Stepped imaging system and detection device

Abstract

The utility model provides a stepped imaging system and a detection device.The stepped imaging system sequentially comprises an objective lens, a spectroscope and a line-scan digital camera from an object end to an image end, the objective lens is used for obtaining a fluorescence signal from a to-be-detected object, the spectroscope is used for dividing the fluorescence signal into a plurality of monochromatic light, and the line-scan digital camera is provided with a plurality of pixel areas; a plurality of monochromatic lights are respectively imaged in corresponding pixel areas, so that the linear array camera can simultaneously detect the plurality of monochromatic lights and realize multi-area imaging of a plurality of fluorescence signals, that is, a single camera can realize multicolor fusion imaging, high simplification of an optical-mechanical system is realized, only upgrading and reconstruction in the aspect of instruments are involved, time is not lost, and the cost is reduced. And the existing fluorescence signal types and distribution do not need to be changed, the biochemical compatibility is high, and the system complexity, the debugging difficulty, the instrument cost and the instrument size are reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of optical imaging, in particular to a multi-stage imaging system and a detection device. BACKGROUND

[0002] A linear array camera, such as a TDI (Time Delay Integration) linear array camera, can be used to perform multi-stage imaging on a detection object. The linear array camera can be precisely controlled by a motion system to achieve n times of exposure and n times of signal detection on the same signal. The signals from the n times of exposure can be superimposed to achieve sensitive detection of weak signals and improve the signal-to-noise ratio and speed of photographing. The TDI order (n) of the linear array camera determines the amplification degree of the signal.

[0003] An optical system using a linear array camera for scanning can improve the signal-to-noise ratio and reduce the exposure time of the acquired image, which has great advantages in detecting weak signals. The working principle and characteristics of the optical system are continuous uniform motion and image acquisition, which requires continuous exposure during photographing. For multi-channel signal detection, in order to ensure the simultaneous imaging of multiple wavelength signals, a multi-camera and multi-lens optical design is usually used, that is, one camera and one lens form one optical path, and one optical path can realize the imaging of one wavelength signal. However, this will lead to high system complexity and instrument cost. SUMMARY

[0004] Therefore, the present application aims to provide a multi-stage imaging system and a detection device, which can detect multiple fluorescent signals by using one linear array camera and reduce the system complexity and instrument cost.

[0005] The multi-stage imaging system provided by the present application comprises, in sequence from the object end to the image end:

[0006] an objective lens, configured to acquire a fluorescent signal from a detection object;

[0007] a light splitter, configured to split the fluorescent signal into multiple monochromatic lights;

[0008] a linear array camera, having a plurality of pixel regions, and the multiple monochromatic lights are respectively imaged on the corresponding pixel regions.

[0009] In some embodiments, the multi-stage imaging system comprises a filter arranged between the light splitter and the linear array camera, and the filter is configured to filter the multiple monochromatic lights before the multiple monochromatic lights enter the linear array camera.

[0010] In some embodiments, the filter comprises a plurality of filter sub-regions corresponding to the pixel regions, and each filter sub-region is configured to transmit the monochromatic light imaged on the corresponding pixel region.

[0011] In some embodiments, the light filtering sub-regions correspond to the pixel regions one by one.

[0012] In some embodiments, each pixel region includes multiple rows of pixels, pixel values of the multiple rows of pixels are used to obtain a detection result corresponding to the pixel region by integral operation, and the multiple pixel regions are arranged in a column direction.

[0013] In some embodiments, each row of pixels includes multiple pixel groups, multiple sub-pixels belonging to the same pixel group are continuously distributed, each pixel region includes a pixel matrix composed of multiple sub-pixels, the multiple sub-pixels include multiple pixel groups respectively belonging to different rows, pixel values of the multiple sub-pixels are used to obtain a detection result corresponding to the pixel region by integral operation in a row direction, and the multiple pixel regions are arranged in an array.

[0014] In some embodiments, two adjacent pixel regions are recorded as a first pixel region and a second pixel region, pixel values of a first matrix region of the first pixel region facing the second pixel region and pixel values of a second matrix region of the second pixel region facing the first pixel region do not participate in integral operation for determining a detection result.

[0015] In some embodiments, in a direction along a line connecting a center of the first pixel region and a center of the second pixel region, a sum of sizes of the first matrix region and the second matrix region ranges from 5 microns to 200 microns.

[0016] In some embodiments, the light splitting mirror includes a dichroic mirror.

[0017] In some embodiments, the number of the linear array cameras is multiple.

[0018] The light splitting mirror is configured to split the fluorescent signal into multiple groups of monochromatic light, each group of monochromatic light includes multiple monochromatic lights, and each group of monochromatic light is configured to be incident on the same linear array camera.

[0019] In some embodiments, the number of the linear array cameras is the same as and one by one corresponds to the number of the light filters; or,

[0020] The number of the light filters is multiple, and there is a target light filter including multiple light filtering regions, the multiple light filtering regions one by one correspond to multiple linear array cameras corresponding to the target light filter.

[0021] Embodiments of the present application also provide a detection device, which includes:

[0022] The multi-stage imaging system.

[0023] A displacement table is configured to carry and move the object to be detected at a preset moving speed.

[0024] In some embodiments, the device further comprises:

[0025] A laser module is configured to generate a laser beam to excite the object to be detected to generate a fluorescence signal; and the objective lens is further configured to converge the laser beam to the object to be detected.

[0026] In some embodiments, the laser module comprises a plurality of light sources, each of which is configured to emit a laser beam to a corresponding sub-region in the detection region of the object to be detected.

[0027] The present application provides a multi-stage imaging system and a detection device. The multi-stage imaging system comprises, in order from the object end to the image end, an objective lens, a beam splitter, and a linear array camera. The objective lens is configured to obtain a fluorescence signal from an object to be detected. The beam splitter is configured to split the fluorescence signal into a plurality of monochromatic lights. The linear array camera has a plurality of pixel regions. The plurality of monochromatic lights are respectively imaged on the corresponding pixel regions. In this way, the linear array camera can simultaneously detect the plurality of monochromatic lights, realizing multi-region imaging of multiple fluorescence signals, i.e., a single camera can realize multi-color fusion imaging. The optical and mechanical system is highly simplified, only involving upgrading and modification of the instrument, without loss of time, and without the need to change the existing types and distribution of fluorescence signals, with high biochemical compatibility, and reducing system complexity, debugging difficulty, and instrument cost and volume. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed in the embodiment description will be briefly introduced. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0029] Figure 1 A structure diagram of a multi-stage imaging system provided by an embodiment of the present application is shown;

[0030] Figure 2 A pixel diagram of a photosensitive surface of a linear array camera provided by an embodiment of the present application is shown;

[0031] Figure 3 A pixel diagram of a photosensitive surface of another linear array camera provided by an embodiment of the present application is shown. DETAILED DESCRIPTION

[0032] In the following, the technical solutions in the embodiments of the present application will be described clearly and completely in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all the other embodiments obtained by a person of ordinary skill in the art without creative effort do not depart from the protection scope of the present application.

[0033] In the following description, a large number of specific details are set forth in order to facilitate a thorough understanding of the present application, but the present application can also be implemented in other manners different from those described herein, and a person of ordinary skill in the art can make similar generalizations without departing from the content of the present application, therefore the present application is not limited to the specific embodiments disclosed below.

[0034] The present application is described in detail in conjunction with the schematic diagram, and in the detailed description of the embodiments of the present application, the cross-sectional view of the device structure is locally enlarged without the general proportion for the convenience of description, and the schematic diagram is only an example, which should not limit the scope of protection of the present application herein. In addition, the three-dimensional spatial dimensions of length, width and depth should be included in actual manufacture.

[0035] At present, the optical system using a linear array camera scanning can improve the signal-to-noise ratio and reduce the exposure time of the collected image at the same time, which has great detection advantages for weak signals. The working principle and characteristics of the optical system are continuous uniform motion and image acquisition, which requires continuous exposure during the shooting process. For the detection of multi-channel signals, in order to ensure the simultaneous imaging of multiple wavelength signals, a multi-camera and multi-lens barrel optical mechanical design is usually used, one camera and one lens barrel form one optical path, and one optical path can realize the imaging of one wavelength signal. However, this will lead to high system complexity and instrument cost.

[0036] For example, when the optical system is applied to a sequencer, the object to be detected is a sequencing chip loaded with a sample to be detected. During the sequencing process, when the excitation light irradiates the nucleotides or nucleotide analogs with different optically detectable markers (such as fluorescent groups) combined on the sample to be detected, these different fluorescent groups will simultaneously emit fluorescent signals corresponding to the emission spectral band. After being uniformly collected by the objective lens, the subsequent optical path is used for light splitting, and the light is transmitted to the optical path of different spectral bands, respectively, and is received by the lens and camera on the respective optical path, converted into an image record, and a photographing and recording is completed. When the types of fluorescent signals are multiple, the corresponding number of branch optical paths must be used to obtain the simultaneous imaging of multiple fluorescent signals.

[0037] If there are space or cost limitations on the instrument layout, the instrument optical system can only be simplified by other means. For example, by multiple separate exposure imaging to reduce the complexity of the optical path, but the time cost will be increased in proportion. Or, by reducing the number of fluorescent signal types, on the one hand, this method has higher requirements for biochemical systems, and on the other hand, it also has higher challenges for bioinformatics analysis systems, involving changes at the sequencing product system level.

[0038] Based on the above technical problems, the embodiment of the present application provides a hierarchical imaging system and a detection device. The hierarchical imaging system sequentially includes an objective lens, a beam splitter and a linear array camera from the object end to the image end. The objective lens is used to obtain a fluorescent signal from a to-be-detected object. The beam splitter is used to divide the fluorescent signal into multiple monochromatic lights. The linear array camera has multiple pixel regions. The multiple monochromatic lights are respectively imaged on the corresponding pixel regions. In this way, the linear array camera can simultaneously detect the multiple monochromatic lights, realize multi-region imaging of multiple fluorescent signals, that is, a single camera can realize multi-color fusion imaging, and the optical and mechanical system is highly simplified, only involving upgrading and modification of the instrument, without loss of time, and without the need to change the existing fluorescent signal types and distribution, with high biochemical compatibility, and reducing system complexity, debugging difficulty and instrument cost and volume.

[0039] In order to better understand the technical solutions and technical effects of the present application, specific embodiments will be described in detail below with reference to the accompanying drawings.

[0040] Referring to Figure 1 The figure is a structural schematic diagram of a hierarchical imaging system provided by the embodiment of the present application. The hierarchical imaging system can sequentially include an objective lens 10, a beam splitter 20 and a linear array camera 30 from the object end to the image end.

[0041] The objective lens 10 is used to obtain a fluorescent signal from a to-be-detected object 50, which can be a complex achromatic flat-field microscopic imaging objective lens. The to-be-detected object 50 can be a sequencing chip loaded with a to-be-measured sample. During the sequencing process, when the excitation light irradiates the nucleotides or nucleotide analogs with different optically detectable markers (such as fluorescent groups) combined on the to-be-measured sample, these different fluorescent groups will simultaneously emit fluorescent signals corresponding to the emission spectral band. These fluorescent signals can be uniformly collected by the objective lens. The fluorescent signal can include multiple monochromatic lights. The number of monochromatic lights can be determined according to actual conditions, for example, it can be 2, 3, 4, etc., or even more, that is, the detection requirements of two-color, three-color or four-color fluorescent signal types can be realized.

[0042] The spectroscope 20 is used to divide the fluorescence signal into multiple monochromatic lights, which can be emitted from different positions of the spectroscope or from the same position of the spectroscope at different angles, realizing the separation of multiple monochromatic lights. Specifically, the spectroscope 20 can include a dichroic mirror, thereby dividing the fluorescence signal into 2 monochromatic lights, or the spectroscope 20 can be other light splitting modules, thereby dividing the fluorescence signal into 2 or more monochromatic lights.

[0043] The linear array camera 30 can perform stepwise imaging on the object to be detected 50, for example, a TDI linear array camera, which has high sensitivity and high signal-to-noise ratio, which makes the TDI camera very suitable for capturing weak fluorescence signals, which is very important in gene sequencing, making it applicable to the sequencing field, and can improve the sensitivity, speed and accuracy of sequencing.

[0044] Specifically, it significantly improves the sensitivity of the image by accumulating the signals of multiple lines, so that it can work in very low light conditions, which makes the camera able to detect weak fluorescence signals in gene sequencing, thereby performing accurate nucleic acid sequence analysis; TDI technology can accumulate signals at the same position, thereby significantly increasing signal strength, effectively improving the signal-to-noise ratio of the image, which is crucial for distinguishing weak fluorescence signals generated during sequencing from background noise; TDI cameras are suitable for detecting high-speed moving objects because they can achieve high-speed image acquisition while maintaining high sensitivity and high signal-to-noise ratio, which means that a large amount of sequence data can be quickly read in gene sequencing, improving sequencing efficiency; Because TDI cameras have extremely high sensitivity and signal-to-noise ratio, they are particularly suitable for low-light or fast-moving object image acquisition, which allows imaging at lower excitation light intensity in gene sequencing, reducing light damage to the sample.

[0045] Currently, in order to realize multispectral imaging, multiple TDI cameras with different spectral responses can be integrated, which provides more dimensional information for material analysis and defect classification, which can help to distinguish different fluorescently labeled nucleotides in gene sequencing, improving the accuracy and reliability of sequencing. However, multiple linear array cameras also result in high complexity and high cost of the system.

[0046] Therefore, the linear array camera 30 in the embodiment of the present application can have a plurality of pixel regions 301 / 302, and a plurality of monochromatic lights are respectively imaged on the corresponding pixel regions, so that the linear array camera can simultaneously detect a plurality of monochromatic lights, realize multi-region imaging of a plurality of fluorescent signals, that is, a single camera can realize multi-color fusion imaging, and can replace the original imaging system with a double optical path layout or a four optical path layout, so that the conventional split optical path and multi-barrel mirror multi-optical path layout can be removed, the signals of different wavebands are imaged in the imaging system in a region-by-region manner, the optical mechanical system is highly simplified, and the integration of the system is improved. According to different degrees of simplification, the number of cameras can be reduced from four to two or even one, the system complexity, debugging difficulty, instrument cost and volume are greatly reduced. Only the instrument is upgraded and modified, without loss of time, and without changing the existing types and distribution of fluorescent signals, the system complexity, debugging difficulty, instrument cost and volume are reduced.

[0047] In the formula, the pixel region refers to a region corresponding to a pixel element of the photosensitive surface of the linear array camera, and the pixel element is also referred to as a sensor or a photosensitive element or a pixel. One pixel region can include a plurality of pixel elements. The linear array camera can include a plurality of linear array sensors, and the extension direction of the linear array sensor is perpendicular to the movement direction of the object to be detected relative to the linear array camera.

[0048] As a possible implementation, the plurality of linear array sensors can correspond to a plurality of rows of pixels respectively, so that the plurality of linear array sensors obtain, as pixel values, detection values corresponding to the plurality of rows of pixels in a single detection. The number of rows of the linear array sensor is the order of the linear array camera, and determines the amplification degree of the signal. Generally, the plurality of linear array sensors can detect the moving object to be detected, so as to obtain, at different times, detection values of a plurality of rows of pixels by detecting the same region of the object to be detected. Integrating the detection values of the plurality of rows of pixels can obtain a row of detection images of the region, and realize accumulation of the detection signal in the time dimension.

[0049] Reference Figure 2 As shown in the figure, it is a pixel diagram of the photosensitive surface of the linear array camera provided by the embodiment of the present application. One row of linear array sensors corresponds to one row of pixels, the number of pixel elements of the linear array sensor is equal to the number of pixels of one row of pixels, x rows of linear array sensors correspond to x rows of pixels, that is, the order of the linear array sensor is x, and each row of pixels includes y pixels. When the plurality of linear array sensors detect the moving object to be detected, the detection values of the plurality of rows of pixels are obtained by detecting the same region of the object to be detected at different times. Integrating the detection values of the plurality of rows of pixels can obtain a row of detection images of the region.

[0050] As another possible implementation, the partial line array sensors in the multi-line array sensor correspond to multiple pixel groups in a row of pixels, so that the partial line array sensors obtain detection values of the multiple pixel groups in a row of pixels as pixel values thereof in a single detection, and the entire line array sensor obtains pixel values of the entire multi-line of pixels in a single detection, at which time the product of the number of rows of the line array sensor and the number of groups of pixel groups in a row of pixels is equal to the order of the line array camera. Generally, the multi-line array sensor can detect a moving object to be detected, so as to obtain detection values of multiple lines of pixels in different times by detecting the same region of the object to be detected, and the detection values of the pixels in each pixel group in the multiple lines can be integrated to obtain a detection image of a row of pixels in the region, so as to realize accumulation of the detection signal in the time dimension.

[0051] Referring to Figure 3 As shown in FIG. 6, the multi-line array sensor can correspond to different pixel groups (denoted as m groups) in a same row of pixels, so that the x rows of line array sensors correspond to xm rows of line array sensors, that is, the end of the line array sensor is xm, and each row of pixels includes y / m pixels. When the multi-line array sensor detects a moving object to be detected, detection values of multiple lines of pixels are obtained by detecting the same region of the object to be detected in different times, and the detection values of the pixels in the multiple pixel groups can be integrated to obtain a detection image of a row of pixels in the region.

[0052] Specifically, for the case that one row of line array sensors corresponds to one row of pixels, each pixel region can include multiple lines of pixels to form a pixel array, and pixel values of the multiple lines of pixels are used to obtain a detection result corresponding to the pixel region by integral operation, and the multiple pixel regions are arranged in the column direction, that is, the total pixel region of the line array camera is divided into multiple pixel regions arranged in the column direction. The number of lines of pixels included in a single pixel region can be determined according to the total order (equal to the total number of lines of the total pixel region) x and the number of pixel regions n, which can be the ratio x / n of the total order and the number of pixel regions, and the number of pixels in a row of a single pixel region is equal to the number of pixels in a row of the line array camera. Figure 2 As shown in FIG. 7, a single pixel region includes x / n lines of pixels, and each line of pixels includes y pixels, and the pixel regions are arranged in the column direction.

[0053] For example, the total pixel area of the linear array camera has x = 256 rows, which includes y columns, i.e. each linear array sensor includes y pixels. If the number of pixel areas n is 2, the fluorescent signals of two different wavebands enter different pixel areas of the same linear array camera through light splitting, the total pixel area of the linear array camera is divided into 2 pixel areas arranged along the column direction, each pixel area includes 128 rows, and each pixel area includes y columns; if the number of pixel areas n is 4, the fluorescent signals of four different wavebands enter different pixel areas of the same linear array camera through light splitting, the total pixel area of the linear array camera is divided into 4 pixel areas arranged along the column direction, each pixel area includes 64 rows, and each pixel area includes y columns.

[0054] Specifically, for the case that multiple rows of linear array sensors correspond to multiple pixel groups in a row of pixels, i.e. multiple rows of linear array sensors correspond to a row of pixels, multiple sub-pixels belonging to the same pixel group in the same row are continuously distributed, each pixel area includes a pixel matrix composed of multiple sub-pixels, the multiple sub-pixels include multiple pixel groups belonging to different rows respectively, the pixel values of the multiple sub-pixels are used to obtain the detection results corresponding to the pixel area to which the multiple sub-pixels belong by integrating by rows, and the multiple pixel areas are arranged in an array, i.e. the total pixel area of the linear array camera is divided into multiple pixel areas arranged in an array.

[0055] Reference Figure 3 As shown in the figure, the number of pixel groups corresponding to a row of pixels is denoted as m, then a row of pixels is divided into m pixel groups, the number of a row of pixels of the linear array camera is denoted as y, then the number of pixels in a single pixel group is equal to the number of pixels in a pixel group corresponding to a single linear array sensor, denoted as y / m, that is, each pixel group includes a row of y / m pixels, and each row of pixels includes m pixel groups. The number of pixel areas is denoted as n, then a column of pixels is divided into n / m pixel groups, the number of rows of pixels included in a single pixel group can be determined according to the total order (equal to the total number of rows of total pixel areas) x of the linear array camera and n / m, which is the ratio of x and n / m, denoted as xm / n, that is, each column includes n / m pixel groups, and each pixel group includes xm / n rows of pixels. That is, every xm / n rows of pixels are divided into m pixel areas along the column direction, and every y / m columns are divided into n / m pixel areas along the row direction. Each pixel area includes mx / n rows and y / m columns of pixels, and the total number of pixels in each pixel area is (mx / n)*(y / m) = xy / n, i.e. the total pixel area is xy, which is divided into n pixel areas, and the n pixel areas are arranged in an array.

[0056] For example, the total pixel area of the linear array camera has x = 256 rows, which includes y columns, that is, each linear array sensor includes y / m pixels, and each pixel group includes y / 2 pixels when the number of pixel groups corresponding to one row of pixels is 2. If the number of pixel areas is 2, two pixel areas are arranged along the row direction, and the number of rows is equal to 256, and the number of columns is y / 2. If the number of pixel areas is 4, four pixel areas are arranged in an array, the number of rows is equal to 128, and the number of columns is y / 2.

[0057] That is, this sub-area imaging reduces the amplification of the signal to a certain extent, but when the signal intensity or irradiation intensity is increased, even if the integration order is reduced, a signal image with sufficient signal-to-noise ratio and intensity can be obtained. The signal intensity, the power of the irradiation excitation light, the type of fluorescent signal, etc. can be determined according to the index of the actual system, which has strong compatibility and wide application range.

[0058] In specific implementation, due to the light splitting characteristics of the light splitter 20, the adjacent areas of the two adjacent pixel areas often have poor light splitting efficiency, at which time the adjacent areas can be excluded from the consideration range of the integration operation to improve the accuracy of the integration operation and the accuracy of the detection result. The two adjacent pixel areas are denoted as a first pixel area and a second pixel area, the matrix area on the side of the first pixel area facing the second pixel area is denoted as a first matrix area, and the matrix area on the side of the second pixel area facing the first pixel area is denoted as a second matrix area. The pixel values of the first matrix area and the second matrix area do not participate in the integration operation for determining the detection result.

[0059] The first matrix area and the second matrix area each include a plurality of pixels arranged in an array. When the first pixel area and the second pixel area are arranged along the row direction, the number of columns of the first matrix area is equal to the number of columns of the first pixel area, and the number of columns of the second matrix area is equal to the number of columns of the second pixel area. The number of rows of the first matrix area and the second matrix area is determined according to actual conditions. For example, the number of rows of the first matrix area and the second matrix area is 8. When the first pixel area and the second pixel area are arranged along the column direction, the number of rows of the first matrix area is equal to the number of rows of the first pixel area, and the number of rows of the second matrix area is equal to the number of rows of the second pixel area. The number of columns of the first matrix area and the second matrix area is determined according to actual conditions. For example, the number of columns of the first matrix area and the second matrix area is 8.

[0060] In the embodiments of the present application, the accuracy of the sub-area imaging is in the order of microns, that is, the spacing between the areas participating in the integration operation in the first matrix area and the second matrix area is in the range of 5-200 microns, that is, in the direction along the line connecting the center of the first pixel area and the center of the second pixel area, the sum of the sizes of the first matrix area and the second matrix area is in the range of 5-200 microns.

[0061] In the embodiments of the present application, the stepwise imaging system can further include a filter 40 between the light splitter and the linear array camera, which is used to filter the multiple monochromatic lights before entering the linear array camera 30, so as to reduce the stray light such as excitation light or other wavelength fluorescent light, etc. The filter 40 can be a filter with high cutoff depth.

[0062] In particular implementation, one linear array camera 30 can correspond to one filter 40, which can transmit the monochromatic light entering the linear array camera 30 and filter the excitation light diffused to the linear array camera 30. When one linear array camera 30 corresponds to one filter 40, the filter 40 can have one filtering sub-region, that is, the filtering effect of each position of the filter 40 is consistent. Of course, the filter 40 can also have multiple filtering sub-regions to realize sub-region filtering, so that the multiple filtering sub-regions are arranged corresponding to the pixel regions, and each filtering sub-region can be used to transmit the monochromatic light imaged on the corresponding pixel region to realize spatial separation of the fluorescent signal in cooperation with sub-region imaging. One filtering sub-region can correspond to one pixel region, that is, the filtering sub-regions and the pixel regions are arranged one by one. One filtering sub-region can also correspond to multiple pixel regions, so as to reduce the complexity of the filter 40.

[0063] One linear array camera 30 can also correspond to multiple filters 40, which are arranged corresponding to the pixel regions to transmit the monochromatic light corresponding to the pixel regions, wherein one filter 40 can correspond to one pixel region or multiple pixel regions.

[0064] In the embodiments of the present application, the number of linear array cameras 30 can be one, which can realize sub-region imaging to realize detection of multiple monochromatic lights. The number of linear array cameras 30 can be multiple, each of which can realize sub-region imaging, so as to realize detection of more kinds of monochromatic light. That is, the linear array camera 30 for sub-region imaging can cooperate with a multi-light-path (such as double light path, triple light path or quadruple light path, etc.) fluorescent imaging system to realize detection of more kinds of fluorescent light, which only needs to change the order or element design (such as light splitter design, light path design, etc.) adapted thereto.

[0065] Specifically, if the number of linear array cameras 30 is multiple, the light splitter 20 can divide the fluorescent signal into multiple groups of monochromatic light, each group of monochromatic light including multiple monochromatic lights, and each group of monochromatic light is used to be incident to the same linear array camera 30, so that the multiple groups of monochromatic light can correspond to the multiple linear array cameras 30 to realize detection of more kinds of fluorescent light.

[0066] When the number of line array cameras 30 is multiple, the number of light filters 40 can be the same as the number of line array cameras 30 and be arranged one by one, at this time, one light filter 40 can include one light filtering sub-region or multiple light filtering sub-regions, for reference to the foregoing description of the single line array camera 30.

[0067] When the number of line array cameras 30 is multiple, the number of light filters 40 can be multiple and less than the number of line array cameras 30, at this time, there is a target light filter including multiple light filtering regions corresponding to multiple line array cameras, that is, the target light filter can be shared by multiple line array cameras 30, and the multiple light filtering regions of the target light filter correspond to the multiple line array cameras 30 one by one, so as to realize the filtering effect of the monochromatic light entering the line array camera 30. The light filtering region corresponding to one line array camera 30 is similar to the single light filter corresponding to one line array camera 30, which can include one light filtering sub-region or multiple light filtering sub-regions, for reference to the foregoing description.

[0068] For example, if the number of line array cameras is 4 and the number of light filters is 4, the line array cameras and the light filters correspond to each other one by one, and each light filter can include multiple light filtering sub-regions; if the number of line array cameras is 4 and the number of light filters is 2, two line array cameras share one light filter, the shared light filter can be divided into two light filtering regions corresponding to the two line array cameras, and one light filtering region corresponding to one line array camera can be divided into multiple light filtering sub-regions corresponding to multiple pixel regions of the line array camera.

[0069] The application provides a staged imaging system, which sequentially includes an objective lens, a light splitter and a line array camera from an object end to an image end, wherein the objective lens is used to obtain a fluorescence signal from a to-be-detected object, the light splitter is used to divide the fluorescence signal into multiple monochromatic lights, and the line array camera has multiple pixel regions, and the multiple monochromatic lights are imaged on the corresponding pixel regions, so that the line array camera can simultaneously detect the multiple monochromatic lights, and multi-region imaging of multiple fluorescence signals is realized, that is, a single camera can realize multi-color fusion imaging, and the optical and mechanical system is highly simplified, only involving upgrading and modification of the instrument, without loss of time, and without the need to change the existing types and distribution of fluorescence signals, and having high biochemical compatibility, and reducing system complexity, debugging difficulty and instrument cost and volume.

[0070] Based on the staged imaging system provided in the foregoing embodiments, the application further provides a detection device, for reference to the foregoing description of the staged imaging system. Figure 1As shown, it comprises a staging imaging system, and a displacement table 60 for carrying and moving the to-be-detected object 50 at a preset moving speed, so as to move the to-be-detected object 50 relative to the linear array camera 30. The to-be-detected object 50 can be a sequencing chip loaded with a to-be-detected sample, which is placed on the displacement table, and when the fluorescence signal excitation and image acquisition are performed, the external control system controls the displacement table 60, and the displacement table 60 carries the sequencing chip to move uniformly and at a high speed.

[0071] The moving direction of the to-be-detected object 50 is perpendicular to the extension direction of one row of linear array sensors of the linear array camera 30, so that different linear array sensors can detect the same detection area of the to-be-detected object 50 at different times, and then integrate and amplify the signals obtained by different linear array sensors to output corresponding high-resolution high-contrast images and save them for subsequent bioinformatics system analysis. Because the area division from the flow cell chip end to the TDI camera end is small and precise, when the whole chip is imaged, the spatial area of the first and last parts can be ignored, and the influence on the data amount can be ignored.

[0072] In the embodiment of the application, the detection device can further include a laser module for generating a laser beam to excite the to-be-detected object to generate a fluorescence signal, and the objective lens can also be used to converge the laser beam to the to-be-detected object.

[0073] The laser module includes a plurality of light sources, and the plurality of light sources are respectively used to emit laser beams to a plurality of corresponding sub-regions in the detection area of the to-be-detected object, so as to realize the precise excitation of different radiation laser light sources, reduce the mutual mixing influence between the signal light damage and the fluorescence signal, and improve the excitation light efficiency.

[0074] The above only describes the preferred embodiments of the application. Although the application has been disclosed as above with the preferred embodiments, it is not intended to limit the application. Any person skilled in the art can make many possible changes and modifications to the technical solutions of the application, or modify equivalent embodiments with equivalent changes, without departing from the scope of the technical solutions of the application. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the application, without departing from the technical solutions of the application, all still belong to the scope of protection of the technical solutions of the application.

Claims

1. A step-and-stitch imaging system, characterized by, The system comprises, in order from the object end to the image end: an objective lens for obtaining a fluorescent signal from an object to be detected; a beam splitter for splitting the fluorescent signal into a plurality of monochromatic lights; a linear array camera having a plurality of pixel regions, the plurality of monochromatic lights being respectively imaged on corresponding pixel regions.

2. The staged imaging system of claim 1, wherein, The system further comprises a filter disposed between the beam splitter and the linear array camera, the filter being configured to filter the plurality of monochromatic lights before the plurality of monochromatic lights enter the linear array camera.

3. The staged imaging system of claim 2, wherein, The filter comprises a plurality of filter sub-regions corresponding to the pixel regions, each filter sub-region being configured to transmit the monochromatic light imaged on the corresponding pixel region.

4. The staged imaging system of claim 3, wherein, The filter sub-regions correspond one-to-one to the pixel regions.

5. The step imaging system according to any one of claims 1 to 4, wherein Each pixel region comprises a plurality of rows of pixels, the pixel values of the plurality of rows of pixels being used to obtain a detection result corresponding to the pixel region by integration operation, and the plurality of pixel regions are arranged in a column direction.

6. The step imaging system according to any one of claims 1 to 4, wherein Each row of pixels comprises a plurality of pixel groups, and a plurality of sub-pixels belonging to the same pixel group are continuously distributed; each pixel region comprises a pixel matrix composed of a plurality of sub-pixels, the plurality of sub-pixels comprising a plurality of pixel groups belonging to different rows respectively, and the pixel values of the plurality of sub-pixels are used to obtain a detection result corresponding to the pixel region by integration operation in a row direction, and the plurality of pixel regions are arranged in an array.

7. The step imaging system according to any one of claims 1 to 6, wherein Two adjacent pixel regions are denoted as a first pixel region and a second pixel region, the pixel values of a first matrix region of the first pixel region facing the second pixel region and the pixel values of a second matrix region of the second pixel region facing the first pixel region do not participate in the integration operation for determining the detection result.

8. The staged imaging system of claim 7, wherein, In a direction along a line connecting the center of the first pixel region and the center of the second pixel region, the sum of the sizes of the first matrix region and the second matrix region ranges from 5 to 200 microns.

9. The step imaging system according to any one of claims 1 to 8, wherein The beam splitter comprises a dichroic mirror.

10. The step imaging system according to any one of claims 1 to 9, wherein, The number of linear array cameras is a plurality. The beam splitter is configured to split the fluorescent signal into a plurality of groups of monochromatic lights, each group of monochromatic lights comprising a plurality of monochromatic lights, and each group of monochromatic lights is configured to be incident on a same linear array camera.

11. The step imaging system according to any one of claims 1 to 10, wherein The system further comprises a filter disposed between the beam splitter and the linear array camera, the filter being configured to filter the plurality of monochromatic lights before the plurality of monochromatic lights enter the linear array camera. The number of linear array cameras is the same as the number of filters and the filters are disposed one-to-one; or, the number of filters is a plurality, and there is a target filter comprising a plurality of filter regions, the plurality of filter regions corresponding one-to-one to a plurality of linear array cameras corresponding to the target filter.

12. A detection device, characterized in that The system comprises: The system of any one of claims 1-11; a displacement stage configured to carry the object to be detected and move the object to be detected at a preset moving speed.

13. The detection device of claim 12, wherein, The apparatus further comprises: a laser module configured to generate a laser beam to excite the object to be detected to generate the fluorescent signal, and the objective lens is further configured to converge the laser beam to the object to be detected.

14. The detection device of claim 13, wherein, The laser module comprises a plurality of light sources, and the plurality of light sources are respectively configured to emit laser beams to a plurality of sub-regions corresponding to the plurality of sub-regions in the detection region of the object to be detected.

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