Measurement device, measurement method, and correction method

Abstract

The purpose of the present invention is to provide a measurement device capable of acquiring a scan image in which inaccuracy caused by error in an encoder encoding the measurement position of a scanner is reduced, a measurement method, and a correction method.　Provided is a measurement device comprising: a measurement unit that acquires object measurement information; a scanning unit that has a drive source and causes a part of the measurement unit to scan back and forth in a first direction; a detection unit that acquires position information that is information pertaining to the position of the part of the measurement unit; a storage unit that stores calibration information for calibrating the position information; a control unit that, in response to the detection unit detecting that the part of the measurement unit is at a prescribed position, acquires the measurement information from the measurement unit in association with the position information from the detection unit; and a calculation unit that, on the basis of the position information associated by the control unit, the measurement information, and the calibration information read from the storage unit, generates corrected measurement information in which the measurement information has been corrected.

Description

Measuring device, measuring method and correction method

[0001] The present invention relates to a measurement device, a measurement method, and a correction method.

[0002] Protein array plates or peptide array plates are known, in which a large number of biological substances having peptide bonds, such as proteins or peptides, are immobilized on a substrate. Using these plates, interactions with a large number of biological substances immobilized on the substrate can be simultaneously analyzed. Such array plates are effective for comprehensively analyzing the interactions between a large number of proteins or peptides and liquid samples derived from living organisms, such as blood, cell extracts, saliva, and interstitial fluid. Such analyses allow the characteristics of the samples to be measured.

[0003] Hereinafter, the fixed sites of samples such as proteins or peptides on a substrate may be referred to as spots. One known method for observing spots that have interacted with a sample is to label the spots with fluorescent probes and identify which spots have interacted. A microarray scanner is known as a device for observing array plates labeled with fluorescent probes (Patent Document 1). Patent Document 1 discloses a device that includes an illumination optical system, a fluorescence detection optical system, and a two-dimensional scanning system. The illumination optical system focuses and irradiates the array plate with laser light. The fluorescence detection optical system detects the amount of fluorescence from the spots labeled with fluorescent probes. The two-dimensional scanning system scans the array plate or the optical system in two dimensions to obtain a fluorescent image of the spots on the array plate. One side of the two-dimensional scanning uses a so-called piston-crank mechanism that converts the rotational motion of an electromagnetic motor into translational motion, and this mechanism scans the illumination optical system. Patent Document 2 also discloses a technology for creating a correction table to correct errors in an encoder that detects the rotational angle position of an electromagnetic motor.

[0004] US Patent Application Publication No. 2009 / 0218513 JP 2016-109436 A

[0005] In measuring devices, the position information output by an encoder, which is a detector that detects the position information of a measuring unit, can contain errors. Therefore, generating measurement information based on the encoder's position information results in inaccurate measurement information. Specifically, deviations occur in the measurement direction. If the output measurement information is an image, it expands or contracts in the measurement direction. In particular, when a magnetic encoder is used as a detector, noise can occur when passing through a reference mark on the scale, or fluctuations in the magnetic field caused by a nearby driving source can degrade position accuracy. The present invention aims to provide a measuring device, measurement method, and correction method that eliminate such deviations. Patent Document 1 describes that the position of a scanned irradiation optical system is measured optically or calculated from the angle of a shaft connected to an electromagnetic motor, but does not recognize the problem of errors in the position measurement means or disclose a method for reducing them.

[0006] In Patent Document 2, a correction table is generated using a high-precision error detection device. This poses a problem in that a separate device is required to generate the correction table. Furthermore, because measurements must be performed in advance, there is also a problem in that it is not possible to respond to changes in the characteristics of the electromagnetic motor due to changes over time, etc. The present invention aims to provide a measurement device, measurement method, and correction method that can acquire scanned images with reduced inaccuracies caused by errors in the encoder that encodes the measurement position of the scanner.

[0007] A measuring device according to an embodiment of the present invention comprises: a measuring unit that acquires measurement information of an object; a scanning unit that has a drive source and that scans a portion of the measuring unit back and forth in a first direction; a detecting unit that acquires position information that is information relating to the position of the portion of the measuring unit; a memory unit that stores calibration information that calibrates the position information; a control unit that, in response to the detecting unit detecting that a portion of the measuring unit is at a predetermined position, associates and acquires the measurement information from the measuring unit and the position information from the detecting unit; and a calculation unit that generates corrected measurement information in which the measurement information is corrected based on the position information and measurement information associated by the control unit and the calibration information read out from the memory unit. A measurement method according to an embodiment of the present invention includes a measurement step of acquiring measurement information of an object using a measurement unit, a scanning step of reciprocatingly scanning a portion of the measurement unit in a first direction, a detection step of acquiring position information that is information about the position of the portion of the measurement unit, a storage step of storing calibration information that calibrates the position information, an information acquisition step of linking the measurement information from the measurement unit with the position information in the detection step in response to detecting that a portion of the measurement unit is at a predetermined position in the detection step, and a calculation step of generating corrected measurement information in which the measurement information has been corrected based on the linked position information, measurement information, and calibration information. Also, a correction method according to an embodiment of the present invention includes a storage step of storing calibration information that calibrates position information that is information about the position of a portion of the measurement unit, and a calculation step of generating corrected measurement information in which the measurement information has been corrected based on the position information, measurement information, and calibration information.

[0008] The measuring device according to the present invention can provide a measuring device, a measuring method, and a correction method that can acquire a scanned image with reduced inaccuracy caused by errors in the encoder that encodes the measurement position of the scanner.

[0009] 1 is a diagram for explaining a measurement method of the present invention. A diagram for explaining a method for acquiring calibration information of the present invention. A diagram for explaining a measurement device of a first embodiment. A diagram for explaining a measurement device of a second embodiment. A diagram for explaining a protein array plate. A diagram for explaining a fluorescent image of a protein array plate. A diagram for explaining deviation in the X direction of a fluorescent image. A diagram for explaining position information of an encoder. A diagram for explaining generation of an error curve from position information of an encoder. A diagram for explaining generation of calibration information. A diagram for explaining the effect of the present invention. A diagram for explaining the relationship between cutoff frequency and error amount. A diagram for explaining updating of calibration information. A diagram for explaining a measurement device of the present invention. A diagram for explaining a measurement method of the present invention. A diagram for explaining the hardware configuration of a control unit.

[0010] A measuring device that is one embodiment of the present invention has a measuring unit that acquires measurement information of an object, a scanning unit that has a drive source and scans a portion of the measuring unit back and forth in a first direction, a detecting unit that acquires position information that is information about the position of the portion of the measuring unit, a memory unit that stores calibration information that calibrates the position information, a control unit that, in response to the detecting unit detecting that a portion of the measuring unit is at a predetermined position, associates and acquires the measurement information from the measuring unit and the position information from the detecting unit, and a calculation unit that generates corrected measurement information in which the measurement information is corrected based on the associated position information and measurement information by the control unit and the calibration information read out from the memory unit.

[0011] An example of the measuring device of this embodiment is shown in Figure 14. In Figure 14, 1001 denotes the measuring device, 1002 denotes the object, 1003 denotes a measurement unit, 1003p denotes a part of the measurement unit, 1004 denotes a scanning unit, 1005 denotes a detection unit, 1006 denotes a storage unit, and 1007 denotes a calculation unit. A driving source is not shown. The object 1002 is not included in the measuring device 1001. Note that Figure 14 shows an example in which the calculation unit 1007 and the storage unit 1006 are included in the control unit 1008, but a control unit that associates and acquires measurement information from the measuring unit 1003 and position information from the detection unit 1005 may be arranged separately from these. The hardware configuration of the control unit 1008 will be described later.

[0012] The detector 1005 is an encoder, specifically, a magnetic encoder, an optical encoder, a circular encoder, or a linear encoder. The encoder periodically samples data. The encoder has a reference mark as a reference point, but noise called crosstalk can occur near the reference mark. Furthermore, if a nearby driving source, such as an electromagnetic motor, affects the magnetic field, the encoder can be affected by the magnetic field and generate errors. The measuring device of this embodiment can reduce the effects of encoder errors, including the effects of crosstalk and magnetic fields described above. Therefore, the measuring device 1001 of this embodiment can obtain highly accurate corrected measurement information even if the encoder does not have high accuracy.

[0013] The driving source may be an actuator, such as an electromagnetic actuator or an ultrasonic vibration actuator. An electromagnetic motor may be used as the electromagnetic actuator. The scanning unit 1004 may scan the measuring unit 1003 using a piston-crank mechanism. The measuring unit 1003 may be scanned in one direction (referred to as the first direction), and the calculation unit 1007 may correct the measurement information for the first direction to generate corrected measurement information. Furthermore, the measuring unit 1003 may be scanned in a second direction perpendicular to the first direction. In this case, the calculation unit 1007 may acquire multiple pieces of corrected measurement information for the first direction based on the second direction, thereby generating two-dimensional corrected measurement information.

[0014] An example of calibration information indicating the correspondence between position information and corrected position information is information indicating the correspondence between the coordinates of multiple points at a predetermined pitch based on the position information output by the detection unit and the corrected coordinates of those multiple points. In this case, the calculation unit can calculate the corrected measurement information at the multiple points based on the measurement information of the multiple points at a predetermined pitch based on the position information output by the detection unit, thereby generating corrected measurement information. This calculation can be performed using techniques such as interpolation or extrapolation.

[0015] The calibration information can be obtained by low-pass filtering position information acquired by the detection unit 1005 at a predetermined sampling frequency with a cutoff frequency that is a predetermined multiplication factor of the frequency of the driving source. Details of the calibration information will be described later. The predetermined multiplication factor is preferably 6.0 or more and 10.0 or less.

[0016] 15 , the measurement method of this embodiment includes a scanning step (S-1501) of acquiring measurement information by scanning a part of the measurement unit back and forth in a first direction using a scanning unit 1004 having a drive source (electromagnetic motor 101), a detection step (S-1502) of acquiring position information that is information about the position of the part of the measurement unit, a storage step (S-1503) of storing calibration information that calibrates the position information, an information acquisition step (S-1504) of linking and acquiring the measurement information from the measurement unit and the position information in the detection step in response to detecting that the part of the measurement unit is in a predetermined position in the detection step, and a calculation step of generating corrected measurement information in which the measurement information is corrected based on the linked position information, measurement information, and calibration information. A measurement step of acquiring measurement information of the target using the measurement unit may be performed before the scanning step.

[0017] In the measurement method of this embodiment, the storage step is performed before the scanning step, and the calibration information can be stored in a readable storage unit. Furthermore, the calibration information stored in the storage unit may be updated in response to a higher-level command from an operator.

[0018] That is, the calibration information can be stored in advance in the storage unit at any timing, for example, before other processes. In this case, the calibration information stored in the storage unit can be used, and there is no need to execute the calibration information acquisition process each time the measurement information acquisition process is executed multiple times.

[0019] Alternatively, a step of calibrating the position information based on the calibration information may be executed each time the detection step is executed. Alternatively, the calibration information may be recorded in a storage unit, and when the performer determines it is necessary, the information acquisition step may be executed to update the calibration information in the storage unit. An example of when the performer determines it is necessary is when the frequency of the drive source is changed. In other words, the calibration information may be updated based on a higher-level command from the performer.

[0020] In addition, the correction method of this embodiment is a correction method that includes a storage process for storing calibration information that calibrates position information, which is information regarding the position of a part of the measurement unit, and a calculation process for generating corrected measurement information in which the measurement information has been corrected based on the position information, measurement information, and the calibration information.

[0021] The hardware configuration of the control unit 1008 will be described with reference to Fig. 16. The control unit 1008 has computer functions. For example, the control unit 1008 may be integrated with a desktop personal computer (PC), laptop PC, tablet PC, smartphone, or the like. The control unit 1008 may also have a function to control other devices according to a predetermined program.

[0022] To realize the functions of a computer that performs calculations and storage, the control unit 1008 includes a CPU (Central Processing Unit) 2006, a RAM (Random Access Memory) 2007, a ROM (Read Only Memory) 2008, and a HDD (Hard Disk Drive) 2009. The control unit 1008 also includes a communication I / F (Interface) 2010, a display device 2011, and an input device 2012. The CPU 2006, RAM 2007, ROM 2008, HDD 2009, communication I / F 2010, display device 2011, and input device 2012 are connected to one another via a bus 2013. The display device 2011 and the input device 2012 may be connected to the bus 2013 via a drive device (not shown) for driving these devices.

[0023] Although FIG. 16 illustrates the components constituting the control unit 1008 as an integrated device, some of these functions may be implemented by external devices. For example, the display device 2011 and input device 2012 may be external devices separate from the components constituting the computer functions, including the CPU 2006. The CPU 2006 performs predetermined operations in accordance with programs stored in the RAM 2007, HDD 2009, etc., and also has the function of controlling the components of the control unit 1008. The RAM 2007 is a volatile storage medium and provides temporary memory space necessary for the operation of the CPU 2006. The ROM 2008 is a nonvolatile storage medium and stores necessary information, such as programs, used in the operation of the control unit 1008. The HDD 2009 is a nonvolatile storage medium and is a storage device that stores information regarding the number and positions of individual independent separation compartments, fluorescent light intensity, etc.

[0024] The communication I / F 2010 is a communication interface based on standards such as Wi-Fi (registered trademark) and 4G, and is a module for communicating with other devices. The display device 2011 is a liquid crystal display, an OLED (organic light-emitting diode) display, or the like, and is used to display moving images, still images, characters, and the like. The input device 2012 is a button, a touch panel, a keyboard, a pointing device, or the like, and is used by the user to operate the control unit 1008. The display device 2011 and the input device 2012 may be integrally formed as a touch panel.

[0025] The hardware configuration shown in FIG. 16 is an example, and other devices may be added, or some devices may not be provided. Also, some devices may be replaced with other devices having similar functions. Furthermore, some functions may be provided by other devices via a network, or the functions constituting this embodiment may be distributed and realized among multiple devices. For example, the HDD 2009 may be replaced with an SSD (Solid State Drive) using semiconductor elements such as flash memory, or may be replaced with cloud storage.

[0026] The present invention will be described in more detail below using an example in which a magnetic encoder is used as a detection unit in a system in which a substrate with spots on a glass slide is irradiated with light to obtain measurement information, but the present application is not limited to the following example. The present invention can also be used with measurement methods other than optical. Furthermore, the present invention is not limited to magnetic encoders, and optical encoders or other encoders can also be used. The effects of the present invention are particularly pronounced when using encoders with low precision.

[0027] First Embodiment A measuring apparatus 1101 according to this embodiment will be described with reference to FIG.

[0028] <Scanning Unit> In the measuring device 1101 of this embodiment, the scanning unit 1004 is composed of an electromagnetic motor 101 as a driving source, a disk 103 attached to the electromagnetic motor 101, a crank 105, a scale 113 including a reference mark 115, a linear guide 107, and a movable stage (X-axis) 109. The crank 105 is rotatably attached to the disk 103 and the movable stage 109. A support unit 116 is fixed to the movable stage 109, supporting a portion of each of an irradiation unit 117i, which is an optical system 117, and a light collecting unit 117r, which is also an optical system 117. The rotational motion of the electromagnetic motor 101 is converted into a linear reciprocating motion by the disk 103 and the crank 105, and the movable stage 109 moves linearly on the linear guide 107. As a result, the focus of the primary light can be moved along the substrate 151. The movable stage 109, guided by the linear guide 107, corresponds to the piston of the piston-crank mechanism.

[0029] <Object> In the measurement device 1101 of this embodiment, the object is an array plate 150, which includes a substrate 151 and spots 153. The substrate 151 is generally a glass slide. Spots 153, which are the measurement objects, are placed on the surface of the glass slide. The spots 153 may be placed on either the front or back surface of the glass slide. The spots 153 contain, for example, a specific protein.

[0030] <Measurement Unit> In measuring device 1101 of this embodiment, measurement unit 1003 corresponds to semiconductor laser 131, irradiation unit 117i, light collecting unit 117r, support unit 116 including portions of irradiation unit 117i and light collecting unit 117r, and optical sensor 145. Irradiation unit 117i is composed of objective lens 121, 90-degree mirror 119, dichroic mirror 137, and collimator lens 135, light collecting unit 117r is composed of objective lens 121, 90-degree mirror 119, dichroic mirror 137, bandpass filter 139, condenser lens 141, and pinhole 143, and part 1003p of the measurement unit including portions of irradiation unit 117i and light collecting unit 117r supported by support unit 116 is composed of objective lens 121, 90-degree mirror 119, and scale 113.

[0031] <Irradiation unit> In the measuring device 1101 of this embodiment, the irradiation unit 117i is composed of an objective lens 121, a 90-degree mirror 119, a dichroic mirror 137, and a collimator lens 135, and is arranged so that the primary light is focused on a plane including the spot 153 on the substrate 151.

[0032] <Primary Light> The light from the semiconductor laser 131 is converted into parallel light by the collimating lens 135, passes through the dichroic mirror 137, and is irradiated onto the substrate 151 via the irradiating unit 117i. This light is the primary light. Here, an example is shown in which a semiconductor laser is used as the light source, but an LED may also be used.

[0033] <Secondary light> Secondary light is light that contains information about the specimen or substrate and is emitted from the focus of the primary light formed on the substrate. Secondary light can be reflected light from the substrate, or fluorescent light from the specimen or substrate that is emitted by irradiation with the primary light.

[0034] <Light collecting unit> Light collecting unit 117r is an optical system that includes objective lens 121, 90-degree mirror 119, dichroic mirror 137, bandpass filter 139, condenser lens 141, and pinhole 143, and guides secondary light from the focal point to the light detection unit. In this example, it corresponds to an optical member that is arranged on the optical path that passes through 90-degree mirror 119 and objective lens 121 shared by irradiation unit 117i and light collecting unit 117r and is reflected by dichroic mirror 137.

[0035] <Light detection unit> The light sensor 145 detects the secondary light from the light collecting unit. The light sensor 145 may be a photodiode or a photomultiplier tube. The secondary light reflected by the dichroic mirror 137 passes through a bandpass filter 139 and is focused on a pinhole 143 by a focusing lens 141. The light that has passed through the pinhole 143 is detected by the light sensor 145.

[0036] <Scanning Unit> In the measuring device 1101 of this embodiment, the scanning unit 1004 is composed of an electromagnetic motor 101 as a drive source, a disk 103, a crank 105, and a scale 113 (reference mark 115). The scanning unit 1004 reciprocates and scans a part 1003p of the measuring unit described above in a first direction.

[0037] <Detection Unit> In the measuring device 1101 of this embodiment, the detection unit 1005 is the encoder 111 in FIG. 3. A scale 113 including a reference mark 115 is attached to the moving stage 109, and a magnetic encoder 111 is fixedly disposed at a position where information on the scale can be detected. The encoder 111 can obtain position information on the moving stage 109 of the scanning unit 1004. The detection unit 1005 obtains position information, which is information on the position of a part 1003p of the measuring unit. In the measuring device 1101 of this embodiment, the position information is obtained by the X-axis as described below. ｎ is.

[0038] <Storage Unit> In the measuring apparatus 1101 of this embodiment, the storage unit 1006 stores calibration information for calibrating the position information. The calibration information will be described below.

[0039] <Control Unit> In the measuring device 1101 of this embodiment, the control unit 1008 is composed of a controller 161, an LD driver 163, a first electromagnetic motor driver 165, a storage unit 1006, and a calculation unit 1007. When the encoder 111 detects that a part 1003p of the measuring unit is in a predetermined position, the control unit 1008 associates and acquires an optical information data string Pn, which is measurement information from the measuring unit 1003, with position information Xn from the encoder 111. The controller 161 controls the LD driver 163 and the first electromagnetic motor driver 165, and acquires optical information from the optical sensor 145 using the position information of the encoder 111 as a reference for data acquisition. The LD driver 163 controls the semiconductor laser 131. The first electromagnetic motor driver 165 controls the electromagnetic motor 101. The control unit 1008 acquires position information of the movable stage 109 using the encoder 111, and acquires optical information from the optical sensor 145 at equal distance intervals based on the position information of the encoder 111 while the movable stage 109 moves from one position to another.

[0040] <Calculation Unit> The calculation unit 1007 and the storage unit 1006 are included in a PC. Calibration information is stored in advance in the storage unit 1006. The calculation unit 1007 reads the calibration information from the storage unit 1006, and calculates the position information Xn and the light information data string Pn, which is measurement information, linked by the control unit 1008, and the corrected position information (X_true) read from the storage unit 1006. ｎ ), the corrected measurement information p_corr obtained by correcting the measurement information based on ｎ The correction of the optical information in the control unit 1008 and the calculation unit 1007 will be described with reference to FIG.

[0041] <S-01 Acquisition of Calibration Information> The calculation unit 1007 reads pre-stored calibration information from the storage unit 1006. The method of generating the calibration information will be described later. The calibration information is a list of the actual positions of the movable stage 109 at the timing of acquiring the optical information (more precisely, values ​​that can be regarded as the actual position information of the movable stage 109 excluding error information without causing any problems) when optical information is acquired at equal distance intervals based on the position information of the encoder 111 while the movable stage 109 moves from one position to another. For example, when optical information is acquired at 10 μm intervals from −10 mm to +10 mm, the set position information (X ｎ、 n is a natural number from 1 to N) is (-10.00, -9.99, -9.98, ..., 9.99, 10.00), while the corrected position information (X_true ｎ ) is stored in the form (-10.007, -9.991, -9.974, ..., 9.993, 9.999).

[0042] <S-02 Acquisition of pseudo-equal pitch light information> The control unit 1008 acquires the pseudo-equal pitch light information by ｎ When it is determined that the light has passed through the optical sensor 145, the optical information is acquired. Here, the optical information is an optical information data string p ｎ The optical information data string p ｎ Since the pitches are generally equal, it is sometimes called pseudo-equal pitch optical information.

[0043] <S-03 Acquisition of equal pitch light information> Information calibration information X_true ｎ Corrected measurement information (p_corr ｎ Corrected measurement information (p_corr ｎ ) is (X_true ｎ， p ｎ ) dataset (X ｎ， p_corr ｎ The data set is generated by interpolating or extrapolating the data set. The interpolation method can be selected from the nearest neighbor interpolation, linear interpolation of two nearby points, polynomial interpolation of multiple nearby points, spline interpolation, and so on.

[0044] The generation of calibration information will now be described. (a) Position Information by the Detection Unit: As shown in Figure 5, a protein array spot with 18 horizontal columns and 45 vertical rows is prepared. Each spot contains the protein BCAR1. The protein BCAR1 is tagged with GST (glutathione S-transferase), and the GST tag is labeled with a fluorescent probe that emits fluorescence in response to light with a wavelength of 670 nm. The size of the spots is approximately 100 μm, with a pitch of 1 mm both vertically and horizontally. Figure 6 shows an example of a two-dimensional image of such a protein array spot acquired using the measurement device shown in Figure 4 (details will be described later). Here, the rotation speed of the electromagnetic motor 101 is 1200 rpm (= 20 rps), the distance from the electromagnetic motor shaft to the connection point of the crank 105 is 15 mm, the length of the crank 105 is 100 mm, and the moving stage 109 scans 30 mm from -15 mm to +15 mm. The scanning direction of the moving stage 109 away from the electromagnetic motor 101 is called the forward path, and the scanning direction toward the electromagnetic motor 101 is called the return path. Figure 6 shows an image of optical information acquired only on the forward path, without correction using calibration information. Figure 7(a) shows the results of measuring the degree to which the center of gravity of the spot is displaced from the correct position from the image in Figure 6. The X direction is the direction in which the moving stage 109 is scanned. Here, the horizontal axis represents the column number of the protein array spot, and the vertical axis represents the amount of displacement in the X direction. There are 45 data points per column. A reference mark is located between columns 7 and 9, and the positive and negative directions of the error are reversed before and after this. Errors also occur in locations other than the reference mark. Similarly, Figure 7(b) shows the results of measuring the degree to which the center of gravity of the spot is displaced from the correct position for an image of optical information acquired only on the return path. Figure 7(b) shows the same trend as Figure 7(a). Figure 7(c) shows Figures 7(a) and 7(b) averaged for each column number and superimposed. Here, the solid line shows the amount of image shift in the forward pass only, and the dotted line shows the amount of image shift in the backward pass only. The fact that the two lines match well shows that this phenomenon does not depend on the scanning direction (forward or backward).This means that even if optical information during two-dimensional scanning is acquired on both the forward and backward paths and combined into a single image, an image containing an error in the X direction will be obtained.

[0045] (b) Calibration Information FIG. 8(a) shows the results of acquiring position information from the encoder 111 at a sampling interval (sampling frequency) of 1 μs (1 MHz) when the electromagnetic motor 101 is operated at a rotational speed of 1,200 rpm using the measurement device shown in FIG. 4 . The horizontal axis represents time, and the vertical axis represents position information. In FIG. 8, the forward path is represented by a solid line, and the backward path is represented by a dotted line. FIG. 8(b) shows the result of applying low-pass filtering to FIG. 8(a) with a cutoff frequency of 180 Hz, which is nine times the rotational speed. FIG. 8(c) shows the result of subtracting FIG. 8(b) from FIG. 8(a). This is equivalent to applying high-pass filtering to FIG. 8(a) with a cutoff frequency of 180 Hz, which is nine times the rotational speed. The inventors discovered that the results of FIG. 7(c) can be expressed by regarding the position information in FIG. 8(b) as the correct value and the position information in FIG. 8(c) as the error amount. That is, when the position information in FIG. 8(b) is plotted on the horizontal axis and the position information in FIG. 8(c) is plotted on the vertical axis, FIG. 9 is obtained, and the inventors of the present application have found that the results in FIG. 9 are in good agreement with the results in FIG. 7(c).

[0046] (c) Method of Acquiring Calibration Information The method of acquiring calibration information derived from this will be described with reference to FIG. 2. <S-11 Driving the Scanning Unit> The scanning unit 1004 is scanned at a predetermined driving frequency. The driving frequency is equal to the rotation speed of the electromagnetic motor 101. <S-12 Acquiring First Position Information> Position information (first position information) of the encoder 111 is acquired at a constant sampling frequency. The sampling frequency may be set to an appropriate value depending on the subsequent steps and the pitch of the optical information to be acquired. <S-13 Acquiring Second Position Information> Second position information is acquired by low-pass filtering the first position information at a cutoff frequency that is a predetermined multiple of the driving frequency. Here, the predetermined multiple is suitably about 6.0 to 10.0 times (described later). <S-14 Generating Calibration Information> Calibration information is generated from the second position information at the timing of acquiring optical information. In the above example, when optical information is acquired at 10 μm intervals from -10 mm to +10 mm, the set position information (X ｎ、 The time indicated by the encoder 111 as (-10.00, -9.99, -9.98, ..., 9.99, 10.00), where n is a natural number from 1 to N, is the timing for acquiring the optical information. Also, the second position information (-10.007, -9.991, -9.974, ..., 9.993, 9.999) at that timing is the corrected position information (X_true ｎ <S-15 Saving of Proofreading Information> The generated proofreading information is stored in the storage unit 1006.

[0047] (d) Supplementary explanation of calibration information S-14 (generation of calibration information) will be further explained using Figure 10. Figure 10(a) plots the relationship between time during scanning and the position of the moving stage. Figure 10(b) is an enlarged view of the area enclosed by a square in Figure 10(a). In addition, the solid line in Figure 10(b) is the position information f(t) measured by the encoder 111, and the dotted line is the position information f(t) obtained by low-pass filtering. ＬＰ (t). At a predetermined position X ｎ From X ｎ＋７ The light information is acquired at time t ｎ From t ｎ＋７ Corrected position information X_trueｎ is X_true ｎ = f ＬＰ (t ｎ ) can be obtained.

[0048] The effect of the correction will now be explained. Figure 11(a) shows an enlarged view of the spot portions of the top four rows of the spot image in Figure 6. The circular lines and crosshairs indicate the region of interest, which is spaced 1 mm vertically and horizontally. Since no correction has been performed here, it can be seen that there are spots that are shifted to the left or right of the region of interest. Figure 11(b) shows an image after correction. The spot image is positioned approximately in the center of the region of interest, confirming the effect of the correction.

[0049] The method for determining the cutoff frequency will now be described. In Figure 12, the horizontal axis shows the ratio of the cutoff frequency to the drive frequency, and the vertical axis shows the standard deviation of the X-direction error amount for all 18 x 45 spots. The solid line shows the optical information acquired only on the forward path, and the dotted line shows the optical information acquired only on the backward path. From this, it can be seen that the standard deviation of the error amount can be reduced if the cutoff frequency is 6 to 10 times the drive frequency. Therefore, a cutoff frequency between 6.0 and 10.0 times the drive frequency is appropriate.

[0050] A specific example of measurement will be described with reference to Fig. 3. Explanation of parts that overlap with the above explanation will be omitted.

[0051] <Primary Light> The semiconductor laser 131 emits laser light with a wavelength of 670 nm and an output of 5 mW. The laser light is converted into parallel light by the collimator lens 135, passes through the dichroic mirror 137, and is focused by the objective lens 121 onto a plane including the spot 153.

[0052] <Secondary Light> Fluorescent light, which is secondary light, is generated by irradiating the spot 153 with primary light.

[0053] <Light Collecting Section> The secondary light is reflected by the dichroic mirror 137 , passes through a bandpass filter 139 with a transmission band of 695 to 730 nm, and is collected on a pinhole 143 by a collecting lens 141 .

[0054] <Photodetector> The photosensor 145 is configured with a photomultiplier tube so as to be able to detect weak secondary light. In the measurement device of this embodiment, calibration information is measured in advance and stored in the storage unit 1006.

[0055] <S-01 Acquisition of Calibration Information> The calculation unit 1007 reads pre-stored calibration information from the storage unit 1006. For example, corrected position information (X_true ｎ ) is (-10.007, -9.991, -9.974, ..., 9.993, 9.999).

[0056] <S-02 Acquisition of pseudo-equal-pitch optical information> The controller 161 in the control unit 1008 acquires position information of the moving stage 109 by the encoder 111, and acquires optical information of the optical sensor 145 at equal distance intervals based on the position information of the encoder 111 while the moving stage 109 moves from one position (position A) to another position (position B). Position A, position B, and the distance interval for acquiring optical information are set in advance so as to match the calibration information acquired in advance. The set position information (X ｎ、 n is a natural number from 1 to N) is (-10.00, -9.99, -9.98, ..., 9.99, 10.00). ｎ Let's say.

[0057] <S-03 Acquisition of equal-pitch optical information> Corrected measurement information (p_corr) obtained by interpolating optical information based on calibration information ｎ ) is generated. ｎ， p ｎ ) dataset (X ｎ， p_corr ｎ ) data set is generated by interpolating or extrapolating.

[0058] According to this embodiment, it is possible to acquire equal-pitch optical information with reduced errors in the position information of the magnetic encoder 111 caused by the reference marks and other factors.

[0059] Second Embodiment This embodiment will be described with reference to Fig. 4. A measuring apparatus 1201 of this embodiment differs from the measuring apparatus 1101 of the first embodiment in that a measuring unit 1003 includes a sub-scanning unit 1202 that scans in a second direction intersecting the first direction.

[0060] <Placement Section> The placement section 207 is configured to be able to hold the array plate 150. In this example, a part of the placement section 207 is hollowed out so that primary light can be irradiated from the rear surface side.

[0061] <Sub-scanning unit> The sub-scanning unit 1202 is also referred to as a second scanning unit. In the measuring device of this embodiment, the sub-scanning unit 1202 is composed of a linear guide 201, a movable table (Y-axis) 203, an electromagnetic motor 205, a mounting unit 207, and a support table 209. The movable table 203 moves on the linear guide 201 by rotating the electromagnetic motor 205. The movable table 203 includes a support table 209 and a mounting unit 207 that is supported by the support table 209 and on which the array plate 150 is placed. As a result, it is possible to scan the substrate in a direction intersecting the scanning direction of the first scanning unit. Because high accuracy is required for scanning in this direction, a pulse electromagnetic motor is suitable for the electromagnetic motor 205.

[0062] <Control Unit> The control unit 1008 is composed of a controller 161, an LD driver 163, a first electromagnetic motor driver 165, a second electromagnetic motor driver 211, a memory unit 1006, and a calculation unit 1007. The controller 161 controls the LD driver 163, the first electromagnetic motor driver 165, and the second electromagnetic motor driver 211, and acquires optical information from the optical sensor 145 using position information from the encoder 111 as a data acquisition reference. The LD driver 163 controls the semiconductor laser 131. The first electromagnetic motor driver 165 controls the electromagnetic motor 101. The second electromagnetic motor driver 211 controls the electromagnetic motor 205. The control unit acquires position information of the movable stage 109 using the encoder 111, and acquires optical information from the optical sensor 145 at equal distance intervals while the movable stage 109 moves from one position to another, using the position information from the encoder 111 as a reference. Furthermore, the control unit controls the sub-scan unit to scan the substrate 151 in a direction perpendicular to the scanning direction of the movable stage 109.

[0063] According to this embodiment, it is possible to acquire optical information from the array plate 150 in two dimensions, and an optical information image can be acquired that reduces errors in the position information of the magnetic encoder 111 caused by reference marks and other factors.

[0064] In the first and second embodiments, the calibration information is acquired in advance before measurement. In this embodiment, the calibration information is updated for each measurement and stored in the storage unit 1006, which is different from the measuring apparatus 1101 of the first embodiment and the measuring apparatus 1201 of the second embodiment.

[0065] For example, if you want to acquire data at a finer pitch or scan at a slower drive frequency depending on the measurement target, it is appropriate to update the calibration information to match those conditions. In that case, the following flow is adopted (see Figure 13).

[0066] <S-31 Input of measurement conditions> The operator inputs the measurement conditions, which are the start position and end position of the optical information acquisition, the pitch of the optical information acquisition, and the drive frequency of the scanning unit 1004.

[0067] <S-32 Determining the Sampling Frequency> The sampling frequency is determined from the optical information acquisition pitch and the drive frequency of the scanning unit 1004. It is desirable that the sampling time interval be equal to or shorter than the time required for the moving stage to move a distance equal to the optical information acquisition pitch when moving at the highest speed. Alternatively, a sufficiently high-speed sampling frequency may be fixed and given.

[0068] <S-33 Generation and storage of calibration information> Calibration information is generated through the flow from S-11 to S-15 and stored in memory.

[0069] According to this embodiment, even if the measurement conditions are changed, by acquiring optimal calibration information, it is possible to acquire an optical information image with reduced errors in position information.

[0070] Fourth Embodiment In this embodiment, the calibration information is updated in response to a higher-level command from the operator. The amount of error in the position information acquired by the encoder 111 may change due to changes over time in the linear guide and the electromagnetic motor. To accommodate such cases, the calibration information may be updated at a timing desired by the operator.

[0071] [Other Embodiments] The calibration information may be prepared separately for the outbound journey and the return journey, and correction may be performed independently for the outbound journey and the return journey. Alternatively, since the characteristics of the outbound journey and the return journey are nearly identical, only one of the calibration information may be adopted and applied to both the outbound journey and the return journey, or an average value may be adopted.

[0072] The present invention is not limited to the above-described embodiments, and various modifications and variations can be made without departing from the spirit and scope of the present invention. Therefore, the following claims are appended to apprise the public of the scope of the present invention.

[0073] This application claims priority based on Japanese Patent Application No. 2023-212822, filed December 18, 2023, the entire contents of which are incorporated herein by reference.

[0074] 101 Electromagnetic motor 103 Disk 105 Crank 107 Linear guide 109 Moving table (X-axis) 111 Encoder 113 Scale 115 Reference mark 116 Supporting part 117i Irradiating part 117r Light collecting part 117 Optical system 119 90-degree mirror 121 Objective lens 131 Semiconductor laser 135 Collimating lens 137 Dichroic mirror. 139 Bandpass filter 141 Condenser lens 143 Pinhole 145 Optical sensor 150 Plate array 151 Substrate 153 Spot 161 Controller 163 LD driver 165 First electromagnetic motor driver 1001 Measuring device 1011 Measuring device of first embodiment 1012 Measuring device of second embodiment 1002 Object 1003 Measuring unit 1003P Part of measuring unit 1004 Scanning unit 1005 Detection unit 1006 Storage unit 1007 Arithmetic unit 1008 Control unit 2006 CPU 2007 RAM 2008 ROM 2009 HDD 2010 Communication I / F 2011 Display device 2012 Input device 2013 Bus

Claims

1. A measuring device having: a measurement unit that acquires measurement information of an object; a scanning unit that has a drive source and reciprocates to scan a part of the measurement unit in a first direction; a detection unit that acquires position information that is information regarding the position of the part of the measurement unit; a memory unit that stores calibration information for calibrating the position information; a control unit that, in response to the detection unit detecting that a part of the measurement unit is at a predetermined position, acquires the measurement information from the measurement unit and the position information from the detection unit in association with each other; and a calculation unit that generates corrected measurement information in which the measurement information is corrected based on the position information and measurement information linked by the control unit and the calibration information read out from the memory unit.

2. The measuring device according to claim 1, wherein the detection unit has an encoder that encodes the position information, and the scanning unit includes a scale by which the encoder detects the position information.

3. The measurement device of claim 2, wherein the encoder comprises a magnetic encoder.

4. The measuring device according to claim 1 or 2, wherein the driving source includes an electromagnetic actuator.

5. A measuring device as described in claim 1 or 2, wherein the scanning unit has a piston crank mechanism including a crank connected to the drive source and a piston connected to a part of the measuring unit, and scans a part of the measuring unit via the piston crank mechanism.

6. The measuring device of claim 1 or 2, wherein the memory unit acquires multiple pieces of measurement information acquired by the measurement unit, and the calculation unit selects at least one piece of measurement information from the multiple pieces of measurement information from the memory unit based on the position information and the calibration information, and generates the corrected measurement information based on the selected at least one piece of measurement information.

7. A measuring device as described in claim 5, comprising a sub-scanning unit which scans the object using a part of the measuring unit in a second direction intersecting the first direction, and a mounting unit on which the object is placed, the sub-scanning unit moving the mounting unit in the second direction relative to the scanning unit.

8. The measuring device according to claim 7, wherein the calculation unit generates two-dimensional measurement information based on the corrected measurement information, the position information, and information relating to the position of a portion of the measuring unit in the second direction.

9. A measuring device according to claim 1 or 2, wherein the measuring section has an irradiating section which irradiates light onto the object, and a light collecting section which collects light from the object.

10. The measuring device according to claim 1 or 2, characterized in that the calibration information includes information corresponding to position information obtained by filtering the position information acquired by the control unit via the detection unit using a low-pass filter having a cutoff frequency corresponding to a predetermined magnification of the frequency of the reciprocating scan of the scanning unit.

11. The measuring device according to claim 10, wherein the predetermined magnification is equal to or greater than 6.0 and equal to or less than 10.

0.

12. A measuring device as described in claim 1 or 2, wherein the calibration information is stored in the memory unit in association with a data set including a plurality of pieces of position information acquired by the control unit from the detection unit corresponding to a plurality of specified positions, and a data set including a plurality of pieces of corrected position information corrected by the calculation unit for correcting the plurality of pieces of position information.

13. A measurement method comprising: a measurement step of acquiring measurement information of an object using a measurement unit; a scanning step of reciprocatingly scanning a part of the measurement unit in a first direction by a scanning unit having a drive source; a detection step of acquiring position information, which is information relating to the position of the part of the measurement unit, using a detection unit; a storage step of storing calibration information for calibrating the position information; an information acquisition step of linking and acquiring the measurement information from the measurement unit and the position information in the detection step in response to detection in the detection step that a part of the measurement unit is at a predetermined position; and a calculation step of generating corrected measurement information in which the measurement information is corrected based on the linked position information, measurement information, and calibration information.

14. The measurement method according to claim 13, wherein the storing step is performed prior to the measuring step, and the calibration information is stored in a readable memory unit.

15. The measurement method according to claim 14, wherein the calibration information stored in the memory unit is updated in response to a higher-level command from an operator.

16. A measurement method according to any one of claims 13 to 15, wherein the calibration information includes information corresponding to position information obtained by filtering the position information acquired by the detection process using a low-pass filter having a cutoff frequency corresponding to a predetermined multiple of the frequency of the reciprocating scan in the scanning process.

17. The measurement method according to claim 16, wherein the predetermined magnification is equal to or greater than 6.0 and equal to or less than 10.

0.

18. A measurement method described in any one of claims 13 to 17, wherein the calibration information is stored in the storage step in association with a data set including a plurality of pieces of position information acquired in the detection step corresponding to a plurality of specified positions, and a data set including a plurality of pieces of corrected position information generated in the calculation step by correcting the plurality of pieces of position information.

19. A measuring device according to any one of claims 13 to 18, wherein the detection unit has an encoder that encodes the position information, and the scanning unit includes a scale by which the encoder detects the position information.

20. The measurement device of claim 19, wherein the encoder comprises a magnetic encoder.

21. The measuring device according to any one of claims 13 to 20, wherein the drive source includes an electromagnetic actuator.

22. A correction method comprising: a storage step of storing calibration information for calibrating position information, which is information relating to the position of a part of a measurement unit; and a calculation step of generating corrected measurement information in which the measurement information has been corrected based on the position information, measurement information, and the calibration information.

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