Capillary Electrophoresis Apparatus

Abstract

This capillary electrophoresis device includes: a light source; a plurality of capillaries; a photo-detection unit; and a plurality of detection optical fibers each having one end face disposed in relation to any one of the capillaries and another end face connected to the photo-detection unit. The light detection unit selectively detects light at the center of the detection optical fiber.

Description

[Technical field]

[0001] The present invention relates to a capillary electrophoresis apparatus. [Background technology]

[0002] Biopharmaceuticals have an excellent effect not found in small molecule drugs, in that antibody molecules modified with glycans are effective against specific targets such as cancer and rare intractable diseases. While small molecule drugs are synthesized through chemical reactions, biopharmaceuticals are produced using the biological functions of cells, so the molecular structure of the product is affected by even slight changes in culture conditions. Immunoglobulin G (IgG), a representative biopharmaceutical, is a large molecule with a molecular weight of about 150,000 and a complex structure, and it is almost impossible to prevent structural heterogeneity. Therefore, quality inspection technology to confirm the safety and efficacy of biopharmaceutical formulations plays an even more important role.

[0003] Because the target substance has a complex structure, there are many test items for biopharmaceuticals, but capillary electrophoresis is used for confirmation tests to confirm that the main components contained in the test object are the target substance, and purity tests to evaluate the content of impurities. In a capillary electrophoresis device, a sample, such as an antibody, is injected into the capillary and electrophoresed, where the sample is separated according to molecular weight and charge, and detected by a detection unit installed near the end of the capillary. Optical methods such as ultraviolet (UV) absorption, native fluorescence (NF), and laser induced fluorescence (LIF) are widely used as detection methods.

[0004] An example of a capillary electrophoresis apparatus is disclosed in US Pat. No. 5,399,633.

[0005] Among these, LIF measurement is the most sensitive detection method, and has long been used to detect sugar chains in antibody drugs, which are difficult to detect using UV absorption or NF, and to detect nucleic acids such as DNA. LIF measurement uses a laser as the light source, and by utilizing the directionality of the laser and the lens effect of the capillary, it is possible to irradiate the laser onto multiple capillaries at once. This allows multiple samples to be analyzed at once, enabling high-throughput analysis. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2016-133373 A Summary of the Invention [Problem to be solved by the invention]

[0007] In LIF measurement, it is possible to analyze multiple capillaries at once, but in order to detect the fluorescence generated from multiple capillaries, it is necessary to arrange multiple lenses or lenses large enough to accommodate multiple capillaries, which tends to make the device large. Therefore, the inventors devised an optical system that collects fluorescence by arranging fibers close to each capillary. With such an optical system, it is possible to detect fluorescence without placing lenses near the capillaries, and there is no restriction on the positional relationship between the capillaries and the detector, improving the freedom of design, which allows the device to be made smaller.

[0008] However, in such a detection optical system, there is a problem in that the fluorescence generated from a specific capillary enters a fiber corresponding to an adjacent capillary, causing significant crosstalk.

[0009] The present invention has been made in view of the above problems, and has an object to provide a capillary electrophoresis device that is small and has low crosstalk. [Means for solving the problem]

[0010] An example of a capillary electrophoresis apparatus according to the present invention is A light source; A plurality of capillaries; A light detection unit; a plurality of detection optical fibers, one end surface of which is disposed in relation to any one of the capillaries and the other end surface of which is connected to the light detection unit; having The light detection unit selectively detects light at the center of the detection optical fiber. It is characterized by: Effect of the Invention

[0011] According to the present invention, it is possible to provide a capillary electrophoresis device that is smaller in size and has less crosstalk than conventional devices, and in some cases, it is also possible to provide a capillary electrophoresis device that is less expensive than conventional devices.

[0012] Problems, configurations, and effects other than those described above will become apparent from the following description of the embodiments. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a schematic diagram showing a configuration example of a capillary electrophoresis apparatus according to a first embodiment of the present invention. [Diagram 2] FIG. 2 is a schematic diagram for explaining a configuration example of a component detection unit of the capillary electrophoresis apparatus of FIG. 1. [Diagram 3] FIG. 1 is a schematic diagram illustrating a mechanism by which crosstalk occurs. [Figure 4] 1 shows an example of light intensity distribution at the light output end of a detection optical fiber. [Diagram 5] 6 shows an example of a simulation result of signal strength and crosstalk in the first embodiment. [Figure 6] Simulation results of the propagation efficiency of an optical fiber and the incidence angle dependence of the light intensity distribution at the light output end. [Figure 7] FIG. 2 is a diagram for explaining the optical path of a light ray incident on an optical fiber. [Figure 8] Calculation results of the incidence angle dependence of the propagation efficiency of an optical fiber. [Figure 9] Schematic diagram of the optical path of light propagating through an optical fiber. [Figure 10] Calculation result of the radius of the area where the light intensity distribution becomes zero after propagation through an optical fiber. [Figure 11] FIG. 11 is a schematic diagram for explaining a configuration example of a component detection unit of a capillary electrophoresis device according to a second embodiment of the present invention. [Figure 12] FIG. 11 is a schematic diagram for explaining a configuration example of a component detection unit of a capillary electrophoresis device according to a third embodiment of the present invention. [Figure 13] FIG. 11 is a schematic diagram for explaining a configuration example of a component detection unit of a capillary electrophoresis device according to Example 4 of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0015] [Example 1] <Basic configuration> (Overall explanation of electrophoresis device) 1 is a schematic diagram showing an example of the configuration of a capillary electrophoresis apparatus 1 according to this embodiment. An electrophoresis medium container 2 and a plurality of sample containers 3 store an electrophoresis medium and a sample, respectively. Prior to measurement, a plurality of capillaries 5 included in a capillary array 11 are connected to these containers, and the electrophoresis medium and the sample are sequentially injected into the plurality of capillaries 5 by electrical means, pressure, or the like. A plurality of injection side electrode tanks 4 and discharge side electrode tanks 7 are filled with a buffer solution, and the capillaries 5 and electrodes 9 are immersed in the buffer solution during electrophoresis.

[0016] When a voltage is applied by the high-voltage power supply 8, the molecules in the sample move from the injection side to the discharge side in the capillary 5 while being separated by electrophoresis according to properties such as molecular weight and charge amount. When each of the migrated molecules reaches the component detection unit 6, it is detected by optical means. Although not shown, the capillary electrophoresis device 1 also has a pressure adjustment unit, a control unit, a signal processing unit, a display unit, a recording unit, etc.

[0017] (Explanation of component detection section) 2 shows an example of the configuration of the component detection unit 6 of the electrophoresis apparatus 1. Excitation light emitted from a light source 101 is irradiated onto a plurality of capillaries 102 along the arrangement direction of a capillary array 103. This makes it possible to irradiate the excitation light onto a plurality of capillaries 102 at once using a single light source 101.

[0018] The component detection unit 6 includes a plurality of detection optical fibers 104. Each of the detection optical fibers 104 corresponds to one of the capillaries 102. One end face of each detection optical fiber 104 is disposed in relation to the corresponding capillary 102, for example, in the vicinity of the corresponding capillary 102. The specific range of "vicinity" can be appropriately determined by a person skilled in the art in consideration of the matters described later in relation to FIG. 5, and can be, for example, the range shown in FIG. 5 (however, larger than 0. For example, 0.1 mm or less, 0.2 mm or less, 0.3 mm or less, 0.4 mm or less, or 0.5 mm or less). The other end face of each detection optical fiber 104 is connected to the light detection unit 108.

[0019] When the sample in the capillary 102 is irradiated with excitation light, fluorescence (autofluorescence or fluorescence from a fluorescent dye) is generated from the sample, and a part of the fluorescence is coupled to a detection optical fiber 104 provided corresponding to each capillary 102. The fluorescence propagates through the detection optical fiber 104 and is guided to a light detection unit 108 including a pinhole 105, a long-pass filter 106, and a light detector 107.

[0020] When the fluorescence is emitted into space from the detection optical fibers 104, the fluorescence from the periphery of the detection optical fibers 104 is blocked by the pinholes 105 provided at the emission ends of the detection optical fibers 104, and only the fluorescence near the center is emitted into space. The fluorescence then passes through a long-pass filter 106 and is detected by a photodetector 107.

[0021] In this way, the pinhole 105 functions as a selective light blocking element, which allows the light detection unit 108 to selectively detect light at the center of the detection optical fiber 104. Here, the "center of the detection optical fiber 104" means, for example, a region including the central axis in a cross section perpendicular to the central axis of the detection optical fiber, and specifically means a disk region centered on the central axis. The radius of the disk region can be appropriately determined by a person skilled in the art in consideration of the matters described below in relation to FIG. 5.

[0022] The long-pass filter 106 is provided to prevent the excitation light scattered by the capillary 102 and coupled into the detection optical fiber 104 from being detected.

[0023] The pinhole 105 plays a role in suppressing crosstalk between capillaries, which occurs when fluorescence generated from a specific capillary 102 is coupled to a detection optical fiber 104 other than the corresponding detection optical fiber 104 .

[0024] As shown in a balloon in FIG. 2, at least one of the area and shape of the opening of the pinhole 105 (i.e., the area of ​​the detection optical fiber 104 to be selectively detected) may be changeable. For example, multiple pinholes with different opening dimensions or shapes may be used by switching as shown in (a), (b), and (c) in FIG. 2, or one pinhole may be configured to be deformed as shown in (a), (b), and (c) to change the opening dimensions or shape. With this configuration, as described later, it is possible to adjust the balance between suppressing loss of signal components and blocking crosstalk. Note that changing the area of ​​the detection optical fiber 104 to be selectively detected in this manner is also possible in other embodiments described later.

[0025] 3 is a diagram for explaining an example of the mechanism by which crosstalk occurs. Fluorescence generated from a capillary 201 enters the corresponding detection optical fiber 203 (solid arrow) and is detected as a signal component. On the other hand, it also enters the detection optical fiber 204 corresponding to the adjacent capillary 202 (dashed arrow) either directly or indirectly after being reflected by the capillary 202, and is detected as a crosstalk component. As shown in the figure, the crosstalk component tends to enter the fiber at a higher angle of incidence than the signal component.

[0026] Figure 4 shows the results of a ray tracing simulation of the intensity distribution at the fiber output end after the fluorescence generated inside the capillary 201 is coupled to and propagates through the detection optical fibers 203 and 204. The simulation conditions were as follows: capillary inner diameter 50 μm, capillary outer diameter 150 μm, inter-capillary distance 500 μm, and distance from the capillary surface to the corresponding input end of the detection optical fiber 300 μm. The detection optical fibers 203 and 204 are multimode, with a core diameter of 400 μm, a cladding diameter of 420 μm, a numerical aperture of 0.5, and a length of 100 mm. The fluorescence emission region inside the capillary 201 was cylindrical with a diameter of 50 μm and a height of 50 μm.

[0027] It can be seen that the light intensity at the output end of the detection optical fiber 203, which corresponds to the signal component, tends to be localized at the center of the fiber, whereas the light intensity at the output end of the detection optical fiber 204, which corresponds to the crosstalk component, tends to be localized in the peripheral area of ​​the fiber. This reflects the property of multimode fibers that light incident on the fiber at a low angle is localized at the center of the fiber, and light incident on the fiber at a high angle is localized in the peripheral area of ​​the fiber. This embodiment makes use of this property of the fiber, and makes it possible to suppress crosstalk by selectively detecting light from the center of the detection optical fiber 104 using the pinhole 105.

[0028] Figure 5 shows the results of a simulation evaluation of the crosstalk suppression effect of this embodiment. As a reference example, the dependence of the signal intensity and crosstalk on the capillary / fiber distance is shown for the cases where the core diameter c of the detection optical fiber is 400 μm and 200 μm, and for the case where a pinhole with a hole diameter PH of 200 μm is installed at the output end of a fiber with a core diameter of 400 μm as a specific configuration of this embodiment.

[0029] Other simulation conditions are the same as those in Fig. 4. As the core diameter c increases, the signal strength increases, but the crosstalk also increases.

[0030] The smaller the capillary / fiber distance, the higher the signal strength and the smaller the crosstalk, so it is desirable to make it as small as possible. However, if it is made too small, the fiber and capillary come into contact with each other, increasing the risk of damage. Therefore, in practice, it is preferable to install the fiber and capillary at a distance of at least several hundred microns.

[0031] For example, when the capillary-fiber distance is 200 μm or more, a large crosstalk of about 2.2% or more occurs when the core diameter is 400 μm. When the core diameter is 200 μm, the signal strength decreases compared to when the core diameter is 400 μm, but the crosstalk is smaller than that, and when the fiber-capillary distance is 0.3 mm or less, the crosstalk is 0.5% or less.

[0032] On the other hand, when a 200 μm pinhole is provided at the output end of a fiber with a core diameter of 400 μm, which is a specific configuration of this embodiment, when the fiber-capillary distance is 200 μm or more, the signal strength is higher and the crosstalk is equal to or lower than when the core diameter is 200 μm. This result means that under conditions where the capillary-fiber distance is to a certain extent, providing a pinhole at the output end of a fiber with a large core diameter, as in this embodiment, can be more advantageous in terms of both signal strength and crosstalk than simply using a fiber with a small core diameter.

[0033] Compared to the reference example with a core diameter of 400 μm, this example with a 200 μm pinhole at the output end of a core diameter of 400 μm reduces the signal strength to about half, while suppressing crosstalk from 4.13% to 0.16%, about 1 / 26. This is due to the effect that the pinhole blocks more crosstalk components than signal components.

[0034] Although it is possible to suppress crosstalk by optimizing the core diameter and numerical aperture of the fiber, the core diameter and numerical aperture of the fiber available are often limited, and the degree of freedom in optimization is extremely low. On the other hand, the hole diameter of the pinhole can be freely set, so the degree of freedom in optimization in this embodiment is high.

[0035] Next, the operating principle of this embodiment and the appropriate width of the light blocking region will be described in detail based on simulations and formulas. Figure 6(a) shows the simulation results of the light propagation efficiency of the fiber (the ratio of the incident light reaching the fiber output end) depending on the light incident angle.

[0036] The simulation was performed with a multimode fiber, a core diameter of 200 μm, a cladding diameter of 220 μm, a numerical aperture of 0.5, and a length of 100 mm. The optical propagation efficiency is approximately 1 up to an incident angle of 30 degrees, which corresponds to the numerical aperture of the fiber, and drops rapidly when the angle exceeds 30 degrees. This is because the components that do not satisfy the total reflection condition within the fiber increase when the incident angle exceeds 30 degrees.

[0037] Figure 6(b) shows the light intensity distribution at the output end of the fiber for each incident angle. We can see that the intensity distribution is roughly uniform within the core up to an incident angle of 30 degrees, whereas the light is localized in the peripheral area when the incident angle exceeds 30 degrees. In other words, the intensity of light incident at an angle larger than the angle corresponding to the numerical aperture of the fiber tends to be localized around the fiber.

[0038] The principle by which such properties occur will be described below with reference to the drawings. Consider a coordinate system with the center of the fiber input end as the origin as shown in Fig. 7. The z-axis is the central axis of the fiber. The x-axis and y-axis are axes that are perpendicular to each other in the radial direction of the fiber.

[0039] Consider a light ray incident on the fiber at an incident angle θ. in Let the unit direction vector k of the incident light ray in and the unit direction vector k of the light ray immediately after refraction at the fiber surface core be represented by the following equations respectively.

Equation

Equation

Equation

Equation

Equation

Equation

Equation

number

number

[0040] The upper limit of the incident angle θ for a ray incident at the position u=0 to satisfy the total reflection condition c0 (the angle of incidence corresponding to the NA of the fiber) is defined as follows:

number

number

number

number

number

number

[0041] Figure 8 compares the results of the ray tracing simulation shown in Figure 6 with the propagation efficiency expressed by Equation 13. The two are qualitatively consistent, which proves that the theory of the incidence angle dependence of the propagation efficiency of the fiber mentioned above is valid.

[0042] Figure 9 is a schematic diagram of the trajectory of a light ray propagating within a fiber, viewed from the fiber input end side, with Fig. 9(a) showing the case where the light ray is incident on the fiber at the center (u=0), and Fig. 9(b) showing the case where the light ray is incident on the fiber at the periphery (u>0). As shown in Fig. 9(a), a light ray incident on the center is repeatedly reflected at the same position, passing through the center of the fiber each time. In contrast, as shown in Fig. 9(b), a light ray incident on the periphery of the fiber has a larger angle of incidence at the core / cladding interface, so it propagates only through the periphery of the fiber without passing through the center of the fiber.

[0043] From the above results, the angle (θ c0 ) or more, the condition for total reflection is satisfied only when the light enters the peripheral area of ​​the fiber, and the light that enters the peripheral area of ​​the fiber is localized in the peripheral area of ​​the fiber. As a result, the light that enters the fiber at an angle equal to or greater than the NA of the fiber is localized in the peripheral area of ​​the fiber after propagating through the fiber.

[0044] Next, the pinhole diameter in this embodiment will be described. From the simulation results shown in FIG. c0In the above case, the radius of the central region where the light intensity is zero in the light intensity distribution at the fiber output end was calculated for each incident angle. Figure 10 shows the value v c and u expressed by Eq. c The results show that the incidence angle dependence of the two is roughly consistent.

[0045] From this, θ c0 The light incident above has a radius of approximately cu at the fiber output end. c Therefore, the crosstalk component to be eliminated is localized in the region of φ(>θ c0 ), the radius of the pinhole r p of

number

[0046] There are two types of crosstalk: a component that is directly incident on the adjacent fiber (hereafter referred to as the direct component) as shown by the dashed line in Figure 3, and a component that is reflected by an adjacent capillary and then incident on the adjacent fiber. The latter component loses strength when reflected, so if a direct component exists, it becomes dominant. The minimum incident angle φ of the direct component on the fiber shown in Figure 3 is min is approximately expressed by the following formula:

number

[0047] For example, p = 500 μm, d = 300 μm, D out= 150 μm, c = 400 μm (simulation conditions for the reference example of c = 400 μm in Figure 5), φ min ≒53 degrees, and the pinhole radius r corresponding to this incident angle p becomes approximately 156 μm when assuming an equal sign in Equation 16. In other words, by setting the pinhole radius to approximately 156 μm, it is possible, in principle, to block all direct components of crosstalk while minimizing loss of signal components.

[0048] [Example 2] (Providing an imaging optical system) Fig. 11 is a schematic diagram showing a configuration example of the component detection unit 6 in the capillary electrophoresis device 1 according to this embodiment. The same components as those shown in Fig. 2 are denoted by the same reference numerals, and their description will be omitted. This embodiment differs from Example 1 in that the light detection unit 108 is further provided with an imaging optical system 303 having lenses 301 and 302.

[0049] As in the first embodiment, the excitation light emitted from the light source 101 is irradiated to the capillaries 102 along the arrangement direction of the capillary array 103, and a part of the fluorescence generated from the sample in the capillaries 102 is coupled to the detection optical fibers 104 provided corresponding to each capillary 102. The fluorescence propagates through the detection optical fibers 104 and is emitted into space, converted into parallel light by the lens 301, passes through the long-pass filter 106, and is then focused at the position of the pinhole 105 by the lens 302. The pinhole 105 blocks the light emitted from the peripheral part of the emission end of the detection optical fiber 104, and as a result, the light emitted from the center of the emission end of the detection optical fiber 104 is detected by the photodetector 107.

[0050] As described above, the light detection unit 108 according to this embodiment includes the imaging optical system 303 that images the light emitted from the light emitting end of the detection optical fiber 104 at the position of the pinhole 105 .

[0051] In this embodiment, the provision of an imaging optical system 303 converts the light emitted from the detection optical fiber 104 into parallel light, allowing the light to be incident almost perpendicularly on the long-pass filter 106, thereby suppressing performance degradation (for example, an increase in the transmittance for excitation light or a decrease in the transmittance for fluorescence) that occurs when the angle of incidence of light on the long-pass filter 106 deviates from the perpendicular.

[0052] Furthermore, by setting the imaging magnification of the imaging optical system 303 to 1 or more, i.e., by enlarging and imaging the light emitted from the exit end of the detection optical fiber 104 at the pinhole position, the required manufacturing accuracy or positional accuracy of the hole diameter of the pinhole 105 can be relaxed.

[0053] [Example 3] (Using optical fiber for connection) Fig. 12 is a schematic diagram showing a configuration example of the component detection unit 6 in the capillary electrophoresis apparatus 1 according to this embodiment. The same components as those shown in Fig. 2 are denoted by the same reference numerals, and their description will be omitted. This embodiment differs from Example 1 in that the light detection unit 108 includes a fiber connector 401, a connecting optical fiber 402, a long-pass filter 106, and a light detector 107.

[0054] As in the first embodiment, the excitation light emitted from the light source 101 is irradiated to the capillaries 102 along the arrangement direction of the capillary array 103, and a part of the fluorescence generated from the sample in the capillaries 102 is coupled to the detection optical fibers 104 provided corresponding to each capillary 102. After propagating through the detection optical fibers 104, the fluorescence is coupled to the connection optical fibers 402 connected to the detection optical fibers 104 via the fiber connector 401.

[0055] The core diameter of the connecting optical fiber 402 is set smaller than the core diameter of the detection optical fiber 104, and only light near the center at the output end of the detection optical fiber 104 is coupled to the connecting optical fiber 402, propagates, and then is guided to the photodetector 107. That is, the connecting optical fiber 402 plays the same role as the pinhole 105 in the first embodiment. Here, the central axes of the detection optical fiber 104 and the connecting optical fiber 402 are positioned to coincide with each other by the fiber connector 401, which is a general-purpose part. As a result, in this embodiment, it is not necessary to align the central axes of the detection optical fiber 104 and the pinhole 105, which is necessary in the first embodiment, and it is possible to more easily achieve performance equivalent to that of the first embodiment.

[0056] The imaging optical system 303 (FIG. 11) of the second embodiment and the connecting optical fiber 402 (FIG. 12) of the third embodiment may be combined. For example, in FIG. 12, the imaging optical system 303 may be used instead of the fiber connector 401. In this case, the imaging optical system 303 forms an image of the light emitted from the light emitting end of the detection optical fiber 104 on the incident end of the connecting optical fiber 402.

[0057] In such a combination, the imaging magnification of the imaging optical system 303 is set to 1 or more, that is, magnified imaging is performed, thereby increasing the degree of freedom in the core diameter of the connecting optical fiber 402. For example, the core diameter of the connecting optical fiber 402 can be set to be equal to or larger than the core diameter of the detection optical fiber 104.

[0058] [Example 4] (Using an image sensor) 13 is a schematic diagram showing a configuration example of the component detection unit 6 in the capillary electrophoresis device 1 according to this embodiment. The same components as those shown in FIG. 2 are denoted by the same reference numerals, and their description will be omitted. This embodiment differs from embodiment 1 in that the light detection unit 108 includes an imaging optical system 303 (including microlens arrays 501 and 502), a long-pass filter 106, an image sensor 503, and a signal processing unit 504.

[0059] As in the first embodiment, the excitation light emitted from the light source 101 is irradiated onto the capillaries 102 along the arrangement direction of the capillary array 103, and a part of the fluorescence generated from the sample in the capillaries 102 is coupled to the detection optical fibers 104 provided corresponding to each capillary 102. The imaging optical system 303 plays a role of forming an image of the light emitted from the emission ends of all the detection optical fibers 104 on the image sensor 503 (more strictly, on, for example, its light receiving portion). As a result, the two-dimensional light intensity distribution of the fluorescence emitted from the detection optical fibers 104 is detected by the image sensor 503 and transferred to the signal processing unit 504.

[0060] The signal processing unit 504 selectively processes light at the center of the detection optical fiber 104 from among the light detected by the image sensor 503. For example, only the intensity of the light at the center is acquired as a signal and added, and the intensity of other light is ignored. That is, in this embodiment, the signal processing unit 504 plays the role of the pinhole 105 in the first embodiment.

[0061] In this embodiment, it is possible to suppress crosstalk by signal processing alone, without providing a pinhole or an optical fiber for connection. In addition, since the size of the detection area can be freely set by the signal processing unit 504, it is easy to optimize the relationship between the signal strength and the crosstalk depending on the application.

[0062] As discussed above, the following statements apply to various embodiments of the present invention. An example of the present invention is A light source; A plurality of capillaries; A light detection unit; a plurality of detection optical fibers, one end surface of which is disposed in relation to any one of the capillaries and the other end surface of which is connected to the light detection unit; having The light detection unit selectively detects light at the center of the detection optical fiber. The present invention relates to a capillary electrophoresis apparatus.

[0063] With this configuration, crosstalk can be suppressed.

[0064] As an example, the light detection unit may include at least a light detector and a selective light blocking element.

[0065] By adopting such a configuration, crosstalk can be suppressed with an inexpensive and simple configuration.

[0066] As an example, the light detection section may include at least a light detector and a connecting optical fiber.

[0067] By adopting such a configuration, crosstalk can be suppressed stably with the configuration.

[0068] As an example, the light detection unit may include at least an imaging element and a signal processing unit, and the signal processing unit may selectively process light from a central portion of the detection optical fiber among the light detected by the imaging element.

[0069] With this configuration, crosstalk can be suppressed only by the signal processing section without using any light-shielding components.

[0070] As an example, the light detection section may further include an imaging optical system that images the light emitted from the light emitting end of the detection optical fiber at the position of the selective light blocking element.

[0071] With such a configuration, it becomes easier to arrange components such as optical filters, and by appropriately setting the imaging magnification, it is possible to improve robustness against misalignment of the selective light blocking elements.

[0072] As an example, the light detection section may further include an imaging optical system that images light emitted from a light emission end of the detection optical fiber on an incident end of the connection optical fiber.

[0073] With such a configuration, it becomes easier to arrange components such as optical filters, and by appropriately setting the imaging magnification, it is possible to improve robustness against misalignment of the connecting optical fiber.

[0074] As an example, the core diameter of the connection optical fiber may be configured to be smaller than the core diameter of the detection optical fiber.

[0075] With this configuration, no pinhole is required.

[0076] As an example, the light detection section may further include an imaging optical system that images the light emitted from the light emitting end of the detection optical fiber on the imaging element.

[0077] Such a configuration makes it easier to arrange components such as optical filters, and by appropriately setting the imaging magnification, it is possible to improve the effect of suppressing crosstalk through signal processing.

[0078] As an example, the light detection unit selectively detects only light in a region within a radius r from the center at the light emission end of the detection optical fiber, where r is given by the following formula:

number

[0079] With this configuration, it is possible to suppress crosstalk while minimizing loss of signal components.

[0080] As an example, the light detection section may be capable of changing at least one of the area and the shape of a region of the detection optical fiber that is selectively detected.

[0081] With this configuration, it becomes possible to appropriately adjust the detection sensitivity and crosstalk depending on the application. [Explanation of symbols]

[0082] 1: Capillary electrophoresis device 2: Electrophoresis medium container 3: Sample container 4: Injection side electrode tank 5: Capillary 6: Component detection section 7: Discharge side electrode tank 8: High voltage power supply 9: Electrode 11: Capillary array 101: Light source 102: Capillary 103: Capillary array 104: Optical fiber for detection 105: Pinhole (selective light blocking element) 106: Long pass filter 107: Photodetector 108: Light detection unit 201, 202: Capillary 203, 204: Optical fiber for detection 301, 302: Lens 303: Imaging optical system 401: Fiber connector 402: Optical fiber for connection 501: Microlens array 503: Image sensor 504: Signal processing unit

Claims

1. A light source; A plurality of capillaries; A light detection unit; a plurality of detection optical fibers, one end surface of which is disposed in relation to any one of the capillaries and the other end surface of which is connected to the light detection unit; having The light detection unit selectively detects light at the center of the detection optical fiber. A capillary electrophoresis apparatus comprising:

2. The light detection unit includes at least a light detector and a selective light blocking element.

2. The capillary electrophoresis apparatus according to claim 1,

3. The light detection unit includes at least a light detector and a connecting optical fiber.

2. The capillary electrophoresis apparatus according to claim 1,

4. the light detection unit includes at least an image sensor and a signal processing unit; The signal processing unit selectively processes light at a central portion of the detection optical fiber among the light detected by the imaging element.

2. The capillary electrophoresis apparatus according to claim 1,

5. The light detection unit further includes an imaging optical system that images the light emitted from the light emission end of the detection optical fiber at the position of the selective light blocking element.

3. The capillary electrophoresis apparatus according to claim 2.

6. The light detection unit further includes an imaging optical system that images the light emitted from the light emission end of the detection optical fiber on the incident end of the connection optical fiber.

4. The capillary electrophoresis apparatus according to claim 3.

7. The core diameter of the connection optical fiber is smaller than the core diameter of the detection optical fiber.

4. The capillary electrophoresis apparatus according to claim 3.

8. The light detection unit further includes an imaging optical system that forms an image of the light emitted from the light emission end of the detection optical fiber on the imaging element.

5. The capillary electrophoresis apparatus according to claim 4.

9. the light detection unit selectively detects only light in a region within a radius r from the center at a light emission end of the detection optical fiber, where r is given by the following formula: [0010] where NA is the numerical aperture of the detection optical fiber, c is the core diameter of the detection optical fiber, p is the spacing between the capillaries; D ｏｕｔ is the outer diameter of the capillary, d is the distance from the surface of the capillary to the light input end of the corresponding detection optical fiber; 2. The capillary electrophoresis apparatus according to claim 1,

10. The light detection unit is capable of changing at least one of the area and the shape of the region of the detection optical fiber that is selectively detected.

2. The capillary electrophoresis apparatus according to claim 1,

Images