JP4449466B2 - Spotting device, spotting method, and controller for spotting device - Google Patents

Description

  The present invention relates to a spotting device, a spotting method, and a control device for a spotting device for spotting a sample adsorbed to a spot pin by movement of the spot pin on a substrate.

  In recent years, genetic information of organisms has been used in a wide range of fields such as the medical field and the agricultural field. However, it is indispensable to specify the base sequence of DNA when using genes. DNA has two polynucleotide strands that are twisted in a spiral shape, and each polynucleotide strand is one-dimensionally composed of four types of bases (adenine: A, guanine: G, cytosine: C, thymine: T). Based on the complementarity of adenine and thymine and guanine and cytosine, the bases of one polynucleotide chain are bonded to the bases of the other polynucleotide chain.

  A DNA microarray has been developed to specify the base sequence of DNA. A DNA microarray is an array of a plurality of types of spots composed of single-stranded DNA probes having a known base sequence arranged on the surface of a substrate. In order to specify the base sequence of DNA using a DNA microarray, a single-stranded DNA sample having an unknown base sequence and fluorescently labeled is hybridized to a complementary spot, and a plurality of arrays arranged in an array are obtained. Spots that emit fluorescence are identified from among the spots. This makes it possible to specify that the single-stranded DNA sample has a base sequence complementary to the fluorescent spot.

  By the way, in manufacturing a DNA microarray, a spotting apparatus described in Patent Document 1 (referred to as a biochip creation apparatus in Patent Document 1) is used. The spotting apparatus described in Patent Document 1 includes a spot pin that adsorbs a single-stranded DNA probe, a substrate mounting table on which a substrate is mounted, and the spot pins in the XYZ directions (the XY plane is the substrate) above the substrate mounting table. An XYZ driving device that is driven in parallel to the mounting table and whose Z direction is perpendicular to the substrate mounting table), and a drive controller that controls the XYZ driving device.

The spotting device described in Patent Literature 1 controls the XYZ driving device with the drive controller, positions the spot pins in the XY plane with the XYZ driving device, and further controls the XYZ driving device with the drive controller. Thus, the spot pin is lowered by the XYZ driving device. When the spot pin is lowered, the single-stranded DNA probe is spotted on the surface of the substrate.
JP 2002-181837 A

  In the conventional spotting device, when the substrate is mounted on the substrate mounting table in an accurate posture, the positioning of the spot pin is defined by the XY coordinates by the XYZ driving device. Can be spotted at the exact position of the surface. However, when the substrate is placed on the substrate mounting table in an incorrect posture, the single-stranded DNA probe cannot be spotted at an accurate position on the surface of the substrate. For example, when the substrate is placed at a position rotated by a predetermined angle around the Z axis from an accurate position on the substrate placement table, the single-stranded DNA probe is spotted at an accurate position in the XY coordinates. Is used as a reference, the single-stranded DNA probe is spotted at a position rotated by a predetermined angle from the position to be spotted.

  Therefore, the present invention has been made in order to solve the above-described problems, and a sample such as a single-stranded DNA probe can be used regardless of the posture of the base material such as the substrate in the XY plane. It is an object of the present invention to provide a spotting device, a spotting method, and a control device for the spotting device that can spot the target at an accurate position on the surface of the substrate.

In order to solve the above problems, the spotting apparatus of the present invention is:
A spot pin for adsorbing a sample;
A light projecting element that projects light toward a solid-state imaging device including a plurality of photoelectric conversion elements arranged along a light receiving surface (hereinafter referred to as uv surface);
A driving device for driving the spot pin and the light projecting element along an XY plane parallel to the uv surface of the solid-state imaging device above the uv surface of the solid-state imaging device ;
A control device for controlling the driving device;
With
The control device is
The driving device drives the light projecting element along the XY plane, scans the uv surface of the solid-state imaging device with the light projecting element, and two photoelectric conversions in a state separated from each other among the plurality of photoelectric conversion elements Coordinate detecting means for detecting XY coordinates in the XY plane for two points in the uv surface of the solid-state imaging device by receiving light of the light projecting element using an element ;
Coordinate conversion means for converting the uv coordinates on the uv surface into XY coordinates on the XY plane for the spot position where the sample is spotted on the uv surface of the solid-state imaging device based on the two XY coordinates detected by the coordinate detection means When,
XY movement control means for operating the driving device to move the spot pin to XY coordinates converted by the coordinate conversion means;
Spotting means for operating the driving device so that a sample is spotted on the uv surface of the solid-state imaging device from the spot pin moved by the XY movement control means;
It is characterized by having.

Preferably, when said one of the XY coordinates of the detected two points by the coordinate detecting means and (X _0, Y _0), and the other as (X _1, Y _1), the coordinate conversion means, wherein The uv coordinates of the spot position where the sample is spotted on the uv surface of the solid-state imaging device are converted into XY coordinates that can be expressed by the following equation (1).

However,

It is.

Preferably, the spotting means, said spotting pin by XY movement controlling means Ru operates the drive so as to lower the spotting pin in position moves.

The spotting method of the present invention is
A spot pin for adsorbing a sample, a light projecting element that projects light toward a solid-state imaging device including a plurality of photoelectric conversion elements arranged along a light receiving surface (hereinafter referred to as uv surface), and the solid-state imaging device A driving device that drives the spot pin and the light projecting element along an XY plane parallel to the uv surface of the solid-state imaging device, and a control device that controls the driving device. a wear method that using a spotting device,
The control device causes the driving device to drive the light projecting element along the XY plane, scans the uv surface of the solid-state imaging device with the light projecting device, and is separated from each other among the plurality of photoelectric conversion elements A coordinate detection step of detecting XY coordinates in the XY plane for two points in the uv surface of the solid-state imaging device by receiving light of the light projecting element using the two photoelectric conversion elements ;
Based on the two XY coordinates detected by the coordinate detection step , the control device converts the uv coordinate on the uv surface to the XY coordinate on the XY plane for the spot position where the sample is spotted on the uv surface of the solid-state imaging device. A coordinate transformation step to transform;
Wherein the controller, and the XY moving control step of operating the drive device to move the spotting pin in transformed XY coordinates by the coordinate conversion step,
A spotting step in which the control device operates the driving device so that a sample is spotted on the uv surface of the solid-state imaging device from the spot pin moved by the XY movement control step;
It is characterized by including.

Preferably, the one of the XY coordinates of two points that have been detected in the coordinate detection step and (X _0, Y _0), when the other as (X _1, Y _1), in the coordinate conversion step, the The uv coordinates of the spot position where the sample is spotted on the uv surface of the solid-state imaging device are converted into XY coordinates that can be expressed by the above equation (1).

Preferably, in the spotting process, wherein the spotting pin by XY movement controlling step Ru operates the drive so as to lower the spotting pin in position moves.

Further, the control device for the spotting device of the present invention is:
A sample is adsorbed along an XY plane parallel to the uv surface of the solid-state imaging device above a solid-state imaging device having a plurality of photoelectric conversion elements arranged along a light receiving surface (hereinafter referred to as uv surface). a spotting pin for, a control device of the destination device that controls the driving device for driving the light projecting elements for projecting light, a toward the solid-state imaging device,
The driving device drives the light projecting element along the XY plane, scans the uv surface of the solid-state imaging device with the light projecting element, and is arranged in a state separated from each other among the plurality of photoelectric conversion elements. Coordinate detecting means for detecting XY coordinates in the XY plane for two points in the uv surface of the solid-state imaging device by receiving light of the light projecting element using two photoelectric conversion elements ;
Coordinate converting means for converting the uv coordinates on the uv surface into XY coordinates on the XY plane for the spot position where the sample is spotted on the uv surface of the solid-state imaging device based on the two XY coordinates detected by the coordinate detecting means. When,
XY movement control means for operating the drive device to move the spot pin to the XY coordinates converted by the coordinate conversion means;
Spotting means for operating the driving device so that a sample is spotted on the uv surface of the solid-state imaging device from the spot pin moved to a predetermined XY coordinate position by the XY movement control means;
It is characterized by providing.

Preferably, when said one of the XY coordinates of the detected two points by the coordinate detecting means and (X _0, Y _0), and the other as (X _1, Y _1), the coordinate conversion means, wherein The uv coordinates of the spot position where the sample is spotted on the uv surface of the solid-state imaging device are converted into XY coordinates that can be expressed by the above equation (1).

Preferably, the spotting means, said spotting pin by XY movement controlling means Ru operates the drive so as to lower the spotting pin in position moves.

In the present invention, by detecting the XY coordinates of two points in the uv surface of the solid-state imaging device that is the base material , the posture of the base material in the XY plane can be grasped, and the base material is accurate in the XY plane. You can see how much you deviate from your posture. Then, since the uv coordinate of the spot position where the sample is spotted on the uv surface of the base material is converted into the XY coordinate based on the two XY coordinates, the XY coordinate of the spot position is the amount that the base material has deviated from the correct posture. Is corrected. Since the XY coordinates of the spot position are corrected and the spot pin is moved to that position, the sample can be spotted at an accurate position in the uv surface of the substrate.

According to the present invention, since the spot position is coordinate-converted from the uv coordinate to the XY coordinate based on the XY coordinates of two points in the uv surface of the solid-state imaging device that is the base material , Even in such a posture, the sample can be spotted at an accurate position in the uv surface of the substrate.

  The best mode for carrying out the present invention will be described below with reference to the drawings. However, although various technically preferable limitations for implementing the present invention are given to the embodiments described below, the scope of the invention is not limited to the following embodiments and illustrated examples.

  FIG. 1 is a perspective view of a spotting device 1 according to an embodiment to which the present invention is applied, and FIG. 2 is a block diagram of a circuit configuration of the spotting device 1. As shown in FIGS. 1 and 2, the spotting device 1 includes a mounting table 2 on which a plurality of base materials 91, 91,... Are placed and a plate 93 containing a plurality of types of samples 92, 92,. Plate mounting table 3 to be mounted, spot pin 4 for adsorbing sample 92, cleaning tank 5 for cleaning spot pin 4, dryer 6 for drying spot pin 4, mounting table 2, plate mounting table 3, An XYZ driving device 7 for driving the spot pin 4 along the XY plane parallel to the upper surface of the mounting table 2 above the cleaning tank 5 and the dryer 6 and driving the spot pin 4 in the vertical direction perpendicular to the XY plane; A plurality of photoelectric conversion elements 20, 20,... (Shown in FIG. 3) provided on each of the base materials 91, 91,..., A light projecting element 8 provided on the XYZ driving device 7, and a display for performing display. An input device 1 including a device 9 and a keyboard Comprising the light projecting element 8, the photoelectric conversion elements 20, 20, ..., XYZ driving unit 7, a control unit 11 for controlling the display device 9 and the input device 10, the. Then, the spotting device 1 controls the XYZ driving device 7 with the control device 11 to move the spot pin 4 to the spot position to be spotted with the XYZ driving device 7, and further the XYZ driving device with the control device 11. 7, the spot pin 4 is lowered at that position by the XYZ driving device 7. That is, the spotting device 1 spots the sample 92 adsorbed on the tip of the spot pin 4 by the movement of the spot pin 4 by the XYZ driving device 7 on the base material 91.

  First, the base material 91 will be described with reference to FIGS. Here, FIG. 3 is a plan view of the base material 91, FIG. 4 is a plan view showing an electrode structure of the photoelectric conversion element 20 provided on the base material 91, and FIG. FIG.

  The base material 91 is a solid-state imaging device in which the photoelectric conversion elements 20, 20,... As pixels are arranged in a matrix on the transparent substrate 17, and has a plate shape as a whole. The photoelectric conversion elements 20, 20,... Are collectively covered with a protective insulating layer 31.

  The transparent substrate 17 is a glass substrate such as quartz glass or a plastic substrate such as polycarbonate or PMMA. The transparent substrate 17 has a property of transmitting light (hereinafter referred to as “light transmission”) and has an insulating property.

  The photoelectric conversion elements 20, 20,... Are elements having a double gate transistor structure. That is, the photoelectric conversion elements 20, 20,... Face the bottom gate electrode 21 formed on the transparent substrate 17, the bottom gate insulating film 22 formed on the bottom gate electrode 21, and the bottom gate electrode 21, respectively. At the same time, an intrinsic semiconductor film 23 sandwiching the bottom gate insulating film 22 with the bottom gate electrode 21, a channel protective film 24 formed on the center of the semiconductor film 23, and both ends of the semiconductor film 23 are formed apart from each other. Impurity semiconductor films 25, 26 formed, source electrode 27 formed on impurity semiconductor film 25, drain electrode 28 formed on impurity semiconductor film 26, and formed on source electrode 27 and drain electrode 28. The top gate insulating film 29 and the semiconductor film 23 are opposed to each other, and the top gate insulating film 29 and the channel protective film 24 are sandwiched between the semiconductor film 23. And Ppugeto electrode 30 comprises a.

  The bottom gate electrode 21 is formed on the transparent substrate 17 for each photoelectric conversion element 20. Further, a plurality of bottom gate lines 41, 41,... Extending in the horizontal direction are formed on the transparent substrate 17, and the photoelectric conversion elements 20, 20,. Each bottom gate electrode 21 is formed integrally with a common bottom gate line 41. The bottom gate electrode 21 and the bottom gate line 41 have conductivity and light shielding properties, and are made of, for example, chromium, a chromium alloy, aluminum, an aluminum alloy, or an alloy thereof.

The bottom gate insulating film 22 is formed in common to all the photoelectric conversion elements 20, 20,..., And the bottom gate electrode 21 and the bottom gate lines 41, 41,. Covered. The bottom gate insulating film 22 has insulating properties and light transmissive properties, and is made of, for example, silicon nitride (SiN) or silicon oxide (SiO ₂ ).

  A semiconductor film 23 is formed for each photoelectric conversion element 20 on the bottom gate insulating film 22. The semiconductor film 23 has a substantially rectangular shape in plan view, and is a layer formed of amorphous silicon or polysilicon that generates electron-hole pairs in an amount corresponding to the amount of received light. A channel protective film 24 is formed on the semiconductor film 23. The channel protective film 24 has insulating properties and light transmissive properties, and is made of, for example, silicon nitride or silicon oxide. The channel protective film 24 protects the interface of the semiconductor film 23 from an etchant used for patterning. When light enters the semiconductor film 23, an amount of electron-hole pairs according to the amount of incident light is generated around the interface between the channel protective film 24 and the semiconductor film 23. In this case, holes are generated as carriers on the semiconductor film 23 side, and electrons are generated on the channel protective film 24 side.

An impurity semiconductor film 25 is formed on one end portion of the semiconductor film 23 so as to partially overlap the channel protective film 24, and an impurity semiconductor film 26 is partially channeled on the other end portion of the semiconductor film 23. It is formed so as to overlap the protective film 24. The impurity semiconductor films 25 and 26 are patterned for each photoelectric conversion element 20. The impurity semiconductor films 25 and 26 are made of amorphous silicon (n ⁺ silicon) containing n-type impurity ions.

  A source electrode 27 patterned for each photoelectric conversion element 20 is formed on the impurity semiconductor film 25. A drain electrode 28 patterned for each photoelectric conversion element 20 is formed on the impurity semiconductor film 26. In addition, a plurality of source lines 42, 42,... And drain lines 43, 43,... Extending in the vertical direction are formed on the bottom gate insulating film 22. The source electrodes 27 of the photoelectric conversion elements 20, 20,... In the same column arranged in the vertical direction are formed integrally with the common source line 42, and photoelectric conversions in the same column arranged in the vertical direction. The drain electrodes 28 of the elements 20, 20,... Are integrally formed with a common drain line 43. The source electrode 27, the drain electrode 28, the source line 42, and the drain line 43 have conductivity and light shielding properties, and are made of, for example, chromium, a chromium alloy, aluminum, an aluminum alloy, or an alloy thereof.

  The top gate insulating film 29 is formed in common to all the photoelectric conversion elements 20, 20,..., And the channel protective film 24, the source electrode 27, the drain electrode 28, and the source line of the photoelectric conversion elements 20, 20,. .. And the drain lines 43, 43,... Are collectively covered. The top gate insulating film 29 has insulating properties and light transmissive properties, and is made of, for example, silicon nitride or silicon oxide.

  A top gate electrode 30 patterned for each photoelectric conversion element 20 is formed on the top gate insulating film 29. Further, a plurality of top gate lines 44, 44,... Extending in the horizontal direction are formed on the top gate insulating film 29, and the photoelectric conversion elements 20, 20, 20 in the same row arranged in the horizontal direction are formed. Each top gate electrode 30 is formed integrally with a common top gate line 44. The top gate electrode 30 and the top gate line 44 are conductive and light transmissive, for example, indium oxide, zinc oxide, tin oxide, or a mixture containing at least one of them (for example, tin-doped indium oxide ( ITO) and zinc-doped indium oxide).

  The protective insulating layer 31 collectively covers the top gate electrode 30 and the top gate lines 44, 44,... Of the photoelectric conversion elements 20, 20,. The protective insulating layer 31 has insulating properties and light transmittance, and is made of silicon nitride or silicon oxide.

  The substrate 91 configured as described above has the surface of the protective insulating layer 31 as a light receiving surface, and the photoelectric conversion elements 20, 20,... Are arranged in a matrix along the light receiving surface. Each photoelectric conversion element 20 is provided so as to convert the amount of light received by the semiconductor film 23 into an electrical signal. Hereinafter, the light receiving surface of the substrate 91 is referred to as the uv surface.

  Here, the base material 91 is detachably attached to the mounting table 2 and is mounted on the mounting table 2. The control device 11 includes a drive circuit that drives a substrate 91 that is a solid-state imaging device. And the control apparatus 11 measures by each of several photoelectric conversion element 20,20 ... provided in the base material 91 by driving the base material 91 mounted in the mounting base 2 with a drive circuit. The light quantity is provided as an electric signal.

  Further, among the photoelectric conversion elements 20, 20, 20, 20 arranged at the four corners of the base material 91, the light amount measured by the two photosensors 20 a, 20 b arranged at both ends of one side and not in a diagonal relationship is controlled. Used for processing of the device 11. When a side connecting the photosensor 20a and the photosensor 20b is a v-axis, a uv coordinate composed of the v-axis and a u-axis orthogonal to the v-axis is defined on the uv surface of the substrate 91.

  Next, each part of the spotting device 1 will be described.

  As shown in FIG. 1, the upper surface of the mounting table 2 is formed flat.

  The upper surface of the plate mounting table 3 is also formed flat. A plurality of recesses arranged in a matrix are formed on the plate 93 placed on the plate placing table 3. One type of sample 92 is stored per recess. Many single-stranded DNA probes contained in a kind of sample 92 have the same known base sequence.

  The cleaning tank 5 is a container opened upward, and water is stored in the cleaning tank 5.

  The dryer 6 blows out the heat generated by the heater as warm air upward by a fan.

  The spot pin 4 has a needle shape extending vertically, the lower tip of the spot pin 4 is sharply formed, and an internal flow path is formed that extends along the center line from the lower tip of the spot pin 4 to the inside. Has been. The spot pin 4 adsorbs the sample 92 to the tip and the internal flow path. Instead of the needle-like spot pin 4, a spot pin with a dropper structure that sucks the sample 92 and sucks the sample 92 may be provided.

  As shown in FIGS. 1 and 2, the XYZ driving device 7 includes a Y guide member 71 extending in the Y direction that defines the XY plane, an X direction orthogonal to the Y direction, and along the Y direction. An X guide member 72 that is movable and attached to the Y guide member 71, a head 73 that is movable along the X direction and is attached to the X guide member 72, and an X guide along the Y guide member 71 A Y drive unit 74 that drives the member 72 in the Y direction, an X drive unit 75 that drives the head 73 in the X direction along the X guide member 72, and the spot pin 4 in the vertical direction perpendicular to the XY plane. And a Z drive unit 76 for driving. For example, a combination of a motor, an endless belt, and a pulley, and a combination of a motor and a ball screw can be applied to both the X drive unit 75 and the Y drive unit 74. The spot pin 4 is attached to the head 73 via a Z drive unit 76. As the Z drive unit 76, for example, an air cylinder, an electromagnetic solenoid or the like can be applied.

  Here, the X coordinate is defined by the extending direction of the X guide member 72, the Y coordinate is defined by the extending direction of the Y guide member 71, and the Z coordinate is defined by the moving direction of the spot pin 4 by the Z drive unit 76. The Therefore, the plane defined by the extending direction of the X guide member 72 and the extending direction of the Y guide member 71 is the XY plane. Since the Y guide member 71 and the X guide member 72 are parallel to the mounting surface of the mounting table 2 and the base material 91 is provided in a flat plate shape, the XY plane is substantially the same as the uv surface. Parallel.

  The light projecting element 8 is attached to the head 73 and is provided so as to be movable along the XY plane together with the spot pin 4. The light projecting element 8 is a light source that emits light in a wavelength region that excites the photoelectric conversion element 20 including a laser diode, an LED, or a cathode tube toward the photoelectric conversion element 20.

  As the display device 9, a liquid crystal display device, a CRT, or an organic EL display device can be applied. The display device 9 is provided so as to perform display according to the display signal input from the control device 11.

  The input device 10 is provided so as to output an operation signal corresponding to the operation to the control device 11 when operated by a user or the like.

  The control device 11 includes a CPU, a ROM that stores a control program that can be read by the CPU, and a RAM that provides a work area for the CPU. The control device 11 is provided so as to perform arithmetic processing in accordance with a ROM control program with a CPU using a RAM as a work area. Accordingly, the control device 11 controls the Y driving unit 74 and the X driving unit 75 to move the spot pin 4 and the light projecting element 8 along the XY plane, or controls the Z driving unit 76 to control the spot pin 4. Are moved up and down, the light projecting element 8 is turned on, an operation signal is input from the input device 10, and the display device 9 is caused to perform a display operation.

  Moreover, the control apparatus 11 functions as the following means by the processing of the CPU according to the control program.

The control device 11 controls the X drive unit 75 and the Y drive unit 74 of the XYZ drive device 7 to move the light projecting element 8 along the XY plane with the XYZ drive device 7, and projects the light projecting element 8 by the movement of the light projecting device 8. The uv surface of the substrate 91 is scanned with the optical element 8 and functions as first coordinate detection means for detecting the XY coordinates of the light projecting element 8 when the photosensor 20a detects the maximum intensity during the scanning. Since the light projecting element 8 faces the photo sensor 20a on the photo sensor 20a when the control device 11 detects the maximum intensity with the photo sensor 20a, the light projection detected by the first coordinate detecting means of the control device 11 The XY coordinates of the element 8 are the same as the XY coordinates of the photosensor 20a. As shown in FIG. 6, the XY coordinates of the photosensor 20a detected by the first coordinate detection means are (X ₀ , Y ₀ ). Here, FIG. 6 shows the XY coordinate system of the XY plane defined by the XYZ driving device 7 and the uv coordinate system of the uv surface of the substrate 91 arranged in the XY coordinate system.

Further, the control device 11 controls the X drive unit 75 and the Y drive unit 74 of the XYZ drive device 7 to move the light projecting element 8 along the XY plane with the XYZ drive device 7, thereby moving the light projecting device 8. Thus, the light projecting element 8 scans the uv surface of the substrate 91 and functions as second coordinate detecting means for detecting the XY coordinates of the light projecting element 8 when the photosensor 20b detects the maximum intensity during the scanning. The XY coordinates of the light projecting element 8 detected by the second coordinate detecting means are the same as the XY coordinates of the photosensor 20b. As shown in FIG. 6, the XY coordinates of the photosensor 20b detected by the second coordinate detection means are (X ₁ , Y ₁ ).

Here, when the position of the photosensor 20a is the origin in the uv coordinate system (when the uv coordinate of the photosensor 20a is (0, 0)), the uv coordinate of the photosensor 20b is (0, B). B is a linear distance from the photosensor 20a to the photo sensor _{20b, B = {(X 1} -X 0) 2 + (Y 1 -Y 0) 2} is ^1/2. Since the uv coordinates and the XY coordinates of the photosensors 20a and 20b are known in this way, a conversion formula for converting from the uv coordinates to the XY coordinates can be obtained. That is, the control unit 11 obtains the coordinates of the photo sensor 20a (X _0, Y ₀₎ and conversion formula for converting the coordinates (X _1, Y ₁₎ of the photo sensor 20b the uv coordinates in the XY coordinates (1), uv By substituting the spot position represented by the coordinates into the conversion formula (1), the spot position is functioned as a coordinate conversion means representing the XY coordinates.
However,
It is.

  Further, the control device 11 serves as an XY movement control unit that operates the X drive unit 75 and the Y drive unit 74 of the XYZ drive unit 7 so as to move the spot pin 4 to the spot position converted into the XY coordinates by the coordinate conversion unit. Function. Further, the control device 11 functions as a Z movement control unit that operates the Z drive unit 76 of the XYZ drive unit 7 so as to lower the spot pin 4 at a position where the spot pin 4 has moved by the XY movement control unit.

  It should be noted that the uv coordinates of the spot position where the sample 92 is to be spotted may be incorporated in advance in the control program, or may be set by the operation of the input device 10 by the user. In any case, the control device 11 converts the uv coordinates of the spot position into XY coordinates by the coordinate conversion means.

  Next, the flow of control processing of the control device 11 according to the control program using FIG. 7, the operation of the spotting device 1 accompanying the control processing of the control device 11, and the point of the sample using the spotting device 1 The wearing method will be described. FIG. 7 is a chart of the process flow of the control device 11.

  First, the operator places the base materials 91, 91,... On the placing table 2, places the plate 93 containing the samples 92, 92,... On the plate placing table 3, and turns on the power of the spotting device 1. To.

  Then, as shown in FIG. 7, the control device 11 controls the X drive unit 75 and the Y drive unit 74 of the XYZ drive device 7, so that the head 73 is moved together with the spot pins 4 and the light projecting elements 8 by the XYZ drive device 7. The spot pin 4, the light projecting element 8, and the head 73 stand by at the standby position (step S 1). This standby position is the origin in the XY plane.

Next, the control device 11 displays an input screen as shown in FIG. 8 on the display device 9 (step S2: input screen display control step). When the screen shown in FIG. 8 is displayed, it is possible to enter numerical values for the items “number of chips”, “spot interval”, “start spot position”, “needle pushing distance”, “needle contact time”, and “spot needle”. It becomes. The “number of chips” is the number of base materials 91 to be mounted on the mounting table 2. The “spot interval” is a distance du between two spot positions adjacent along the u-axis direction of the uv surface and a distance dv between two spot positions adjacent along the v-axis direction of the uv surface. (See FIG. 9). The “start position” is the first spot position closest to the photosensor 20a and is a spot position (coordinates (u ₁ , v ₁ )) expressed in uv coordinates (see FIG. 9). The “needle pushing distance” is a distance for pushing the spot pin 4 into the base material 91, and has the same meaning as the strength for spotting the spot pin 4 on the uv surface of the base material 91. The “needle contact time” is the time during which the spot pin 4 is in contact with the uv surface of the substrate 91. The “spot needle” means the type of the spot pin 4 and is the diameter of the spot formed by the spot pin 4.

  In accordance with the input screen, the user performs numerical input operations on the input device 10 for each item of “number of chips”, “spot interval”, “start spot position”, “needle pushing distance”, “needle contact time”, and “spot needle”. On the other hand, an operation signal is output from the input device 10 to the control device 11, and the control device 11 inputs the numerical value of each item from the input device 10 (step S3: input process).

  Next, the control device 11 sets the uv coordinates of the spot position to be spotted from the input numerical values of the items “spot interval” and “start spot position” (step S4: uv coordinate setting step). Setting of the uv coordinate of the spot position will be described with reference to FIG. FIG. 9 is a diagram for explaining the uv coordinates of the spot position set by the control device 11.

As shown in FIG. 9, the control device 11 sets the uv coordinate system so that the photosensor 20a is the origin and the line connecting the photosensor 20a and the photosensor 20b is the v-axis. Then, the control device 11 sets the coordinates (u ₁ , v ₁ ) of the spot position to be initially spotted from the input numerical value of “start spot position”. Next, the control device 11 sets the uv coordinates of the spot position for each distance du in the positive direction of the u-axis and for each distance dv in the positive direction of the v-axis, starting from the spot position to be spotted first. . The distance du and the distance dv are input numerical values of “spot interval”. Thus, the uv coordinates of each of the plurality of spot positions arranged in a matrix are set, the distance between the spot positions adjacent in the u-axis direction is the distance du, and the distance between the spot positions adjacent in the v-axis direction is dv. Become. In FIG. 9, a white square represents the position of the photosensor 20a in the uv coordinate system, a black square represents the position of the photosensor 20b in the uv coordinate system, and a white circle is about to be spotted. The spot position to be displayed.

  After setting the uv coordinates of each spot position, the control device 11 calculates a conversion formula (1) for performing coordinate conversion from the uv coordinate system to the XY coordinate system (step S5). The process of step S5 will be described with reference to FIG. FIG. 10 is a flowchart of the subroutine in step S5.

As shown in FIG. 10, the control device 11 detects the position of the photosensor 20a in the XY coordinate system (step S51: first coordinate detection step). More specifically, when the control device 11 controls the X drive unit 75 and the Y drive unit 74, the head 73 is moved along the XY plane together with the light projecting element 8 by the XYZ drive device 7. The uv surface of the substrate 91 is scanned by the optical element 8. The control device 11 inputs the light intensity measured by the photosensor 20a during scanning. The position of the head 73 (position of the light projecting element 8) in the XY coordinate system when the light intensity becomes maximum is the photosensor 20a. The control device 11 detects the XY coordinates. That is, if the light projecting element 8 is positioned on the photosensor 20a, the light intensity detected by the photosensor 20a is maximized, and the XY coordinates of the photosensor 20a are detected based on the position of the light projecting element 8 at that time. be able to. Here, it is assumed that the detected XY coordinates of the photosensor 20a are (X ₀ , Y ₀ ).

Next, similarly to the detection of the XY coordinates of the photosensor 20a, the control device 11 detects the position of the photosensor 20b in the XY coordinate system (step S52: second coordinate detection step). Let the detected XY coordinates of the photosensor 20b be (X ₁ , Y ₁ ).

Next, the control unit 11, the coordinates of the photo sensor 20a (X _0, Y ₀₎ and obtaining the conversion equation (1) from the coordinates (X _1, Y ₁₎ of the photo sensor 20b (step S53). This conversion formula (1) is a formula for converting the uv coordinate system to the XY coordinate system. In addition, the process of step S52 may be performed before the process of step S51.

  After the calculation of the conversion formula (1), when the control device 11 controls the X driving unit 75 and the Y driving unit 74, the head 73 is moved to the top of the cleaning tank 5 together with the spot pins 4 by the XYZ driving device 7, and then controlled. When the device 11 controls the Z drive unit 76, the spot pin 4 is moved up and down by the XYZ drive device 7 (step S6: pre-cleaning step). Here, when the spot pin 4 descends, the tip of the spot pin 4 is immersed in the water of the cleaning tank 5 and the spot pin 4 is cleaned.

  Next, when the control device 11 controls the X drive unit 75 and the Y drive unit 74, the head 73 is moved onto the dryer 6 together with the spot pins 4 by the XYZ drive device 7 (step S7: pre-drying step). . When the spot pin 4 is positioned on the dryer 6, hot air blows out from the dryer 6 toward the spot pin 4, and the spot pin 4 is dried.

  Next, when the control device 11 controls the X drive unit 75 and the Y drive unit 74, the XYZ drive device 7 moves the head 73 together with the spot pins 4 to the top of the plate mounting table 3, and then the control device 11 drives the Z drive. When the unit 76 is controlled, the spot pin 4 is moved up and down by the XYZ driving device 7 (step S8: sample adsorption step). Here, when the spot pin 4 descends, the tip of the spot pin 4 is immersed in the sample 92, and the sample 92 is adsorbed on the tip of the spot pin 4.

  Next, the control device 11 substitutes the uv coordinates of the first spot position obtained in step S4 into u and v of the conversion formula (1), and converts the uv coordinates of the spot position into XY coordinates ( Step S9: Coordinate conversion step).

  Next, the control device 11 controls the X driving unit 75 and the Y driving unit 74 so as to move the spot pin 4 to the XY coordinates of the spot position obtained by the conversion, and the X driving unit 75 and the Y driving unit. 74 is operated (step S10: XY movement control step). Thereby, the spot pin 4 is moved to the converted XY coordinates together with the head 73.

  Next, the control device 11 controls the Z drive unit 76 so as to move the spot pin 4 up and down at that position to operate the Z drive unit 76 (step S11: Z movement control step). As a result, the spot pin 4 moves up and down in the converted XY coordinates, and when the spot pin 4 descends, the tip of the spot pin 4 comes into contact with the uv surface of the base material 91, and the sample 92 becomes the uv surface of the base material 91. To be spotted. After the spot pin 4 is lowered, the control device 11 keeps the spot pin 4 stopped for the input numerical value of “needle contact time”, and then the Z drive unit 76 raises the spot pin 4.

  Next, as in the case of step S6, the control device 11 controls the X drive unit 75, the Y drive unit 74, and the Z drive unit 76, so that the head 73 is cleaned together with the spot pins 4 by the XYZ drive device 7. The spot pin 4 is moved up and down by the XYZ driving device 7 and the spot pin 4 is cleaned (step S12: post-cleaning step).

  Next, as in step S7, the control device 11 controls the X drive unit 75 and the Y drive unit 74, so that the spot pin 4 is moved onto the dryer 6 by the XYZ drive device 7, The spot pin 4 is dried (step S13: post-cleaning step).

  Next, the control device 11 controls the X drive unit 75 and the Y drive unit 74 of the XYZ drive device 7, whereby the spot pin 4 is moved to the standby position by the XYZ drive device 7 (step S14).

  Thereafter, when the spotting of the sample 92 has not been completed for all spot positions (Step S15: No), the control device 11 is set in Step S4 by repeating the processing in Steps S6 to S14. The spotting is sequentially performed on the XY coordinates of each spot position. When the spotting of the sample 92 has been completed for all spot positions (step S15: Yes), the processing flow of the control device 11 ends.

  In the embodiment as described above, by detecting the XY coordinates of the photosensors 20a and 20b, the posture of the base material 91 on the XY plane can be grasped, and the base material 91 can be determined from the accurate posture on the XY plane. You can see if it is off to some extent Then, since the uv coordinates of the set spot position are converted into XY coordinates based on the XY coordinates of the photosensors 20a and 20b, the XY coordinates of the spot position are corrected by the amount of deviation of the base material 91 from the correct posture. . Therefore, regardless of the posture of the base material 91 in the XY plane, the sample can be spotted at an accurate position in the uv surface of the base material 91.

  In addition, the target to which the single-stranded DNA probe is spotted is a base material 91 that is a solid-state imaging device, and two XY coordinates on the uv surface are detected using the photosensors 20a and 20b of the base material 91. It is not necessary to provide the spotting device 1 with hardware for detecting the XY coordinates of two points on the uv surface. Therefore, the structure of the spotting device 1 is simplified.

  The present invention is not limited to the above-described embodiment, and various improvements and design changes may be made without departing from the spirit of the present invention.

  For example, in the above embodiment, the light projecting element 8 is provided in the head 73, but the light projecting element 8 may not be provided in the head 73. However, it is necessary to provide a surface irradiation device that irradiates light from the lower side to the upper side of the substrate 91 on the upper surface of the mounting table 2. In this case, since the bottom gate electrode 21 of the double gate transistors 20, 20,... Has a light shielding property, the light emitted from the surface irradiation device does not enter the semiconductor film 23 directly. On the other hand, light is transmitted between the double gate transistors 20, 20,. Then, the double gate transistor 20 on which the spot pin 4 is positioned detects the spot pin 4 by receiving the light transmitted through the base material 91 and reflected by the spot pin 4. On the other hand, the double gate transistor 20 in which the spot pin 4 is not located above does not receive the reflected light and therefore does not detect the spot pin 4. Accordingly, the XY coordinate of the spot pin 4 when the maximum intensity is detected by the photosensor 20a during scanning is the XY coordinate of the photosensor 20a, and the XY of the spot pin 4 when the maximum intensity is detected by the photosensor 20b. The coordinates are XY coordinates of the photosensor 20b.

  In the above embodiment, the XY coordinates of two predetermined points on the uv surface of the base material 91 are detected by the photosensors 20a and 20b. Instead, the uv surface of the base material 91 is detected by an electronic imaging device (CCD camera, CMOS). Type camera). In this case, two predetermined XY coordinates on the uv surface are detected by marking two predetermined locations on the uv surface of the base material 91 and imaging the uv surface of the base material 91 with an electronic imaging device. .

  In the above embodiment, the needle-like spot pin 42 is used. Instead of the needle-like spot pin 4, an inkjet head (droplet discharge head) that discharges the sample 92 by a piezo element, a heating element or the like is used as the spot pin. It may be provided as. In this case, the ink jet head does not necessarily have a means for moving in the vertical direction (Z-axis direction).

1 is a perspective view of a spotting device 1 in an embodiment of the present invention. 2 is a block diagram of a circuit configuration of the spotting device 1. FIG. 3 is a plan view of a base material 91. FIG. 3 is a plan view of one pixel of a base material 91. FIG. It is sectional drawing which follows the plane VV of FIG. It is the figure which showed the base material 91 arrange | positioned at XY coordinate system with the uv coordinate system of the base material 91. FIG. 4 is a chart showing a flow of control processing by the control device 11 of the spotting device 1. It is a figure of the input screen displayed on the display apparatus 9 controlled by the control apparatus 11. FIG. It is explanatory drawing for demonstrating the setting method of the uv coordinate of a spot position. It is the chart which showed the flow of the subroutine in step S5 of FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Spotting apparatus 4 ... Spot pin 7 ... XYZ drive apparatus 11 ... Control apparatus (Coordinate detection means, coordinate conversion means, XY movement control means, Z movement control means)
DESCRIPTION OF SYMBOLS 20 ... Photoelectric conversion element 20a, 20b ... Photo sensor 91 ... Base material 92 ... Sample

Claims (9)

A spot pin for adsorbing a sample;
A light projecting element that projects light toward a solid-state imaging device including a plurality of photoelectric conversion elements arranged along a light receiving surface (hereinafter referred to as uv surface);
A driving device for driving the spot pin and the light projecting element along an XY plane parallel to the uv surface of the solid-state imaging device above the uv surface of the solid-state imaging device ;
A control device for controlling the driving device;
With
The control device is
The driving device drives the light projecting element along the XY plane, scans the uv surface of the solid-state imaging device with the light projecting element, and two photoelectric conversions in a state separated from each other among the plurality of photoelectric conversion elements Coordinate detecting means for detecting XY coordinates in the XY plane for two points in the uv surface of the solid-state imaging device by receiving light of the light projecting element using an element ;
Coordinate conversion means for converting the uv coordinates on the uv surface into XY coordinates on the XY plane for the spot position where the sample is spotted on the uv surface of the solid-state imaging device based on the two XY coordinates detected by the coordinate detection means When,
XY movement control means for operating the drive device to move the spot pin to the XY coordinates converted by the coordinate conversion means;
Spotting means for operating the driving device so that a sample is spotted on the uv surface of the solid-state imaging device from the spot pin moved by the XY movement control means;
A spotting device comprising: When one of the two XY coordinates detected by the coordinate detection means is (X ₀ , Y ₀ ) and the other is (X ₁ , Y ₁ ), the coordinate conversion means is the solid-state imaging device. The spotting apparatus according to claim 1, wherein the spotting position where the sample is spotted on the uv surface of the spot is converted into an XY coordinate expressed by the following equation (1).

However,

It is. Said spotting means, a point of claim 1, wherein the benzalkonium operates the drive so as to lower the spotting pin in a position where the spotting pin is moved by the XY moving control means Landing gear. A spot pin for adsorbing a sample, a light projecting element that projects light toward a solid-state imaging device including a plurality of photoelectric conversion elements arranged along a light receiving surface (hereinafter referred to as uv surface), and the solid-state imaging device A driving device that drives the spot pin and the light projecting element along an XY plane parallel to the uv surface of the solid-state imaging device, and a control device that controls the driving device. a wear method that using a spotting device,
The control device causes the driving device to drive the light projecting element along the XY plane, scans the uv surface of the solid-state imaging device with the light projecting device, and is separated from each other among the plurality of photoelectric conversion elements A coordinate detection step of detecting XY coordinates in the XY plane for two points in the uv surface of the solid-state imaging device by receiving light of the light projecting element using the two photoelectric conversion elements ;
Based on the two XY coordinates detected by the coordinate detection step , the control device converts the uv coordinate on the uv surface to the XY coordinate on the XY plane for the spot position where the sample is spotted on the uv surface of the solid-state imaging device. A coordinate transformation step to transform;
Wherein the controller, and the XY moving control step of operating the drive device to move the spotting pin in transformed XY coordinates by the coordinate conversion step,
A spotting step in which the control device operates the driving device so that a sample is spotted on the uv surface of the solid-state imaging device from the spot pin moved by the XY movement control step;
The spotting method characterized by including. When one of the two XY coordinates detected in the coordinate detection step is (X ₀ , Y ₀ ) and the other is (X ₁ , Y ₁ ), in the coordinate conversion step, the solid-state imaging device 5. The spotting method according to claim 4 , wherein the uv coordinates of the spot position where the sample is spotted on the uv surface of the uv are converted into XY coordinates represented by the following formula (1).

However,

It is. In the spotting process, the point of claim 4 or 5, wherein the benzalkonium operates the drive so as to lower the spotting pin in a position where the spotting pin is moved by the XY moving control step How to wear. A sample is adsorbed along an XY plane parallel to the uv surface of the solid-state imaging device above a solid-state imaging device having a plurality of photoelectric conversion elements arranged along a light receiving surface (hereinafter referred to as uv surface). a spotting pin for, a control device of the destination device that controls the driving device for driving the light projecting elements for projecting light, a toward the solid-state imaging device,
The driving device drives the light projecting element along the XY plane, scans the uv surface of the solid-state imaging device with the light projecting element, and is arranged in a state separated from each other among the plurality of photoelectric conversion elements. Coordinate detecting means for detecting XY coordinates in the XY plane for two points in the uv surface of the solid-state imaging device by receiving light of the light projecting element using two photoelectric conversion elements ;
Coordinate conversion means for converting the uv coordinates on the uv surface into XY coordinates on the XY plane for the spot position where the sample is spotted on the uv surface of the solid-state imaging device based on the two XY coordinates detected by the coordinate detection means When,
XY movement control means for operating the drive device to move the spot pin to the XY coordinates converted by the coordinate conversion means;
Spotting means for operating the driving device so that a sample is spotted on the uv surface of the solid-state imaging device from the spot pin moved to a predetermined XY coordinate position by the XY movement control means;
A control device for a spotting device, comprising: When one of the two XY coordinates detected by the coordinate detection means is (X ₀ , Y ₀ ) and the other is (X ₁ , Y ₁ ), the coordinate conversion means is the solid-state imaging device. The spotting device control device according to claim 7 , wherein the uv coordinate of the spot position where the sample is spotted on the uv surface is converted into an XY coordinate expressed by the following formula (1).

However,

It is. Said spotting means, points of claim 7 or 8, wherein the benzalkonium operates the drive so as to lower the spotting pin in a position where the spotting pin is moved by the XY moving control means Control device for landing gear.