Specimen measuring device, method of controlling specimen measuring device, and program

Abstract

To stably acquire an optical signal with a simple configuration even when variation in scanning speed occurs in a specimen measuring device.SOLUTION: A specimen measuring method includes irradiating an array substrate with condensed primary light, detecting secondary light from a spot and outputting a detection signal, relatively changing an irradiation position of the primary light with respect to the array substrate, acquiring information on a relative position of the primary light with respect to the array substrate, and converting the detection signal acquired in a predetermined period into digital data. The specimen measuring method further includes holding information on a target position Pt set with respect to an irradiation position of the primary light, determining that the irradiation position has reached the target position Pt based on the information on the relative position, selecting digital data including digital data corresponding to the predetermined period from the digital data based on the determination result, and transferring the selected digital data to storage means for storing the digital data.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present disclosure relates to a specimen measurement device for measuring a specimen, a specimen measurement method, and a program.

Background Art

[0002] A protein array plate or a peptide array plate in which a large number of biological substances having peptide bonds such as proteins and peptides are immobilized on a substrate is known. By using this, the interactions with a large number of biological substances immobilized on the substrate are examined at once. That is, these array plates are effective for comprehensively analyzing the interactions between a liquid specimen derived from a living body, such as blood, cell extract, saliva, and interstitial fluid, and a large number of proteins or peptides. By such analysis, the characteristics of the specimen are measured. Hereinafter, the immobilization sites of proteins or peptides on the substrate are referred to as spots.

[0003] As a method for observing spots that have received an interaction with a specimen, a method of identifying spots that have received an interaction by labeling the spots with a fluorescent probe is known. Also, as a device for observing an array plate labeled with a fluorescent probe, a fluorescence image scanner is known (Patent Document 1). The fluorescence image scanner disclosed in Patent Document 1 has an irradiation optical system, a fluorescence detection optical system, and a two-dimensional scanning system. The irradiation optical system has a function of condensing and irradiating a laser beam onto the array plate. The fluorescence detection optical system has a function of detecting the amount of fluorescence from spots irradiated with the laser beam and labeled with a fluorescent probe. The two-dimensional scanning system has a function of changing the irradiation position of the laser beam on the array plate by two-dimensionally scanning the array plate or the optical system, and acquiring a captured image reflecting the amount of fluorescence excited by the laser beam at the spots. Also, a confocal optical system is used as the fluorescence detection optical system.

[0004] In addition, Patent Document 2 discloses a technique for adjusting the phase of a sampling clock for detecting the amount of fluorescence light from a spot according to the scanning timing of two-dimensional scanning and obtaining equally spaced optical signals. In these prior art two-dimensional scanning mechanisms, in the main scanning direction, a laser beam is reciprocally scanned at high speed by a piston crank mechanism or a galvanometer scanner mechanism. Further, in these prior arts, the amount of fluorescence light from the spot is converted into an analog signal by a highly sensitive sensor such as a photomultiplier tube, and further converted into optical signal data as a digital value by AD conversion. Generally, AD conversion requires a predetermined conversion time determined by the clock frequency of the AD converter and peripheral circuits.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] In a conventional fluorescence image scanner, the movement time required for the condenser of the irradiated laser beam to move between the points where optical signals are to be acquired is determined in consideration of the scanning speed of the two-dimensional scanning mechanism. Specifically, the clock frequency of the AD converter and peripheral circuits is determined so that the AD conversion ends in a time shorter than the movement time. However, due to mechanical vibrations and the like when the laser beam is reciprocally scanned by the two-dimensional scanning mechanism, local variations in the scanning speed of the laser beam occur. For this reason, variations occur in the time taken to scan between the points where optical signals are to be acquired. As a result, there is a risk of missing the acquisition of an optical signal because the next point where an optical signal is to be acquired is passed through before the AD conversion of the optical signal at the previous point is completed. If an attempt is made to acquire optical signals at short acquisition intervals in order to improve the image quality of the captured image, the likelihood of such problems occurring is further increased.

[0007] To address such problems, it is conceivable to select an A / D converter with a higher speed and shorter conversion time, or to use a more robust scanning mechanism to sufficiently reduce local speed variations. However, implementing these countermeasures leads to an increase in the cost and size of the device. On the other hand, if the reciprocating scanning speed is reduced in consideration of local speed variations, the imaging time will become longer. Also, if the acquisition interval is increased without changing the scanning speed, a sufficient number of optical signal data may not be acquired, and there is a risk of a decrease in measurement accuracy.

[0008] The present disclosure is in view of such a situation, and an object thereof is to provide a specimen measurement device and a control method for the specimen measurement device that can stably acquire optical signal data even when variations in scanning speed occur with a simple configuration.

Means for Solving the Problems

[0009] In order to solve the above problems, a specimen measurement device according to an aspect of the present disclosure is a specimen measurement device that optically measures the characteristics of a specimen using an array substrate provided with spots in an array, light irradiation means for irradiating the condensed primary light to the array substrate for a predetermined period, light detection means for detecting secondary light from the spot at a predetermined period and outputting a detection signal, scanning means for changing the irradiation position of the primary light with respect to the array substrate, position acquisition means for acquiring information regarding the irradiation position, conversion means for converting the detection signal acquired at a predetermined period into digital data, first holding means for holding information on a target position Pt regarding the irradiation position, second holding means for holding the digital data, determination means for determining whether or not the irradiation position corresponds to the target position Pt, storage means for storing the digital data, Transfer means for selecting, according to the determination result of the determination means, data corresponding to the timing when the irradiation position reaches the target position Pt from the digital data held in the second holding means and transferring the data to the storage means. Also, a control method for a specimen measurement apparatus according to an aspect of the present disclosure is a control method for a specimen measurement apparatus including: a first holding means for holding a target position regarding the irradiation position of primary light in order to optically measure the characteristics of a specimen using an array substrate provided with spots in an array; a second holding means for holding a detection signal detected by measuring secondary light from the spots as digital data; and a storage means for storing the irradiation position and the digital data in association with each other, the method including: A light irradiation step of irradiating the array substrate with the condensed primary light for a predetermined period; A light detection step of detecting secondary light from the spots at a predetermined period and outputting a detection signal; A scanning step of changing the irradiation position of the primary light with respect to the array substrate; A position acquisition step of acquiring information regarding the irradiation position; A conversion step of converting the detection signal acquired at a predetermined period into the digital data, including: A determination step of determining whether or not the irradiation position corresponds to the target position Pt; A transfer step of selecting, according to the determination result determined in the determination step, data corresponding to the timing when the irradiation position reaches the target position Pt from the digital data held in the second holding means and transferring the data to the storage means.

Advantages of the Invention

[0010] According to an aspect of the present disclosure, there is provided a specimen measurement apparatus capable of stably acquiring optical signal data even when variations in scanning speed occur with a simple configuration, and a control method for the specimen measurement apparatus.

Brief Description of the Drawings

[0011]

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Embodiments for Carrying Out the Invention

[0012] Hereinafter, exemplary embodiments for carrying out the present disclosure will be described in detail with reference to the accompanying drawings. Note that the following embodiments do not limit the invention according to the claims. Although a plurality of features are described in the embodiments, not all of these plurality of features are essential to the invention, and the plurality of features may be arbitrarily combined. Furthermore, the dimensions, materials, shapes, relative positions of components, etc. described in the following embodiments are arbitrary and can be changed according to the configuration of the device to which the present disclosure is applied or various conditions. Also, in the accompanying drawings, the same reference numerals are used between the drawings to indicate the same or functionally similar elements, and redundant explanations are omitted.

[0013] <The First Embodiment> Hereinafter, with reference to FIGS. 3 to 11, a first embodiment of the present disclosure in which the above-described array plate is placed on the specimen measuring device shown in FIG. 1 to perform specimen measurement will be described. Here, first, the schematic configuration of the specimen measuring device according to the present disclosure will be described with reference to FIG. 1. The specimen measuring device 1 shown in FIG. 1 measures an array plate 101 on which a large number of spots of biological substances are immobilized and fluorescently labeled. The specimen measuring device 1 includes an objective optical system, a conversion means, a scanning means, and a detection means. The objective optical system is configured for irradiating excitation light and receiving fluorescence, which will be described later. The conversion means is configured to convert the received fluorescence into an electrical signal. The scanning means is configured to scan the excitation light relative to the array plate 101, and the detection means is configured to detect information about the specimen from the received fluorescence. Each of the following configurations will be sequentially described.

[0014] <Objective optical system> As shown in FIG. 1, the specimen measuring device 1 includes an objective optical system 129 as an optical system for acquiring a fluorescence image of the array plate 101. The objective optical system 129 is configured such that the emitted light from the light source 102 passes through the objective lens and focuses on the sample surface, and the secondary light passes through the objective lens again and the light focused on a light sensor 105, which will be described later, passes through a pinhole and is received. The objective optical system 129 shares coaxial elements with each other, and includes a light irradiation means 122 that irradiates the condensed primary light onto the array plate 101 for a predetermined period, and a light detection means 125 that detects the secondary light from the spot at a predetermined period and outputs a detection signal.

[0015] <Light irradiation means> The light irradiation means 122 includes a light projecting unit 104 having an objective lens for irradiating the condensed primary light onto the array plate 101, a confocal optical system 103 having a beam splitter and a pinhole (not shown), and a light source 102. Note that the light projecting unit 104 may be equivalently referred to as an objective lens, a light emitting unit, a primary light emitting unit, a primary light emitting unit, etc.

[0016] <Light detection means> The light detection means 125 includes a light projection unit 104 that collects the secondary light from the spot, a confocal optical system 103, and a light sensor 105. The light sensor 105 is composed of a detection element capable of detecting the wavelength of the secondary light with high sensitivity and a high dynamic range, and a photomultiplier tube (PMT), a semiconductor sensor, etc. are adopted.

[0017] The light source 102 is a semiconductor laser that emits light near wavelengths of 670 nm and 780 nm (hereinafter referred to as excitation light). In the specimen measurement device 1, the emission and stop of light of each wavelength can be independently controlled. The confocal optical system 103 guides the excitation light from the light source 102 to the array plate 101, and guides the fluorescence from the spot on the array plate 101 and the reflected light from the surface of the slide glass to the light sensor. In the example here, the confocal optical system 103 is composed of a pinhole, a filter, a dichroic mirror, a quarter-wave plate, a deflection beam splitter, and a lens. By using the confocal optical system 103, the influence of the autofluorescence component from the slide glass is reduced, and the signal-to-noise ratio when measuring the fluorescence component derived from the spot is increased. The light projection unit 104 is used to condense and irradiate the excitation light onto the spot on the array plate 101, and includes a prism for directing the excitation light in the direction of the array plate 101 and a lens for condensing the excitation light onto the spot on the array plate 101. Note that the forms of the confocal optical system 103 and the light projection unit 104 are not limited to the examples here, and various known configurations can be substituted as long as the same functions can be obtained.

[0018] The light sensor 105 is provided to convert fluorescence into an electrical signal, and is composed of a photomultiplier tube for acquiring fluorescence and a photodiode for acquiring reflected light. The light sensor 105 is capable of separately acquiring the fluorescence from the spot on the array plate 101 and the reflected light from the surface of the array plate 101. Also, the light sensor 105 is composed of a plurality of photomultiplier tubes corresponding to a plurality of wavelengths of the light source 102, photodiodes, etc.

[0019] <Conversion means> As shown in FIG. 18, the specimen measurement device 1 includes conversion means 146 that converts a detection signal acquired at a predetermined period into digital data. The conversion means 146 is composed of an AD converter 705 disposed in the reception circuit 106 and an AD converter control circuit 306 that controls the reception circuit 106. As shown in FIG. 18 or FIG. 7 to be described later, the reception circuit 106 is a reception circuit that amplifies a detection signal from a photomultiplier tube 701 included in the optical sensor 105 and converts it into a digital value. The reception circuit 106 includes an amplification circuit (current-voltage conversion amplifier 702), a level conversion circuit (level conversion circuit 703), a filter circuit (filter circuit 704), and an AD converter (ADC 705), etc.

[0020] <Scanning means> As shown in FIG. 1, the specimen measurement device 1 includes scanning means 130 that changes the irradiation position Pi of primary light on the array plate 101. The scanning means 130 includes main scanning means 130x that moves the light projection unit 104 in the X direction in the two dimensions and sub-scanning means 130y that moves the array plate 101 in the Y direction as a mechanism for two-dimensionally scanning the light projection unit 104 with respect to the array plate 101. The main scanning means 130x includes a pulse motor 107, a linear stage 109, a motor driver 115, and a piston crank mechanism 120. The piston crank mechanism 120 includes a crank 118 and a connecting rod 119. The sub-scanning means 130y includes a linear stage 112y, a pulse motor 113, and a motor driver 114. The scanning means 130 further includes z-direction scanning means 130z that moves the array plate 101 in the Z direction perpendicular to the plane defined by the XY directions with respect to a base material (not shown). The z-direction scanning means 130z includes a linear stage 112z that moves the linear stage 109 in the Z direction, a pulse motor 110 that drives the linear stage 112z, and a motor driver 111 that controls the pulse motor 110. The scanning means 130 is fixed to a scanning means base material (housing) not shown. Here, a pulse motor or the like is exemplified as a drive source that generates a driving force, but other known drive mechanisms such as other motors may be used as the drive source.

[0021] The piston crank mechanism 120 reciprocates the light projecting unit 104 in the short side direction of the array plate 101. Due to the reciprocating motion of the light projecting unit 104, the excitation light from the light source 102 is scanned in the short side direction of the array plate 101. Here, the short side direction of the array plate 101 is referred to as the main scanning direction, and the reciprocating scan by the piston crank mechanism 120 is referred to as the main scan. Also, the stroke of the main scan shown here is 30 mm. The operation direction of the light projecting unit 104 in the main scanning direction is limited by a guide (not shown) in the main scanning direction. The pulse motor 107 is a pulse motor for rotating the piston crank mechanism 120 at high speed. The pulse motor 107 shown here adopts a rotation speed in the range of 100 to 10,000 rpm, and preferably 500 to 2,000 rpm is adopted.

[0022] <Position acquisition means> The specimen measurement device 1 includes a position acquisition means 138 (see FIG. 3) for acquiring position information regarding the irradiation position of the primary light on the array plate 101. The position acquisition means 138 includes a linear encoder 108 that moves integrally with the light projecting unit 104 shown in FIG. 1, and a coordinate calculation circuit 310, which will be described later. The linear encoder 108 is a linear encoder installed in the piston crank mechanism 120, and measures the position of the light projecting unit 104 in the main scanning direction. The linear encoder 108 outputs a phase difference pulse voltage composed of phase A, phase B, and phase Z according to the position in the main scanning direction.

[0023] Here, with reference to FIG. 16, the specific configuration of the piston crank mechanism 120 used in the specimen measurement device 1 shown in FIG. 1 will be described. FIG. 16 shows an example of the schematic configuration of the piston crank mechanism 120. The piston crank mechanism 120 includes a piston crank portion 123 including a crank 118 and a connecting rod 119, and a rotational drive portion 121. FIG. 16 shows the positional relationship among the crank 118, the connecting rod 119, and the light projecting portion 104 in the piston crank mechanism 120. The crank 118 is a crank constituting the piston crank mechanism 120, and is connected to the rotation shaft of the pulse motor 107 and the connecting rod 119 via a joint. In the present embodiment, the pulse motor 107 constitutes the rotational drive portion 121 in the present disclosure and is connected to one end of the crank 118. The other end of the crank 118 is connected to one end of the connecting rod 119. The other end of the connecting rod 119 is connected to the light projecting portion 104. With such a configuration, due to the rotational movement of the rotational drive portion 121, the light projecting portion 104 can perform a one-dimensional reciprocating movement along the direction of the arrow shown in FIG. 16.

[0024] The linear stage 109 moves the array plate 101 in a direction orthogonal to the main scanning in the horizontal plane. The linear stage 109 is composed of a ball screw, an origin sensor, and the like. Hereinafter, the scanning in the direction orthogonal to the main scanning in the horizontal plane will be referred to as sub-scanning. There is a mounting table for mounting the array plate 101 on the linear stage 109, and the user mounts the array plate 101 to be measured on the mounting table in advance. The pulse motor 110 is connected to the linear stage 109. The rotational movement of the pulse motor 110 is converted into a linear movement by the ball screw of the linear stage 109. The motor driver 111 rotates the pulse motor 110. When the motor driver 111 inputs a signal of one pulse to the pulse motor 110, the pulse motor 110 rotates by 0.72°, and here, the array plate 101 moves 2 μm in the sub-scanning direction.

[0025] The linear stage 112z moves the array plate 101 in the vertical direction. The linear stage 112z is composed of a ball screw, a home sensor, etc. Hereinafter, the vertical scanning is referred to as height scanning. The pulse motor 113 is connected to the linear stage 112z. The rotational motion of the pulse motor 113 is converted into a linear motion by the ball screw of the linear stage 112z. The motor driver 114 rotates the pulse motor 113. When the motor driver 114 inputs a signal of 1 pulse to the pulse motor 113, the pulse motor 113 rotates by 0.72°, and here the array plate 101 moves 1 μm upward in the vertical direction (height scanning). The motor driver 115 rotates the pulse motor 107. When the motor driver 115 inputs a signal of 1 pulse to the pulse motor 107, the pulse motor 107 rotates by 0.72°, and here the light projecting unit 104 moves along the main scanning direction. Note that the configuration described here regarding the relative movement of the light projecting unit 104 (the irradiation position of the excitation light) with respect to the array plate 101 is an example, and as long as relative movement between these configurations is possible, it is not limited as to how any of these configurations move.

[0026] The specimen measurement device 1 further includes a controller circuit 116. The controller circuit 116 controls the entire specimen measurement device 1 and is composed of an FPGA, a CPU, a memory, embedded software, etc. More specifically, the controller circuit 116 controls the light source 102, the motor driver 111, the motor driver 114, and the motor driver 115 to scan the excitation light on the array plate 101 in the main scanning direction, the sub-scanning direction, and the height direction. Also, the controller circuit 116 acquires information regarding the irradiation position Pi of the irradiation light (primary light) output from the linear encoder 108 and the optical signal data from the optical sensor 105. Then, the controller circuit 116 holds these by the first holding means 171 and the second holding means 172 (see FIG. 17) described later. The first holding means 171 holds the information regarding the irradiation position Pi for a period (at least temporarily) that can be read by the determination means 173 (see FIG. 17) described later by storing the information regarding the irradiation position Pi in a readable state.

[0027] The controller circuit 116 includes means for acquiring the height information and tilt information of the array plate 101 therein, and means for generating pulse trains for main scanning, sub-scanning, and height scanning. These means correspond to the motor control circuits 307 to 309 and the coordinate calculation circuit 310, which will be described later and are shown in FIG. 3. Also, as shown in FIG. 3, the controller circuit 116 includes an AD converter control circuit 306 as AD converter control means and a synchronization circuit 311 as synchronization control means. Further, the controller circuit 116 includes a data acquisition control circuit 312 as data acquisition control means and a memory 303 as storage means, respectively. That is, in the embodiments described below, these means provided in the controller circuit 116 are constituted by various circuits shown in FIG. 3. In this case, the AD converter control means issues a conversion instruction to the AD converter 705 (see FIG. 7) of the reception circuit 106, AD-converts the electrical signal corresponding to the amount of light of the optical sensor 105, and acquires optical signal data which is a digital value. At that time, in the following embodiments, the controller circuit 116 uses these configurations to acquire optical signal data at a period shorter than the shortest time required for the irradiation position Pi of the primary light to pass through the interval from the target position Pt.

[0028] The synchronization circuit 311, which is a synchronization control means, controls the sub-scanning and height scanning in synchronization with the position information Iip of the irradiation position Pi of the primary light. Thereby, when the light projecting unit 104 corresponding to the irradiation position Pi of the primary light is outside the imaging range on the array plate 101, the thickness and inclination of the array plate 101 are corrected, and the excitation light is focused on the surface where the spot is fixed over the entire array plate 101. Further, the synchronization circuit 311 controls the light emission of the light source 102 and the timing of transfer of the optical signal data to the memory. As synchronization control, when the irradiation position Pi of the primary light reaches the target position Pt so that the excitation light can be irradiated at a predetermined position, the synchronization circuit 311 instructs the data acquisition control means to transfer the optical signal data to the memory 303. Also, when the light projecting unit 104 reaches a position where the excitation light can be irradiated at a predetermined position near the end of the array plate 101, the synchronization circuit 311 controls the start of the sub-scanning and height scanning, and the light emission (on) and stop (off) of the semiconductor lasers of each wavelength of the light source 102.

[0029] <First holding means> Here, in the present embodiment, the details of the synchronization circuit 311 provided in the specimen measurement apparatus 1 will be described with reference to FIG. 17. FIG. 17 is a block diagram showing the functional configuration provided in the synchronization circuit 311 in the present embodiment. In the present embodiment, the synchronization circuit 311 includes a first holding means 171, a second holding means 172, and a determination means 173. The first holding means 171 shown in FIG. 17 holds the data Itp related to the target position Pt regarding the irradiation position Pi. Here, although the configuration in which the first holding means 171 is arranged in the synchronization circuit 311 is illustrated, the arrangement of the first holding means 171 is not limited to this example.

[0030] <Second holding means> Also, as shown in FIG. 17, the synchronization circuit 311 in the present embodiment also includes a second holding means 172 that holds the digital data converted from the detection signal by the conversion means 146. Here, although the configuration in which the second holding means 172 is arranged in the synchronization circuit 311 is illustrated, the arrangement of the second holding means 172 is not limited to this example.

[0031] <Determination means> Also, as shown in FIG. 17, the synchronization circuit 311 in the present embodiment includes a determination means 173 for determining whether or not the irradiation position Pi has reached the target position Pt. The determination means 173 determines that the irradiation position Pi of the primary light has reached the target position Pt based on information regarding the relative position obtained from the linear encoder 108 or the like. Here, a configuration in which the determination means 173 is arranged in the synchronization circuit 311 is illustrated, but the arrangement of the second holding means 172 is not limited to this example.

[0032] <Transfer means> Further, as shown in FIG. 3, the specimen measurement apparatus 1 includes a data acquisition control circuit 312 (see FIG. 3) that selects data corresponding to the irradiation position corresponding to the target position from the digital data held by the second holding means 172 according to the determination result by the determination means 173. The memory control circuit 304 connected to the data acquisition control circuit 312 functions as a transfer means for transferring the selected data to the storage means (memory 303) in the present embodiment. The data acquisition control circuit 312 temporarily stores the optical signal data from the AD converter control means, and the memory control circuit 304 transfers the latest optical signal data to the memory based on the synchronization control instruction from the synchronization circuit 311. In the following embodiments, when new optical signal data is acquired without an instruction from the synchronization circuit 311, the old optical signal data is overwritten. Thereby, the acquisition of the optical signal data is performed at a constant cycle, but the optical signal data acquired at the closest time when the irradiation position Pi of the primary light reaches the target position Pt is selectively transferred to and stored in the memory 303.

[0033] The specimen measurement device 1 shown in FIG. 3 further includes a user interface 117. The user interface 117 is used to receive instructions from the user and display results, and is composed of a keyboard, a mouse, and a display. The controller circuit 116 receives a shooting instruction for the array plate 101 and presents image data based on the optical signal data to the user via the user interface 117. Also, when shooting the array plate 101, the user designates the shooting range, the pixel pitch in the main scanning direction, and the sub-scanning direction via the GUI on the user interface 117.

[0034] Next, with reference to FIG. 2, the specimen targeted by the present disclosure will be described. Note that FIG. 2(a) is a top view of the array plate 101, and FIG. 2(b) is a side view of the array plate 101. The array plate 101 includes a slide glass 201 that is a substrate, and spots 202 provided on the slide glass 201. A biological substance containing a peptide bond is immobilized on each spot 202. A large number of spots 202 are provided on the slide glass 201, and one type of biological substance is immobilized on one spot. In the following embodiments, the diameter of the spot is about 100 μm, and the spot interval (the distance from the end of one spot to the end of the next spot) is 200 μm. Also, the length in the short side direction of the array plate is 25 mm, and the length in the long side direction is 75 mm.

[0035] Here, taking the point 203 at the upper left (corner) of the array plate 101 as the origin, the rightward direction in the short side direction as the positive direction of the X axis, and the downward direction in the long side direction as the Y axis direction. When the unit of the X and Y coordinates is μm, the coordinates of the four corners of the array plate are (0, 0), (25000, 0), (0, 75000), and (25000, 75000), respectively. Assuming that the stroke of the piston crank mechanism 120 is 30 mm, the stroke is 5 mm longer than the length of the array plate 101. That is, in the main scanning, the excitation light scans up to a range 2.5 mm long on the left and right of the array plate, and the X coordinate of the scanning range is in the range of -2500 to 27500.

[0036] On one hand, on the slide glass 201, the spot 202 is provided within the range of the area 204. That is, on the slide glass 201, there are areas where the spot 202 exists and areas where it does not exist due to convenience in creating the spot 202 and convenience for the user to hold. In the following embodiments, the coordinates of the four corners of the area 204 are respectively (2000, 2000), (23000, 2000), (2000, 65000), and (23000, 65000). Also, the range of the Y coordinate of the sub-scan can be specified by the user.

[0037] FIG. 3, which was partially described earlier, is a block diagram showing the internal configuration of the controller circuit 116 according to the first embodiment of the present disclosure. The controller circuit 116 has a CPU 301 for operating control software that controls the entire specimen measurement device 1. The CPU 301 is composed of a microprocessor, a cache memory, and the like. Also, the CPU 301 is connected to various peripheral circuits described later via a bus 302. Further, the CPU 301 can include an image processing unit 301a, and images the characteristics of the specimen using digital data based on the optical signal data stored in the memory 303 described later.

[0038] The various peripheral circuits include a memory 303, a memory control circuit 304, a light source control circuit 305, an AD converter control circuit 306, motor control circuits 307 - 309, a coordinate calculation circuit 310, and a synchronization circuit 311. Further, the various peripheral circuits further include a data acquisition control circuit 312, a communication circuit 313, and a UI (User Interface) control circuit 314.

[0039] <Storage unit> The memory 303 is equivalently referred to as a storage means and stores data of pixel values and coordinate values constituting the fluorescence image. The memory 303 may further store imaging conditions input from the user, control parameters of the specimen measuring device 1, and optical signal data. The memory 303 is composed of DDR (Double Data Rate), 4-SDRAM (Synchronous Dynamic Random Access Memory), SSD (Solid State Drive), etc. The memory control circuit 304 controls the memory 303 based on an access command to the memory 303 obtained via the bus 302. The light source control circuit 305 is a light source control circuit for the CPU 301 to control the light source 102 and is composed of an interface conversion circuit, a DA converter, etc. The CPU 301 can control the on / off of the laser irradiation of the light source 102 and the amount of excitation light irradiated via the light source control circuit 305. The light source control circuit 305 is equivalently referred to as an element of the light irradiation means 122 configured to turn on / off the light emission of the light source 102.

[0040] The AD converter control circuit 306 controls the AD converter of the above-described receiving circuit 106 based on an instruction from the CPU 301 and acquires optical signal data. The AD converter control circuit 306 outputs a conversion start signal to the AD converter of the receiving circuit 106. The AD converter samples the analog signal in the receiving circuit at the timing when the conversion start signal is input, converts this into optical signal data, and outputs it to the AD converter control circuit 306. The AD converter control circuit 306 transfers the optical signal data input from the AD converter to the data acquisition control circuit 312.

[0041] The motor control circuit 307 generates a control signal to the motor driver 115 for the main scanning motor based on an instruction from the CPU 301. When the CPU 301 instructs the rotational speed, acceleration, movement amount, rotational direction, and rotation start timing of the pulse motor 107, the motor control circuit 307 generates a drive pulse voltage corresponding thereto. The motor control circuit 308 generates a control signal to the motor driver 111 for the sub-scanning motor based on an instruction from the CPU 301. When the CPU 301 instructs the rotational speed, acceleration, movement amount, rotational direction, and rotation start timing of the pulse motor 110, the motor control circuit 308 generates a drive pulse voltage corresponding thereto. The motor control circuit 309 generates a control signal to the motor driver 114 for the height scanning motor based on an instruction from the CPU 301. When the CPU 301 instructs the rotational speed, acceleration, movement amount, rotational direction, and rotation start timing of the pulse motor 113, the motor control circuit 309 generates a drive pulse voltage corresponding thereto.

[0042] The coordinate calculation circuit 310 counts two phase difference pulse signals of phase A and phase B from the linear encoder 108 and calculates the position of the light projecting unit 104. Here, the resolution of the linear encoder 108 is set to 1 μm. When the level of the phase A signal or the phase B signal changes and the phase of the phase A signal is advanced more than that of the phase B signal, the coordinate calculation circuit 310 increases the coordinates of the light projecting unit 104 by 1 μm. When the level of the phase A signal or the phase B signal changes and the phase of the phase B signal is advanced more than that of the phase A signal, the coordinate calculation circuit 310 decreases the coordinates of the light projecting unit 104 by 1 μm.

[0043] The synchronization circuit 311 generates trigger signals to be transmitted to the data acquisition control circuit 312, the motor control circuit 308, the motor control circuit 309, and the light source control circuit 305 based on the coordinate information obtained from the coordinate calculation circuit 310. Hereinafter, the trigger signal to the data acquisition control circuit 312 is referred to as a data acquisition trigger signal. The trigger signal to the motor control circuit 308 is referred to as a sub-scanning trigger signal. The trigger signal to the motor control circuit 309 is referred to as a height scanning trigger signal. Further, the trigger signal to the light source control circuit 305 is referred to as a wavelength switching trigger signal.

[0044] When the motor control circuit 308 receives the sub-scanning trigger signal, it outputs a drive pulse train corresponding to the movement amount of one pixel pitch in the sub-scanning direction to the motor driver 111. The pixel pitch in the sub-scanning direction is specified by the user at the start of imaging and is stored in the memory 303. When the motor control circuit 309 receives the height scanning trigger signal, it outputs a drive pulse train corresponding to the movement amount in the height scanning direction to the motor driver 114. The movement amount in the height scanning direction is calculated by the CPU 301. The calculation method will be described later.

[0045] The data acquisition control circuit 312 transfers the optical signal data output from the AD converter control circuit 306 to the memory 303 via the memory control circuit 304. In the present embodiment, the data acquisition control circuit 312 is composed of a buffer memory, a DMA controller, and the like. When the data acquisition control circuit 312 receives the data acquisition trigger signal from the synchronization circuit 311, it transfers the latest optical signal data stored in the internal buffer memory to the memory 303.

[0046] The communication circuit 313 connects the specimen measurement device 1 to an external network. In the present embodiment, the communication circuit 313 uses a communication protocol conforming to the Ethernet (registered trademark) standard as the communication method. By connecting the specimen measurement device 1 to an external PC or server, the communication circuit 313 enables remote control of specimen imaging and storage of data in an external large-capacity storage.

[0047] The UI control circuit 314 connects the specimen measurement device 1 to the user interface 117. The UI control circuit 314 is composed of an input circuit from a keyboard or a mouse and an image display circuit for controlling a display. Also, the user interface 117 can constitute a monitor. In this case, an image is displayed to the user on the display screen, and operation instructions from the user are received.

[0048] In addition, in this embodiment, the peripheral circuits constituting the controller circuit 116 are mounted on a semiconductor chip such as an FPGA or an ASIC. And these peripheral circuits operate in synchronization with a clock. In this embodiment, a clock frequency of 1.00 MHz is adopted.

[0049] Subsequently, with reference to FIGS. 4, 5, and 6, the imaging operation of the array plate 101 in this embodiment will be described. FIG. 4 shows an operation flow when the array plate 101 is imaged by the specimen measurement device 1 according to this embodiment. FIG. 5 is a diagram for explaining the mode of sub-scanning on the array plate 101 in the imaging operation. FIG. 5(a) is a view of the array plate 101 seen from above, and FIG. 5(b) is a diagram schematically showing the trajectory of the excitation light on the array plate 101. Also, FIG. 6 is a diagram for explaining the positional relationship of the height scanning of the array plate 101 in the imaging operation. FIGS. 6(a) and 6(b) are diagrams showing an example of the array plate 101 seen from the side. Note that in FIGS. 6(a) and 6(b), the thickness and inclination of the array plate 101 installed in the specimen measurement device 1 are different.

[0050] When an instruction to start imaging of the array plate 101 is input by the user via the user interface 117, the processing after step S401 is started. In step S401, the CPU 301 reads the imaging conditions specified by the user via the user interface 117 and stores them in the memory 303. Also, the CPU 301 sets information based on the imaging conditions in various circuits within the controller circuit 116.

[0051] As shooting conditions, a point 501(X1, Y1) indicating the shooting range on the array plate 101, a point 502(X2, Y2), a pixel pitch Xp in the main scanning direction, a pixel pitch Yp in the sub-scanning direction, and a rotation speed Xs in the main scanning direction are input. In this embodiment, it is assumed that X1 = 500, X2 = 22500, Y1 = 500, Y2 = 64500, Xp = 2 μm, Yp = 2 μm, and Xs = 1200 rpm are input. Here, a rectangular shooting area 503 with the points 501 and 502 on the array plate 101 as diagonals is referred to as the shooting area. Also, calculate the number of pixels Nx in the main scanning direction = (X2 - X1) / Xp and the number of pixels Ny in the sub-scanning direction = (Y2 - Y1) / Yp in advance. In this embodiment, according to the above settings, Nx = 11000 and Ny = 32000. When the reading of the shooting conditions and the above settings are completed, the flow proceeds to step S402.

[0052] In step S402, the CPU 301 acquires the height information and tilt information of the array plate 101. Here, the moving amount of the linear stage 112 required to focus the excitation light on the upper surface of the slide glass 201 that constitutes the array plate 101, that is, the surface on the side where the spot 202 is located, is referred to as height information. Also, the tilt in the sub-scanning direction of the array plate 101 is referred to as tilt information. In step S402, Z coordinates Z3 and Z4, which are height information for two Y coordinates Y3 and Y4, are acquired by measurement.

[0053] In this embodiment, it is assumed that Y3 = 750 and Y4 = 65000 are input. Here, if the tilt is as shown in Fig. 6(a), then Z4 > Z3, and if the tilt is as shown in Fig. 6(b), then Z3 < Z4. The method for acquiring the height information will be described later. Also, the tilt information K is calculated by the following formula 1. K = (Z4 - Z3) / (Y4 - Y3) (Formula 1) When the tilt is acquired, the flow proceeds to step S403.

[0054] In step S403, the CPU 301 calculates the target height of each row of the spot according to the shooting conditions, the height information, and the tilt information K. The target height Z(Y) at the coordinate Y of an arbitrary sub-scanning position is given by the following formula 2. Note that the target height 601 corresponds to the Z coordinate of the surface of the array plate 101 in FIGS. 6(a) and 6(b). Z(Y)=K×(Y - Y3)+Z3 (Formula 2) When the target height is calculated, the flow proceeds to step S404.

[0055] In step S404, the CPU 301 issues instructions to the motor control circuits 307, 308, and 309 to move the array plate 101 and the light projecting unit 104 to the shooting start position. In this embodiment, the X coordinate of the shooting start position is the end of the scanning range of the piston crank mechanism 120, and the X coordinate value is set to -2500. Also, the Y coordinate of the shooting start position is Y1 specified by the shooting conditions. Further, the Z coordinate Z1 of the shooting start position is represented by Z(Y1) in Formula 1. When the array plate 101 and the light projecting unit 104 are moved to the shooting start position, the flow proceeds to step S405.

[0056] In step S405, the CPU 301 issues an instruction to the motor control circuit 307 to rotate the pulse motor 107 at a rotational speed Xs. As a result, the light projecting unit 104 starts a reciprocating motion in the X direction. At this time, the X coordinate of the light projecting unit 104 is calculated for each clock by the linear encoder 108 and the coordinate calculation circuit 310, and the calculation result is output to the synchronization circuit 311. Information regarding the relative position of the light projecting unit 104 with respect to the array plate 101, which is calculated, is temporarily stored in a buffer memory provided in the synchronization circuit in this embodiment, and is transmitted to the memory 303 and stored here as needed. When the reciprocating motion is started, the flow proceeds to step S406.

[0057] In step S406, the CPU 301 issues an instruction to the light source control circuit 305 to start the light emission of the light source 102. Thereby, light irradiation (excitation light irradiation, hereinafter referred to as light irradiation) of the array plate 101 is started via the light projection unit 104. At this time, using the synchronization circuit 311, the array plate 101 is irradiated while alternately switching two types of light with wavelengths of 670 nm and 780 nm between the forward path and the return path of the main scan. Thus, in the present embodiment, instead of simultaneously receiving each fluorescence caused by the two types of light with the photosensor 105, the fluorescence caused by the light of each wavelength is received separately by the photosensor 105. Thereby, crosstalk between wavelengths that may occur due to simultaneous reception is reduced, and the measurement accuracy of the optical signal data is improved. When the light irradiation is started, the flow proceeds to step S407.

[0058] In step S407, the synchronization circuit 311 determines whether or not the irradiation position Pi of the primary light on the array plate 101 has reached the wavelength switching position. Specifically, the synchronization circuit 311 determines that the wavelength switching position has been reached when the X coordinate of the irradiation position of the light irradiated from the light projection unit 104 on the array plate 101 output from the coordinate calculation circuit 310 has shifted to predetermined positions X3 and X4 outside the imaging region. Here, the irradiation position of this light is obtained as the relative position of the light projection unit 104 in the XY plane on the array plate 101. In the present embodiment, the coordinates of positions X3 and X4 are set in advance and stored in the synchronization circuit 311. Further, the positions X3 and X4, which are the wavelength switching positions, are set at positions closer to the stroke end of the light projection unit 104 than the positions X1 and X2, which are the line feed positions. This is because it takes a certain amount of time to switch the wavelength, and the wavelength switching is completed while the light projection unit 104 is outside the imaging range. In the present embodiment, position X3 = 200 is adopted, and position X4 = 22800 is adopted.

[0059] When it is determined by the synchronization circuit 311 that the light irradiation position has reached the wavelength switching position by the synchronization circuit 311, the synchronization circuit 311 outputs a wavelength switching trigger signal to the light source control circuit 305, and the flow proceeds to step S421. Also, when it is determined by the synchronization circuit 311 that the wavelength switching position has not been reached, the synchronization circuit 311 does not output a wavelength switching trigger signal, and the flow proceeds to step S408.

[0060] In step S408, the synchronization circuit 311 determines whether or not the irradiation position Pi of the primary light has reached the line feed position. The synchronization circuit 311 determines that the line feed position has been reached when the X coordinate of the light projecting unit 104 output from the coordinate calculation circuit 310 shifts from within the imaging region to outside the imaging region. In the present embodiment, when the current main scanning direction is the return path direction (the direction in which the X coordinate decreases), the synchronization circuit 311 determines that the line feed position has been reached when the X coordinate of the light projecting unit 104 becomes smaller than X1. Also, in the present embodiment, the synchronization circuit 311 does not determine that the line feed position has been reached when the X coordinate of the light projecting unit 104 becomes larger than X2.

[0061] Note that the scanning in the forward path direction is represented by the locus 504 in FIG. 5(b). The scanning in the return path direction is represented by the locus 506 in FIG. 5(b), follows the same locus as the locus in the forward path direction in the reverse direction, and returns to the line feed position. The initial value of the main scanning direction is the forward path direction, and thereafter, every time the stroke end is reached, the change of the scanning direction between the return path direction and the forward path direction is alternately repeated.

[0062] When it is determined by the synchronization circuit 311 that the line feed position has been reached, the synchronization circuit 311 outputs a sub-scanning trigger signal and a height scanning trigger signal, and causes the processes of step S417 and step S418 to be executed in parallel. When it is determined by the synchronization circuit 311 that the line feed position has not been reached, the synchronization circuit 311 does not output a sub-scanning trigger signal and a height scanning trigger signal, and the flow proceeds to step S409.

[0063] In step S409, the determination means 173 included in the synchronization circuit 311 determines whether or not the irradiation position Pi of the primary light has reached the target position Pt. The point 507 in Fig. 5(b) indicates the position of the pixel imaged on the array plate 101. The target position Pt in the present embodiment is the point at which the optical signal data is acquired on the array plate 101 to generate a pixel. The X coordinate P(N) of the Nth target position Pt is represented by the following formula 3. P(N)=X1+Xp×N (N = 0, 1, … Nx-1) (Formula 3) The target positions are a plurality of points on the locus, the pitch in the X direction is Xp, and the pitch in the Y direction is Yp. In the present embodiment, it coincides with the point 507 which is the position of the pixel. Also, the initial value of the target position Pt is P(0), and it is stored in a buffer memory or the like provided inside the synchronization circuit 311. In the determination of the first target position Pt, when the X coordinate of the light projecting unit 104 output from the coordinate calculation circuit 310 passes P(0) in the forward path direction (the direction in which the X coordinate increases), it is determined that the target position Pt has been reached. In the determination of the target position Pt after the second time, when the X coordinate of the light projecting unit 104 output from the coordinate calculation circuit 310 passes the target position Pt whose target position Pt has been updated by the irradiation position Pi in step S411 described later, it is determined that the target position Pt has been reached. In the present embodiment, the target position is generated each time according to the pixel pitch at the time of image generation and the position information Iip of the irradiation position Pi from the linear encoder 108 obtained by the synchronization circuit 311. Information regarding the target position Pt is stored in the buffer memory provided in the synchronization circuit 311 each time. Also, the information regarding the target position Pt can be transferred to the memory 303 and stored here as needed. That is, in the present embodiment, the synchronization circuit 311 temporarily holds the target position Pt calculated each time from the relative position of the light projecting unit 104 with respect to the array plate 101 and the pixel pitch. Then, the synchronization circuit 311 determines whether or not the irradiation position Pi of the primary light has reached the target position Pt from the held target position and the position information obtained from the encoder.

[0064] When it is determined by the synchronization circuit 311 that the target position Pt has been reached, the synchronization circuit 311 outputs a data acquisition trigger signal, and the flow proceeds to step S410. When it is determined by the synchronization circuit 311 that the target position Pt has not been reached yet, the synchronization circuit 311 does not output a data acquisition trigger signal, and the flow proceeds to step S412.

[0065] In step S410, the AD converter control circuit 306 outputs a conversion start signal, receives the output voltage from the optical sensor 105, amplifies and filters it in the receiving circuit 106, and then performs AD conversion. In the present embodiment, the conversion start signal is a signal with a constant period, and the period is longer than the conversion time of the AD converter but shorter than the time taken for the light projecting unit 104 to move by the pixel pitch Xp. The AD-converted optical signal data is temporarily stored in the buffer memory inside the data acquisition control circuit 312. The buffer memory can store one optical signal data for one AD converter, and the latest optical signal data is overwritten and stored each time AD conversion is performed. In the present embodiment, an AD converter corresponding to the wavelength of each light source is provided, and optical signal data reflecting the amount of fluorescence excited by the wavelength of each light source is stored.

[0066] When the data acquisition control circuit 312 receives the data acquisition trigger signal, it reads out the optical signal data stored in the buffer memory and outputs it to the memory control circuit 304 via the internal DMA controller and bus 302. The memory control circuit 304 stores the optical signal data at a specified address in the memory 303. The address of the memory 303 is incremented each time the data acquisition trigger signal is received.

[0067] After the data acquisition control circuit 312 stores Nx×Ny pieces of optical signal data corresponding to the wavelengths of the respective light sources in the memory 303, it sets the internal data acquisition completion register to 1. When the data acquisition control circuit 312 has not stored Nx×Ny pieces of optical signal data corresponding to the wavelengths of the respective light sources in the memory 303, it sets the internal data acquisition completion register to 0. When the optical signal data at the target position Pt is stored, the flow proceeds to step S411.

[0068] Subsequently, in step S411, the first holding means 171 (synchronization circuit 311) updates the target position Pt held internally. When the current main scanning direction is the forward path direction (the direction in which the X coordinate increases), the target position Pt(N) is incremented to P(N + 1) and updated. When the current main scanning direction is the return path direction (the direction in which the X coordinate decreases), the target position Pt(N) is updated to P(N - 1). After updating the target position Pt, the flow proceeds to step S412.

[0069] In step S412, the CPU 301 determines whether the acquisition of the optical signal data has been completed. The CPU 301 reads the data acquisition completion register of the data acquisition control circuit 312. If the value is 1, it determines that the acquisition of the optical signal data has been completed and causes the flow to proceed to step S413. If the value is 0, it determines that the acquisition of the optical signal data has not been completed and causes the flow to proceed to step S407.

[0070] In step S413, the CPU 301 issues an instruction to the light source control circuit 305 to stop the emission of the light source 102. As a result, the light irradiation to the array plate 101 via the light projection unit 104 is stopped. After the stop of the light irradiation, the flow proceeds to step S414.

[0071] In step S414, the CPU 301 issues an instruction to the motor control circuit 307 to stop the rotation of the pulse motor 107. As a result, the reciprocating movement of the light projecting unit 104 in the X direction stops. After the reciprocating movement stops, the flow proceeds to step S415. In step S415, the CPU 301 issues instructions to the motor control circuits 307, 308, and 309 to move the array plate 101 and the light projecting unit 104 to the stop position. The X coordinate, Y coordinate, and Z coordinate of the stop position are 0. The movement to the stop position is carried out by returning each axis to the origin using the Z-phase pulse signal of the linear encoder 108, the origin sensor signal in the linear stage 109, and the origin sensor signal of the linear stage 112. When the array plate 101 and the light projecting unit 104 return to the origin for each axis, the flow proceeds to step S416.

[0072] In step S416, the CPU 301 reads out Nx×Ny pieces of optical signal data corresponding to the wavelengths of the respective light sources from the memory 303, performs processes of data compression and format conversion, and creates a photographed image file in TIFF format. The photographed image file is stored in the memory 303 and presented to the user via the UI control circuit 314 and the user interface 117. Also, according to an instruction from the user, the photographed image file can be transferred to an external data server via the communication circuit 313.

[0073] In step S417, the CPU 301 issues an instruction to the motor control circuit 308 to move the array plate 101 by Yp in the sub-scanning direction. Assuming that the movement amount of the array plate 101 when one voltage pulse signal is sent to the motor driver 111 is My, the number of pulses output by the motor control circuit 308 to the motor driver 111 is Yp / My. In this embodiment, My = 2 μm. The locus of the light irradiation position during sub-scanning is represented by the locus 505 in FIG. 5(b), and the movement distance in the Y direction at that time is Yp. The motor control circuit 308 outputs a pulse signal to the motor driver 111 at a speed such that the sub-scanning is completed while the light projecting unit 104 is outside the imaging region in the main scanning direction, based on an instruction from the CPU 301.

[0074] In step S418, the CPU 301 reads the target heights before and after the secondary scan from the memory 303. That is, it reads Z(Y + Yp) and Z(Y), and calculates the movement amount of the height scan. Although the movement amount of the height scan varies depending on the current Y coordinate, the number of output pulses and the rotation direction of the motor are calculated so that the height in the Z direction after the movement is closest to the target height Z(Y + Yp) at the Y coordinate after the secondary scan in step S417.

[0075] Here, the calculation direction is described as follows. Let Mz be the movement amount of the array plate 101 when a voltage pulse signal is sent to the motor driver 114 by one pulse. In this embodiment, Mz = 1 μm. Also, let RoundMz(x) be the multiple of Mz closest to a certain number x, let ABS(x) be the absolute value of a certain number, and let Sign(x) be the sign of a certain number. Also, the multiple of Mz closest to the target height is called the target pulse number. The target pulse number takes discrete values and corresponds to the pulse number 602 at each spot position in FIGS. 6(a) and 6(b). Here, the number of pulses output from the motor control circuit 309 to the motor driver 114 is represented by the following equation 4. Zp = ABS(RoundMz(Z(Y + Yp)) - RoundMz(Z(Y))) (Equation 4) In Equation 4, RoundMz(Z(Y)) becomes a discrete value close to the surface of the array plate 101 as shown by the pulse number 602 in FIGS. 6(a) and 6(b).

[0076] Also, the inclination direction Dir in the height direction of the array plate 101 is represented by the following equation 5. Dir = Sign(RoundMz(Z(Y + Yp)) - RoundMz(Z(Y))) (Equation 5) In Equation 5, the positive direction of Dir is set as vertically upward, and the direction in which the distance between the light projecting unit 104 and the array plate 101 increases. When the inclination mode of the array plate 101 is as shown in FIG. 6(a), the value of Dir is 1, and when it is as shown in FIG. 6(b), the value of Dir is -1. When the target height is read, the flow proceeds to step S419.

[0077] In step S419, the CPU 301 issues an instruction to the motor control circuit 309 to move the array plate 101 by Zp in the direction canceling the tilt direction Dir. When the value of Dir is positive, the array plate is moved downward, and when the value of Dir is negative, the array plate is moved upward. At this time, the number of pulses output from the motor control circuit 309 to the motor driver 111 is Zp / Mz. Based on the instruction from the CPU 301, the motor control circuit 309 outputs a pulse signal to the motor driver 114 at a speed such that the height scanning is completed while the light projecting unit 104 is outside the imaging area in the main scanning direction. When the sub-scanning in step S417 and the height scanning in step S419 are completed, the flow proceeds to step S420.

[0078] In step S420, the synchronization circuit 311 increments the current Y coordinate by Yp from the Y coordinate up to that point, and the flow proceeds to step S412.

[0079] In step S421, the light source control circuit 305 switches the emission and stop of the semiconductor lasers of 670 nm and 780 nm based on the information of the wavelength switching trigger signal from the synchronization circuit 311. More specifically, when the current main scanning direction is the forward path direction (the direction in which the X coordinate increases), the 780 nm laser is emitted when the X coordinate of the light projecting unit 104 exceeds the position X3. Also, the emission of the 780 nm laser is stopped when it exceeds the position X4. When the main scanning direction is the forward path direction (the direction in which the X coordinate increases), the emission of the 670 nm laser is stopped. When the current main scanning direction is the return path direction (the direction in which the X coordinate decreases), the 670 nm laser is emitted when the X coordinate of the light projecting unit 104 becomes smaller than the position X4. Also, the 670 nm laser is stopped when it becomes smaller than the position X3. When the main scanning direction is the forward path direction (the direction in which the X coordinate increases), the emission of the 780 nm laser is stopped. When the switching of the irradiation light is completed, the flow proceeds to step S412.

[0080] By executing the above processing, irradiation of the laser light of two wavelengths on each spot of the array plate 101 and imaging of the spots based on the fluorescence caused by the laser light are completed.

[0081] Next, the optical sensor 105 and the receiving circuit 106 in the specimen measuring apparatus 1 in the present embodiment will be described with reference to the drawings. FIG. 7 is a functional block diagram showing details of the optical sensor 105 and the receiving circuit 106 of the specimen measuring apparatus 1 according to the present embodiment.

[0082] The optical sensor 105 used in the present embodiment includes photomultiplier tubes 701 and 710, and photodiodes 709 and 711. The photomultiplier tube 701 is excited by light of 780 nm, converts the amount of fluorescence generated from the specimen into a current, and outputs this. The photodiode 709 converts the amount of reflected light of the light of 780 nm by the array plate 101 into a current and outputs this. The photomultiplier tube 710 is excited by light of 670 nm, converts the amount of fluorescence generated from the specimen into a current, and outputs this. The photodiode 711 converts the amount of reflected light of the light of 670 nm by the array plate 101 into a current and outputs this.

[0083] The receiving circuit 106 includes a current-voltage conversion (IV) amplifier 702, a level conversion circuit 703, a filter circuit 704, and an analog-to-digital converter (ADC) 705. The current-voltage conversion amplifier 702 outputs a voltage proportional to the current from the photomultiplier tube 701. In this embodiment, the output voltage range of the current-voltage conversion amplifier is set to -10V to 10V. The level conversion circuit 703 is a circuit that converts the level of the output voltage from the current-voltage conversion amplifier 702 to half, and is composed of a resistor network and a clamp circuit. By the level conversion circuit, negative voltages are clamped to 0V, and positive voltages are converted to half of their voltage levels by a voltage divider circuit. In this embodiment, since the voltage of the fluorescence signal is approximately 0V or higher from the direction of the current from the photomultiplier tube 701, by providing the level conversion circuit 703, the range to be converted to a digital value by the subsequent ADC 705 is limited to positive voltages, enhancing the resolution of the digital value. As a result, the output voltage range after level conversion becomes 0V to 5V. The filter circuit 704 cuts high-frequency signals of 500 kHz or higher among the output voltages of the level conversion circuit 703. By providing the filter circuit 704, aliasing generated during sampling is removed. The ADC 705 is a 16-bit ADC that converts the output from the filter circuit 704 into digital values from 0 to 65535.

[0084] The ADC control circuit 306 and the ADC 705 exchange control signals 706, 707, and 708. The control signal 706 is a conversion start signal that starts sampling and AD conversion. The control signal 707 is a clock signal when transferring optical signal data from the ADC 705 to the ADC control circuit 306. In this embodiment, the clock frequency of the clock signal 707 is set to 50 MHz. The control signal 708 is a data signal when transferring optical signal data from the ADC 705 to the ADC control circuit 306. The ADC 705 drives the control signal 708 in synchronization with the clock of the clock signal 707, and outputs optical signal data, which is the digital value of the AD conversion result, to the ADC control circuit 306.

[0085] Each of the photodiodes 709 and 711 and the photomultiplier tube 710 also outputs optical signal data to the AD converter control circuit 306 by means of a reception circuit similar to that of the photomultiplier tube 701. In the configuration shown in FIG. 7, the AD converter control circuit 306 controls the timing of the conversion start signal of each AD converter 705 to obtain the light amounts of the fluorescence and reflected light at 670 nm and the fluorescence and reflected light at 780 nm at arbitrary timings.

[0086] FIG. 8 is a timing chart showing the operation timings of main scanning, sub-scanning, height scanning, light irradiation, and optical signal data acquisition in the specimen measuring apparatus of the present embodiment. The horizontal axis of these timing charts is time. The timing chart 801 shows the operation timing of the main scanning, and indicates that the piston crank mechanism 120 rotates at the time shown by the hexagon and the main scanning of the light projecting unit 104 is being performed. The X-axis position 802 corresponds to the position of the light projecting unit 104 in the X-axis direction on the vertical axis, and shows the change in the position of the light projecting unit 104 on the X-axis over time with the horizontal axis being time. It is shown that the light projecting unit 104 reciprocates by the piston crank mechanism 120, and the speed is fast near the center of the stroke in the X-axis direction and slow near the end of the stroke.

[0087] The timing chart 803 shows the operation timing of the sub-scan. The pulse motor 110 operates at the time indicated by the hexagon, indicating that the sub-scan is being performed. The timing chart 804 shows the operation timing of the height scan. The pulse motor 113 operates at the time indicated by the hexagon, indicating that the height scan is being performed. The timing chart 805 shows the operation timing of the optical signal data acquisition during the 780 nm excitation light irradiation. The photomultiplier tube 701 and the receiving circuit 106 operate at the time indicated by the hexagon, indicating that the optical signal data acquisition derived from the 780 nm excitation light is being performed. The timing chart 806 shows the operation timing of the optical signal data acquisition during the 670 nm excitation light irradiation. The photomultiplier tube 701 and the receiving circuit 106 operate at the time indicated by the hexagon, indicating that the optical signal data acquisition derived from the 670 nm excitation light is being performed. The timing chart 807 shows the operation timing of the 780 nm laser in the light source 102. The 780 nm excitation light emits at the time indicated by the hexagon, indicating that it is irradiated onto the array plate 101 through the light projecting unit 104. The timing chart 808 shows the operation timing of the 670 nm laser in the light source 102. The 670 nm excitation light emits at the time indicated by the hexagon, indicating that it is irradiated onto the array plate 101 through the light projecting unit 104.

[0088] Thus, in this embodiment, when the X coordinate of the light projecting unit 104 moves in the forward path direction, the array plate 101 is irradiated with the 780 nm excitation light, and the optical signal data generated by the 780 nm excitation light is acquired. On the other hand, when the X coordinate of the light projecting unit 104 moves in the return path direction, the array plate 101 is irradiated with the 670 nm excitation light, and the optical signal data generated by the 670 nm excitation light is acquired. By acquiring the optical signal data with different excitation wavelengths in the forward path direction and the return path direction in this way, the influence of the positional deviation of the images in the forward path and the return path caused by mechanical errors of the piston crank mechanism 120, delay times of the receiving circuit 106, etc. is reduced.

[0089] As shown in FIG. 8, when the X coordinate of the main scan acquired by the linear encoder 108 reaches X1 during the forward movement, the acquisition of the optical signal data based on the excitation light of 780 nm is started. Then, when the X coordinate of the main scan acquired by the linear encoder 108 reaches X2 during the backward movement, the acquisition of the optical signal data based on the excitation light of 670 nm is started. When the X coordinate of the main scan reaches X1 during the backward movement, it is determined that the acquisition of the optical signal data in the backward direction is completed, and the sub-scan trigger and the height scan trigger are output, and the sub-scan and the height scan for moving to the next line are performed.

[0090] When the X coordinate of the main scan acquired by the linear encoder 108 reaches X3 during the forward movement, the irradiation of the excitation light of 780 nm is started. When the X coordinate of the main scan reaches X4 during the forward movement, it is determined that the acquisition of the optical signal data of 780 nm is completed, and the irradiation of the excitation light of 780 nm is stopped. Also, when the X coordinate of the main scan acquired by the linear encoder 108 reaches X4 during the backward movement, the irradiation of the excitation light of 670 nm is started. When the X coordinate of the main scan reaches X3 during the backward movement, it is determined that the acquisition of the optical signal data of 670 nm is completed, and the irradiation of the excitation light of 670 nm is stopped.

[0091] Subsequently, the difference between the control method of the specimen measuring apparatus 1 according to the present disclosure and the control method of the specimen measuring apparatus in the prior art will be described with reference to FIGS. 9(a) to 9(f). Here, first, with reference to FIGS. 9(a) and 9(b), the problems when the optical signal data is sampled in synchronization with simply reaching the X coordinate specified in advance in the main scan direction as in the prior art will be described.

[0092] Figure 9(a) shows a timing chart of the main scan that is executed under ideal conditions with little vibration in the piston crank mechanism 120 and the like. Specifically, it shows the operation timings of the AD converter 705 of the reception circuit 106, the AD converter control circuit 306, and the data acquisition control circuit 312. In Figure 9(a), the position of the light projection unit in the main scan is indicated by the X coordinate 901. However, Figure 9(a) is an enlarged view of the vicinity of the center of the stroke of the X-axis position 802 of the light projection unit 104 in Figure 8. In Figure 9(a), the output signal from the linear encoder 108 is converted into the X coordinate by the coordinate calculation circuit 310 and shown as a timing chart 902 corresponding to the encoder coordinate. Note that in Figure 9(a), for convenience, the coordinate at the start point is described as 0.

[0093] Figure 9(a) shows the voltage of the conversion start signal 706 output by the AD converter control circuit 306 to the AD converter 705 of the reception circuit 106. Here, every time the X coordinate of the light projection unit 104 advances by 2 μm specified as Xp, the conversion start signal 706 rises. When the AD converter 705 detects the rising of the voltage of the conversion start signal 706, it samples the fluorescence signal output from the filter circuit 704. The timing chart 904 shows the sampling timing of the signal performed within the AD converter 705. The AD converter 705 operates and sampling is performed at the time indicated by the hexagon in the timing chart 904. The fluorescence signal after sampling is held within the AD converter 705 and converted into a digital value.

[0094] Timing chart 905 shows the timing of the conversion of the fluorescence signal into a digital value performed within the AD converter 705. The hexagon indicates the time when the AD converter 705 operates, showing that the conversion into a digital value is being performed. Timing chart 906 shows the timing when the AD converter 705 outputs the optical signal data to the AD converter control circuit 306. At the time indicated by the hexagon, a data signal 708 consisting of an optical signal is transmitted together with the clock signal 707, showing that the output of the digital value is being performed. The AD converter control circuit 306 sequentially transfers the optical signal data acquired from the AD converter 705 to the memory 303. Timing chart 907 shows the timing when the AD converter control circuit 306 transfers the digital value received to the memory 303 via the bus 302. At the time indicated by the hexagon, the bus 302 operates, showing that the output of the digital value is being performed.

[0095] The AD converter 705 is operating from the start of sampling shown in the timing chart 904 until the completion of the output of the digital value shown in the timing chart 906, and cannot start sampling the next fluorescence signal. This period is referred to as the busy period of the AD converter. Timing chart 908 shows the busy period of the AD converter 705. During the busy period indicated by the arrow, the AD converter 705 is operating, showing that it cannot start sampling even if the conversion start signal 706 is input during that period. In this embodiment, the length of this busy period is 800 ns.

[0096] As shown in Fig. 9(a), during the main scan, there is little vibration. In an ideal state, there is little rapid change in the slope of the X coordinate 901, indicating little variation in the main scan speed. In this case, there is little variation in the timing of the conversion start signal indicated by the voltage change, and its rise is outside the busy period shown in the timing chart 908. Therefore, in such a case, the acquisition of the optical signal data is performed without omission in synchronization with the X coordinate.

[0097] However, in reality, due to vibrations of the piston crank mechanism 120 or the like, the scanning of the light projecting unit 104 does not result in a simple position change. FIG. 9(b) is a timing chart showing the operation timings of the AD converter 705, the AD converter control circuit 306, and the data acquisition control circuit 312 of the reception circuit 106 when there is such a main scanning vibration. The X coordinate 901 indicated by the dotted line is the same as the X coordinate 901 in FIG. 9(a), and shows the change in the X coordinate of the main scanning in an ideal case. Since the timing charts 902 to 908 are the same as the timing charts 902 to 908 in FIG. 9(a) respectively, the description here is omitted. The solid line 909 shows the change in the X coordinate of the actual main scanning when there is vibration, and it can be seen that it vibrates complexly at a high frequency in the positive and negative directions compared to the change indicated by the dotted line as the X coordinate 901. In such a case, when viewed globally, the main scanning is performed at the same average speed as in FIG. 9(a), but when viewed locally, the variation in speed becomes large.

[0098] Therefore, the variation in the coordinate value of the linear encoder shown in the timing chart 902 is large, and there may be a case where the irradiation position Pi on the X coordinate advances by 2 μm and passes the next target position Pt at a timing earlier than expected. In that case, as shown in FIG. 9(b), the conversion start signal indicated by the rising edge of the voltage in the timing chart 903 rises within the busy period indicated by the timing chart 908. According to the example in FIG. 9(b), in the timing chart 904, the timings 910 and 911 are shown as examples when the conversion start signal is sent within the busy period. In such a case, the corresponding fluorescence signal cannot be acquired, and since the AD converter 705 cannot perform AD conversion, an acquisition leak of the optical signal data occurs.

[0099] As described above, the main scanning may have a variation in speed due to vibrations or the like. If sampling is simply performed in synchronization with the X coordinate of the main scanning as in the prior art, the occurrence of this speed variation may lead to an acquisition leak of the optical signal data due to the conversion start signal being output within the busy period of the AD converter.

[0100] This disclosure is in view of such a situation, and next, with reference to FIGS. 9(c) to (f), an example of an optical signal data acquisition method according to the first embodiment will be described.

[0101] FIG. 9(c) is a timing chart showing the operation timings of the AD converter 705, the AD converter control circuit 306, and the data acquisition control circuit 312 of the reception circuit 106 in an ideal case where the main scanning vibration is small in the present embodiment. The present embodiment shown in FIG. 9(c) differs from the conventional example shown in FIG. 9(a) in the following points. Specifically, it is the timing of the voltage rise of the conversion start signal 706 indicated by the timing chart 903 and the data transfer timing from the AD converter control circuit 306 to the memory 303 indicated by the hexagon in the timing chart 907. Note that the change in the X coordinate 901 and the timing charts 902, 904, 905, 906, 908 are the same as those described in FIG. 9(a), so the description here is omitted.

[0102] In the timing chart 903, in the example shown in FIG. 9(a), the timing of the voltage rise of the conversion start signal was synchronized with the coordinates output from the coordinate calculation circuit 310. In contrast, in the present embodiment shown in FIG. 9(c), the conversion start signal 706 operates so that the voltage rises at a constant frequency regardless of the output coordinates from the coordinate calculation circuit 310. Here, the frequency of the voltage rise is set to 1 MHz. This period is 1 us, which is longer than the length of the busy period of 800 ns, so the voltage rise of the conversion start signal 706 always occurs outside the busy period.

[0103] In the timing chart 907, in the example of FIG. 9(a), the optical signal data after AD conversion was sequentially transferred to the memory 303 in response to the acquisition of the optical signal data from the AD converter 705. On the other hand, in the example of FIG. 9(c), the operation timing of data transfer to the memory 303 is synchronized with the coordinates output from the coordinate calculation circuit 310. That is, at the timing when the X coordinate advances by 2 μm and reaches the target position Pt, a data acquisition trigger signal is output from the synchronization circuit 311 to the data acquisition control circuit 312. The data acquisition control circuit 312 transfers the latest digital value that has been output to the ADC control circuit up to that time to the memory 303. In this way, although the AD conversion is performed asynchronously with the X coordinate of the main scan shown in the timing chart 902, by synchronizing the transfer of the optical signal data with the X coordinate, the optical signal data close to the initial target position Pt is transferred to the memory 303.

[0104] FIG. 9(d) is a timing chart showing the operation timing of the AD converter 705, the AD converter control circuit 306, and the data acquisition control circuit 312 of the reception circuit 106 when there is vibration in the main scan in the present embodiment. The difference between the example of FIG. 9(d) and the example of FIG. 9(b) lies in the rising timing of the voltage of the conversion start signal 706 shown in the timing chart 903 and the data transfer timing from the AD converter control circuit 306 to the memory 303 shown in the timing chart 907. Note that since the change in the X coordinate 901 and the timing charts 902, 904, 905, 906, 908, and the solid line 909 are the same as those described in FIG. 9(b), the description here is omitted.

[0105] In the timing chart 903, in the example shown in FIG. 9(b), the timing of the rising edge of the driving voltage of the conversion start signal was synchronized with the coordinates output from the coordinate calculation circuit 310. On the other hand, in the present embodiment shown in FIG. 9(d), the conversion start signal 706 operates such that the voltage rises at a constant frequency regardless of the output coordinates from the coordinate calculation circuit 310. Here, the frequency of the voltage rise is set to 1 MHz. This period is 1 us, which is longer than the length of the busy period, 800 ns. Therefore, due to the vibration of the main scan, even if the coordinates of the linear encoder reach the target position Pt within the busy period, the voltage rise of the conversion start signal always occurs outside the busy period.

[0106] In the timing chart 907, in the example shown in FIG. 9(b), the optical signal data after AD conversion was sequentially transferred to the memory 303 in response to the acquisition of the optical signal data from the AD converter 705. On the other hand, in the example shown in FIG. 9(d), the timing of data transfer to the memory 303 is synchronized with the coordinates output from the coordinate calculation circuit 310. That is, at the timing when the X coordinate of the irradiation position Pi of the primary light advances by 2 μm and the irradiation position Pi reaches the target position Pt, a data acquisition trigger signal is output from the synchronization circuit 311 to the data acquisition control circuit 312. The data acquisition control circuit 312 transfers the latest digital value output to the ADC control circuit up to that time to the memory 303. Thus, in the present embodiment, although the AD conversion is performed asynchronously with the X coordinate of the main scan shown in the timing chart 902, the transfer of the optical signal data is synchronized with the X coordinate. By adopting such a configuration, while preventing the omission of optical signal data acquisition due to passing through the target position Pt within the busy period, the optical signal data that is close to being equally spaced at the original target position Pt is transferred to the memory 303.

[0107] Above, the example where the scanning speed is high near the center of the stroke of the X-axis position 802 in FIG. 8 has been described with reference to FIGS. 9(a) to 9(d). Below, with reference to FIGS. 9(e) and 9(f), an example where the scanning speed is low near the end of the stroke of the X-axis position 802 in FIG. 8 will be described.

[0108] Figure 9(e) is a timing chart showing the operation timings of the AD converter 705, the AD converter control circuit 306, and the data acquisition control circuit 312 of the reception circuit 106 when ideal main scanning with little vibration in the main scanning is performed in the present embodiment. In Figure 9(e), the X coordinate 901 indicates the change in position during the main scanning, and it is an enlarged view of the vicinity of the stroke end of the X-axis position 802 in Figure 8. Compared with the example in Figure 9(c), the slope of the change in the X coordinate 901 is smaller because the scanning speed is slower.

[0109] The operations of the timing charts 902 to 908 are the same as the example in Figure 9(c). That is, the voltage rise of the conversion start signal 706 operates at a constant frequency regardless of the difference in the moving speed of the X coordinate. Here, the frequency of the voltage rise is set to 1 MHz. This period is 1 us, which is longer than the length of the busy period of 800 ns, so the voltage rise of the conversion start signal always occurs outside the busy period.

[0110] In the example of Figure 9(e), in the timing chart 907, the operation timing of the data transfer to the memory 303 is synchronized with the coordinates output from the coordinate calculation circuit 310. That is, at the timing when the X coordinate of the irradiation position Pi of the primary light advances by 2 μm and the irradiation position Pi reaches the target position Pt, a data acquisition trigger signal is output from the synchronization circuit 311 to the data acquisition control circuit 312. The data acquisition control circuit 312 transfers the latest digital value output to the ADC control circuit to the memory 303 until that time. Note that, unlike the example in Figure 9(c), when the scanning speed is slow, AD conversion for the optical signal data at the next scanning position may be performed before the previous optical signal data is transferred to the memory 303. In this case, the data acquisition control circuit 312 overwrites the old optical signal data with the new optical signal data and holds only the latest optical signal data. The optical signal data obtained at the timing indicated by the hatched hexagon in the timing chart 906 is overwritten and thus not transferred to the memory. As a result, the number of optical signal data transferred to the memory 303 becomes smaller than the number of optical signal data to be AD-converted.

[0111] In this way, by transferring only the latest optical signal data to the memory 303 in synchronization with the X coordinate, only the optical signal data whose irradiation position Pi of the primary light is close to the target position Pt is selected and stored in the memory 303. Therefore, compared with the case of simply performing AD conversion at a constant frequency and sequentially storing the acquired optical signal data in the memory 303, the capacity of the memory 303 and the data communication volume are reduced. Also, in the case of simply performing AD conversion at a constant frequency and sequentially storing the acquired optical signal data in the memory 303, there is a large variation in the acquisition interval of the optical signal data depending on the scanning speed. However, with the method of this embodiment, optical signal data that is nearly equally spaced is acquired even when the scanning speed changes significantly.

[0112] FIG. 9(f) is a timing chart showing the operation timings of the AD converter 705, the AD converter control circuit 306, and the data acquisition control circuit 312 of the reception circuit 106 when there is main scanning vibration in this embodiment. The dotted line shown as the X coordinate 901 is the X coordinate of the main scanning in an ideal case, similar to the X coordinate 901 in FIG. 9(e). Since the timing charts 902 to 908 are the same as the timing charts 902 to 908 in FIG. 9(e) respectively, the description here is omitted. The solid line 909 shows the change in the actual X coordinate of the main scanning when there is vibration, and it can be seen that it vibrates complexly at a high frequency in the positive and negative directions compared with the change in the X coordinate 901 shown by the dotted line. In such a case, overall, the main scanning is performed at the same average speed as in FIG. 9(e), but locally, the variation in speed becomes large.

[0113] As a result, in the timing chart 902, the timing at which the irradiation position Pi of the primary light passes through the target position Pt is shifted, and the temporal relationship between the voltage rising timing of the data acquisition trigger signal and the timing of the conversion start signal is different from the ideal case shown in FIG. 9(e). As a result, the optical signal data transferred to the memory 303 is different between the example case of FIG. 9(e) and the example case of FIG. 9(f). More specifically, when there is no vibration, the third optical signal data from the left in the timing chart 906 of FIG. 9(e) is transferred to the memory 303. On the other hand, when there is vibration, the second optical signal data from the left in the timing chart 906 of FIG. 9(f) is transferred to the memory 303. Thus, even when there is vibration, it is possible to selectively transfer optical signal data close to the target position Pt to the memory, and acquire optical signal data that is close to being equally spaced.

[0114] Such local vibrations change not only with position and speed but also due to aging deterioration, etc., making it difficult to predict in advance. According to the optical signal data acquisition method according to the present embodiment, while reflecting such changing situations and preventing acquisition omission of optical signal data, optical signal data that is close to being equally spaced at the initial target position Pt is acquired.

[0115] Here, in the present embodiment, the process of acquiring the height information of the array plate 101 in the specimen measuring apparatus 1 will be described with reference to FIGS. 10 and 11. FIG. 10 is an operation flow when acquiring the height information of the array plate 101 using the specimen measuring apparatus 1 according to the present embodiment. The difference from the imaging operation is that during height information acquisition, sub-scanning is not performed, and reflected optical signal data is acquired while performing height scanning at an equal pitch, and this is analyzed to calculate the height of the array plate surface. In height information acquisition, the photodiode 709 in the optical sensor 105 is used.

[0116] FIG. 11 is a diagram for explaining the positional relationship of the height scanning of the array plate in the height information acquisition operation. FIGS. 11(a) and 11(b) are views of the array plate 101 seen from the side. FIG. 11(c) is a plot of the amount of reflected light acquired by the optical sensor 105 during height scanning for each height, where the horizontal axis indicates the magnitude of the light amount and the vertical axis indicates the acquired height.

[0117] When the height information acquisition process is started, first, in step S1001, the CPU 301 sets parameters for height information acquisition in the synchronization circuit 311. The parameters to be set include the Y coordinate Yh of the position where height information is acquired, the pixel pitch Xp in the main scanning direction, and the pixel pitch Zp in the height scanning direction. Also included are the points 1101(X5, Z5), 1102(X6, Z6) indicating the height scanning range on the XZ plane, and the rotational speed Xs in the main scanning direction.

[0118] In this embodiment, a rectangular region 1103 with the points 1101 and 1102 on the XZ plane as diagonals is referred to as the height scanning region. Here, in advance, the number of pixels Nx = (X6 - X5) / Xp in the main scanning direction and the number of pixels Nz = (Z6 - Z5) / Zp in the height scanning direction are calculated. In this embodiment, let X5 = 500, X6 = 22500, Z5 = 2000, Z6 = 6000, Xp = 10 [μm], Zp = 10 [μm], and Xs = 1200 [rpm]. In this case, Nx = 2200 and Nz = 400. After setting the parameters, the flow proceeds to step S1002.

[0119] In the height information acquisition process, unlike the imaging process, the acquisition interval of the optical signal data may be large. Therefore, the time required for height information acquisition is shortened and the data volume is reduced. In step S1002, the CPU 301 issues instructions to the motor control circuits 307, 308, and 309 to move the array plate 101 and the light projecting unit 104 to the height information acquisition start position. In the present embodiment, the X coordinate of the height information acquisition start position is the end of the scanning range of the piston crank mechanism 120, and the X coordinate value is set to -2500. The Y coordinate of the height information acquisition start position is set to Yh specified by a parameter. Further, the Z coordinate of the height information acquisition start position is set to Z5 specified by a parameter. After the movement is completed, the flow proceeds to step S1003.

[0120] In step S1003, the CPU 301 starts the main scanning in the same manner as in step S405 of the imaging process, and the flow proceeds to step S1004. In step S1004, the CPU 301 starts irradiating the light source 102 with excitation light of 760 nm, and the flow proceeds to step S1005. Note that in step S1004, irradiation with excitation light of 670 nm is not performed.

[0121] In step S1005, the synchronization circuit 311 determines whether or not the light projecting unit 104 has reached the line feed position. Specifically, when the X coordinate of the light projecting unit 104 output from the coordinate calculation circuit 310 moves from within the imaging region to outside the imaging region, the synchronization circuit 311 determines that the line feed position has been reached. When the current main scanning direction is the forward path direction (the direction in which the X coordinate increases), it is determined that the line feed position has been reached when the X coordinate of the light projecting unit 104 exceeds X6. The scanning in the forward path direction is represented by the locus 1104 of the light projecting unit 104 shown in FIG. 11(b). Further, when the current main scanning direction is the return path direction (the direction in which the X coordinate decreases), the synchronization circuit 311 determines that the line feed position has been reached when the X coordinate of the light projecting unit 104 becomes smaller than X5. The scanning in the return path direction is represented by the locus 1106 of the light projecting unit 104 shown in FIG. 11(b). The initial value of the main scanning direction is the forward path direction, and thereafter, every time the stroke end is reached, the scanning direction is alternately repeated and changed between the return path direction and the forward path direction. Such scanning may be alternatively referred to as bullock plowing scanning.

[0122] In the height information acquisition process, unlike the imaging process, the wavelength of the light irradiation may be of one type. Therefore, line breaks can be performed both on the forward and return paths, shortening the time required for height information acquisition. When the light projecting unit 104 reaches the line break position, the synchronization circuit 311 outputs a height scanning trigger signal, and the flow proceeds to step S1014. When the light projecting unit 104 has not reached the line break position, the synchronization circuit 311 does not output a height scanning trigger signal, and the flow proceeds to step S1006.

[0123] In step S1006, the determination means 173 incorporated in the synchronization circuit 311 determines whether the irradiation position Pi has reached the target position Pt in the same manner as in step S409 of the imaging process. The target position Pt is a plurality of points on a locus such as the point 1108 illustrated in FIG. 11(b), and is arranged with a pitch in the X direction of Xp and a pitch in the Z direction of Zp. When it is determined by the synchronization circuit 311 that the light projecting unit 104 has reached the target position Pt, the synchronization circuit 311 outputs a data acquisition trigger signal, and the flow proceeds to step S1007. When it is determined by the synchronization circuit 311 that the light projecting unit 104 has not yet reached the target position Pt, the synchronization circuit 311 does not output a data acquisition trigger signal, and the flow proceeds to step S1009.

[0124] In step S1007, the AD converter control circuit 306 and the data acquisition control circuit 312 perform the same process as in step S410 of the imaging process to acquire optical signal data, and the flow proceeds to step S1008. However, here, after the data acquisition control circuit 312 stores N×Nz pieces of optical signal data in the memory 303, it sets the internal data acquisition completion register to 1. When Nx×Nz pieces of optical signal data are not stored in the memory 303, the data acquisition control circuit 312 sets the internal data acquisition completion register to 0. After the acquisition of the optical signal data, the flow proceeds to step S1008. In step S1008, the synchronization circuit 311 updates the target position Pt held internally in the same manner as in step S411 of the imaging process, and the flow proceeds to step S1009.

[0125] In step S1009, the CPU 301 determines, in the same manner as in step S412 of the imaging process, whether or not the acquisition of the optical signal data has been completed. If the CPU 301 determines that the acquisition of the optical signal data has been completed, the flow proceeds to step S1010. If the CPU 301 determines that the acquisition of the optical signal data has not been completed, the flow proceeds to step S1005.

[0126] In step S1010, the CPU 301 issues an instruction to the light source control circuit 305 in the same manner as in step S413 of the imaging process to stop the emission of the light source 102, and the flow proceeds to step S1011. In step S1011, the CPU 301 issues an instruction to the motor control circuit 307 in the same manner as in step S414 of the imaging process to stop the rotation of the pulse motor 107 and end the main scanning, and the flow proceeds to step S1012. In step S1012, the CPU 301 issues an instruction to the motor control circuits 307, 308, and 309 in the same manner as in step S415 of the imaging process to move the array plate 101 and the light projecting unit 104 to the stop positions, and the flow proceeds to step S1013.

[0127] In step S1013, the CPU 301 reads out the Nx×Nz pieces of optical signal data stored in the memory 303, analyzes them, and calculates the height information of the array plate. Specifically, the Nx pieces of optical signal data acquired at the same height are added and averaged to obtain the average light amount for each height. When the obtained average light amounts are arranged for each Z coordinate, as shown in FIG. 11(c), there are two peaks corresponding to the front and back surfaces of the array plate 101. More specifically, in FIG. 11(c), peak 1109 indicates the peak due to the reflected light from the front surface of the array plate 101, and peak 1110 indicates the peak due to the reflected light from the back surface of the array plate 101. Among these peaks, the Z coordinate 1111 indicating the peak 1109 with a larger Z coordinate, that is, the peak corresponding to the front surface, is used as the height information corresponding to the position Yh. When the height information is obtained, the height information acquisition process is terminated.

[0128] In step S1014, the CPU 301 issues an instruction to the motor control circuit 309 to move the array plate 101 by Zp in the height scanning direction. Here, assuming that the moving amount of the array plate 101 when a voltage pulse signal is sent to the motor driver 114 by one pulse is Mz, the number of pulses output by the motor control circuit 309 to the motor driver 114 is Zp / Mz. The height scanning is represented by the trajectories 1105 and 1107 in Fig. 11(b), and the moving distance in the Z direction is Zp. Based on the instruction from the CPU 301, the motor control circuit 309 outputs a pulse signal to the motor driver 114 at a speed such that the height scanning is completed while the light projecting unit 104 is outside the imaging area in the main scanning direction. When the scanning in the height direction corresponding to one pulse is completed, the flow proceeds to step S1015.

[0129] In step S1015, the synchronization circuit 311 increments the current Z coordinate by Zp from the previous Z coordinate, and the flow proceeds to step S1009. When the process of obtaining tilt information in the imaging process is executed in step S402, the height information acquisition process shown in Fig. 10 is performed twice for the Y coordinates Y3 and Y4, the Z coordinates Z3 and Z4 in each case are obtained, and the tilt information K is obtained using Equation 1.

[0130] In this embodiment, an example has been described in which the imaging area 503 covers the entire area 204 and all the spots on the array plate 101 are imaged, but the present invention is not limited to this. That is, it is also possible for the user to set an arbitrary part of the area 204 as the imaging area 503. Thereby, by scanning only a part including the spot of interest, the imaging time can be shortened.

[0131] In addition, in this embodiment, an example in which height information is acquired using the peak position of the reflected light from the surface of the slide glass has been described, but the method for acquiring height information is not limited to this. Height information may be acquired using the peak position of the luminance of the fluorescence signal from some spots on the array plate. In this case, it is necessary to apply light to some spots for acquiring height information, but since it is not necessary to acquire reflected light with an optical sensor, the number of components of the optical system can be reduced.

[0132] In addition, in this embodiment, an example in which two wavelengths from the light source are switched between the forward path and the return path has been described, but the method for controlling the light source is not limited to this. The excitation light of two wavelengths may be simultaneously irradiated in both the forward path and the return path, and the fluorescence derived from each excitation light may be separated and acquired by the optical system. In that case, since it travels twice in one round trip, the imaging time can be shortened to about half.

[0133] As described above, the specimen measurement apparatus according to the present disclosure described as the first embodiment optically measures the characteristics of a specimen using an array substrate provided with spots in an array. The specimen measurement apparatus 1 includes a light irradiation unit, a light detection unit, a scanning unit, a position acquisition unit, a conversion unit, a first holding unit, a second holding unit, a determination unit, a storage unit, and a transfer unit. Further, the present disclosure can also constitute a specimen measurement method for operating these units as follows. In this embodiment, the light projection unit 104 constitutes one aspect of the light irradiation unit in the present disclosure, which irradiates the array substrate (array plate 101) with the condensed primary light (excitation light having wavelengths of 670 nm and 780 nm) for a predetermined period. The optical sensor 105 constitutes one aspect of the light detection unit in the present disclosure, which detects the secondary light, which is the fluorescence from the spot 202 irradiated with the primary light, at a predetermined period and outputs the optical signal data as a detection signal. The piston crank mechanism 120, the linear stage 109, and motors and the like associated therewith constitute one aspect of the scanning unit in the present disclosure, which relatively changes the irradiation position of the primary light with respect to the array substrate. The coordinate calculation circuit 310 constitutes one aspect of the position acquisition unit 138 in the present disclosure, which acquires information regarding the irradiation position of the primary light with respect to the array substrate. The receiving circuit 106 including the AD converter 705 and the AD converter control circuit 306 constitute one aspect of the conversion means 146 in the present disclosure that converts the detection signal acquired during a predetermined period into digital data. Note that the predetermined period described here corresponds to the period defined by the encoder coordinates 0 and 1 in the timing chart 902 illustrated in FIG. 9(f).

[0134] In the present disclosure, the first holding means 171 is included in the synchronization circuit 311 as a buffer memory as shown in FIG. 17. That is, the synchronization circuit 311 calculates a target position Pt set as a position for acquiring optical signal data with respect to the irradiation position of the primary light, and holds this in the buffer memory arranged in the synchronization circuit 311, constituting one aspect of the first holding means 171 in the present disclosure. Note that the X coordinate P(N) of the N-th target position Pt is represented by X1 + Xp × N (Xp: pitch in the X direction). However, the holding of the target position Pt is not limited to being executed by the synchronization circuit 311, and it may be held by the coordinate calculation circuit 310 that calculates the X coordinate of the light projection unit 104 based on the output of the linear encoder 108. The second holding means 172 is included in the synchronization circuit 311 as a buffer memory as shown in FIG. 17, and holds the digital data converted by the conversion means 146 shown in FIG. 18. In the memory 303, among the digital data held by the second holding means 172, the data transferred by the transfer means described later is stored in association with the information regarding the irradiation position Pi, constituting the storage means in the present disclosure. Therefore, the memory 303 may be paraphrased as storage means that stores the irradiation position Pi and the digital data in association with each other.

[0135] Further, the determination means 173 constitutes one aspect of the determination means in the present disclosure for determining that the irradiation position Pi of the primary light has reached the target position Pt based on information regarding the relative position obtained from the linear encoder 108 or the like. The data acquisition control circuit 312 selects digital data corresponding to the data output (the left two hexagons in the timing chart 906) in the predetermined period in FIG. 9(f) according to the determination result by the determination means 173 that the irradiation position Pi has reached the target position Pt. The memory control circuit 304 constitutes one aspect of the transfer means in the present disclosure for transferring the digital data thus selected to the memory 303. In the present disclosure, the data acquisition control circuit 312 and the memory control circuit 304 are disclosed as separate configurations, but they can also be treated as an integrated configuration. That is, the data acquisition control circuit 312 is, in other words, a transfer means for selecting the digital data held in the second holding means 172 according to the determination result by the determination means 173 and transferring it to the storage means (memory 303). The selected digital data is the digital data held in the second holding means 172 and becomes the data corresponding to the irradiation position Pi corresponding to the target position Pt.

[0136] The specimen measurement device 1 may further include a light source 102 and a light source control circuit 305. The light source 102 is optically coupled to the light irradiation means and emits primary light that is guided to the light projection unit 104. The light source control circuit 305 constitutes the light source control means in the present embodiment and controls the on / off of the light emission of the light source 102. Further, the light irradiation means in the present embodiment includes an objective optical system 129 that condenses primary light on the array plate 101. The light detection means is optically coupled to the objective optical system 129 to constitute a light sensor 105 of the light detection unit in the present embodiment that guides and detects secondary light from the spot on the array plate 101. Also, as described above, the scanning means includes a piston crank mechanism 120, a linear stage 109, and motors and the like associated therewith. The piston crank mechanism 120 includes a rotation drive unit 121 and a piston crank unit 123 in the present embodiment. The rotation drive unit 121 is composed of a motor or the like and rotates a drive shaft, and constitutes one aspect of the rotation drive unit in the present disclosure. The rotation drive unit is connected to one end of the crank 118, which is one end of the piston crank unit 123, and converts the rotational motion of the rotation axis into a one-dimensional reciprocating motion. The other end of the connecting rod 119, one end of which is connected to the other end of the crank 118, which is the other end of the piston crank unit 123, is connected to the objective optical system 129 (light projection unit 104). By having such a structure, the scanning means can reciprocate the objective optical system (see FIG. 16).

[0137] In the present embodiment, as shown by the spot positions in FIG. 2(a), Pt is arranged to be equally spaced on the array substrate (on the array plate 101). Further, information regarding the target position Pt is held as data in the first holding means 171. The data Itp related to the target position Pt held in the first holding means 171 is updated according to the movement or relative change of the irradiation position by the main scanning means. Further, the conversion means (AD converter 705) converts the detected optical signal data into digital data within a predetermined period shorter than the time required for the main scanning means to scan between adjacent target positions Pt with primary light. Further, the transfer means (data acquisition control circuit 312) preferentially selects digital data closer to the end of a predetermined period among the digital data and transfers it to the memory 303. In the present embodiment, the data of the hexagon (immediately before the number 2 in the encoder coordinate timing chart 902) without the second hatching from the left in the data output timing chart 906 in FIG. 9(f) is selected and transferred to the memory 303. Although the immediately preceding data is most preferably the transfer target, it may be possible to select and transfer the immediately preceding two data, the data immediately before the immediately preceding one, etc. by using a buffer memory or the like.

[0138] In addition, the specimen measurement device 1 according to the present disclosure further includes an imaging unit (image processing unit 301a) that images the characteristics of a specimen based on digital data stored in a storage unit (memory 303). The specimen measurement device 1 uses the digital data assigned to each pixel (target position Pt) by the image processing unit 301a to image the characteristics of the specimen and displays this on the user interface 117. Further, the specimen measurement device 1 according to the present disclosure further includes a buffer memory that temporarily stores the converted digital data. In the present embodiment, such a buffer memory is provided in the data acquisition control circuit 312. When a plurality of converted digital data are obtained within the time required to scan the target positions Pt where the irradiation positions of the primary light are continuous, the temporarily stored digital data are overwritten by the digital data obtained immediately thereafter. In the example shown in FIG. 9(f), in the timing chart 906 showing data output, the data indicated by the leftmost hatched hexagon is overwritten by the data indicated by the next white hexagon. This process is executed by the data acquisition control circuit 312.

[0139] Note that the present disclosure is also understood as a control method for a specimen measurement device. This control method includes an optical irradiation step, an optical detection step, a scanning step, a position acquisition step, and a conversion step, which are executed by the controller circuit 116 using the above-described configuration, and further includes a determination step and a transfer step. The optical irradiation step is a process that continues to be executed after step S406 in FIG. 4, and irradiates the array substrate with the condensed primary light for a predetermined period. The optical detection step is a process executed in step S410, and detects the secondary light from the spot at a predetermined period and outputs a detection signal from the optical sensor 105. The scanning step is a process that continues to be executed after step S405, and changes the irradiation position of the primary light on the array substrate. The position acquisition step is a process executed in step S405 in combination with the scanning step, and acquires information regarding the irradiation position. The conversion step is a process executed in step S410, and converts the detection signal acquired from the optical sensor 105 at a predetermined period into digital data. The determination step is a process executed in step S409, and determines whether or not the irradiation position Pi corresponds to the target position Pt. The transfer step selects, according to the determination result determined in the determination step, data corresponding to the timing when the irradiation position Pi reaches the target position Pt from the digital data held in the second holding means 172, and transfers it to the storage means (memory 303). By repeatedly executing these steps, it is possible to obtain digital data in a mode in which an image related to the specimen can be generated.

[0140] As described above, in the specimen measurement apparatus 1 according to the present embodiment, the AD conversion of the signal from the optical sensor is performed at regular intervals. As a result, even when the irradiation position Pi passes through the target position Pt during the AD conversion due to local speed variations in the main scan, the acquisition of the optical signal data is prevented from being missed, and the fluorescence signal is stably acquired. On the other hand, the transfer of the acquired optical signal data to the memory is synchronized with the position of the light projecting unit. As a result, even when a drive mechanism such as the piston crank mechanism 120 with a large speed change depending on the position is used, the optical signal data acquired at positions close to the equally spaced target positions Pt is stored in the memory. Furthermore, there is no need for a high-speed AD converter for coping with local speed variations in the main scan or a robust scanning mechanism for reducing speed variations. As a result, a large number of fluorescence signals are acquired at short intervals, realizing high-precision measurement and shortening of the imaging time while preventing an increase in the cost of the specimen measurement apparatus.

[0141] <Second Embodiment> The second embodiment of the present disclosure will be described below. The second embodiment is different from the first embodiment in that, in the acquisition of optical signal data, more optical signal data than the number of pixels is acquired, and one pixel data is generated from the plurality of acquired optical signal data. More specifically, in the first embodiment, the position of the pixel and the target position Pt corresponded one-to-one, but there was a possibility that the luminance variation of the image occurred due to the random noise of the photomultiplier tube. Therefore, in the present embodiment, a large amount of optical signal data is acquired at intervals finer than the pixel pitch, and they are averaged to generate one pixel data, thereby reducing the influence of the random noise of the photomultiplier tube and improving the measurement accuracy and image quality.

[0142] Note that the configuration of the specimen measurement apparatus, the configuration of the array plate, and the internal functional configuration of the controller circuit in the present embodiment are the same as those illustrated in FIGS. 1, 2, and 3, respectively. Therefore, the same reference numerals are used, and the description here is omitted. Below, the operation flow when the array plate is imaged by the specimen measurement apparatus of the present embodiment will be described with reference to FIGS. 5, 6, 12, and 13.

[0143] Figure 12 shows the operation flow when the specimen measurement device 1 according to the present embodiment takes a picture of the array plate 101. When an instruction to start taking a picture of the array plate 101 is input by the user via the user interface 117, the processing after step S1201 starts. In step S1201, the CPU 301 reads the imaging conditions specified by the user via the user interface 117 and stores them in the memory 303. Further, the CPU 301 sets information based on the imaging conditions in various circuits within the controller circuit 116.

[0144] As the imaging conditions, a point 501 (X1, Y1) indicating the imaging range on the array plate 101, a point 502 (X2, Y2), the pixel pitch Xp in the main scanning direction, the pixel pitch Yp in the sub-scanning direction, and the rotation speed Xs in the main scanning direction are input. In the present embodiment, in addition to these, an oversampling rate Rx is further input. The oversampling rate in the present embodiment corresponds to the number of optical signal data (digital data obtained from the detection signal) acquired to generate one pixel. When Rx = 5, one pixel data is generated from five optical signal data acquired at intervals of 1 / 5 of the pixel pitch Xp.

[0145] In the present embodiment, it is assumed that X1 = 500, X2 = 22500, Y1 = 500, Y2 = 64500, Xp = 10 μm, Yp = 10 μm, Xs = 1200 rpm, and Rx = 5 are input. In this case, the sampling pitch Sx in the main scanning direction is 2 μm. Here, a rectangular region 503 with the points 501 and 502 on the array plate 101 as diagonals is referred to as the imaging region. Also, calculate the number of pixels Nx = (X2 - X1) / Xp in the main scanning direction and the number of pixels Ny = (Y2 - Y1) / Yp in the sub-scanning direction. In the present embodiment, according to the above settings, Nx = 2200 and Ny = 6400. When the above settings are completed, the flow proceeds to step S1202.

[0146] Here, the processes executed from step S1202 to step S1208 are the same as the processes executed from step S402 to step S408 described in the first embodiment. Therefore, the description of the processes executed in these steps here is omitted.

[0147] In step S1209, the synchronization circuit 311 determines whether the light projecting unit 104 has reached the target position Pt. The point 507 in FIG. 5(b) indicates the position of the pixel imaged on the array plate 101. The target position in this embodiment is the point where the optical signal data is acquired on the array plate 101 to generate a pixel. The X coordinate P(N) of the Nth target position Pt is represented by the following equation 6. P(N)=X1+(Xp / Rx)×N (N = 0, 1, … Nx×Rx - 1) (Equation 6) The target positions are a plurality of points on the trajectory, the pitch in the X direction is Xp / Rx, and the pitch in the Y direction is Yp.

[0148] Here, the positional relationship between the target position and the pixel position will be described with reference to FIG. 13. FIG. 13 is an enlarged view of a part of FIG. 5(b). The points 1301, 1302, and 1303 indicated by 〇 are the pixel positions and are the same as those indicated by the point 507 in FIG. 5(b). The interval between the point 1301 and the point 1302 is Xp, and the interval between the point 1301 and the point 1303 is Yp. Also, the points 1304 to 1308 indicated by × are the target positions, and the intervals therebetween are evenly arranged at Xp / Rx centered on the pixel w. In this embodiment, this interval is 2 μm. In this embodiment, the optical signal data is acquired at five locations from the target position 1304 to 1308 and added and averaged to generate the luminance value of the pixel 1302. That is, the number of the initially acquired optical signal data is Rx times more than the number of pixels.

[0149] Also, the initial value of the target position Pt is P(0), which is stored in a buffer memory or the like provided inside the synchronization circuit 311. In the determination of the first target position Pt, when the X coordinate of the light projection unit 104 output from the coordinate calculation circuit 310 passes P(0) in the forward path direction (the direction in which the X coordinate increases), it is determined that the target position Pt has been reached. In the determination of the target position Pt after the second time, when the X coordinate of the light projection unit 104 output from the coordinate calculation circuit 310 passes the target position Pt at which the irradiation position Pi is updated in step S1211 described later, it is determined that the target position Pt has been reached.

[0150] When it is determined by the synchronization circuit 311 that the target position Pt has been reached, the synchronization circuit 311 outputs a data acquisition trigger signal, and the flow proceeds to step S1210. When it is determined by the synchronization circuit 311 that the target position Pt has not been reached yet, the synchronization circuit 311 does not output a data acquisition trigger signal, and the flow proceeds to step S1212.

[0151] In step S1210, the AD converter control circuit 306 outputs a conversion start signal, receives the output voltage from the optical sensor 105, amplifies and filters it in the receiving circuit 106, and then performs AD conversion. In the present embodiment, the conversion start signal is a signal with a fixed period, and the period is longer than the conversion time of the AD converter but shorter than the time it takes for the light projection unit 104 to move the distance Xp / Rx. The AD-converted optical signal data is temporarily stored in the buffer memory inside the data acquisition circuit 312. The buffer memory can store one optical signal data for one AD converter, and the latest optical signal data is overwritten and stored each time AD conversion is performed. In the present embodiment, an AD converter corresponding to the wavelength of each light source is provided, and optical signal data reflecting the amount of fluorescence excited by the wavelength of each light source is stored.

[0152] When the data acquisition control circuit 312 receives a data acquisition trigger signal, it reads out the optical signal data stored in the buffer memory and outputs it to the memory control circuit 304 via the internal DMA controller and bus 302. The memory control circuit 304 stores the optical signal data at a specified address in the memory 303. The address of the memory 303 is incremented each time the data acquisition trigger signal is received.

[0153] After the data acquisition control circuit 312 stores Nx×Rx×Ny pieces of optical signal data corresponding to the wavelength of each light source in the memory 303, it sets the internal data acquisition completion register to 1. When the data acquisition control circuit 312 has not stored Nx×Rx×Ny pieces of data corresponding to the wavelength of each light source in the memory 303, it sets the internal data acquisition completion register to 0. When the optical signal data at the target position Pt is stored, the flow proceeds to step S1211.

[0154] Note that the processing executed in each of steps S1211 to S1215 in this embodiment is the same as the processing executed in each of steps S411 to S415 in the first embodiment. Therefore, the description of the processing executed in these steps here is omitted.

[0155] In step S1216, the CPU 301 reads out Rx×Nx×Ny pieces of optical signal data corresponding to the wavelengths of the respective light sources from the memory 303 and performs image formation processing. In the image formation processing, an addition average of the Rx pieces of optical signal data in the main scanning direction is performed to generate one pixel data. The pixel data of point 1302 is generated by performing an addition average of the five pieces of optical signal data from points 1304 to 1308, and this is stored in the memory 303. As a result of the image formation processing, the number of pixel data corresponding to the wavelengths of the respective light sources becomes Nx×Ny. The optical signal data is divided into a signal component reflecting the fluorescence amount and a random noise component derived from the optical sensor and the reception circuit. By performing the addition average, the signal component remains as it is, and the noise component can be reduced to 1 / √Rx, leading to an improvement in S / N. After the CPU 301 performs the image formation processing for each wavelength of the respective light sources, the flow proceeds to step S1217.

[0156] Subsequently, in step S1217, the CPU 301 reads out Nx×Ny pieces of pixel data corresponding to the wavelengths of the respective light sources from the memory 303, performs processing of data compression and format conversion, and creates a photographed image file in TIFF format. The photographed image file is stored in the memory 303 and presented to the user via the UI control circuit 314 and the user interface 117. Also, according to an instruction from the user, the photographed image file can be transferred to an external data server via the communication circuit 313.

[0157] Regarding the processing executed in each of steps S1218 to S1222 in this embodiment, it is the same as the processing executed in each of steps S417 to S421 in the first embodiment. Therefore, the description of the processing executed in these steps here is omitted.

[0158] In this embodiment, oversampling is performed in the main scanning direction to acquire optical signal data at intervals finer than the pixel pitch. However, in the sub-scanning direction, oversampling is not performed, and optical signal data is acquired at the same interval as the pixel pitch. This prevents an increase in the shooting time. In this embodiment, the oversampling rate Rx is input from the user via the user interface 117. However, the acquisition method is not limited to this, and it may be obtained from the memory 303 based on predetermined conditions. The memory 303 functions as a shooting condition holding means in this embodiment, which holds the oversampling rate Rx corresponding to the number of digital data acquired to generate one pixel, input as a shooting condition. The user interface 117 functions as an input unit that receives a command for the oversampling rate Rx from the outside in this embodiment. In this embodiment, an example is described in which the image formation process and the averaging process executed during the process are performed by causing the image processing unit 301a in the CPU 301 to function as an averaging means. Specifically, in this embodiment, the image processing unit 301a averages a plurality of digital data stored in the memory 303 as an averaging means, thereby generating pixel data indicating the characteristics of the specimen. However, the entity that executes image formation or image processing is not limited to this example. An image formation circuit may be mounted after the data acquisition control circuit 312 in the FPGA of the controller circuit 116, and the image formation process may be performed by hardware. In that case, the number of data can be reduced by addition averaging before transferring the optical signal data to the memory 303, and effects such as reduction of the memory capacity and reduction of the shooting time can be obtained.

[0159] In this embodiment, an example of simply performing addition averaging in the image formation process has been described. However, a more complex image formation algorithm may be used. Weighted addition processing may be used to increase the weight of the optical signal data of the point 1306 close to the position of the point 1302 and decrease the weight of the optical signal data of the points 1304 and 1308 far from the position of the point 1302.

[0160] As described above, in the imaging process according to the present embodiment, AD conversion is performed at a fixed cycle, but the transfer of the acquired optical signal data to the memory is synchronized with the position of the light projecting unit. As a result, even when vibration occurs in the main scanning, a large amount of optical signal data can be stably acquired at fine intervals. Further, by averaging them to generate one pixel data, the influence of noise in the optical sensor and the receiving circuit is reduced, and the measurement accuracy and the image quality are improved.

[0161] <Third Embodiment> The third embodiment of the present disclosure will be described below. The third embodiment is different from the second embodiment in that the voltage range of the optical signal data is adjusted before averaging in the image forming process, and the value of the pixel data is adjusted after averaging.

[0162] Note that the configuration of the specimen measuring device, the configuration of the array plate, and the internal functional configuration of the controller circuit in the present embodiment are the same as those illustrated in FIGS. 1, 2, and 3, respectively. Therefore, the same reference numerals will be used and the description thereof will be omitted here. Further, the configurations of the optical sensor 105 and the controller circuit 116 are the same as those described in the first embodiment, and the operation flow at the time of imaging is also the same as that described in the second embodiment. In the following, the same reference numerals will be used for the same configurations or processes, and the present embodiment will be described with reference to FIGS. 7, 12, and 14.

[0163] FIG. 14(a) shows the relationship between the output voltage of the current-voltage conversion amplifier 702 (see FIG. 7) in the third embodiment and the digital value of the output of the AD converter 705. In the figure, the horizontal axis represents time and the vertical axis represents voltage. In FIG. 14(a), the output voltage 1401 is the output voltage of the current-voltage conversion amplifier 702 when the amount of light incident on the optical sensor 105 is large. When the amount of incident light is large, the output voltage 1401 becomes a positive voltage. On the other hand, the output voltage 1402 is the output voltage of the current-voltage conversion amplifier 702 when the amount of light incident on the optical sensor 105 is weak. The output voltage 1402 becomes a voltage around 0 V on average, but may become a slightly negative voltage due to the voltage offset of the optical sensor and the receiving circuit. In this case, if only the positive voltage is assigned from 0 to 65535 and averaged, the negative voltage will be clamped to 0, and the averaged voltage will be slightly offset in the positive direction.

[0164] Therefore, in the third embodiment, in the level conversion circuit 703 inside the receiving circuit 106, the range 1403 indicated by the arrow that can cover the output voltage 1401 and the output voltage 1402 is converted from 0 V to 5 V. Here, let the upper limit value of the range 1403 be Tmax and the lower limit value be Tmin. Tmax and Tmin are obtained in advance. In this embodiment, Tmax = 10 V and Tmin = -0.3 V. Since the AD conversion range is from 0 V to 5 V, the relationship between the input voltage Vin and the output voltage Vout of the level conversion circuit 703 is the relationship shown in the following Equation 7. Vout = 5×(Vin - Tmin) / (Tmax - Tmin) (Equation 7) In this embodiment, the resistance values of the resistance network of the level conversion circuit 703 are set for the input and output to amounts that satisfy the conditions shown in Equation 7. Also, the digital value D output by the AD converter 705 has the relationship shown in the following Equation 8. D = (Vout / 5)×65535 = (Vin - Tmin) / (Tmax - Tmin)×65535 (Equation 8)

[0165] FIG. 14(b) is a diagram showing the input / output relationship from voltage level conversion inside the receiving circuit 106 to the AD converter. In this figure, the horizontal axis represents the input voltage Vin of the level conversion circuit, and the vertical axis represents the digital value after AD conversion. In the receiving circuit 106 of this embodiment, level conversion and AD conversion are performed such that -0.3V corresponds to a digital value of 0 and 10V corresponds to a digital value of 65535. By providing such level conversion, signals that would have had an output voltage less than 0V due to the offset voltages of the optical sensor 105 and the receiving circuit 106 when the light amount is weak can be acquired without omission.

[0166] However, if the pixel data averaged in this way is imaged, even if the average value is 0V, the digital value will be a larger value by the amount of 0.3V offset. For this reason, the luminance will be increased by that amount even in areas where there is no signal, and the areas on the imaging image where there are no spots 202 on the array plate 101 will also become brighter. The difference between the imaging process of this embodiment and the imaging process of the second embodiment is that in the image formation process of step S1216 in FIG. 12, after calculating the pixel data at the target position Pt by averaging, level conversion is performed again on each pixel data to adjust the output pixel data. Since the processes other than step S1216 in FIG. 12 are the same as the processes executed in each step of the second embodiment, the description here is omitted.

[0167] Here, in the image formation process of step S1216, let the pixel data after level conversion be L. Assuming that the pixel data when the average value of the voltage Vin is 0V is Pzero, then Pzero = -Tmin / (Tmax - Tmin)×65535. In this embodiment, since Tmax = 10V and Tmin = -0.3V, Pzero = 1908. FIG. 14(c) is a diagram showing the input-output relationship of pixel level conversion in the image formation process. In the figure, the horizontal axis represents the pixel data of the target position Pt after averaging, and the vertical axis represents the output pixel data L after pixel level conversion. In the image formation process of this embodiment, when Pt ≤ PZero, the output pixel data L = 0, and when Pt = 65535, it is linearly converted so that L = 65535. That is, when Pt is greater than or equal to Pzero, the relationship between L and Pt satisfies the relationship shown in the following formula 9. L = 65535 / (65535 - Pzero)×(Pt - Pzero) (Formula 9) When Pt is less than Pzero, L becomes 0. Then, the output pixel data is stored in the memory 303, and the flow proceeds to step S1217.

[0168] Note that in this embodiment, an example where the maximum value is the same before and after pixel level conversion has been used for explanation. However, when the maximum value of the pixel data after averaging becomes smaller than 65535 due to saturation of the receiving circuit or the like, the maximum value may also be converted in the image formation process. Further, when the maximum value of the pixel data after averaging is limited to 62000 or less due to saturation inside the receiving circuit or the like, the range from 1908 to 62000 of the pixel data of the target position Pt after averaging may be assigned to 0 to 65535 of the output pixel data L.

[0169] That is, in this embodiment, the image processing unit 301a, as an averaging means, performs averaging of the digital data converted from the detection signals in the first range including positive and negative detection signals, exemplified by the range 1403 in FIG. 14(a), by the AD converter control circuit 306. Then, the image processing unit 301a performs level conversion to assign a partial range of the first range to the pixel value for the averaged data.

[0170] Note that, regarding the pixel-level conversion process in this embodiment as well, similar to the averaging process executed in the second embodiment, an image forming circuit can be implemented after the data acquisition control circuit 312 in the FPGA of the controller circuit 116, and the process can be performed in hardware. In that case, there are effects such as reducing the data transfer amount to the memory 303 and reducing the shooting time.

[0171] As described above, in the shooting process according to this embodiment, when performing oversampling, the range for AD-converting the optical signal is widened to also acquire negative values near 0V. And thereby, when the amount of light incident on the optical sensor 105 is weak, the phenomenon that the average value of the optical signal data is offset in the positive direction is prevented. Also, by performing pixel-level conversion again after averaging, the phenomenon that the area without a signal in the captured image becomes bright is prevented.

[0172] <Fourth Embodiment> The fourth embodiment of the present disclosure will be described below. The fourth embodiment is different from the first embodiment in that the target position Pt is shifted in the forward path and the return path so that the deviation between the predetermined target position and the position where the optical signal data actually stored in the memory is sampled is reduced.

[0173] Note that the configuration of the array plate of the specimen measuring device and the internal functional configuration of the controller circuit in this embodiment are the same as those illustrated in FIGS. 1, 2, and 3, respectively. For this reason, the same reference numerals are used, and the description here is omitted. Also, the configurations of the optical sensor 105 and the controller circuit 116 are the same as those described in the first embodiment, and the operation flow when shooting is also the same as that described in the first embodiment. In the following, the same reference numerals are used for the same configurations or processes, and this embodiment will be described with reference to FIGS. 1, 7, 9(f), 15, and 16.

[0174] In Fig. 9(f), let the trigger period of the AD conversion in the timing chart 903 be Ta, and let the delay time from when the linear encoder 108 detects that the light projection unit 104 has actually passed the X coordinate to when data transfer is performed be Td1. Also, let the delay time from when the AD converter 705 performs sampling as shown in the timing chart 904 to when it outputs the optical signal data as shown in the timing chart 906 be Td2. And let the moving speed of the light projection unit 104 be Vx. In this case, Vx is the slope of the dotted line shown as the X coordinate 901.

[0175] The optical signal data in the timing chart 907 transferred to the memory is the optical signal data that was sampled and AD-converted before the irradiation position Pi passes the target position Pt. The second optical signal data from the left in Fig. 9(f) is transferred when the coordinate of the light projection unit 104 is 2, but is actually sampled when the encoder coordinate is 1.

[0176] Considering the delay time, the difference dt between the time when the irradiation position Pi passes the target position Pt and the time when the optical signal data stored in the memory is sampled is between (Td2 - Td1) and (Td2 - Td1 + Ta). And the deviation between the predetermined target position and the position where the optical signal data actually stored in the memory is sampled is ideally the value obtained by multiplying dt by Vx, which is between (Td2 - Td1)×Vx and (Td2 - Td1 + Ta)×Vx.

[0177] Note that Td1 is a constant value determined by the linear encoder 108, the coordinate calculation circuit 310, the synchronization circuit 311, and the data acquisition control circuit 312, and is set to 250 ns in this embodiment. Td2 is a constant value determined by the reception circuit 106 and the AD converter control circuit 306, and is set to 800 ns in this embodiment. Also, assuming the frequency of the AD converter 705 is 1 MHz, Ta is 1 us. Vx is a value that varies between 0 m / s and 2 m / s depending on the rotation angle of the piston crank mechanism 120. Limited to within the imaging region 503, Vx varies between 1 m / s and 2 m / s. In this case, the deviation of the target position Pt is 0.55 μm to 1.55 μm when Vx is around 1 m / s on the forward path, but increases to about 1.1 μm to 3.1 μm when Vx is around 2 m / s. The reason for the deviation having a range is that the sampling and the position of the light projection unit 104 are asynchronous, and it varies depending on at which timing within the period Ta the irradiation position Pi passes the target position Pt. For the return path, the amount of position deviation is the same but the direction of deviation is reversed. Therefore, in this embodiment, by shifting the target position Pt, the fixed part of the position deviation, (Td2 - Td1) × Vx, is corrected.

[0178] FIG. 15 is a diagram showing the target position Pt in this embodiment. The points 1301, 1302, and 1303 in FIG. 15 are the positions of the pixels, which are the same as the pixel positions in the second embodiment described with reference to FIG. 13. Also, the points 1304 to 1308 indicated by × are points evenly arranged at intervals of Xp / Rm centered on the pixels, which are the same as the target positions described with reference to FIG. 13. Further, the point 1511 indicated by × is the point obtained by shifting the point 1304 by Xp / Rm in the return path direction, and the point 1512 is the point obtained by shifting the point 1308 by Xp / Rm in the forward path direction.

[0179] In FIG. 15, the point indicated by □ is the target position when the light projecting unit 104 is moving in the forward path direction, and is the target position for acquiring fluorescence signal data with respect to excitation light of 760 nm. When generating a pixel of a captured image based on the excitation light of 760 nm at point 1302, the additive average of the optical signal data sampled at five positions from point 1501 to point 1505 is used. The point indicated by △ is the target position when the light projecting unit 104 is moving in the return path direction, and is the target position for acquiring fluorescence signal data with respect to excitation light of 670 nm. When generating a pixel of a captured image based on the excitation light of 670 nm at point 1302, the additive average of the optical signal data sampled at five positions from point 1506 to point 1510 is used.

[0180] Note that the points indicated by □, ×, and △ are drawn with a shift in the Y-axis direction for ease of viewing in the figure, but actually the Y coordinates of the three are the same. The target position indicated by □ is shifted by (Td2 - Td1) × Vx in the return path direction from the position indicated by ×. Similarly, the target position indicated by △ is shifted by (Td2 - Td1) × Vx in the forward path direction from the position indicated by ×. That is, in the present embodiment, the target position is set to be shifted between the forward path and the return path according to the delay time that occurs during conversion to digital data by the AD converter control circuit 306. Thereby, by generating a data acquisition trigger earlier than passing through the position that is actually desired to be acquired, the position shift resulting from the delay time occurring in the reception circuit 106 and the controller circuit 116 is corrected.

[0181] Note that in the present embodiment, the amount of position shift is obtained as follows. Referring to FIG. 16, which is an enlarged view of the periphery of the piston crank mechanism 120 shown in FIG. 1, the position x of the light projecting unit 104 is expressed by the following equation 10 using the length r of the crank 118, the length l of the connecting rod 119, and the angle θ of the pulse motor 107.

Equation

Equation

[0182] As described above, in the imaging process according to this embodiment, the target position Pt is shifted in the forward and return paths in consideration of the speed of the piston crank mechanism 120 and the delay times of the linear encoder 108, the receiving circuit 106, and the controller circuit 116 in advance. Thereby, it is possible to reduce the displacement between the predetermined target position and the position where the optical signal data actually stored in the memory is sampled, and highly accurate optical signal data acquisition becomes possible.

[0183] In this embodiment, an example of shifting the position at the sampling stage to acquire optical signal data has been described. However, the displacement between the forward and return paths may be corrected by other methods. The target position is made the same in the forward and return paths as indicated by the × marks in FIG. 15, but the optical signal data used when generating the pixels of the forward path and when generating the pixels of the return path in the image formation process may be shifted. When generating the pixel data of point 1304, five optical signal data from point 1511 and point 1304 to point 1307 may be averaged in the forward path, and five optical signal data from point 1305 to point 1308 and point 1512 may be averaged in the return path. In this method, the correction effect of the displacement is limited by the acquisition interval Xp / Rm of the optical signal data, but the displacement between the forward and return paths is corrected by a simple method.

[0184] <Other Embodiments> The present disclosure can also be implemented by supplying software (program) that realizes one or more functions of the various embodiments described above to a system or device via a network or a storage medium, and having a computer of the system or device read and execute the program. The computer may have one or more processors or circuits, and may include a plurality of separate computers or a network of a plurality of separate processors or circuits in order to read and execute executable instructions on the computer.

[0185] At this time, the processor or circuit may include a central processing unit (CPU), a microprocessing unit (MPU), or a graphics processing unit (GPU). Further, the processor or circuit may include an application specific integrated circuit (ASIC) or a field programmable gateway (FPGA). Further, the processor or circuit may include a digital signal processor (DSP), a data flow processor (DFP), or a neural processing unit (NPU).

[0186] As described above, according to the specimen measuring device of the present disclosure, even when there is a variation in the scanning speed while the cost is low, an optical signal can be stably acquired. As a result, a large number of optical signals are acquired at short intervals. As a result, while preventing an increase in the cost of the device, high-precision measurement and shortening of the imaging time are realized.

[0187] The above disclosure includes the following configurations, methods, and programs. (Configuration 1) A specimen measuring device that optically measures the characteristics of a specimen using an array substrate provided with spots in an array, light irradiation means for irradiating the array substrate with the condensed primary light for a predetermined period; light detection means for detecting secondary light from the spot at a predetermined period and outputting a detection signal; scanning means for changing an irradiation position of the primary light with respect to the array substrate; position acquisition means for acquiring information regarding the irradiation position; Converting means for converting the detection signal detected at the predetermined period into digital data; First holding means for holding information on a target position Pt regarding the irradiation position; Second holding means for holding the digital data; Determining means for determining whether or not the irradiation position corresponds to the target position Pt; Storage means for storing the digital data; Transfer means for selecting, according to the determination result of the determining means, data corresponding to the timing when the irradiation position reaches the target position Pt from the digital data held by the second holding means and transferring the data to the storage means, the specimen measurement device comprising the same. (Configuration 2) The specimen measurement device according to Configuration 1, further comprising imaging condition holding means for holding an oversampling rate corresponding to the number of digital data acquired to generate one pixel as an imaging condition. (Configuration 3) The specimen measurement device according to Configuration 2, further comprising an input unit for receiving an instruction of the oversampling rate from the outside. (Configuration 4) The specimen measurement device according to any one of Configurations 1 to 3, further comprising a light source optically coupled to the light irradiation means and light source control means for controlling on / off of light emission of the light source. (Configuration 5) The light irradiation means includes an objective optical system for condensing the primary light on the array substrate; The specimen measurement device according to any one of Configurations 1 to 4, wherein the light detection means includes a light detection unit optically coupled to the objective optical system and through which the secondary light is guided. (Configuration 6) The specimen measurement device according to Configuration 5, wherein the scanning means includes a rotation drive unit and a piston crank unit for converting the rotational movement of the rotation drive unit into a one-dimensional reciprocating movement and reciprocatingly moving the objective optical system. (Configuration 7) The specimen measurement device according to any one of Configurations 1 to 6, wherein the target position Pt is arranged at equal intervals on the array substrate. (Configuration 8) The target position Pt held by the first holding means is updated based on the movement or the change of the irradiation position, and the specimen measurement device according to any one of Configurations 1 to 7. (Configuration 9) The conversion means converts the detection signal into digital data during a period shorter than the time required for the primary light to scan between adjacent target positions Pt, and the specimen measurement device according to any one of Configurations 1 to 8. (Configuration 10) The transfer means preferentially selects digital data closer to the end of the predetermined period among the digital data and transfers it to the storage means, and the specimen measurement device according to any one of Configurations 1 to 9. (Configuration 11) The specimen measurement device according to any one of Configurations 1 to 10 further includes imaging means for imaging the characteristics of the specimen based on the digital data stored in the storage means. (Configuration 12) The specimen measurement device according to any one of Configurations 1 to 11 further includes averaging means for averaging a plurality of digital data stored in the storage means to generate pixel data indicating the characteristics of the specimen. (Configuration 13) The averaging means performs level conversion for assigning a partial range in the first range to pixel values with respect to the data after averaging the digital data converted from the detection signals in the first range including positive and negative detection signals by the conversion means, and the specimen measurement device according to Configuration 12. (Configuration 14) The scanning means reciprocally scans the irradiation position of the primary light on the array substrate, and the target position Pt is set to be shifted between the forward path and the return path according to the delay time generated during the conversion of the detection signal into digital data by the conversion means, and the specimen measurement device according to any one of Configurations 1 to 13. (Configuration 15) The sample measurement device according to any one of Configurations 1 to 14, further comprising a buffer memory for temporarily storing the converted digital data, wherein in the buffer memory, when a plurality of converted digital data are obtained within the time required to scan the target position Pt where the irradiation positions of the primary light are continuous, the temporarily stored digital data are overwritten by the digital data obtained immediately thereafter. (Method 1) In order to optically measure the characteristics of a sample using an array substrate provided with spots in an array, a first holding means for holding a target position regarding the irradiation position of primary light, a second holding means for holding a detection signal detected by measuring secondary light from the spot as digital data, and a storage means for storing the irradiation position and the digital data in association with each other. A control method for a sample measurement device, comprising: A light irradiation step of irradiating the array substrate with the condensed primary light for a predetermined period; A light detection step of detecting secondary light from the spot at a predetermined period and outputting a detection signal; A scanning step of changing the irradiation position of the primary light with respect to the array substrate; A position acquisition step of acquiring information regarding the irradiation position; A conversion step of converting the detection signal acquired at a predetermined period into the digital data, and A determination step of determining whether or not the irradiation position corresponds to the target position Pt; A transfer step of selecting data corresponding to the timing when the irradiation position reaches the target position Pt from the digital data held in the second holding means according to the determination result determined in the determination step and transferring the data to the storage means. A control method for a sample measurement device. (Program) A program that, when executed by a computer, causes the computer to execute each step of the sample measurement method described in Method 1.

[0188] The present disclosure has been described with reference to the embodiments and variations. However, the present disclosure is not limited to the above embodiments and variations. Inventions modified within the scope not contrary to the spirit of the present disclosure, and inventions equivalent to the present disclosure are also included in the present disclosure. Also, the above-described embodiments and variations may be appropriately combined within the scope not contrary to the spirit of the present disclosure.

Explanation of Reference Numerals

[0189] 1: Specimen measurement device 129: Objective optical system (122, 125) 122: Light irradiation means (104, 103, 102) 125: Light detection means (104, 103, 105) 130: Scanning means (130x, 130y, 130z) 130x: Main scanning means (107, 120, 118, 119) 130y: Sub-scanning means (112, 113, 114) 138: Position acquisition means (108, 310) 146: Conversion means (751, 306) 171: First holding means (311, Variation 303) 172: Second holding means (311, Variation 303) 173: Determination means (311) 304: Transfer means

Claims

1. A specimen measurement device that optically measures a characteristic of a specimen using an array substrate on which spots are provided in an array, a light irradiation means for irradiating the array substrate with the condensed primary light for a predetermined period of time; a light detection means for detecting the secondary light from the spot at a predetermined period and outputting a detection signal; a scanning means for changing an irradiation position of the primary light on the array substrate; A position acquisition means for acquiring information regarding the irradiation position; A conversion means for converting the detection signal detected at the predetermined period into digital data; A first storage means for storing information on a target position Pt related to the irradiation position; A second storage means for storing the digital data; a determination means for determining whether the irradiation position corresponds to the target position Pt; a storage means for storing said digital data; a transfer means for selecting data corresponding to the timing at which the irradiation position reached the target position Pt from the digital data stored in the second storage means in accordance with the judgment result of the judgment means, and transferring the data to the memory means.

2. 2. The specimen measurement device according to claim 1, further comprising an imaging condition storage means for storing, as an imaging condition, an oversampling rate corresponding to the number of digital data acquired to generate one pixel.

3. The specimen measurement device according to claim 2 , further comprising an input unit that receives a command for the oversampling rate from an external source.

4. The specimen measurement device according to claim 1 , further comprising: a light source optically coupled to the light irradiation means; and a light source control means for controlling the on / off of light emission from the light source.

5. the light irradiating means includes an objective optical system that condenses the primary light onto the array substrate; The specimen measurement device according to claim 1 , wherein the light detection means comprises a light detection section that is optically coupled with the objective optical system and to which the secondary light is guided.

6. The specimen measurement device according to claim 5 , wherein the scanning means comprises: a rotary drive unit; and a piston crank unit that converts the rotary motion of the rotary drive unit into one-dimensional reciprocating motion to reciprocate the objective optical system.

7. The specimen measurement device according to claim 1 , wherein the target positions Pt are arranged at equal intervals on the array substrate.

8. The specimen measurement device according to claim 1 , wherein the target position Pt held in the first holding means is updated based on the movement or change of the irradiation position.

9. 3. The specimen measurement device according to claim 1, wherein the conversion means converts the detection signal into digital data in a period shorter than a time required for the primary light to scan between adjacent target positions Pt.

10. 3. The specimen measurement device according to claim 1, wherein the transfer means preferentially selects, from the digital data, digital data closer to an end of the predetermined period and transfers it to the storage means.

11. The specimen measurement device according to claim 1 , further comprising imaging means for imaging characteristics of the specimen based on the digital data stored in the memory means.

12. 3. The specimen measurement device according to claim 1, further comprising an averaging means for averaging a plurality of digital data stored in the memory means to generate pixel data indicative of a characteristic of the specimen.

13. The sample measurement device described in claim 12, wherein the averaging means performs level conversion on the averaged digital data converted by the conversion means from a first range of detection signals including positive and negative detection signals, thereby assigning a portion of the first range to pixel values.

14. The specimen measurement device according to claim 1 or 2, wherein the scanning means scans the irradiation position of the primary light back and forth on the array substrate, and the target position Pt is set to be shifted between the forward and return paths according to a delay time that occurs when the conversion means converts the primary light into digital data.

15. The specimen measurement device of claim 1 or 2, further comprising a buffer memory for temporarily storing the converted digital data, wherein when a plurality of converted digital data are obtained in the buffer memory within the time required for the irradiation position of the primary light to scan consecutive target positions Pt, the temporarily stored digital data is overwritten by the digital data obtained immediately thereafter.

16. A method for controlling a specimen measurement device, comprising: a first holding means for holding a target position for an irradiation position of a primary light, a second holding means for holding a detection signal detected by measuring the secondary light from the spots as digital data, in order to optically measure a characteristic of a specimen using an array substrate on which spots are provided in an array; and a storage means for storing the irradiation position and the digital data in association with each other, a light irradiation step of irradiating the array substrate with the concentrated primary light for a predetermined period of time; a light detection step of detecting secondary light from the spot at a predetermined period and outputting a detection signal; a scanning step of changing an irradiation position of the primary light on the array substrate; a position acquisition step of acquiring information regarding the irradiation position; A conversion step of converting the detection signal acquired at a predetermined period into the digital data, a determination step of determining whether the irradiation position corresponds to the target position Pt; A control method for a specimen measurement device including a transfer step of selecting data corresponding to the timing at which the irradiation position reached the target position Pt from the digital data stored in the second holding means depending on the judgment result determined in the judgment step, and transferring the data to the memory means.

17. A program for causing a computer to execute each step of the method for controlling a specimen measurement device according to claim 16.

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