Capillary electrophoresis device and optical performance diagnosis method thereof

Abstract

The purpose of the present invention is to provide a capillary electrophoresis device capable of confirming optical performance without performing special work, and a method for diagnosing optical performance thereof. To this end, the capillary electrophoresis device according to the present invention comprises: a capillary array comprising a plurality of capillaries; a light source that oscillates the laser light; a detector that detects light emitted when the capillary array is irradiated with laser light; and a control unit that performs a predetermined process on the basis of a signal from the detector, the control unit extracting a predetermined absolute value relating to an optical index on the basis of an image captured by the detector, and calculating the optical index by comparing the extracted absolute value with a predetermined reference value.

Description

Technical Field

[0001] The invention relates to a capillary electrophoresis device and an optical performance diagnosis method thereof. Background Art

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

[0003] Patent Document 1: Japanese Patent Application Publication No. 2007-212449 Summary of the invention Technical problem to be solved by the invention

[0004] However, when confirming the optical performance of the capillary electrophoresis device 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 device and an optical performance diagnosis method thereof that can confirm optical performance without performing special operations. Technical means for solving technical problems

[0006] In order to solve the above-mentioned problems, the capillary electrophoresis device of the present invention includes: a capillary array composed of a plurality of capillaries; a light source for oscillating laser light; a detector for detecting light emitted when the capillary array is irradiated with laser light; and a control unit for performing prescribed processing based on a signal from the detector, wherein the control unit extracts a prescribed 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, a capillary electrophoresis device and an optical property diagnosis method thereof can be provided, which can confirm optical properties without performing special operations. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 is a schematic diagram of the capillary electrophoresis apparatus. Figure 2 FIG. 1 is a diagram schematically showing the path of laser light in an optical irradiation system of a capillary electrophoresis apparatus. Figure 3A It is a diagram showing a shield array for correction. Figure 3BThis is a diagram showing a capillary array for analysis. Figure 4A FIG. 1 is a diagram showing an example of an image obtained when only the upper beam is irradiated onto the shield array. Figure 4B FIG. 1 is a diagram showing an example of an image obtained when only the lower beam is irradiated onto the shield array. Figure 5 1 is a diagram showing an example of an image obtained when the upper and lower beams are irradiated onto the shield array. Figure 6 is the long wavelength side peak ( Figure 5 Graph of an example of light intensity distribution in the Y-axis direction at the dotted line 504). Figure 7 1 is a conceptual diagram showing the light intensity waveform of the upper light beam, the light intensity waveform of the lower light beam, and their combined waveform. Figure 8 FIG. 1 is a diagram showing an example of an image obtained when the capillary array is irradiated with upper and lower light beams. Fig. 9 This is a diagram showing an example of the distribution of signal intensity at the upper and lower centers of the capillary array when irradiated with upper and lower light beams. DETAILED DESCRIPTION

[0009] use Figure 1 The structure of a capillary electrophoresis device according to an embodiment of the present invention will be described. Figure 1 Schematic diagram of the capillary electrophoresis device of this embodiment. Figure 1 As shown, the capillary electrophoresis device 101 includes a capillary array 117 composed of one or more capillaries 102, a thermostatic bath 118 for maintaining the capillary 102 at a constant temperature, a high voltage power supply 104 for applying voltage to the capillary 102, a pump mechanism 103 for injecting a polymer into the capillary 102, and a conveying mechanism 125. The conveying mechanism 125 is a mechanism for conveying a buffer container 121, a cleaning container 122, a waste liquid container 123, and a sample container 124 to a capillary cathode end 127.

[0010] The capillary array 117 includes a cartridge 129 provided at one end, a capillary head 112 provided at the other end, and a detection unit 116 formed between the cartridge 129 and the capillary head 112 and detecting a sample electrophoresed in the capillary 102. The capillary array 117 is composed of, for example, 24 capillaries 102, and when the measurement method is changed, capillaries having different capillary lengths are replaced. In addition, when a capillary 102 is found to be damaged or deteriorated in quality, it is also replaced with a new capillary array 117.

[0011] The capillary 102 is formed of a glass tube with an inner diameter of 50 μm and an outer diameter of 320 μm, and the surface is coated with polyimide to improve strength. However, in the capillary 102, the polyimide coating is removed from the detection unit 116 irradiated by the laser, so that the internal light emission is easily leaked to the outside. The interior of the capillary 102 is filled with a separation medium for providing a migration difference during electrophoresis by a pump mechanism 103. In this embodiment, a high viscosity solution, i.e., a polymer, is used as the separation medium.

[0012] The capillary cathode end 127 is fixed by a metal hollow electrode 126, and the front end of the capillary 102 protrudes about 0.5 mm from the hollow electrode 126. In addition, all the hollow electrodes 126 installed on each capillary 102 are integrally installed on the clamp 129. Moreover, all the hollow electrodes 126 are connected to the high-voltage power supply 104 mounted on the device body, and operate as cathode electrodes when a voltage such as electrophoresis or sample introduction is applied.

[0013] The capillary end on the opposite side to the capillary cathode end 127 is bound and bonded together by a capillary head 112. The capillary head 112 is connected to the block 107 in a pressure-tight manner. Then, a new polymer is filled in the capillary 102 by the pump mechanism 103. In order to improve the performance of the measurement, the capillary 102 is refilled with the polymer in each measurement.

[0014] The optical system is composed of a light irradiation mechanism 114 for irradiating the detection section 116, an array holder 105 for holding the detection section 116, a spectrometer 132 for splitting the light emitted in the detection section 116 into each wavelength, and a two-dimensional detector 115 for detecting the split light. When detecting a sample in the capillary 102 separated by electrophoresis, the detection section 116 is irradiated by the light irradiation mechanism 114, the light emitted from the detection section 116 is split 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 sends the detected image data to a control section (not shown).

[0015] The control unit controls the operation of the high voltage power supply 104, etc., or calculates the analysis result of the sample based on the signal detected by the two-dimensional detector 115. In addition, the control unit is connected to an input unit for inputting settings, an output unit for displaying analysis results, etc., and a storage unit for storing analysis results, etc. (none of which is shown in the figure).

[0016] The constant temperature bath 118 is covered with a heat insulating material, and the interior thereof is controlled at a constant temperature by a heating and cooling mechanism 120. In addition, a fan 119 circulates and stirs the air in the constant temperature bath 118, thereby maintaining the temperature of the capillary array 117 uniform and constant.

[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. A flow path is provided in the block 107 to connect the plunger pump 106, the polymer container 109, the anode buffer container 110, and the capillary array 117. In the flow path between the plunger pump 106 and the polymer container 109, a check valve 108 is provided to prevent the polymer from flowing back. In the flow path between the block 107 and the anode buffer container 110, an electric valve 113 is provided. When the polymer is filled into the chamber 128 of the plunger pump 106 and the capillary array 117, the electric valve 113 is closed to prevent the buffer from flowing into the anode buffer container 110. When electrophoresis is performed, the electric valve 113 is opened, and the anode electrode 111 and the capillary cathode 127 are energized.

[0018] The conveying mechanism 125 has three motors and linear actuators (not shown) and can move on three axes of up and down, left and right, and depth. In addition, more than one container can be placed on the moving table 130 of the conveying mechanism 125. Moreover, the moving table 130 is provided with an electric handle 131, which can grasp or release each container. Therefore, the buffer container 121, the cleaning container 122, the waste liquid container 123, and the sample container 124 can be conveyed to the clamping head 129 as needed. Unnecessary containers are stored in a specified storage position in the device.

[0019] Figure 2 1 is a diagram schematically showing the path of laser light in the optical irradiation system of the capillary electrophoresis device according to the present embodiment. The light irradiation mechanism 114 in the present embodiment includes: a laser unit 133, which is a light source for oscillating laser light 140; a beam splitter 136, which splits the laser light 140 into two; a reflector 134, which changes the path of the laser light 140; and a focusing lens 137, which focuses the laser light 140. A polarizing plate 135, which is an optical element that transmits only polarized light in one direction, is inserted in the optical path from the laser unit 133 to the beam splitter 136. One of the laser light 140 split by the beam splitter 136 is guided to the lower side of the capillary array by the reflector 134, and the other is guided to the upper side of the capillary array by the reflector 134. Then, each laser beam 140 is focused by the focusing lens 137 and enters the capillary array from the upper end or the lower end, and the fluorescence emitted from the detection section 116 of each capillary 102 is detected by the two-dimensional detector 115. The following description assumes that a CCD camera is used as the two-dimensional detector 115.

[0020] In addition, although Figure 2102, but in this embodiment, the capillary array is composed of 24 capillaries 102, and each capillary 102 is arranged and fixed on the reference base 138 in the detection unit 116. In this specification, the imaginary straight line perpendicular to each capillary axis in the imaginary plane formed by the central axis (capillary axis) of each capillary on the reference base 138 is called the optical axis 139. In this embodiment, the capillary array is composed of 24 capillaries 102, and the first capillary from the bottom is marked as CAP1, and the 24th capillary from the bottom (the first capillary from the top) is marked as CAP24, but the number of capillaries 102 is not limited to 24.

[0021] Here, the optical performance of the capillary electrophoresis device depends on the position accuracy of the optical axis of the laser, the position accuracy of the CCD camera, the focus accuracy, etc. The optical performance before shipment is adjusted in the manufacturing process, but after shipment, the optical performance needs to be confirmed regularly or when the capillary array is replaced, and adjusted as needed. The following describes a method for diagnosing the optical performance of the capillary electrophoresis device involved in this embodiment. Before describing the embodiments of the present invention, a comparative example is first described.

[0022] (Comparative Example) In the comparative example, in the diagnosis of optical performance, the Figure 3A The shield array 141 is used for correction. The shield array 141 and Figure 3B The analytical capillary array 117 shown is different in that no voltage for electrophoresis is applied and no DNA is put in. The shield array 141 seals both ends of the capillary, which is filled with a polymer solution (EG: ethylene glycol / Urea: urea) and cut into a length that is easy to handle (about 20 cm).

[0023] In the comparative example, after the capillary electrophoresis device leaves the factory, the optical performance is mainly diagnosed by the service engineer using the shielding array 141. When the service engineer sets the shielding array 141 in the array bracket 105 and irradiates the polymer solution (EG / UREA) filled in each capillary with laser, a Raman signal is obtained. The service engineer uses dedicated software to visually determine the peak value of the Raman signal contained in the camera image obtained by the CCD camera. Since the optical performance includes multiple indicators, the service engineer needs to obtain an image through the CCD camera for each indicator and manually read the required value. The read value is sent to the control unit, which calculates the optical indicator.

[0024] Here, in the comparative example, the image captured by the CCD camera does not contain the actual capillary array, but contains a pseudo signal based on the shielding array that imitates the capillary array, so the calculated optical index is relative. Therefore, the service engineer determines whether the calculated optical index is within the predetermined target value (specification) for the shielding array, and adjusts the optical axis of the laser, the position of the CCD camera, etc. as needed. After the optical diagnosis is completed, the service engineer removes the calibration shielding array from the capillary electrophoresis device and installs the analytical capillary array used for actual electrophoresis on the capillary electrophoresis device.

[0025] The diagnostic method of the comparative example performed by the service engineer is described in detail below for each optical index.

[0026] <Laser Beam Over lapping> As described above, in the capillary electrophoresis device of the present embodiment, laser is irradiated from the top and bottom of the capillary array. The laser irradiated to the capillary array from the upper side is called the upper beam, and the laser irradiated to the capillary array from the lower side is called the lower beam. In the comparative example, the coaxiality of the optical axis of the upper beam and the optical axis of the lower beam are calculated using the image of the Raman scattered light obtained when only the upper beam is irradiated and the image of the Raman scattered light obtained when only the lower beam is irradiated. Here, in the case of irradiating only the upper beam for shooting, the service engineer or the like sets a shading plate on the optical path of the lower beam, and the CCD camera is used to shoot. In the case of irradiating only the lower beam for shooting, the service engineer or the like sets a shading plate on the optical path of the upper beam, and the CCD camera is used to shoot.

[0027] Figure 4A is a diagram showing an example of an image obtained when only the upper beam is irradiated onto the shield array, Figure 4B is a diagram showing an example of an image obtained when only the lower beam is irradiated to the shield array. Figure 4A In the process, the short wavelength side peak 302 at the upper and lower center of the shielding array is determined while visually confirming, and Figure 4B In the process, the short-wavelength side peak 305 at the upper and lower centers of the shield array is determined while visually checking. Then, the control unit extracts the X coordinate of the peak 302 when only the upper beam 301 is irradiated and the X coordinate of the peak 305 when only the 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. When the output optical index is not within the range of the specified target value, that is, when the deviation between the optical axis of the upper beam and the optical axis of the lower beam is larger than the specification, the service engineer or the like adjusts the optical axis of the laser.

[0028] <Grating Rotation Angle> In the comparative example, when calculating the index of the horizontal rotation angle, a new single image is used, different from the two images used in calculating the index of the coaxiality of the upper and lower light beams. Figure 5 is a diagram showing an example of an image obtained when the upper and lower beams are irradiated to the shield array. Figure 5 The long wavelength side peak and the short wavelength side peak of the end (CAP1 or CAP24) of the shield array are determined while visually checking the captured image shown. Then, the control unit calculates ( Figure 5 The deviation of the Y coordinate of the dotted line 401 is calculated, and the optical index related to the horizontal rotation angle of the spectrometer 132 and the CCD camera is output according to the calculated deviation. When the output optical index is not within the range of the specified target value, that is, when the horizontal rotation angle is larger than the specification, the service engineer or the like adjusts the position of the spectrometer 132.

[0029] <Vertical rotation angle (CCD Rotation Angle)> In the comparative example, when calculating the index of the vertical rotation angle, Figure 5 The service engineer is waiting at Figure 5 The short-wavelength side peak of the upper end (CAP24) of the shield array and the short-wavelength side peak of the lower end (CAP1) of the shield array are determined while visually checking the captured image shown. Then, the control unit calculates ( Figure 5 The calculated deviation is used to calculate the deviation of the X coordinate of the beam splitter 132 and the vertical rotation angle of the CCD camera. When the output optical index is not within the range of the specified target value, that is, when the vertical rotation angle is larger than the specification, the service engineer or the like adjusts the position of the CCD camera.

[0030] <Vertical Error(Upper / Lower Location)> In the comparative example, when calculating the index of vertical error, Figure 5 The service engineer is waiting at Figure 5 The position of the upper end (CAP24) and the lower end (CAP1) of the shield array are determined while visually checking the captured image shown. Then, the control unit calculates the distance 404 (Upper Location) from the corner end of the upper figure to the upper end of the shield array and the distance 405 (Lower Location) from the corner end of the lower figure 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> In the comparative example, when calculating the index of light intensity focus error, Figure 5 The service engineer is waiting at Figure 5 On the captured image shown, the short wavelength side peak (501a) and the long wavelength side peak (501b) at the upper end (CAP24) of the shielding array, the short wavelength side peak (501c) and the long wavelength side peak (501d) at the center (CAP12) of the shielding array, and the short wavelength side peak (501e) and the long wavelength side peak (501f) at the lower end (CAP1) of the shielding array are determined while visually confirming. Then, the control unit outputs an optical index related to the light intensity focus error based on the light intensity at each peak. The light intensity focus error is an index indicating the degree of reduction in light intensity (Intensity) caused by the focus offset of the CCD camera.

[0032] <Signal Half Width (FWHM)> In the comparative example, the half-value width of the signal is also calculated using Figure 6 of the image. Figure 6 is the long wavelength side peak ( Figure 5 The control unit extracts the half-value width 502 of the long-wavelength side 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 half-value width of the signal based on each extracted half-value width 502.

[0033] <Adjacent capillary noise (stray light)> During laser irradiation, if stray light (leakage light) appears in the gap between adjacent capillaries arranged along the Y-axis direction (corresponding to the valley portion of the waveform), it may affect the signal at the capillary position. Figure 6 The light intensity in the gap 503 between each capillary is extracted from the image, and an optical index related to stray light is output according to the extracted light intensity.

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

[0035] <Signal Strength Deviation Correction (Normalization)> Since there are individual differences in the optical system of the capillary electrophoresis device, the light intensity obtained by the CCD camera when the laser unit 133 irradiates the laser light has deviations. Therefore, a constant light intensity can be obtained by adjusting the power of the laser unit 133. The correction value required to normalize the light intensity is the same as the signal-to-noise ratio, and the capillary array is used.

[0036] (Example) In the embodiment, in the diagnosis of optical properties, a shielding array is not used, and a capillary array 117 (see FIG. Figure 3B ), the capillary head 112 is connected to the pump mechanism 103. In addition, in the embodiment, there is no need for manual operation by a service engineer or the like, and the control unit of the capillary electrophoresis device automatically diagnoses the optical performance. The diagnosis trigger can be indicated by the input unit when the user of the capillary electrophoresis device is not analyzing, or can be indicated by the terminal device when the control unit is connected to an external monitoring terminal device via a network. Moreover, in the diagnosis of the embodiment, the control unit automatically determines the peak of the Raman signal from a main image taken by the CCD camera, extracts its coordinates, light intensity, etc., and outputs each optical index through a batch process. The optical index is described in detail below.

[0037] <Laser Beam Over lapping> In the embodiment, the CCD camera captures, as a single common image, Raman scattered light synthesized when laser light is irradiated from the top and bottom of the capillary array simultaneously. Figure 7 1 is a conceptual diagram showing the light intensity waveform of the upper light beam, the light intensity waveform of the lower light beam, and their combined waveform. Figure 8 FIG. 1 is a diagram showing an example of an image acquired when the capillary array is irradiated with upper and lower light beams. Fig. 9 : is a diagram showing an example of the distribution of signal intensity at the upper and lower centers of the capillary array when the upper and lower light beams are irradiated. Figure 8 and Fig. 9 In the figure, the horizontal axis (X axis) represents the wavelength information of the Raman scattered light when the base sequence of the DNA of the sample is irradiated with laser, the left side of the X axis is the short wavelength side, and the right side of the X axis is the long wavelength side. Figure 8 The vertical axis (Y-axis) direction in represents the position information of the capillary.

[0038] like Figure 7 As shown, one image captured by the CCD camera includes a synthesized waveform 603 that synthesizes the light intensity waveform 601 of the upper light beam and the light intensity waveform 602 of the lower light beam. When the optical axis of the upper light beam deviates from the optical axis of the lower light beam, the peak value of the synthesized waveform decreases and the half-value width of the peak increases compared to the case where there is no deviation.

[0039] Therefore, in Figure 8 In an image shown in FIG. 1 , the control unit determines the long wavelength side peak 705 at the upper and lower centers (CAP12) of the capillary array through image processing, as shown in FIG. Fig. 9 As shown, the half-value width 702 at the long-wavelength side peak 705 is extracted. Then, the control unit compares the extracted half-value width 702 with a reference value pre-stored in the storage unit, and outputs an optical index related to the coaxiality of the upper and lower beams.

[0040] Since the light intensity on the long wavelength side is higher than that on the short wavelength side, it has the advantage of being easy to determine the half-value width, but the coaxiality index can also be calculated by extracting the half-value width 703 of the short wavelength side peak 706 and comparing it with the reference value for the short wavelength. In addition, the index can be calculated using both the long wavelength side peak 705 and the short wavelength side peak 706. Since the light intensity changes due to the influence of focus shift can also be considered, it is also possible to assume that the focus shift is given a correction coefficient for the half-value width. In addition, the control unit can also determine a specified absolute value (such as a peak value) other than the half-value width based on the synthetic waveform contained in one image, and calculate the index by comparing the absolute value with a predetermined reference value. In either case, since the absolute value detected using the actual capillary array is compared with the reference value instead of the relative value detected using the shielding array as in the comparative example, a higher-precision index can be calculated.

[0041] <Grating Rotation Angle> Control Department Figure 8 In the one image shown, the long-wavelength side peak and the short-wavelength side peak of the end (CAP1 or CAP24) of the capillary array are determined by image processing, and the deviation of the Y coordinate of each peak is calculated. In addition, 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 deviation. This optical index is calculated based on the absolute value detected by the capillary array actually used in electrophoresis, and thus becomes an index with higher accuracy than the case of the comparative example.

[0042] <Vertical rotation angle (CCD Rotation Angle)> exist Figure 8In one of the images shown, the control unit determines the short-wavelength side peak at the upper end (CAP24) of the capillary array and the short-wavelength side peak at the lower end (CAP1) of the capillary array by image processing. In addition, the control unit calculates the deviation of the X coordinates of each determined peak, and outputs an optical index related to the vertical rotation angle of the spectrometer 132 and the CCD camera based on the calculated deviation. This optical index is calculated based on the absolute value detected using the capillary array actually used in electrophoresis, and thus becomes a more accurate index than the case of the comparative example.

[0043] <Vertical Error(Upper / Lower Location)> exist Figure 8 In one of the images shown, the control unit determines the position of the upper end (CAP24) of the capillary array and the position of the lower end (CAP1) of the capillary array by image processing. Furthermore, the control unit calculates the distance from the corner end in the upper figure to the upper end of the capillary array (Upper Location) and the distance from the corner end in the lower figure to the lower end of the capillary array (Lower Location), and outputs an optical index related to the vertical direction error based on the calculated values. This optical index is calculated based on the absolute value detected using the capillary array actually used in electrophoresis, and thus becomes an index with higher accuracy than the case of the comparative example.

[0044] <Focus & Intensity> exist Figure 8 In one image shown, the control unit determines the short-wavelength side peak and the long-wavelength side peak at the upper end (CAP24) of the capillary array, the short-wavelength side peak and the long-wavelength side peak at the center (CAP12) of the capillary array, and the short-wavelength side peak and the long-wavelength side peak at the lower end (CAP1) of the capillary array through image processing. In addition, the control unit outputs an optical index related to the light intensity focus error based on the light intensity at each peak. This optical index is calculated based on the absolute value detected using the capillary array actually used in electrophoresis, and thus becomes an index with higher accuracy than the case of the comparative example.

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

[0046] <Adjacent capillary noise (stray light)> The control unit extracts the light intensity in the gap 503 between each capillary from the same image as above, and outputs an optical index related to stray light based on the extracted light intensity. This optical index is calculated based on the absolute value detected using the capillary array actually used in electrophoresis, and thus is a more accurate index than the comparative example.

[0047] <Signal-to-Noise Ratio (SN Ratio)> When calculating the signal-to-noise ratio, it is basically the same as the comparative example, but in the embodiment, the following diagnosis is further performed. For example, the control unit divides an image in a bright state into multiple intervals in the wavelength direction (X-axis direction), calculates the collective light intensity in each interval, and calculates the peak collective light intensity. Next, the control unit divides an image in a dark state into the same intervals, and calculates the peak collective light intensity in the same way. Then, the control unit calculates the signal-to-noise ratio based on the ratio of the peak collective light intensities calculated for each state. Thus, by dividing the X-axis direction into multiple intervals, a low-pass filter-like effect is generated, and the influence of sharp noise can be removed. In addition, based on the signal intensity of the peak value of the image in the dark state, an index related to the influence of the dark current noise of the CCD camera can also be calculated. Moreover, each signal deviation of the multiple intervals of the image divided into the bright state can also be indexed.

[0048] <Signal Strength Deviation Correction (Normalization)> Signal intensity deviation correction was performed in the same manner as in the comparative example.

[0049] As described above, in the embodiment, the capillary array used in the actual analysis is used to calculate the coaxiality of the upper and lower light beams, the horizontal rotation angle, the vertical rotation angle, the vertical direction error, the light intensity focus error, the signal half-value width, and the adjacent capillary noise. That is, since all optical indices are absolute indices, accurate optical performance diagnosis and accurate optical adjustment can be performed by comparing with the predetermined absolute target value (specification). In addition, even if the service engineer does not operate manually, the capillary electrophoresis device will automatically output each optical index, so the diagnosis of optical performance becomes simple.

[0050] (Variation Example) The results of the diagnosis by the automatic optical diagnosis function as described above, i.e., the optical indexes, are accumulated in the storage unit of the capillary electrophoresis device. Therefore, the control unit can also output the time series changes of the optical indexes stored in the storage unit to the output unit through the operation of the input unit of the user or the service engineer. The time series changes of the optical indexes can be used for fault prediction, etc.

[0051] In addition, each optical index output by the automatic optical diagnosis function can be continuously sent to the monitoring terminal device connected to the control unit via the network regardless of whether it is within the target value (specification) range, and a notification can be sent from the control unit to the monitoring terminal device when it is not within the target value range. When the optical index is not within the target value range, a service engineer or the like goes to the installation site of the capillary electrophoresis device to perform optical adjustments, etc.

[0052] The present invention is not limited to the above-mentioned embodiments and variations, and various variations are possible. For example, the control unit may be divided into an action control unit for controlling the actions of various parts of the capillary electrophoresis device and a diagnosis control unit for diagnosing optical performance based on signals from a CCD camera. Description of symbols

[0053] 101 ...capillary electrophoresis device, 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 ...electric valve, 114 ...light irradiation mechanism, 115 ...two-dimensional detector, 116 ...detection unit, 117 ...capillary array, 118 ...constant temperature bath, 119 ...fan, 120 ...heating and cooling machine structure, 121... buffer container, 122... cleaning container, 123... waste liquid container, 124... sample container, 125... conveying mechanism, 126... hollow electrode, 127... capillary cathode, 128... chamber, 129... loading head, 130... moving stage, 131... handle, 132... beam splitter, 133... laser unit, 134... reflecting mirror, 135... polarizer, 136... beam splitter, 137... focusing lens, 138... reference base, 139... optical axis, 140... laser, 141... shielding array.

Claims

1. A capillary electrophoresis device, comprising: A capillary array composed of a plurality of capillaries; a light source to cause the laser to oscillate; a detector for detecting light emitted when laser light is irradiated onto the capillary array; as well as The capillary electrophoresis device is characterized in that the control unit performs a predetermined process based on the signal from the detector. The control unit extracts a predetermined absolute value related to an optical index based on the image captured by the detector, and calculates the optical index by comparing the extracted absolute value with a predetermined reference value.

2. The capillary electrophoresis device according to claim 1, characterized in that: The detector uses a common image to capture Raman scattered light synthesized when the laser is irradiated from above and below the capillary array. The control unit extracts a predetermined absolute value from a composite waveform of Raman scattered light included in the one image, and calculates an optical index related to the coaxiality of the upper and lower laser beams by comparing the absolute value with the reference value.

3. The capillary electrophoresis device according to claim 2, characterized in that: The control unit extracts a half-value width of a peak included in the synthesized waveform, and calculates an optical index related to the coaxiality of the upper and lower laser beams by comparing the extracted half-value width with a reference value.

4. The capillary electrophoresis device according to claim 1, characterized in that: It also includes a storage unit for storing the optical index. The control unit outputs the time-series change of the optical index stored in the storage unit.

5. A method for diagnosing the optical performance of a capillary electrophoresis device, which is a method for diagnosing the optical performance of a capillary electrophoresis device, characterized in that: include: A step of acquiring an image captured by a detector in a state where the capillary array for electrophoresis is mounted; A step of extracting a prescribed absolute value related to the optical index based on the acquired image; as well as A step of calculating an optical index by comparing the extracted absolute value with a predetermined reference value.

Images