Biological sample image acquisition device and gene sequencer

Abstract

A biological sample image acquisition device (100) comprises a support (30) and an optical imaging component (50), the biological sample image acquisition device (100) further comprising: a plurality of movable platforms (40) movably connected to the support (30) for placing a biological sample (20) and driving the biological sample (20) to move, the plurality of movable platforms (40) being arranged in an array on the support (30), the plurality of movable platforms (40) being movable relative to the support (30) and the forces acting on the support (30) during movement being mutually offset, so as to avoid vibration of the support (30) and the biological sample (20) caused by the movement of the movable platforms (40), the optical imaging component (50) acquiring images of the biological sample (20) on the movable platforms (40) when the plurality of movable platforms (40) move in the same direction and at the same speed relative to the center of the array. The present application also provides a gene sequencer comprising the biological sample image acquisition device (100).

Description

Technical Field

[0001] The present invention relates to the technical field of biological sample information collection, and in particular to a biological sample image collection device and a gene sequencer. Background Art

[0002] At present, the devices for collecting biological sample information, such as gene sequencers, generally use an optical system to collect and image the fluorescence emitted by the fluorescent groups carried by the bases in the biological sample (nucleic acid) placed on the platform, so as to identify the bases and complete the sample information collection. With the development of optical technology, there are increasingly higher requirements for the throughput of biological sample information collection devices such as gene sequencers. In order to improve the throughput of biological sample information collection devices, the first method is to increase the throughput by increasing the field of view of the optical system, and the second method is to design a movable platform to increase the flux by driving the sample to move through the platform. The faster the movement speed of the platform, the greater the flux obtained. The first method requires the redesign of the existing optical system, and the optical system with a large field of view has a complex structure and high cost; the second method is that the faster the platform moves, the stronger the impact on the optical system will be, and the vibration caused by the impact will cause the imaging quality of the optical system to decrease. In this way, the existing biological sample information collection device does not have the advantages of simple structure and high-quality image acquisition of samples. Summary of the invention

[0003] In view of this, it is necessary to provide a biological sample image acquisition device and a gene sequencer that have a simple structure and can obtain high-quality images of biological samples.

[0004] A biological sample image acquisition device, comprising a support and an optical imaging component, the biological sample image acquisition device also comprising:

[0005] A plurality of movable platforms are movably connected to the support member, and are used to place biological samples and drive the biological samples to move. The plurality of movable platforms are arranged in an array on the support member, and the plurality of movable platforms can move relative to the support member, and the forces acting on the support member during movement can offset each other, so as to avoid vibration of the biological samples caused by the movement of the movable platforms;

[0006] The optical imaging component collects images of biological samples on the movable platforms when the multiple movable platforms move relative to the supporting platform.

[0007] Furthermore, the optical imaging assembly includes: a light source output element for outputting light; a first dichroic mirror for receiving and reflecting the light output by the light source output element; an objective lens placed above the movable platform, for focusing the light reflected by the first dichroic mirror onto a biological sample to excite fluorescent markers in the biological sample to produce fluorescence, and projecting the fluorescence to the first dichroic mirror; the first dichroic mirror is also used to transmit the fluorescence projected by the objective lens; an image sensor element for sensing the received light to form a fluorescent image of the biological sample; and a light guide element for guiding the fluorescence transmitted by the first dichroic mirror to the image sensor element.

[0008] Furthermore, the biological sample image acquisition device includes a plurality of objective lenses and an image sensor, and the light-sensitive range of the image sensor is greater than the sum of the imaging ranges of the plurality of objective lenses.

[0009] Furthermore, a plurality of objective lenses are arranged above each of the movable platforms, and the objective lenses are spaced at equal distances from each other. The projections of the objective lenses divide the biological sample into a plurality of parts with equal spacings.

[0010] Furthermore, it includes multiple objective lenses and a sample position exchange component, the focusing surfaces of all the objective lenses are located at different heights above the movable platform, each objective lens is used to focus light on a slide on a biological sample including multiple slides, when the multiple movable platforms move relative to the supporting component so that the multiple objective lenses respectively collect the fluorescence located on one slide, the sample position exchange component exchanges the positions of the biological samples under the multiple objective lenses.

[0011] Furthermore, the sample position exchange component is a rotating platform connected to the multiple movable platforms at the same time, the multiple movable platforms are movably connected to the rotating platform, and the rotating platform is rotatably arranged on a support member, and can rotate around the center of the array on a plane parallel to the movable platforms to interchange positions of the multiple movable platforms.

[0012] Furthermore, the sample position exchange component includes a manipulator and multiple rotating platforms respectively connected to the multiple movable platforms. The manipulator places the biological sample on one movable platform on another movable platform. The multiple movable platforms are respectively movably connected to the multiple rotating platforms. The multiple rotating platforms can drive the biological sample to rotate on a plane parallel to the movable platform.

[0013] Furthermore, the number of the movable platforms is an even number, all the movable platforms are arranged on the support member in a rectangular shape, and the even number of movable platforms move towards or away from the symmetry axis of the rectangle at the same time.

[0014] Furthermore, the plurality of movable platforms are evenly arranged in a circle on the support, the angles between every two movable platforms are equal, and all movable platforms move towards or away from the center of the circle at the same time.

[0015] A gene sequencer comprises the above-mentioned biological sample image acquisition device.

[0016] The multiple movable platforms of the above-mentioned biological sample image acquisition device and gene sequencer are arranged in an array on the support, and when the multiple movable platforms move, the forces acting on the support cancel each other out, thereby avoiding vibration of the support and the biological sample caused by the movement of the movable platforms, allowing the objective lens to obtain accurate fluorescence distribution, so that the image sensor for sensing light forms a high-quality fluorescence image of the biological sample. Compared with the existing technology, the biological sample image acquisition device has the advantages of simple structure and the ability to obtain high-quality images of biological samples. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The present invention is a schematic diagram of a biological sample image acquisition device in a first embodiment.

[0018] Figure 2 yes Figure 1 Schematic diagram of the light source output in .

[0019] Figure 3 for Figure 1 Schematic diagram of the movement of the movable platform in.

[0020] Figure 4 is a schematic diagram of a biological sample image acquisition device in another embodiment.

[0021] Figure 5A yes Figure 1 A schematic diagram showing a movable platform corresponding to a plurality of objective lenses in one embodiment.

[0022] Figure 5B yes Figure 1 A schematic diagram of a movable platform corresponding to a plurality of objective lenses in another embodiment.

[0023] Figure 6 yes Figure 1 Schematic diagram of part of the biological sample image acquisition device when the biological sample in the image is a double-layer slide.

[0024] Figure 7 yes Figure 1 Schematic diagram of a portion of a biological sample image acquisition device when the biological sample is a multi-layer slide.

[0025] Figure 8 yes Figure 1 Schematic diagram of the arrangement of the movable platform in another embodiment.

[0026] Fig. 9 is with Figure 8 Schematic diagram of the light source output component matched with the movable platform in FIG.

[0027] Fig.10 yes Figure 1 Schematic diagram of the arrangement of the movable platform in another embodiment.

[0028] Main component symbols

[0029]

[0030] DETAILED DESCRIPTION

[0031] The present invention will be described in further detail below with reference to the accompanying drawings.

[0032] In order to more clearly understand the above-mentioned purpose, features and advantages of the present invention, the present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be noted that the embodiments of the present application and the features in the embodiments can be combined with each other without conflict.

[0033] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. The embodiments described are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0035] See also Figure 1 The present invention provides a biological sample image acquisition device 100, which is used to acquire an image of a biological sample 20.

[0036] The biological sample image acquisition device 100 includes a support 30, a plurality of movable platforms 40 and an optical imaging assembly 50. A plurality of shock-absorbing pads 32 are provided at the bottom of the support 30. The plurality of movable platforms 40 are movably connected to the support 30, and are used to place the biological sample 20 and drive the biological sample 20 to move. The plurality of movable platforms 40 are arranged in an array on the support 30, and the plurality of movable platforms can move relative to the support, and the forces acting on the support during movement can offset each other, so as to avoid vibration of the support 30 and the biological sample 20 caused by the movement of the movable platforms 40. Specifically, the plurality of movable platforms 40 offset the forces acting on the support during movement by moving in the same direction and at the same speed relative to the array center of the plurality of movable platforms 40, and the same direction movement includes moving close to the array center and moving away from the array center. The optical imaging assembly 50 is placed above the movable platform 40, and is used to collect images of the biological sample 20 on the movable platform 40 when the plurality of movable platforms 40 move in the same direction and at the same speed relative to the array center.

[0037] The optical imaging assembly 50 includes a light source output member 51, an objective lens 52 disposed above the movable platform 40, a first dichroic mirror (also translated as "dichroic mirror") 53, a light guide member 54 and an image sensor 55. The light source output member 51 is used to output light. The first dichroic mirror 53 is arranged one-to-one with the objective lens 52, disposed between the objective lens 52 and the light source output member 51, and is used to receive the light output by the light source output member 51 and reflect the received light output by the light source output member 51 to the objective lens 52. The objective lens 52 is used to focus the light reflected by the first dichroic mirror 53 onto the biological sample 20 on the movable platform 40, so as to excite the fluorescent marker in the biological sample 20 to generate fluorescence, and project the fluorescence onto the first dichroic mirror 53 through the objective lens 52. In this embodiment, the objective lens 52 is connected to a lifting member 56, and the objective lens 52 moves up and down with the lifting member 56 to adjust the focusing position of the objective lens 52 to be located on the biological sample 20. The first dichroic mirror 53 is also used to transmit the fluorescence projected by the objective lens 52 to the light guide 54. The light guide 54 is arranged one-to-one with the first dichroic mirror 53, and is used to guide the fluorescence transmitted by the first dichroic mirror 53 to the image sensor 55. The image sensor 55 senses the received light to form a fluorescence image of the biological sample 20.

[0038] like Figure 1The fluorescent markers in the biological sample 20 placed on the movable platform 40 shown in the figure respectively generate lights of different wavelengths under the excitation of the light of specific wavelength. The light guide 54 includes a second dichroic mirror 541, a first reflector 542, a second reflector 543, a first tube mirror 544 and a second tube mirror 545. The second dichroic mirror 541 receives the fluorescence transmitted by the first dichroic mirror 53 and transmits the light of the first wavelength in the fluorescence to the first reflector 542, and also reflects the light of the second wavelength in the fluorescence to the second reflector 543. The first reflector 542 reflects the light to the first tube mirror 544, and the second reflector 543 reflects the light to the second tube mirror 545. In this embodiment, the number of the first reflector 542 is two, and the number of the second reflector 543 is one. In other embodiments, the number of the first reflectors 542 may be one or three or more, and the number of the second reflectors 543 may be two or more, which is specifically determined according to the relative positions between the first barrel lens 544 and the second dichroic mirror 541 and between the second barrel lens 545 and the second dichroic mirror 541. The first barrel lens 544 and the second barrel lens 545 respectively converge the light received by each to the image sensor 55. The image sensor 55 senses the light of the first barrel lens 544 and the second barrel lens 545 to form a fluorescent image of the biological sample 20. In this embodiment, the image sensor 55 includes a first image sensor 551 and a second image sensor 552. The first image sensor 551 receives the light converged by the first barrel lens 544 to form a first sample image. The second image sensor 552 receives the light converged by the second barrel lens 545 to form a second sample image.

[0039] In another embodiment, the fluorescent marker in the biological sample 20 placed on the movable platform 40 generates fluorescence under the excitation of light. Figure 1 The difference of the light guide 54 shown is that it includes a first reflector 542 but does not include the second dichroic mirror 541, and the first reflector 542 directly receives the fluorescence transmitted by the first dichroic mirror 53 and emits the fluorescence to the image sensor 55. Correspondingly, the image sensor 55 includes a first image sensor 551 but does not include a second image sensor 552.

[0040] like Figure 1 The biological sample image acquisition device 100 shown includes two movable platforms 40 , on which a biological sample 20 is placed respectively. The biological sample image acquisition device 100 is used to acquire images of the two biological samples 20 placed on the two movable platforms 40 .

[0041] The biological sample image acquisition device 100 includes two objective lenses 52, two first dichroic mirrors 53, two light guides 54 and the image sensor 55 placed above the two movable platforms 40. The light source output element 51 is used to output the excitation light to the two first dichroic mirrors 53. Specifically, Figure 2 The light source output element 51 is placed between the two first dichroic mirrors 53, and includes a laser emitter 511, a collimating lens 512, a beam splitter prism 513 and a reflector 514. The laser emitter 511 is used to output laser light (or "excitation light"). The collimating lens 512 is used to collimate the laser light and then emit it to the beam splitter prism 513. The beam splitter prism 513 splits the laser light into two laser light paths 5131 and 5132, wherein one laser light path 5131 is reflected to one of the first dichroic mirrors 53 by the reflector 514, and the other laser light path 5132 is directly emitted to the other first dichroic mirror 53 after passing through the beam splitter prism 513, so that the laser light output by the light source output element 51 is emitted to the two first dichroic mirrors 53. The beam splitter prism 513 can be a 50 / 50 beam splitter prism 513, which splits the laser light into two laser light paths 5131 and 5132 with equal power. The two first dichroic mirrors 53 reflect the light outputted by the light source output element 51 onto the two objective lenses 52, and transmit the fluorescence excited on the two biological samples 20 projected by the two objective lenses 52 to the two light guides 54. The image sensor 55 is placed between the two first dichroic mirrors 53, and is used to receive the light introduced by the two light guides 54 to form the fluorescence images of the two biological samples 20. The light-sensitive range of the image sensor 55 is greater than the sum of the imaging ranges of the two objective lenses 52, so that the images of the two biological samples 20 can be formed on the same image sensor 55. In another embodiment, the light-sensitive range of the image sensor 55 is the same as the imaging range of one objective lens 52, and the biological sample image acquisition device 100 includes two image sensors 55 of the same number as the objective lenses 52, and each image sensor 55 forms a fluorescence image of the biological sample 20.

[0042] Please also see Figure 3 ,like Figure 1In the biological sample image acquisition device 100 shown, the two movable platforms 40 are symmetrical along a first axis X and a second axis Y perpendicular to the first axis X, and the center of the array is the intersection of the first axis X and the second axis Y. The image sensor 55 is a line array camera, a TDI (time delay integration) camera or a surface array camera. The two movable platforms 40 can move in a direction parallel to the first axis X and in a direction parallel to the second axis Y. When the biological sample image acquisition device 100 acquires an image of a biological sample 20, the two movable platforms 40 move in the same direction and at the same speed from the first edge of the two biological samples 20 relative to the center of the array to the second edge of the two biological samples 20 opposite to the first edge, parallel to the first axis X, so that the two objective lenses 52 acquire the fluorescence of a row of the biological sample 20 excited and parallel to the first axis X. Then, the two movable platforms 40 move in the same direction and at the same speed parallel to the second axis Y relative to the center of the array to one end corresponding to the second edge of another row of the two biological samples 20 parallel to the first axis X, and then move along the first axis X to one end corresponding to the first edge of another row, so that the two objective lenses 52 acquire the fluorescence of the other row of the biological sample 20 excited and parallel to the first axis X. This process is repeated, and scanning is performed line by line, so that the two objective lenses 52 acquire all the fluorescence on the biological sample 20. The multiple rows of fluorescence acquired by each objective lens 52 are incident on the image sensor 55 through the corresponding first dichroic mirror 53 and the light guide 54 to form a fluorescence image of the biological sample 20. In another embodiment, the two movable platforms 40 move from the first edge to the second edge of the biological sample 20 parallel to the first axis X, obtain the fluorescence of a row parallel to the first axis X, and then return to the first edge of the two biological samples 20 along the first axis X, and then move parallel to the second axis Y and at the same direction and speed relative to the center of the array to one end corresponding to the first edge of another row parallel to the first axis X on the two biological samples 20, and then move along the first axis X to one end corresponding to the second edge of the other row, so that the two objective lenses 52 can obtain the fluorescence of the other row parallel to the first axis X excited on the biological sample 20. This is repeated, scanning line by line, so that the two objective lenses 52 can obtain all the fluorescence on the biological sample 20. The scanning method of the biological sample 20 can also be other methods, such as the two movable platforms 40 starting from the center position of the two biological samples 20 to scan line by line to obtain all the fluorescence on the two biological samples 20. The specific scanning method is determined according to needs and design, and is not listed here. It can be understood that the two movable platforms 40 can move closer to or away from the center of the array when moving along the first axis X, and the two movable platforms 40 can also move closer to or away from the center of the array when moving along the second axis Y, which is specifically determined by the positions at which the two objective lenses 52 are initially set on the biological sample 20.When collecting images of two biological samples 20, the two movable platforms 40 move in the same direction and at the same speed at the center of the array, and the forces acting on the two movable platforms 40 during movement are opposite to the directions of the forces acting on the support members 30 and cancel each other out, thereby preventing the entire support member 30 and the biological samples 20 placed on the movable platforms 40 from vibrating, allowing the objective lens 52 to obtain accurate fluorescence distribution, thereby allowing the image sensor 55 to form a high-quality image of the biological sample 20.

[0043] In another embodiment, the width of the area on the biological sample 20 where the image needs to be collected is within the field of view of the objective lens 52, and the image sensor 55 is a linear array camera, a TDI (time delay integration) camera or a surface array camera. Figure 3 The difference between the two movable platforms 40 shown is that the two movable platforms 40 can move in a direction parallel to the first axis X, but cannot move in a direction parallel to the second axis Y. When the biological sample image acquisition device 100 acquires an image of a biological sample 20, the two movable platforms 40 respectively move from two divergent edges of the two biological samples 20 to the other edge of the two biological samples 20 in the same direction and at the same speed, parallel to the first axis X, relative to the center of the array, so that the two objective lenses 52 acquire the fluorescence excited on the biological sample 20 and parallel to the first axis X, thereby acquiring the fluorescence of the area on the biological sample 20 where the image needs to be acquired. The fluorescence acquired by each objective lens 52 is incident on the image sensor 55 through the corresponding first dichroic mirror 53 and the light guide 54 to form a fluorescence image of the biological sample 20.

[0044] See also Figure 4 , is a schematic diagram of a biological sample image acquisition device 200 provided in another embodiment, wherein the biological sample image acquisition device 200 and Figure 1 The difference between the biological sample image acquisition device 100 shown is that the biological sample image acquisition device 200 includes two movable platforms 40, wherein an objective lens 52 is disposed above one movable platform 40, and an objective lens 52 is not disposed above the other movable platform 40. Correspondingly, the biological sample image acquisition device 200 only includes a first dichroic mirror 53 and a light guide 54 corresponding to one objective lens 52. The biological sample image acquisition device 200 is used to acquire an image of a biological sample 20 on the movable platform 40 on which the objective lens 52 is disposed. The process of acquiring an image of the biological sample 20 by the biological sample image acquisition device 200 is consistent with that of the biological sample image acquisition device 100. During the acquisition process, the two movable platforms 40 move simultaneously, thereby avoiding the vibration of the entire support member 30 and the biological sample 20 caused by the movement of only the movable platform 40 below the objective lens 52, thereby obtaining a high-quality image of the biological sample 20.

[0045] like Figure 5A and5B In another embodiment, Figure 1 The difference of the objective lens 52 in the biological sample image acquisition device 100 shown is that two objective lenses 52 are arranged above each movable platform 40, the distance between the two objective lenses 52 is half the length or width of the biological sample 20, and one of the objective lenses 52 faces the edge of the biological sample. Figure 5A As shown, the distance between the two objective lenses 52 is half the length of the biological sample 20. Figure 5B As shown, the distance between the two objective lenses 52 is half the width of the biological sample 20. The two objective lenses 52 on one of the movable platforms 40 are respectively symmetrical with the two objective lenses 52 on the other movable platform 40 about the center of the array. In this way, when the travel of the movable platform 40 along the first axis X or the second axis Y is half the length or width of the biological sample 20, the two objective lenses 52 corresponding to each movable platform 40 can obtain the fluorescence excited on the biological sample 20, thereby obtaining an image of the entire biological sample 20. In another embodiment, three, four or more objective lenses 52 are arranged above each movable platform 40, and the intervals between the objective lenses 52 are equal. The projection of the objective lenses 52 divides the biological sample 20 into multiple parts with equal spacing. The multiple objective lenses 52 on one of the movable platforms 40 are respectively symmetrical with the multiple objective lenses 52 on the other movable platform 40 about the center of the array. In this way, when the movement distance of the movable platform 40 along the first axis X or the second axis Y is one-third, one-quarter or less of the length or width of the biological sample 20, three, four or more objective lenses 52 corresponding to each movable platform 40 can acquire the fluorescence excited on the biological sample 20, thereby obtaining an image of the entire biological sample 20.

[0046] See also Figure 6 , is a schematic diagram of a biological sample image acquisition device 300 provided in another embodiment, wherein the biological sample image acquisition device 300 and Figure 1 Similar to the biological sample image acquisition device 100 in FIG. 1 , only the biological sample image acquisition device 300 and the biological sample image acquisition device 100 are shown here. Figure 1 The biological sample image acquisition device 300 is different from the biological sample image acquisition device 100 in FIG. Figure 1The difference between the biological sample image acquisition device 100 in the embodiment is that the biological sample image acquisition device 300 further includes a sample position exchange component 60, and the focusing surfaces of the two objective lenses 52 placed above the two movable platforms 40 are located at different heights above the movable platforms 40. The two objective lenses 52 are used to focus light on different layers of the biological sample 20 on the double-layer slide, thereby stimulating the fluorescent markers on the slides at different heights to produce fluorescence, so that the two objective lenses 52 collect the fluorescence on different slides. When the two movable platforms 40 move in the same direction and at the same speed relative to the center of the array so that the two objective lenses 52 respectively collect the fluorescence on one slide, the sample position exchange component 60 exchanges the positions of the two biological samples 20 under the two objective lenses 52. After the movable platforms 40 exchange the positions of the two biological samples 20, the two movable platforms 40 move again in the same direction and at the same speed relative to the center of the array so that the two objective lenses 52 respectively collect the fluorescence on the other slide. In this way, the fluorescence on the biological sample 20 on the double-layer slide is collected by the two objective lenses 52, so that the image sensor 55 obtains the fluorescence image of the biological sample 20. The sample position exchange component 60 shown in FIG5 is connected to a rotating platform at the same time as the two movable platforms 40. The two movable platforms 40 are movably connected to the rotating platform. The rotating platform is rotatably arranged on the support member 30 and can be rotated 180 degrees around the center of the array on a plane parallel to the movable platforms 40 to exchange the positions of the two movable platforms 40, thereby exchanging the positions of the two biological samples 20 relative to the two objective lenses 52. Please refer to Figure 7 In another embodiment, the sample position exchange component 60 in the biological sample image acquisition device 400 includes a manipulator 62, and the manipulator 62 places the biological sample 20 located on one movable platform 40 on another movable platform 40 to exchange the positions of the two biological samples 20. Furthermore, considering that the positions of the biological samples 20 after the exchange by the manipulator 62 are different from the original positions, the sample position exchange component also includes two rotating platforms 64 respectively connected to the two movable platforms 40. The rotating platforms 64 can drive the biological samples 20 to rotate on a plane parallel to the movable platform 40, so as to adjust the positions of the two biological samples 20 to match the positions of the two objective lenses 52, so as to facilitate the collection of the fluorescence excited by the biological samples 20. In such a case Figure 7 In the illustrated embodiment, the two rotating platforms 64 are respectively placed on the movable platform 40 at a side away from the support 30, and the biological sample 20 is placed on the rotating platform 64. In another embodiment, the two rotating platforms 64 are respectively placed under the movable platform 40, between the movable platform 40 and the support 30, and the biological sample 20 is placed on the movable platform 40.

[0047] Please continue reading Figure 7 , is a schematic diagram of a biological sample image acquisition device 400 provided in another embodiment, wherein the biological sample image acquisition device 400 and Figure 6Similar to the biological sample image acquisition device 300 in FIG. 1 , only the biological sample image acquisition device 400 and the biological sample image acquisition device 300 are shown here. Figure 6 The biological sample image acquisition device 400 is different from the biological sample image acquisition device 300 in FIG. Figure 6 The difference between the biological sample image acquisition device 300 in FIG. 1 and FIG. 2 is that the number of objective lenses 52 disposed above the two movable platforms 40 is greater than 2 and is equal to the number of layers of a single slide. The focusing planes of all objective lenses 52 disposed above the two movable platforms 40 are located at different heights above the movable platforms 40. Each objective lens 52 is used to focus light on a different layer of a slide of the biological sample 20, thereby stimulating the fluorescent markers of the biological sample 20 located on different layers of each slide to produce fluorescence, so that different objective lenses 52 collect fluorescence on different slides. In another embodiment, the number of objective lenses 52 disposed above the two movable platforms 40 may be equal, such as both being Figure 5A 5B, of course, it can be 3, 4 or more; it can also be different, such as 1 above one movable platform 40 and 2 above another movable platform 40. The height of the focal plane of the objective lens 52 above the movable platform 40 can be greater than the height of the focal plane of the objective lens 52 above the other movable platform 40, such as Figure 6 The heights of the focal planes of the multiple objective lenses 52 on the left are all greater than the heights of the focal planes of the multiple objective lenses 52 on the right; they may also be partially greater than the height of the focal plane of the objective lens 52 above another movable platform 40, and partially less than the height of the focal plane of the objective lens 52 above another movable platform 40. The basic principle is to ensure that the biological samples 20 on each layer of the slide are collected by the corresponding objective lens 52. When the two movable platforms 40 move in the same direction and at the same speed relative to the center of the array so that the objective lens 52 above one movable platform 40 has collected the fluorescence on the corresponding slide, the sample position exchange component 60 exchanges the positions of the two biological samples 20 under the objective lens 52. Figure 7 The sample position exchange member 60 shown in the figure is the manipulator 62 and the two rotating platforms 64. It can be understood that the sample position exchange member 60 can also be Figure 6 After the movable platforms 40 exchange the positions of the two biological samples 20, the two movable platforms 40 move again in the same direction and at the same speed relative to the center of the array so that the objective lenses 52 above the movable platforms 40 respectively collect the fluorescence on the remaining slides of the biological samples 20. In this way, the fluorescence on the multi-layer slides is collected by multiple objective lenses 52, so that the image sensor 55 obtains the fluorescence image of the biological sample 20.

[0048] See also Figure 8, is another embodiment of the arrangement of the movable platforms 40. In this embodiment, the number of the movable platforms 40 is an even number greater than 2, and all the movable platforms 40 are arranged on the support member 30 in a rectangular shape, and the center of the array is the center of the rectangle. Fig. 9 The light source output element 51 outputs an even number of light beams greater than 2, and the light beams are projected one-to-one onto the first dichroic mirrors 53 corresponding to each movable platform 40, and are focused by the corresponding objective lens 52, so that the fluorescent markers in the biological sample 20 on each movable platform 40 generate fluorescence. The light source output element 51 includes a laser emitter 515, an optical splitter 516, and a plurality of collimators 517. The laser emitter 515 outputs laser light, and the optical splitter 516 includes a laser inlet and a plurality of laser outlets. The optical splitter 516 divides the laser light input from the laser inlet into a plurality of laser lights of equal power and outputs them from the plurality of laser outlets. The number of the collimators 517 is the same as the number of the objective lenses 52, and is used to collimate the laser light output from the plurality of laser outlets into parallel light, and project it onto the plurality of first dichroic mirrors 53, and then onto the plurality of objective lenses 52. The light source output member 51 may further include a plurality of reflectors (not shown) for directing the parallel light output by the collimator 517 to the first dichroic mirror 53 according to the position of the first dichroic mirror 53. When collecting an image of the biological sample 20, all movable platforms 40 approach or move away from the two symmetric axes of the rectangle, such as Figure 8 The first axis X and the second axis Y in the movable platform 40 are moved so that the objective lens 52 located above the movable platform 40 collects the fluorescence, and the light is guided to the image sensor 55 through the first dichroic mirror 53 and the light guide 54 to generate a plurality of fluorescence images of the biological samples 20. Since an even number of movable platforms 40 move toward or away from the symmetry axis of the rectangle, during the movement, the forces of all movable platforms 40 relative to the support member 30 cancel each other out, thereby preventing the entire support member 30 and the biological sample 20 placed on the movable platform 40 from vibrating, so that the objective lens 52 obtains accurate fluorescence distribution, and the image sensor 55 forms a high-quality fluorescence image of the biological sample 20.

[0049] See also Fig.10, is an arrangement of the movable platforms 40 in another embodiment. In this embodiment, a plurality of the movable platforms 40 are evenly arranged on the support 30 in a circular shape, the angle α between every two movable platforms 40 is equal, and the center of the array is the center of the circle. When collecting an image of the biological sample 20, all the movable platforms 40 move toward or away from the center of the circle so that the objective lens 52 located above the movable platform 40 collects fluorescence, and guides the light into the image sensor 55 through the first dichroic mirror 53 and the light guide 54 to generate a plurality of fluorescent images of the biological samples 20. As the plurality of movable platforms 40 move toward or away from the center of the circle, during the movement, the forces acting on the support 30 by all the movable platforms 40 cancel each other, thereby preventing the support 30 as a whole and the biological sample 20 placed on the movable platform 40 from vibrating, so that the objective lens 52 obtains accurate fluorescence distribution, and the image sensor 55 forms a high-quality fluorescent image of the biological sample 20.

[0050] Figure 8 and Fig.10 The movable platform 40 may also include Figure 6 and Figure 7 The sample position exchange member 60 is used to replace the biological sample 20 under the objective lens 52, thereby completing the acquisition of images of biological samples 20 whose number is greater than 2 and includes multiple layers of slides.

[0051] The multiple movable platforms 40 of the above-mentioned biological sample image acquisition devices 100, 200, 300, and 400 are arranged in an array on the support member 30, and move in the same direction and at the same speed relative to the array center of the multiple movable platforms 40. The forces acting on the multiple movable platforms 40 and the forces on the support member 30 offset each other, which can avoid the movement of the movable platforms 40 causing vibrations to the entire support member 30 and the biological sample 20, so that the objective lens 52 obtains accurate fluorescence distribution, thereby allowing the image sensor 55 to form a high-quality fluorescence image of the biological sample 20. Compared with the prior art, the biological sample 20 image acquisition device has both a simple structure and the ability to obtain high-quality images of the biological sample 20.

[0052] The present application also provides a gene sequencer, which includes any of the above biological sample image acquisition devices 100, 200, 300, and 400. Since the image quality of the biological sample 20 acquired by the biological sample image acquisition device is high, it is beneficial for the gene sequencer to analyze the base sequence more accurately.

[0053] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solution of the present invention.

Claims

1. A biological sample image acquisition device, comprising a support and an optical imaging component, It is characterized in that The biological sample image acquisition device further comprises: A plurality of movable platforms are movably connected to the support member, and are used to place biological samples and drive the biological samples to move. The plurality of movable platforms are arranged in an array on the support member, and the plurality of movable platforms can move relative to the support member, and the forces acting on the support member during movement can offset each other, so as to avoid vibration of the support member and the biological samples caused by the movement of the movable platforms; The optical imaging component collects images of biological samples on the movable platforms when the multiple movable platforms move relative to the supporting platform.

2. The biological sample image acquisition device according to claim 1, It is characterized in that The optical imaging assembly comprises: A light source output component, used for outputting light; A first dichroic mirror, used for receiving and reflecting light output by the light source output element; an objective lens, placed above the movable platform, for focusing the light reflected by the first dichroic mirror onto the biological sample to excite the fluorescent marker in the biological sample to generate fluorescence, and projecting the fluorescence onto the first dichroic mirror; The first dichroic mirror is also used to transmit the fluorescence projected by the objective lens; An image sensor, configured to sense the received light to form a fluorescent image of the biological sample; and The light guide is used to guide the fluorescence transmitted by the first dichroic mirror to the image sensor.

3. The biological sample image acquisition device according to claim 2, It is characterized in that The biological sample image acquisition device comprises a plurality of objective lenses and an image sensor, and the light-sensitive range of the image sensor is greater than the sum of the imaging ranges of the plurality of objective lenses.

4. The biological sample image acquisition device according to claim 2, It is characterized in that A plurality of objective lenses are arranged above each of the movable platforms, and the objective lenses are spaced at equal distances from each other. The projections of the objective lenses divide the biological sample into a plurality of parts with equal intervals.

5. The biological sample image acquisition device according to claim 1, It is characterized in that It includes multiple objective lenses and a sample position exchange component. The focusing surfaces of all the objective lenses are located at different heights above the movable platform. Each objective lens is used to focus light on a slide of a biological sample including multiple slides. When the multiple movable platforms move relative to the support component so that the multiple objective lenses respectively collect the fluorescence located on one slide, the sample position exchange component exchanges the positions of the biological samples under the multiple objective lenses.

6. The biological sample image acquisition device according to claim 5, It is characterized in that The sample position exchange component is a rotating platform connected to the multiple movable platforms at the same time. The multiple movable platforms are movably connected to the rotating platform. The rotating platform is rotatably arranged on a support and can be rotated around the center of the array on a plane parallel to the movable platforms to exchange the positions of the multiple movable platforms.

7. The biological sample image acquisition device according to claim 5, It is characterized in that The sample position exchange component includes a manipulator and multiple rotating platforms respectively connected to multiple movable platforms. The manipulator places the biological sample on one movable platform on another movable platform. The multiple rotating platforms can drive the movable platforms to rotate on a plane parallel to the movable platforms.

8. The biological sample image acquisition device according to any one of claims 1 to 7, It is characterized in that The number of the movable platforms is an even number, and all the movable platforms are arranged on the support member in a rectangular shape, and the even number of movable platforms move towards or away from the symmetry axis of the rectangle at the same time.

9. The biological sample image acquisition device according to any one of claims 1 to 7, It is characterized in that The multiple movable platforms are evenly arranged on the support member in a circular shape, the angles between every two movable platforms are equal, and all movable platforms move towards or away from the center of the circle at the same time.

10. A gene sequencer, It is characterized in that The invention comprises a biological sample image acquisition device as claimed in any one of claims 1 to 9.

Images