A high-throughput automatic focusing analysis device, system and method

Abstract

The present invention relates to the field of microscopic analysis devices, and discloses a high-throughput autofocus analysis device, system and method. A loading mechanism is used to load a sample carrier, and at least two loading positions for loading samples are provided on the sample carrier. The loading mechanism drives the sample carrier to translate in at least one direction, so that the loading positions on the sample carrier are located at observation positions in sequence; a microscopic imaging mechanism sequentially obtains microscopic images of samples in the loading positions located at the observation positions; an autofocus mechanism is drivingly connected to the microscopic imaging mechanism to adjust the object distance C between the objective lens of the microscopic imaging mechanism and the sample at the observation position based on a triangular laser ranging method before obtaining the microscopic imaging, so that the image is clear; a light source mechanism provides a light source to the sample at the observation position. The high-throughput autofocus analysis device of the present invention can realize autofocus based on a triangular laser ranging method, and provides a light source for the sample at the observation position through a light source mechanism, so as to keep the image clear at all times, and is easy to operate and has high work efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of microscopic analysis devices, and in particular to a high-throughput automatic focusing analysis device, system and method. Background Art

[0002] Fluorescence microscopic analysis devices are widely used in the field of biological cell analysis. Existing fluorescence microscopic analysis devices are constantly developing in the direction of intelligence, automation, integration and efficiency.

[0003] The basic principle of the fluorescence microscopy analysis device is: the light of various spectral lines emitted by the fluorescent light source; after passing through the excitation filter, only a certain wavelength of ultraviolet light is allowed to pass; after passing through the reflector, the sample is excited to produce fluorescence. Usually, the wavelength of the fluorescence generated by the excitation is much larger than the wavelength of the light that excites the sample, and it is visible light. The fluorescence generated in this way and a part of the target fluorescence excitation light that passes through the sample are imaged by the objective lens, and the human eye or camera can observe the fluorescence image with the eyepiece. However, there are still many problems with the current fluorescence microscopy analysis device, which are mainly reflected in: 1. The staff needs to focus manually; 2. The staff needs to manually adjust the fluorescent light source, and then obtain the target fluorescence excitation light of a specific wavelength to excite the sample to be tested to emit light; 3. When observing and analyzing multiple samples to be tested, the staff needs to manually replace the samples to be tested and place them in the observation position; 4. Each observation of a sample requires the staff to manually complete the focus again; 5. When the samples are very different, the staff needs to readjust the magnification, refocus, and readjust the fluorescent light source. The operation is very complicated, and each step requires the staff to repeat the operation. Therefore, the work efficiency is low, the flexibility of use is poor, the automation level is low, and the operation is time-consuming and laborious.

[0004] Therefore, there is an urgent need to provide a high-throughput automatic focusing analysis device, system and method, which can achieve efficient automatic focusing and have the advantages of high automation level, simple and convenient operation and high work efficiency. The method based on the device can achieve efficient automatic focusing microscopic analysis. Summary of the invention

[0005] An object of the present invention is to provide a high-throughput autofocus analysis device, which can achieve efficient autofocus and has the advantages of high automation level, simple and convenient operation and high work efficiency.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] A high-throughput automatic focusing analysis device, comprising:

[0008] A loading mechanism, used for loading a sample carrier, the sample carrier is provided with at least two loading positions, the loading positions are used for loading samples, and the loading mechanism is also used for driving the sample carrier to translate along at least one direction, so that the loading positions on the sample carrier are located at observation positions in sequence;

[0009] A microscopic imaging mechanism, configured to sequentially obtain microscopic images of the samples in the carrying positions located at the observation positions;

[0010] An autofocus mechanism is drivingly connected to the microscopic imaging mechanism, and the autofocus mechanism is configured to adjust the object distance C between the objective lens of the microscopic imaging mechanism and the sample at the observation position based on a triangular laser ranging method before acquiring the microscopic imaging, so as to make the object image clear;

[0011] The light source mechanism is configured to provide light source to the sample at the observation position.

[0012] Optionally, the autofocus mechanism includes:

[0013] A laser reflecting mirror, which is fixed between the objective lens and the sample at the observation position;

[0014] A triangulated laser rangefinder, configured to emit an incident light α with an incident angle of δ to a reflective surface of the laser reflector, wherein the incident light α is reflected to generate a first reflected light β, wherein the first reflected light β is irradiated on the surface of the sample to generate a return light γ, wherein the return light γ is reflected by the reflective surface to generate a second reflected light θ, and further configured to receive the second reflected light θ, generate a laser image, and calculate a measured distance A based on the laser image according to geometric trigonometric theorems;

[0015] A focus shift assembly, wherein the objective lens is arranged at an output end of the focus shift assembly, and the focus shift assembly is configured to adjust the object distance C so that the object distance C is equal to the target object distance C0;

[0016] Among them, the height of the base of the triangle formed by the line L connecting the emission point of the incident light ray α and the receiving point of the second reflected light ray θ as the base and the intersection angle of the extended lines of the incident light ray α and the second reflected light ray θ as the vertex is equal to the measurement distance A.

[0017] Optionally, the focus shift component is also configured to adjust the object distance C of the sample on the reference bearing position to the object distance C0, and then adjust the object distance C of the samples on the remaining bearing positions to the target object distance C0 based on the measurement distance A corresponding to the reference bearing position and the measurement distances A corresponding to the remaining bearing positions.

[0018] Optionally, the laser reflection mirror is a semi-transparent and semi-reflective mirror, and the first reflected light β and the returning light γ are coaxial with the axis of the objective lens relative to the normal of the sample.

[0019] Optionally, the light source mechanism comprises:

[0020] The fluorescence component comprises a fluorescence light source and at least two filter cubes, wherein the fluorescence light source can selectively provide target fluorescence excitation light to a sample at an observation position through any of the filter cubes.

[0021] Optionally, the focus shift component is further configured to perform deviation correction on the object distance C based on the target fluorescent excitation light and / or the filter cube.

[0022] Optionally, the light source mechanism further includes:

[0023] The automatic filter switching component is drivingly connected to the at least two filter cubes, and the automatic filter switching component is configured to enable one of the at least two filter cubes to cooperate with the fluorescent light source to provide target fluorescent excitation light to the sample at the observation position.

[0024] Optionally, the automatic filtering switching component includes:

[0025] A filter carrier having at least two filter cube fixing positions disposed thereon, and each of the filter cubes is fixed one-to-one on each of the filter cube fixing positions;

[0026] A carrier displacement assembly, wherein the filter carrier is arranged at the output end of the carrier displacement assembly, and the carrier displacement assembly is configured to drive the filter carrier to move so that one of the at least two filter cubes moves to the docking position and cooperates with the fluorescent light source to provide target fluorescent excitation light to the sample at the observation position.

[0027] Optionally, the light source mechanism comprises:

[0028] A bright field light source is disposed above the object-carrying mechanism, and is configured to provide bright field light to the sample at the observation position.

[0029] Optionally, the object carrying mechanism comprises:

[0030] A sample carrier, used for carrying the sample carrier;

[0031] The translation assembly is configured to carry the sample carrier, and the translation assembly can automatically translate the sample carrier so that one of the samples on the at least two carrying positions is selectively transported to the observation position.

[0032] Optionally, the translation assembly comprises:

[0033] Frame;

[0034] A first displacement driving component is disposed on the frame;

[0035] A second displacement driving component is arranged at the output end of the first displacement driving component, and the first displacement driving component is configured to drive the second displacement driving component to move along a first direction. The sample carrier is fixed to the output end of the second displacement driving component, and the second displacement driving component is configured to drive the sample carrier to move along a second direction, and the first direction is perpendicular to the second direction.

[0036] Optionally, the number of the objective lenses is at least two, and the microscopic imaging mechanism further comprises:

[0037] An objective lens switching assembly, each objective lens is fixed to an output end of the objective lens switching assembly, and the objective lens switching assembly is configured to selectively drive one of at least two objective lenses to face the sample at the observation position.

[0038] Optionally, the microscopic imaging mechanism further comprises:

[0039] A tube lens, coaxially arranged on a side of the objective lens away from the observation position;

[0040] The camera is arranged on a side of the tube lens away from the objective lens, so as to obtain microscopic images.

[0041] Another object of the present invention is to provide an automatic focusing analysis system, which can achieve efficient automatic focusing and has the advantages of high automation level, simple and convenient operation and high work efficiency.

[0042] To achieve this object, the present invention adopts the following technical solutions:

[0043] A high-throughput auto-focus analysis system comprises the high-throughput auto-focus analysis device as described above, and also comprises a master control mechanism, wherein the master control mechanism comprises:

[0044] a storage module configured to store a microscopic analysis execution strategy for analyzing a sample;

[0045] An execution module is configured to control the translation assembly according to the microscopic analysis execution strategy so that the samples on the multiple carrying positions are sequentially transported to the observation position according to a preset order; and

[0046] Controlling the automatic filter switching assembly so that one of the at least two filter cubes cooperates with the fluorescent light source to provide target fluorescent excitation light to the sample at the observation position; and

[0047] The autofocus mechanism is controlled to adjust the object distance C to the target object distance C0, so that the microscopic imaging mechanism acquires a microscopic image.

[0048] Another object of the present invention is to provide an auto-focus analysis method, which can achieve efficient auto-focusing and high working efficiency.

[0049] To achieve this object, the present invention adopts the following technical solutions:

[0050] A high-throughput auto-focus analysis method, based on the high-throughput auto-focus analysis device as described above, comprises the following steps:

[0051] Determine the loading position to be analyzed on the loading mechanism, and transport the sample carried on the loading position to be analyzed to the observation position;

[0052] Providing light source to the sample at the observation position through the light source mechanism;

[0053] Based on the triangulated laser distance measurement, the object distance C between the objective lens and the sample at the observation position is adjusted to make the image clear;

[0054] A microscopic image of the sample at the observation position is captured by a microscopic imaging mechanism.

[0055] Optionally, when adjusting the object distance C between the objective lens and the sample at the observation position based on the triangular laser ranging method, the triangular laser rangefinder emits an incident light ray α to the laser reflector, and the incident light ray α is reflected by the laser reflector and irradiates the sample at the observation position, and the measured distance A is obtained.

[0056] Optionally, the light source provided by the light source mechanism is a fluorescent light source, and providing the light source to the sample at the observation position through the light source mechanism includes the following steps:

[0057] A filter cube is determined from at least two filter cubes, and the fluorescent light source is filtered by the filter cube to provide target fluorescent excitation light to the sample at the observation position.

[0058] Optionally, the object distance C is corrected for deviation according to the filter cube and / or the target fluorescent excitation light.

[0059] Beneficial effects of the present invention:

[0060] Compared with the existing microscopic analysis device, the loading mechanism of the high-throughput automatic focusing analysis device of the present invention enables the loading position on the sample carrier to be located at the observation position in sequence, and the automatic focusing mechanism is drivingly connected to the microscopic imaging mechanism. The automatic focusing mechanism can detect and adjust the object distance between the objective lens of the microscopic imaging mechanism and the sample at the observation position based on the triangulated laser ranging method to ensure a clear image, and it can provide a light source for the sample at the observation position through the light source mechanism to assist in the analysis of at least two samples. The advantage is that it can realize automatic focusing analysis, keep the image clear at all times, and has the advantages of convenient operation and high work efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 It is a structural stereoscopic schematic diagram of a high-throughput autofocus analysis device provided by the present invention;

[0062] Figure 2 It is one of the side schematic diagrams of the high-throughput autofocus analysis device provided by the present invention;

[0063] Figure 3 This is the second side view schematic diagram of the high-throughput autofocus analysis device provided by the present invention;

[0064] Figure 4 It is a schematic diagram of the automatic focusing mechanism of the high-throughput automatic focusing analysis device provided by the present invention when measuring the distance of a sample;

[0065] Figure 5 This is one of the schematic diagrams of the triangulated laser ranging of the autofocus mechanism provided by the present invention;

[0066] Figure 6 This is the second schematic diagram of the triangulated laser ranging of the autofocus mechanism provided by the present invention;

[0067] Figure 7 It is a schematic diagram of the circuit relationship between the master control mechanism and other mechanisms provided by the present invention;

[0068] Figure 8 It is a schematic diagram of the relationship between the object distance when the high-throughput automatic focusing analysis device provided by the present invention irradiates the surface of the object to be measured through the transparent slide;

[0069] Fig. 9 It is a schematic diagram of the relationship between the object distance when the high-throughput autofocus analysis device in other embodiments provided by the present invention directly irradiates the surface of the object to be measured.

[0070] In the figure:

[0071] M, first direction; N, second direction; O, normal;

[0072] 100. Sample carrier;

[0073] 1. Carrying mechanism; 11. Sample stage; 12. Translation assembly; 121. Frame; 1211. Top plate; 122. First displacement driving component; 123. Second displacement driving component; 124. Middle bearing plate; 125. Bright field light source carrier plate;

[0074] 2. Microscopic imaging mechanism; 21. Objective lens; 22. Objective lens switching assembly; 23. Tube lens; 24. Camera;

[0075] 3. Autofocus mechanism; 31. Laser reflector; 32. Triangulation laser rangefinder; 321. Laser emitting component; 322. Laser receiving component; 3221. Laser imaging surface; 3222. Receiving lens; 33. Focus displacement component;

[0076] 4. Fluorescent assembly; 41. Fluorescent light source; 42. Filter cube;

[0077] 5. Automatic filter switching assembly; 51. Filter carrier; 52. Carrier displacement assembly;

[0078] 6. Bright field light source;

[0079] 7. General control mechanism; 71. Storage module; 72. Execution module. DETAILED DESCRIPTION

[0080] In order to make the technical problem solved by the present invention, the technical solution adopted and the technical effect achieved more clearly, the technical solution of the present invention is further explained below with reference to the accompanying drawings and through specific implementation methods.

[0081] In the description of the present invention, unless otherwise clearly specified and limited, the terms "connected", "connected", and "fixed" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0082] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0083] In the description of this embodiment, the terms "upper", "lower", "left", "right" and other directions or positional relationships are based on the directions or positional relationships shown in the drawings, and are only for the convenience of description and simplification of operation, rather than indicating or implying that the device or element referred to must have a specific direction, be constructed and operate in a specific direction, and therefore cannot be understood as limiting the present invention. In addition, the terms "first" and "second" are only used to distinguish in the description and have no special meaning.

[0084] like Figure 1-4As shown, this embodiment provides a high-throughput autofocus analysis device, and also proposes an autofocus analysis system including the high-throughput autofocus analysis device and an autofocus analysis method based on the high-throughput autofocus analysis device, which has the advantages of high automation level, high flexibility, simple and convenient operation and high work efficiency, and can achieve efficient autofocus. In the figure, M represents the first direction and N represents the second direction.

[0085] like Figure 1-4 As shown, the high-throughput autofocus analysis device includes a loading mechanism 1, a microscopic imaging mechanism 2, an autofocus mechanism 3 and a light source mechanism. The loading mechanism 1 is used to carry a sample carrier 100, and at least two loading positions are provided on the sample carrier 100, and the loading positions are used to carry samples (not shown in the figure); specifically, the loading positions can be positioning and accommodating grooves (not shown in the figure) for positioning and placing samples (not shown in the figure), and the sample carrier 100 can be kept horizontally fixed in the loading mechanism 1. The loading mechanism 1 is also used to drive the sample carrier 100 to translate in at least one direction, so that the loading positions on the sample carrier 100 are located at the observation positions in sequence. The microscopic imaging mechanism 2 is configured to sequentially obtain microscopic images of the sample in the carrying position at the observation position; the autofocus mechanism 3 is connected to the microscopic imaging mechanism 2 by driving, and the autofocus mechanism 3 is configured to adjust the object distance C between the objective lens 21 of the microscopic imaging mechanism 2 and the sample at the observation position based on the triangular laser ranging method before obtaining the above-mentioned microscopic imaging, and adjust the object distance C to make the object image clear; the light source mechanism is configured to provide a light source to the sample at the observation position. Specifically, the light source mechanism includes a fluorescent component 4 and an automatic filter switching component 5, the fluorescent component 4 includes a fluorescent light source 41 and at least two filter cubes 42, and the fluorescent light source 41 can selectively provide target fluorescent excitation light to the sample at the observation position through any filter cube 42 to make the sample at the observation position fluorescent; the automatic filter switching component 5 is connected to the at least two filter cubes 42 by driving, and the automatic filter switching component 5 is configured so that one of the at least two filter cubes 42 cooperates with the fluorescent light source 41 to provide target fluorescent excitation light to the sample at the observation position.

[0086] Compared with the existing microscopic analysis device, the autofocus mechanism 3 of the high-throughput autofocus analysis device of this embodiment is connected to the microscopic imaging mechanism 2 by driving, and the autofocus mechanism 3 can adjust the object distance C between the objective lens 21 of the microscopic imaging mechanism 2 and the sample at the observation position based on the triangular laser ranging method, so as to make the image clear, with high detection accuracy and short time consumption; and it can provide a light source for the sample at the observation position through the light source mechanism to assist in sample analysis; specifically, the automatic filter switching component 5 is connected to at least two filter cubes 42 by driving, and the automatic filter switching component 5 can make at least one of the two filter cubes 42 cooperate with the fluorescent light source 41 of the fluorescent component 4 to provide the target fluorescent excitation light to the sample at the observation position, thereby stimulating the fluorescence of the sample with fluorescent substances, and flexible fluorescence microscopic analysis can be performed. It has the advantages of being able to realize automatic focus analysis, keep the image clear at all times, and has the advantages of convenient operation and high work efficiency, and can realize the automation of filter switching, and can automatically adjust the filter cube 42 according to the sample requirements to provide the required target fluorescent excitation light, with high flexibility and convenient operation.

[0087] Since a large number of samples need to be analyzed in actual analysis, in order to further improve work efficiency and enhance the level of automation. Figure 1-3 As shown, in this embodiment, the loading mechanism 1 includes a sample carrier 11 and a translation assembly 12. The sample carrier 11 is used to carry a sample carrier plate 100, and a plurality of carrying positions are provided on the sample carrier plate 100, so that a plurality of samples can be placed on the sample carrier 11; the translation assembly 12 is configured to carry the sample carrier 11, and the translation assembly 12 can automatically translate the sample carrier 11, so that a plurality of samples can be selectively transported to an observation position, and then the plurality of samples can be automatically transported to the observation position respectively through the translation assembly 12, so as to assist in completing the microscopic analysis of the plurality of samples, without manual adjustment, and greatly improving the work efficiency.

[0088] Specifically, if Figure 1-4As shown, in this embodiment, the translation assembly 12 includes a frame 121, a first displacement driving component 122 and a second displacement driving component 123. The first displacement driving component 122 is arranged on the frame 121; the second displacement driving component 123 is arranged at the output end of the first displacement driving component 122, the first displacement driving component 122 is configured to drive the second displacement driving component 123 to move horizontally along a first direction, the sample carrier 11 is fixed to the output end of the second displacement driving component 123, the second displacement driving component 123 is configured to drive the sample carrier 11 to move horizontally along a second direction, the first direction is perpendicular to the second direction, M in the figure represents the first direction, and N represents the second direction. More specifically, in this embodiment, the frame 121 includes a top plate 1211 and pillars (not shown in the figure) fixed to both sides of the top plate 1211. The middle part of the top plate 1211 is hollowed out to avoid affecting the microscopic analysis; the first displacement driving component 122 includes a ball screw nut transmission mechanism (not shown in the figure) and a first horizontal bottom plate (not shown in the figure). The first horizontal bottom plate is connected to the top plate 1211 through a slide rail slider guide assembly (not shown in the figure) and is arranged on the top plate 1211. The first horizontal bottom plate can slide back and forth along a first direction. The ball screw nut transmission mechanism is arranged on the top plate 1211 and is drivingly connected to the first horizontal bottom plate to drive the first horizontal bottom plate to slide back and forth along the first direction; similarly, the second displacement driving component 123 includes a second horizontal bottom plate (not shown in the figure) and also has a set of corresponding ball screw nut transmission mechanisms. The second horizontal bottom plate is arranged on the first horizontal bottom plate through another set of slide rail slider guide assemblies. The corresponding ball screw nut transmission mechanism is used to drive the second horizontal bottom plate to slide back and forth along the second direction. The ball screw nut transmission mechanism has high working accuracy and can achieve precise control of displacement, thereby ensuring that the sample can be accurately docked at the observation position. It should be noted that the displacement strokes of the second displacement driving component 123 and the first displacement driving component 122 are respectively detected by existing grating rulers, thereby achieving accurate detection and control of the displacement.

[0089] Furthermore, if Figure 1-3 As shown, in order to realize the automatic switching of the filter cube 42, specifically, the filter automatic switching component 5 includes a filter carrier 51 and a carrier displacement component 52. At least two filter cube fixing positions are set on the filter carrier 51, and each filter cube 42 is fixed to each filter cube fixing position one by one; the filter carrier 51 is set at the output end of the carrier displacement component 52, and the carrier displacement component 52 is configured to drive the filter carrier 51 to move, so that at least one of the two filter cubes 42 moves to the docking position, and cooperates with the fluorescent light source 41 to provide the target fluorescent excitation light to the sample at the observation position. Specifically, as Figure 1-3As shown, a middle bearing plate 124 is fixedly arranged in the middle part between the two pillars of the frame 121, a bearing plate displacement assembly 52 is fixed on the middle bearing plate 124, and the filter bearing plate 51 is connected to the middle bearing plate 124 through a slide rail slider. The bearing plate displacement assembly 52 includes a bearing plate displacement servo motor (not shown in the figure), and the output end of the bearing plate displacement servo motor is transmission-connected with the filter bearing plate 51, thereby driving the filter bearing plate 51 to move, thereby realizing automatic switching of the filter cube 42. More specifically, four filter cube fixing positions can be provided on the filter bearing plate 51, and a filter cube 42 is respectively arranged on each filter cube fixing position. The four filter cubes 42 can respectively provide green light, blue light, purple light and red light, thereby meeting different fluorescence usage requirements, greatly improving its versatility, and having a simple structure and low cost. It should be noted that since the structure of the filter cube 42 is a prior art, it will not be described in detail.

[0090] Furthermore, if Figure 1-3 As shown, in this embodiment, the light source mechanism includes a bright field light source 6 in addition to the fluorescent light source 41. The bright field light source 6 is disposed above the carrier mechanism 1, and is configured to provide bright field light to the sample at the observation position. In this embodiment, the microscopic imaging mechanism 2, the autofocus mechanism 3, the fluorescent component 4, and the automatic filter switching component 5 are all located below the carrier mechanism 1, and a light-transmitting observation hole is provided on the carrying position of the sample carrier 11, and the microscopic imaging mechanism 2 can microscopically observe the sample at the observation position through the light-transmitting observation hole. Specifically, as Figure 1-4 As shown, a bright field light source carrier plate 125 is suspended above the object-carrying mechanism 1, and the four corners of the bright field light source carrier plate 125 are connected to the middle carrier plate 124 through connecting columns, thereby ensuring that the bright field light source carrier plate 125 is suspended, and the bright field light source carrier plate 125 and the middle carrier plate 124 form a storage and avoidance space, and the object-carrying mechanism 1 can move freely in the storage and avoidance space to achieve sample switching. The structure of the entire high-throughput autofocus analysis device is compact and reasonably designed. In addition, it should be noted that the second horizontal bottom plate of the second displacement driving component 123 and the first horizontal bottom plate of the first displacement driving component 122 are both hollowed out, thereby ensuring that the microscopic imaging mechanism 2 can pass through the light-transmitting observation hole opened on the sample carrier 11 parked at the observation position to microscopically observe the corresponding sample.

[0091] Since fluorescence microscopy analysis requires high focusing accuracy, and in large-scale sample analysis, it is also necessary to compress the focusing time to improve work efficiency, the low-precision laser ranging method is not suitable for actual focusing work. Figure 4-6As shown, in this embodiment, the autofocus mechanism 3 adopts the triangular laser ranging principle to realize auxiliary ranging focusing, and the autofocus mechanism 3 includes a laser reflector 31, a triangular laser rangefinder 32, a focus displacement assembly 33 and a control module (not shown in the figure). The laser reflector 31 is fixedly arranged between the objective lens 21 and the sample at the observation position. Specifically, the laser reflector 31 is fixed on the lower surface of the top plate 1211 by a fixed bracket (not shown in the figure), and the triangular laser rangefinder 32 is also fixed on the lower surface of the top plate 1211. The positions of the laser reflector 31 and the triangular laser rangefinder 32 will not move. The triangular laser rangefinder 32 is configured to emit a laser to the laser reflector 31 to detect and calculate the measured distance A. Specifically, in this embodiment, the triangular laser rangefinder 32 is configured to emit an incident light α with an incident angle of δ to the reflective surface of the laser reflector 31, and the wavelength of the incident light α is 655nm. The incident light α is reflected to generate a first reflected light β, and the first reflected light β is irradiated on the surface of the sample to generate a return light γ; the return light γ is reflected by the reflective surface of the laser reflector 31 to generate a second reflected light θ. The triangular laser rangefinder 32 is also configured to receive the second reflected light θ, generate a laser image, and calculate the measured distance A based on the laser image according to the geometric trigonometric theorem, so as to obtain the first spacing C1 from the laser reflector 31 to the sample along the axial direction of the objective lens 21 according to the measured distance A and the distance conversion formula.

[0092] The height of the base of the triangle formed by the line L connecting the emission point of the incident light α and the receiving point of the second reflected light θ as the base and the intersection angle of the extended lines of the incident light α and the second reflected light θ as the vertex is equal to the measured distance A.

[0093] Specifically, if Figure 4-6 As shown, in this embodiment, the first reflected light β and the returning light γ are coaxial with the axis of the objective lens 21 relative to the normal of the sample, that is, the laser reflector 31 is located directly between the objective lens 21 and the observation position. In order to minimize the influence on the observation of the objective lens 21, the laser reflector 31 is a semi-transparent and semi-reflective mirror, and the thickness of the laser reflector 31 is 650nm. In addition, the laser reflector 31 is inclined at 45 degrees to the horizontal plane, and the incident light α is located in the horizontal plane and emits the incident light α to the laser reflector 31. The second spacing C2 between the objective lens 21 and the laser reflector 31 along its own axis is known (when the objective lens 21 is at a known position, the second spacing C2 is a known constant. In other embodiments, a position measuring device is also included for measuring the second spacing C2), and C2 is used to calculate the object distance C (the specific calculation formula and method of the object distance C will be described in detail below). On the basis of completing the measurement of the object distance C, the objective lens 21 can be driven to move. As Figure 4-6As shown, the autofocus mechanism 3 also includes a focus displacement component 33. The objective lens 21 is arranged at the output end of the focus displacement component 33, and the focus displacement component 33 is configured to adjust the object distance C between the objective lens 21 and the sample at the observation position along the axial direction, so that the object distance C is equal to the target object distance C0. The control module is electrically connected to the triangulated laser rangefinder 32 and the focus displacement component 33, and the control module is configured to be able to obtain the target object distance C0, the first spacing C1 and the second spacing C2, and calculate the object distance C between the sample and the objective lens 21 to control the movement of the focus displacement component 33 so that the object distance C is equal to the target object distance C0, thereby realizing automatic detection of the object distance C and automatic focusing. In some embodiments, for samples on different carrying positions, the above-mentioned method can be adopted to determine the object distance C between the sample and the objective lens 21 and control the movement of the focus displacement component 33 so that the object distance C is equal to the target object distance C0. In other embodiments, in order to reduce the amount of calculation, a reference carrying position can be first determined, and its corresponding measurement distance (denoted as A) can be measured to obtain its corresponding measurement distance (denoted as A). ref ), determine the object distance C between the sample on the reference carrier and the objective lens 21 and control the focus displacement assembly 33 to move so that the object distance C is equal to the target object distance C0. Subsequently, when focusing on the samples on the remaining carriers, it is only necessary to measure the measured distance (denoted as A1), and A1 minus A ref The difference obtained is the change in object distance. If the difference is greater than zero, the control module controls the focus displacement component 33 to drive the objective lens 21 closer to the sample and move the corresponding change to achieve focus, and when the difference is less than zero, the control module controls the focus displacement component 33 to drive the objective lens 21 away from the sample and move the corresponding change to achieve focus.

[0094] Specifically, if Figure 4-6 As shown, for the specific calculation principle of measuring distance A, the triangular laser rangefinder 32 includes a laser emitting component 321 and a laser receiving component 322. The emitting point of the laser emitting component 321, the receiving point of the laser receiving component 322 and the mirror-symmetrical imaging point of the sample in the laser reflector 31 are connected to form a triangle; the distance between the emitting point of the laser emitting component 321 and the receiving point of the laser receiving component 322 is B, B is a known constant, the angle between the line L connecting the emitting point of the laser emitting component 321 and the receiving point of the laser receiving component 322 and the incident light α is ε, ε is a known constant, and the angle between the line L and the second reflected light θ is ζ.

[0095] More specifically, if Figure 4-6As shown, in this embodiment, the laser receiving component 322 includes a laser imaging surface 3221 and a receiving lens 3222. The receiving lens 3222 is used to receive the second reflected light θ and project the second reflected light θ onto the laser imaging surface 3221. The laser imaging surface 3221 is parallel to the connecting line L. According to the triangle similarity principle, it can be known that ζ is equal to the angle formed by the second reflected light θ projected onto the laser imaging surface 3221. Therefore, the calculation formula of ζ can be obtained, ζ=arcsin(X / (X 2 +Y 2 ) 1 / 2 );

[0096] X represents the distance between the receiving point and the laser imaging surface 3221;

[0097] Y represents the distance between a vertical line passing through the receiving point and perpendicular to the laser imaging surface 3221 and a laser image generated by the second reflected light ray θ on the laser imaging surface 3221 .

[0098] From this, it can be seen that since the angle ε between the line L connecting the emitting point of the laser emitting component 321 and the receiving point of the laser receiving component 322 and the incident light ray α is a known fixed constant, B is also a constant. At the same time, when ζ is calculated, the measured distance A can be finally obtained based on the side-angle relationship of the geometric triangle (two angles and one side are known).

[0099] Specifically, when the triangle formed by the line L connecting the emission point of the incident light ray α and the receiving point of the second reflected light ray θ as the base and the intersection angle of the extended lines of the incident light ray α and the second reflected light ray θ as the vertex is an isosceles triangle, the formula for measuring the distance A is:

[0100] A = B / 2*X / Y;

[0101] In addition, according to the geometric trigonometric theorem, as described above, when the angle ζ between the second reflected light ray θ and the laser imaging surface 3221 is calculated, and the angle ε between the line L connecting the emission point of the incident light ray α and the receiving point of the second reflected light ray θ and the incident light ray α, and the length B of the line L are known, that is, when the two angles of one side are known, the measurement distance A can also be calculated according to the geometric trigonometric theorem, and it is not necessary to use A=B / 2*X / Y in this embodiment for calculation. Since the calculation process is a conventional calculation, it will not be repeated. At this point, the measurement distance A is obtained.

[0102] It should be noted that the sample carrier 100 of the present invention is preferably a transparent carrier, which includes an upper surface and a lower surface, and the sample to be measured is placed on the upper surface of the transparent carrier. The triangulated laser rangefinder 32 can obtain the measured distance A corresponding to the upper surface. u and the measured distance A corresponding to the lower surface l . You can use A uor A l As previously described, measure the distance A. Combined Figure 4-6 It can be seen that the distance conversion formula is:

[0103] A=D+C1;

[0104] Among them, D represents the distance from the intersection point of the base of the triangle formed by the line L connecting the emission point of the incident light ray α and the receiving point of the second reflected light ray θ as the base, and the intersection angle of the extended lines of the incident light ray α and the second reflected light ray θ as the vertex angle, and D is a known constant.

[0105] Therefore, given A and known D, C1 can be calculated.

[0106] Furthermore, if Figure 4-6 and Figure 8 As shown, in this embodiment, preferably, the measurement distance A corresponding to the lower surface l As the measuring distance A mentioned above, in order to focus more accurately, the object distance is corrected using the thickness C3 of the transparent carrier (in other embodiments, the object distance may not be corrected using the thickness C3 of the transparent carrier). Therefore, in this embodiment, the object distance C=C1+C2+C3; wherein C3 is the known thickness of the transparent carrier, and the second distance C2 is known (when the objective lens 21 is located at a known position. In other embodiments, the second spacing C2 can be measured, for example, by calibrating the initial distance between the objective lens 21 and the laser reflector 31 according to the grating ruler, and then obtaining the second spacing C2 in real time according to the movement of the objective lens 21 measured by the grating ruler), so the object distance C can be obtained.

[0107] When C3 is unknown, since the laser reflector 31 does not change the geometric triangulation theorem of the triangulation laser rangefinder 32, C3 can still be measured and calculated by the triangulation laser rangefinder 32, so it will not be described in detail.

[0108] Furthermore, it is conceivable that in other embodiments, the measured distance A corresponding to the upper surface u As the measurement distance A mentioned above, Fig. 9 As shown, the thickness of the transparent carrier sheet does not need to be considered, and thus the object distance C=C1+C2.

[0109] Finally, the object distance C can be calculated based on the geometric trigonometric relationship.

[0110] In summary, when the positions of the objective lens 21, the laser reflector 31, the laser emitting component 321 and the laser receiving component 322, and the thickness C3 of the transparent slide do not change, the change in the object distance C is the change in C1 and C2. Therefore, by obtaining C1, C2 and C3, the change in the object distance C can be easily obtained, thereby assisting in adjusting the object distance C for focusing. The advantage is that, in this embodiment, by adding a laser reflector 31, the incident light α is reflected by the laser reflector 31 and irradiated onto the surface of the sample, and the return light γ is reflected by the laser reflector 31 and captured by the laser receiving component 322, which realizes the bending change of the laser light path, making the position arrangement of the laser emitting component 321 and the laser receiving component 322 more flexible. According to the principle of mirror imaging, although it causes the laser light path to bend and change, it does not affect the distance measurement, and the distance measurement can still be performed through the geometric trigonometric theorem. The test accuracy is high, the test accuracy can reach the micron level, and the time consumption is short. It can be suitable for distance measurement in a small space. It has broad application prospects, which is conducive to the application of high-precision autofocus in fluorescence microscopy analysis of large quantities of samples.

[0111] As for the specific structure of the focus shift component 33, specifically, Figure 1-4 As shown, the focus displacement assembly 33 includes a focus motor, a vertical slide block, a slide block support plate, and an adapter plate (all not shown in the figure). The slide block support plate is vertically fixed on the middle bearing plate 124, and the adapter plate is slidably connected to the slide block support plate through the vertical slide block, so that it can move in the vertical direction. The focus motor is fixed on the slide block support plate, and the output end of the focus motor is connected to the adapter plate. The objective lens 21 is arranged on the adapter plate, and then the adapter plate is driven by the focus motor to drive the objective lens 21 to move in a focusing linear direction in the vertical direction. It is conceivable that in other embodiments, the focus displacement assembly 33 can also be other linear displacement devices.

[0112] At the same time, in order to accurately obtain the distance of the focus straight line movement, to obtain the second spacing C2. In this embodiment, the self-position measuring device is a focus moving grating ruler (not shown in the figure), and the focus moving grating ruler is an existing grating ruler, and then the displacement of the objective lens 21 along the vertical direction can be calculated. Specifically, it can be imagined that on the basis of setting the initial values ​​of the objective lens 21 and the laser reflector 31, the second spacing C2 can be calculated based on the displacement difference of the initial position of the objective lens 21 compared to the set initial value of the objective lens 21, and the specific details will not be repeated.

[0113] Furthermore, since different magnifications of objective lenses 21 are used in actual analysis, manual replacement is inefficient, difficult, and inconvenient. Figure 2As shown, in this embodiment, the number of objective lenses 21 is at least two. Specifically, there are three, namely, four-fold, ten-fold, and twenty-fold objective lenses. In addition to the objective lens 21, the microscopic imaging mechanism 2 also includes an objective lens switching assembly 22, and also includes a tube lens 23 and a camera 24. Each objective lens 21 is respectively fixed to the output end of the objective lens switching assembly 22, and the objective lens switching assembly 22 is configured to selectively drive one of the at least two objective lenses 21 to face the sample at the observation position; the tube lens 23 is coaxially arranged on the side of the objective lens 21 away from the sample at the observation position; the camera 24 is arranged on the side of the tube lens 23 away from the objective lens 21, for obtaining microscopic imaging. The microscopic imaging mechanism 2 realizes the electric adjustment and switching of the objective lens 21 through the objective lens switching assembly 22, which is convenient and simple to operate, saving time and effort. Specifically, the objective lens switching component 22 is fixedly connected to the output end of the focus displacement component 33. The objective lens switching component 22 includes an objective lens switching motor, a connecting base plate, an objective lens carrier plate, and an objective lens switching slide slider (not shown in the figure). The output end of the focus displacement component 33 is connected to the connecting base plate through the objective lens switching slide slider. The objective lens switching motor is fixed on the connecting base plate and the output end of the objective lens switching motor is connected to the objective lens carrier plate. Three objective lens fixing holes are provided on the objective lens carrier plate (not shown in the figure). The three objective lenses 21 are respectively fixedly installed on each objective lens fixing hole position. Then, under the drive of the objective lens switching motor, the objective lens carrier plate moves horizontally to realize the switching of different objective lenses 21.

[0114] Furthermore, the objective lens switching assembly 22 also includes an objective lens switching grating ruler, which is an existing grating ruler and can be used to accurately measure and monitor the moving distance and actual position of the objective lens carrier, and the details are not repeated here.

[0115] Furthermore, in the analysis of a large number of samples, a specific microscopic analysis execution strategy is generally formed to centrally process the same type of samples. When different types of samples need to be analyzed using different microscopic analysis execution strategies, it is necessary to adjust the relevant settings or parameters of the objective lens 21, the object carrier mechanism 1, the microscopic imaging mechanism 2, the autofocus mechanism 3, and the filter automatic switching component 5 of the high-throughput autofocus analysis device step by step, which is cumbersome and inconvenient. Therefore, in order to further solve this problem.

[0116] like Figure 7As shown, the present embodiment also provides an autofocus analysis system including the high-throughput autofocus analysis device of the present embodiment, and the autofocus analysis system also includes a master control mechanism 7, which mainly includes a storage module 71 and an execution module 72. The master control mechanism 7 is electrically connected to the object loading mechanism 1, the microscopic imaging mechanism 2, the autofocus mechanism 3, the fluorescent component 4, the filter automatic switching component 5 and the bright field light source 6. The storage module 71 is configured to store the microscopic analysis execution strategy. The execution module 72 is configured to be able to control the translation component 12 so that the samples on each carrying position are transported to the observation position in sequence according to a preset order according to the microscopic analysis execution strategy; at the same time, control the automatic filter switching component 5 so that at least one of the two filter cubes 42 cooperates with the fluorescent light source 41 to provide target fluorescent excitation light to the sample at the observation position; at the same time, when objective lenses 21 of different magnifications are used, control the movement of the objective lens switching component 22 so that one of the multiple objective lenses 21 is facing the observation position; at the same time, receive the object distance signal detected by the automatic focusing mechanism 3, and control the automatic focusing mechanism 3 to adjust the object distance C to the target object distance C0, so that the microscopic imaging mechanism 2 obtains a microscopic image.

[0117] Since the master control mechanism 7 has a storage module 71 for storing microscopic analysis execution strategies, the staff can call various microscopic analysis execution strategies stored in the storage module 71 through the execution module 72, and quickly and automatically adjust the relevant settings or parameters of the objective lens 21, the object carrier mechanism 1, the microscopic imaging mechanism 2, the automatic focusing mechanism 3, and the automatic filter switching component 5 according to the microscopic analysis execution strategy. Specifically, the microscopic analysis execution strategy can be one, two, or more, and the staff can selectively call and use one of the microscopic analysis execution strategies through the execution module 72 to achieve rapid adjustment, without the need for the staff to repeatedly control the settings step by step, so the working efficiency of the high-throughput automatic focusing analysis device is greatly improved, and the high-throughput automatic focusing analysis device is realized through the master control mechanism 7. Efficient and flexible coordinated control of various mechanism components of the high-throughput automatic focusing analysis device has a wide range of application prospects.

[0118] It is conceivable that, in addition to executing the microscopic analysis execution strategy of the storage module 71, the execution module 72 can also exit the execution of the microscopic analysis execution strategy, so that the staff can individually and electrically control the working status of each mechanism, which will not be described in detail.

[0119] In addition, based on the high-throughput auto-focus analysis device of this embodiment, the high-throughput auto-focus analysis method of this embodiment includes the following steps:

[0120] Determine the loading position to be analyzed on the loading mechanism 1, and transport the sample carried on the loading position to be analyzed to the observation position;

[0121] Providing light source to the sample at the observation position through the light source mechanism;

[0122] Adjust the object distance C between the objective lens 21 and the sample at the observation position based on the triangulated laser distance measurement, and adjust the object distance C through the automatic focusing mechanism 3 to make the object image clear;

[0123] The microscopic image of the sample at the observation position is captured by the microscopic imaging mechanism 2 .

[0124] Furthermore, when adjusting the object distance C between the objective lens 21 and the sample at the observation position based on the triangular laser ranging method, the autofocus analysis method of this embodiment emits an incident light ray α to the laser reflector 31 through the triangular laser rangefinder 32. The incident light ray α is reflected by the laser reflector 31 and irradiates the sample at the observation position, and the measured distance A is obtained. The specific calculation process is as described above, so it will not be repeated here. It is based on the triangular laser test principle, and finally calculates the object distance C, with high measurement accuracy and short time consumption.

[0125] Further, as mentioned above, the light source provided by the light source mechanism is a fluorescent light source 41, and the step of providing the light source to the sample at the observation position through the light source mechanism specifically includes the following steps:

[0126] A filter cube 42 is determined from at least two filter cubes 42, and the fluorescent light source 41 provides target fluorescent excitation light to the sample at the observation position after being filtered by the filter cube 42, so as to perform fluorescence analysis.

[0127] In addition, since the fluorescent light emitted by the fluorescent light source 41 may interfere with the laser light emitted by the triangulated laser rangefinder 32 (different fluorescent wavelengths produce different interferences), the characteristics of the filter cube 42 itself (such as the material and thickness of the lenses of the filter cube 42) may also affect the obtained measured distance A.

[0128] Further, when the first spacing C1 is obtained, the object distance C is corrected for deviation according to the filter cube 42 and / or the target fluorescent excitation light. Specifically, the correction test method is to turn on and off the fluorescent light source 41, conduct multiple tests to obtain the measured distances A measured in two cases, and then obtain the deviation value by comparison, so as to further correct the deviation of the object distance C. The specific test steps will not be repeated.

[0129] The above contents are only preferred embodiments of the present invention. For ordinary technicians in this field, according to the concept of the present invention, there will be changes in the specific implementation methods and application scopes. The content of this specification should not be understood as limiting the present invention.

Claims

1. A high-throughput autofocus analysis device, characterized in that: include: A loading mechanism (1) for loading a sample carrier (100), wherein the sample carrier (100) is provided with at least two loading positions, wherein the loading positions are used to load samples, and the loading mechanism (1) is also used to drive the sample carrier (100) to translate in at least one direction, so that the loading positions on the sample carrier (100) are located at observation positions in sequence; A microscopic imaging mechanism (2) is configured to sequentially obtain microscopic images of the samples in the carrying positions located at the observation positions; An autofocus mechanism (3) is drivingly connected to the microscopic imaging mechanism (2), and the autofocus mechanism (3) is configured to calculate and adjust the object distance C between the objective lens (21) of the microscopic imaging mechanism (2) and the sample at the observation position based on a triangulated laser ranging method before acquiring the microscopic imaging, so as to make the object image clear; A light source mechanism, configured to provide a light source to the sample at the observation position; The automatic focusing mechanism (3) comprises: A laser reflection mirror (31), which is fixed between the objective lens (21) and the sample at the observation position; A triangulated laser rangefinder (32) is configured to emit an incident light α with an incident angle δ to a reflective surface of the laser reflector (31), wherein the incident light α is reflected to generate a first reflected light β, wherein the first reflected light β is irradiated on the surface of the sample to generate a return light γ, wherein the return light γ is reflected by the reflective surface to generate a second reflected light θ, and further configured to receive the second reflected light θ, generate a laser image, and calculate a measured distance A based on the laser image according to geometric trigonometric theorems; A focus displacement component (33), wherein the objective lens (21) is arranged at an output end of the focus displacement component (33), and the focus displacement component (33) is configured to adjust the object distance C so that the object distance C is equal to the target object distance C0; Among them, the height of the base of the triangle formed by the line L connecting the emission point of the incident light ray α and the receiving point of the second reflected light ray θ as the base and the intersection angle of the extended lines of the incident light ray α and the second reflected light ray θ as the vertex is equal to the measurement distance A.

2. The high-throughput autofocus analysis device according to claim 1, characterized in that: The focus displacement component (33) is further configured to adjust the object distance C of the sample on the reference bearing position to the object distance C0, and then adjust the object distance C of the sample on the remaining bearing positions to the target object distance C0 based on the measurement distance A corresponding to the reference bearing position and the measurement distances A corresponding to the remaining bearing positions.

3. The high-throughput autofocus analysis device according to claim 1, characterized in that: The laser reflection mirror (31) is a semi-transparent and semi-reflective mirror, and the first reflected light β and the returning light γ are coaxial with the axis of the objective lens (21) relative to the normal line of the sample.

4. The high-throughput autofocus analysis device according to claim 1, characterized in that: The light source mechanism comprises: The fluorescence component (4) comprises a fluorescence light source (41) and at least two filter cubes (42). The fluorescence light source (41) can selectively provide target fluorescence excitation light to a sample at an observation position through any one of the filter cubes (42).

5. The high-throughput autofocus analysis device according to claim 4, characterized in that: The focus shift component (33) is further configured to perform deviation correction on the object distance C based on the target fluorescent excitation light and / or the filter cube (42).

6. The high-throughput autofocus analysis device according to claim 4, characterized in that: The light source mechanism also includes: The automatic filter switching component (5) is drivingly connected to the at least two filter cubes (42), and the automatic filter switching component (5) is configured to enable one of the at least two filter cubes (42) to cooperate with the fluorescent light source (41) to provide target fluorescent excitation light to the sample at the observation position.

7. The high-throughput autofocus analysis device according to claim 6, characterized in that: The automatic light filtering switching component (5) comprises: A filter carrier (51) having at least two filter cube fixing positions disposed thereon, and each of the filter cubes (42) is fixed one-to-one to each of the filter cube fixing positions; A carrier displacement component (52), wherein the filter carrier (51) is arranged at an output end of the carrier displacement component (52), and the carrier displacement component (52) is configured to drive the filter carrier (51) to move so that one of the at least two filter cubes (42) moves to a docking position, and cooperates with the fluorescent light source (41) to provide target fluorescent excitation light to the sample at the observation position.

8. The high-throughput autofocus analysis device according to claim 1, characterized in that: The light source mechanism comprises: A bright field light source (6) is arranged above the object carrying mechanism (1), and the bright field light source (6) is configured to provide bright field light to the sample at the observation position.

9. The high-throughput autofocus analysis device according to claim 1, characterized in that: The object carrying mechanism (1) comprises: A sample carrier (11), used for carrying the sample carrier plate (100); The translation component (12) is configured to carry the sample carrier (11), and the translation component (12) can automatically translate the sample carrier (11) so that one of the samples on the at least two carrying positions is selectively transported to the observation position.

10. The high-throughput autofocus analysis device according to claim 9, characterized in that: The translation assembly (12) comprises: Frame (121); A first displacement driving component (122) is disposed on the frame (121); The second displacement driving component (123) is arranged at the output end of the first displacement driving component (122), and the first displacement driving component (122) is configured to drive the second displacement driving component (123) to move along a first direction. The sample carrier (11) is fixed to the output end of the second displacement driving component (123), and the second displacement driving component (123) is configured to drive the sample carrier (11) to move along a second direction, and the first direction is perpendicular to the second direction.

11. The high-throughput autofocus analysis device according to claim 1, characterized in that: The number of the objective lenses (21) is at least two, and the microscopic imaging mechanism (2) further comprises: An objective lens switching assembly (22), each of the objective lenses (21) is respectively fixed to an output end of the objective lens switching assembly (22), and the objective lens switching assembly (22) is configured to selectively drive one of at least two objective lenses (21) to face the sample at the observation position.

12. The high-throughput autofocus analysis device according to claim 1, characterized in that: The microscopic imaging mechanism (2) further comprises: A tube lens (23) is coaxially arranged on a side of the objective lens (21) away from the observation position; A camera (24) is arranged on a side of the tube lens (23) away from the objective lens (21) for acquiring microscopic images.

13. A high-throughput auto-focus analysis system, comprising the high-throughput auto-focus analysis device according to any one of claims 1 to 12, characterized in that: The system further comprises a general control mechanism (7), wherein the general control mechanism (7) comprises: A storage module (71) configured to store a microscopic analysis execution strategy for analyzing a sample; An execution module (72) is configured to control the translation assembly (12) according to the microscopic analysis execution strategy, so that the samples on the plurality of carrying positions are transported to the observation position in sequence according to a preset order; and Controlling the automatic filter switching component (5) so that one of the at least two filter cubes (42) cooperates with the fluorescent light source (41) to provide target fluorescent excitation light to the sample at the observation position; and The automatic focusing mechanism (3) is controlled to adjust the object distance C to the target object distance C0, so that the microscopic imaging mechanism (2) acquires a microscopic image.

14. A high-throughput autofocus analysis method, based on the high-throughput autofocus analysis device according to any one of claims 1 to 12, characterized in that: The following steps are involved: Determining a loading position to be analyzed on the loading mechanism (1), and transporting the sample carried on the loading position to be analyzed to an observation position; Providing light source to the sample at the observation position through the light source mechanism; Based on triangulated laser distance measurement, an object distance C between an objective lens (21) and a sample at an observation position is adjusted to make the object image clear; The microscopic image of the sample at the observation position is captured by the microscopic imaging mechanism (2).

15. The auto-focus analysis method according to claim 14, wherein: When adjusting the object distance C between the objective lens (21) and the sample at the observation position based on the triangular laser distance measurement method, an incident light ray α is emitted to the laser reflection mirror (31) through the triangular laser distance meter (32), and the incident light ray α is reflected by the laser reflection mirror (31) and irradiated on the sample at the observation position, and the measured distance A is obtained.

16. The auto-focus analysis method according to claim 15, characterized in that: The light source provided by the light source mechanism is a fluorescent light source (41). Providing the light source to the sample at the observation position through the light source mechanism includes the following steps: A filter cube (42) is determined from at least two filter cubes (42), and a fluorescent light source (41) is filtered by the filter cube (42) to provide target fluorescent excitation light to a sample at an observation position.

17. The auto-focus analysis method according to claim 16, wherein: The object distance C is corrected for deviation according to the filter cube (42) and / or the target fluorescent excitation light.

Images