Capillary electrophoresis apparatus and method for diagnosing its optical performance

Abstract

The purpose of the present invention is to provide a capillary electrophoresis device that can confirm optical performance without performing a specialized task, and an optical performance diagnostic method for the capillary electrophoresis device. In order to achieve said purpose, the present invention is a capillary electrophoresis device comprising: a capillary array formed by a plurality of capillaries; a light source that oscillates laser light; a detector that detects light emitted when the capillary array is irradiated with the laser light; and a control unit that performs prescribed processing on the basis of signals from the detector. The control unit extracts a prescribed absolute value related to an optical index on the basis of an image captured by the detector, and calculates the optical index by comparing the extracted absolute value and a predetermined reference value.

Description

[Technical Field]

[0001] The present invention relates to a capillary electrophoresis apparatus and a method for diagnosing its optical performance. [Background technology]

[0002] Capillary electrophoresis devices are widely used as devices for analyzing DNA base sequences or base lengths. In capillary electrophoresis devices, the positional relationship of the optical system may be displaced when the capillary array is replaced. Therefore, as described in Patent Document 1, for example, a technique is known for normalizing data obtained by electrophoresis using wavelength calibration data acquired before shipment. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-212449 Summary of the Invention [Problem to be solved by the invention]

[0004] However, when checking the optical performance of a capillary electrophoresis apparatus after shipment, manual operation by a service engineer or the like is required.

[0005] An object of the present invention is to provide a capillary electrophoresis apparatus and a method for diagnosing its optical performance that can be confirmed without requiring specialized work. [Means for solving the problem]

[0006] In order to solve the above-mentioned problems, the present invention provides a capillary electrophoresis device comprising a capillary array composed of a plurality of capillaries, a light source that emits laser light, a detector that detects light emitted when the laser light is irradiated onto the capillary array, and a control unit that performs predetermined processing based on a signal from the detector, wherein the control unit extracts a predetermined absolute value related to an optical index based on an image captured by the detector, and calculates the optical index by comparing the extracted absolute value with a predetermined reference value. [Effects of the Invention]

[0007] According to the present invention, it is possible to provide a capillary electrophoresis apparatus and a method for diagnosing the optical performance thereof, which can be checked without requiring specialized work. [Brief explanation of the drawings]

[0008] [Figure 1] Schematic diagram of a capillary electrophoresis apparatus. [Figure 2] FIG. 2 is a diagram schematically illustrating the path of a laser beam in an optical irradiation system of a capillary electrophoresis device. [Figure 3A] A diagram showing a calibration shield array. [Figure 3B] FIG. 1 shows an analytical capillary array. [Figure 4A] FIG. 10 is a diagram showing an example of an image acquired when only the upper beam is irradiated onto the shield array. [Figure 4B] FIG. 10 is a diagram showing an example of an image acquired when only the lower beam is irradiated onto the shield array. [Figure 5] FIG. 10 is a diagram showing an example of an image acquired when upper and lower beams are irradiated onto a shield array. [Figure 6] 6 is a diagram showing an example of a light intensity distribution in the Y-axis direction at the long wavelength peak (dotted line 504 in FIG. 5). [Figure 7] 4A and 4B are conceptual diagrams showing the light intensity waveforms of the upper beam, the light intensity waveforms of the lower beam, and a composite waveform of these. [Figure 8] 10A and 10B are diagrams showing examples of images acquired when upper and lower beams are irradiated onto a capillary array. [Figure 9] 10A and 10B are diagrams showing examples of signal intensity distributions at the upper and lower centers of a capillary array when irradiated with upper and lower beams. DETAILED DESCRIPTION OF THE INVENTION

[0009] The configuration of a capillary electrophoresis apparatus according to an embodiment of the present invention will be described with reference to Fig. 1. Fig. 1 is a schematic diagram of the capillary electrophoresis apparatus according to this embodiment. As shown in Fig. 1, a capillary electrophoresis apparatus 101 includes a capillary array 117 composed of one or more capillaries 102, a thermostatic bath 118 that maintains the capillaries 102 at a constant temperature, a high-voltage power supply 104 that applies a voltage to the capillaries 102, a pump mechanism 103 that injects a polymer into the capillaries 102, and a transport mechanism 125. The transport mechanism 125 transports a buffer container 121, a washing container 122, a waste liquid container 123, and a sample container 124 to a capillary cathode end 127.

[0010] The capillary array 117 has a load header 129 provided at one end, a capillary head 112 provided at the other end, and a detection unit 116 formed between the load header 129 and the capillary head 112 to detect samples undergoing electrophoresis in the capillaries 102. The capillary array 117 is composed of, for example, 24 capillaries 102, and is replaced with capillaries of a different length when the measurement method is changed. Also, if a capillary 102 is damaged or its quality deteriorates, it is replaced with a new capillary array 117.

[0011] The capillary 102 is formed from a glass tube with an inner diameter of 50 μm and an outer diameter of 320 μm, and its surface is coated with polyimide to improve its strength. However, the polyimide coating has been removed from the detection unit 116 of the capillary 102, where the laser light is irradiated, to allow the internal light emission to easily leak to the outside. The interior of the capillary 102 is filled with a separation medium, which creates a migration difference during electrophoresis, by a pump mechanism 103. In this embodiment, a polymer, which is a highly viscous solution, is used as the separation medium.

[0012] The capillary cathode ends 127 are fixed through respective metallic hollow electrodes 126, and the tips of the capillaries 102 protrude about 0.5 mm from the hollow electrodes 126. All of the hollow electrodes 126 provided for each capillary 102 are mounted together on a load header 129. All of the hollow electrodes 126 are electrically connected to the high-voltage power supply 104 mounted in the main body of the device, and function as cathode electrodes when voltage is applied for electrophoresis, sample introduction, etc.

[0013] The capillary ends opposite the capillary cathode end 127 are bound together and glued by the capillary head 112. The capillary head 112 is connected to the block 107 in a pressure-tight and airtight manner. Then, new polymer is filled into the capillary 102 by the pump mechanism 103. The polymer in the capillary 102 is refilled for each measurement to improve the measurement performance.

[0014] The optical system is composed of a light irradiation mechanism 114 that irradiates the detection unit 116, an array holder 105 that holds the detection unit 116, a spectrometer 132 that separates the emitted light in the detection unit 116 into individual wavelengths, and a two-dimensional detector 115 that detects the separated light. When detecting a sample in the capillary 102 that has been separated by electrophoresis, the light irradiation mechanism 114 irradiates the detection unit 116, and the emitted light from the detection unit 116 is separated by the spectrometer 132 and then detected by the two-dimensional detector 115. The two-dimensional detector 115 is, for example, a CCD camera, and transmits detected image data to a control unit (not shown).

[0015] The control unit controls the operation of the high-voltage power supply 104 and other components, and calculates the analysis results of the sample based on signals detected by the two-dimensional detector 115. The control unit is also connected to an input unit for inputting settings and the like, an output unit for displaying analysis results and the like, and a storage unit for storing analysis results and the like (all of which are not shown).

[0016] The thermostatic bath 118 is covered with a heat insulating material, and its interior is controlled to a constant temperature by a heating and cooling mechanism 120. A fan 119 circulates and agitates the air inside the thermostatic bath 118, thereby maintaining the temperature of the capillary array 117 uniformly and constantly.

[0017] The pump mechanism 103 is composed of a plunger pump 106, a block 107, a check valve 108, an electric valve 113, a polymer container 109, and an anode buffer container 110. The block 107 is provided with a flow path that connects the plunger pump 106, the polymer container 109, the anode buffer container 110, and the capillary array 117. The flow path between the plunger pump 106 and the polymer container 109 is provided with a check valve 108 to prevent backflow of the polymer. The flow path between the block 107 and the anode buffer container 110 is provided with an electric valve 113. When the chamber 128 of the plunger pump 106 and the capillary array 117 are filled with polymer, the electric valve 113 closes to prevent the buffer solution from flowing in from the anode buffer container 110. When electrophoresis is performed, the electric valve 113 opens, and electricity is applied to the anode electrode 111 and the capillary cathode end 127.

[0018] The transport mechanism 125 is equipped with three electric motors and linear actuators (not shown), and is movable in three directions: up and down, left and right, and depth. One or more containers can be placed on the moving stage 130 of the transport mechanism 125. The moving stage 130 is also equipped with an electric grip 131, which can grasp and release each container. This allows the buffer container 121, washing container 122, waste container 123, and sample container 124 to be transported to the load header 129 as needed. Unnecessary containers are stored in a designated storage area within the device.

[0019] 2 is a diagram schematically illustrating the path of a laser beam in the optical irradiation system of the capillary electrophoresis device according to this embodiment. The light irradiation mechanism 114 in this embodiment includes a laser unit 133, which is a light source that emits laser beam 140, a beam splitter 136 that splits the laser beam 140 into two beams, a reflecting mirror 134 that changes the path of the laser beam 140, and a condenser lens 137 that condenses the laser beam 140. A polarizer 135, which is an optical element that transmits only unidirectionally polarized light, is inserted in the optical path between the laser unit 133 and the beam splitter 136. One beam of the laser beam 140 split by the beam splitter 136 is guided downward of the capillary array by the reflecting mirror 134, and the other beam is guided upward of the capillary array by the reflecting mirror 134. Furthermore, each laser beam 140 is focused by a focusing lens 137, and then enters the capillary array from the upper or lower end, and the fluorescence emitted from the detection unit 116 of each capillary 102 is detected by a two-dimensional detector 115. In the following description, it is assumed that a CCD camera is used as the two-dimensional detector 115.

[0020] 2 shows only five capillaries 102, but in this embodiment, the capillary array is made up of 24 capillaries 102, and the capillaries 102 are aligned and fixed to the reference base 138 in the detection unit 116. In this specification, an imaginary line that is on an imaginary plane formed by the central axes (capillary axes) of the capillaries on the reference base 138 and is perpendicular to each capillary axis is referred to as the optical axis 139. In this embodiment, the capillary array is made up of 24 capillaries 102, and the first capillary from the bottom is referred to as CAP1, and the 24th capillary from the bottom (first from the top) is referred to as CAP24, but the number of capillaries 102 is not limited to 24.

[0021] The optical performance of a capillary electrophoresis device depends on the positional accuracy of the optical axis of the laser light, the positional accuracy of the CCD camera, the focusing accuracy, etc. The optical performance before shipment is adjusted during the manufacturing process, but even after shipment, the optical performance must be checked periodically or when replacing the capillary array, and adjusted as necessary. A method for diagnosing the optical performance of a capillary electrophoresis device according to this embodiment will now be described. Before describing examples of the present invention, a comparative example will first be described.

[0022] (Comparative Example) In the comparative example, a calibration shield array 141 shown in Fig. 3A is used to diagnose optical performance. Unlike the analytical capillary array 117 shown in Fig. 3B, the shield array 141 is in a state where no voltage for electrophoresis is applied and does not contain DNA. In the shield array 141, both ends of the capillaries are sealed, filled with a polymer solution (EG: ethylene glycol / Urea), and cut to an easy-to-handle length (approximately 20 cm).

[0023] In the comparative example, after shipping of the capillary electrophoresis device, a service engineer primarily diagnoses the optical performance using the shield array 141. The service engineer or the like sets the shield array 141 in the array holder 105 and irradiates the polymer solution (EG / UREA) filled in each capillary with laser light, obtaining a Raman signal. The service engineer or the like uses dedicated software to visually identify the peak values ​​of the Raman signal contained in the image captured by the CCD camera. Because the optical performance includes multiple indices, the service engineer or the like must capture an image with the CCD camera for each indices and manually read the required values. The read values ​​are sent to the control unit, which then calculates the optical indices.

[0024] In the comparative example, the image captured by the CCD camera contains pseudo signals from a shield array simulating a capillary array, rather than an actual capillary array, so the calculated optical index is relative. Therefore, a service engineer or the like determines whether the calculated optical index falls within a target value (specification) predetermined for the shield array, and adjusts the optical axis of the laser light and the position of the CCD camera, if necessary. After the optical diagnosis is completed, the service engineer or the like removes the calibration shield array from the capillary electrophoresis device and installs an analytical capillary array for actual electrophoresis into the capillary electrophoresis device.

[0025] The diagnostic method of the comparative example performed by the service engineer will be specifically described below for each optical indicator.

[0026] <Coaxiality of upper and lower beams (Laser Beam Overlapping)> As described above, in the capillary electrophoresis apparatus of this embodiment, laser light is irradiated from above and below the capillary array. The laser light irradiated from above the capillary array is sometimes referred to as the upper beam, and the laser light irradiated from below the capillary array is sometimes referred to as the lower beam. In the comparative example, the coaxiality of the optical axes of the upper and lower beams is calculated using an image of Raman scattered light obtained when only the upper beam is irradiated and an image of Raman scattered light obtained when only the lower beam is irradiated. When imaging with only the upper beam irradiated, a service engineer or the like installs a light shield in the optical path of the lower beam and then uses a CCD camera. When imaging with only the lower beam irradiated, a service engineer or the like installs a light shield in the optical path of the upper beam and then uses a CCD camera.

[0027] FIG. 4A shows an example of an image acquired when only the upper beam is irradiated onto the shield array, and FIG. 4B shows an example of an image acquired when only the lower beam is irradiated onto the shield array. In FIG. 4A, a service engineer visually identifies short-wavelength peak 302 at the vertical center of the shield array, and in FIG. 4B, a short-wavelength peak 305 at the vertical center of the shield array. The control unit then extracts the X coordinate of peak 302 when only upper beam 301 is irradiated and the X coordinate of peak 305 when only lower beam 304 is irradiated, and outputs an optical index related to the coaxiality of the upper and lower beams based on the difference between these coordinates. If the output optical index is not within a predetermined target value range, i.e., if the deviation between the optical axes of the upper and lower beams is greater than specified, the service engineer adjusts the optical axis of the laser light.

[0028] <Grating Rotation Angle> In the comparative example, when calculating the index for the horizontal rotation angle, a new image is used in addition to the two images used to calculate the index for the coaxiality of the upper and lower beams. Figure 5 shows an example of an image acquired when the upper and lower beams are irradiated onto the shield array. A service engineer or the like visually checks and identifies the long-wavelength peak and the short-wavelength peak at the end of the shield array (CAP1 or CAP24) on the captured image shown in Figure 5. The control unit then calculates the deviation in the Y coordinate when connecting the peaks (dotted line 401 in Figure 5) and outputs optical indices related to the horizontal rotation angle of the spectrometer 132 and the CCD camera based on the calculated deviation. If the output optical indices are not within the predetermined target value range, i.e., if the horizontal rotation angle is larger than the specifications, the service engineer or the like adjusts the position of the spectrometer 132.

[0029] <Vertical rotation angle (CCD rotation angle)> In the comparative example, the image in FIG. 5 is also used when calculating the vertical rotation angle index. A service engineer or the like visually checks and identifies the short-wavelength peak at the upper end (CAP24) of the shield array and the short-wavelength peak at the lower end (CAP1) of the shield array on the captured image as shown in FIG. 5. The control unit then calculates the X-coordinate deviation when connecting the peaks (dotted line 403 in FIG. 5) and outputs optical indices related to the vertical rotation angle of spectrometer 132 and the CCD camera based on the calculated deviation. If the output optical indices are not within the range of the predetermined target value, i.e., if the vertical rotation angle is larger than the specification, the service engineer or the like adjusts the position of the CCD camera.

[0030] <Vertical direction error (Upper / Lower Location)> In the comparative example, the image in Fig. 5 is also used when calculating an index of vertical direction error. A service engineer or the like visually checks and identifies the position of the upper end (CAP24) of the shield array and the position of the lower end (CAP1) of the shield array on a captured image such as that shown in Fig. 5. The control unit then calculates the distance 404 (Upper Location) from the upper edge of the field of view to the upper end of the shield array, and the distance 405 (Lower Location) from the lower edge of the field of view to the lower end of the shield array, and outputs an optical index related to the vertical direction error based on the calculated values.

[0031] <Focus & Intensity> The image shown in Figure 5 is also used when calculating the light intensity focus error index in the comparative example. A service engineer or other person visually checks and identifies the short wavelength peak (501a) and long wavelength peak (501b) at the top end (CAP24) of the shield array, the short wavelength peak (501c) and long wavelength peak (501d) at the center (CAP12) of the shield array, and the short wavelength peak (501e) and long wavelength peak (501f) at the bottom end (CAP1) of the shield array on the captured image shown in Figure 5. The control unit then outputs an optical index related to the light intensity focus error based on the light intensity at each peak. This light intensity focus error is an index that indicates the degree of reduction in light intensity due to focus deviation of the CCD camera.

[0032] <Signal half width (FWHM)> In the comparative example, when calculating the index of the signal half width, the image in Fig. 6 is used. Fig. 6 is a diagram showing an example of the light intensity distribution in the Y-axis direction at the long wavelength peak (dotted line 504 in Fig. 5). The control unit extracts the half width 502 of the long wavelength peak at the position of each capillary from the upper end (CAP24) to the lower end (CAP1) of the shield array, and outputs an optical index related to the signal half width based on each extracted half width 502.

[0033] <Adjacent capillary noise (stray light)> When irradiating with laser light, if stray light (leakage light) appears in the gaps (corresponding to the valleys of the waveform) between adjacent capillaries arranged in the Y-axis direction, it may affect the signal at the position of the capillary. Therefore, the control unit extracts the light intensity in the gaps 503 between each capillary from the image in Figure 6, and outputs an optical index related to the stray light based on the extracted light intensity.

[0034] <Signal-to-noise ratio (SN ratio)> Unlike the above-mentioned indices, when calculating the signal-to-noise ratio, a capillary array is used, and the control unit calculates an optical index related to the signal-to-noise ratio based on the ratio of the peak light intensity in a bright state when the capillary array is irradiated with a laser beam to the peak light intensity in a dark state when the capillary array is not irradiated with a laser beam.

[0035] <Signal strength deviation correction (Normalization)> Since capillary electrophoresis devices have individual differences in their optical systems, variations occur in the light intensity obtained by the CCD camera when laser light is irradiated by the laser unit 133. Therefore, a constant light intensity is obtained by adjusting the power of the laser unit 133. As with the signal-to-noise ratio, a capillary array is used to obtain the correction value required to normalize the light intensity.

[0036] (Example) In the embodiment, a shield array is not used to diagnose optical performance. Instead, an analytical capillary array 117 (see FIG. 3B) for performing actual electrophoresis is used, and the capillary head 112 is connected to the pump mechanism 103. Furthermore, in the embodiment, the control unit of the capillary electrophoresis device automatically diagnoses optical performance, eliminating the need for manual operation by a service engineer or the like. The trigger for the diagnosis may be input via the input unit when the user of the capillary electrophoresis device is not performing analysis, or may be input from an external monitoring terminal device if the control unit is connected to the terminal device via a network. Furthermore, in the diagnosis according to the embodiment, the control unit automatically identifies the peak of the Raman signal, mainly from one image captured by a CCD camera, and extracts its coordinates, light intensity, etc., thereby outputting each optical indicator in a single batch processing. Each optical indicator will be described in detail below.

[0037] <Coaxiality of upper and lower beams (Laser Beam Overlapping)> In the embodiment, a CCD camera captures a single common image of the combined Raman scattered light generated when laser light is simultaneously irradiated from above and below the capillary array. FIG. 7 is a conceptual diagram showing the light intensity waveforms of the upper and lower beams and their combined waveform. FIG. 8 is a diagram showing an example of an image acquired when the upper and lower beams are irradiated onto the capillary array. FIG. 9 is a diagram showing an example of the signal intensity distribution at the center of the top and bottom of the capillary array when the upper and lower beams are irradiated. In FIGS. 8 and 9, the horizontal axis (X-axis) indicates the wavelength information of the Raman scattered light generated when the base sequence of the DNA sample is irradiated with laser light, with the left side of the X-axis representing the shorter wavelength side and the right side of the X-axis representing the longer wavelength side. In addition, the vertical axis (Y-axis) in FIG. 8 indicates the position information of the capillary.

[0038] As shown in Figure 7, one image captured by the CCD camera contains a composite waveform 603, which is a combination of a light intensity waveform 601 of the upper beam and a light intensity waveform 602 of the lower beam. When the optical axes of the upper and lower beams are misaligned, the peak value of the composite waveform decreases and the half-width of the peak increases compared to when there is no misalignment.

[0039] Therefore, the control unit identifies a long wavelength peak 705 at the center (CAP12) of the top and bottom of the capillary array in one image shown in Fig. 8 by image processing, and extracts a half width 702 of the long wavelength peak 705 as shown in Fig. 9. Furthermore, the control unit compares the extracted half width 702 with a reference value stored in advance in the storage unit, thereby outputting an optical index related to the coaxiality of the top and bottom beams.

[0040] Although the advantage of this method is that the light intensity is higher on the long wavelength side than on the short wavelength side, it is easier to identify the half-width. Alternatively, the coaxiality index may be calculated by extracting the half-width 703 of the short wavelength peak 706 and comparing it with a reference value for short wavelengths. The index may also be calculated using both the long wavelength peak 705 and the short wavelength peak 706. Since the light intensity may change due to focal shift, a correction coefficient may be applied to the half-width to account for focal shift. Furthermore, the control unit may identify a predetermined absolute value (e.g., peak value) other than the half-width from the composite waveform included in one image and compare that absolute value with a predetermined reference value to calculate the index. In any case, since the reference value is compared with an absolute value detected using an actual capillary array, rather than a relative value detected using a shield array as in the comparative example, a highly accurate index can be calculated.

[0041] <Grating Rotation Angle> The control unit uses image processing to identify the long-wavelength peak and the short-wavelength peak at the end of the capillary array (CAP1 or CAP24) in an image such as that shown in Figure 8, and calculates the Y-coordinate shift of each peak. Furthermore, the control unit outputs an optical index related to the horizontal rotation angle of the spectrometer 132 and the CCD camera based on the calculated shift. This optical index is calculated based on an absolute value detected using a capillary array actually used for electrophoresis, and therefore is a more accurate index than the comparative example.

[0042] <Vertical rotation angle (CCD rotation angle)> The control unit uses image processing to identify the short wavelength peak at the upper end (CAP24) of the capillary array and the short wavelength peak at the lower end (CAP1) of the capillary array in an image such as that shown in Fig. 8. Furthermore, the control unit calculates the X-coordinate shift of each identified peak and outputs optical indices related to the vertical rotation angle of the spectrometer 132 and the CCD camera based on the calculated shift. Because this optical indices is calculated based on absolute values ​​detected using a capillary array actually used for electrophoresis, it is an index with higher accuracy than the comparative example.

[0043] <Vertical direction error (Upper / Lower Location)> The control unit uses image processing to identify the position of the upper end (CAP24) of the capillary array and the position of the lower end (CAP1) of the capillary array in one image such as that shown in Fig. 8. Furthermore, the control unit calculates the distance from the upper edge of the field of view to the upper end of the capillary array (Upper Location) and the distance from the lower edge of the field of view to the lower end of the capillary array (Lower Location), and outputs an optical index related to vertical direction error based on the calculated values. This optical index is calculated based on absolute values ​​detected using a capillary array actually used for electrophoresis, and therefore is a more accurate index than the comparative example.

[0044] <Focus & Intensity> In one image such as that shown in Figure 8, the control unit uses image processing to identify the short- and long-wavelength peaks at the top end (CAP24) of the capillary array, the short- and long-wavelength peaks at the center (CAP12) of the capillary array, and the short- and long-wavelength peaks at the bottom end (CAP1) of the capillary array. Furthermore, the control unit outputs an optical index related to the light intensity focus error based on the light intensity at each peak. Because this optical index is calculated based on absolute values ​​detected using a capillary array actually used for electrophoresis, it is a more accurate index than the comparative example.

[0045] <Signal half width (FWHM)> The control unit extracts the half-width of the long wavelength peak at each capillary position from the upper end (CAP24) to the lower end (CAP1) of the capillary array from one image similar to that described above, and outputs an optical index related to the signal half-width based on each extracted half-width. This optical index is calculated based on the absolute value detected using the capillary array actually used for electrophoresis, and therefore is an index with higher accuracy than the comparative example.

[0046] <Adjacent capillary noise (stray light)> The control unit extracts the light intensity in the gap 503 between each capillary from one image similar to that described above, and outputs an optical index related to stray light based on the extracted light intensity. This optical index is calculated based on an absolute value detected using a capillary array actually used for electrophoresis, and therefore is an index with higher accuracy than the comparative example.

[0047] <Signal-to-noise ratio (SN ratio)> The signal-to-noise ratio is calculated basically in the same manner as in the comparative example, but in the embodiment, the following diagnosis is further performed. For example, the control unit divides one image in the bright state into multiple sections in the wavelength direction (X-axis direction), calculates the aggregate light intensity within each section, and calculates the peak aggregate light intensity. Next, the control unit divides one image in the dark state into similar sections and similarly calculates the peak aggregate light intensity. Then, the control unit calculates the signal-to-noise ratio based on the ratio of the peak aggregate light intensities calculated for each state. In this way, dividing the X-axis direction into multiple sections creates a low-pass filter-like effect, making it possible to remove the influence of steep noise. Furthermore, it is possible to calculate an index related to the influence of dark current noise of the CCD camera from the signal intensity of the peak value of the dark state image. Furthermore, it is possible to index the signal variation for each of the multiple sections into which the bright state image is divided.

[0048] <Signal strength deviation correction (Normalization)> The signal intensity deviation correction is performed in the same manner as in the comparative example.

[0049] As described above, in the embodiment, the optical indices of the coaxiality of the upper and lower beams, the horizontal rotation angle, the vertical rotation angle, the vertical direction error, the light intensity focus error, the signal half-width, and the adjacent capillary noise are calculated using the capillary array actually used for analysis. In other words, since all optical indices are absolute indices, accurate optical performance diagnosis and accurate optical adjustment are possible by comparing them with predetermined absolute target values ​​(specifications). Furthermore, the capillary electrophoresis device automatically outputs each optical indices without the need for manual operation by a service engineer or the like, simplifying the diagnosis of optical performance.

[0050] (Variation) The results of the diagnosis by the automatic optical diagnosis function as described above, i.e., each optical index, are stored in the memory unit of the capillary electrophoresis device. Therefore, when a user or a service engineer operates the input unit, the control unit can output the time-series changes in the optical indexes stored in the memory unit to the output unit. The time-series changes in the optical indexes can be used for failure prediction, etc.

[0051] Furthermore, each optical index output by the automatic optical diagnosis function may be continuously transmitted to a monitoring terminal device connected to the control unit via a network, regardless of whether it is within the target value (specification) range, or a notification may be transmitted from the control unit to the monitoring terminal device if it is not within the target value range. If the optical index is not within the target value range, a service engineer or the like will visit the installation site of the capillary electrophoresis device and perform optical adjustments, etc.

[0052] The present invention is not limited to the above-described embodiments and modifications, and various modifications are possible. For example, the control unit may be divided into an operation control unit that controls the operation of each unit of the capillary electrophoresis device, and a diagnosis control unit that diagnoses the optical performance based on a signal from the CCD camera. [Explanation of symbols]

[0053] 101...capillary electrophoresis apparatus, 102...capillary, 103...pump mechanism, 104...high-voltage power supply, 105...array holder, 106...plunger pump, 107...block, 108...check valve, 109...polymer container, 110...anode buffer container, 111...anode electrode, 112...capillary head, 113...motor valve, 114...light irradiation mechanism, 115...two-dimensional detector, 116...detection unit, 117...capillary array, 118...thermostat, 119...fan, 120...heating / cooling mechanism , 121...buffer container, 122...washing container, 123...waste container, 124...sample container, 125...transport mechanism, 126...hollow electrode, 127...capillary cathode end, 128...chamber, 129...load header, 130...moving stage, 131...grip, 132...spectroscope, 133...laser unit, 134...reflection mirror, 135...polarizer, 136...beam splitter, 137...condensing lens, 138...reference base, 139...optical axis, 140...laser light, 141...shield array

Claims

1. a capillary array composed of a plurality of capillaries; a light source that emits laser light; a detector for detecting light emitted when the capillary array is irradiated with laser light; a control unit that performs predetermined processing based on a signal from the detector, the detector captures a common image of the combined Raman scattered light when the laser light is irradiated from above and below the capillary array used for electrophoresis; The control unit calculates an optical index related to the coaxiality of the upper and lower laser beams by comparing the half-width or peak value of the peak extracted from the composite waveform of the Raman scattered light included in the one image with a predetermined reference value.

2. 2. The capillary electrophoresis apparatus according to claim 1, Further provided is a storage unit that stores the optical indicator, The control unit outputs the time-series changes in the optical indices stored in the storage unit.

3. 1. A method for diagnosing optical performance of a capillary electrophoresis device, comprising: a step of acquiring an image captured by a detector when a capillary array used for electrophoresis is mounted and laser light is irradiated from above and below the capillary array; extracting a half-width or a peak value of a peak from a composite waveform of Raman scattered light included in the acquired image; calculating an optical index relating to the coaxiality of the upper and lower laser beams by comparing the extracted half width or the extracted peak value with a predetermined reference value; A method for diagnosing optical performance of a capillary electrophoresis apparatus, comprising:

Images