Optical imaging system and genetic sequencing device

Abstract

This disclosure provides an optical imaging system and a gene sequencing device. By setting a distortion compensation mirror and placing it between the tube lens and the imaging sensor, residual distortion in the image can be compensated with high precision while ensuring that the focal length, magnification and image quality performance of the original optical system remain basically unchanged. This improves the geometric consistency of imaging and the positioning accuracy of gene sequencing clusters. Moreover, the structure is simple and easy to process and integrate.

Description

Technical Field

[0001] This disclosure relates to the field of optical technology, and more specifically, to an optical imaging system and a gene sequencing device. Background Technology

[0002] A gene sequencer is a sophisticated analytical device used to analyze the nucleic acid sequence information in biological samples. It is widely used in life science research, clinical diagnosis, drug development, and precision medicine. Gene sequencers typically achieve high-throughput reading of the base sequence by amplifying, labeling, and stepwise detecting nucleic acid molecules.

[0003] With the continuous improvement of sequencing throughput and imaging field of view, gene sequencers are placing higher demands on optical systems in terms of distortion control. Especially under conditions of large field of view and high resolution imaging, optical distortion may cause the geometric position of sequencing clusters to shift, thereby affecting subsequent image analysis and base interpretation results. Summary of the Invention

[0004] This disclosure provides at least one optical imaging system and a gene sequencing device.

[0005] In a first aspect, embodiments of this disclosure provide an optical imaging system, including:

[0006] The light source, and the objective lens, tube lens, distortion compensation lens, and imaging sensor arranged sequentially from the object side to the image side; among them, The light source is used to emit excitation light onto the sequencing object, thereby exciting the sequencing object to generate a fluorescence signal; The objective lens and the tube lens are used to guide the fluorescence signal to the distortion compensation lens; The distortion compensation mirror is located between the tube lens and the imaging sensor, and is used to compensate for the distortion of the fluorescence signal before transmitting it to the imaging sensor; The imaging sensor is used to receive the fluorescence signal and generate and output a fluorescence image.

[0007] In one optional implementation, the distortion compensation mirror is a monolithic lens.

[0008] In one optional implementation, the distortion compensation lens is an even-order aspherical lens.

[0009] In one optional embodiment, the distortion compensation mirror includes an object-side surface and an image-side surface; the radius of curvature of the image-side surface is greater than the radius of curvature of the object-side surface.

[0010] In one optional embodiment, the image-side surface is convex, and the object-side surface is concave.

[0011] In one optional embodiment, the radius of curvature of the object-side surface satisfies: 29000mm≤R1≤29200mm; the radius of curvature of the image-side surface satisfies: 29300mm≤R2≤29400mm; wherein, R1 is the radius of curvature of the object-side surface, and R2 is the radius of curvature of the image-side surface.

[0012] In one optional embodiment, the center thickness of the distortion compensation mirror along the optical axis is between 3 mm and 10 mm.

[0013] In one optional embodiment, the distance between the center of the image-side surface and the image plane is between 5 mm and 10 mm.

[0014] In one optional implementation, the aspherical coefficients of the distortion compensation mirror include 4th-order terms and 6th-order terms.

[0015] In one optional implementation, the aspheric coefficient satisfies: The absolute value of the fourth-order aspheric coefficient of the object-side surface is smaller than the absolute value of the fourth-order aspheric coefficient of the image-side surface. The absolute value of the sixth-order aspheric coefficient of the object-side surface is less than the absolute value of the sixth-order aspheric coefficient of the image-side surface.

[0016] In one optional implementation, the aspheric coefficient satisfies: The fourth-order aspheric coefficient of the object-side surface and the image-side surface is less than 0; the sixth-order aspheric coefficient of the object-side surface and the image-side surface is greater than 0.

[0017] In one optional embodiment, the distortion compensation mirror is made of glass.

[0018] Secondly, embodiments of this disclosure also provide a gene sequencing device, including a fluid system, a computer system, and an optical imaging system as described in the first aspect, or any embodiment of the first aspect; wherein, The flow channel in the fluid system receives the sequencing object, which comes into contact with the reagent and undergoes a chemical reaction in order to carry a fluorescent label. The optical imaging system is configured to excite the fluorescent label carried by the sequencing object and detect the fluorescence signal generated by the excitation of the fluorescent label to output a fluorescence image; The computer system is configured to acquire the fluorescence image from the optical imaging system and identify the gene sequence of the sequencing object based on the fluorescence image.

[0019] It should be understood that the above general description and the following detailed description are merely exemplary and explanatory, and are not intended to limit the technical solutions of this disclosure.

[0020] To make the above-mentioned objects, features and advantages of this disclosure more apparent and understandable, preferred embodiments are described below in detail with reference to the accompanying drawings. Attached Figure Description

[0021] To more clearly illustrate the technical solutions of the embodiments of this disclosure, the accompanying drawings used in the embodiments will be briefly described below. These drawings are incorporated in and constitute a part of this specification. They illustrate embodiments conforming to this disclosure and, together with the specification, serve to explain the technical solutions of this disclosure. It should be understood that the following drawings only show some embodiments of this disclosure and should not be considered as limiting the scope. Those skilled in the art can obtain other related drawings based on these drawings without creative effort.

[0022] Figure 1 Schematic diagrams of optical imaging systems provided in some embodiments of this disclosure are shown; Figure 2 A schematic diagram showing the position of the distortion compensation mirror in the optical path provided in some embodiments of this disclosure is shown; Figure 3 A side view of a distortion compensation mirror provided in some embodiments of this disclosure is shown; Figure 4a A schematic diagram of the distortion rate of an optical imaging system in the prior art is shown; Figure 4b A schematic diagram of the distortion rate of the optical imaging system in an embodiment of this disclosure is shown; Figure 5a A schematic diagram of the modulation transfer function of an optical imaging system in the prior art is shown; Figure 5b A schematic diagram of the modulation transfer function of the optical imaging system in an embodiment of this disclosure is shown; Figure 6a A schematic diagram of wavefront aberration in an optical imaging system in the prior art is shown; Figure 6b A schematic diagram of the wavefront aberration of an optical imaging system in an embodiment of this disclosure is shown; Figure 7a A schematic diagram of transverse chromatic aberration in an optical imaging system of the prior art is shown; Figure 7b A schematic diagram of the transverse chromatic aberration of an optical imaging system according to an embodiment of this disclosure is shown; Figure 8 An embodiment of the present disclosure illustrates a gene sequencing device. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of the embodiments of this disclosure clearer, the technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this disclosure, and not all of them. The components of the embodiments of this disclosure described and shown herein can generally be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of this disclosure is not intended to limit the scope of the claimed disclosure, but merely represents selected embodiments of this disclosure. All other embodiments obtained by those skilled in the art based on the embodiments of this disclosure without inventive effort are within the scope of protection of this disclosure.

[0024] The following section will first introduce the sequencing pretreatment and sequencing process.

[0025] Library Construction: The genomic DNA or RNA molecules to be sequenced are broken down using physical or chemical methods, such as by ultrasound. After breaking, DNA or RNA fragments are formed. First, enzymes are used to fill in the ends of the DNA or RNA fragments. Then, specific enzymes are used to ligate specific DNA or RNA sequences (usually, this specific DNA or RNA sequence is also called a linker) to the ends of the fragments, forming a mixture of DNA or RNA. This mixture of DNA or RNA is also known in the industry as a library.

[0026] To save sequencing costs, multiple samples are typically sequenced simultaneously in a sequencer. To differentiate the sequencing results of different samples, when preparing libraries for each sample, a DNA or RNA sequence (usually containing 6-8 bases) is included in the adapters to identify the sample's origin. This DNA or RNA sequence can also be called a sample tag (or index, barcode). Understandably, each sample's library adapter contains its own unique sample tag.

[0027] Typically, library construction is performed outside of the sequencer, for example, by obtaining the library through experimental procedures in the laboratory.

[0028] Amplification reaction: Taking the amplification of a library via bridge PCR (polymerase chain reaction) as an example, after constructing the library, it can be seeded onto a sequencing chip for amplification. The adapters at both ends of the library are complementary to the first type of amplification primer on the sequencing chip; therefore, complementary hybridization allows the library to be seeded onto the sequencing chip.

[0029] After the library is seeded onto the sequencing chip, it can be used as a template for amplification. For example, the amplification process can begin by adding dNTPs and polymerase to the sequencing chip. The polymerase will synthesize a new DNA strand along the template strand, starting with the first amplification primer. This new DNA strand is completely complementary to the template strand and is therefore called the complementary strand of the template strand. This complementary strand is covalently linked to the sequencing chip. Next, NaOH solution is added to the sequencing chip for rinsing. In the presence of NaOH solution, the template strand and the complementary strand unwind, and the template strand is washed away with the alkali solution, while the complementary strand covalently linked to the sequencing chip is retained. Next, a neutral liquid is added to the sequencing chip to neutralize the NaOH solution. The entire environment within the sequencing chip becomes neutral, allowing the other end of the complementary strand to continue complementary hybridization with the second amplification primer on the sequencing chip. Then, dNTPs and polymerase are added. The polymerase synthesizes a completely new DNA strand, starting from the second amplification primer and continuing along the complementary strand. At this point, the new DNA strand is completely complementary to the complementary strand and identical to the template strand. NaOH solution is then added again to untie the two strands. This yields two covalently linked and complementary strands for the sequencing chip. Repeating this process will exponentially increase the number of DNA strands.

[0030] After amplification, the sequencing chip retains two identical DNA double strands, one matching the template strand and the other the complementary strand. Specific reaction reagents are then added to the chip to cleave the DNA strand synthesized from one of the amplification primers. For example, the DNA strand matching the complementary strand is cleaved, leaving the strand matching the template strand. NaOH solution is then added to the chip for rinsing. The alkali solution unwinds the DNA double strands, and the cleaved strands are washed away, leaving only single-stranded DNA on the chip. The number of single-stranded DNA strands on the chip at this point is exponentially higher than at the start of amplification, forming DNA clusters. All single-stranded DNA strands within a cluster are identical. Adding a neutral solution allows for sequencing of all single-stranded DNA within the cluster under neutral conditions.

[0031] It should be noted that the amplification reaction described above can be performed outside the sequencer, such as amplifying the library in the laboratory through experimental procedures, or it can be performed inside the sequencer. When the amplification reaction is performed inside the sequencer, the library involved in the amplification reaction and various reaction reagents (e.g., dNTPs, polymerase, NaOH alkaline solution, neutral solution, etc.) can be added to the sequencing chip through the sequencer's liquid circuit system. Furthermore, the amplification reaction described above is merely exemplary, and this application is not limited to the bridge PCR amplification method; other amplification methods can also be used, such as loop-mediated isothermal amplification (LAMP), nucleic acid-equation-based amplification (NASBA), rolling circle amplification (RCA), and multiplex probe amplification (MPA).

[0032] Sequencing reaction: Taking the sequencing-by-synthesis principle as an example, during sequencing, four fluorescently labeled dNTPs are added to the sequencing chip via a liquid circuit system. Each dNTP can only be synthesized with one of the four bases ATCG, and the 3' end of each dNTP is blocked by a blocking group (including but not limited to an azide group). Then, polymerase is added to the sequencing chip via the liquid circuit system. Through the action of the polymerase, one of the four dNTPs will be synthesized with a complementary base on the single strand being sequenced. Since the 3' end of the dNTP is blocked by a blocking group, only one dNTP can be extended on the single strand being sequenced at a time. After synthesis, specific chemical reagents are added to the sequencing chip via the liquid circuit system to flush away excess dNTPs and polymerase. Next, the fluorescent labels of the dNTPs synthesized on the single strands can be excited by the optical imaging system, causing the fluorescent labels to emit fluorescent signals. Since the fluorescent labels of the dNTPs on each single strand in a cluster will emit the same fluorescent signal, the fluorescent signal is amplified. Therefore, the optical imaging system can collect the fluorescent signal and generate a fluorescent image.

[0033] By processing and analyzing fluorescence images using a computer system, it can be determined which type of dNTP was synthesized onto the sequenced single strand. Then, based on the complementarity principle, it can be deduced which base on the sequenced single strand was synthesized with the dNTP. This completes one sequencing cycle.

[0034] Next, specific chemical reagents are added to the sequencing chip via a liquid circuit system to remove the blocking groups and fluorescent labels, thereby exposing the 3'-terminal hydroxyl groups of the dNTPs.

[0035] Next, proceed to the next sequencing cycle and repeat the above process.

[0036] As we can understand, one sequencing cycle can detect one base, and through multiple sequencing cycles, multiple bases in the sequenced single strand can be detected. Specifically, the number of sequencing cycles can be determined based on the set sequencing read length, for example, 150 or 300 sequencing cycles.

[0037] Of course, it should also be noted that the above sequencing reactions are merely illustrative, and this application is not limited to using the principle of sequencing by synthesis; other sequencing principles may also be used.

[0038] Research has revealed that in gene sequencing scenarios, optical distortion causes nonlinear distortions in the geometry of clusters within images, such as barrel or pincushion distortion. This severely reduces image fidelity and measurement accuracy, directly impacting image quality and causing cluster displacement within the image. Image analysis software needs to locate each cluster based on preset benchmarks; optical distortion can lead to incorrect cluster positioning, potentially assigning the resolved base signals to the wrong clusters, directly generating sequencing errors and severely affecting the accuracy of base identification. Traditional methods for correcting optical distortion primarily rely on optimizing the lens curvature, thickness, materials, and lens spacing of the imaging sensor (e.g., camera) in the optical imaging system. However, optimizing distortion often requires balancing with other aberrations (such as field curvature and astigmatism) as well as system size and weight, resulting in overall performance that fails to meet the requirements of gene sequencing scenarios in terms of distortion alone.

[0039] Based on the above research, this disclosure provides an optical imaging system and a gene sequencing device. By setting a distortion compensation mirror and placing it between the tube lens and the imaging sensor, the residual distortion in the image can be compensated with high precision while ensuring that the focal length, magnification and image quality performance of the original optical system remain basically unchanged. This improves the geometric consistency of imaging and the positioning accuracy of gene sequencing clusters. Moreover, the structure is simple and easy to process and integrate.

[0040] The shortcomings of the above solutions are the result of the inventor's practical experience and careful research. Therefore, the discovery process of the above problems and the solutions proposed in this disclosure below should be considered as the inventor's contribution to this disclosure.

[0041] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0042] like Figure 1 As shown, Figure 1 This is a schematic diagram of the structure of an optical imaging system provided in an embodiment of the present disclosure.

[0043] This disclosure provides an optical imaging system comprising: a light source 1, and an objective lens 2, a tube lens 3, a distortion compensation lens 4, and an imaging sensor 5 arranged sequentially along the object-side to image-side direction; wherein... The light source 1 is used to emit excitation light to the sequencing object (e.g., a sample library), exciting the fluorescent label carried by the sequencing object to generate a fluorescent signal; the objective lens 2 and the tube lens 3 are used to guide the fluorescent signal to the distortion compensation lens 4; the distortion compensation lens 4 is located between the tube lens 3 and the imaging sensor 5, and is used to perform distortion compensation on the fluorescent signal before transmitting it to the imaging sensor 5; the imaging sensor 5 is used to receive the fluorescent signal and generate and output the fluorescent image.

[0044] The light source 1 can be a laser generator used to emit laser light; of course, the light source 1 can also be an LED light source used to emit LED light. Whether it is laser light or LED light, it can be called excitation light, used to excite the fluorescent label carried by the sequencing object to generate a fluorescent signal.

[0045] In the above embodiments, a distortion compensation mirror 4 is provided between the tube lens 3 and the imaging sensor 5 to correct the distortion (or compensate for distortion) of the fluorescence signal of the guiding imaging sensor 5, thereby improving the geometric consistency of imaging and the accuracy of cluster positioning.

[0046] In some embodiments, the distortion compensation mirror 4 is a single lens. Preferably, the distortion compensation mirror 4 can be designed as an even-order aspherical lens. This configuration, with a simple structure, introduces a compensation amount opposite to the original system distortion direction through an axisymmetric aspherical surface shape, thereby achieving high-precision distortion correction without significantly affecting the system's focal length, magnification, and image quality.

[0047] In some possible implementations, the optical imaging system also includes a filter 6 located between the tube lens 3 and the distortion compensation mirror 4, used to filter the wavelengths of excitation light and stray light, while the fluorescence wavelength can pass through.

[0048] The optical imaging system may also include a dichroic mirror 7, located between the objective lens 2 and the tube lens 3, which has the characteristics of partial high reflectivity and partial high transmittance, and can reflect the excitation light to the objective lens 2 and transmit the fluorescence emitted by the sequencing object to the tube lens 3 as much as possible.

[0049] A light source shaping device 8 can also be provided between the dichroic mirror 7 and the light source 1 to shape the excitation light emitted by the light source 1 before directing it toward the dichroic mirror 7.

[0050] See Figure 2 As shown, Figure 2 This is a schematic diagram showing the position of the distortion compensation mirror in the optical path according to some embodiments of this disclosure. In this embodiment, the distortion compensation mirror 4 is located away from the tube lens 3 and close to the image plane. For example, the distance between the center of the image-side surface and the image plane is between 5 mm and 10 mm.

[0051] Since distortion is mainly manifested in the geometric position shift of the image plane, setting the distortion compensation mirror 4 in the range close to the image plane is beneficial to directly correct the imaging position, improve the distortion compensation efficiency, and reduce the impact on the imaging performance of the objective lens 2 and the tube lens 3.

[0052] In a specific implementation, the distance between the distortion compensation mirror 4 and the image plane can be adjusted according to the packaging size of the imaging sensor and the system structure.

[0053] Figure 3 This is a side view of a distortion compensation mirror provided in some embodiments of this disclosure. See also... Figure 3 As shown, the distortion compensation mirror 4 includes an object-side surface S1 and an image-side surface S2. In some embodiments, the radius of curvature of the image-side surface S2 is greater than that of the object-side surface S1. Thus, by setting different radii of curvature between the object-side surface S1 and the image-side surface S2 of the distortion compensation mirror 4, light can be refracted to different degrees when passing through the distortion compensation mirror 4, thereby introducing the desired geometric correction amount on the image side. The setting that the radius of curvature of the image-side surface S2 is greater than that of the object-side surface S1 facilitates fine adjustment of distortion near the image plane, improving compensation accuracy.

[0054] In this design, the image-side surface S2 of the distortion compensation mirror 4 is convex, while the object-side surface S1 is concave. By setting the object-side surface S1 to be concave and the image-side surface S2 to be convex, the distortion compensation mirror 4 can achieve the required refractive power with a relatively small thickness while ensuring the continuity of the optical path. This facilitates distortion compensation within a limited space. This structural design helps to effectively correct residual distortion of the system without introducing additional complex aberrations.

[0055] In some embodiments, the radius of curvature of the object-side surface S1 satisfies: 29000mm≤R1≤29200mm; the radius of curvature of the image-side surface S2 satisfies: 29300mm≤R2≤29400mm; where R1 is the radius of curvature of the object-side surface S1 and R2 is the radius of curvature of the image-side surface S2.

[0056] By controlling the radius of curvature within the above range, the distortion compensation mirror 4 can accurately match the distortion curve of the original optical imaging system under the working conditions of the gene sequencing optical imaging system, achieving a stable and repeatable distortion compensation effect.

[0057] In specific implementations, the specific values ​​of R1 and R2 can be finely adjusted according to the system field of view size, image plane position and target distortion compensation amount, but are not limited to the above-mentioned value range.

[0058] Preferably, R1 is 29099.19 mm and R2 is 29348.23 mm. The thickness at the center of the distortion compensation lens 4 can be 5 mm.

[0059] In some embodiments, the aspherical coefficients of the distortion compensation mirror 4 include 4th-order and 6th-order terms. By introducing 4th-order and 6th-order aspherical terms, higher-order distortions can be finely adjusted while maintaining axisymmetry, thereby more accurately matching the distortion distribution of the original optical system and improving the accuracy and stability of distortion compensation.

[0060] For example, the aspheric coefficient satisfies: The absolute value of the fourth-order aspheric coefficient of the object-side surface S1 is smaller than the absolute value of the fourth-order aspheric coefficient of the image-side surface S2. The absolute value of the sixth-order aspheric coefficient of the object-side surface S1 is smaller than the absolute value of the sixth-order aspheric coefficient of the image-side surface S2.

[0061] Thus, by making the image-side surface S2 bear a larger amount of aspherical modulation, the main distortion compensation effect can be concentrated near the image plane, thereby improving the compensation efficiency and reducing the impact on the previous imaging optical path.

[0062] In some implementations, the aspheric coefficient satisfies: The fourth-order aspheric coefficients of the object-side surface S1 and the image-side surface S2 are less than 0; the sixth-order aspheric coefficients of the object-side surface S1 and the image-side surface S2 are greater than 0.

[0063] This combination of aspherical coefficient symbols can create a compensation trend opposite to barrel or pincushion distortion under axisymmetric conditions, enabling the distortion compensation mirror to produce the desired geometric correction effect while avoiding the introduction of asymmetric aberrations.

[0064] Preferably, the 4th-order term of the aspheric coefficient of the object-side surface S1 is -1.4779E-05, and the 6th-order term is 9.0302E-09; the 4th-order term of the aspheric coefficient of the image-side surface S2 is -2.2641E-05, and the 6th-order term is 1.5554E-08.

[0065] The distortion compensation mirror 4 can be made of glass, such as fused silica.

[0066] For example, the following content describes the effect of distortion compensation lens 4 with R1 being 29099.19mm, R2 being 29348.23mm, the thickness of the center of distortion compensation lens 4 being 5mm, the 4th order term of the aspheric coefficient of the object-side surface S1 being -1.4779E-05, the 6th order term being 9.0302E-09, and the 4th order term of the aspheric coefficient of the image-side surface S2 being -2.2641E-05, the 6th order term being 1.5554E-08.

[0067] refer to Figure 4a and Figure 4b , Figure 4a This is a schematic diagram of the distortion rate of optical imaging systems in the prior art. Figure 4b This is a schematic diagram illustrating the distortion rate of the optical imaging system in an embodiment of this disclosure. Figure 4a and Figure 4b The horizontal axis represents the maximum distortion rate of the image, and the vertical axis represents the field of view. As shown in the figure, the maximum distortion rate of the image in the embodiments of this disclosure approaches 0 at various field of view sizes, while the maximum distortion rate of the optical imaging system in the prior art reaches 0.9314%. The distortion rate of the optical imaging system in the embodiments of this disclosure is significantly better than that of the prior art.

[0068] refer to Figure 5a and Figure 5b , Figure 5a This is a schematic diagram of the modulation transfer function of an optical imaging system in the prior art. Figure 5b This is a schematic diagram of the modulation transfer function of the optical imaging system in an embodiment of this disclosure. Figure 5a and Figure 5b In the diagram, the horizontal axis represents the spatial frequency, and the vertical axis represents the optical transfer function (OTF) magnitude. Different curves represent the modulation transfer function for the corresponding wavelengths of light. At a spatial frequency of 45 cycles / mm, the OTF magnitudes for each wavelength in both the prior art and the embodiments of this disclosure are between 0.5 and 0.6; at a spatial frequency of 60 cycles / mm, the OTF magnitudes for each wavelength in both the prior art and the embodiments of this disclosure are between 0.4 and 0.5. It is evident that the modulation transfer functions of the optical imaging systems in the prior art and the embodiments of this disclosure are similar, and the distortion compensation mirror has a relatively small impact on the modulation transfer function.

[0069] refer to Figure 6a andFigure 6b , Figure 6a This is a schematic diagram of wavefront aberration in existing optical imaging systems. Figure 6b This is a schematic diagram of the wavefront aberration of the optical imaging system in an embodiment of this disclosure. Figure 6a and Figure 6b The horizontal axis represents the field of view in the +Y direction, and the vertical axis represents the root mean square wavefront error. Figure 6a and Figure 6b The curves corresponding to each other are basically consistent, which shows that the influence of the root mean square wavefront difference of the distortion compensation mirror pair in the optical imaging system of this embodiment is relatively small.

[0070] refer to Figure 7a and Figure 7b , Figure 7a This is a schematic diagram of the transverse chromatic aberration in an existing optical imaging system. Figure 7b This is a schematic diagram of the transverse chromatic aberration of the optical imaging system in an embodiment of this disclosure. Figure 7a and Figure 7b The horizontal axis represents chromatic aberration, the vertical axis represents the field of view, and different curves represent the chromatic aberration along the vertical axis for the corresponding wavelength. Specifically, in both the prior art and the embodiments of this disclosure, the chromatic aberration of light with a wavelength of 0.5750 μm is equal to 0 in any field of view. However, at a wavelength of 0.6050 μm, the chromatic aberration curves of the prior art and this disclosure are in opposite directions, with the prior art curve being slightly smoother than that of this disclosure, but the overall shape is similar. For a wavelength of 0.5450 μm, the curves of the prior art and this disclosure are in the same direction, but the slope of the prior art curve is higher (e.g., when the horizontal axis is 0.8, the field of view value of the prior art is close to 0.36, while that of this disclosure is close to 0.3), and the overall similarity of the curves remains high.

[0071] In some embodiments, the effective focal length (EFFL) of the optical imaging system in the prior art is 20.62325 mm, and the paraxial magnification is 19.94803 times; the paraxial EFFL of the optical imaging system in the embodiments of this disclosure is 20.62325 mm, and the paraxial magnification is 19.94975 times. It can be seen that the distortion compensation lens has little effect on the paraxial EFFL and paraxial magnification.

[0072] The optical imaging system provided in this embodiment can compensate for residual image distortion with high precision while ensuring that the focal length, magnification and image quality performance of the original optical system remain basically unchanged. This improves the geometric consistency of imaging and the accuracy of gene sequencing cluster localization. The system also has a simple structure and is easy to process and integrate.

[0073] Furthermore, this disclosure also provides a gene sequencing device, which includes a fluid system, a computer system, and an optical imaging system of any one of the above; wherein, The flow channel in the fluid system receives the sequencing object, which comes into contact with the reagent and undergoes a chemical reaction in order to carry a fluorescent label. The optical imaging system is configured to excite the fluorescent label carried by the sequencing object and detect the fluorescence signal generated by the excitation of the fluorescent label to output a fluorescence image; The computer system is configured to acquire the fluorescence image from the optical imaging system and identify the gene sequence of the sequencing object based on the fluorescence image.

[0074] See Figure 8 The image shows a gene sequencing device according to an embodiment of this disclosure. The gene sequencing device includes: a sequencing chip 81, a chip platform 82, a reagent storage container 83, a liquid path system 84, an optical imaging system 85, a computer system 86, and a waste liquid storage container 87, wherein: Sequencing chip 81 is configured to provide reaction regions for amplification and sequencing reactions; Chip platform 82, configured to fix and support sequencing chip 81; The reagent storage container 83 is configured to store one or more mixed sample libraries, or one or more reagents; The liquid system 84 is configured to controllably deliver one or more mixed sample libraries and one or more reagents from the reagent storage container 83 to the sequencing chip 81 for amplification and sequencing reactions in the sequencing chip 82, and to controllably deliver the waste liquid after the reaction from the sequencing chip 81 to the waste liquid storage container 87. An optical imaging system 85 is configured to excite and acquire fluorescence signals during sequencing reactions and generate fluorescence images based on the fluorescence signals. The optical imaging system 85 can be implemented as described above, such as... Figures 1-3 The optical imaging system described in the article is implemented.

[0075] Computer system 86 is configured to acquire fluorescence images from optical imaging system 85 and identify the base sequences of a sample library based on the fluorescence images; Waste liquid storage container 87 is configured to store waste liquid generated after the reaction.

[0076] The gene sequencing device provided in this embodiment can compensate for residual image distortion with high precision while ensuring that the focal length, magnification and image quality performance of the original optical system remain basically unchanged. This improves the geometric consistency of imaging and the positioning accuracy of gene sequencing clusters. The device also has a simple structure and is easy to process and integrate.

[0077] Obviously, those skilled in the art can make various modifications and variations to this disclosure without departing from its spirit and scope. Therefore, this disclosure is also intended to include such modifications and variations if they fall within the scope of the claims of this disclosure and their equivalents.

Claims

1. An optical imaging system, characterized in that, include: The light source, and the objective lens, tube lens, distortion compensation lens, and imaging sensor arranged sequentially from the object side to the image side; among them, The light source is used to emit excitation light onto the sequencing object, thereby exciting the sequencing object to generate a fluorescence signal; The objective lens and the tube lens are used to guide the fluorescence signal to the distortion compensation lens; The distortion compensation mirror is located between the tube lens and the imaging sensor, and is used to compensate for the distortion of the fluorescence signal before transmitting it to the imaging sensor; The imaging sensor is used to receive the fluorescence signal and generate and output a fluorescence image.

2. The optical imaging system according to claim 1, characterized in that, The distortion compensation mirror is a single lens.

3. The optical imaging system according to claim 1, characterized in that, The distortion compensation lens is an even-order aspherical lens.

4. The optical imaging system according to claim 1, characterized in that, The distortion compensation mirror includes an object-side surface and an image-side surface; the radius of curvature of the image-side surface is greater than the radius of curvature of the object-side surface.

5. The optical imaging system according to claim 4, characterized in that, The image-side surface is convex; the object-side surface is concave.

6. The optical imaging system according to claim 4, characterized in that, The radius of curvature of the object-side surface satisfies: 29000mm≤R1≤29200mm; the radius of curvature of the image-side surface satisfies: 29300mm≤R2≤29400mm; where R1 is the radius of curvature of the object-side surface and R2 is the radius of curvature of the image-side surface.

7. The optical imaging system according to claim 4, characterized in that, The center thickness of the distortion compensation mirror on the optical axis is between 3 mm and 10 mm.

8. The optical imaging system according to claim 4, characterized in that, The distance between the center of the image side surface and the image plane is between 5 mm and 10 mm.

9. The optical imaging system according to claim 3, characterized in that, The aspherical coefficients of the distortion compensation mirror include 4th-order and 6th-order terms.

10. A gene sequencing device, characterized in that, This includes a fluid system, a computer system, and an optical imaging system as described in any one of claims 1 to 9; wherein, The flow channel in the fluid system receives the sequencing object, which comes into contact with the reagent and undergoes a chemical reaction in order to carry a fluorescent label. The optical imaging system is configured to excite the fluorescent label carried by the sequencing object and detect the fluorescence signal generated by the excitation of the fluorescent label to output a fluorescence image; The computer system is configured to acquire the fluorescence image from the optical imaging system and identify the gene sequence of the sequencing object based on the fluorescence image.

Images