Light detection device

Abstract

This light detection device is provided with: a flow path array in which the axes of a plurality of tubes are arranged in parallel to each other and which constitutes a flow path plane; an irradiation optical system that is provided with a light source and that irradiates light from the light source such that the vibration direction of an electric field component of the light is parallel to the flow path plane, the optical axis of the light being included in the flow path plane, and the optical axis forming a predetermined angle [theta] 0 with respect to a direction orthogonal to the axis of the tube in the flow path plane; and a light detection system that detects light emitted from the plurality of tubes, respectively. The refractive index of the surrounding environment is set as n0, the refractive index of the material of the tube is set as n1, the refractive index of the substance inside the tube is set as n2, and the refractive index of the light in the material of the tube and the angle of the light inside the tube, which are determined on the basis of a predetermined formula according to the refractive index and the predetermined angle, are set as n0, n1, and n2. The given angle [theta] 0 satisfies given formula 1 and formula 2.

Description

Technical Field

[0001] The present invention relates to a light detection device, and more particularly to a device for detecting fluorescence emitted from a fluorescent substance in a flow path array. Background Art

[0002] There is a measurement technique that uses fluorescence to detect substances flowing through multiple flow paths and analyzes them. As an example of such a technique, there is the analysis of molecules using a capillary electrophoresis device. For example, DNA labeled with a fluorescent dye is electrophoresed in a capillary and separated according to each size. Excitation light is irradiated to the detection part provided on the capillary, and the generated fluorescence is detected. In these devices, multiple flow paths are sometimes installed to improve the throughput of the measurement. In a capillary electrophoresis device, several to dozens of capillaries are sometimes installed.

[0003] In an apparatus that uses multiple flow paths to detect fluorescence for measurement, in order to measure the fluorescence of a sample in the flow paths, it is necessary to irradiate the interior of each flow path with excitation light. As a method of irradiating multiple flow paths with excitation light at the same time, a method of irradiating the excitation light from the side of the flow paths arranged in a row (array) is known.

[0004] Patent document 1 shows a structure for irradiating excitation light from the side of a capillary array. Compared with a method of dividing the excitation light and irradiating it to each flow path, this method can more efficiently utilize the power of the excitation light. In fluorescence measurement, only a very small part of the excitation light is used for the excitation of the fluorescent body, and most of it passes through the flow path unchanged. In a structure in which the excitation light is incident from the side of the array, the excitation light that is not used for excitation can be reused for the excitation of the sample in the next flow path. As a result, the output requirements of the light source can be reduced compared with the method of dividing the excitation light. In addition, there is an advantage that an optical system for dividing the excitation light is not required.

[0005] In a structure in which the excitation light is incident from the side of the flow channel array, the light beam of the excitation light must pass through the interior of all the capillaries without a large loss. In particular, when the flow channel is a capillary having a circular cross section, it is known that this state is not achieved under arbitrary conditions, and it is not achieved unless specific conditions related to the inner and outer diameters, refractive index, etc. of the capillary are satisfied (Patent Document 2). This condition is caused by the fact that when the light beam passes through the capillary, the capillary acts as a rod lens due to its circular cross section.

[0006] For example, when the capillary is placed in the air and the inside is air, the capillary acts as a rod lens with a negative focal length, that is, a concave rod lens. In this case, the excitation light will be diffused by the capillary, and the power of the excitation light will be greatly lost during the propagation in the capillary array. When used as a structure of a fluorescence detection device, parameters such as the capillary diameter and the material filled inside are adjusted to avoid such a situation.

[0007] Prior Art Literature

[0008] Patent Literature

[0009] Patent Document 1: Japanese Patent Application Publication No. 2014-194362

[0010] Patent Document 2: JP Patent No. 3536851 Summary of the invention

[0011] Problems to be solved by the invention

[0012] In a device that uses multiple parallel channels for fluorescence detection, in order to make the measurement performance of each channel uniform, it is desirable that the power of the excitation light irradiated to each channel is uniform. In addition, in order to improve the detection sensitivity and reduce the requirements for the light source output, it is desirable that the power loss of the excitation light irradiated to the channel is as small as possible.

[0013] On the other hand, in the method of incident excitation light from the side of the aforementioned flow path array, surface reflection loss occurs at the interface of each flow path. As a result, the power of the irradiated excitation light is smaller the farther the flow path is from the incident side of the excitation light. As a means of making the power of the excitation light irradiated to each flow path uniform, there is a method of irradiating the excitation light from two directions on the side of the array and correcting the signal amount detected by the variable optical concentration filter relative to the excitation light power. However, in these methods, the device structure is complicated. In addition, in these techniques, although the power of the excitation light for each flow path is uniform, the loss of the excitation light is not reduced.

[0014] In addition, in the method of arranging multiple flow paths in an array for detection, crosstalk between detection channels also becomes a problem. The reflection of the fluorescence signal on the flow path surface and the aberration of the detection optical system become the cause of crosstalk in the measurement of each flow path. Since crosstalk becomes noise in fluorescence detection, it becomes the cause of reducing detection sensitivity and dynamic range, so it is desired to reduce it as much as possible.

[0015] The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to reduce the surface reflection loss of excitation light in a photodetection device, thereby making the power of the excitation light irradiated to each flow path more uniform.

[0016] In one example, particularly when the flow path is a capillary having a circular cross section, the purpose is to configure the light beam to pass through a plurality of capillaries with little loss. In another example, the purpose is to reduce crosstalk caused by surface reflection of fluorescence in the above structure.

[0017] Means for solving problems

[0018] An example of the light detection device involved in the present invention comprises: a flow path array, which is arranged so that the axes of a plurality of tubes are parallel to each other to form a flow path plane; an irradiation optical system, which comprises a light source, irradiates light from the light source so that the vibration direction of the electric field component of the light is parallel to the flow path plane, the optical axis of the light is contained in the flow path plane, and the optical axis forms a given angle θ0 in the flow path plane relative to the direction orthogonal to the axis of the tube; and a light detection system, which detects the light emitted from the plurality of tubes respectively, sets the refractive index of the surrounding environment to n0, sets the refractive index of the material of the tube to n1, sets the refractive index of the substance inside the tube to n2, and with respect to the angle θ1 of the light in the material of the tube determined as mathematical formula 1 according to the refractive index and the given angle and the angle θ2 of the light inside the tube, the given angle θ0 satisfies equations 1 and 2 in the following mathematical formula 2:

[0019]

Mathematical formula 1

[0020]

[0021]

Mathematical formula 2

[0022] .

[0023] An example of the light detection device involved in the present invention comprises: a flow path substrate, which has a plurality of flow paths arranged in parallel with each other in the interior to form a flow path plane; an irradiation optical system, which has a light source, irradiates light from the light source so that the vibration direction of the electric field component of the light is parallel to the flow path plane, the optical axis of the light is contained in the flow path plane, and the optical axis forms a given angle θ0 in the flow path plane relative to the direction orthogonal to the axis of the flow path; and a light detection system, which detects the light emission from the plurality of flow paths respectively, the refractive index of the material of the flow path substrate is set to n0, the refractive index of the material inside the flow path is set to n1, and the given angle θ0 satisfies mathematical formula 3,

[0024]

Mathematical formula 3

[0025] .

[0026] Effects of the Invention

[0027] According to the light detection device according to the present invention, it is possible to reduce the reflection loss of the excitation light at the flow path surface and improve the uniformity of the power of the excitation light for a plurality of flow paths.

[0028] In one example, particularly when the flow path is a capillary having a circular cross section, the light beam can be configured to pass through a plurality of capillaries with little loss by adjusting the angle of the light beam with respect to a direction perpendicular to the axis of the capillary.

[0029] In other examples, by directing fluorescence generated from only a portion of locations on the plurality of capillaries to a fluorescence detector, crosstalk between channels measuring the capillaries can be reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 is a schematic diagram related to light propagating in a flow path array.

[0031] Figure 2 It is the graph on the left side of equation (7).

[0032] Figure 3 This is a schematic diagram related to light propagating in a flow channel array provided in a flow channel substrate.

[0033] Figure 4 This is a graph showing the number of flow paths and the angle range for achieving the effect of equalizing the excitation light power.

[0034] Figure 5 It is a configuration diagram of a fluorescence detection device 500 according to Embodiment 1 of the present invention.

[0035] Figure 6 This is a graph showing the dependency of the optical power irradiated to the last capillary on the capillary distance.

[0036] Figure 7 This is a diagram showing the cross-sectional shape of the capillary observed at a cross section including the excitation light.

[0037] Figure 8 This is a graph related to the dependency of the optical power irradiated to the last capillary on the capillary pitch in the first embodiment.

[0038] Fig. 9 This is a graph of the excitation light power irradiated to each capillary.

[0039] Fig.10 It is a configuration diagram of a fluorescence detection device 1000 according to Embodiment 2 of the present invention.

[0040] Fig.11 Schematic diagram of the situation where crosstalk occurs due to fluorescence reflection at the capillary surface.

[0041] Fig.12 is the simulation result of fluorescence reflection at the capillary surface.

[0042] Fig.13 This is a schematic diagram showing a state in which crosstalk is reduced in the fluorescence detection device 1000 according to the second embodiment.

[0043] Fig.14 This is a diagram showing the crosstalk reduction effect of the fluorescence detection device 1000 according to the second embodiment.

[0044] Fig.15 This is a diagram of a structure using an optical slit in the fluorescence detection device 1000 according to the second embodiment. DETAILED DESCRIPTION

[0045] Before describing a specific embodiment, the range of light incident angles on the array that can improve the uniformity of the excitation light power for multiple channels is derived. Figure 1 The structure of the flow path array to which the embodiment of the present invention is applied is shown in FIG. Figure 1 In the flow channel array 100, a plurality of flow channels 102 formed of a material with a refractive index of n1 are arranged in an ambient environment 101 with a refractive index of n0. An inner cavity 103 exists in the flow channel 102, and a material (liquid, gel, etc.) with a refractive index of n2 is injected into the inner cavity 103.

[0046] Light from the light source is incident from the side of the flow channel array 100. Figure 1 In the embodiment, the light is incident from both sides of the same optical path, but it can also be configured so that the light is incident from only one side.

[0047] The light propagates in the flow path and irradiates the inner cavity 103 of all the flow paths 102. In this structure, the light propagates in the plane defined by the flow path array (the plane containing the central axis of all the flow paths). In addition, the light from the light source is expected to have high linearity in order to efficiently irradiate the flow path array, and therefore, laser light is mainly used.

[0048] The incident angle of the light incident on the side of the array is set to θ0. That is, the optical axis of the light from the light source forms a given angle θ0 with respect to the direction orthogonal to the axis of the flow path 102 in the flow path plane. In this case, the propagation angles θ1 and θ2 in the regions of the refractive indexes n1 and n2 are determined by the following formula according to Snell's law.

[0049]

Mathematical formula 4

[0050]

[0051] In addition, θ1 represents the angle of the light in the material of the flow channel 102 , and θ2 represents the angle of the light inside the flow channel 102 .

[0052] In order to obtain the effects of reducing surface reflection loss and improving the uniformity of the excitation light power described in the present disclosure, it is preferred to make the polarization direction of the irradiated light parallel to the plane defined by the flow path array. It can also be stated another way: the vibration direction of the electric field component of the light from the light source is parallel to the flow path plane, and the optical axis of the light from the light source is contained in the flow path plane. In addition, even if the vibration direction of the electric field component deviates slightly from the direction parallel to the plane defined by the flow path array, as long as the angle between the vibration direction and the plane defined by the flow path array is small enough, the effect of improving the uniformity of the excitation light power described in the present disclosure can be obtained to a certain extent. In addition, even in the case where the polarized light is elliptically polarized light, the same is true as long as most of the electric field component is contained in the plane defined by the flow path array.

[0053] exist Figure 1 In such a channel array 100, there are four interfaces for one channel 102. That is, these are four interfaces where the refractive index changes are n0→n1, n1→n2, n2→n1, and n1→n0. When the polarization of light is within the plane defined by the channel array, the amplitude transmittance t of light at these interfaces is expressed as follows based on Fresnel's equation.

[0054]

Mathematical formula 5

[0055]

[0056] The subscript of the transmittance indicates each interface. The amplitude transmittance of the corresponding amount of one flow path is the product of the above, and is expressed as follows.

[0057]

Mathematical formula 6

[0058]

[0059] In Patent Document 2, light from the light source is incident perpendicularly to the long axis of the array. That is, θ0 = 0°. In this case, the amplitude transmittance t of the corresponding amount of one flow path is c Become the following formula.

[0060]

Mathematical formula 7

[0061]

[0062] It is known that when polarized light is p-polarized light at a certain optical interface, there is an incident angle at which the transmittance becomes higher than when the incident angle is 0°. In particular, there is an angle at which all light is transmitted, and this angle is known as the Brewster angle. Figure 1 In such a structure, by setting the angle θ0 within an appropriate range, the light transmittance of the flow path can be increased (reflection loss can be reduced) compared with the case where the incident angle is 0°, thereby making the power of light irradiated to each flow path more uniform.

[0063] The range in which the above-mentioned effect can be obtained is represented by the intensity transmittance T of the light in the flow path represented by the square of the amplitude transmittance. c The range is larger than that of 0°. That is, θ0 can be selected within the angle range that satisfies the following formula.

[0064]

Mathematical formula 8

[0065]

[0066] If this formula is written down specifically, it becomes the following formula.

[0067]

Mathematical formula 9

[0068]

[0069] In the situation assumed in the present disclosure, since the left bracket contains a positive real number, it can also be rewritten as follows.

[0070]

Mathematical formula 10

[0071]

[0072] exist Figure 2 The following graph is described in FIG. 1 : It is assumed that the flow path is surrounded by air, the flow path material is quartz glass, and the flow path cavity is filled with water. The value of the left side of equation (7) is shown when n0=1, n1=1.46, and n2=1.33. Figure 2 The region where the value of exceeds 1 is the range in which the uniformity improvement effect of the excitation light power can be obtained. This range is determined by the lower limit of 0° and the upper limits of n0, n1, and n2, and is 69.1° under the above conditions. In the left side of equation (7), the inclination of θ0 near 0° is approximately zero, and the angle range in which a significant loss reduction effect can actually be obtained is narrower than the above.

[0073] When the left side of equation (6) is expanded with respect to θ0 and the terms of the third order or higher with respect to θ0 are ignored, the following equation (8) is obtained.

[0074]

Mathematical formula 11

[0075]

[0076] The second term of formula (8) represents the increase in intensity transmittance. As an example, in a capillary electrophoresis device, sometimes the capillaries are arranged in dozens of rows. In such a case, even if the change in the second term is small, the overall loss is reduced and the excitation light power is homogenized. For example, when n0=1, n1=1.46, n2=1.33, and the number of flow paths is 20, if θ0=0°, the power of the light irradiated to the last flow path becomes 23.7% relative to the power of the light before incident on the flow path array. In contrast, when the transmittance improvement effect (the second term of formula (8)) is 0.01 (because it is an approximation, it is not strict, in Figure 2 The light power irradiating the final flow path is reduced to 28.6%, which is an improvement of about 5%.

[0077] Thus, the lower limit angle at which the improvement effect can actually be obtained is the value of the second term of the formula (8) exceeding 0.01. If this is expressed numerically as the range of the angle θ0, it becomes the following formula.

[0078]

Mathematical formula 12

[0079]

[0080] In the above example, when n0=1, n1=1.46, and n2=1.33, the value on the right is 17.8°.

[0081] Patent document 1 shows a structure in which excitation light is incident at an angle to the flow channel array. The purpose of this structure is to prevent return light to the light source caused by light reflection from the capillary, and the angle is set to be several degrees. On the other hand, the range of angles required for uniform irradiation light power is clearly different from the angle range of several degrees shown in Patent document 1, as calculated previously.

[0082] When the light from the light source is incident at an angle of several degrees, the reflection loss reduction effect caused by the angle is negligible, which is substantially the same as the case where the incident angle is set to 0°. In addition, in order to obtain the effect of uniformizing the irradiated light power, the polarized light of the excitation light needs to be in the plane defined by the flow path, but there is no record of this condition in Patent Document 1. On the other hand, as long as it is the structure disclosed in the present invention, the excitation light must not be reflected in the direction of the light source, and therefore, return light is also prevented.

[0083] In the above example, when n0=1, n1=1.46, and n2=1.33, the angle at which the intensity transmittance reaches its peak is Figure 2 At this time, the reflection loss caused by the flow path is minimized, which is most advantageous for making the power of the irradiated excitation light uniform.

[0084] Under the above conditions, the reflection loss at the interface between air (n0=1) and silica glass (n1=1.46) is dominant, and the angle at which the transmittance becomes peak reflects this influence and becomes a value close to the Brewster angle of 55.6° at the interface between air and silica glass. As described above, when the reflection loss at a specific interface is significantly large, if the conditions are set so that the incident angle with respect to the interface becomes the Brewster angle, it becomes a substantially optimal angle for reducing the loss.

[0085] In the case described above, formula (8) can be further simplified. For example, the flow path 102 is made of resin, glass, etc., is arranged in the air, and is filled with an aqueous solution, gel, etc. In such a case, in most cases n0=1, n1=1.4~1.5, and n2=1.3~1.5. In such a case, the reflection loss caused by the interface between the air and the flow path is dominant. At this time, the interfaces to be considered are reduced to two, n0→n1 and n1→n0, and formula (7) is simplified to the following formula.

[0086]

Mathematical formula 13

[0087]

[0088] If θ1 is deleted from the above equation according to Snell's law and the equation is rewritten as an inequality with respect to θ0, the equation becomes as follows.

[0089]

Mathematical formula 14

[0090]

[0091] In addition, the arcsin function represents the inverse function of the sin function.

[0092] The formula (9) can also be simplified, and the angle range of θ0 that can obtain a practical effect can be expressed as follows when combined with the formula (11).

[0093]

Mathematical formula 15

[0094]

[0095] The above formula (12) can also be applied to Figure 3 The construction of such a situation. Figure 3 In the structure, the flow path array 100 is provided on a flow path substrate 301 having a refractive index n0. The flow path substrate 301 has a plurality of cavities 103 therein. The plurality of cavities 103 are arranged so that their axes are parallel to each other. Each cavity 103 functions as a flow path, and the flow path substrate 301 constitutes a flow path plane.

[0096] A substance (liquid, gel, etc.) with a refractive index n1 is injected into each inner cavity 103 (i.e., inside the fluid path substrate 301). In this case, the angle range in which the effect of improving the uniformity of the excitation light power can be obtained becomes the same as that of equation (12). In this case, θ0 is defined as the propagation angle of the light from the light source in the fluid path substrate 301.

[0097] Patent Document 1 shows a structure in which excitation light is irradiated from both sides of a flow path array in order to improve the deviation in the power of the irradiated excitation light caused by reflection loss at the flow path interface. On the other hand, with the structure disclosed herein, even if light is irradiated from one side, more uniform light irradiation can be achieved compared to the case where light is incident from both sides at θ0=0°.

[0098] When the above conditions are specifically written down, the following formula (13) is obtained.

[0099]

Mathematical formula 16

[0100]

[0101] Here, N is the number of channels, and ceil is a rounding function. The left side of formula (13) represents the ratio of the power of the light irradiated to the inner cavity of the channel where the power of the irradiated light is the lowest to the power of the light irradiated to the inner cavity of the channel where the power of the irradiated light is the highest, when the light from the light source is divided into two parts and incident from both sides of the channel array at an incident angle of 0°. In this structure, the channel where the power of the irradiated light is the lowest is the channel located in the center of the channel array, and the channel where the power of the irradiated light is the highest is the channel located at both ends of the channel array.

[0102] The right side of formula (13) expresses the ratio of the power of the light irradiated to the inner cavity of the flow path where the power of the irradiated light is the lowest to the power of the light irradiated to the inner cavity of the flow path where the power of the irradiated light is the highest when the light from the light source is incident from one side at an angle θ0. The power of the irradiated light is the highest in the flow path where the light is first irradiated, and is the lowest in the flow path at the end on the light emitting side (opposite to the incident side).

[0103] As described above, when θ0 satisfies the formula (13), more uniform light irradiation can be achieved.

[0104] In addition, equation (13) assumes that light is incident from only one side of the flow channel array, but it can also be Figure 1 As shown, light enters from opposite sides of the flow channel array. In this way, more uniform light irradiation can be achieved. In addition, as the light entering from both sides, the light from a single light source can be split and used, or the light from multiple light sources can be used.

[0105] Figure 4 When n0=1, n1=1.46, and n2=1.33, the angle range that satisfies the above formula (13) is indicated by oblique lines for each number of flow paths. Figure 4 In the example, equation (13) is evaluated for each number of flow paths and incident angle, and the area satisfying equation (13) is indicated by the oblique lines. When θ0 is within this angle range, more uniform light power can be irradiated by light irradiation from one side than when light is incident from both sides of the array at an incident angle of 0°.

[0106] In applications where the uniformity of the excitation light power in each channel is particularly important, higher uniformity of the excitation light power can be obtained by irradiating the excitation light from both sides of the channel in addition to using the configuration disclosed herein. In this case, the angle range only needs to satisfy equation (7).

[0107] In addition, the structure of the present disclosure is described by taking a fluorescence detection device that detects fluorescence as an example, but as long as the detection principle of generating signal light by irradiating excitation light, the structure of the present disclosure can also be used in a light detection device that detects light other than fluorescence. As an example, the object to be detected may be phosphorescence, Raman scattered light, or scattered light caused by an object flowing in a flow path.

[0108] <Implementation Method 1>

[0109] Figure 5 1 is a block diagram of a fluorescence detection device 500 according to Embodiment 1 of the present invention. Here, as an example of the structure, an example of performing fluorescence detection of a sample in a capillary array is described.

[0110] The fluorescence detection device 500 is an example of a light detection device, and includes a capillary array 501, a fluorescence excitation optical system 502, and a fluorescence detection optical system 503. In addition, the fluorescence detection device 500 is, as an example, a detection device in an electrophoresis system. In this case, it is preferred that Figure 5 In addition to the structure, the apparatus also includes a power supply for electrophoresis, a device for injecting gel into the capillary, etc., but in this figure, only the detection part involved in this embodiment is recorded.

[0111] The capillary 504 is an example of a tube constituting a flow path, and may also be referred to as a narrow-diameter tube. The cross-sectional shape of the tube is, for example, circular, but is not limited thereto. In addition, generally, the capillary is coated with polyimide or the like, but the coating is removed at the location where detection is performed.

[0112] The capillary array 501 is a flow channel array constituting a flow channel plane. The capillary array 501 has a structure in which a plurality of capillaries 504 are arranged with their axes parallel to each other.

[0113] The fluorescence excitation optical system 502 functions as an irradiation optical system, and irradiates light (laser in this embodiment) to the capillary array 501. The fluorescence excitation optical system 502 includes a laser source 505, a polarization control element 506, and a lens 507. The laser source 505 is an example of a light source, and a light source other than laser may also be used.

[0114] The laser beam 508 emitted from the laser source 505 is controlled by the polarization control element 506 so that the electric field vibration direction is within the plane defined by the capillary array 501. Thereafter, the laser beam 508 is focused by the lens 507 and incident on the side surface of the capillary array 501.

[0115] The laser beam 508 propagates inside the capillary array 501 and irradiates the measurement object inside the capillary. Figure 5 In addition to those shown, there are also mechanisms for adjusting the position of the optical axis by means of a reflecting mirror, a mechanism for adjusting the power of the laser output by attenuating the laser output, and the like.

[0116] The fluorescence detection optical system 503 is a detection optical system. Fluorescence emitted from the measurement object is detected by the fluorescence detection optical system 503. The fluorescence detection optical system 503 includes lenses 509 and 510, a wavelength filter 511, a grating 512, and a camera 513.

[0117] The fluorescence emitted from the measurement object is collimated by the lens 509. The wavelength filter 511 removes the excitation light and allows the fluorescence to pass through. The fluorescence passes through the grating 512 and the propagation angle changes according to the wavelength. Then, it is focused on the camera 513 through the lens 510. In this way, the fluorescence detection optical system 503 guides the light from each capillary 504 to the camera 513. The camera 513 is an example of a light detection system, and detects the light from each capillary 504 respectively. By performing spectral separation, the spectrum of the fluorescence emitted from the measurement object is observed on the camera 513.

[0118] exist Figure 5 In the example of the case where the fluorescence detection optical system 503 is a spectroscopic optical system, such as when multiple types of fluorescent pigments are detected by electrophoresis, the fluorescence detection optical system 503 does not necessarily have to be a spectroscopic optical system. In the case where only one type of fluorescent pigment is detected and spectroscopic analysis is not required, the generated fluorescence can be directly detected by the detector. In addition, when spectroscopic analysis is performed, the spectroscopic optical element does not necessarily have to be a grating, and spectroscopic analysis can also be performed by other spectroscopic optical elements such as a prism.

[0119] The light irradiation to the capillary array 501 can be Figure 1 At this time, the angle range of θ0 that can achieve the effect of uniformizing the excitation light power on the capillary can be obtained by the above-mentioned method.

[0120] In the calculation of the above angle range, each interface is treated as a plane, but the capillary 504 has a circular cross section, and the interface where the excitation light is incident is not a plane. However, as long as the laser beam 508 is focused on the capillary array 501 to a smaller diameter than the inner diameter and outer diameter of the capillary 504, the above discussion can be approximately applied.

[0121] On the other hand, when the flow path has a circular cross section, additional restrictions are imposed on its inner diameter, outer diameter, and pitch. This is because the flow path functions as a rod lens, and Patent Document 2 shows the conditions for the case where the laser is incident perpendicularly to the capillary array (θ0=0°). However, when the laser is incident at an angle relative to the capillary array (θ0>0°), the restrictions change compared to the perpendicular case.

[0122] First, consider the case where light is incident perpendicularly to the capillary array. The cross section of the capillary is circular, and the light irradiated near the center of the capillary passes through four interfaces. Using the paraxial approximation, calculate the ABCD matrix for the capillary. The light incident on the capillary (i) passes through the outer interface of the capillary, (ii) propagates inside the capillary, (iii) passes through the inner interface of the capillary, (iv) propagates in the inner cavity of the capillary, (v) passes through the inner interface of the capillary, (vi) propagates inside the capillary, and (vii) passes through the outer interface of the capillary. Each ABCD matrix is ​​as follows.

[0123]

Mathematical formula 17

[0124]

[0125] (Although (ii) inside the capillary and (vi) inside the capillary are the same matrix, they are given different symbols for convenience.)

[0126] The ABCD matrix of the entire capillary is calculated by the product of the above matrices.

[0127]

Mathematical formula 18

[0128]

[0129] The focal length f of the lens effect given to the light by the capillary tube is calculated as follows from the ABCD matrix of the above equation (15).

[0130]

Mathematical formula 19

[0131]

[0132] In addition, the subscript "21" in the denominator represents the 2-row and 1-column components of the matrix.

[0133] The following describes the conditions that the derived focal length and the spacing of the capillaries should satisfy. In the following, the capillaries are arranged at equal intervals with a spacing of distance d. The focal length of the capillary in the cross-sectional direction is set to f. In the calculation, the configuration of the equally spaced capillaries can be regarded as a configuration obtained by repeating the units of "space at distance d / 2", "capillary", and "space at distance d / 2". In the ABCD matrix, the propagation of distance d / 2 and the effect of the lens with focal length f are respectively represented by the following formulas.

[0134]

Mathematical formula 20

[0135]

[0136] The optical effect of the aforementioned unit is represented by the following matrix.

[0137]

Mathematical formula 21

[0138]

[0139] When there are n capillaries, that is, when the above unit is repeated n times, the optical effect is represented by the following formula.

[0140]

Mathematical formula 22

[0141]

[0142] In order for the entire amount of light incident from the end of the capillary array to pass through all the capillaries in the array, the light that has passed through the capillary must be incident on the next capillary without diverging. Since the ABCD matrix describes the influence of the height and angle from the optical axis on the light, this condition is in other words that the following formula does not diverge with respect to n.

[0143]

Mathematical formula 23

[0144]

[0145] This can be further rephrased as a condition that the absolute value of the eigenvalue with the largest absolute value among the eigenvalues ​​of the matrix of equation (18) is equal to or less than 1.

[0146] If the eigenvalue is calculated from the matrix of equation (18), the following equation is obtained.

[0147]

Mathematical formula 24

[0148]

[0149] When the second square root of equation (19) is positive, the absolute value of the negative eigenvalue exceeds 1 and diverges with respect to n. On the other hand, when the second square root is negative, the absolute values ​​of the two eigenvalues ​​become 1 and do not diverge. Therefore, the condition for uniformly irradiating all capillaries can be expressed as follows.

[0150]

Mathematical formula 25

[0151]

[0152] Furthermore, it can be seen that since d is a positive value, f must have a positive value in order to satisfy the above formula.

[0153] The following shows the results of studying the above conditions by comparing with ray tracing simulation. In the simulation, 10 capillaries with an outer diameter of 300μm and an inner diameter of 100μm are arranged. The refractive index of the material constituting the capillary is set to 1.46, the refractive index of the substance filled in the capillary is set to 1.41, and the refractive index of the surrounding environment is set to 1. The laser is incident perpendicularly to the array from the side. The diameter of the irradiated beam is set to 20μm. The polarization of the light is set to the long axis direction of the flow path. In the simulation, the power irradiated to the inner diameter part of each capillary is calculated by ray tracing.

[0154] exist Figure 6 In the graph, the power of light irradiated to the inner diameter of the 10th (last) capillary is plotted relative to the capillary spacing. The power of light reaching the 10th capillary is 54% due to surface reflection loss at the capillary, even if the spacing is the smallest at 300μm (the same value as the outer diameter). It can be seen that the power irradiated to the 10th capillary decreases from a spacing of approximately 1200μm. On the other hand, the right side of equation (20) calculated under the above conditions becomes 1240μm. The above 1240μm is shown in the graph by a dotted line. From this result, it can be seen that the range of the capillary spacing allowed under the conditions of equation (20) can be specified.

[0155] Next, the case where light is incident on the capillary array at an angle of θ0 is described. As in the calculation related to transmittance described above, the refractive index of the surrounding environment is set to n0, the refractive index of the capillary material is set to n1, and the refractive index of the substance filled in the capillary cavity is set to n2. In addition, the angles of propagation in the substances of each refractive index are set to θ0, θ1, and θ2.

[0156] Assume that the cross section of the capillary is circular. That is, in the cross section based on the plane perpendicular to the axis of the capillary, the inner and outer circumferences of the capillary are circular. If the cross section ( Figure 7 If we observe the capillary through the dotted line in (a), the cross section of the capillary becomes Figure 7(b) shows an ellipse. If the outer diameter of the capillary (radius R out ), then the uniaxial radius of the ellipse with respect to the cross section becomes R out , the radius of the major axis becomes R out / cosθ0. The light is incident on the ellipse from the major axis direction.

[0157] If the above situation is taken into consideration and the previous ABCD matrix is ​​rewritten for the case of an ellipse, it becomes the following formula.

[0158]

Mathematical formula 26

[0159]

[0160] The method for deriving the condition for light from the light source to pass through all the capillaries is the same as the case where light is incident perpendicularly to the axis of the capillary. That is, the focal length f calculated based on the ABCD matrix of the capillaries calculated in equation (15) and using equation (16) only needs to satisfy the condition of equation (20). However, since the above calculation is performed in the form of observing a surface having an angle θ0 with respect to the cross-sectional direction of the capillary array, the conditional expression of equation (20) is transformed into the following equation for the actual capillary spacing d.

[0161]

Mathematical formula 27

[0162]

[0163] If we summarize the above, the outer radius R of the capillary out and the inner radius R in , the matrix represented by equation (21) can be used to calculate the matrix of equation (15). Then, the focal length f in the direction orthogonal to the axis of the capillary can be calculated using the 2-row and 1-column components of the matrix of equation (15) and equation (16). When the focal length f satisfies equation (22) for the spacing d of the capillaries in the flow channel array, the power irradiated to the capillary can be increased.

[0164] The following is a comparison of the above conditions with the ray tracing simulation. Figure 6 The calculation of the graph is the same as that of the graph of , only the incident angle of the light beam is different. The angle of the incident excitation light is set to θ0 = 55.6°. This is the Brewster angle when the interface is a plane in the surrounding environment with a refractive index of 1 and the capillary material with a refractive index of 1.46.

[0165] exist Figure 8In the figure, the power of light irradiated to the inner diameter of the 10th (last) capillary is plotted relative to the capillary spacing. The effect of this embodiment suppresses the loss of light power caused by surface reflection of the capillary. Therefore, in the case of a capillary spacing of 300μm, even the 10th capillary is irradiated with 99.6% of the light power before incident on the array. In the case of θ0=0°, the light power irradiated to the 10th capillary is 54%, and it can be seen that the reflection loss is reduced by the effect of this embodiment.

[0166] The power irradiated to the 10th capillary decreases from the pitch of 600 μm. On the other hand, the right side of the formula (22) calculated under the above conditions becomes 615 μm. The above 615 μm is shown by a dotted line in the graph. The result shows that the range of the permissible capillary pitch can be defined by formula (22).

[0167] exist Fig. 9 The use and Figure 6 as well as Figure 8 The same simulation model shows a graph of the power of the excitation light irradiated to each of the 10 capillaries when the capillary spacing is set to 300 μm. The power of the excitation light is marked as 100% before it enters the array. In the structure where the excitation light is irradiated from both sides of the array, it is assumed that the excitation light is split into two beams with the same success rate.

[0168] When incident light is incident from one side of the array at an incident angle of 0°, the irradiated power decreases according to the capillary number. On the other hand, when the incident angle is set to 55.6°, the reflection loss is suppressed to a small level, and the power of the irradiated excitation light becomes more uniform.

[0169] When the incident angle is set to 0° and the excitation light is incident from both sides of the array, the deviation of the excitation light power is further suppressed compared with the case of irradiation from one side at an incident angle of 0°. The coefficient of variation of the excitation light power of all 10 lines in this case (the value obtained by dividing the standard deviation by the average value) is 1.5%. On the other hand, the coefficient of variation of the excitation light power when incident from one side at an incident angle of 55.6° is 0.1%, and the power of the excitation light is more uniform than when irradiated from both sides.

[0170] In addition, even when the excitation light is irradiated from both sides, 20% of the power of the excitation light will be lost due to reflection loss. On the other hand, if the structure of this embodiment is used, almost all of the power of the excitation light can be used for the excitation of fluorescence. Furthermore, when the excitation light is irradiated from both sides, a mechanism for splitting the light beam and a mechanism for adjusting so that the two light beams are incident on the array in a coaxial state are sometimes required, and the irradiation optical system becomes complicated. If the structure of this embodiment is used, the effect of uniformizing the power of the excitation light can be obtained simply by having an angled structure in the excitation light.

[0171] In the above, it is shown that in Embodiment 1, by making the angle θ0 a certain angle, the reflection loss of the excitation light is reduced, so that the power of the excitation light irradiated to each capillary can be uniform. In the method of this embodiment, in addition to the above-mentioned effects, by adjusting the angle θ0, when θ0=0°, even when the conditions required for light irradiation from the side of the capillary array are not met, irradiation of the excitation light can be performed.

[0172] As an example, the outer diameter of the capillary is set to 300 μm, the inner diameter is set to 50 μm, the refractive index of the material constituting the capillary is set to 1.46, the refractive index of the substance filled in the capillary is set to 1.33, and the refractive index of the surrounding environment is set to 1. This condition is roughly equivalent to the case where water is filled in a quartz glass capillary placed in the air.

[0173] If the excitation light is incident at θ0 = 0°, the focal length calculated in equation (16) becomes -866 μm. Since the focal length is a negative value, equation (20) cannot be satisfied regardless of the capillary spacing. In this case, the excitation light propagating in the capillary array will diverge due to the concave lens effect of the capillary and will not be able to illuminate all the capillaries.

[0174] Under the above conditions, if the angle θ0 is set to 55.6°, the focal length is 652 μm, which is a positive value, and the condition of equation (22) can be satisfied. In addition, the effect of reducing the surface reflection loss mentioned above can also be obtained at the same time. Even in the existing case of θ0=0°, when the excitation light cannot be irradiated to the entire capillary, the condition for the excitation light to propagate in the capillary can be satisfied by adjusting the value of the angle θ0 in this way.

[0175] In the structure of the present embodiment, the excitation light propagates obliquely in the capillary array. Therefore, the position where the excitation light is irradiated (the position where fluorescence detection is performed) changes for each capillary. For example, when the fluorescence detection device of the present embodiment is applied to an electrophoresis device, the effective length of electrophoresis changes due to the above-mentioned influence. In such a case, it is preferred to stagger the configuration of each capillary in sequence. For example, when the fluorescence detection points are staggered by 0.1 mm in the axial direction of the capillary, the capillaries in the array are staggered to form a step shape of 0.1 mm each.

[0176] Furthermore, by propagating the excitation light obliquely in the capillary array, the length of the portion where fluorescence is generated in the inner cavity of the capillary becomes longer than when the excitation light is irradiated in a direction perpendicular to the axis of the capillary. in When the propagation angle of light in the capillary cavity is set to θ2, the effect is 2R in As a result, the detection resolution when fluorescence detection is performed on the capillary is deteriorated.

[0177] As an example, when the excitation light is incident at an angle of 55.6° on a capillary with an inner diameter of 50 μm, a refractive index of the surrounding environment of 1, and a refractive index of 1.41 in the inner cavity, the length of the light-emitting region increases by about 36 μm. The magnitude of the effect on the overall measurement depends on the type of measurement performed and the structure of the flow path array. In the case where it is necessary to suppress this effect, the incident angle can be set small within the angle range that obtains the effect of this embodiment.

[0178] In Embodiment 1, a configuration is described in which a light detection device is considered to be used as a detection device in a capillary electrophoresis device. However, the configuration of the present disclosure is not limited to the above and can be applied to other measurement devices that perform optical measurement on a channel array.

[0179] <Implementation method 1: aggregation>

[0180] When the laser beam 508 is incident from the side of the capillary array 501, the fluorescence detection device 500 involved in the present embodiment 1 makes the laser beam 508 have an angle in the plane defined by the capillary array relative to the direction orthogonal to the axis of the capillary. The angle is set to satisfy the condition of formula (7) or formula (13). In addition, the polarization direction of the laser beam 508 is set to a direction parallel to the plane defined by the capillary. Furthermore, the spacing of the capillaries is set to satisfy the condition of formula (22). According to the above structure, the surface reflection loss caused by the capillary is reduced, and the power of the laser irradiated to each capillary can be made more uniform compared with the case where the laser is incident perpendicularly to the capillary. In addition, by adjusting the laser incident angle to adjust the restrictions related to the outer diameter, inner diameter, and configuration conditions of the capillary, it is possible to achieve irradiation conditions that cannot be achieved by a structure in which light is incident perpendicularly to the capillary.

[0181] <Implementation Method 2>

[0182] Fig.10 FIG. 1 is a diagram showing a structure of a fluorescence detection device 1000 according to Embodiment 2 of the present invention. The structure of the fluorescence detection device 1000 can be similar to that of the capillary array 501 and the fluorescence excitation optical system 502. Figure 5 The structure of the embodiment 1 shown is the same. The fluorescence detection optical system 1001 includes an optical fiber array 1002 for guiding fluorescence and a fluorescence detection device 1003. The optical fiber array 1002 is composed of a plurality of optical fibers.

[0183] A wavelength filter for removing the excitation light and guiding only the fluorescence to the detector may be provided at the front stage of the fluorescence detection device 1003. In addition, in the fluorescence detection device 1000, the fluorescence guided by the optical fiber is directly guided to the detection device, but the detection optical system is not limited to this method. As an example, the rear end of the optical fiber array 1002 may be connected to Figure 5 The fluorescence detection optical system 503 shown in FIG. 5 is connected to detect the fluorescence after separation.

[0184] exist Fig.10 In the structure shown, the incident angle of the excitation light to the capillary array is set to the angle range shown in Embodiment 1. In this case, in addition to the effects shown in Embodiment 1, crosstalk between detection channels of the detection capillaries can be reduced.

[0185] The reason why crosstalk can be reduced is described below. Crosstalk here refers to the situation where fluorescence is mixed into a channel different from the channel for detecting the capillary that emits fluorescence.

[0186] There are several reasons for the generation of such crosstalk. Fig.10In the case of the structure shown in FIG. 5 , since the fluorescence generated in the inner cavity of the capillary 504 is radiated in all directions, a part of the light may sometimes invade the optical fiber provided for the adjacent capillary. Figure 5 In the fluorescence detection optical system 503 shown, the contour of the spectral image formed on the camera 513 becomes blunt due to aberrations of the lenses 509 and 510, and the contour may overlap with the portion of the capillary adjacent to the detection.

[0187] Among the causes of crosstalk, the structure of this embodiment can reduce the crosstalk caused by the surface reflection of the capillary. Since the fluorescence generated in a capillary irradiates all directions as mentioned above, the adjacent capillary is also irradiated with the fluorescence. A part of the fluorescence is reflected on the surface of the capillary, and according to its reflection angle and position, it will be incident on the optical fiber used to detect the adjacent capillary.

[0188] In this case, the fluorescence that travels vertically from the light-emitting site to the adjacent capillary contributes more to the crosstalk. Fig.11 This situation is shown schematically. Fig.11 The fluorescence emitted from the light emitting portion 504c in the left capillary 504a is radiated in all directions with equal intensity, but what is actually detected is only the light that travels toward the detector side assumed to be located in front of the paper surface.

[0189] The light that travels perpendicularly from the left capillary 504a to the right capillary 504b is reflected on the left half of the right capillary 504b. However, since the capillary 504b is cylindrical, the light reflected in the region 504d easily enters the detector located in front of the paper. The region 504d can be said to be a part that has a large influence on the crosstalk. Even if the fluorescence irradiated outside the region 504d is reflected on the surface of the capillary 504b, it will not propagate toward the detector.

[0190] Fig.12 This situation is shown by simulation. Fig.12 In the simulation, a capillary array with a diameter of 150 μm, an inner diameter of 50 μm, and a pitch of 150 μm is set. The refractive index of the surrounding environment is set to 1, the refractive index of the capillary material is set to 1.46, and the refractive index of the capillary lumen is set to 1.41. In the simulation, an imaging system and a detection camera with NA 0.36 are set on the front side of the paper, and a simulation is set to obtain a fluorescent image of the fluorescence generated in the capillary lumen.

[0191] exist Fig.12 In the image, the portion corresponding to the two adjacent capillaries on the camera is cut out and displayed. The positional relationship between the capillaries is Fig.11 The schematic diagram is similar, Fig.12 (a) and Fig.11 The capillary 504a corresponds to, Fig.12(b) and Fig.11 Corresponding to the capillary 504b.

[0192] The capillary 504a on the left side emits light. Fig.12 The blackened portion of the image (a) is the luminescent portion. The capillary 504b on the right does not emit light. Fig.12 In the image, the image is constructed so that the higher the fluorescence intensity, the darker the black. Fig.12 (a) and Fig.12 The darkest part in (b) has the same density. This is because the color scale is set in each image. Fig.12 (b) The fluorescence intensity ratio of the image Fig.12 (a) small.

[0193] and Fig.12 The capillary 504b corresponding to (b) does not emit light, but there is a black portion on the left side of the capillary. This portion is equivalent to Fig.11 Thus, the fluorescence reflected on the capillary surface enters the channel of the adjacent capillary for detection and is observed as crosstalk.

[0194] The following explains why the crosstalk caused by the above reasons can be reduced by making the excitation light incident at an angle. Fig.13 Shown in Fig.11 The portion detected by the optical fiber is added to the schematic diagram with a dotted line. Fig.13 When the light is irradiated at an incident angle of 0° as in (a), the light-emitting parts are arranged at the same angle of 0°, that is, horizontally, on each capillary. As a result, the light-emitting parts of adjacent capillaries are close to the parts where crosstalk is generated by the surface reflection mentioned above. Therefore, the fluorescence reflected on the surface easily enters the optical fiber.

[0195] On the other hand, if Fig.13 As in (b), the excitation light is irradiated at an angle to the capillary array, and the light-emitting parts are also arranged at an angle on the capillary, that is, they are arranged far apart in the axial direction of the capillary. On the other hand, the part where crosstalk is generated by surface reflection becomes the part that is closest to the capillary array. Fig.13 The positions of the light emitting part and the crosstalk generating part are the same when the angle of (a) is 0°, so the positions of the light emitting part and the crosstalk generating part can be distanced in the axial direction. As a result, the fluorescence reflected on the capillary surface is unlikely to enter the optical fiber used to measure the adjacent capillary, and the crosstalk is reduced.

[0196] Fig.14 The above effect was quantitatively demonstrated by ray tracing simulation. In this simulation, eight φ150μm capillaries were arranged at a pitch of 175μm, and an optical fiber with a core diameter of 100μm and NA0.4 was set at a distance of 50μm from the capillary at the light-emitting portion of each capillary.

[0197] exist Fig.14 In the example, it is assumed that capillary No. 4 emits light, and the power of the excitation light introduced into the optical fiber for detecting capillary No. 4 is set to 100%. The fluorescence detected in the capillary array other than No. 4 is the crosstalk caused by No. 4. When the excitation light is incident perpendicularly to the capillary array, the crosstalk generated in the capillary adjacent to the emitting capillary is about 2.2%. On the other hand, when the excitation light is irradiated at an angle of 55.6°, the crosstalk generated in the adjacent capillary is reduced to about 0.6%.

[0198] The crosstalk reduction effect is produced by increasing the distance between the fluorescent light emitting portion and the portion where crosstalk is generated by surface reflection in the axial direction, and selectively detecting only the fluorescence. In particular, in the present embodiment, in the fluorescence detection optical system 1001, only the light from the portion where light is generated in the capillary 504 is guided to the detector by the optical fiber, and the portion around the portion (the portion where no light is generated) can be optically shielded, thereby reducing crosstalk.

[0199] As a means of selectively extracting only the fluorescence, an optical element other than an optical fiber may be used. Fig.15 In this way, the fluorescence detection optical system 1001 may also include an optical slit member 514 ( Fig.15 (In the figure, only the shape of the slit portion is shown by a dotted line). The slit of the optical slit member 514 is sized to allow only light from the fluorescence detection site to pass therethrough.

[0200] In the fluorescence detection optical system 1001, the slit of the optical slit member 514 can be arranged only corresponding to the portion generating light in each capillary 504. In this way, since the optical slit member 514 optically shields the portion surrounding the portion generating light in each capillary 504 (the portion not generating light), it is possible to reduce crosstalk while allowing the fluorescence to be detected to pass efficiently.

[0201] <Implementation method 2: aggregation>

[0202] The fluorescence detection device 1000 according to Embodiment 2 makes the laser beam 508 angled with respect to a direction orthogonal to the axis of the capillary when the laser beam 508 is incident from the side of the capillary array 501. The fluorescence generated in each capillary is guided to the fluorescence detection device 1003 by the optical fiber array 1002. With the above configuration, crosstalk caused by the fluorescence being reflected on the surface of the capillary and incident on the optical fiber provided for the adjacent capillary can be reduced.

[0203] <About Modifications>

[0204] The present invention is not limited to the aforementioned embodiments, and includes various variations. For example, the aforementioned embodiments are described in detail to explain the present invention in an easy-to-understand manner, but are not necessarily limited to all structures described. In addition, a part of the structure of a certain embodiment can be replaced with the structure of another embodiment, and in addition, the structure of another embodiment can be added to the structure of a certain embodiment. In addition, other structures can be added, deleted, or replaced to a part of the structure of each embodiment.

[0205] Description of Reference Numerals

[0206] 100 Stream Array

[0207] 101 Surrounding Environment

[0208] 102 flow path

[0209] 103 Lumen

[0210] 301 flow path substrate

[0211] 500 Fluorescence Detection Device

[0212] 501 Capillary Array

[0213] 502 Fluorescence Excitation Optical System

[0214] 503 Fluorescence detection optical system

[0215] 504 (504a, 504b) Capillary

[0216] 505 Laser Source

[0217] 506 Polarization Control Element

[0218] 507 Lens

[0219] 508 Laser Beam

[0220] 509 Lens

[0221] 510 lens

[0222] 511 wavelength filter

[0223] 512 Grating

[0224] 513 Camera

[0225] 514 Optical Slit Component

[0226] 1000 Fluorescence detection device

[0227] 1001 Fluorescence detection optical system

[0228] 1002 Fiber Array

[0229] 1003 Fluorescence detection device.

Claims

1. A light detection device, characterized in that: have: a flow path array, in which the axes of the multiple tubes are arranged parallel to each other, forming a flow path plane; an irradiation optical system including a light source, irradiating light from the light source so that the vibration direction of the electric field component of the light is parallel to the flow path plane, the optical axis of the light is contained in the flow path plane, and the optical axis forms a given angle θ0 in the flow path plane with respect to a direction orthogonal to the axis of the tube; and a light detection system for detecting light emission from the plurality of tubes, respectively, The refractive index of the surrounding environment is set to n0, the refractive index of the material of the tube is set to n1, and the refractive index of the substance inside the tube is set to n2. With respect to the angle θ1 of the light in the material of the tube and the angle θ2 of the light inside the tube determined as Mathematical Formula 1 based on the refractive index and the given angle, the given angle θ0 satisfies Formula 1 and Formula 2 in the following Mathematical Formula 2: 【Mathematical formula 1】 【Mathematical formula 2】 。 2. The light detection device according to claim 1, wherein: When the number of the tubes is set to N, the given angle θ0 further satisfies the following formula: 【Mathematical formula 3】 。 3. The light detection device according to claim 1, wherein: Light from the light source is incident on the flow channel array from opposite sides.

4. The light detection device according to claim 1, wherein: The tube is a capillary tube whose inner and outer circumferences are circular in a cross section based on a plane perpendicular to the axis of the tube. About the outer radius R of the tube out and the inner radius R in The focal length in the direction orthogonal to the axis of the tube calculated by the 2-row and 1-column components of the matrix represented by Formula 4 and calculated by Formula 5, i.e., Formula 6, satisfies Formula 7 relative to the spacing d of the tubes in the flow channel array, 【Mathematical formula 4】 【Mathematical formula 5】 【Mathematical formula 6】 【Mathematical formula 7】 。 5. The light detection device according to claim 4, wherein: The light detection device comprises: a detection optical system that guides the light emitted from the plurality of tubes to the light detection system, In the detection optical system, non-luminescent portions in the periphery of portions where light is generated in the plurality of tubes are optically shielded.

6. The light detection device according to claim 5, wherein: The detection optical system comprises an optical fiber, The optical fiber guides only the light emitted from the portion generating the light to the detector, thereby optically shielding the portion that does not generate the light.

7. The light detection device according to claim 5, wherein: The detection optical system comprises: an optical slit member arranged in association with the plurality of tubes; The optical slit member optically shields a portion where the light emission is not generated.

8. A light detection device, characterized in that: have: A flow path substrate having a plurality of flow paths arranged in parallel with each other in the interior thereof, constituting a flow path plane; an irradiation optical system including a light source, irradiating light from the light source so that the vibration direction of the electric field component of the light is parallel to the flow path plane, the optical axis of the light is contained in the flow path plane, and the optical axis forms a given angle θ0 in the flow path plane with respect to a direction orthogonal to the axis of the flow path; and a light detection system for detecting light emission from the plurality of flow paths, respectively, Let the refractive index of the material of the flow path substrate be n0, let the refractive index of the substance inside the flow path be n1, and the given angle θ0 satisfies Mathematical Formula 8, 【Mathematical formula 8】 。

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