CAPILLAR ELECTROPHORESIS DEVICE AND OPTICAL POWER DIAGNOSTIC METHOD FOR THE SAME

Abstract

An object of the present invention is to provide a capillary electrophoresis device and an optical power diagnostic method for the same, capable of verifying optical power without requiring any specific action. Accordingly, the capillary electrophoresis device according to the present invention comprises a capillary arrangement containing a plurality of capillaries, a light source that causes laser light to oscillate, a detection unit that detects light emitted when the capillary arrangement is irradiated with the laser light, and a control unit that performs predetermined processing based on a signal emanating from the detection unit.The control unit also extracts a predetermined absolute value with respect to an optical index based on an image captured by the detection unit and calculates the optical index by comparing the extracted absolute value with a predetermined reference value.

Description

Technical area

[0001] The present invention relates to a capillary electrophoresis apparatus and an optical performance diagnostic method for the same. State of the art

[0002] Capillary electrophoresis devices are widely used as devices for analyzing DNA base sequences or base lengths. In any capillary electrophoresis device, there is a possibility that the positional relationship of an optical system may shift when a capillary assembly is replaced. Therefore, for example, as described in Patent Literature 1, a technique is known in which data obtained by electrophoresis is normalized using wavelength calibration data obtained before shipment. Literature listPatent literature

[0003] Patent Literature 1: Japanese Patent Application Laid-Open No. 2007-212449 Summary of the inventionTechnical problem

[0004] However, checking the optical performance of a capillary electrophoresis device after shipment still requires manual operation by a service technician or the like.

[0005] An object of the present invention is to provide a capillary electrophoresis apparatus and an optical performance diagnostic method for the same, which are capable of checking an optical performance without having to perform a special operation. Solution to the problem

[0006] To solve the above-described problem, a capillary electrophoresis apparatus according to the present invention includes a capillary array including a plurality of capillaries, a light source that causes laser light to oscillate, a detection unit that detects light emitted when the capillary array is irradiated with the laser light, and a control unit that performs predetermined processing based on a signal output from the detection unit. The control unit extracts a predetermined absolute value related to an optical index based on an image captured by the detection unit and calculates the optical index by comparing the extracted absolute value with a predetermined reference value. Advantageous effects of the invention

[0007] According to the present invention, it is possible to provide a capillary electrophoresis apparatus and an optical performance diagnosis method for the same capable of checking an optical performance without performing a special operation. Brief description of the drawings Fig. Figure 1 is a schematic representation of a capillary electrophoresis apparatus. Fig. 2 is a schematic diagram illustrating a laser light path in an optical irradiation system of the capillary electrophoresis apparatus. Fig. Figure 3A is a schematic diagram illustrating a calibration shield assembly. Fig. Figure 3B is a schematic diagram illustrating an analysis capillary arrangement. Fig. 4A is a schematic diagram illustrating an example of an image acquired when the shielding assembly is irradiated with only an upper beam. Fig. Figure 4B is a schematic diagram illustrating an example of an image acquired when the shielding assembly is irradiated with only a lower beam. Fig. 5 is a schematic diagram illustrating an example of an image acquired when the shielding assembly is irradiated with the upper and lower beams. Fig. Figure 6 is a schematic diagram showing an example of a light intensity distribution of long wave peaks (dashed line 504 in Fig. 5) in a Y-axis direction. Fig. 7 is a conceptual schematic diagram illustrating a light intensity waveform of the upper beam, a light intensity waveform of the lower beam, and a combined waveform of the upper and lower beams. Fig. 8 is a schematic diagram illustrating an example of an image acquired when the capillary array is irradiated with the upper and lower beams. Fig. 9 is a schematic diagram illustrating an example of a signal intensity distribution of the center of the capillary array in a vertical direction when the capillary array is irradiated with the upper and lower beams. Description of the embodiments

[0008] A configuration of a capillary electrophoresis apparatus according to an embodiment of the present invention will be described with reference to Fig. 1. Here, Fig. 1 is a schematic diagram of the capillary electrophoresis apparatus according to the present embodiment. As shown in Fig. As illustrated in Figure 1, the capillary electrophoresis apparatus 101 includes a capillary assembly 117 containing one or more capillaries 102, a constant-temperature 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 pumping mechanism 103 that injects polymer into the capillaries 102, and a conveying mechanism 125. The conveying mechanism 125 is a mechanism that conveys a buffer container 121, a cleaning container 122, a waste liquid container 123, and a sample container 124 to capillary cathode ends 127.

[0009] The capillary array 117 further includes a loading head 129 provided at one end, a capillary head 112 provided at the other end, and a detection unit 116 formed between the loading head 129 and the capillary head 112, which detects sample electrophoresis in the capillaries 102. When the capillary array 117 includes, for example, 24 capillaries 102 and a measurement method is changed, the capillary array 117 is replaced with one having a different capillary length. Furthermore, even if a capillary 102 is damaged or deteriorates, it is replaced with a new capillary array 117.

[0010] The capillaries 102 are formed from glass tubes with an inner diameter of 50 µm and an outer diameter of 320 µm, and their surfaces are coated with polyimide to improve their strength. However, the polyimide coating is removed from the capillaries 102 at the detection unit 116, which is irradiated with laser light, so that light emitted from the inside easily leaks out. The inside of each of the capillaries 102 is also filled with a separation medium by a pumping mechanism 103 to provide a migration difference during electrophoresis. Hereinafter, in the present embodiment, a polymer, which is a highly viscous solution, is used as the separation medium.

[0011] The capillary cathode ends 127 are fixed by hollow metal electrodes 126, and tips of the capillaries 102 protrude approximately 0.5 mm from the hollow electrodes 126. Moreover, the hollow electrodes 126 provided for each of the capillaries 102 are all integrally attached to the charging head 129. Furthermore, all the hollow electrodes 126 are electrically connected to the high-voltage power supply 104 mounted on a main body of the device and function as cathode electrodes when a voltage is applied, such as during electrophoresis or sample introduction.

[0012] Capillary end sections located opposite the capillary cathode ends 127 are further bundled and connected to each other by the capillary head 112. For this purpose, the capillary head 112 is connected to a block 107 in a pressure-tight and airtight manner. Furthermore, the capillaries 102 are filled with new polymer by the pump mechanism 103. The refilling of polymer into the capillaries 102 is performed for each measurement to improve the measurement performance.

[0013] An optical system also includes 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 light emitted in the detection unit 116 into wavelengths, and a secondary detection unit 115 that detects the separated light. To detect a sample in the capillaries 102 that has been separated by electrophoresis, the light irradiation mechanism 114 irradiates the detection unit 116, the spectrometer 132 separates light emitted by the detection unit 116, and the secondary detection unit 115 detects the sample. The secondary detection unit 115 is embodied, for example, as a CCD camera and transmits detected image data to a control unit (not shown).

[0014] The control unit itself further controls the operation of the high-voltage power supply 104 and the like, and calculates the sample analysis results based on a signal detected by the secondary detection unit 115. Furthermore, the control unit is connected to an input unit for inputting settings and the like, an output unit for displaying the analysis results and the like, and a storage unit for storing the analysis results and the like (the units are not shown).

[0015] The constant-temperature bath 118 is covered with a heat-insulating material, and the inside of the constant-temperature bath 118 is controlled to a set temperature by a heating and cooling mechanism 120. Furthermore, a fan 119 circulates and moves air in the constant-temperature bath 118 to keep the temperature of the capillary assembly 117 uniform and constant.

[0016] The pumping mechanism 103 further includes a piston pump 106, the block 107, a check valve 108, an electric valve 113, a polymer tank 109, and an anode buffer tank 110. The block 107 is provided with a flow path that connects the piston pump 106, the polymer tank 109, the anode buffer tank 110, and the capillary assembly 117. Furthermore, the check valve 108 is provided in a flow path between the piston pump 106 and the polymer tank 109, preventing a corresponding polymer from flowing back. Furthermore, the electric valve 113 is provided in a flow path between the block 107 and the anode buffer tank 110. In order to fill a chamber 128 of the piston pump 106 and the capillary arrangement 117 with polymer, the electric valve 113 is closed, preventing a buffer solution from the anode buffer container 110 from flowing into them.To perform electrophoresis, the electric valve 113 is also opened and an anode electrode 111 and the capillary cathode ends 127 are supplied with energy.

[0017] The conveying mechanism 125 further includes three electric motors and a linear actuator (not shown) and is capable of moving in three axes: vertical, horizontal, and depth. Furthermore, one or more containers can be placed on a moving stage 130 of the conveying mechanism 125. Furthermore, the moving stage 130 is provided with an electric handle 131 that can grip and release each container. Therefore, it is possible to convey the buffer container 121, the cleaning container 122, the waste liquid container 123, and the sample container 124 to the loading head 129 as needed. An unused container can also be stored in a designated storage space within the device.

[0018] Fig. Figure 2 is a schematic diagram illustrating a laser light path in an optical irradiation system of the capillary electrophoresis apparatus according to the present embodiment. The light irradiation mechanism 114 according to the present embodiment includes a laser unit 133, which is a light source that causes laser light 140 to oscillate, a beam splitter 136 that splits the laser light 140 into two beams, a reflecting mirror 134 that changes the path of the laser light 140, and a condenser lens 137 that condenses the laser light 140. A polarizer 135, which is an optical element that transmits light polarized in only one direction, is also inserted into an optical path between the laser unit 133 and the beam splitter 136.Here, one of the beams of laser light 140 split by the beam splitter 136 is directed to the bottom of the capillary array by the reflecting mirror 134, and the other is directed to the top of the capillary array by the reflecting mirror 134. Further, after each of the beams of laser light 140 is condensed by the condenser lens 137, the beam enters the capillary array from an upper or lower end, and fluorescence emitted from the detection unit 116 of each of the capillaries 102 is detected by the secondary detection unit 115. The following description assumes a case where a CCD camera is used as the secondary detection unit 115.

[0019] Although Fig. While only 5 capillaries 102 are illustrated in FIG. 2, the capillary array actually includes 24 capillaries 102, and each of the capillaries 102 is fixed side by side along a reference base 138 in the detection unit 116 in the present embodiment. Furthermore, in this specification, a virtual straight line orthogonal to each capillary axis on a virtual plane formed by the central axis (capillary axis) of each capillary on the reference base 138 is referred to as an optical axis 139. Furthermore, in this embodiment, the capillary array includes 24 capillaries 102, with the first capillary from the bottom being referred to as CAP1, and the 24th capillary from the bottom (the first capillary from the top) being referred to as CAP24, although the number of capillaries 102 need not be limited to 24.

[0020] In this case, the optical performance of the capillary electrophoresis device depends on the positional accuracy of the optical axis of the laser light, the positional accuracy of the CCD camera, the accuracy of the focal point, and the like. The optical performance before shipment is adjusted in a manufacturing process, although after shipment, it is also necessary to check the optical performance periodically or at the time of replacing the capillary assembly and adjust it as needed. Accordingly, a method for diagnosing the optical performance of the capillary electrophoresis device according to the present embodiment will be described below. Here, before describing examples of the present invention, a comparative example will be illustrated first. (Comparison example)

[0021] In the comparative example, a calibration shielding arrangement 141, which is shown in Fig. 3A is used to diagnose the optical performance. In contrast to the capillary assembly 117 for analysis, which is shown in Fig. As illustrated in Figure 3B, the shield assembly 141 is in a state where no voltage is applied for electrophoresis and no DNA has been induced. Both ends of each of the capillaries are sealed in the shield assembly 141, the shield assembly 141 is filled with a polymer solution (EG: ethylene glycol / urea: urea), and the shield assembly is cut to a length (approximately 20 cm), making it easy to handle.

[0022] Here, in the present comparative example, after shipping the capillary electrophoresis apparatus, a service technician mainly uses the shielding assembly 141 to diagnose the optical performance. To this end, the service technician or the like sets the shielding assembly 141 in an assembly holder 105, and the polymer solution (EG / UREA) with which each capillary is filled is irradiated with laser light, so that a Raman signal can be obtained. The service technician or the like then uses dedicated software to visually identify a peak value and the like of the Raman signal included in an image captured by the CCD camera. Accordingly, since the optical performance here includes a plurality of indexes, it is necessary for the service technician or the like to use the CCD camera to capture an image for each of the indexes and manually read a required value.The read value is then transmitted to the control unit and the control unit calculates an optical index.

[0023] In the comparative example, the image captured by the CCD camera further includes a pseudo signal obtained from the shield assembly simulating a capillary array instead of the actual capillary array, making the optical index thus calculated merely relative. Therefore, the service technician or the like determines whether the calculated optical index falls within a predetermined target value (specification) for the shield assembly, and accordingly adjusts the optical axis of the laser light, the position of the CCD camera, and the like. Furthermore, when the optical diagnosis is completed, the service technician or the like removes the calibration shield assembly from the capillary electrophoresis device and attaches the analysis capillary assembly to the capillary electrophoresis device for actual electrophoresis.

[0024] A diagnostic procedure according to the comparative example, which is performed by the service technician, is further described in detail for each optical index. <Koaxialität des oberen und unteren Strahls (Laserstrahlüberlappung)>

[0025] As described above, in the capillary electrophoresis apparatus according to the present embodiment, the capillary array is irradiated with laser light from above and below the capillary array. Specifically, the laser light irradiated from above the capillary array may be referred to as the upper beam, and the laser light irradiated from below the capillary array may be referred to as 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 is calculated using an image of Raman scattered light obtained when irradiation is performed only with the upper beam and an image of Raman scattered light obtained when irradiation is performed only with the lower beam.In a case where imaging is performed by irradiating only the upper beam, the service technician or the like uses the CCD camera to perform imaging in a state where a light-shielding plate is disposed on the optical path of the lower beam. On the other hand, in a case where imaging is performed by irradiating only the lower beam, the service technician or the like uses the CCD camera to perform imaging in a state where a light-shielding plate is disposed on the optical path of the upper beam.

[0026] Fig. 4A is a schematic diagram illustrating an example of an image acquired when the shielding assembly is irradiated with only the upper beam. Fig. 4B is also a schematic diagram illustrating an example of an image captured when the shielding assembly is irradiated with only the lower beam. The service technician or the like identifies a short-wavelength peak 302 of the center of the shielding assembly in the vertical direction while observing the short-wavelength peak 302 in Fig. 4A and identifies a short-wave peak 305 of the center of the shielding assembly in the vertical direction, while the short-wave peak 305 in Fig. 4B. Then, the control unit extracts an X coordinate of the peak 302 obtained when irradiation is performed only with the upper beam 301 and an X coordinate of the peak 305 obtained when irradiation is performed only with the lower beam 304, and outputs an optical index regarding the coaxiality of the upper and lower beams based on the difference between these coordinates. Furthermore, in a case where the output optical index is not within a range of a predetermined target value, that is, in a case where a shift between the optical axis of the upper beam and the optical axis of the lower beam is larger than a specification, the service technician or the like adjusts the optical axis of the laser light. <Horizontaler Rotationswinkel (Gitterrotationswinkel)>

[0027] In the comparison example, to calculate an index for a horizontal rotation angle, a new frame is used separate from the two images used to calculate the index for the coaxiality of the upper and lower beams. Fig. Figure 5 is a schematic diagram illustrating an example of an image captured when the shielding assembly is irradiated with the upper and lower beams. The service technician or the like identifies a long-wavelength peak and a short-wavelength peak of an end portion (CAP1 or CAP24) of the shielding assembly while observing the peaks on such a captured image, as shown in Fig. 5, visually verified. Then, the control unit calculates a displacement between Y coordinates when the peaks are connected as a line (dashed line 401 in Fig. 5), and outputs an optical index regarding the horizontal rotation angle of the spectrometer 132 and the CCD camera based on the calculated displacement. In a case where the output optical index is not within a range of a predetermined target value, that is, in a case where the horizontal rotation angle is greater than a specification, the service technician or the like further adjusts the position of the spectrometer 132. <Vertikaler Rotationswinkel (CCD-Rotationswinkel)>

[0028] In the comparison example, to calculate an index for a vertical rotation angle, the Fig. 5 is used. The service technician or the like identifies a shortwave peak of an upper end (CAP24) of the shielding assembly and a shortwave peak of a lower end (CAP1) of the shielding assembly while observing the peaks on such a captured image as in Fig. 5, visually verified. Then, the control unit calculates a displacement between X-coordinates when the peaks are connected as a line (dashed line 403 in Fig. 5), and outputs an optical index regarding the vertical rotation angle of the spectrometer 132 and the CCD camera based on the calculated displacement. In a case where the output optical index is not within a range of a predetermined target value, that is, in a case where the vertical rotation angle is greater than a specification, the service technician or the like further adjusts the position of the CCD camera. <Fehler in vertikaler Richtung (oberer / unterer Ort)>

[0029] In the comparison example, to calculate an index for an error in the vertical direction, the Fig. 5 is used. The service technician or the like identifies the position of the upper end (CAP24) of the shield assembly and the position of the lower end (CAP1) of the shield assembly while checking the positions on such a captured image as in Fig. 5, visually inspected. Then, the control unit calculates a distance 404 (upper location) from an upper viewing angle edge to the upper end of the shielding assembly and a distance 405 (lower location) from a lower viewing angle edge to the lower end of the shielding assembly, and outputs an optical index regarding the error in the vertical direction based on the calculated values. <Lichtintensitäts-Brennpunktfehler (Fokus & Intensität)>

[0030] In the comparative example, to calculate an index for a light intensity focus error, the Fig. 5 is used. The service technician or the like identifies a short-wavelength peak (501a) and a long-wavelength peak (501b) of the upper end (CAP24) of the shielding assembly, a short-wavelength peak (501c) and a long-wavelength peak (501d) of the middle (CAP12) of the shielding assembly, and a short-wavelength peak (501e) and a long-wavelength peak (501f) of the lower end (CAP1) of the shielding assembly while observing the peaks on such a captured image as in Fig. 5, visually inspected. The control unit then outputs an optical index regarding the light intensity focus error based on the light intensity at each peak. This light intensity focus error is an index indicating the degree of decrease in light intensity (intensity) due to a shift in the focal point of the CCD camera. <Signalhalbbreite („Signal Half Width“ - FWHM)>

[0031] In the comparison example, to calculate an index for a signal half-width, a Fig. 6 illustrated image is used. Fig. Figure 6 is a schematic diagram showing an example of a light intensity distribution of long wave peaks (dashed line 504 in Fig. 5) in the Y-axis direction. The control unit extracts half-widths 502 of long-wavelength peaks obtained from the positions of the capillaries from the upper end (CAP24) to the lower end (CAP1) of the shielding assembly, and outputs an optical index regarding the signal half-width based on each of the extracted half-widths 502. <Rauschen (Streulicht) zwischen benachbarten Kapillaren>

[0032] When stray light (outgoing light) appears at air gaps (portions corresponding to valleys of a wavelength) between the adjacent capillaries arranged in the Y-axis direction at the time of laser light irradiation, the stray light may affect signals from the positions of the capillaries. Therefore, the control unit extracts light intensities of the air gaps 503 between the capillaries from the Fig. 6 and outputs an optical index regarding the scattered light based on the extracted light intensities. <Signal-Rausch-Verhältnis (SR-Verhältnis)>

[0033] To calculate a signal-to-noise ratio, the capillary array is used in contrast to the indices described above. The control unit then calculates an optical index related to the signal-to-noise ratio based on the ratio of a peak light intensity in a bright state when the capillary array is irradiated with laser light to a peak light intensity in a dark state when the capillary array is not irradiated with laser light. <Signalintensitäts-Abweichungskorrektur (Normalisierung)>

[0034] Because there are individual differences in the optical system between capillary electrophoresis devices, the light intensity obtained by the CCD camera varies when the laser unit 133 performs laser light irradiation. Therefore, the power of the laser unit 133 is adjusted to maintain a constant light intensity. For a correction value required to normalize the light intensity, the capillary array is used for this purpose, as with the signal-to-noise ratio. (Application example)

[0035] In the application example of the present invention, the shielding assembly is not used to diagnose the optical power, but the analysis capillary assembly 117 (see Fig. 3B) is used to actually perform electrophoresis, and the capillary head 112 is connected to the pumping mechanism 103. Furthermore, in the application example, manual operation by the service technician or the like is not required, and the control unit of the capillary electrophoresis device automatically diagnoses the optical performance. As a trigger for the diagnosis, an instruction may be provided via the input unit during a period when a user of the capillary electrophoresis device is not performing analysis, or an instruction may be provided from an external monitoring terminal in a case where the control unit is connected to the monitoring terminal via a network.Furthermore, in the diagnosis in the application example, the control unit outputs each optical index in a single-batch processing by automatically identifying a peak of a Raman signal and the like mainly from a single image captured by the CCD camera and extracting a coordinate, a light intensity, and the like therefrom. The following description is performed for each optical index. <Koaxialität des oberen und unteren Strahls (Laserstrahlüberlappung}>

[0036] In the application example, the CCD camera captures a single image of combined Raman scattered light when the capillary array is simultaneously irradiated with laser light from above and below the capillary array. Fig. Figure 7 is a conceptual schematic diagram prepared for this purpose, illustrating a light intensity waveform of the upper beam, a light intensity waveform of the lower beam, and a combined waveform of the upper and lower beams. Fig. Figure 8 is also a schematic diagram illustrating an example of an image acquired when the capillary array is irradiated with the upper and lower beams. Fig. 9 is a schematic diagram illustrating an example of a signal intensity distribution of the center of the capillary array in the vertical direction when the capillary array is irradiated with the upper and lower beams. Fig. 8 and Fig. Figure 9 shows the direction of the horizontal axis (X-axis) wavelength information of Raman scattered light obtained when a DNA base sequence of a sample is irradiated with laser light. The left side of the X-axis indicates a short wavelength side, and the right side of the X-axis indicates a long wavelength side. In addition, Fig. 8 the direction of the vertical axis (Y-axis) position information of the capillaries.

[0037] As in Fig. As illustrated in Figure 7, a single image captured by the CCD camera includes a combined waveform 603 obtained by combining the upper beam light intensity waveform 601 and the lower beam light intensity waveform 602. Here, in a case where the upper beam optical axis and the lower beam optical axis shift from each other, a peak value of the combined waveform decreases and a half-width of the peak increases, compared to a case where the optical axes do not shift from each other.

[0038] Therefore, the control unit identifies a long-wavelength peak 705 of the center (CAP12) of the capillary array in the vertical direction in a single image, as shown in Fig. 8, by image processing and extracts a half-width 702 of the long-wavelength peak 705, as in Fig. 9. Further, the control unit outputs an optical index regarding the coaxiality of the upper and lower beams by comparing the extracted half-width 702 with a reference value stored in advance in the storage unit.

[0039] Since the light intensity on the long-wavelength side is higher than the light intensity on the short-wavelength side, there is an advantage in that the half-width can be easily identified. However, a half-width 703 of a short-wavelength peak 706 can be extracted, and a coaxiality index can be calculated by comparing it with a short-wavelength reference value. Furthermore, the index can be calculated using both the long-wavelength peak 705 and the short-wavelength peak 706. Since it is considered that the light intensity changes due to a focal point shift, a half-width correction coefficient can be provided accordingly, assuming a focal point shift.Furthermore, the control unit can identify a predetermined absolute value (e.g., a peak value) different from the half-width from the combined waveform contained in the frame and calculate the index by comparing the absolute value with the predetermined reference value. In any case, an absolute value detected using the actual capillary array is compared with the reference value without a relative value detected using the shielding array as in the comparative example, and thus a highly accurate index can be calculated. <Horizontaler Rotationswinkel (Gitterrotationswinkel)>

[0040] The control unit identifies a long-wave peak and a short-wave peak of an end section (CAP1 or CAP24) of the capillary array in such a single image as in Fig. 8, through image processing, and calculates a displacement between the Y coordinates of the peaks. Furthermore, the control unit outputs an optical index regarding the rotation angle of the spectrometer 132 and the CCD camera in the horizontal direction based on the calculated displacement. Since this optical index is calculated based on the absolute value detected using the capillary array actually used for electrophoresis, the optical index represents a more accurate index compared to the comparative example. <Vertikaler Rotationswinkel (CCD-Rotationswinkel)>

[0041] The control unit identifies the shortwave peak of the upper end (CAP24) of the capillary array and the shortwave peak of the lower end (CAP1) of the capillary array in such a single image as in Fig. 8, by image processing. Furthermore, the control unit calculates a displacement between the X coordinates of the identified peaks and outputs an optical index related to the vertical rotation angle of the spectrometer 132 and the CCD camera based on the calculated displacement. Likewise, since this optical index is calculated based on the absolute value detected using the capillary array actually used for electrophoresis, the optical index represents a more accurate index compared to the comparative example. <Fehler in vertikaler Richtung (oberer / unterer Ort)>

[0042] The control unit identifies the position of the upper end (CAP24) of the capillary array and the position of the lower end (CAP1) of the capillary array in such a frame as in Fig. 8, by image processing. Furthermore, the control unit calculates a distance (upper location) from the upper viewing angle edge to the upper end of the capillary array and a distance (lower location) from the lower viewing angle edge to the lower end of the capillary array, and outputs an optical index regarding an error in the vertical direction based on the calculated values. Similarly, since this optical index is calculated based on the absolute value detected using the capillary array actually used for electrophoresis, the optical index in this case represents a more accurate index compared to the comparative example. <Lichtintensitäts-Brennpunktfehler (Fokus & Intensität)>

[0043] The control unit identifies a shortwave peak and a longwave peak of the upper end (CAP24) of the capillary array, a shortwave peak and a longwave peak of the middle (CAP12) of the capillary array, and a shortwave peak and a longwave peak of the lower end (CAP1) of the capillary array in such a single image as in Fig. 8, by image processing. Furthermore, the control unit outputs an optical index regarding a light intensity focus error based on the light intensity of each of the peaks. Since this optical index is calculated based on the absolute value detected using the capillary array actually used for electrophoresis, the optical index in this case is similarly a more accurate index compared to the comparative example. <Signalhalbbreite („Signal Half Width“ - FWHM) >

[0044] The control unit extracts half-widths of long-wavelength peaks obtained from the positions of the capillaries from the upper end (CAP24) to the lower end (CAP1) of the capillary array from a single image, as described above, and outputs an optical index related to a signal half-width based on the extracted half-widths. Since this optical index is calculated based on the absolute value detected using the capillary array actually used for electrophoresis, the optical index in this case also represents a more accurate index compared to the comparative example. <Rauschen (Streulicht) zwischen benachbarten Kapillaren>

[0045] The control unit extracts light intensities obtained from the air gaps 503 between the capillaries from a single image, as described above, and outputs an optical index regarding stray light based on the extracted light intensities. Since this optical index is calculated based on the absolute value detected using the capillary array actually used for electrophoresis, the optical index in this case also represents a more accurate index compared to the comparative example. <Signal-Rausch-Verhältnis (SR-Verhältnis)>

[0046] A signal-to-noise ratio is basically calculated in a similar manner to the comparative example, but the following diagnosis is performed in this application example. For example, the control unit divides a frame in a bright state into a plurality of sections in a wavelength direction (X-axis direction), calculates a collective light intensity in each of the sections, and calculates a collective peak light intensity. Subsequently, the control unit divides a frame in a dark state into sections in a similar manner and calculates a collective peak light intensity, likewise in a similar manner. After that, the control unit calculates the signal-to-noise ratio based on the ratio of the collective peak light intensities calculated for each of the states.By dividing the X-axis direction into a plurality of sections in this way, an effect similar to a low-pass filter is created, and the effect of strong noise can be removed. Furthermore, it is also possible to calculate an index regarding the effect of dark current noise of the CCD camera from the signal intensity of the peak value of the image in the dark state. Furthermore, it is also possible to index a variation of signals for each of the plurality of sections obtained by dividing the image in the bright state. <Signalintensitäts-Abweichungskorrektur (Normalisierung)>

[0047] The signal intensity deviation correction is performed by a similar method as in the comparative example.

[0048] As described above, in the example, the optical indices for the coaxiality of the upper and lower beams, the horizontal rotation angle, the vertical rotation angle, the error in the vertical direction, the light intensity focus error, the signal at half maximum width, and the noise from the adjacent capillaries are calculated using the capillary array actually used for analysis. That is, since all optical indices are absolute indices, accurate optical performance diagnosis and optical adjustment can be performed by comparing them with predetermined absolute target values ​​(specifications). Furthermore, the capillary electrophoresis device automatically outputs each of the optical indices without manual operation by the service technician or the like, making it easy to diagnose the optical performance. (Modifications)

[0049] The results of the automatic optical diagnosis function as described above, that is, the optical indices are accumulated in the storage unit of the capillary electrophoresis device. Therefore, an operation performed on the input unit by the user or service technician can cause the control unit to output changes in the optical indices accumulated in the storage unit over time to the output unit. The changes in the optical indices occurring over time can be used accordingly for failure prediction or the like.

[0050] Furthermore, the optical indexes output by the automatic optical diagnosis function can be continuously transmitted to the monitoring terminal connected to the control unit via the network, regardless of whether the optical indexes are within the ranges of the set values ​​(specifications). If the optical indexes are not within the ranges of the set values, the control unit can also transmit a notification to the monitoring terminal. If the optical indexes are not within the ranges of the set values, a service technician or the like can also go to the location where the capillary electrophoresis device is installed and perform optical adjustment or the like.

[0051] The present invention is not limited to the examples and modifications described above; various modifications may be made. For example, the control unit described above may also 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 performs optical performance diagnosis based on a signal from the CCD camera. List of reference symbols 101 Capillary electrophoresis device 102 capillaries 103 Pump mechanism 104 High-voltage power supply 105 arrangement holders 106 Piston pump 107 Block 108 Check valve 109 polymer containers 110 anode buffer tanks 111 Anode electrode 112 Capillary head 113 electric valve 114 Light irradiation mechanism 115 secondary detection unit 116 Detection unit 117 Capillary arrangement 118 Constant temperature bath 119 fans 120 Heating and cooling mechanism 121 buffer tanks 122 cleaning containers 123 waste liquid containers 124 sample containers 125 Conveyor mechanism 126 hollow electrode 127 Capillary cathode end 128 Chamber 129 Charging head 130 movement stage 131 handle 132 spectrometers 133 Laser unit 134 reflecting mirror 135 Polarizer 136 beam splitters 137 Condenser lens 138 Reference base 139 optical axis 140 laser light 141 Shielding arrangement QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] JP 2007

[0003] JP 212449

[0003]

Claims

[1] A capillary electrophoresis device comprising: a capillary array including a plurality of capillaries; a light source that causes laser light to oscillate; a detection unit that detects light emitted when the capillary array is irradiated with the laser light; and a control unit that performs predetermined processing based on a signal output from the detection unit, wherein the control unit extracts a predetermined absolute value with respect to an optical index based on an image captured by the detection unit 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, wherein the detection unit records a single image of Raman scattered light that is combined when the capillary array is irradiated with the laser light from above and below the capillary array, and the control unit extracts a predetermined absolute value from a combined waveform of the Raman scattered light included in the frame and calculates an optical index regarding the coaxiality of the upper and lower laser light by comparing the absolute value with the reference value. [3] The capillary electrophoresis apparatus according to claim 2, wherein the control unit extracts a half-width of a peak included in the combined waveform and calculates an optical index regarding the coaxiality of the upper and lower laser lights by comparing the extracted half-width with a reference value. [4] The capillary electrophoresis device according to claim 1, further comprising: a storage unit that stores the optical index, wherein the control unit outputs changes in the optical index stored in the storage unit over time. [5] An optical performance diagnostic method for a capillary electrophoresis device, the method comprising: a step of capturing an image taken by a detection unit in a state where a capillary array to be used for electrophoresis is mounted; a step of extracting a predetermined absolute value regarding an optical index based on the captured image; and a step of calculating the optical index by comparing the extracted absolute value with a predetermined reference value.

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