Light homogenization device, gene sequencing system and control method of gene sequencing system

Abstract

The present invention discloses a light homogenizing device, a gene sequencing system and a control method of the gene sequencing system, wherein the light homogenizing device comprises: a light source, the light source is used to generate a laser signal; an aperture, the aperture is coupled to the light source, the aperture is used to filter the incident laser signal to form a filter signal; an even-order aspheric reflector, the even-order aspheric reflector is coupled to the aperture, the even-order aspheric reflector is used to form a target light homogenizing beam according to the filter signal; wherein the target light homogenizing beam is used to excite a sample to be detected to generate a fluorescence signal; the shape and size of the target light homogenizing beam matches the shape and size of a camera imaging surface; wherein the camera is used to collect the fluorescence signal in the imaging surface. The light homogenizing device of the present invention can achieve a better excitation lighting effect.

Description

Technical Field

[0001] The present invention relates to the technical field of gene sequencing, and in particular to a light homogenizing device, a gene sequencing system and a control method of the gene sequencing system. Background Art

[0002] At present, based on the excitation characteristics of fluorescent dyes to lasers, a corresponding illumination area can be formed by lasers to excite and illuminate the fluorescent dyes in the illumination area, thereby obtaining corresponding fluorescence signals. However, due to the Gaussian distribution characteristics of lasers, the light intensity at the center of the illumination area is stronger, while the light intensity at the edge of the illumination area is weaker, resulting in poor excitation illumination effect. Summary of the invention

[0003] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides a light homogenizing device, a gene sequencing system and a control method of the gene sequencing system, wherein the light homogenizing device can achieve a better excitation lighting effect.

[0004] In the first aspect, the present application provides a light homogenizing device, which includes: a light source, which is used to generate a laser signal; an aperture, which is placed behind the light source along the optical axis of the laser signal, and is used to spatially filter the incident laser signal to form a filtered signal; an even-order aspheric reflector, which is placed behind the aperture along the optical axis of the filtered signal, and is used to form a target homogenizing beam according to the filtered signal; wherein the target homogenizing beam is used to excite a sample to be detected to generate a fluorescence signal; the shape and size of the target homogenizing beam match the shape and size of a camera imaging surface; wherein the camera is used to collect the fluorescence signal within the imaging surface.

[0005] In this embodiment, the light homogenizing device performs spatial filtering on the collimated laser signal through an aperture, filters out the edge portion of the laser signal with weak light intensity, and preliminarily improves the uniformity of the laser signal, thereby obtaining a filtered signal; the light homogenizing device also shapes and homogenizes the filtered signal through an even-order aspheric reflector to obtain a target homogenizing light beam whose shape and size match the shape and size of the camera imaging surface. The target homogenizing light beam is evenly distributed in light intensity, and can avoid accelerating the photobleaching speed and damaging the sample to be detected while ensuring the signal-to-noise ratio required for camera imaging. In addition, since the shape and size of the target homogenizing light beam match the shape and size of the camera imaging surface, the photobleaching of the non-imaging area and the phototoxicity to DNA (sample to be detected) can be reduced. The light homogenizing device in this embodiment can achieve a better excitation lighting effect through a simple structure.

[0006] In some embodiments, the surface shape formula of the even-order aspheric reflector satisfies the following relationship:

[0007] Wherein, c is the curvature, k is the conic coefficient, and α 1 is the second-order aspheric coefficient, and α 2 is the fourth-order aspheric coefficient, and α 3 is the sixth-order aspheric coefficient, and α 3 is the eighth-order aspheric coefficient, and x, y are the specific coordinate positions on the aspheric surface.

[0008] In some embodiments, k = -146.5, and α 1 = 0, and α 2 = 1.848E-4, and α 3 = -4.159E-6, and α 4 = 3.216E-8.

[0009] In some embodiments, the even-order aspheric mirror satisfies the following relationship: 14.6 < f < 16.1, where f is the focal length of the even-order aspheric mirror.

[0010] In some embodiments, the light homogenizing device further includes: an objective lens, which is placed behind the even-order aspheric mirror along the optical axis of the target homogenized light beam, and the objective lens is used to perform a converging operation on the target homogenized light beam to form a converged optical signal.

[0011] In a second aspect, the present application further provides a gene sequencing system, which is used to test a sample to be detected to generate a detection result. The gene sequencing system includes: the light homogenizing device as described in any one of the above embodiments; a biochip, which carries the sample to be detected, and the biochip is used to be irradiated by the target homogenized light beam to excite and generate a fluorescence signal; at least one fluorescence spectroscopy module, which is used to perform a spectroscopy operation on fluorescence signals of different wavelengths; at least one fluorescence acquisition module, which is used to acquire the fluorescence signals after the spectroscopy operation and generate an image signal; a processing module, which is connected to the fluorescence acquisition module, and the processing module is used to generate a detection result according to the image signal.

[0012] In some embodiments, the gene sequencing system also includes: a translation stage, the translation stage is used to carry the biochip; wherein the shape of the biochip is rectangular; the shape of the target uniform light beam is elliptical or quasi-elliptical or rectangular; the translation stage is also connected to the processing module; wherein the processing module is also used to control the movement of the translation stage so that the short axis of the target uniform light beam moves relative to the long side of the biochip, and the short axis of the target uniform light beam is parallel to the long side of the biochip, so that the camera scans the biochip; wherein the imaging surface of the camera is a rectangular imaging surface, and the length-to-width ratio of the rectangular imaging surface is L:W; the ratio of the long and short axes of the spot of the target uniform light beam is L:W; wherein L and W are both positive integers.

[0013] In some embodiments, the gene sequencing system also includes: an objective lens, which is used to converge the target uniform light beam to form a converged light signal; the objective lens is also used to collect the fluorescence signal; and a first dichroic mirror, which is used to reflect or transmit the target uniform light beam and the fluorescence signal respectively.

[0014] In some embodiments, the fluorescence spectrometer module includes: at least one dichroic mirror, and the dichroic mirror is placed behind the first dichroic mirror along the optical axis of the fluorescence signal.

[0015] In some embodiments, the fluorescence collection module includes: a tube lens, which is placed behind the fluorescence spectrometer module along the optical axis of the fluorescence signal; a filter, which is placed behind the tube lens along the optical axis of the fluorescence signal; and a camera, which is placed behind the filter along the optical axis of the fluorescence signal.

[0016] In the third aspect, the present application also provides a control method for a gene sequencing system, which is applied to a gene sequencing system as described in any of the above embodiments, comprising: obtaining a scanning control signal; according to the scanning control signal, controlling the movement of a translation stage so that the short axis of the target uniform light beam moves relative to the long side of the biochip, and the short axis of the target uniform light beam is parallel to the long side of the biochip; during the movement of the translation stage, sequentially obtaining image signals from the camera to scan the biochip, thereby obtaining the detection result.

[0017] In some embodiments, the imaging surface of the camera is a rectangular imaging surface, and the shape of the target uniform light beam is an ellipse, a quasi-ellipse, or a rectangle; the length-to-width ratio of the rectangular imaging surface is L:W; the ratio of the major and minor axes of the spot of the target uniform light beam is L:W; wherein L and W are both positive integers.

[0018] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The present invention will be further described below with reference to the accompanying drawings and embodiments, wherein:

[0020] Figure 1 A schematic diagram of the structure of a light homogenizing device according to an embodiment of the present invention;

[0021] Figure 2 A schematic diagram of a working principle of a sample to be detected according to an embodiment of the present invention;

[0022] Figure 3 A long-axis light intensity distribution diagram of a target uniform light beam according to an embodiment of the present invention;

[0023] Figure 4 A short-axis light intensity distribution diagram of a target uniform light beam according to an embodiment of the present invention;

[0024] Figure 5 Another structural schematic diagram of the light homogenizing device according to an embodiment of the present invention;

[0025] Figure 6 A schematic diagram of a gene sequencing system according to an embodiment of the present invention;

[0026] Figure 7 Another schematic diagram of the framework of the gene sequencing system according to an embodiment of the present invention;

[0027] Figure 8 A schematic diagram of a working principle of a biochip according to an embodiment of the present invention;

[0028] Fig. 9 A schematic diagram of the structure of a gene sequencing system according to an embodiment of the present invention;

[0029] Fig.10 A flow chart of a control method of a gene sequencing system according to an embodiment of the present invention.

[0030] Figure numerals: light homogenizing device 100, light source 110, aperture 120, even-order aspheric reflector 130, sample to be detected 200, objective lens 140, gene sequencing system 300, biochip 310, fluorescence collection module 320, fluorescence spectrometer module 330, processing module 340, translation stage 350, first dichroic mirror 360, first dichroic mirror 331, second dichroic mirror 332, third dichroic mirror 333, first reflector 334, tube lens 321, filter 322, camera 323, second reflector 370. DETAILED DESCRIPTION

[0031] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and cannot be understood as limiting the present invention.

[0032] In the description of the present invention, it should be understood that descriptions involving orientations, such as up, down, front, back, left, right, etc., and orientations or positional relationships indicated are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0033] In the description of the present invention, "several" means more than one, "many" means more than two, "greater than", "less than", "exceed", etc. are understood to exclude the number itself, and "above", "below", "within", etc. are understood to include the number itself. If there is a description of "first" or "second", it is only used for the purpose of distinguishing the technical features, and cannot be understood as indicating or implying the relative importance or implicitly indicating the number of the indicated technical features or implicitly indicating the order of the indicated technical features.

[0034] In the description of the present invention, unless otherwise clearly defined, terms such as setting, installing, connecting, etc. should be understood in a broad sense, and technicians in the relevant technical field can reasonably determine the specific meanings of the above terms in the present invention based on the specific content of the technical solution.

[0035] In the description of the present invention, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0036] It should be noted that when the sample to be detected is detected, the fluorescent dye in the sample to be detected is excited and illuminated by the laser signal, and the corresponding fluorescent signal can be obtained. For example, in some application scenarios, it is necessary to detect the gene sequence in the sample to be detected. To this end, the laser signal is irradiated on the sample to be detected, so that the sample to be detected generates a corresponding fluorescent signal under the excitation of the laser signal, and the fluorescent signal is scanned and imaged by the camera, so that the gene sequence can be detected.

[0037] In the related art, based on the characteristics of the Gaussian distribution of the laser signal, when the laser signal is used to excite and illuminate the fluorescent dye in the illumination area, since the light intensity in the center of the illumination area is stronger and the light intensity at the edge of the illumination area is weaker, the excitation efficiency of the fluorescent dye in the center of the illumination area is high, and the intensity of the fluorescent signal emitted is also higher, while the excitation efficiency of the fluorescent dye at the edge of the illumination area is low, and the intensity of the fluorescent signal emitted is also lower. In order to improve the excitation efficiency of the fluorescent dye at the edge of the illumination area, so as to increase the intensity of the fluorescent signal emitted, so as to achieve the signal-to-noise ratio required by the camera to image the fluorescent signal, it is necessary to increase the power of the laser signal to compensate for the disadvantage of low excitation efficiency at the edge of the illumination area. However, when the power of the laser signal is increased, the laser intensity in the center of the illumination area is too large, which easily leads to an increase in the photobleaching rate, thereby increasing the error rate of the detection result of the sample to be detected.

[0038] It is understandable that in the related art, by using a light-shaping optical device to homogenize the laser signal, a target homogenized light beam with a relatively uniform light intensity can be obtained. However, the related light-shaping optical device is generally a structure of a whole set of lenses, which has the problems of large size and high cost, and after homogenization, a Kohler lighting module is required to further homogenize the light. Therefore, when the light-shaping optical device of the related art is applied to the light-shaping device, the structure of the light-shaping device will be complicated and the optical path will be long.

[0039] To this end, the present application provides a light homogenization device that can achieve a better excitation lighting effect, has a simple structure, and is easy to implement.

[0040] See also Figure 1 to Figure 2 In the first aspect, the present application provides a light homogenizing device 100, which includes: a light source 110, which is used to generate a laser signal; an aperture 120, which is placed behind the light source 110 along the optical axis of the laser signal, and the aperture 120 is used to spatially filter the incident laser signal to form a filtered signal; an even-order aspheric reflector 130, which is placed behind the aperture 120 along the optical axis of the filtered signal, and the even-order aspheric reflector 130 is used to form a target homogenizing beam according to the filtered signal; wherein the target homogenizing beam is used to excite a sample 200 to be detected to generate a fluorescence signal.

[0041] It is understandable that the light homogenizing device 100 in this embodiment includes a light source 110, an aperture 120 and an even-order aspheric reflector 130. The light source 110 is used to generate a laser signal, and the aperture 120, the even-order aspheric reflector 130 and the sample 200 to be detected are sequentially arranged along the optical axis of the laser signal.

[0042] It can be understood that the light source 110 is used to generate a collimated laser signal, and the spot shape of the laser signal is circular. The laser signal is transmitted to the aperture 120. The aperture 120 refers to a device that limits the light beam in the optical system. When the laser signal is incident on the aperture 120, the aperture 120 can filter the light beam of the laser signal, thereby blocking the edge portion of the laser signal with weak light intensity, so as to facilitate the subsequent even-order aspheric reflector 130 to further homogenize the laser signal.

[0043] It can be understood that the laser signal is a circular spot of Gaussian distribution, that is, in the spot area (illumination area) of the laser signal, the light intensity presents a Gaussian distribution characteristic. To this end, the light homogenizing device 100 in this embodiment is provided with a corresponding even-order aspheric reflector 130, and the even-order aspheric reflector 130 is used to perform a homogenizing operation on the incident filtered signal to form a uniform illumination spot of a target homogenizing beam with a certain shape and size. Compared with the illumination spot that is not homogenized and only filtered by the aperture space, the light intensity distribution in the illumination area of ​​the target homogenizing beam is more uniform. In addition, the even-order aspheric reflector 130 is also used to reflect the target homogenizing beam so that the target homogenizing beam is irradiated on the sample 200 to be detected. The light homogenizing device 100 of this embodiment can perform a homogenizing operation on the filtered signal through the even-order aspheric reflector 130 to obtain a target homogenizing beam with uniform light intensity distribution. When the target homogenizing beam is used to excite and illuminate the sample 200 to be detected, the light intensity in each illumination area is uniform, and there will be no problem of inconsistent excitation efficiency. Therefore, the light homogenizing device 100 of this embodiment can achieve a better excitation lighting effect with a simple structure.

[0044] It is understandable that the sample to be detected 200 generates a fluorescence signal under the excitation illumination of the target uniform light beam, and the shape and size of the target uniform light beam are the same as the shape and size of the fluorescence signal. Among them, the fluorescence signal can characterize different detection results of the sample to be detected 200. For example, suppose that the sample to be detected 200 contains different gene sequences, and different gene sequences can be marked by fluorescence of different spectra. Then, when the target uniform light beam excites and illuminates the sample to be detected 200, different gene sequences in the sample to be detected 200 can generate fluorescence signals of different spectra after being excited. Therefore, the detection result of the gene sequence of the sample to be detected 200 can be obtained through different fluorescence signals.

[0045] It is understandable that in order to obtain the detection result of the sample to be detected 200, the fluorescence signal generated by the sample to be detected 200 can be scanned and imaged by the camera 323 to obtain the corresponding detection result. Specifically, the fluorescence signal is transmitted to the imaging surface of the camera 323, and the camera 323 can scan and image the light within its imaging surface to obtain an image signal corresponding to the fluorescence signal. In addition, the camera 323 needs to scan and image multiple areas of the sample to be detected 200 to obtain image signals of different areas, thereby obtaining detection results of different areas. However, in the related art, the efficiency of the camera 323 in scanning and imaging multiple areas of the sample to be detected 200 is low. Specifically, the homogenization effect of the homogenization shaping optical device in the related art is isotropic, that is, the circular light spot of the filtered signal after passing through the homogenization shaping optical device, the target homogenization beam formed is still a circular light spot, then the fluorescence signal generated by the sample to be detected 200 according to the target homogenization beam is also a circular light spot. In some application scenarios, such as Figure 2 As shown, the imaging surface A of the camera 323 may be rectangular or in other shapes. In order to allow all the fluorescent signals to enter the imaging surface A of the camera 323 for imaging, the target uniform light beam can only excite and illuminate a small area of ​​the sample 200 to be detected, so as to obtain a fluorescent signal with a smaller circular spot B. Figure 2 As shown in FIG. 1 , since the imaging surface A of the camera 323 is rectangular, except for the portion of the circular spot B that can collect the fluorescence signal, the rest of the imaging surface A of the camera 323 is not scanned for the fluorescence signal, which easily leads to low efficiency of the scanning imaging of the camera 323. In order to allow the fluorescence signal to completely cover the imaging surface A of the camera 323 to improve the efficiency of the scanning imaging of the camera 323, as shown in FIG. Figure 2 As shown, the circular spot C of the target uniform light beam needs to be larger than the imaging surface A of the camera 323 so that the fluorescence signal can completely cover the imaging surface A of the camera 323. However, the camera 323 can only scan and image the fluorescence signal of the imaging part (the part located within the imaging surface A), and the part of the fluorescence signal exceeding the imaging surface A of the camera 323 cannot be scanned and imaged by the camera 323, that is, no corresponding detection result is obtained. Therefore, it is necessary to move the sample 200 to be detected so that the exceeding part enters the imaging surface A of the camera 323, and use the target uniform light beam for excitation illumination again to generate the corresponding fluorescence signal. It can be understood that after the exceeding part is excited and illuminated more than once, it is possible to cause photobleaching of the area, thereby reducing the signal-to-noise ratio of the imaging of the camera 323. And it will damage the substance in the sample 200 to be detected, affecting the subsequent detection results. It can be seen from this that in the related art, the efficiency of the camera 323 in scanning and imaging multiple areas of the sample 200 to be detected is low.

[0046] It is understandable that, in order to improve the scanning imaging efficiency of the camera 323, the even-order aspheric reflector 130 of the light homogenizing device 100 in this embodiment can not only perform light homogenization operation on the filter signal, but also be used to shape the filter signal. Specifically, the even-order aspheric reflector 130 can shape the shape of the laser signal into an ellipse or a quasi-ellipse, so that the formed target homogenized light beam excites and illuminates the sample 200 to be detected in the illumination area, and generates an ellipse or a quasi-ellipse fluorescence signal, wherein the shape and size of the target homogenized light beam match the imaging surface A of the camera 323, that is, match the shape and size of the light spot of the fluorescence signal.

[0047] In a specific embodiment, Figure 2 As shown, when the imaging surface A of the camera 323 is a rectangle with an aspect ratio L:W of 2:1, the laser signal is filtered by the aperture 120 to form a filtered signal, and is incident on the reflection surface of the even-order aspheric reflector 130. The even-order aspheric reflector 130 performs homogenization and shaping operations on the filtered signal to form a target homogenized light beam. After the target homogenized light beam is reflected from the even-order aspheric reflector 130, it first converges and then diverges, and finally irradiates the sample 200 to be detected for excitation illumination. The illumination area formed by the target homogenized light beam on the sample 200 to be detected is an elliptical light spot D, and the major-minor axis ratio of the elliptical light spot D is 2:1. At this time, the shape and size of the target homogenized light beam match the shape and size of the imaging surface A of the camera 323, that is, the shape and size of the fluorescence signal match the shape and size of the imaging surface A of the camera 323. When the target uniform light beam is irradiated on the sample 200 to be detected, since the illumination area formed by the target uniform light beam is elliptical, multiple areas of the sample 200 to be detected can be excited and illuminated at the same time, and since the imaging surface A of the camera 323 is coordinated with the target uniform light beam, the camera 323 can scan and image all the generated fluorescence signals, thereby effectively improving the scanning imaging efficiency of the camera 323 and avoiding damage caused by excessive excitation illumination of the same area of ​​the sample 200 to be detected multiple times.

[0048] It can be understood that when the aspect ratio of the imaging surface A of the camera 323 is equal to the ratio of the major and minor axes of the target uniform light beam spot D, the shape and size of the imaging surface A of the camera 323 match the shape and size of the target uniform light beam spot D. Similarly, when the imaging surface A of the camera 323 is of other shapes, the parameters of the even-second aspheric reflector 130 can be reasonably set to obtain the target uniform light beam spot D whose shape and size match the imaging surface, thereby improving the detection efficiency of the sample 200 to be detected.

[0049] It can be understood that since the light homogenizing device 100 in this embodiment performs light homogenization and shaping operations on the laser signal through the reflection surface of the even-order aspheric reflector 130, it is only necessary to design and manufacture the reflection surface of the even-order aspheric reflector 130 accordingly, and there is no need to add additional reflectors. This can reduce the volume of the light homogenizing device 100 and simplify the structure to a certain extent.

[0050] In this embodiment, the light homogenizing device 100 filters the collimated laser signal through the aperture 120 to adjust the light intensity of the laser signal and filter out the edge portion of the laser signal with weak light intensity, thereby obtaining a filtered signal; the light homogenizing device 100 also shapes and homogenizes the filtered signal through the even-order aspheric reflector 130 to obtain a target homogenizing light beam whose shape and size match the shape and size of the imaging surface of the camera 323. The target homogenizing light beam is evenly distributed in light intensity, and can avoid accelerating the photobleaching speed and damaging the sample 200 to be detected while ensuring the signal-to-noise ratio required for imaging by the camera 323. In addition, since the shape and size of the target homogenizing light beam match the shape and size of the imaging surface of the camera 323, the efficiency of scanning imaging by the camera 323 can be effectively improved. In this embodiment, the light homogenizing device 100 can achieve a better excitation lighting effect through a simple structure.

[0051] Please refer to 1. Figure 3 and Figure 4 In some embodiments, the surface shape formula of the even-order aspheric reflector 130 satisfies the following relationship:

[0052] Where c is the curvature, k is the cone coefficient, α 1 is the second-order aspheric coefficient, α 2 is the fourth-order aspheric coefficient, α 3 is the sixth-order aspheric coefficient, α 3 is the eighth-order aspheric coefficient, and x and y are the specific coordinate positions of the aspheric surface.

[0053] It can be understood that when the even-order aspheric reflector 130 satisfies the above formula, the target uniform light beam of the elliptical light spot can be obtained after the filter signal is reflected by the even-order aspheric reflector 130. In addition, by setting specific surface parameters: curvature, cone coefficient, second-order aspheric coefficient, fourth-order aspheric coefficient, sixth-order aspheric coefficient, eighth-order aspheric coefficient, and determining the specific coordinate position of the aspheric surface, target uniform light beams of different shapes and sizes can be obtained, that is, the major and minor axes of the elliptical light spot are different. It can be seen from the above content that by making the target uniform light beam of the elliptical light spot match the rectangular imaging surface of the camera 323, the efficiency of scanning imaging of the camera 323 can be improved. And the target uniform light beam formed by the even-order aspheric reflector 130 in this embodiment has a good uniform light effect, which can achieve a better excitation lighting effect.

[0054] Specifically, Figure 3 is the light intensity distribution diagram in the long axis direction of the spot of the target uniform light beam, Figure 4 is the light intensity distribution diagram in the short axis direction of the spot of the target uniform light beam. In this embodiment, the length of the long axis of the spot of the target uniform light beam is 1.6 mm, and the length of the short axis is 0.8 mm as an example to calculate the illumination uniformity. Specifically, the minimum light intensity in the illumination area is divided by the maximum light intensity to obtain the illumination uniformity. Among them, the uniformity in the long axis direction is 81%, and the uniformity in the short axis direction is 85%. It can be understood that when the illumination uniformity reaches more than 75%, the extraction efficiency of the effective information of the center and edge of the illumination area corresponding to the photographing position of the camera 323 by the imaging algorithm is almost the same. Therefore, the uniform light device 100 of this embodiment can well meet the actual use requirements.

[0055] Please refer to Figure 1 and Figure 2 In some embodiments, k = -146.5, α 1 = 0, α 2 = 1.848E-4, α 3 = -4.159E-6, α 4 = 3.216E-8.

[0056] It can be understood that this embodiment is described by taking the aspect ratio of the length and width of the imaging surface of the camera 323 as 2:1 as an example. When the surface shape parameters of the even aspherical mirror 130 are set as above, after the filtering signal is shaped and uniformly illuminated by the even aspherical mirror 130, an elliptical spot with a long and short axis ratio of 2:1 is formed, and the fluorescence signal is also an elliptical spot D with a long and short axis ratio of 2:1, and the size of the elliptical spot matches the size of the imaging surface A of the camera 323. At this time, as Figure 2 shown, the spot D of the fluorescence signal can completely enter the imaging surface A of the camera 323. From the above, it can be seen that under the condition of ensuring a good excitation illumination effect, the camera 323 can simultaneously scan and image multiple regions of the sample to be detected 200.

[0057] In some embodiments, the even aspherical mirror 130 satisfies the following relationship: 14.6 < f < 16.1, where f is the focal length of the even aspherical mirror 130.

[0058] It can be understood that the focal length f of the even aspherical mirror 130 satisfying the above relationship can enable the even aspherical mirror 130 to achieve a better shaping and uniform illumination effect and generate a target uniform light beam with a long and short axis ratio of 2:1. Similarly, when the surface shape parameters of the even aspherical mirror 130 are changed, its focal length f also needs to be changed accordingly, and this embodiment will not be described one by one here.

[0059] See also Figure 5 In some embodiments, the light homogenizing device 100 further includes: an objective lens 140, wherein the objective lens 140 is placed behind the even-order aspheric reflector 130 along the optical axis of the target light homogenizing beam, and the objective lens 140 is used to converge the target light homogenizing beam to form a converged light signal.

[0060] It is understandable that the filtered signal is reflected by the even-order aspheric reflector 130 to form a target uniform light beam, which first converges and then diverges, and finally irradiates the sample 200 to be detected. Since the target uniform light beam will also diverge during the divergence process, energy loss will be caused. For this reason, the uniform light device 100 in this embodiment is provided with a corresponding objective lens 140, which is used to converge the target uniform light beam to obtain a converged light signal, and the converged light signal can be focused on the sample 200 to be detected. It can be seen that the converged light signal is a focused target uniform light beam, and therefore, the shape of the converged light signal is still the same as the target uniform light beam.

[0061] It is understandable that the energy of the target uniform light beam that has not been converged by the objective lens 140 is relatively divergent, and the converged light signal obtained after convergence by the objective lens 140 is more concentrated than the target uniform light beam. Therefore, the loss of energy can be avoided. In addition, in some application scenarios, it may be necessary to change the size of the imaging surface of the camera 323. From the above content, it can be seen that in order to ensure the efficiency of the scanning imaging of the camera 323, the size of the fluorescence imaging area should be changed with the size of the imaging surface of the camera 323. To this end, the uniform light device 100 in this embodiment can perform different convergence operations on the target uniform light beam by replacing different objective lenses 140 to generate converged light signals of different sizes, and the size of the fluorescence imaging area will also change accordingly. Therefore, by setting the objective lens 140, the size of the fluorescence signal can be flexibly adjusted to adapt to the camera 323 with different imaging surfaces. In addition, in this embodiment, the objective lens 140 is also used to collect the fluorescence signal generated by the sample 200 to be detected, so as to transmit it to the camera 323 for scanning imaging.

[0062] See also Figure 6In the second aspect, the present application further provides a gene sequencing system 300, which is used to test a sample 200 to be detected to generate a detection result. The gene sequencing system 300 includes: a light homogenizing device 100 as described in any of the above embodiments; a biochip 310, wherein the biochip 310 carries a sample 200 to be detected, and the biochip 310 is used to be irradiated and excited by the target homogenizing light beam to generate a fluorescence signal; at least one fluorescence spectrometer module 330, wherein the fluorescence spectrometer module 330 is used to perform spectroscopic operations on fluorescence signals of different wavelengths; at least one fluorescence collection module 320, wherein the fluorescence collection module 320 is used to collect the fluorescence signal after the spectroscopic operation and generate an image signal; and a processing module 340, wherein the processing module 340 is connected to the fluorescence collection module 320, and the processing module 340 is used to generate a detection result according to the image signal.

[0063] It can be understood that the gene sequencing system 300 in this embodiment includes a light homogenizing device 100, a biochip 310, a fluorescence collection module 320, a camera 323 and a processing module 340. Among them, the biochip 310 is used to generate a corresponding fluorescence signal with a target homogenizing light beam, and a fluorescence spectroscopic module 330 and a fluorescence collection module 320 are sequentially arranged along the optical axis of the fluorescence signal, and the fluorescence collection module 320 is also used to connect with the processing module 340.

[0064] Specifically, the light homogenizing device 100 is used to generate a target homogenizing light beam and irradiate it on the biochip 310, and the biochip 310 can generate a corresponding fluorescence signal according to the target homogenizing light beam. It can be seen from the above content that a corresponding image signal can be obtained by imaging the fluorescence signal, and the detection result of the biochip 310 can be obtained according to the image signal. In order to efficiently scan and image the fluorescence signal and ensure the accuracy of the detection result, the gene sequencing system 300 in this embodiment is provided with a corresponding fluorescence spectrometer module 330 and a fluorescence collection module 320. The fluorescence spectrometer module 330 is used to perform spectroscopic operation on the fluorescence signal to transmit the fluorescence signal to different fluorescence collection modules 320, and the fluorescence collection module 320 is used to efficiently collect the fluorescence signal to form a collection signal, while preventing the fluorescence signal from being affected by external interference and affecting the detection result.

[0065] It is understandable that, since the image signal generated by the fluorescence acquisition module 320 can only represent the image information of the fluorescence signal, in order to obtain the corresponding detection result, it is necessary to process the information in the image signal. To this end, the gene sequencing system 300 in this embodiment is also provided with a corresponding processing module 340, which is used to analyze and process the information in the image signal to obtain the detection result.

[0066] In a specific embodiment, the gene sequencing system 300 is used to detect the gene sequence on the biochip 310. Since different bases in the gene sequence can generate fluorescent signals of different spectra under the excitation illumination of the target uniform light beam, after the camera 323 scans and images the fluorescent signals with different spectra, the image signal obtained includes different spectral components. The processing module 340 can obtain a specific gene sequence, that is, a detection result, by analyzing the spectral components.

[0067] It can be seen that the contents of the above-mentioned embodiment of the light homogenizing device 100 are applicable to the embodiment of the present gene sequencing system 300. The functions specifically implemented by the embodiment of the present gene sequencing system 300 are the same as those of the above-mentioned embodiment of the light homogenizing device 100, and the beneficial effects achieved are also the same as those achieved by the above-mentioned embodiment of the light homogenizing device 100.

[0068] See also Figure 7 and Figure 8 In some embodiments, the gene sequencing system 300 further includes: a translation stage 350, wherein the translation stage 350 is used to carry the biochip 310; wherein the shape of the biochip 310 is rectangular; the shape of the target uniform light beam is elliptical or quasi-elliptical or rectangular; the translation stage 350 is also connected to the processing module 340; wherein the processing module 340 is also used to control the translation stage 350 to move so that the short axis of the target uniform light beam moves relative to the long side of the biochip 310, and the short axis of the target uniform light beam is parallel to the long side of the biochip 310, so that the camera 323 scans the biochip 310; wherein the imaging surface of the camera 323 is a rectangular imaging surface, and the length-to-width ratio of the rectangular imaging surface is L:W; the ratio of the long-to-short axis of the light spot of the target uniform light beam is L:W; wherein L and W are both positive integers.

[0069] It is understandable that, from the above content, the camera 323 can only image the fluorescent signal within its imaging surface A. Therefore, in order to scan and image different areas of the biochip 310, the gene sequencing system 300 in this embodiment is provided with a corresponding displacement stage 350, which is used to carry the biochip 310 and is also used to connect with the processing module 340. The displacement stage 350 can be moved under the control of the processing module 340 to move the biochip 310, so that the target uniform light beam can excite and illuminate different areas of the biochip 310.

[0070] In a specific embodiment, Figure 8As shown, the biochip 310 is rectangular, the imaging surface A of the camera 323 is a rectangular imaging surface, and the length-width ratio of the rectangular imaging surface A is L:W, and the major-minor axis ratio of the light spot D of the target homogenized light beam is L:W. When the displacement stage 350 is in the initial position, the light spot D of the target homogenized light beam excites and illuminates the X1 area of ​​the biochip 310, and generates a corresponding fluorescence signal. The camera 323 generates an image signal according to the above working principle, and the image signal is received by the processing module 340, thereby generating a corresponding detection result x1. When the processing module 340 obtains the detection result, the processing module 340 is also used to generate a first control signal, and the displacement stage 350 moves according to the first control signal, so that the light spot D of the target homogenized light beam irradiates the X2 area of ​​the biochip 310, and the detection result x2 is obtained according to the above steps. The displacement stage 350 continues to move, so that the camera 323 can scan and image the X3, X4... and other areas on the biochip 310, thereby obtaining different detection results on the biochip 310.

[0071] It can be understood that when the length-width ratio of the rectangular imaging surface A of the camera 323 is 2:1 and the ratio of the long axis to the short axis of the spot D of the target uniform light beam is 2:1, compared with the circular laser signal in the related art, the target uniform light beam of this embodiment can excite and illuminate a larger area in the biochip 310, and scan and image it through the corresponding camera 323. Therefore, the scanning and detection efficiency of the gene sequencing system 300 of this embodiment is relatively high, thereby being able to increase the output of gene sequencing data per unit time.

[0072] See also Fig. 9 In some embodiments, the gene sequencing system 300 further includes: an objective lens 140, which is used to converge the target uniform light beam to form a converged light signal; the objective lens 140 is also used to collect the fluorescence signal; and a first dichroic mirror 360, which is used to reflect or transmit the target uniform light beam and the fluorescence signal respectively.

[0073] It can be understood that in order to distinguish the optical paths of the target uniform light beam and the fluorescence signal so as to collect the fluorescence signal for imaging to the corresponding fluorescence collection module 320, the gene sequencing system 300 in this embodiment is provided with a corresponding first dichroic mirror 360, and the first dichroic mirror 360 is used to split the target uniform light beam and the fluorescence signal.

[0074] Specifically, Fig. 9As shown, when the target homogenizing light beam is incident on the surface of the first dichroic mirror 360, the first dichroic mirror 360 reflects the target homogenizing light beam so that the target homogenizing light beam irradiates the biochip 310, or focuses the target homogenizing light beam to the biochip 310 through the objective lens 140. When the fluorescence signal is incident on the surface of the first dichroic mirror 360, the first dichroic mirror 360 transmits the fluorescence signal so that the fluorescence signal is incident on the fluorescence collection module 320. Similarly, the first dichroic mirror 360 can also transmit the target homogenizing light beam and reflect the fluorescence signal to split the target homogenizing light beam and the fluorescence signal.

[0075] Please refer again Fig. 9 In some embodiments, the fluorescence spectrometer module includes: at least one dichroic mirror, which is placed behind the first dichroic mirror 360 along the optical axis of the fluorescence signal.

[0076] It is understandable that since the fluorescent signal usually contains a variety of different spectral components, in some application scenarios, the gene sequencing system 300 may only need to detect certain spectral components (bands). To this end, the gene sequencing system 300 in this embodiment is provided with a corresponding dichroic mirror, which can transmit or reflect the fluorescent signal of the required band, and reflect or transmit the fluorescent signal of other bands, so as to collect the fluorescent signal of a specific band and provide it to the fluorescent acquisition module 320 for scanning and imaging, avoiding interference from fluorescent signals of other bands.

[0077] Please refer again Fig. 9 In some embodiments, the fluorescence collection module 320 includes: a tube lens 321, which is placed behind the fluorescence spectrometer module 330 along the optical axis of the fluorescence signal; a filter 322, which is placed behind the tube lens 321 along the optical axis of the fluorescence signal; and a camera 323, which is placed behind the filter 322 along the optical axis of the fluorescence signal.

[0078] Specifically, after being transmitted through the dichroic mirror, the fluorescent signal is transmitted to the sleeve lens 321 for convergence, and then the residual interference signal in the fluorescent signal, such as the target uniform light beam, is filtered out through the filter 322, and finally transmitted to the camera 323 for scanning and imaging.

[0079] It is understandable that gene sequencing can detect four bases in a gene, and the four bases can generate fluorescence signals of different spectra (bands) under the excitation illumination of the target uniform light beam. In order to perform comprehensive gene sequencing, this embodiment sets four corresponding fluorescence collection modules 320 to form four channels to detect the four bases in the gene respectively. Among them, the four bases are A, T, G, and C, and the bands of the fluorescence signals generated are f1, f2, f3, and f4 respectively.

[0080] Specifically, when the fluorescence signal passes through the first dichroic mirror 331, the fluorescence signal of the specific frequency f1 is transmitted by the first dichroic mirror 331, thereby entering the corresponding fluorescence collection module 320, and transmitted to the sleeve lens 321 for convergence, and then the interference signal remaining in the fluorescence signal is filtered out by the filter 322, and finally transmitted to the camera 323 for scanning and imaging, so as to obtain the detection result of the base A in the biochip 310. The first dichroic mirror 331 is also used to reflect the fluorescence signal of the remaining frequencies so that it is transmitted to the second dichroic mirror 332, and the second dichroic mirror 332 can reflect the fluorescence signal of the specific frequency f2 in the fluorescence signal, so that the fluorescence signal of the frequency f2 enters the corresponding fluorescence collection module 320 for scanning and imaging, so as to obtain the detection result of the base T in the biochip 310. The second dichroic mirror 332 is also used to transmit the fluorescence signals of the remaining frequencies so as to transmit them to the third dichroic mirror 333. The third dichroic mirror 333 can reflect the fluorescence signal of the specific frequency f3 so that the fluorescence signal of the frequency f3 enters the corresponding fluorescence collection module 320 for scanning and imaging, so as to obtain the detection result of the base G in the biochip 310. The third dichroic mirror 333 is also used to transmit the fluorescence signals of the remaining frequencies so as to transmit them to the first reflector 334. The first reflector 334 can reflect the incident fluorescence signal so that the fluorescence signal of the frequency f4 is reflected into the corresponding fluorescence collection module 320 for scanning and imaging, so as to obtain the detection result of the base C in the biochip 310. In addition, the sleeve lens 321 can also receive the fluorescence signal emitted by the first dichroic mirror 360 through the second reflector 370. The second reflector 370 can reflect the fluorescence signal so as to transmit the reflected fluorescence signal to the first dichroic mirror 331, thereby improving the integration of the gene sequencing system 300 and reducing its distribution volume.

[0081] It is understandable that the number of dichroic mirrors in the fluorescence collection module 320 and the fluorescence spectrometry modules 330 to 330 may be increased or decreased according to actual needs to detect fluorescence signals of different wavelength bands respectively, which is not limited in this embodiment.

[0082] See also Fig.10 and Figure 8In a third aspect, the present application further provides a control method of a gene sequencing system 300, which is applied to the gene sequencing system 300 as described in any one of the above embodiments, comprising: step S101, obtaining a scanning control signal;

[0083] Step S102, controlling the translation stage 350 to move according to the scanning control signal;

[0084] Step S103, sequentially acquiring image signals from the camera 323 during the movement of the translation stage 350;

[0085] It can be understood that, according to the scanning control signal, the displacement stage 350 is controlled to move so that the short axis of the target uniform light beam moves relative to the long side of the biochip 310, and the short axis of the target uniform light beam is parallel to the long side of the biochip 310; during the movement of the displacement stage 350, the image signals from the camera 323 are acquired in sequence; the biochip 310 is scanned to obtain the detection result.

[0086] It can be understood that, from the above content, when the processing module 340 generates a detection result based on the image signal, the processing module 340 is also used to generate a first control signal, namely a scanning control signal, to control the movement of the translation stage 350. The translation stage 350 can move according to a preset time period and a moving distance. Within the preset time period, the camera 323 can scan and image the biochip 310 after the movement to obtain the corresponding detection result. The translation stage 350 moves a preset moving distance, which can make the light spot of the target uniform light beam irradiate different areas of the biochip 310. Specifically, as Figure 8 As shown, the long axis of the target uniform light beam spot is perpendicular to the long side of the biochip 310, and the target uniform light beam moves along the long side of the biochip 310, so that the camera 323 scans and images the X1 area, X2 area, etc. on the biochip 310 to obtain the detection result.

[0087] It can be understood that since the long side of the chip corresponds to the short axis of the target fluorescence signal, that is, the long side of the chip corresponds to the short side of the camera 323, compared with the scanning method in which the long side of the chip corresponds to the short side of the camera 323, the single movement distance of the displacement stage 350 can be shortened, thereby improving the scanning efficiency of the camera 323.

[0088] It can be seen that the contents of the above-mentioned gene sequencing system 300 embodiment are all applicable to the embodiment of the present control method, the functions specifically implemented by the present control method embodiment are the same as those of the above-mentioned gene sequencing system 300 embodiment, and the beneficial effects achieved are also the same as those achieved by the above-mentioned gene sequencing system 300 embodiment.

[0089] In some embodiments, the imaging surface of the camera 323 is a rectangular imaging surface, and the shape of the target uniform light beam is elliptical or quasi-elliptical or rectangular; the length-to-width ratio of the rectangular imaging surface is L:W; the ratio of the major and minor axes of the spot of the target uniform light beam is L:W; wherein L and W are both positive integers.

[0090] In a specific embodiment, the imaging surface of the camera 323 is a rectangular imaging surface, and the shape of the target uniform light beam is an ellipse or a quasi-ellipse or a rectangle. As can be seen from the above content, when the length-width ratio of the rectangular imaging surface and the ratio of the long and short axes of the light spot of the target uniform light beam are both L:W, the shape and size of the imaging surface of the camera 323 are matched with the shape and size of the target uniform light beam. At this time, the scanning efficiency of the camera 323 on the biochip 310 is higher, which can increase the output of sequencing data per unit time.

[0091] The embodiments of the present invention are described in detail above in conjunction with the accompanying drawings, but the present invention is not limited to the above embodiments. Various changes can be made within the knowledge of ordinary technicians in the relevant technical field without departing from the purpose of the present invention. In addition, the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

Claims

1. A light homogenizing device, characterized in that: The light homogenizing device comprises: A light source, the light source is used to generate a laser signal; An aperture, the aperture being placed behind the light source along the optical axis of the laser signal, the aperture being used to perform spatial filtering on the incident laser signal to form a filtered signal; An even-order aspheric reflector is placed behind the aperture along the optical axis of the filtered signal, and a surface formula of the even-order aspheric reflector satisfies the following relationship: ， ； Where c is the curvature, k is the cone coefficient, is the second-order aspheric coefficient, is the fourth-order aspheric coefficient, is the sixth-order aspheric coefficient, is the eighth-order aspheric coefficient, x and y are the specific coordinate positions of the aspheric surface, c= , , =0, =1.848E-4, = 4.159E-6, =3.216E-8, the even-order aspheric reflector satisfies the following relationship: 14.6 , wherein f is the focal length of the even-order aspheric reflector, and the even-order aspheric reflector is used to form a target uniform light beam of an elliptical light spot according to the filtered signal; wherein the target uniform light beam is used to excite the sample to be detected to generate a fluorescence signal; The major and minor axes of the elliptical spot of the target uniform light beam match the aspect ratio of the camera imaging plane; wherein the camera is used to collect the fluorescence signal within the imaging plane.

2. The light homogenizing device according to claim 1, characterized in that: Also includes: An objective lens is placed behind the even-order aspheric reflector along the optical axis of the target uniform light beam, and is used to converge the target uniform light beam to form a converged light signal.

3. A gene sequencing system, characterized in that: The gene sequencing system is used to test the test sample to generate a test result, and the gene sequencing system includes: The light homogenizing device according to any one of claims 1 to 2; A biochip, the biochip carrying a sample to be detected, the biochip being used to be illuminated and excited by the target uniform light beam to generate a fluorescent signal; At least one fluorescence spectrometer module, the fluorescence spectrometer module is used to perform spectrometry operations on fluorescence signals of different wavelengths; At least one fluorescence collection module, the fluorescence collection module is used to collect the fluorescence signal after the spectroscopic operation and generate an image signal; A processing module, wherein the processing module is connected to the fluorescence acquisition module, and the processing module is used to generate a detection result according to the image signal.

4. The gene sequencing system according to claim 3, characterized in that: Also includes: A translation stage, the translation stage is used to carry the biochip; wherein the biochip is rectangular in shape; the target uniform light beam is elliptical or quasi-elliptical or rectangular in shape; the translation stage is also connected to the processing module; Wherein, the processing module is further used to control the translation stage to move so that the short axis of the target uniform light beam moves relative to the long side of the biochip, and the short axis of the target uniform light beam is parallel to the long side of the biochip, so that the camera scans the biochip; The imaging surface of the camera is a rectangular imaging surface, and the length-width ratio of the rectangular imaging surface is L:W; the ratio of the major axis and minor axis of the spot of the target uniform light beam is L:W; wherein L and W are both positive integers.

5. The gene sequencing system according to claim 3, characterized in that: Also includes: An objective lens, the objective lens being used to converge the target uniform light beam to form a converged light signal; The objective lens is also used to collect the fluorescence signal; A first dichroic mirror, wherein the first dichroic mirror is used to reflect or transmit the target uniform light beam and the fluorescent signal respectively.

6. The gene sequencing system according to claim 5, characterized in that: The fluorescence spectrometer module comprises: At least one dichroic mirror is placed behind the first dichroic mirror along the optical axis of the fluorescent signal.

7. The gene sequencing system according to claim 3, characterized in that: The fluorescence collection module comprises: A sleeve lens, wherein the sleeve lens is placed behind the fluorescence spectrometer module along the optical axis of the fluorescence signal; an optical filter, the optical filter being placed behind the tube lens along the optical axis of the fluorescent signal; A camera is placed behind the filter along the optical axis of the fluorescent signal.

8. A method for controlling a gene sequencing system, characterized in that: A gene sequencing system as claimed in any one of claims 3 to 7, comprising: Obtaining a scanning control signal; According to the scanning control signal, the translation stage is controlled to move so that the short axis of the target uniform light beam moves relative to the long side of the biochip, and the short axis of the target uniform light beam is parallel to the long side of the biochip; During the movement of the translation stage, image signals from the camera are acquired in sequence to perform a scanning operation on the biochip, thereby obtaining the detection result.

9. The control method of the gene sequencing system according to claim 8, characterized in that: The imaging surface of the camera is a rectangular imaging surface, and the shape of the target uniform light beam is an ellipse or a quasi-ellipse or a rectangle; the length-to-width ratio of the rectangular imaging surface is L:W; the ratio of the major and minor axes of the spot of the target uniform light beam is L:W; wherein L and W are both positive integers.

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