Scanning imaging system for biochip

Abstract

A scanning imaging system (100) for a biochip, comprising a damping module (1), an objective table (2) and an optical engine module (3), wherein the damping module (1) comprises a damping bottom plate (11) and optical engine supporting frames (12) located on opposite sides of the damping bottom plate (11); in a first direction (z), the height of the optical engine supporting frames (12) is greater than the thickness of the damping bottom plate (11); the first direction (z) is perpendicular to a plane where the damping bottom plate (11) is located; the objective table (2) is located on the damping bottom plate (11) and is configured to carry a biochip (7); the objective table (2) can move in a second direction (x) and a third direction (y); in the second direction (x) and the third direction (y), the maximum moving distance of the objective table (2) is at least 20 cm; the second direction (x) and the third direction (y) are orthogonal to each other and are parallel to the plane where the damping bottom plate (11) is located; the optical engine module (3) is supported by two optical engine supporting frames (12); the optical engine module (3) covers an area where the damping bottom plate (11) is located, and is not in contact with the objective table (2); and the optical engine module (3) comprises an objective (32) and an optical imaging unit, and is configured to perform scanning imaging on the biochip (7).

Description

Biochip scanning imaging system Technical Field

[0001] The present application relates to the technical field of biological tissue imaging, for example, to a scanning imaging system for a biochip. Background Art

[0002] Based on the principle of specific interactions between biological molecules, biochips capture biological components through biological probes on the biochip and integrate the biochemical analysis process on the chip surface, thereby achieving high-throughput and rapid detection of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), peptides, proteins and other biological components.

[0003] In one embodiment, a scanning imaging system scans and images the biomacromolecules, cells, and tissues captured by the biochip, and then detects and analyzes the biological sample based on the resulting image. However, the imaging area of ​​most scanning imaging instruments is less than 7 cm, which is too small to meet the imaging requirements of large tissue sections required for the development of spatiotemporal omics.

[0004] Summary of the Invention

[0005] The present application provides a biochip scanning imaging system to meet the imaging requirements of large-scale tissues on large-scale biochips.

[0006] The present application provides a biochip scanning imaging system comprising:

[0007] A shock-absorbing module, comprising a shock-absorbing base plate and optical mechanical support frames located on opposite sides of the shock-absorbing base plate, wherein the height of the optical mechanical support frames is greater than the thickness of the shock-absorbing base plate along a first direction, wherein the first direction is perpendicular to the plane of the shock-absorbing base plate;

[0008] A stage, located on the shock-absorbing base plate and configured to carry the biochip; the stage is movable in a second direction and a third direction, wherein the maximum movable distance of the stage in the second direction is at least 20 cm, and the maximum movable distance of the stage in the third direction is at least 20 cm; the second direction and the third direction are orthogonal and parallel to the plane of the shock-absorbing base plate;

[0009] The optomechanical module is supported by two optomechanical support frames; the optomechanical module covers the area where the shock-absorbing base plate is located and does not contact the objective stage; the optomechanical module includes an objective lens and an optical imaging unit, and the optical axis of the objective lens is parallel to the first direction; the optomechanical module is configured to scan and image the biochip through the optical imaging unit and the objective lens.

[0010] Optionally, the optical imaging unit includes a first light path guiding module, a second light path guiding module, a light source module and a camera module;

[0011] The first light path guiding module includes at least one first optical lens; the first optical lens includes at least one of a first dichroic mirror and a semi-transparent and semi-reflective mirror; the second light path guiding module includes a second dichroic mirror; the second dichroic mirror, the first optical lens, and the objective lens are sequentially arranged along a coaxial optical axis along a first direction, the first optical lens and the second dichroic mirror are both arranged at 45 degrees relative to a first plane, and the mirror surface of the first optical lens and the mirror surface of the second dichroic mirror are perpendicular to each other; the first plane is an intersection plane of the second direction and the third direction;

[0012] The illumination light emitted by the light source module is reflected by the first optical lens and then incident on the biochip through the objective lens; the return light from the biochip is emitted to the first optical lens through the objective lens, is transmitted by the first optical lens, and is incident on the second dichroic mirror, and then reflected by the second dichroic mirror and incident on the camera module.

[0013] Optionally, the light source module includes a laser light source module, and the camera module includes a black and white camera module;

[0014] The first optical lens includes a first dichroic mirror; the laser emitted by the laser light source module is reflected by the first dichroic mirror and then incident on the biochip through the objective lens; the fluorescence excited on the biochip is emitted to the first dichroic mirror through the objective lens, is transmitted through the first dichroic mirror and then incident on the second dichroic mirror, and then reflected by the second dichroic mirror and incident on the black and white camera module.

[0015] Optionally, the light source module includes a white light source module, and the camera module includes a color camera module;

[0016] The first optical lens includes a semi-transparent and semi-reflective mirror; the white light emitted by the white light source module is reflected by the semi-transparent and semi-reflective mirror and then incident on the biochip through the objective lens; the reflected light of the biochip is emitted to the semi-transparent and semi-reflective mirror through the objective lens, is transmitted through the semi-transparent and semi-reflective mirror, and then is incident on the second dichroic mirror, and then reflected by the second dichroic mirror and incident on the color camera module.

[0017] Optionally, the light source module includes a laser light source module and a white light source module; the camera module includes a black and white camera module and a color camera module; the optical imaging unit also includes a light source switching module and a camera switching module;

[0018] The light emitting direction of the laser light source module is parallel to the first direction, the light emitting direction of the white light source module is parallel to the second direction, the light source switching module includes a first linear motion assembly and a first reflector, and the first reflector is arranged at 45 degrees relative to the first plane; the first optical lens includes at least one first dichroic mirror and a semi-transparent semi-reflective mirror arranged side by side, and the first light path guide module also includes a second linear motion assembly;

[0019] The first linear motion assembly is configured to drive the first reflector to move along the third direction, and the second linear motion assembly is configured to drive the first optical lens to move along the third direction, so that the first reflector and one of the first dichroic mirrors share an optical axis along the second direction, and the laser beam emitted by the laser light source module is reflected by the first reflector and incident on the first dichroic mirror; or the first linear motion assembly is configured to drive the first reflector to move along the third direction, and the second linear motion assembly is configured to drive the first optical lens to move along the third direction, so that the white light source module and the semi-transparent half-reflecting mirror share an optical axis along the second direction, and the first reflector is not in the optical path of the white light source module and the semi-transparent half-reflecting mirror;

[0020] The black and white camera module includes a first tube lens, and the color camera module includes a second tube lens. The optical axis of the first tube lens is parallel to the second direction, and the optical axis of the second tube lens is parallel to the third direction. The camera switching module includes a third linear motion assembly and a second reflector. The second reflector is arranged at a 45-degree angle relative to a second plane. The second plane is the intersection of the first direction and the second direction.

[0021] The third linear motion component is configured to drive the second reflector to move along the first direction, so that when the white light source module is working, the second reflector and the second dichroic mirror share the optical axis along the second direction, and the reflected light of the second dichroic mirror is reflected by the second reflector and then incident on the second tube mirror; or, the third linear motion component is configured to drive the second reflector to move along the first direction, so that when the laser light source module is working, the first tube mirror and the second dichroic mirror share the optical axis along the second direction, and the second reflector is not in the optical path of the first tube mirror and the second dichroic mirror, and the reflected light of the second dichroic mirror is incident on the first tube mirror.

[0022] Optionally, the optical imaging unit further includes a filter module;

[0023] The filter module includes at least one filter, which is located in the light path between the second dichroic mirror and the black and white camera module. When the laser light source module is working, the reflected light of the second dichroic mirror is filtered by the filter and then incident on the black and white camera module.

[0024] Optionally, the filter module includes at least two filters and a fourth linear motion component;

[0025] The fourth linear motion component is configured to drive the filter to move along the third direction, so that when the laser light source module is working, the black and white camera module, one of the filters and the second dichroic mirror are aligned with the optical axis in sequence along the second direction.

[0026] Optionally, the first optical lens includes two first dichroic mirrors; the wavelength range of light transmitted by one of the first dichroic mirrors includes 508nm to 548nm and 660nm to 950nm; the wavelength range of light transmitted by the other first dichroic mirror is 558nm to 600nm;

[0027] The wavelength range of the reflected light of the second dichroic mirror is 400 nm to 750 nm.

[0028] Optionally, the optical-mechanical module further includes an autofocus unit; the autofocus unit is configured to adjust the position of the objective lens in the first direction so that the biochip is always in the focal plane of the objective lens.

[0029] Optionally, the autofocus unit includes an optical detection module and a fifth linear motion component;

[0030] The optical detection module is configured to detect whether the biochip is located in the focal plane of the objective lens;

[0031] The fifth linear motion component is configured to move the objective lens along the first direction to a target distance according to the detection result.

[0032] Optionally, the optical detection module includes a detection component and a third reflector connected to form an optical path along a third direction; the third reflector and the second dichroic mirror are arranged along the first direction with a common optical axis and at 45° relative to the first plane; the detection light emitted by the detection component is reflected by the third reflector, and then transmitted to the biochip through the second dichroic mirror, the first optical lens and the objective lens in sequence, and then reflected by the biochip, and then passes through the objective lens, the first optical lens and the second dichroic mirror in sequence to enter the third reflector, and then reflected by the third reflector and enter the detection component.

[0033] Optionally, the detection light is near-infrared light.

[0034] Optionally, the fifth linear motion component includes an objective lens holder, and the objective lens is fixed on the objective lens holder; the objective lens holder includes a first holder section and a second holder section that are integrally formed and orthogonal to each other; wherein the first holder section is parallel to the first plane and includes a first opening that passes through the first holder section along the first direction; the objective lens is inserted into the first opening and fixed on the first holder section.

[0035] Optionally, the camera module includes an imaging camera, and the imaging camera is a line array camera.

[0036] Optionally, the two optical machine support frames are arranged opposite to each other along the second direction, and a side of the optical machine support frame close to the optical machine module includes a right-angled corner extending along the third direction and a raised portion adjacent to the right-angled corner, an optical machine slide rail extending along the third direction is provided on the right-angled corner, and the optical machine slide rail includes at least two sliders, each slider is mounted with a support block, and a side of the support block close to the optical machine module is flush with a side of the raised portion close to the optical machine module;

[0037] The optical-mechanical module includes an optical-mechanical base plate, wherein at least two groups of first bolt mounting holes and a plurality of fixing bolt mounting holes are provided in the area where the optical-mechanical base plate and the optical-mechanical support frame overlap; the first bolt mounting holes are provided in a one-to-one correspondence with the support blocks, each group of first bolt mounting holes includes a supporting bolt mounting hole and at least two equiaxial shoulder bolt mounting holes, and spring washers are provided in the equiaxial shoulder bolt mounting holes; and the fixing bolt mounting holes are provided in correspondence with the protrusions;

[0038] During the non-objective lens maintenance phase, the fixing bolts are inserted into the fixing bolt mounting holes and connected to the raised portions, the equiaxial shoulder bolts are inserted into the equiaxial shoulder bolt mounting holes and connected to the support blocks, and the support bolts are inserted into the support bolt mounting holes and are not tightened.

[0039] During the objective lens maintenance stage, the fixing bolt is not connected to the protrusion, the equiaxial shoulder bolt is inserted into the equiaxial shoulder bolt mounting hole and connected to the support block, and the support bolt is inserted into the support bolt mounting hole and is tightened, so that the optical machine module slides along the optical machine slide rail and the optical machine base plate is separated from the protrusion; the compression degree of the spring gasket during the objective lens maintenance stage is greater than the compression degree of the spring gasket during the non-objective lens maintenance stage.

[0040] Optionally, the scanning imaging system further includes a frame module, and the shock absorption module is fixed on the frame module;

[0041] The rack module includes a box body; the electrical control device, reagent storage device and waste liquid recovery device of the scanning imaging system are integrated in the box body; the side wall of the box body is provided with a communication interface and a power interface; the bottom of the box body is installed with multiple universal wheels and multiple support and leveling foot cups.

[0042] Optionally, the shock absorption module further includes a plurality of shock absorber modules, and the shock absorber modules include shock absorbers, shock absorber support frames and shock absorber mounting frames;

[0043] The shock absorber support frame is located on the side of the optical machine support frame away from the shock absorber base plate and is fixed on the box; the shock absorber mounting frame is fixed on the side wall of the optical machine support frame away from the shock absorber base plate; the shock absorber is located between the shock absorber support frame and the shock absorber mounting frame, and is respectively connected to the shock absorber support frame and the shock absorber mounting frame.

[0044] Optionally, the two optical machine support frames are arranged opposite to each other along the second direction; the optical machine support frame includes at least one second opening passing through the optical machine support frame along the second direction, and the second opening does not overlap with the position of the shock absorber mounting frame.

[0045] Optionally, a vacuum adsorption platform is provided on the stage, and a negative pressure pump is integrated in the box, and the negative pressure pump is connected to the vacuum adsorption platform to adsorb the biochip.

[0046] Optionally, a plurality of protective structures are provided on the box body;

[0047] The protective structure includes a first protective section and a second protective section that are integrally formed and orthogonal to each other; wherein the first protective section is perpendicular to the plane of the shock-absorbing base plate and is located on the same side of the shock-absorbing base plate and the optical machine support frame; the second protective section is located on the side of the first protective section away from the shock-absorbing module and is connected to the box body;

[0048] During the imaging process, the first protection section does not contact the shock absorption module; during the transportation process, the first protection section leans against the shock absorption module and contacts at least one of the shock absorption base plate and the optical machine support frame. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] FIG1 is a schematic structural diagram of a biochip scanning imaging system provided in an embodiment of the present application;

[0050] FIG2 is a schematic structural diagram of a vibration reduction module in the scanning imaging system shown in FIG1 ;

[0051] FIG3 is a schematic diagram of the optical principle of a scanning imaging system provided in an embodiment of the present application;

[0052] FIG4 is a schematic structural diagram of an optical-mechanical module in the scanning imaging system shown in FIG1 ;

[0053] FIG5 is an enlarged structural diagram of the light source switching module in the optical-mechanical module shown in FIG4 ;

[0054] FIG6 is an enlarged structural diagram of the first light path guiding module in the optical-mechanical module shown in FIG4 ;

[0055] FIG7 is an enlarged structural diagram of any camera module in the optical-mechanical module shown in FIG4 ;

[0056] FIG8 is an enlarged structural diagram of a camera switching module in the optical-mechanical module shown in FIG4 ;

[0057] FIG9 is an enlarged structural diagram of the filter module in the optical-mechanical module shown in FIG4 ;

[0058] FIG10 is a disassembled diagram of a system related to fluorescence imaging in a scanning imaging system provided in an embodiment of the present application;

[0059] FIG11 is a schematic diagram of the optical principle of fluorescence imaging of a scanning imaging system provided in an embodiment of the present application;

[0060] FIG12 is a disassembled diagram of a system related to bright field imaging in a scanning imaging system provided in an embodiment of the present application;

[0061] FIG13 is a schematic diagram of the optical principle of bright field imaging of a scanning imaging system provided in an embodiment of the present application;

[0062] FIG14 is an enlarged structural diagram of the fifth linear motion assembly in the optical-mechanical module shown in FIG4 ;

[0063] FIG15 is a disassembled diagram of a system related to autofocus in a scanning imaging system provided in an embodiment of the present application;

[0064] FIG16 is a schematic diagram of a planar structure of a scanning imaging system provided in an embodiment of the present application;

[0065] FIG17 is a schematic diagram of an enlarged structure of the area marked by the elliptical dotted line in FIG16;

[0066] FIG18 is a schematic diagram of the state of the scanning imaging system provided in an embodiment of the present application during the objective lens maintenance stage;

[0067] FIG19 is a schematic structural diagram of a rack module in a scanning imaging system shown in FIG1 ;

[0068] FIG20 is a schematic structural diagram of a rack module in another scanning imaging system shown in FIG1 .

[0069] Reference numerals:

[0070] 100-Scanning Imaging System;

[0071] 1 - shock absorption module; 11 - shock absorption base plate; 12 - optical machine support frame; 121 - right-angled notch; 122 - raised portion; 123 - second opening; 13 - shock absorber module; 131 - shock absorber; 132 - shock absorber support frame; 133 - shock absorber mounting frame; 14 - optical machine slide rail; 141 - slider; 142 - support block; 143 - track;

[0072] 2- stage;

[0073] 3- Optical-mechanical module;

[0074] 30-optical detection module; 301-detection component; 302-third reflector;

[0075] 31- optical machine base plate;

[0076] 32-objective lens; 320-fifth linear motion assembly; 3200-objective lens bracket; 3201-first bracket subsection; 3202-second bracket subsection;

[0077] 33-first optical path guide module; 331-first optical lens; 3311-first dichroic mirror; 3312-semi-transparent and semi-reflective mirror; 332-second linear motion assembly;

[0078] 34-second optical path guide module; 341-second dichroic mirror;

[0079] 35-light source module; 351-laser light source module; 3511-optical fiber; 352-white light source module;

[0080] 36 - camera module; 361 - black and white camera module; 3611 - first tube lens; 3612 - fourth reflector; 3613 - black and white imaging camera; 362 - color camera module; 3621 - second tube lens; 3622 - fifth reflector; 3623 - color imaging camera;

[0081] 37-light source switching module; 371-first reflector; 372-first linear motion component;

[0082] 38-camera switching module; 381-second reflector; 382-third linear motion component;

[0083] 39- filter module; 391- filter; 392- fourth linear motion component;

[0084] 310-first bolt mounting hole; 3101-support bolt mounting hole; 3102-equiaxial shoulder bolt mounting hole; 312-fixing bolt mounting hole; 313-spring washer; 3111-support bolt; 3112-equiaxial shoulder bolt;

[0085] 4-Rack module; 41-Box; 42-Electrical control device; 421-Linear motion assembly controller; 422-Displacement controller; 43-Reagent storage device; 44-Waste liquid recovery device; 45-Communication interface; 46-Power interface; 47-Universal wheel; 48-Support and leveling foot cup; 49-Negative pressure monitoring module; 410-Negative pressure pump; 411-Waste liquid pump; 412-Pure water tank;

[0086] 5- Vacuum adsorption platform;

[0087] 6-protection structure; 61-first protection division; 62-second protection division;

[0088] 7-Biochip;

[0089] z-first direction; x-second direction; y-third direction. DETAILED DESCRIPTION

[0090] The following will describe the technical solutions in the embodiments of the present application in conjunction with the accompanying drawings. The embodiments described are only part of the embodiments of the present application, not all of the embodiments. The terms "first", "second", etc. in the specification and claims of this application and the above-mentioned drawings are only used to distinguish similar objects and have no substantive meaning.

[0091] FIG1 is a schematic structural diagram of a biochip scanning and imaging system provided in an embodiment of the present application, and FIG2 is a schematic structural diagram of a shock-absorbing module in the scanning and imaging system shown in FIG1 . As shown in FIG1 and FIG2 , the scanning and imaging system 100 provided in an embodiment of the present application includes a shock-absorbing module 1, a stage 2, and an optical-mechanical module 3; the shock-absorbing module 1 includes a shock-absorbing base plate 11 and an optical-mechanical support frame 12 located on opposite sides of the shock-absorbing base plate 11; along a first direction z, the height of the optical-mechanical support frame 12 is greater than the thickness of the shock-absorbing base plate 11; the first direction z is perpendicular to the plane where the shock-absorbing base plate 11 is located; the stage 2 is located on the shock-absorbing base plate 11 and is configured to carry the biochip 7; the stage 2 can move along the second direction x and the third direction y; along the second direction x, the maximum moving distance of the stage 2 is at least 20 cm, and along the third direction y, the maximum moving distance of the stage 2 is at least 20 cm; the second direction x and the third direction y are orthogonal to each other and are both parallel to the plane where the shock-absorbing base plate 11 is located; the optomechanical module 3 is supported by two optomechanical support frames 12; the optomechanical module 3 covers the area where the shock-absorbing base plate 11 is located and has no contact with the stage 2; the optomechanical module 3 includes an objective lens and an optical imaging unit, and the optical axis of the objective lens is parallel to the first direction z; the optomechanical module 3 is configured to scan and image the biochip 7 through the optical imaging unit and the objective lens.

[0092] As shown in Figure 1, the scanning imaging system 100 mainly includes an optical machine module 3, a shock-absorbing module 1 and a rack module 4. The rack module 4 has a box body 41. The shock-absorbing module 1 is fixed on the box body 41 of the rack module 4. The optical machine module 3 has an optical machine base plate 31. The optical machine base plate 31 is mounted on the optical machine support frame 12 of the shock-absorbing module 1. The optical machine module 3 is supported by the optical machine support frame 12. The stage 2 configured to carry the biochip 7 is arranged on the shock-absorbing base plate 11 of the shock-absorbing module 1. Since the thickness of the shock-absorbing base plate 11 is less than the height of the optical machine support frame 12, the stage 2 and the shock-absorbing base plate 11 are located below the optical machine base plate 31 and are covered by the optical machine base plate 31.

[0093] The optical machine module 3 is the core part of the entire scanning imaging system, including an objective lens and an optical imaging unit, which is mainly configured to magnify and image the biological tissue slices on the biochip 7 and transmit the image information to the computer software for processing. For example, the objective lens is located at the geometric center of the optical machine base plate 31, and the optical axis of the objective lens is parallel to the first direction z. By setting an opening on the optical machine base plate 31 that passes through the optical machine base plate 31 along the first direction z, the objective lens can be connected to the biochip 7 on the lower stage 2 by an optical path. The optical imaging unit mainly includes a light source module configured for illumination, a camera module configured for imaging, and an optical path guide module configured for adjusting the propagation direction of light. The light from the light source module can be transmitted to the biochip 7 through the objective lens through the optical path adjustment unit, and the return light of the biochip 7 collected by the objective lens can be transmitted to the camera module to achieve imaging. The optical imaging unit is integrated on the optical machine base plate 31. The structure of the optical imaging unit will be explained later and will not be repeated here.

[0094] The shock absorption module 1 is located between the rack module 4 and the optical machine module 3 and is configured to isolate the entire scanning imaging system from vibration interference and maintain stable operation. As shown in Figures 1 and 2 , the shock absorption module 1 includes a shock absorption base plate 11, an optical machine support frame 12, and multiple shock absorber modules 13; the shock absorber module 13 includes a shock absorber 131, a shock absorber support frame 132, and a shock absorber mounting frame 133; the shock absorber support frame 132 is located on the side of the optical machine support frame 12 away from the shock absorption base plate 11 and is fixed to the box 41 of the rack module 4; the shock absorber mounting frame 133 is fixed to the side wall of the optical machine support frame 12 away from the shock absorption base plate 11; the shock absorber 131 is located between the shock absorber support frame 132 and the shock absorber mounting frame 133 and is connected to the shock absorber support frame 132 and the shock absorber mounting frame 133 respectively. As shown in FIG. 2 , optionally, the shock absorber mounting frame 133 is mounted on the upper area of ​​the side wall of the optical machine support frame 12 . Such a configuration is beneficial for lowering the center of gravity and improving structural stability.

[0095] As shown in Figure 2 , two optical engine supports 12 are optionally arranged opposite each other along the second direction x. Each optical engine support 12 includes at least one second opening 123 extending through the optical engine support 12 along the second direction x. The second opening 123 does not overlap with the location of the shock absorber mounting bracket 133. The provision of the second opening 123 allows the optical engine support 12 to be hollowed out to reduce weight, lower its center of gravity, and improve structural stability.

[0096] For example, referring to Figure 2, in this embodiment, the shock absorption module 1 includes four shock absorber modules 13, and every two shock absorber modules 13 are symmetrically arranged on both sides of the optical machine support frame 12 along the third direction y, and the second opening 123 is arranged at the center of the optical machine support frame 12, so that the structure of the shock absorption module 1 is symmetrical, and the shock absorption effect at multiple positions is more uniform.

[0097] Figure 2 only takes the top view shape of the shock-absorbing base plate 11 as a rectangle, and the second direction x and the third direction y are the long side direction and the short side direction of the rectangle as an example. In other embodiments, the top view shape of the shock-absorbing base plate 11 can be any other shape, and the embodiments of the present application are not limited to this, as long as the second direction x and the third direction y are orthogonal and parallel to the plane where the shock-absorbing base plate 11 is located.

[0098] As shown in Figures 1 and 2 , the stage 2 is mounted on a shock-absorbing base plate 11 and is movable along a second direction x and a third direction y. The maximum movement distance along both the second direction x and the third direction y is at least 20 cm. Thus, the stage 2 can carry the biochip 7 and move together. By moving the object being photographed, panoramic scanning imaging of large-scale biochips can be achieved, resolving the problem that scanning imaging systems have a small imaging area and can only perform panoramic scanning imaging on small-scale biochips. For example, the scanning imaging system of an embodiment of the present application can perform panoramic scanning imaging on large-scale tissues on large-scale biochips measuring 13 cm*13 cm.

[0099] The rack module 4 is located below the shock absorbing module 1 and is configured to support the entire scanning imaging system. At the same time, the fluid devices (such as reagent storage devices) and electronic and electrical control devices required for the operation of the scanning imaging system are integrated into the rack module 4. The structure of the rack module 4 will be described later and will not be repeated here.

[0100] In summary, the scanning imaging system provided in the embodiment of the present application is configured to include a shock-absorbing module 1 including a shock-absorbing base plate 11 and an optical machine support frame 12, and to configure the height of the optical machine support frame 12 to be greater than the thickness of the shock-absorbing base plate 11; a stage 2 movable along the second direction x and the third direction y is configured on the shock-absorbing base plate 11; and the optical machine support frame 12 is utilized to provide support for the optical machine module 3, so that the optical machine module 3 can scan and image the biochip 7 on the stage 2 through the objective lens and the optical imaging unit; and since the maximum moving distance of the stage 2 along the second direction x and the third direction y is at least 20 cm, the stage 2 can move with the biochip 7, and by moving the photographed object, panoramic scanning imaging of large-size biochips can be achieved, thereby solving the problem that the scanning imaging system has a small imaging area and can only perform panoramic scanning imaging of small-size biochips.

[0101] Based on the above embodiment, FIG3 is a schematic diagram of the optical principle of the scanning imaging system provided by the embodiment of the present application. As shown in FIG3 , optionally, the optical imaging unit includes a first light path guiding module 33, a second light path guiding module 34, a light source module 35 and a camera module 36; the first light path guiding module 33 includes at least one first optical lens 331; the first optical lens 331 includes at least one of a first dichroic mirror and a semi-transparent semi-reflective mirror; the second light path guiding module 34 includes a second dichroic mirror 341; the second dichroic mirror 341, the first optical lens 331 and the objective lens 32 are sequentially arranged along the first direction z on a common optical axis, the first optical lens 331 and the second dichroic mirror 341 are both arranged at 45° relative to the first plane, and the mirror surface of the first optical lens 331 and the mirror surface of the second dichroic mirror 341 are perpendicular to each other; The first plane is the intersection plane of the second direction x and the third direction y; the illumination light emitted from the light source module 35 is reflected by the first optical lens 331 and then incident on the biochip 7 through the objective lens 32; the return light of the biochip 7 is emitted to the first optical lens 331 through the objective lens 32, is transmitted through the first optical lens 331, and then is incident on the second dichroic mirror 341, and then reflected by the second dichroic mirror 341 and incident on the camera module 36.

[0102] A dichroic mirror, also known as a two-color mirror, is characterized by being almost completely transparent to light of a certain wavelength and almost completely reflecting light of other wavelengths. The sum of the transmittance and reflectance of a semi-transparent and semi-reflective mirror to light is 100%. According to the imaging requirements of different samples, a suitable light source module 35 and camera module 36 can be selected and equipped with a corresponding first optical lens 331 and a second dichroic mirror 341. In this embodiment, by setting the mirror surface of the first optical lens 331 and the mirror surface of the second dichroic mirror 341 to be perpendicular to each other, the light source module 35 and the camera module 36 can be dispersed in different areas of the optical machine base plate 31, making the layout of the optical imaging unit more reasonable and helping to reduce the impact on light propagation.

[0103] In one embodiment, optionally, the light source module 35 includes a laser light source module, and the camera module 36 includes a black and white camera module; accordingly, the first optical lens 331 includes a first dichroic mirror; the laser emitted by the laser light source module is reflected by the first dichroic mirror and then incident on the biochip 7 through the objective lens 32; the fluorescence excited on the biochip 7 is emitted to the first dichroic mirror through the objective lens 32, is transmitted through the first dichroic mirror, and then incident on the second dichroic mirror 341, and then reflected by the second dichroic mirror 341 and incident on the black and white camera module. For example, when imaging a sample stained with a fluorescent dye (hereinafter referred to as fluorescence imaging), the light source module 35 can be a laser light source, the camera module 36 can be a black and white camera, the first optical lens 331 can be a first dichroic mirror capable of reflecting laser light and transmitting fluorescence, and the second dichroic mirror 341 can be a dichroic mirror capable of reflecting fluorescence. This allows the laser light source to be reflected by the first dichroic mirror and incident on the biochip 7 through the objective lens 32, thereby stimulating the fluorescent dye bound to the surface of the biochip 7 to produce fluorescence. This fluorescent light is collected by the objective lens 32 and then incident on the second dichroic mirror 341 through the first dichroic mirror. After being reflected by the second dichroic mirror 341, it is incident on the black and white camera, thereby achieving fluorescence imaging. The wavelength ranges of the transmitted and reflected light of the first and second dichroic mirrors 341 can be set according to actual needs.

[0104] In another embodiment, the light source module 35 optionally includes a white light source module, and the camera module 36 includes a color camera module; the first optical lens 331 includes a semi-transparent and semi-reflective mirror; the white light emitted by the white light source module is reflected by the semi-transparent and semi-reflective mirror, then incident on the biochip 7 through the objective lens 32; the reflected light from the biochip 7 is emitted toward the semi-transparent and semi-reflective mirror through the objective lens 32, then incident on the second dichroic mirror 341 after being transmitted through the semi-transparent and semi-reflective mirror, and then incident on the color camera module after being reflected by the second dichroic mirror 341. For example, when imaging a sample stained with hematoxylin-eosin (HE), the image can be formed by the reflected light of the sample, which is bright field imaging. At this time, the light source module 35 can use a white light source, the camera module 36 can use a color camera, the first optical lens 331 can use a semi-transparent and semi-reflective mirror, and the second dichroic mirror 341 can use a dichroic mirror that can reflect white light, so that the white light source is reflected by the semi-transparent and semi-reflective mirror and then enters the biochip 7 through the objective lens 32. The reflected light of the biochip 7 is collected by the objective lens 32 and then enters the second dichroic mirror 341 through the semi-transparent and semi-reflective mirror, and then reflected by the second dichroic mirror 341 and enters the color camera to achieve bright field imaging.

[0105] In another embodiment, optionally, the scanning imaging system has both fluorescence imaging function and bright field imaging function to improve the integration and practicality of the scanning imaging system.

[0106] For example, Figure 4 is a structural schematic diagram of the optical-mechanical module in the scanning imaging system shown in Figure 1, Figure 5 is an enlarged structural schematic diagram of the light source switching module in the optical-mechanical module shown in Figure 4, Figure 6 is an enlarged structural schematic diagram of the first optical path guide module in the optical-mechanical module shown in Figure 4, Figure 7 is an enlarged structural schematic diagram of any camera module in the optical-mechanical module shown in Figure 4, Figure 8 is an enlarged structural schematic diagram of the camera switching module in the optical-mechanical module shown in Figure 4, and Figure 9 is an enlarged structural schematic diagram of the filter module in the optical-mechanical module shown in Figure 4. 4 to 9 , optionally, the light source module 35 includes a laser light source module 351 and a white light source module 352; the camera module 36 includes a black and white camera module 361 and a color camera module 362; the optical imaging unit also includes a light source switching module 37, a camera switching module 38 and a filter module 39; the light emitting direction of the laser light source module 351 is parallel to the first direction z, the light emitting direction of the white light source module 352 is parallel to the second direction x, the light source switching module 37 includes a first linear motion component 372 and a first reflector 371, the first reflector 371 is set at 45° relative to the first plane, and the first linear motion component 372 is set to drive the first reflector 371 to move along the third direction y; the first optical lens 331 includes at least one first dichroic mirror 3311 and a semi-transparent semi-reflective mirror 3312 set side by side, and the first light path guide module 33 also includes a first dichroic mirror 3311 and a semi-transparent semi-reflective mirror 3312 set side by side. It includes a second linear motion component 332, which is configured to drive the first optical lens 331 to move along the third direction y; the black and white camera module 361 includes a first tube lens 3611, and the color camera module 362 includes a second tube lens 3621. The optical axis direction of the first tube lens 3611 is parallel to the second direction x, and the optical axis direction of the second tube lens 3621 is parallel to the third direction y; the camera switching module 38 includes a third linear motion component 382 and a second reflector 381. The second reflector 381 is set at 45° relative to the second plane. The second plane is the intersection plane of the first direction z and the second direction x. The third linear motion component 382 is configured to drive the second reflector 381 to move along the first direction z; the filter module 39 includes at least one filter 391, and the filter 391 is located in the optical path between the second dichroic mirror 341 and the first tube lens 3611. When the laser light source module 351 is working, the reflected light from the second dichroic mirror 341 is filtered by at least one filter 391 and then incident on the black and white camera module 361 .

[0107] The light source switching module 37 is configured to switch between the laser light source module 351 and the white light source module 352, and the camera switching module 38 is configured to switch between the black and white camera module 361 and the color camera module 362. As described above, during fluorescence imaging, the laser light source module 351 and the black and white camera module 361 should be in operation, while during brightfield imaging, the white light source module 352 and the color camera module 362 should be in operation.

[0108] As shown in Figures 4 and 5, the laser light source module 351 is installed vertically and is connected to an external laser through an optical fiber 3511. It can emit laser light along a first direction z. The white light source module 352 is installed horizontally and can emit white light along a second direction x. The two can be installed and connected through the main optical path frame; the light source switching module 37 includes a first linear motion component 372 and a first reflector 371. The first reflector 371 is set at 45° relative to the first plane. The first linear motion component 372 can drive the first reflector 371 to move along the third direction y. In this way, when the first reflector 371 moves to the intersection position of the optical axes of the laser light source and the white light source, the laser light can be reflected by the first reflector 371 to the first optical path guide module 33, and the light source can be switched to a laser light source. Conversely, if the first reflector 371 is not at the intersection position of the optical axes of the laser light source and the white light source, the white light can be incident on the first optical path guide module 33, and the light source can be switched to a white light source.

[0109] Similarly, in combination with Figures 4, 7 and 8, the optical axes of the first tube lens 3611 of the black and white camera module 361 and the second tube lens 3621 of the color camera module 362 are orthogonal, wherein the first tube lens 3611 and the reflected light path of the second dichroic mirror 341 share a common optical axis, while the second tube lens 3621 and the reflected light path of the second dichroic mirror 341 are orthogonal to each other. The second reflector 381 is driven to move along the first direction z by the third linear motion component 382 in the camera switching module 38, thereby realizing switching between the black and white camera module 361 and the color camera module 362. Exemplarily, the second reflector 381 is set at 45° relative to the second plane. In this way, when the second reflector 381 moves downward to be coaxial with the reflected light path of the second dichroic mirror 341, the reflected light of the second dichroic mirror 341 can be reflected to the second tube lens 3621 and received by the color camera module 362 to achieve color imaging. On the contrary, when the second reflector 381 is positioned upward, the reflected light of the second dichroic mirror 341 will be directed to the first tube lens 3611 and received by the black and white camera module 361 to achieve black and white imaging, thereby realizing the switching between the black and white camera module 361 and the color camera module 362.

[0110] The relative position relationship between the laser light source module 351 and the white light source module 352 provided in the embodiment of the present application is for illustration only and is not limiting. In other embodiments, the positions of the laser light source module 351 and the white light source module 352 can be interchanged. In addition, the positions of the black and white camera module 361 and the color camera module 362 can also be interchanged. The embodiment of the present application does not limit this.

[0111] As described above, during fluorescence imaging, the first optical lens 331 in the first optical path guiding module 33 uses a dichroic mirror, and during brightfield imaging, the first optical lens 331 in the first optical path guiding module 33 uses a semi-transparent, semi-reflective mirror. As shown in FIG6 , to take into account both fluorescence imaging and brightfield imaging functions, the first optical lens 331 in this embodiment includes at least one first dichroic mirror 3311 and a semi-transparent, semi-reflective mirror 3312 arranged side by side, and the first optical path guiding module 33 also includes a second linear motion component 332, which is used to drive the first optical lens 331 to move along the third direction y. Different first optical lenses 331 are moved to the optical path between the light source module 35 and the objective lens 32 according to different imaging requirements. The principle is similar to that of the light source switching module 37 and will not be explained in detail here.

[0112] Figure 6 illustrates an example in which the first optical lens 331 includes two first dichroic mirrors 3311. In this way, the imaging requirements of the two fluorescent channels can be met. The number of the first dichroic mirrors 3311 in the first optical path guiding module 33 can be set according to the actual fluorescent channel requirements. The embodiment of the present application does not limit this.

[0113] For example, in one embodiment, one of the first dichroic mirrors 3311 can optionally reflect 488nm and 637nm lasers and transmit the fluorescence excited by the lasers, with wavelengths of 508nm to 548nm and 660nm to 950nm respectively; the other first dichroic mirror 3311 can reflect 532nm lasers and transmit the fluorescence excited by the lasers, with wavelengths of 558nm to 600nm. In addition, the reflectivity and transmittance of the semi-transparent and semi-reflective mirrors 3312 for white light can be 50% respectively, or other ratios, which are not limited in this embodiment of the present application. The wavelength range of the reflected light of the second dichroic mirror 341 can be 400nm to 750nm. In this way, the second dichroic mirror 341 can reflect both the above-mentioned fluorescence and white light (400nm to 760nm).

[0114] During fluorescence imaging, by placing a filter in front of the first tube lens 3611 of the black and white camera module 361, that is, in the optical path between the second dichroic mirror 341 and the first tube lens 3611, excess stray light signals can be removed to ensure image quality. The required filters can be set accordingly based on the fluorescence wavelength band used for fluorescence imaging. For example, as shown in FIG9 , in this embodiment, a filter module 39 can be provided to include two filters 391 and a fourth linear motion assembly 392 corresponding to the fluorescence wavelength band transmitted by the two first dichroic mirrors 3311. The fourth linear motion assembly 392 can be used to drive the filters 391 to move along the third direction y, thereby moving the required filters 391 into the imaging optical path according to different fluorescence channels. This arrangement is for illustrative purposes only. In other embodiments, a larger number of filters 391 can be provided as needed, and this embodiment of the present application is not limited thereto.

[0115] The above embodiment illustrates the arrangement of a filter 391 in the optical path between the black-and-white camera module 361 and the second dichroic mirror 341 when the scanning imaging system has both fluorescence imaging and brightfield imaging functions, and is not intended to be limiting. In other embodiments, similar designs can be employed when the scanning imaging system only has fluorescence imaging. For example, the optical imaging unit can include a filter module 39, which includes at least one filter 391. The filter 391 is positioned in the optical path between the second dichroic mirror 341 and the black-and-white camera module 361 (and can be positioned in the optical path between the second dichroic mirror 341 and the light-entering lens of the black-and-white camera module 361). This ensures that when the laser light source module 351 is operating, light reflected from the second dichroic mirror 341 is filtered by the filter 391 before entering the black-and-white camera module 361, thereby ensuring image quality. When the filter module 39 includes at least two filters 391, the filter module 39 can be set to also include a fourth linear motion component 392, and the fourth linear motion component 392 is used to drive the filter 391 to move along the third direction y, so that when the laser light source module 351 is working, the black and white camera module 361 (which can be the light input tube lens of the black and white camera module 361), one of the filters 391 and the second dichroic mirror 341 are sequentially coaxial along the second direction x.

[0116] The following describes the working process of the scanning imaging system based on fluorescence imaging and bright field imaging respectively.

[0117] For example, FIG10 is a disassembled diagram of a system related to fluorescence imaging in a scanning imaging system provided by an embodiment of the present application (FIG10 omits structures such as the optical machine base plate 31 in FIG4 in order to clearly show the optical device), and FIG11 is a schematic diagram of the optical principle of fluorescence imaging in a scanning imaging system provided by an embodiment of the present application. In conjunction with FIG4 to FIG11, during the fluorescence imaging process, the laser light source module 351 is started, the black and white camera module 361 is started, the first linear motion component 372 is controlled to drive the first reflector 371 to move along the third direction y, and the second linear motion component 332 is controlled to drive the first optical lens 331 to move along the third direction y, so that the first reflector 3 71 and one of the first dichroic mirrors 3311 are coaxial along the second direction x, and the first dichroic mirror 3311 is coaxial with the second dichroic mirror 341 and the objective lens 32 along the first direction z. At the same time, the third linear motion component 382 is controlled to drive the second reflector 381 to move along the first direction z, and the fourth linear motion component 392 is controlled to drive the filter 391 to move along the third direction y, so that when the laser light source module 351 is working, the first tube lens 3611, the filter 391 and the second dichroic mirror 341 are coaxial in sequence along the second direction x, and the second reflector 381 is not in the optical path of the first tube lens 3611 and the second dichroic mirror 341. In this way, the laser beam emitted by the laser light source module 351 is reflected by the first reflector 371 and then incident on the first dichroic mirror 3311. After being reflected by the first dichroic mirror 3311, it is incident on the biochip 7 through the objective lens 32 and excites fluorescence. The fluorescence is collected by the objective lens 32 and then passes through the first dichroic mirror 3311 to enter the second dichroic mirror 341, and is reflected by the second dichroic mirror 341. The reflected light of the second dichroic mirror 341 is filtered by the filter 391 and then incident on the first tube lens 3611, and then reflected by the fourth reflector 3612 integrated in the black and white camera module 361 to the black and white imaging camera 3613, thereby realizing fluorescence imaging.

[0118] FIG12 is a disassembly diagram of a system related to bright field imaging in a scanning imaging system provided in an embodiment of the present application (FIG12 omits structures such as the optical machine base plate 31 in FIG4 in order to clearly display the optical device), and FIG13 is a schematic diagram of the optical principle of bright field imaging in a scanning imaging system provided in an embodiment of the present application. In combination with FIG4 to FIG9 and FIG12 and FIG13, during the bright field imaging process, the white light source module 352 is started, the color camera module 362 is started, the first linear motion component 372 is controlled to drive the first reflector 371 to move along the third direction y, and the second linear motion component 332 is controlled to drive the first optical The lens 331 moves along the third direction y so that the white light source module 352 and the semi-transparent and semi-reflective mirror 3312 share the same optical axis along the second direction x, and the first reflector 371 is not in the optical path of the white light source module 352 and the semi-transparent and semi-reflective mirror 3312, and the semi-transparent and semi-reflective mirror 3312 share the same optical axis with the second dichroic mirror 341 and the objective lens 32 along the first direction z. At the same time, the third linear motion component 382 is controlled to drive the second reflector 381 to move along the first direction z, so that when the white light source module 352 is working, the second reflector 381 and the second dichroic mirror 341 share the same optical axis along the second direction x. In this way, the white light beam emitted by the white light source module 352 is incident on the semi-transparent and semi-reflective mirror 3312, and is reflected by the semi-transparent and semi-reflective mirror 3312 before being incident on the biochip 7 through the objective lens 32. The reflected light of the biochip 7 is collected by the objective lens 32 and is incident on the second dichroic mirror 341 through the semi-transparent and semi-reflective mirror 3312, and is reflected by the second dichroic mirror 341. The reflected light of the second dichroic mirror 341 is reflected by the second reflector 381 and is incident on the second tube lens 3621, and is then reflected by the fifth reflector 3622 integrated in the color camera module 362 to the color imaging camera 3623, thereby realizing bright field imaging.

[0119] Based on any of the above embodiments, optionally, the optical-mechanical module 3 further includes an autofocus unit; the autofocus unit is configured to adjust the position of the objective lens 32 in the first direction z so that the biochip 7 is always in the focal plane of the objective lens 32, thereby achieving autofocus during the imaging process and improving the imaging quality.

[0120] As shown in FIG4 , the autofocus unit optionally includes an optical detection module 30 and a fifth linear motion assembly 320 . The optical detection module 30 is configured to detect whether the biochip 7 is within the focal plane of the objective lens 32 . The fifth linear motion assembly 320 is configured to move the objective lens 32 along a first direction z by a target distance based on the detection result. Through the interaction between the optical detection module 30 and the fifth linear motion assembly 320 , the objective lens 32 is focused in real time during the imaging process to accelerate imaging speed and improve imaging quality. The target distance is related to the actual detection result, which will be explained later and is not further elaborated here.

[0121] As shown in FIG4 , optionally, the optical detection module 30 includes a detection assembly 301 and a third reflector 302 that form an optical path along the third direction y; the third reflector 302 and the second dichroic mirror 341 are arranged along the first direction z coaxially and at a 45° angle relative to the first plane. FIG14 is an enlarged structural schematic diagram of the fifth linear motion assembly in the optical-mechanical module shown in FIG4 . As shown in FIG14 , optionally, the fifth linear motion assembly 320 includes an objective lens holder 3200 , to which the objective lens 32 is fixed; the objective lens holder 3200 includes a first holder section 3201 and a second holder section 3202 that are integrally formed and orthogonal to each other; wherein the first holder section 3201 is parallel to the first plane and includes a first opening that passes through the first holder section 3201 along the first direction z; the objective lens 32 is inserted into the first opening and fixed to the first holder section 3201; the fifth linear motion assembly 320 can move the objective lens 32 along the first direction z.

[0122] FIG15 is a disassembled diagram of a system related to autofocus in a scanning imaging system provided by an embodiment of the present application (FIG15 omits structures such as the optical machine base plate 31 in FIG4 in order to clearly show the optical device). In combination with FIG15 and FIG11 (or FIG13), the principle of autofocus is that, during the scanning imaging process, the optical detection module 30 is controlled to start, and the detection light emitted by the detection component 301 is reflected by the third reflector 302 and can be sequentially transmitted through the second dichroic mirror 341, the first optical lens 331 and the objective lens 32. To the biochip 7, and then after being reflected by the biochip 7, it passes through the objective lens 32, the first optical lens 331 and the second dichroic mirror 341 in sequence and is incident on the third reflector 302, and then is reflected by the third reflector 302 and is incident on the detection component 301, so as to detect whether the biochip 7 is located in the focal plane of the objective lens 32, and control the fifth linear motion component 320 to move the objective lens 32 along the first direction z to the target distance according to the detection result, so that the biochip 7 is always in the focal plane of the objective lens 32, thereby realizing automatic focusing.

[0123] Optionally, the detection light is near-infrared light, and the second dichroic mirror 341 , the first dichroic mirror 3311 and the semi-transparent and semi-reflective mirror 3312 can all transmit near-infrared light (780 nm to 2526 nm).

[0124] Exemplarily, the optical detection module 30 emits near-infrared light, which is reflected by the third reflector 302 and then converged on the sample through the objective lens 32. The near-infrared light reflected by the sample can return along the original path. After the light spot is detected by the detection component 301 in the optical detection module 30, the fifth linear motion component 320 can be controlled by the detected signal to move the objective lens 32 along the first direction z, thereby realizing the real-time focusing function during the scanning imaging process.

[0125] During the scanning imaging process, the near-infrared light emitted by the optical detection module 30 is converged on the sample through the objective lens 32, and the near-infrared light reflected by the sample is returned along the original path. If the light spot is divided into two signals by the detection component 301 in the optical detection module 30, it is defocused. Moreover, there will be different signal values ​​in the focal plane and at different defocus distances. Therefore, the target distance that the fifth linear motion component 320 needs to move can be determined based on the defocus distance of the detection signal (the target distance is greater than or equal to zero).

[0126] Since the tissue surface is covered with reagents, the evaporation of the liquid can easily lead to defocusing, resulting in unclear imaging. The technical solution of the embodiment of the present application can cooperate with the fifth linear motion component 320 and the optical detection module 30 in the autofocus unit, so that during the movement of the stage 2, the signal values ​​returned from the biochip 7 are all signal values ​​of the focal plane, that is, the biochip 7 is always in the focal plane of the objective lens 32, so that real-time autofocus can be achieved while scanning and imaging, thereby improving the speed of scanning imaging and the imaging quality of the scanning imaging system.

[0127] Optionally, camera module 36 includes an imaging camera, which is a line scan camera. As shown in Figure 11, monochrome camera module 361 includes a monochrome imaging camera 3613, and color camera module 362 includes a color imaging camera 3623. Both monochrome imaging camera 3613 and color imaging camera 3623 can be line scan cameras. Compared to area scan cameras, line scan cameras offer advantages such as higher sensitivity, higher responsiveness, and a wider dynamic range. They can effectively increase scanning and imaging speeds, significantly reducing scanning time when imaging large-scale biochips.

[0128] As shown in Figures 1, 2 and 4, the two optical machine support frames 12 are arranged opposite to each other along the second direction x, and the side of the optical machine support frame 12 close to the optical machine module 3 includes a right-angled corner 121 extending along the third direction y and a raised portion 122 adjacent to the right-angled corner 121. An optical machine slide rail 14 extending along the third direction y is provided on the right-angled corner 121. The optical machine slide rail 14 includes a track 143 and at least two sliders 141. A support block 142 is installed on each slider 141. The support block 142 is close to the side of the optical machine module 3 and the raised portion 122 is close to the optical machine module 3. The optical-mechanical module 3 includes an optical-mechanical base plate 31. The area where the optical-mechanical base plate 31 overlaps with the optical-mechanical support frame 12 is provided with at least two groups of first bolt mounting holes 310 and a plurality of fixing bolt mounting holes 312. The first bolt mounting holes 310 correspond one-to-one with the support blocks 142. Each group of first bolt mounting holes 310 includes a supporting bolt mounting hole 3101 and at least two equiaxial shoulder bolt mounting holes 3102. Spring washers 313 are provided in the equiaxial shoulder bolt mounting holes 3102. The fixing bolt mounting holes 312 correspond to the protrusions 122. One group of first bolt mounting holes 310 corresponds to one support block 142.

[0129] For example, FIG16 is a schematic diagram of the planar structure of a scanning imaging system provided by an embodiment of the present application, and FIG17 is an enlarged schematic diagram of the structure of the area marked by the elliptical dotted line in FIG16 . FIG16 and FIG17 show the bolt installation state in each bolt mounting hole during the non-objective lens maintenance stage. In combination with FIG2 , FIG4 , FIG16 and FIG17 , during the non-objective lens maintenance stage, the fixing bolt can be inserted into the fixing bolt mounting hole 312 to connect with the raised portion 122, the equiaxial shoulder bolt 3112 can be inserted into the equiaxial shoulder bolt mounting hole 3102 to connect with the support block 142, and the support bolt 3111 can be inserted into the support bolt mounting hole 3101 and be in a non-tightened state, so that the equiaxial shoulder bolt 3112 and the fixing bolt can be used to fix the optical machine base plate 31 of the optical machine module 3 to the optical machine support frame 12. 17 , the support bolt 3111 being in an untightened state may mean that there is a certain gap D between the bottom of the nut of the support bolt 3111 and the support bolt mounting hole 3101 , so that the support bolt 3111 has space to continue to be tightened downward.

[0130] 16 and 17 , during the objective lens maintenance stage, that is, when the objective lens 32 needs to be repaired or replaced, the fixing bolt in the fixing bolt mounting hole 312 can be loosened so that the fixing bolt is not connected to the protrusion 122, and the equiaxial shoulder bolt 3112 is kept inserted into the equiaxial shoulder bolt mounting hole 3102 and connected to the support block 142, and the support bolt 3111 is continued to be tightened downward so that the support bolt 3111 is inserted into the support bolt mounting hole 3101 and is in a tightened state. In this way, the support bolt 3111 can be used to support the optical machine module 3, so that the lower surface of the optical machine base plate 31 is separated from the upper surface of the protrusion 122 of the optical machine support frame 12, and the optical machine module 3 is slid along the optical machine slide rail 14, so as to facilitate the maintenance or replacement of the objective lens 32. Since the shock-absorbing module 1 provides soft support for the optical-mechanical module 3 to achieve a shock-absorbing effect, and the optical-mechanical module 3 has many devices and is heavy, if the optical-mechanical module 3 maintains contact with the optical-mechanical support frame 12 during the sliding process, the shock-absorbing module 1 may be deformed, affecting the supporting force and the reinstallation after the objective lens is repaired. The technical solution of this embodiment supports the optical-mechanical module 3 through supporting bolts, so that the optical-mechanical base plate 31 is separated from the protrusion 122, thereby avoiding contact friction between the optical-mechanical module 3 and the optical-mechanical support frame 12 during the sliding process, thereby avoiding deformation of the shock-absorbing module 1 and ensuring the structural stability of the scanning imaging system.

[0131] Since the supporting bolts support the optical machine module 3 and the optical machine base plate 31 moves upward, the spring gasket 313 in the equiaxial shoulder bolt mounting hole 3102 is compressed, so that the compression degree of the spring gasket 313 in the objective lens maintenance stage is greater than the compression degree of the spring gasket 313 in the non-objective lens maintenance stage; when the objective lens 32 is repaired, the supporting bolts 3111 can be loosened. At this time, the spring gasket 313 can be restored to its original state, and the optical machine base plate 31 contacts the raised portion 122 of the optical machine support frame 12. Then, the fixing bolts in the fixing bolt mounting holes 312 can be tightened to re-fix the optical machine module 3 on the optical machine support frame 12.

[0132] For example, Figure 18 is a schematic diagram of the state of the scanning imaging system provided by an embodiment of the present application during the objective lens maintenance stage. As shown in Figure 18, the embodiment of the present application arranges an optical machine slide rail 14 on the optical machine support frame 12 and cleverly arranges a bolt connection method between the optical machine base plate 31 and the optical machine support frame 12. When the objective lens 32 needs to be replaced or repaired, the optical machine module 3 can be slid out half of the machine position to facilitate the replacement or repair of the objective lens. Moreover, during the sliding process, there is no friction between the optical machine base plate 31 of the optical machine module 3 and the raised portion 122 of the optical machine support frame 12, thereby ensuring the structural stability of the scanning imaging system.

[0133] As described above, the scanning imaging system further includes a rack module 4, to which the shock absorbing module 1 is fixed. For example, FIG19 is a schematic structural diagram of a rack module in one scanning imaging system shown in FIG1 , and FIG20 is a schematic structural diagram of a rack module in another scanning imaging system shown in FIG1 . FIG19 and FIG20 respectively illustrate the structure of the rack module 4 from different perspectives. As shown in FIG19 and FIG20 , the rack module 4 includes a housing 41, in which an electrical control device 42, a reagent storage device 43, and a waste liquid recovery device 44 of the scanning imaging system are integrated; a communication interface 45 and a power interface 46 are provided on the side walls of the housing 41; and a plurality of universal wheels 47 and a plurality of support and leveling foot cups 48 are installed at the bottom of the housing 41.

[0134] As shown in Figures 19 and 20, the electrical control device 42 includes a linear motion component controller 421 and a displacement controller 422, wherein the linear motion component controller 421 is configured to control the movement of the first linear motion component 372, the second linear motion component 332, the third linear motion component 382 and the fourth linear motion component 392; the displacement controller 422 is configured to control the movement of the stage 2 on the first plane (xy plane) and the movement of the fifth linear motion component 320 in the first direction z. Among them, the reagent storage device 43 can be a refrigerator. The waste liquid recovery device 44 is configured to store recovered waste liquid. For example, waste liquid recovery can be performed by a waste liquid pump 411. A pure water bucket 412 can be provided next to the waste liquid recovery device 44 in the box body 41, which is configured to store pure water. The power interface 46 on the side wall of the box body 41 is configured to connect to a power source, and the communication interface 45 is configured to communicate with other devices (such as a computer) for signal transmission. Universal wheels 47 are provided at the bottom of the box 41 to facilitate the movement of the scanning imaging system, and support and leveling feet 48 at the bottom of the box 41 are provided to support and level the scanning imaging system.

[0135] As shown in conjunction with Figures 2 and 20 , a vacuum adsorption platform 5 is provided on the stage 2. A negative pressure pump 410 is also integrated within the housing 41. The negative pressure pump 410 is connected to the vacuum adsorption platform 5 to adsorb the biochip 7. For example, the vacuum adsorption platform 5 may be provided with a plurality of through holes. By connecting the negative pressure pump 410 to the vacuum adsorption platform 5, the negative pressure pump 410 can be used to draw air, thereby reducing the pressure below the vacuum adsorption platform 5 to a lower level than the pressure above the vacuum adsorption platform 5, thereby adsorbing the biochip 7. As shown in Figure 20 , the negative pressure pump 410 and the waste liquid pump 411 may be integrated.

[0136] In addition, as shown in FIG. 20 , the box body 41 further includes a negative pressure monitoring module 49 , which is configured to monitor the magnitude of the negative pressure to ensure the adsorption force on the biochip 7 .

[0137] Referring to Figure 18, optionally, a plurality of protective structures 6 are further provided on the box body 41; the protective structure 6 includes a first protective section 61 and a second protective section 62, which are integrally formed and orthogonal to each other; wherein the first protective section 61 is perpendicular to the plane where the shock-absorbing base plate 11 is located, and is located on the same side of the shock-absorbing base plate 11 and the optical machine support frame 12; the second protective section 62 is located on the side of the first protective section 61 away from the shock-absorbing module 1, and is connected to the box body 41; during the imaging process, the first protective section 61 does not contact the shock-absorbing module 1; during transportation, the first protective section 61 rests on the shock-absorbing module 1 and contacts at least one of the shock-absorbing base plate 11 and the optical machine support frame 12. With such a configuration, the protective structure 6 can be used to prevent the optical machine module 3 from being detached due to the possible rollover of the shock-absorbing module 1 during transportation, and the shock-absorbing module 1 and the optical machine module 3 are protected by the protective structure 6 to prevent damage to the equipment.

[0138] As shown in Figure 18, the protective structure 6 is L-shaped. During the transportation of the scanning imaging system, the first protective section 61 of the protective structure 6 is placed against the shock-absorbing module 1, so that the first protective section 61 contacts the shock-absorbing base plate 11 and the optical machine support frame 12. This provides a certain degree of support for the shock-absorbing module 1, preventing the shock-absorbing module 1 from tipping over during transportation and effectively protecting the equipment. Furthermore, during the imaging process, the protective structure 6 can be removed so that the first protective section 61 does not contact the shock-absorbing module 1, thereby reducing the impact on the shock absorption effect.

[0139] In summary, the scanning imaging system provided in the embodiment of the present application can realize panoramic scanning imaging of large-sized biochips, and the maximum scanning stroke can reach 20cm*20cm. It can solve the problem that the scanning imaging system has a small imaging area and can only perform panoramic scanning imaging on small-sized biochips, and the scanning imaging speed is fast and the imaging quality is high. In addition, except for the laser and computer, all components of the scanning imaging system can be integrated into the whole machine. The structure of the scanning imaging system is more compact, the layout is reasonable and simple, and it is convenient to install and debug. The maintenance and replacement of internal instruments (such as objective lenses) are also more convenient.

[0140] The above embodiments do not limit the scope of protection of this application. Various modifications, combinations, sub-combinations and substitutions can be made according to design requirements and other factors.

Claims

1. A biochip scanning imaging system, comprising: A shock absorbing module, the shock absorbing module comprising a shock absorbing base plate and an optical machine support frame located on two opposite sides of the shock absorbing base plate, wherein along a first direction, the height of the optical machine support frame is greater than the thickness of the shock absorbing base plate, wherein the first direction is perpendicular to the plane where the shock absorbing base plate is located; a stage, located on the shock-absorbing base plate, configured to carry the biochip; the stage can move along a second direction and a third direction, the maximum moving distance of the stage along the second direction is at least 20 cm, and the maximum moving distance of the stage along the third direction is at least 20 cm; the second direction and the third direction are orthogonal and parallel to the plane where the shock-absorbing base plate is located; An optomechanical module is supported by two optomechanical support frames; the optomechanical module covers the area where the shock-absorbing base plate is located and has no contact with the objective stage; the optomechanical module includes an objective lens and an optical imaging unit, and the optical axis of the objective lens is parallel to the first direction; the optomechanical module is configured to scan and image the biochip through the optical imaging unit and the objective lens.

2. The scanning imaging system according to claim 1, wherein: The optical imaging unit includes a first light path guiding module, a second light path guiding module, a light source module and a camera module; The first light path guiding module comprises at least one first optical lens; each first optical lens comprises at least one of a first dichroic mirror and a semi-transparent and semi-reflective mirror; the second light path guiding module comprises a second dichroic mirror; the second dichroic mirror, the at least one first optical lens and the objective lens are sequentially arranged with a common optical axis along the first direction, the at least one first optical lens and the second dichroic mirror are both arranged at 45° relative to the first plane, and the mirror surface of the at least one first optical lens and the mirror surface of the second dichroic mirror are perpendicular to each other; the first plane is the intersection plane of the second direction and the third direction; The illumination light emitted by the light source module is reflected by the at least one first optical lens and then incident on the biochip through the objective lens; the return light of the biochip is emitted toward the at least one first optical lens through the objective lens, is transmitted through the at least one first optical lens and then incident on the second dichroic mirror, and then reflected by the second dichroic mirror and then incident on the camera module.

3. The scanning imaging system according to claim 2, wherein: The light source module includes a laser light source module, and the camera module includes a black and white camera module; The first optical lens includes the first dichroic mirror; the laser emitted by the laser light source module is reflected by the first dichroic mirror and then incident on the biochip through the objective lens; the fluorescence excited on the biochip is emitted toward the first dichroic mirror through the objective lens, is transmitted through the first dichroic mirror and then incident on the second dichroic mirror, and then is reflected by the second dichroic mirror and then incident on the black and white camera module.

4. The scanning imaging system according to claim 2, wherein: The light source module includes a white light source module, and the camera module includes a color camera module; The first optical lens includes the semi-transparent and semi-reflective mirror; the white light emitted by the white light source module is reflected by the semi-transparent and semi-reflective mirror and then incident on the biochip through the objective lens; the reflected light of the biochip is emitted toward the semi-transparent and semi-reflective mirror through the objective lens, is transmitted through the semi-transparent and semi-reflective mirror, and then is incident on the second dichroic mirror, and then reflected by the second dichroic mirror and incident on the color camera module.

5. The scanning imaging system according to claim 2, wherein: The light source module includes a laser light source module and a white light source module; the camera module includes a black and white camera module and a color camera module; the optical imaging unit also includes a light source switching module and a camera switching module; The light emitting direction of the laser light source module is parallel to the first direction, the light emitting direction of the white light source module is parallel to the second direction, the light source switching module includes a first linear motion component and a first reflector, and the first reflector is arranged at 45° relative to the first plane; the first optical lens includes at least one first dichroic mirror and a semi-transparent semi-reflective mirror arranged side by side, and the first light path guiding module also includes a second linear motion component; The first linear motion component is configured to drive the first reflector to move along the third direction, and the second linear motion component is configured to drive the first optical lens to move along the third direction, so that the first reflector and one of the first dichroic mirrors share an optical axis along the second direction, and the laser beam emitted by the laser light source module is incident on the first dichroic mirror after being reflected by the first reflector; or, the first linear motion component is configured to drive the first reflector to move along the third direction, and the second linear motion component is configured to drive the first optical lens to move along the third direction, so that the white light source module and the semi-transparent and semi-reflective mirror share an optical axis along the second direction, and the first reflector is not in the optical path of the white light source module and the semi-transparent and semi-reflective mirror; The black-and-white camera module includes a first tube lens, and the color camera module includes a second tube lens, the optical axis direction of the first tube lens is parallel to the second direction, and the optical axis direction of the second tube lens is parallel to the third direction; the camera switching module includes a third linear motion component and a second reflector, the second reflector is arranged at 45 degrees relative to a second plane, and the second plane is the intersection plane of the first direction and the second direction; The third linear motion assembly is configured to drive the second reflector to move along the first direction, so that when the white light source module is working, the second reflector and the second dichroic mirror share a common optical axis along the second direction, and the reflected light of the second dichroic mirror is incident on the second tube mirror after being reflected by the second reflector; or, the third linear motion assembly is configured to drive the second reflector to move along the first direction, so that when the laser light source module is working, the first tube mirror and the second dichroic mirror share a common optical axis along the second direction, and the second reflector is not in the optical path of the first tube mirror and the second dichroic mirror, and the reflected light of the second dichroic mirror is incident on the second tube mirror. To the first tube mirror.

6. The scanning imaging system according to claim 3 or 5, wherein: The optical imaging unit also includes a filter module; The filter module includes at least one filter, and the at least one filter is located in the light path between the second dichroic mirror and the black and white camera module. When the laser light source module is working, the reflected light of the second dichroic mirror is filtered by the at least one filter and then incident on the black and white camera module.

7. The scanning imaging system according to claim 6, wherein: The filter module includes at least two filters and a fourth linear motion component; The fourth linear motion component is configured to drive the at least two filters to move along the third direction, so that when the laser light source module is working, the black and white camera module, one of the filters and the second dichroic mirror are sequentially coaxial along the second direction.

8. The scanning imaging system according to claim 5, wherein: The at least one first optical lens includes two first dichroic mirrors, wherein the wavelength range of the transmitted light of one of the first dichroic mirrors includes 508nm-548nm and 660nm-950nm, and the wavelength range of the transmitted light of the other first dichroic mirror is 558nm-600nm; The wavelength range of the reflected light of the second dichroic mirror is 400nm to 750nm.

9. The scanning imaging system according to claim 2, wherein: The optical-mechanical module further comprises an auto-focusing unit; the auto-focusing unit is configured to adjust the position of the objective lens in the first direction so that the biochip is always in the focal plane of the objective lens.

10. The scanning imaging system according to claim 9, wherein: The autofocus unit includes an optical detection module and a fifth linear motion component; The optical detection module is configured to detect whether the biochip is located in the focal plane of the objective lens; The fifth linear motion component is configured to drive the objective lens to move a target distance along the first direction according to the detection result.

11. The scanning imaging system according to claim 10, wherein: The optical detection module includes a detection component and a third reflector connected to form an optical path along the third direction; the third reflector and the second dichroic mirror are arranged along the first direction with a common optical axis and are arranged at 45° relative to the first plane; the detection light emitted by the detection component is reflected by the third reflector, and then transmitted to the biochip through the second dichroic mirror, the first optical lens and the objective lens in sequence, and then reflected by the biochip, it passes through the objective lens, the first optical lens and the second dichroic mirror in sequence to enter the third reflector, and then reflected by the third reflector and enters the detection component.

12. The scanning imaging system according to claim 11, wherein: The detection light is near infrared light.

13. The scanning imaging system according to claim 10, wherein: The fifth linear motion component includes an objective lens holder, and the objective lens is fixed on the objective lens holder; the objective lens holder includes a first holder section and a second holder section that are integrally formed and orthogonal to each other; wherein the first holder section is parallel to the first plane and includes a first opening that passes through the first holder section along the first direction; the objective lens is inserted into the first opening and fixed on the first holder section.

14. The scanning imaging system according to claim 2, wherein: The camera module includes an imaging camera, and the imaging camera is a line array camera.

15. The scanning imaging system according to claim 1, wherein: Two optical machine support frames are arranged opposite to each other along the second direction, and a side of the optical machine support frame close to the optical machine module includes a right angle cutout extending along the third direction and a raised portion adjacent to the right angle cutout, and an optical machine slide rail extending along the third direction is arranged on the right angle cutout, and the optical machine slide rail includes at least two sliders, each slider is equipped with a support block, and a side of the support block close to the optical machine module is flush with a side of the raised portion close to the optical machine module; The optical machine module comprises an optical machine base plate, wherein at least two groups of first bolt mounting holes and a plurality of fixing bolt mounting holes are arranged in the area where the optical machine base plate overlaps with the optical machine support frame; the first bolt mounting holes are arranged in a one-to-one correspondence with the support blocks, each group of first bolt mounting holes comprises a supporting bolt mounting hole and at least two equiaxial shoulder bolt mounting holes, and a spring gasket is arranged in each equiaxial shoulder bolt mounting hole; the plurality of fixing bolt mounting holes are arranged in correspondence with the protrusions; In the non-objective lens maintenance stage, the fixing bolt is inserted into the fixing bolt mounting hole and connected to the protrusion, the equiaxial shoulder bolt is inserted into the equiaxial shoulder bolt mounting hole and connected to the support block, and the supporting bolt is inserted into the supporting bolt mounting hole and is in a non-tightened state; During the objective lens maintenance stage, the fixing bolt is not connected to the raised portion, the equiaxial shoulder bolt is inserted into the equiaxial shoulder bolt mounting hole and connected to the support block, and the supporting bolt is inserted into the supporting bolt mounting hole and is in a tightened state, so that the optical machine module slides along the optical machine slide rail and the optical machine base plate is separated from the raised portion; the degree of compression of the spring gasket during the objective lens maintenance stage is greater than the degree of compression of the spring gasket during the non-objective lens maintenance stage.

16. The scanning imaging system according to claim 1, wherein: The scanning imaging system further comprises a frame module, and the shock absorbing module is fixed on the frame module; The rack module includes a box body; the electrical control device, reagent storage device and waste liquid recovery device of the scanning imaging system are integrated in the box body; the side wall of the box body is provided with a communication interface and a power supply interface; the bottom of the box body is installed with multiple universal wheels and multiple support and leveling foot cups.

17. The scanning imaging system according to claim 16, wherein: The shock absorbing module further comprises a plurality of shock absorber modules, wherein the shock absorber modules comprise shock absorbers, shock absorber support frames and shock absorber mounting frames; The shock absorber support frame is located on a side of the optical machine support frame away from the shock absorbing base plate, and is fixed on the box body; the shock absorber mounting frame is fixed on a side wall of the optical machine support frame away from the shock absorbing base plate; the shock absorber is located between the shock absorber support frame and the shock absorber mounting frame, and is respectively connected to the shock absorber support frame and the shock absorber mounting frame.

18. The scanning imaging system according to claim 17, wherein: The two optical machine support frames are arranged opposite to each other along the second direction; each optical machine support frame includes at least one second opening penetrating the optical machine support frame along the second direction, and the second opening does not overlap with the position of the shock absorber mounting frame.

19. The scanning imaging system according to claim 16, wherein: A vacuum adsorption platform is arranged on the stage, and a negative pressure pump is integrated in the box. The negative pressure pump is connected to the vacuum adsorption platform to adsorb the biochip.

20. The scanning imaging system according to claim 16, wherein: The box body is also provided with a plurality of protective structures; Each protection structure includes a first protection sub-section and a second protection sub-section which are integrally formed and orthogonal to each other; wherein the first protection sub-section is perpendicular to the plane where the shock-absorbing base plate is located, and is located on the same side of the shock-absorbing base plate and the optical machine support frame; the second protection sub-section is located on a side of the first protection sub-section away from the shock-absorbing module, and is connected to the box body; During the imaging process, the first protection section does not contact the shock absorbing module; during the transportation process, the first protection section abuts against the shock absorbing module and contacts at least one of the shock absorbing base plate and the optical machine support frame.

Images