, here, as an example, two reaction containers 25A and 25B are arranged in the reaction unit 6, two washing containers 27A and 27B are arranged in the washing unit 7, and the biochip 50 that has completed the reaction process is provided. The drying process is performed immediately.

  First, as shown in FIG. 37, the biochip 50A mounted on the first box 30 in the delivery unit 9 is sucked and held by the manipulator 11 of the suction holding device 26 and transferred to the cleaning unit 7, and the biochip 50A is washed. 7 is immersed in the cleaning liquid 28 of the cleaning container 27A. Next, the manipulator 11 releases the adsorption holding to the biochip 50A in the cleaning container 27A, and the manipulator 11 of the adsorption holding device 26 adsorbs and holds the biochip 50B mounted in the first box 30, as shown in FIG. Then, the biochip 50B is immersed in the cleaning liquid 28 of the cleaning container 27B in the cleaning unit 7. In the above processing of the biochip 50A and the biochip 50B by the manipulator 11, the nozzle 16 of the manipulator 11 may be replaced or cleaned before the processing from the viewpoint of contamination of foreign matters.

  Next, as shown in FIG. 39, the manipulator 11 adsorbs and holds the biochip 50 </ b> A in the cleaning container 27 </ b> A that has been subjected to the cleaning process to the reaction unit 6 and transfers the biochip 50 </ b> A to the reaction unit 6. The biochip 50A is immersed in the specimen 53. The manipulator 11 in which the biochip 50A is immersed in the specimen 53 releases the adsorption hold on the biochip 50A, and then holds the biochip 50C from the first box 30 and transfers it to the cleaning unit 7, as shown in FIG. The biochip 50C is immersed in the cleaning liquid 28 of the cleaning container 27A in the cleaning unit 7. Then, the manipulator 11 that has released the adsorption and holding of the biochip 50C immersed in the cleaning liquid 28 adsorbs and holds the biochip 50B in the cleaning container 27B that has been subjected to the cleaning process, transfers the biochip 50B to the reaction unit 6, and the reaction in the reaction unit 6 The biochip 50B is immersed in the specimen 53 of the container 25B.

  Next, as shown in FIG. 41, the manipulator 11 sucks and holds the biochip 50 </ b> A for which the reaction process has been completed, and transfers the biochip 50 </ b> A to a position facing the drying device 28 in the drying unit 8. Then, the biochip 50A subjected to the drying process is transferred to the measurement unit MS described above by the manipulator 11, and the measurement process is performed. The biochip 50A for which the measurement process has been completed is transferred by the manipulator 11 to the first storage box.

  The manipulator 11 that has completed the transfer processing of the biochip 50A to the measurement unit MS releases the adsorption holding for the biochip 50A, and then adsorbs and holds the biochip 50C in the cleaning container 27A that has completed the cleaning processing, thereby reacting. 42, the biochip 50C is immersed in the specimen 53 of the reaction vessel 25A in the reaction unit 6 as shown in FIG. Next, the manipulator 11 that has released the adsorption and holding of the biochip 50C immersed in the specimen 53 adsorbs and holds the biochip 50B in the reaction vessel 25B that has completed the reaction process, and transfers the biochip 50B to the drying unit 8. The biochip 50B is transferred to a position facing the drying device 28. Then, the biochip 50B subjected to the drying process is transferred to the measurement unit MS described above by the manipulator 11, and the measurement process is performed. In the above processing of the biochip 50A, the biochip 50B, and the biochip 50C by the manipulator 11, the nozzle 16 of the manipulator 11 may be replaced or washed before the processing from the viewpoint of contamination of the specimen. The replaced or cleaned nozzle 16 is a consumable because it is discarded after being used in the related process described above.

  Thereafter, the manipulator 11 sequentially transfers the biochip 50 to the related processing unit in the next process as soon as one process is completed for the biochip 50C and the other biochip 50D, and performs the related processing. Even when a single manipulator 11 is used, efficient screening can be performed.

  The preferred embodiments according to the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the examples. Various shapes, combinations, and the like of the constituent members shown in the above-described examples are examples, and various modifications can be made based on design requirements and the like without departing from the gist of the present invention.

  For example, in the above-described embodiment, the array box 20 has been described as being capable of supporting a plurality (three in the figure) of biochips 50. However, the present invention is not limited to this. For example, only one biochip 50 can be supported. It is good also as a structure.

Moreover, in the said embodiment, although the structure which adsorbs and hold | maintains the biochip 50 by negative-pressure attraction | suction was illustrated, it is not limited to this, For example, the magnetic attachment holding | maintenance using the magnetic force of an electromagnet or an electrostatic force is used. It may be configured to perform suction holding such as electrostatic holding.
Moreover, since the manipulator 11 of the above embodiment can adsorb and hold the biochip 50 and the adapter 70 with the nozzle 16, the biochip 50 and the adapter 70 can be easily handled.

  In the above-described embodiment, the configuration in which only one measuring unit MS is provided is illustrated. However, the present invention is not limited to this, and is independent as in the case of using a plurality of manipulators 11, a plurality of reaction vessels 25, and the like. Thus, a configuration in which a plurality of measurement units MS are provided so that measurement is possible may be employed. In this case, since an error may occur in the measurement results among the plurality of measurement units MS, for example, each measurement unit MS measures in advance with respect to the same measurement object, and a correction value for each measurement unit MS from all measurement results. Ask for. In actual measurement, each measurement unit MS may correct the measurement result obtained by each measurement unit MS with a correction value corresponding to each measurement unit MS.

Moreover, in the said embodiment, although the several manipulator 11 illustrated the structure which can move integrally or collectively by the suspension part 18, it is not limited to this structure. For example, as shown in FIG. 43, the manipulators 11 are three-dimensionally independent of each other depending on the progress of screening and the processing speed of the biochip 50 in each related process (eg, reaction process or measurement process). (Alternatively, it may be configured to be movable in a one-dimensional or two-dimensional manner), and may be configured to perform, for example, the above-described reaction processing, measurement processing, and pipeline screening. Further, the plurality of support bases 61 arranged on the measurement stage ST shown in FIG. 36 and the plurality of imaging devices 60 as shown in FIG. 44 depend on the progress of screening, the processing speed of the biochip 50 in each related process, and the like. For example, the above-described pipeline-type screening may be performed so as to be movable in a three-dimensional (or one-dimensional or two-dimensional) manner independently of each other. As shown in FIG. 44, for example, the measurement unit (detection device) MS includes a plurality of manipulators 11 integrally formed by the suspension unit 18 and a three-dimensional (or one-dimensional or And a plurality of imaging devices 60 movable in a two-dimensional manner. When measuring the biochip 50 in the configuration as shown in FIG. 44, the measurement unit (detection device) MS can perform measurement alignment and focus adjustment on the biochip 50 by moving the imaging device 60 in a predetermined direction. is there. Further, for example, the measurement unit (detection device) MS excludes the suspension unit 18 as shown in FIG. 43 in the configuration of FIG. 44, and the plurality of manipulators 11 and the plurality of imaging devices 60 are each independently three-dimensional (or The configuration may be movable in a one-dimensional or two-dimensional manner.
Further, screening is performed by providing a plurality of apparatus groups including the manipulator 11, the mounting unit 1, the marking unit 2, the reading unit 4, the dispensing device 5, the reaction unit 6, the cleaning unit 7, the drying unit 8, the measuring unit MS, and the like described above. The structure which implements may be sufficient. In such a configuration, for example, an auxiliary manipulator is prepared, and the load status of each device group is monitored, and when a device group with a large load is generated, the auxiliary manipulator appropriately assists transfer in the device group. It is good also as a structure which does.
In addition, the manipulator 11 in the above embodiment may be configured to be used in common with the same manipulator in each related process (eg, dispensing process, reaction process, measurement process, etc.). In this case, it is desirable that the nozzle 16 of the manipulator 11 be detached and replaced for each related process from the viewpoint of contamination of the specimen or foreign matter.

  25 ... Reaction vessel, 26, 29, 80 ... Adsorption holding device (adsorption holding unit), 30 ... First box (array holder), 50 ... Biochip (biomolecule array), 51 ... Biomolecule, 52 ... Substrate, 61 ... Support base (predetermined position for measurement, array holder), 70 adapter (holding part), 120 ... array box (body for biomolecule array), SC ... screening device, MS ... measuring part (detection device)

Claims (10)

A substrate, formed on a first surface of said substrate, and a screening method using a biochip having a target and capable of specifically reacting biomolecules contained in the sample,
A dispensing process for dispensing the sample into a reaction container;
Wherein in a state where the second surface is a surface opposite adsorbed and held by the suction holding means and the first surface of the substrate in the biochip, said biochip dispensed the specimen into the reaction vessel A reaction treatment for immersing the target and the biomolecule to react;
A cleaning process for cleaning the biochip after the reaction process ;
A drying treatment you drying the biochip after the cleaning process,
Using the biochip after the drying treatment, a detection treatment for detecting the affinity between the target and the biomolecule;
-Containing steam cleaning method. The screening method according to claim 1,
A transfer process for transferring the biochip after the drying process to a measurement unit in a state where the second surface of the substrate of the biochip is held by the adsorption holding unit in order to perform the detection process; ,
The detection process is based on a result obtained by imaging the biomolecule of the biochip after the transfer process with the imaging unit in a state where the adsorption holding with respect to the biochip is released by the adsorption holding unit. To detect the affinity between the target and the biomolecule
Screening method. The screening method according to claim 2, wherein
A second dispensing process for dispensing the second sample into the second reaction container;
After the adsorption holding on the biochip is released by the adsorption holding means for performing the detection process, the biochip is different from the biochip, and includes a second substrate and a first surface of the second substrate. The second substrate of the second substrate in the second biochip having a second biomolecule formed on the first surface of the second substrate and capable of specifically reacting with the second target contained in the second specimen. The second sample dispensed in the second reaction container is secondly dispensed in the second reaction container in a state where the second substrate second surface opposite to the substrate first surface is adsorbed and held by the adsorption holding means. A second reaction process in which a biochip is immersed to react the second target with the second biomolecule.
Screening method. In the screening method according to any one of claims 1 to 3,
In order to perform the cleaning process, a second transfer process of transferring the biochip after the reaction process to the cleaning unit in a state where the second surface of the substrate of the biochip is held by the adsorption holding unit. When,
In order to perform the drying process, a third transfer process of transferring the biochip after the cleaning process to the drying unit in a state where the second surface of the substrate in the biochip is held by the adsorption holding unit. Including
The cleaning process is performed by cleaning the biochip after the second transfer process in a state in which the second surface of the substrate in the biochip is adsorbed and held by the adsorption holding unit.
  The drying process is to dry the biochip after the third transfer process in a state in which the second surface of the substrate in the biochip is adsorbed and held by the adsorption holding means.
In the reaction process, the second transfer process, the cleaning process, the third transfer process, and the drying process, the second surface of the substrate in the biochip is absorbed and held by the adsorption holding means. Do in state
Screening method. In the screening method according to any one of claims 1 to 4,
In the reaction process, the second surface of the substrate in the biochip is adsorbed and held by the adsorption holding means, and the biochip is immersed in the sample dispensed in the reaction container, A stirring process for stirring the sample dispensed in the reaction container by rotating the adsorption holding means around an axis parallel to the vertical axis
Screening method. A dispensing unit for dispensing a sample containing a target into a reaction container;
An adsorption holding unit configured to adsorb and hold a biochip having a substrate and a biomolecule formed on the first surface of the substrate and capable of specifically reacting with the target;
A drive unit for moving the suction holding unit;
A cleaning section for cleaning the biochip;
A drying section for drying the biochip;
A support part for supporting the biochip;
An imaging unit for imaging the biomolecule of the biochip;
A dispensing process for dispensing the sample into the reaction container by the dispensing unit, and a second surface of the biochip opposite to the first surface of the substrate is adsorbed and held in the adsorption holding unit. In this state, a reaction process in which the adsorption holding unit is moved by the driving unit so that the biochip is immersed in the sample dispensed in the reaction container, and the target and the biomolecule are reacted. A transfer process of transferring the biochip after the reaction process to the cleaning unit in a state where the second surface of the substrate of the biochip is adsorbed and held by the adsorption holding unit; and the bio process after the transfer process A cleaning process for cleaning the chip by the cleaning unit, and the biochip after the cleaning process in the state in which the second surface of the substrate of the biochip is suction-held by the suction-holding unit. A second transfer process for transferring to the drying unit; a drying process for drying the biochip after the second transfer process to the drying unit; and the second surface of the substrate in the biochip is adsorbed to the adsorption holding unit. A third transfer process for transferring the biochip after the drying process to the support unit in a state of being held, and the biochip after the third transfer process is supported by the support unit. Control is performed to execute an imaging process that causes the imaging unit to image the biomolecule of the chip and a detection process that detects the affinity between the target and the biomolecule based on a result obtained by the imaging process. A control unit;
A screening apparatus comprising: The screening apparatus according to claim 6, wherein
The control unit, as the imaging process, supports the biochip after the third transfer process on the support unit, and releases the adsorption hold on the biochip to the bioretention unit. Let the imaging unit image the biomolecule of the chip
Screening equipment. The screening apparatus according to claim 7, wherein
The dispensing unit dispenses a second specimen containing a second target into a second reaction container,
The adsorption holding unit includes a second substrate and a second biomolecule formed on the first surface of the second substrate that is the first surface of the second substrate and capable of specifically reacting with the second target. Adsorbing and holding a second biochip having
The control unit causes the adsorption holding unit to perform the second dispensing process for dispensing the second sample into the second reaction container by the dispensing unit, and the adsorption holding for the biochip after the third transfer process. After the release, in the state where the second substrate second surface of the second substrate in the second biochip opposite to the second substrate first surface is adsorbed and held by the adsorption holding unit, The adsorption holding unit is moved by the driving unit so that the second biochip is immersed in the second sample dispensed in the second reaction container, and the second target reacts with the second biomolecule. And controlling to execute the second reaction process.
Screening equipment. In the screening apparatus according to any one of claims 6 to 8,
The reaction process, the transfer process, the cleaning process, the second transfer process, and the drying process are performed in a state where the second surface of the substrate in the biochip is adsorbed and held by the adsorption holding unit. Control to run
Screening equipment. In the screening apparatus according to any one of claims 6 to 9,
In the reaction process, the second surface of the substrate in the biochip is adsorbed and held by the adsorption holding unit, and the biochip is immersed in the sample dispensed in the reaction container, The adsorption holding unit is rotated around an axis parallel to a vertical axis by a driving unit to stir the sample dispensed in the reaction container and to react the target with the biomolecule.
Screening equipment.

Images