Optical imaging system and sequencer

Abstract

The invention provides an optical imaging system, and the system comprises an illumination module which is used for transmitting illumination laser; the carrying platform module is used for carrying a sample, and the sample carries a fluorophore; the light guiding module is located on a light path of the illumination laser and used for receiving and guiding the illumination laser to the carrying table module, the illumination laser excites the fluorophore to generate detection fluorescence when irradiating the sample, and the light guiding module is further located on a light path of the detection fluorescence and used for receiving the detection fluorescence; the imaging module is used for receiving the detection fluorescence from the light guiding module and generating a fluorescence image of the sample according to the detection fluorescence, and the fluorescence image is used for acquiring base sequence information of the sample; the illumination module, the light guiding module, the carrying table module and the imaging module are connected to the main body frame, and the main body frame is used for keeping the relative positions of the illumination module, the light guiding module, the carrying table module and the imaging module. The invention further provides a sequencer.

Description

Technical Field

[0001] This application relates to the field of gene sequencing technology, and particularly to an optical imaging system and a sequencer including the optical imaging system. Background Art

[0002] With the rapid development of gene detection technology, traditional sequencers for gene detection include an optical system for collecting fluorescence images. To collect accurate fluorescence images, there are high requirements for the stability and precision of the optical path structure of the optical system. Summary of the Invention

[0003] A first aspect of this application provides an optical imaging system, including:

[0004] An illumination module for emitting illumination laser;

[0005] A stage module for carrying a sample, where the sample carries fluorescent groups;

[0006] An optical guiding module located on the optical path of the illumination laser, for receiving and guiding the illumination laser to the stage module. When the illumination laser irradiates the sample, the fluorescent groups are excited to generate detection fluorescence. The optical guiding module is also located on the optical path of the detection fluorescence for receiving the detection fluorescence;

[0007] An imaging module for receiving the detection fluorescence from the optical guiding module and generating a fluorescence image of the sample according to the detection fluorescence, where the fluorescence image is used to obtain base sequence information of the sample; and

[0008] A main body frame, to which the illumination module, the optical guiding module, the stage module and the imaging module are connected. The main body frame is used to maintain the relative positions among the illumination module, the optical guiding module, the stage module and the imaging module.

[0009] A second aspect of this application further provides a sequencer, including:

[0010] The optical imaging system as described above;

[0011] An image processing system electrically connected to the imaging module, for obtaining base sequence information of the sample according to the fluorescence image generated by the imaging module.

[0012] For the above optical imaging system and sequencer, by fixing and maintaining the relative positions among the illumination module, the optical guiding module, the stage module and the imaging module through the main body frame, it is beneficial to improve the stability and precision of the optical path structure formed by each functional module in the optical imaging system. Description of the Drawings

[0013] Figure 1 Schematic diagram of the module structure of the optical imaging system according to an embodiment of the present application.

[0014] Figure 2 Exploded view of a partial structure of the optical imaging system according to an embodiment of the present application.

[0015] Figure 3 is Figure 2 Schematic perspective view of the top plate in

[0016] Figure 4 is Figure 2 Schematic view of the structure of the middle plate.

[0017] Figure 5 is Figure 2 Partial schematic perspective view of the optical system in

[0018] Figure 6 is Figure 5 Schematic perspective view of a stereo structure of the camera assembly in

[0019] Figure 7 is Figure 5 Another schematic perspective view of the stereo structure of the camera assembly in

[0020] Figure 8 is Figure 5 Another schematic perspective view of the stereo structure of the camera assembly in

[0021] Figure 9 is Figure 5 Schematic perspective view of the structure of the mirror assembly in

[0022] Figure 10 is Figure 5 Schematic perspective view of the structure of the dichroic mirror assembly in

[0023] Figure 11 is Figure 5 Exploded view of the dichroic mirror assembly in

[0024] Description of main element symbols

[0025] Optical imaging system 100 Left and right adjusting member 415

[0026] Main body frame 10 Up and down adjusting member 416

[0027] Bottom plate 11 Rotating adjusting member 417

[0028] Counterbore 1511 Boss 4171

[0029] Side plate 12 Mirror assembly 42

[0030] Top plate 13 Mirror 421

[0031] Surfaces 131, 132, mounting base 422

[0032] Mounting holes 133, horizontal mounting plate 4221

[0033] Vertical plate 14, vertical mounting plate 4222

[0034] First mounting portion 141, positioning holes 4223, 4251, 4152, 5241, 5233, 5251, 5253, 5234, 5235, 5226

[0039] Second mounting portion 142, bolts 4225, 4253

[0040] Support frame 15, horizontal adjusting member 423

[0041] Support plate 151, adjusting holes 4231, 4241, 5223, 5231, 5227

[0044] Support column 152, vertical adjusting member 424

[0045] Vibration isolation device 153, fixing bracket 425

[0046] Illumination module 20, barrel lens assembly 43

[0047] Stage module 30, dichroic mirror assembly 52

[0048] Imaging module 40, dichroic mirror 521

[0049] Camera assembly 41, lens frame 522

[0050] Camera 411, mounting bracket 5221

[0051] Camera fixing seat 412, connecting portion 5222

[0052] Imaging module 40, adapter block 523

[0053] Camera assembly 41, first auxiliary adjusting member 524

[0055] Camera 411, pins 5242, 5252, 5254

[0057] Camera fixing seat 412, second auxiliary adjusting member 525

[0059] Slot holes 4121, 4131, receiving space S 4133, 4134

[0061] Fixing holes 4122, 4123, screws 4141, 4151, 4223, 4224, 4161 4251, 4252

[0064] Camera base 413, chute 5236

[0065] Front - rear adjusting member 414

[0066] The following specific embodiments will further illustrate the present application in conjunction with the above - mentioned drawings. Specific embodiments

[0067] The present application provides a sequencer. The sequencer includes an optical imaging system and an image processing system. The optical imaging system is used to collect multiple fluorescence images of a nucleic acid sample, and the image processing system is used to perform a preset process on the multiple fluorescence images to obtain the base sequence information of the nucleic acid sample.

[0068] Please refer to Figure 1 , the optical imaging system 100 of this embodiment includes an illumination module 20, a stage module 30, an imaging module 40, and an optical guiding module 50. The illumination module 20 is used to emit illumination laser, and the illumination laser is used to irradiate the nucleic acid sample. The stage module 30 is used to carry a sequencing chip. A nucleic acid sample is carried on the surface of the sequencing chip away from the stage module 30. The nucleic acid sample carries a fluorescent group. When the fluorescent group is irradiated by the illumination laser, it is excited to generate detection fluorescence. The imaging module 40 is used to receive the detection fluorescence to generate a fluorescence image of the nucleic acid sample. The optical guiding module 50 is located on the optical paths of the illumination laser and the detection fluorescence, and is used to guide the illumination laser emitted by the illumination module 20 to the nucleic acid sample, and is used to guide the detection fluorescence to the imaging module 40.

[0069] Different bases (including bases A, T, G, C) on the nucleic acid sample carry different types of fluorescent groups, and different types of fluorescent groups generate detection fluorescence with different wavelengths when excited by the illumination laser. The imaging module 40 generates different fluorescence images based on the detection fluorescence with different wavelengths. By processing the multiple fluorescence images generated by the imaging module 40, the base sequence information of the nucleic acid sample can be obtained.

[0070] Due to the limited field of view of the illumination laser, it is difficult for the illumination laser to completely cover the surface of the nucleic acid sample. In this embodiment, by controlling the stage module 30 to synchronously drive the displacement of the sequencing chip, different positions on the surface of the nucleic acid sample can be successively located within the field of view of the illumination laser. This process can be referred to as the scanning process of the illumination laser on the nucleic acid sample. Through the above scanning process, fluorescence images of all regions of the nucleic acid sample (each region has one or more corresponding fluorescence images) can be obtained to acquire the base sequence information of all regions of the nucleic acid sample.

[0071] Please refer to Figure 2 , the optical imaging system 100 further includes a main frame 10. The illumination module ( Figure 2 not shown in the figure), the stage module ( Figure 2 not shown in the figure), the imaging module 40, and the light guiding module 50 are connected to the main frame 10. The main frame 10 is used to fix the illumination module, the stage module, the imaging module 40, and the light guiding module 50, and maintain the relative positional relationship among the illumination module, the stage module, the imaging module 40, and the light guiding module 50.

[0072] In this embodiment, the main frame 10 includes a bottom plate 11, two side plates 12, a top plate 13, a vertical plate 14, and a support frame 15. The two side plates 12 are integrally formed with the bottom plate 11, and the connection part adopts an arc transition, so that the bottom plate 11 and the two side plates 12 are integrally in a "U" shape and form a receiving space S. The stage module can be fixedly arranged on the surface of the bottom plate 11 and is located within the receiving space S. The stage module 30 is used to carry the sequencing chip and can be displaced in three directions, thereby driving the sequencing chip to displace synchronously, so that the illumination laser can irradiate different positions on the sequencing chip, and thus irradiate different positions of the sample.

[0073] The top plate 13 is fixedly connected to the surfaces of the two side plates 12 away from the bottom plate 11. The top plate 13 has parallel surfaces 131 and 132. The surface 132 is located between the bottom plate 11 and the surface 131. The surface 132 of the top plate 13 adopts a honeycomb structure (refer to Figure 3 ), which is beneficial to reducing the overall weight of the system and lowering the center of gravity. An installation hole 133 penetrating through the surfaces 131 and 132 is also opened on the top plate 13 for installing the objective lens.

[0074] The support frame 15 includes a support plate 151 and four support columns 152. The support plate 151 is a rectangular thin plate as a whole, and the four support columns 152 are fixedly connected to two opposite short sides in pairs.

[0075] On each of the two long sides of the support plate 151, five M6 countersunk holes 1511 are formed. The countersunk holes 1511 are used to fix the support plate 151 to the tabletop or external instruments. The support plate 151 is also provided with screw holes for fixedly connecting the support plate 151 to the bottom plate 11. One end of each support column 152 is fixedly connected to the support plate 151, and the other end is connected with a vibration isolation device 153. Each vibration isolation device 153 contains two damping pads (not shown in the figure). As a whole, it can support the weight of the optical machine over 100 kg and can isolate vibration frequencies above 30 HZ. Each vibration isolation device 153 is fixedly installed on the outer surface (the surface away from the accommodation space S) of the side plate 12 by screws. When the support plate 15 is assembled to the side plate 12, the support plate 151 and the bottom plate 11 are arranged substantially parallel, and the bottom plate 11 is suspended relative to the support plate 151.

[0076] Please refer to Figure 2 and Figure 4 simultaneously. The vertical plate 14 is fixedly connected to the surface 131 and extends in a direction away from the surface 131. The vertical plate 14 includes a fixedly connected first mounting portion 141 and a second mounting portion 142, wherein the first mounting portion 141 is connected between the top plate 13 and the second mounting portion 142. The imaging module 40 is partially fixed to the first mounting portion 141 and partially fixed to the second mounting portion 142, and the light guiding module 50 is fixed to the first mounting portion 141. The vertical plate 14 is assembled and fixed by the first mounting portion 141 and the second mounting portion 142. Compared with the vertical plate 14 formed by integrally molding the first mounting portion 141 and the second mounting portion 142, it is beneficial to simplify the process.

[0077] Please refer to Figure 5 In this embodiment, the imaging module 40 includes a camera assembly 41, a mirror assembly 42, a tube lens assembly 43, and a filter assembly 44. The filter assembly 44 is used to transmit the detection fluorescence of a preset wavelength. The detection fluorescence of the preset wavelength transmitted by the filter assembly 44 is successively guided to the camera assembly 41 through the tube lens assembly 43 and the mirror assembly 42. The camera assembly 41 includes a camera 411. In this embodiment, the camera 411 is a Time Delay Integration (TDI) camera, that is, a line array camera. The photosensitive surface of the camera 411 is used to sense the detection fluorescence, and corresponding electrical signals are output according to the sensed detection fluorescence to generate a fluorescence image. The cameras 411 in the two imaging channels are used to receive detection fluorescence of different wavelengths to generate fluorescence images.

[0078] Please refer to Figures 6 to 8 simultaneously. The camera assembly 41 further includes a camera fixing base 412, a camera base 413, a front and rear adjusting member 414, a left and right adjusting member 415, an up and down adjusting member 416, and a rotation adjusting member 417.

[0079] The camera fixing base 412 is fixedly connected to the first mounting portion 141. Two slotted pin holes are provided on the camera fixing base 412. With the cooperation of positioning pins, the approximate position of the imaging focal plane of the camera 411 in the optical axis direction can be determined. In this embodiment, the camera fixing base 412 is a substantially rectangular block. At the four corner positions of the camera fixing base 412, there are respectively provided long slot holes 4121 perpendicular to the optical axis direction. Screws passing through the slot holes 4121 can fix the entire camera assembly 41 on the first mounting portion 141.

[0080] A fixing hole 4122 is formed on one side of the camera fixing base 412 parallel to the optical axis. The left - right adjusting member 415 is connected to the camera fixing base 412 through the fixing hole 4122. The left - right adjusting member 415 includes a screw rod 4151. By slightly rotating the screw rod 4151, the camera fixing base 412 can be precisely pushed to displace in the direction perpendicular to the optical axis and parallel to the top plate 13 until the central pixel of the camera 411 in the displacement direction coincides with the optical axis.

[0081] Two fixing holes 4123 are formed on one side of the camera fixing base 412 perpendicular to the optical axis. The front - rear adjusting member 414 is fixed to the camera fixing base 412 through the fixing holes 4123. The camera base 413 is connected to the surface of the camera fixing base 412 away from the top plate 13. The front - rear adjusting member 414 includes a screw rod 4141, and the screw rod 4141 is buckled on the camera base 413. By slightly rotating the fine - tuning screw rod 4141, the camera base 413 can be pushed to drive the camera 411 to move back and forth on the camera fixing base 412 along the direction parallel to the optical axis and parallel to the top plate 13, realizing the adjustment of the focal plane position of the camera 411.

[0082] The camera base 413 is generally in a "T" - shaped structure and is fixedly connected to the surface of the camera fixing base 412 away from the top plate 13. In this embodiment, the surface of the camera base 413 directly contacting the camera fixing base 412 is substantially rectangular, and long slot holes 4131 along the optical axis direction are respectively provided at its four corners. The slot holes 4131 cooperate with the positioning pins on the camera fixing base 412 to provide guidance for the fine - tuning of the camera 411 in the direction parallel to the optical axis.

[0083] A threaded hole 4132 is formed at the top end of the camera base 413 away from the top plate 13. The up - down adjusting member 416 includes a screw rod 4161, and the screw rod 4161 is connected to the threaded hole 4132. Four long slot holes 4133 are also formed on the camera base 413. Cooperating with the up - down adjusting member 416, by slightly rotating the screw rod 4161, the camera 411 can be driven to displace in the direction perpendicular to the optical axis and the top plate 13, facilitating the alignment of the central pixel of the camera 411 in the displacement direction with the optical axis.

[0084] The rotation adjustment member 417 is integrally a frame structure with a central opening, and the central opening corresponds to the photosensitive surface of the camera 411. A boss 4171 is formed at the top end of the rotation adjustment member 417 away from the camera fixing base 412. A slot-shaped hole and a threaded hole are formed on the boss 4171. By cooperating with precision adjustment screws and setscrews, precise rotation adjustment of the camera 411 in a plane perpendicular to the optical axis can be achieved. Four arc-shaped slot holes 4134 are also formed on the camera base 413. By cooperating with the rotation adjustment member 417, the angular position of the camera 411 can be fixed after the rotation adjustment of the camera 411 is completed.

[0085] The front-back adjustment member 414, the left-right adjustment member 415, the up-down adjustment member 416, and the rotation adjustment member 417 respectively finely adjust the position and angle of the camera 411 in different dimensions, which is beneficial to improving the consistency of multiple indexes such as the imaging quality of the cameras in the two imaging channels and the performance of the optical system.

[0086] Please refer to Figure 9 , the mirror assembly 42 includes a mirror 421, a mounting base 422, a horizontal adjustment member 423, a vertical adjustment member 424, and a fixing frame 425. The mounting base 422 has a horizontal mounting plate 4221 and a vertical mounting plate 4222 fixedly connected to the horizontal mounting plate 4221. The horizontal mounting plate 4221 and the horizontal adjustment member 423 are connected to the surface 131 of the top plate 13. The extending direction of the vertical mounting plate 4222 is perpendicular to the horizontal mounting plate 4221. The vertical adjustment member 424 and the fixing frame 425 are connected to the vertical mounting plate 4222. The fixing frame 425 is integrally a rectangular frame structure, and the mirror 421 is fixed within the frame structure of the fixing frame 425. In this embodiment, a gap is left between the mirror 421 and the fixing frame 425, which is beneficial to reducing the stress on the mirror 421 and improving the imaging quality. Glue can be injected on the surface of the mirror 421 parallel to the light-receiving surface (the surface for receiving and reflecting the detected fluorescence) to fix the mirror 421 to the fixing frame 425, preventing the mirror 421 from being deformed by lateral stress (the stress parallel to the light-receiving surface of the mirror) so as to cause a decrease in imaging quality. When the mirror 421 is installed on the fixing frame 425, it is perpendicular to the top plate 13.

[0087] A positioning hole 4223 is also formed on the horizontal mounting plate 4221. By inserting a pin into the positioning hole 4223, the entire mirror assembly 42 can be positioned at a corresponding position on the surface 131. Two adjustment holes 4231 are provided on the horizontal adjustment member 423, respectively located on both sides of the fixing hole 4223. The extending direction of the adjustment hole 4231 is perpendicular to the extending direction of the fixing hole 4223. By inserting a setscrew into the adjustment hole 4231, the horizontal mounting plate 4221 can be pushed to rotate and finely adjust around the axis of the pin in the fixing hole 4223. That is, the horizontal mounting plate 4221 can be pushed to rotate and finely adjust around an axis perpendicular to the top plate 13. When the horizontal mounting plate 4221 rotates, it drives the vertical mounting plate 4222, the fixing bracket 425, and the mirror 421 to rotate synchronously. Two fixing holes 4224 are also formed on the horizontal mounting plate 4221. When the mirror 421 rotates to a preset angular position, the mirror 421 can be locked in the rotation direction through the bolt 4225 and the fixing hole 4224.

[0088] A positioning hole 4251 is formed on the fixing bracket 425. By inserting a pin into the positioning hole 4251, the fixing bracket 425 and the mirror 421 can be positioned at corresponding positions on the vertical mounting plate 4222 as a whole. Two adjustment holes 4241 are provided on the vertical adjustment member 424, respectively located on both sides of the positioning hole 4251. The extending direction of the adjustment hole 4241 is perpendicular to the extending direction of the positioning hole 4152. By inserting setscrews into the two adjustment holes 4241, the fixing bracket 425 can be pushed to rotate and finely adjust around the axis of the pin in the fixing hole 4251. That is, the fixing bracket 425 can be pushed to rotate and finely adjust around an axis parallel to the top plate 13. When the fixing bracket 425 rotates, it drives the mirror 421 to rotate synchronously. Two fixing holes 4252 are also formed on the fixing bracket 425. When the mirror 421 rotates to a preset angular position, the fixing bracket 425 and the mirror 421 can be locked in the rotation direction through the bolt 4253 and the fixing hole 4252.

[0089] The mirror 421 can be adjusted and fixed at multiple different angular dimensions, which is beneficial for the turning point and turning angle of the turning optical path to reach an ideal state.

[0090] Please refer to Figure 5 again. In this embodiment, the light guiding module 50 includes an objective lens assembly 51 and a dichroic mirror assembly 52. The objective lens assembly 51 is used to guide the illumination laser from the illumination module to the sequencing chip. The dichroic mirror assembly 52 is located on the optical path of the illumination laser and the detected fluorescence, and is used to reflect the illumination laser to the sequencing chip and transmit the detected fluorescence. The detected fluorescence is finally received by the camera 411.

[0091] Please refer to Figure 10 and Figure 11, the dichroic mirror assembly 52 includes a dichroic mirror 521, a mirror frame 522, an adapter block 523, a first auxiliary adjustment member 524, and a second auxiliary adjustment member 525. The mirror frame 522, the first auxiliary adjustment member 524, and the second auxiliary adjustment member 525 are respectively connected to the adapter block 523, and the adapter block 523 is fixed to the vertical plate 14 by four bolts 5230.

[0092] The mirror frame 522 has a mounting bracket 5221 and a connecting portion 5222. The mounting bracket 5221 is a frame structure with a mounting hole in the center, and the dichroic mirror 521 is mounted in the mounting hole. In this embodiment, there is a gap between the dichroic mirror 521 and the mounting bracket 5221, which is beneficial to reducing the stress in the direction parallel to the light-receiving surface of the dichroic mirror 521. In this embodiment, the dichroic mirror 521 is fixed to the mounting bracket 5221 by injecting glue on the surface of the dichroic mirror 521 parallel to the light-receiving surface, which is beneficial to avoiding extrusion of the dichroic mirror 521 in the direction parallel to the light-receiving surface S during the curing process of the glue. In other embodiments of the present application, the dichroic mirror 521 can be directly placed in the mounting hole of the mounting bracket 5221 without using other structures (such as injecting glue) for fixation. Since the dichroic mirror 521 itself has a certain inclination (the light-receiving surface forms a 45° angle with the surface 131), it can also be kept in the mounting hole without falling off when directly placed.

[0093] The connecting portion 5222 includes a first extension portion 5224 and a second extension portion 5225 extending outward from the mounting bracket 5221. The first extension portion 5224 and the second extension portion 5225 are respectively connected to opposite sides of the adapter block 523. In this embodiment, the structures of the first extension portion 5224 and the second extension portion 5225 are basically the same. Taking the first extension portion 5224 as an example, a positioning hole 5226 and two adjustment holes 5227 located on both sides of the positioning hole 5226 are provided on the first extension portion 5224. The extending direction of the positioning hole 5226 is parallel to the light-receiving surface of the dichroic mirror 521, and the extending direction of the adjustment hole 5227 is parallel to the light-receiving surface of the dichroic mirror 521 and perpendicular to the extending direction of the positioning hole 5226. The first extension portion 5224 can be positioned on the adapter block 523 by inserting a pin into the positioning hole 5226. Since the adapter block 523 is also connected to the first mounting portion 141, by inserting a setscrew into the adjustment hole 5227 and adjusting the insertion depth of the setscrew in the two adjustment holes 5227, the mirror frame 522 can be pushed to finely rotate axially around the pin in the positioning hole 5226, thereby synchronously pushing the dichroic mirror 521 to finely rotate axially around the pin in the positioning hole 5226.

[0094] The first auxiliary adjusting member 524 is provided with a positioning hole 5241, and the adapter block 523 is provided with a positioning hole 5233 corresponding to the positioning hole 5241. By inserting the pin 5242 into the positioning holes 5241 and 5233, the first auxiliary adjusting member 524 can be positioned on the adapter block 523. The first auxiliary adjusting member 524 is also provided with two adjusting holes 5243. By inserting the set screws into the two adjusting holes 5243, the dichroic mirror 521 and the lens frame 522 can be pushed to linearly displace in a direction perpendicular to the dichroic mirror 521.

[0095] The second auxiliary adjusting member 525 is provided with positioning holes 5251 and 5253, and the adapter block 523 is correspondingly provided with positioning holes 5235 and 5234. By inserting the pin 5252 into the positioning hole 5251 and the positioning hole 5235, and inserting the pin 5254 into the positioning holes 5253 and 5234, the second auxiliary adjusting member 525 can be fixed to the adapter block 523. Among them, the pin 5252 is in close fit with the positioning holes 5251 and 5235, so that the pin 5252 is fastened in the positioning holes 5251 and 5235; while the positioning hole 5234 has a space reserved for fine adjustment of the pin 5254. The extending directions of the positioning holes 5251, 5253, 5235 and 5234 are parallel to the light-receiving surface (the surface for receiving the detected fluorescence) of the dichroic mirror 521.

[0096] The adapter block 523 is provided with two adjusting holes 5231. The extending directions of the two adjusting holes 5231 are perpendicular to the extending directions of the positioning holes 5251, 5253, 5235 and 5234 and parallel to the light-receiving surface of the dichroic mirror 521. By respectively pushing two set screws into the two adjusting holes 5231 and respectively controlling the depths of the two set screws pushed into the adjusting holes 5231, the fine adjustment rotation of the lens frame 522 and the dichroic mirror 521 around the axis of the pin 5252 can be controlled.

[0097] In this embodiment, the adapter block 523 is further provided with a sliding groove 5236, and the length extending direction of the sliding groove 5236 is perpendicular to the light-receiving surface of the dichroic mirror 521. The first auxiliary adjusting member 524 and the second auxiliary adjusting member 525 are fixed in the sliding groove 5236, and the positioning holes 5233, 5234 and 5235 are opened in the sliding groove 5236.

[0098] In this embodiment, by forming the connecting portion 5222 and connecting the connecting portion 5222 with the adapter block 523, it is beneficial to avoid opening holes in the mounting frame 5221, thereby avoiding squeezing the dichroic mirror 521 in the plane direction parallel to the dichroic mirror 521 during the process of locking or adjusting the position of the dichroic mirror 521, which is beneficial to releasing stress, avoiding deformation of the dichroic mirror 521 due to force, and further beneficial to improving the imaging quality of the fluorescence image.

[0099] Please refer to Figure 5, in the optical imaging system 100 of this embodiment, the imaging module 40 and a part of the light guiding module 50 are fixed to the vertical plate 14, so that the detected fluorescence is incident on the imaging module 40 from the light guiding module 50 in a direction perpendicular to the top plate 13. Some functional modules in the optical imaging system 100 are arranged in a direction perpendicular to the surface 131, which is beneficial to reducing the area of the surface 131.

[0100] For the above-mentioned optical imaging system 100 and the sequencer of this application, precise assembly of each functional module (including the illumination module 20, the stage module 30, the imaging module 40, and the light guiding module 50) in the optical imaging system 100 is achieved through the main body frame 10. By analyzing the vibration frequency data through ANSYS simulation, its first-order vibration frequency exceeds 260 HZ, greatly reducing the resonance risk caused by the internal vibration source of the optical imaging system 100, and vibration frequencies above 30 HZ can be filtered out.

[0101] In this embodiment, the first mounting portion 141 forms a closed space for accommodating a part of the imaging module 40, a part of the light guiding module 50, etc., so that the optical path located in the first mounting portion 141 is isolated from ambient light.

[0102] Furthermore, the adapter block 523 of the dichroic mirror assembly 52 is directly fixed to the first mounting portion 141 of the vertical plate 14 by bolts. When the dichroic mirror assembly 52 is fixed to the first mounting portion 141, the dichroic mirror 521 and the mounting bracket 5221 are located in the closed space of the first mounting portion 141, while the connecting portion 5222, the adapter block 523, the first auxiliary adjusting member 524, and the second auxiliary adjusting member 525 are exposed outside the closed space of the first mounting portion 141, which is beneficial to improving the convenience when finely adjusting the dichroic mirror assembly 52.

[0103] Those of ordinary skill in the art of this technology should recognize that the above embodiments are only used to illustrate this application, rather than to limit this application. As long as within the scope of the substantial spirit of this application, appropriate changes and variations made to the above embodiments fall within the scope claimed by this application.

Claims

1. An optical imaging system, characterized in that: include: An illumination module, used for emitting illumination laser; A stage module, used for carrying a sample, wherein the sample carries a fluorescent group; A light guiding module is located on the optical path of the illumination laser and is used to receive and guide the illumination laser to the stage module. When the illumination laser irradiates the sample, the fluorescent group is excited to generate detection fluorescence. The light guiding module is also located on the optical path of the detection fluorescence and is used to receive the detection fluorescence. An imaging module, used for receiving the detection fluorescence from the light guiding module, and generating a fluorescence image of the sample according to the detection fluorescence, wherein the fluorescence image is used for obtaining base sequence information of the sample; as well as A main frame, wherein the lighting module, the light guiding module, the stage module and the imaging module are connected to the main frame, and the main frame is used to maintain the relative positions among the lighting module, the light guiding module, the stage module and the imaging module.

2. The optical imaging system according to claim 1, wherein: The main framework includes: Base plate; Two side panels, the two side panels are integrally formed with the bottom panel to form a receiving space, the stage module is connected to the surface of the bottom panel and is located in the receiving space; A top plate, fixedly connected to a side of the two side plates away from the bottom plate; and A vertical plate is fixedly connected to a surface of the top plate away from the bottom plate, and the imaging module and a part of the light guiding module are connected to the vertical plate.

3. The optical imaging system according to claim 2, wherein: The vertical plate includes a first mounting portion and a second mounting portion fixedly connected to each other, the first mounting portion is fixedly connected to the top plate, and the second mounting portion is fixedly connected to an end of the first mounting portion away from the top plate; Part of the imaging module is connected to the second mounting portion, part of the light guiding module is fixedly connected to the first mounting portion, and part of the light guiding module is fixedly connected to the second mounting portion.

4. The optical imaging system according to claim 2, wherein: The main frame also includes a support frame, which includes a support plate, a plurality of process columns and a plurality of vibration isolation devices; One end of each of the support columns is fixedly connected to the support plate, the other end of each of the process columns is fixedly connected to a vibration isolation device, and each of the vibration isolation devices is fixedly connected to the side plate; The bottom plate is parallel to the support plate and is suspended relative to the support plate.

5. The optical imaging system according to claim 2, wherein: The light guide assembly includes a dichroic mirror assembly, the dichroic mirror assembly including: A dichroic mirror, a mirror frame and an adapter block, wherein the dichroic mirror is fixedly mounted on the mirror frame, and the mirror frame is connected to the adapter block; The mirror frame can be displaced relative to the adapter block in a direction perpendicular to the light receiving surface of the dichroic mirror.

6. The optical imaging system according to claim 5, characterized in that: It also includes a first auxiliary adjustment member, wherein the first auxiliary adjustment member is connected to the adapter block; The first auxiliary adjustment member is provided with a positioning hole and an adjustment hole and includes a pin located in the positioning hole. The first auxiliary adjustment member is fixed to the adapter block through the pin, and the mirror frame and the dichroic mirror can be linearly translated in a direction perpendicular to the light-receiving surface of the dichroic mirror.

7. The optical imaging system according to claim 5, characterized in that: It also includes a second auxiliary adjustment member, which is provided with a positioning hole and an adjustment hole and includes a pin installed in the positioning hole and the adjustment hole. The second auxiliary adjustment member is fixed to the adapter block through the pin, and the mirror frame and the dichroic mirror can rotate around the axial direction of the pin.

8. The optical imaging system according to claim 2, wherein: The imaging module comprises a reflector, a mounting base, a horizontal adjustment member, a vertical adjustment member and a fixing frame, wherein the reflector is mounted on the fixing frame, the fixing frame, the horizontal adjustment member and the vertical adjustment member are respectively connected to the mounting base, and the mounting base is connected to the vertical plate; The horizontal adjustment member is used to adjust the mounting base, the fixing frame and the reflector to rotate around an axis perpendicular to the top plate, and the vertical adjustment member is used to adjust the fixing frame and the reflector to rotate around an axis parallel to the top plate.

9. The optical imaging system according to claim 2, wherein: The imaging module includes a camera assembly, which includes a camera, a camera fixing seat, a camera base, a front-to-back adjustment member, a left-to-right adjustment member, an up-and-down adjustment member, and a rotation adjustment member; The camera is mounted on the camera base, the camera fixing seat is connected to the vertical board, the camera base is connected to the surface of the camera fixing seat away from the top board, the left-right adjustment member and the front-back adjustment member are respectively connected to the camera fixing seat and the vertical board, and the up-down adjustment member and the rotation adjustment member are connected to the camera base; The left-right adjustment member is used to adjust the displacement of the camera in a direction perpendicular to the optical axis and parallel to the top plate, the front-back adjustment member is used to adjust the displacement of the camera relative to the camera fixed seat in a direction parallel to the optical axis, the up-down adjustment member is used to adjust the displacement of the camera in a direction perpendicular to the optical axis and the top plate, and the rotation adjustment member is used to adjust the rotation of the camera around an axis parallel to the optical axis.

10. A sequencer, characterized in that: include: The optical imaging system according to any one of claims 1 to 9; An image processing system is electrically connected to the imaging module and is used to obtain base sequence information of the sample according to the fluorescent image generated by the imaging module.

Images