Driving device, imaging system and sequencing system

Abstract

The invention discloses a driving device, an imaging system and a sequencing system. The driving device is used for the imaging system, the imaging system comprises an optical correction device, the driving device is connected with the optical correction device, and the driving device is used for driving the optical correction device to move so that the optical correction device can be moved into or out of an imaging light path of the imaging system. The driving device provided by the embodiment of the invention can correct the aberration between the first surface and the second surface of the to-be-detected sample by driving the optical correction device to move into or out of the imaging light path of the imaging system, so that the imaging system can clearly image the first surface and the second surface of the to-be-detected sample, and the sequencing efficiency and the sequencing flux are improved.

Description

Technical Field

[0001] The present invention relates to the field of gene sequencing, and in particular to a driving device, an imaging system and a sequencing system. Background Art

[0002] Gene sequencing technology refers to the technical means of obtaining DNA or RNA base sequences through detection. The currently dominant sequencing technology is high-throughput sequencing technology. In high-throughput sequencing technology, the nucleic acid molecules to be detected are fixed on the surface of the biochip used. During sequencing, the bases with optically detectable markers are combined with the bases on the nucleic acid molecules in a complementary base pairing manner, and then the optically detectable markers are excited by excitation light to generate optical signals. The excited optical signals are collected by an imaging system to form images, and the base types on the nucleic acid molecules can be identified based on analysis of the images.

[0003] In existing technologies, imaging systems are usually designed to image a certain surface, while a biochip may include multiple surfaces on which the nucleic acid molecules to be tested are respectively fixed. When the imaging system images other surfaces, the image quality obtained usually cannot meet the sequencing requirements, resulting in reduced sequencing efficiency and sequencing throughput. Summary of the invention

[0004] The invention provides a driving device, an imaging system and a sequencing system.

[0005] The driving device of the embodiment of the present application is used in an imaging system, which includes an optical correction device. The driving device is connected to the optical correction device and is used to drive the optical correction device to move so that the optical correction device moves into or out of the imaging light path of the imaging system.

[0006] The driving device of the embodiment of the present application can correct the aberration between the first surface and the second surface of the sample to be inspected by driving the optical correction device to move into or out of the imaging light path of the imaging system, so that the imaging system can clearly image the first surface and the second surface of the sample to be inspected, thereby improving the sequencing efficiency and sequencing throughput.

[0007] The imaging system of the embodiment of the present application includes a driving device, an objective lens and an image sensor. When the optical correction device moves into the imaging light path, the optical correction device is located between the objective lens and the image sensor.

[0008] The imaging system of the present solution corrects the aberration between the first surface and the second surface of the sample to be tested by an optical correction device, so that the imaging system can clearly image both the first surface and the second surface of the sample to be tested, thereby improving sequencing efficiency and sequencing throughput.

[0009] In some embodiments, when the optical correction device moves into the imaging light path, the image sensor collects a first optical signal generated by the first surface of the sample to be tested; when the optical correction device moves out of the imaging light path, the image sensor collects a second optical signal generated by the second surface of the sample to be tested.

[0010] Thus, when the optical correction device moves into the imaging light path, the imaging system can clearly image the first surface of the sample to be inspected; when the optical correction device moves out of the imaging light path, the imaging system can clearly image the second surface of the sample to be inspected.

[0011] In certain embodiments, when the optical correction device is moved into the imaging optical path, the optical correction device is located on the optical axis of the objective lens.

[0012] In this way, when the optical correction device is moved into the imaging light path, the aberration generated when the imaging system images the first surface of the sample to be inspected can be eliminated, so as to improve the resolution of the imaging system and enable the imaging system to clearly image the first surface of the sample to be inspected.

[0013] In some embodiments, the center deviation between the optical correction device and the objective lens does not exceed 0.5 mm.

[0014] When the center deviation between the optical correction device and the objective lens satisfies the above conditions, the image quality correction effect of the optical correction device can be improved, thereby improving the imaging quality of the first surface of the sample to be inspected by the imaging system.

[0015] In some embodiments, the first surface is located between the objective lens and the second surface.

[0016] In this way, the imaging quality of the imaging system for the first surface and the second surface is different.

[0017] In some embodiments, there is a fluid between the first surface and the second surface, and the optical correction device is used to reduce or eliminate the aberration caused by the fluid.

[0018] In this way, the imaging quality of the second surface by the imaging system can be improved.

[0019] In certain embodiments, the optical correction device includes a lens group that is used to eliminate spherical aberration.

[0020] In this way, the optical correction device can eliminate the spherical aberration generated when the imaging system images the first surface of the sample to be inspected through the lens group.

[0021] In some embodiments, the lens group includes a first lens, a second lens, and a third lens arranged in sequence, and the optical power of the first lens, the second lens, and the third lens combined is approximately 0, and the allowable error is ±1%.

[0022] In this way, the lens group adopts a three-lens structure with fewer lenses and smaller volume; the lens group is matched with the infinite conjugate objective lens, and can clearly converge the optical signal on the first surface onto the image plane of the image sensor.

[0023] In some embodiments, the first lens has negative optical power, the second lens has positive optical power, and the third lens has negative optical power; the object side surface of one lens and the image side surface of another lens in a group of adjacent lenses are arranged opposite to each other.

[0024] In this way, the optical power of the combination of the first lens, the second lens and the third lens can be made substantially 0, with an allowable error of ±1%.

[0025] In some embodiments, the object side of the first lens is a plane at the optical axis of the first lens, and the image side of the first lens is a concave surface at the optical axis of the first lens; and / or,

[0026] The object side of the second lens is convex at the optical axis of the second lens, and the image side of the second lens is convex at the optical axis of the second lens; and / or,

[0027] The object side surface of the third lens is a concave surface at the optical axis of the third lens, and the image side surface of the third lens is a flat surface at the optical axis of the third lens.

[0028] Thus, the first lens can provide negative optical power, the second lens can provide positive optical power, and the third lens can provide negative optical power.

[0029] In some embodiments, a spectroscopic component is arranged between the objective lens and the image sensor, and the spectroscopic component is used to split the optical signal collected by the objective lens into multiple light beams of different wavelengths. There are multiple image sensors, and each image sensor is used to collect a light beam of at least one wavelength and form an image.

[0030] In this way, the light from the objective lens is split by the beam splitting component to form multiple light beams, and the light beams are converged to the corresponding image sensor for imaging, so as to realize the simultaneous detection of different optical signals emitted by the sample to be inspected.

[0031] In some embodiments, the spectroscopic component is used to split the optical signal collected by the objective lens into a first light beam and a second light beam, and the image sensor includes a first image sensor and a second image sensor, the first image sensor is used to collect the first light beam and form an image, and the second image sensor is used to collect the second light beam and form an image.

[0032] In this way, the light from the objective lens is split into two light beams by the beam splitting component, and the two light beams are converged to the corresponding image sensor for imaging, so as to realize the simultaneous detection of different optical signals emitted by the sample to be inspected.

[0033] In certain embodiments, the beam splitting assembly includes a first dichroic mirror, a first reflector, and a second reflector;

[0034] The first dichroic mirror is arranged on the optical axis of the objective lens and is tilted relative to the optical axis of the objective lens. The first dichroic mirror is used to split the optical signal collected by the objective lens into a first light beam and a second light beam, so that the first light beam is transmitted to the first reflector and the second light beam is reflected to the second reflector. The first reflector is used to reflect the first light beam toward the first image sensor, and the second reflector is used to reflect the second light beam toward the second image sensor.

[0035] In this way, the spectroscopic component can separate optical signals of different wavelength bands and different fluxes, so that the first image sensor and the second image sensor can simultaneously image different optical signals.

[0036] In some embodiments, the first dichroic mirror and the first reflector are disposed perpendicularly.

[0037] In this way, the first reflector can change the optical path of the first light beam, so that the first image sensor can be arranged at a suitable position, so as to make the structure of the imaging system more compact.

[0038] In some embodiments, the first dichroic mirror and the second reflector are arranged in parallel.

[0039] In this way, the second reflector can change the optical path of the second light beam, so that the second image sensor can be arranged at a suitable position, thereby making the structure of the imaging system more compact.

[0040] In some embodiments, the imaging system includes a first tube lens and a second tube lens, the first tube lens is arranged between the first image sensor and the first reflector, and is used to converge the first light beam to the first image sensor; the second tube lens is arranged between the second image sensor and the second reflector, and is used to converge the second light beam to the second image sensor.

[0041] Thus, the first tube lens cooperates with the objective lens to converge the first light beam to the first image sensor for imaging, and the second tube lens cooperates with the objective lens to converge the second light beam to the second image sensor for imaging.

[0042] In some embodiments, the imaging system includes a first filter and a second filter, the first filter is arranged between the first tube lens and the first reflector, and is used to filter the first light beam entering the first tube lens; the second filter is arranged between the second tube lens and the second reflector, and is used to filter the second light beam entering the second tube lens.

[0043] In this way, the filter can filter light, allowing the fluorescent band to pass through and cutting off the unnecessary laser band, thereby improving the imaging quality of the image sensor.

[0044] In certain embodiments, the imaging system includes a light source assembly for emitting an excitation beam toward the sample through the objective lens.

[0045] In this way, the light source assembly can excite the bases with optically detectable labels bound to the biological molecules to generate optical signals, thereby achieving base sequence determination of the biological molecules.

[0046] In some embodiments, the light source assembly includes a first light source and a first lens disposed on an illumination light path of the first light source, and the first lens is used to control the aperture of a light beam of the first light source entering the objective lens.

[0047] In this way, by adjusting the first lens to control the beam aperture of the first light source entering the objective lens, not only the structure of the imaging system is simplified, the difficulty of debugging the imaging system is reduced, and the transmittance is improved, but also the illumination beam can evenly illuminate the entire field of view, which is beneficial to improving the excitation efficiency and imaging quality.

[0048] In some embodiments, a bandpass filter is disposed between the first lens and the objective lens, and the bandpass filter is used to perform bandpass filtering on the light passing through the first lens.

[0049] In some embodiments, the imaging system includes a second dichroic mirror disposed between the bandpass filter and the objective lens, the second dichroic mirror is disposed on the optical axis of the objective lens and tilted relative to the optical axis of the objective lens, and the second dichroic mirror is used to reflect light passing through the bandpass filter to the objective lens and to transmit light from the objective lens.

[0050] Thus, the second dichroic mirror reflects the illumination beam emitted by the first light source through the bandpass filter to the objective lens, so that the illumination beam emitted by the first light source irradiates the sample to be tested after passing through the objective lens, thereby stimulating the sample to be tested to generate fluorescence of multiple wavelengths.

[0051] In some embodiments, the imaging system includes an autofocus device, which includes a second light source and a focus sensor. The second light source is used to project a light beam emitted by the second light source onto a sample to be inspected through an objective lens; the focus sensor is used to receive the light beam reflected from the sample to be inspected and collimated by the objective lens, and convert the light signal into an electrical signal so that the objective lens moves according to the electrical signal so that the sample to be inspected is located on the focal plane of the objective lens.

[0052] In this way, the autofocus device is mainly used to mark the object distance after the objective lens completes focusing, and monitors the change in object distance in real time during gene sequencing, and corrects it to ensure that the system is always in clear focus, ensure the accuracy of image capture by the image sensor, and finally obtain a clear image within the focal depth range.

[0053] In some embodiments, the imaging system also includes a third dichroic mirror, which is disposed on the optical axis of the objective lens. The third dichroic mirror is used to reflect the light beam emitted by the second light source so that the light beam emitted by the second light source is projected onto the sample to be inspected through the objective lens, and reflects the light beam reflected from the sample to be inspected to the focus sensor. The third dichroic mirror is also used to allow the light beam from the objective lens to pass through.

[0054] In this way, the reflectivity and light transmittance of the third dichroic mirror are fully utilized to arrange the light path, thereby improving the utilization rate of the space and making the structure more compact.

[0055] In some embodiments, the image sensor is an image sensor of an area scan camera or an image sensor of a line scan camera.

[0056] In this way, area array imaging or line scan imaging can be achieved.

[0057] In some embodiments, the driving device includes a driving member and a transmission assembly connected to the driving member, the transmission assembly is connected to the optical correction device, and the driving member drives the optical correction device to move through the transmission assembly.

[0058] In this way, the optical correction device can be moved into or out of the imaging light path through the driving member and the transmission assembly, so that the imaging system can clearly image the first surface and the second surface of the sample to be inspected, respectively.

[0059] In some embodiments, the transmission assembly includes a screw and a slider mounted on the screw, the screw is connected to a driving member, the slider is connected to the optical correction device, and the driving member is used to drive the screw to rotate, thereby driving the slider and the optical correction device to move.

[0060] In this way, the optical correction device can be moved into or out of the imaging light path by rotating the lead screw, so that the imaging system can clearly image the first surface and the second surface of the sample to be inspected, respectively.

[0061] In some embodiments, the driving device further includes a base and a slide rail disposed on the base, the slider is slidably disposed on the slide rail, and the driving member is mounted on the base.

[0062] In this way, the slide rail can not only make the optical correction device move more smoothly, but also make the optical correction device remain in the same plane when moving into or out of the imaging light path.

[0063] In some embodiments, the optical correction device includes a lens barrel, a lens group, and a bracket. The lens group is disposed in the lens barrel, and the bracket connects the lens barrel and the transmission assembly.

[0064] In this way, the lens barrel can carry the lens group, and the bracket is connected to the transmission assembly, so that the transmission assembly can drive the bracket to move, thereby moving the lens group into or out of the imaging light path.

[0065] In certain embodiments, the driving device further comprises a detection device, and the detection device is used to limit the movement range of the optical correction device.

[0066] In this way, the movement range of the optical correction component into or out of the imaging optical path can be limited by the detection device.

[0067] In some embodiments, the detection device includes a first detector and a second detector, the first detector is used to trigger a first signal when the optical correction device moves into the imaging light path, and the second detector is used to trigger a second signal when the optical correction device moves out of the imaging light path, and the driving device stops working according to the first signal or the second signal.

[0068] In this way, the first detector and the second detector can limit the movement stroke of the optical correction device and serve as a zero point reset, and can also limit the movement range of the optical correction device.

[0069] In some embodiments, the first detector is disposed on the side when the optical correction device moves into the imaging light path, the second detector is disposed on the side when the optical correction device moves out of the imaging light path, and the detection device includes a trigger member that moves synchronously with the optical correction device;

[0070] When the optical correction device moves into the imaging optical path, the trigger cooperates with the first detector to cause the first detector to trigger a first signal. When the optical correction device moves out of the imaging optical path, the trigger cooperates with the second detector to cause the second detector to trigger a second signal.

[0071] In this way, the triggering member causes the first detector and the second detector to trigger signals, thereby controlling the movement stroke of the optical correction device on the slide rail.

[0072] The sequencing system of the embodiment of the present application includes an imaging system.

[0073] The imaging system of the present solution corrects the aberration between the first surface and the second surface of the sample to be tested by an optical correction device, so that the imaging system can clearly image both the first surface and the second surface of the sample to be tested, thereby improving sequencing efficiency and sequencing throughput.

[0074] The imaging method of the embodiment of the present application uses an imaging system to image a sample to be inspected, the sample to be inspected includes a first surface and a second surface, the imaging system includes an objective lens, an optical correction device and an image sensor, the optical correction device can be moved into or out of the imaging light path of the imaging system, and the imaging method includes:

[0075] When the optical correction device moves out of the imaging light path, using the image sensor to collect a second optical signal generated by the second surface of the sample to be inspected;

[0076] Controlling the optical correction device to move into the imaging light path so that the optical correction device is located between the objective lens and the image sensor;

[0077] An image sensor is used to collect a first optical signal generated by a first surface of the sample to be inspected.

[0078] In this way, the aberration between the first surface and the second surface of the sample to be tested is corrected by the optical correction device, so that the imaging system can clearly image the first surface and the second surface of the sample to be tested, thereby improving sequencing efficiency and sequencing throughput.

[0079] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0081] Figure 1 is a schematic structural diagram of a driving device according to an embodiment of the present invention;

[0082] Figure 2 is a schematic structural diagram of an imaging system according to an embodiment of the present invention;

[0083] Figure 3 is a schematic structural diagram of an imaging system according to an embodiment of the present invention;

[0084] Figure 4 is a schematic diagram of an imaging optical path of an imaging system according to an embodiment of the present invention;

[0085] Figure 5 is a schematic diagram of an imaging optical path of an imaging system according to an embodiment of the present invention;

[0086] Figure 6 is a wavefront error curve diagram of imaging by the imaging system according to an embodiment of the present invention;

[0087] Figure 7 is a wavefront error curve diagram of imaging by the imaging system according to an embodiment of the present invention;

[0088] Figure 8 is a schematic structural diagram of a lens assembly according to an embodiment of the present invention;

[0089] Fig. 9 It is a schematic flow chart of the imaging method according to an embodiment of the present invention.

[0090] Explanation of reference numerals: 100, imaging system; 10, objective lens; 20, optical correction device; 21, lens group; 22, first lens; 221, object side surface of the first lens; 222, image side surface of the first lens; 23, second lens; 231, object side surface of the second lens; 232, image side surface of the second lens; 24, third lens; 241, object side surface of the third lens; 242, image side surface of the third lens; 25, lens barrel; 26, bracket; 30, image sensor; 31, first image sensor; 32, second image sensor; 40, spectrometer; 41, first dichroic mirror; 42, first reflector; 43, second reflector; 51, first tube lens; 52, second tube lens; 53, first filter ; 54, second filter; 55, bandpass filter; 56, second dichroic mirror; 57, third dichroic mirror; 60, light source assembly; 61, first light source; 62, first lens; 70, autofocus device; 71, second light source; 72, focus sensor; 80, driving device; 81, driving member; 82, transmission assembly; 83, screw rod; 84, slider; 85, base; 86, slide rail; 87, mounting bracket; 90, detection device; 91, first detector; 92, second detector; 93, trigger; 200, sample to be detected; 210, first surface; 211, first optical signal; 220, second surface; 221, second optical signal; 230, first light beam; 240, second light beam. DETAILED DESCRIPTION

[0091] The embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and cannot be understood as limiting the present invention.

[0092] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first" and "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "multiple" is two or more, unless otherwise clearly and specifically defined.

[0093] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, an electrical connection, or mutual communication; it can be a direct connection, or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0094] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0095] The disclosure below provides many different embodiments or examples to realize different structures of the present invention. In order to simplify the disclosure of the present invention, the parts and settings of specific examples are described below. Of course, they are only examples, and the purpose is not to limit the present invention. In addition, the present invention can repeat reference numbers and / or reference letters in different examples, and this repetition is for the purpose of simplicity and clarity, which itself does not indicate the relationship between the various embodiments and / or settings discussed. In addition, the present invention provides various specific examples of processes and materials, but those of ordinary skill in the art can be aware of the application of other processes and / or the use of other materials.

[0096] See also Figure 1 The driving device 80 of the embodiment of the present application is used in the imaging system 100, and the imaging system 100 includes an optical correction device 20. The driving device 80 is connected to the optical correction device 20, and the driving device 80 is used to drive the optical correction device 20 to move so that the optical correction device 20 moves into or out of the imaging light path of the imaging system 100.

[0097] The driving device 80 of the embodiment of the present application can correct the aberration between the first surface 210 and the second surface 220 of the sample 200 to be inspected by driving the optical correction device 20 to move into or out of the imaging light path of the imaging system 100, so that the imaging system 100 can clearly image the first surface 210 and the second surface 220 of the sample 200 to be inspected, thereby improving the sequencing efficiency and sequencing throughput.

[0098] Specifically, the driving method of the driving device 80 includes but is not limited to electric and hydraulic, and the driving device 80 can be a cylinder, or a combination of a motor and a screw 83, or a combination of a motor and a belt. The optical correction device 20 can be fixed to the driving device 80 by fasteners such as bolts.

[0099] See also Figure 2 The imaging system 100 of the embodiment of the present application includes a driving device 80, an objective lens 10 and an image sensor 30. When the optical correction device 20 moves into the imaging light path, the optical correction device 20 is located between the objective lens 10 and the image sensor 30.

[0100] The imaging system 100 of the embodiment of the present application corrects the aberration between the first surface 210 and the second surface 220 of the sample 200 to be inspected by the optical correction device 20, so that the imaging system 100 can clearly image the first surface 210 and the second surface 220 of the sample 200 to be inspected, thereby improving sequencing efficiency and sequencing throughput.

[0101] Specifically, the objective lens 10 is used to collect the first optical signal 211 from the first surface 210 and the second optical signal 221 from the second surface 220. The objective lens 10 may be a ready-made objective lens 10, such as an infinite conjugate objective lens 10, or a customized objective lens 10. The focal length of the objective lens 10 may be set according to the requirements of the imaging system 100.

[0102] The image sensor 30 is used to collect the first optical signal 211 collected by the objective lens 10 and form an image when the optical correction device 20 moves into the imaging optical path, and is used to collect the second optical signal 221 collected by the objective lens 10 and form an image when the optical correction device 20 moves out of the imaging optical path. The image sensor 30 is any sensor that can sense optical image information and convert it into a usable output signal, including but not limited to CCD and CMOS, and the image sensor 30 may include one or more sensors.

[0103] See also Figure 2 and Figure 3 In some embodiments, when the optical correction device 20 moves into the imaging light path, the image sensor 30 collects a first optical signal 211 generated by the first surface 210 of the sample to be tested 200; when the optical correction device 20 moves out of the imaging light path, the image sensor 30 collects a second optical signal 221 generated by the second surface 220 of the sample to be tested 200.

[0104] Thus, when the optical correction device 20 moves into the imaging light path, the imaging system 100 can clearly image the first surface 210 of the sample 200 to be inspected; when the optical correction device 20 moves out of the imaging light path, the imaging system 100 can clearly image the second surface 220 of the sample 200 to be inspected.

[0105] Please combine Figure 4 When the optical correction device 20 is moved into the imaging optical path, the depth of field of the imaging system 100 is as follows: Figure 4 As shown, the optical correction device 20 can correct the aberration between the first surface 210 and the second surface 220 of the sample 200 to be inspected, so the imaging system 100 can clearly image the first surface 210 of the sample 200 to be inspected; Figure 5 When the optical correction device 20 is moved out of the imaging light path, the depth of field of the imaging system 100 is as follows: Figure 5 As shown, the imaging system 100 can therefore clearly image the second surface 220 of the sample 200 to be inspected.

[0106] See also Figure 2 In some embodiments, when the optical correction device 20 is moved into the imaging light path, the optical correction device 20 is located on the optical axis of the objective lens 10.

[0107] In this way, when the optical correction device 20 is moved into the imaging light path, the aberration generated when the imaging system 100 images the first surface 210 of the sample 200 to be inspected can be eliminated, so as to improve the resolution of the imaging system 100 when imaging the first surface 210, so that the imaging system 100 can clearly image the first surface 210 of the sample 200 to be inspected.

[0108] Specifically, in some embodiments, the optical correction device 20 is disposed parallel to the objective lens 10 , and the optical correction device 20 is perpendicular to the optical axis of the objective lens 10 .

[0109] In some embodiments, the center deviation between the optical correction device 20 and the objective lens 10 does not exceed 0.5 mm.

[0110] When the center deviation between the optical correction device 20 and the objective lens 10 satisfies the above conditions, the image quality correction effect of the optical correction device 20 can be improved, thereby improving the imaging quality of the first surface 210 of the sample 200 to be inspected by the imaging system 100.

[0111] Specifically, the center deviation between the optical correction device 20 and the objective lens 10 refers to the distance between the optical axis of the optical correction device 20 and the optical axis of the objective lens 10. The smaller the center deviation between the optical correction device 20 and the objective lens 10, the higher the imaging quality of the imaging system 100 on the first surface 210 of the sample 200 to be inspected.

[0112] See also Figure 2 In some embodiments, the first surface 210 is located between the objective lens 10 and the second surface 220. The imaging system 100 has different imaging qualities for the first surface 210 and the second surface 220.

[0113] Specifically, when the sample 200 to be tested is a gene sequencing chip, the first surface 210 may be the interface between the cover glass and the flow channel, and the second surface 220 may be the interface between the slide glass and the flow channel.

[0114] In some embodiments, there is a fluid between the first surface 210 and the second surface 220, and the optical correction device 20 is used to reduce or eliminate the aberration caused by the fluid.

[0115] In this way, the imaging quality of the second surface 220 by the imaging system 100 can be improved.

[0116] Specifically, when the medium between the first surface 210 and the second surface 220 changes, the imaging quality of the second surface 220 by the imaging system 100 also changes.

[0117] See also Figure 1 In some embodiments, the optical correction device 20 includes a lens group 21, and the lens group 21 is used to eliminate spherical aberration.

[0118] In this way, the optical correction device 20 can eliminate the spherical aberration generated when the imaging system 100 images the first surface 210 of the sample 200 to be inspected through the lens group 21 .

[0119] Specifically, the number of lenses in the lens group 21 may be 3, 4, or 5, etc., and the specific number may be set according to the requirements of the imaging system 100. Figure 6 and Figure 7 , Figure 6 is a wavefront error curve diagram of imaging the first surface 210 of the sample 200 to be inspected by the imaging system 100 when the optical correction device 20 moves into the imaging optical path, Figure 7 is a wavefront error curve diagram of the imaging system 100 imaging the second surface 220 of the sample 200 to be inspected when the optical correction device 20 moves out of the imaging light path, such as Figure 6 and Figure 7 As shown, the image quality of the images obtained after the imaging system 100 respectively images the first surface 210 and the second surface 220 of the sample 200 to be inspected reaches the diffraction limit.

[0120] See also Figure 8 In some embodiments, the lens group 21 includes a first lens 22, a second lens 23 and a third lens 24 arranged in sequence, and the optical focal length of the first lens 22, the second lens 23 and the third lens 24 after being combined is approximately 0, and the allowable error is ±1%.

[0121] Thus, the lens group 21 adopts a three-lens structure with fewer lenses and smaller volume; the lens group 21 matches the infinite conjugate objective lens 10 and can clearly converge the optical signal on the first surface 210 onto the image plane of the image sensor 30 .

[0122] Specifically, the first lens 22, the second lens 23 and the third lens 24 are arranged along the light propagation direction (eg Figure 8 The components are arranged in sequence as shown by the dotted arrows in FIG.

[0123] The optical focal length represents the refraction ability of the optical imaging system 100 to the incident parallel light beam. The larger the optical focal length, the more obvious the angle deflection of the outgoing light beam. When the optical focal length is greater than 0, the outgoing light beam is convergent; when the optical focal length is less than 0, the outgoing light beam is divergent; when the optical focal length is 0, it is a plane refraction.

[0124] In some embodiments, the first lens 22 has negative optical power, the second lens 23 has positive optical power, and the third lens 24 has negative optical power; the object side surface of one lens and the image side surface of another lens in a group of adjacent lenses are arranged opposite to each other.

[0125] In this way, the optical power of the combination of the first lens 22, the second lens 23 and the third lens 24 can be made substantially 0, and the allowable error is ±1%.

[0126] Specifically, the first lens 22, the second lens 23 and the third lens 24 are used to balance the aberration together, so that the incident and emitted fluorescent signals passing through the lens group 21 are both collimated light beams.

[0127] See also Figure 8 In some embodiments, the object side surface 221 of the first lens is a plane at the optical axis of the first lens 22, and the image side surface 222 of the first lens is a concave surface at the optical axis of the first lens 22; and / or

[0128] The object side surface 231 of the second lens is a convex surface at the optical axis of the second lens 23, and the image side surface 232 of the second lens is a convex surface at the optical axis of the second lens 23; and / or,

[0129] The object-side surface 241 of the third lens is a concave surface at the optical axis of the third lens 24 , and the image-side surface 242 of the third lens is a flat surface at the optical axis of the third lens 24 .

[0130] In this way, the first lens 22 can provide negative optical power, the second lens 23 can provide positive optical power, and the third lens 24 can provide negative optical power.

[0131] Specifically, with the lens as the boundary, the side where the object is located is the object side, and the surface of the lens close to the object side can be called the object side; with the lens as the boundary, the side where the image of the object is located is the image side, and the surface of the lens close to the image side can be called the image side. The first lens 22 and the third lens 24 are plano-concave lenses, so that the optical correction device 20 is easy to install and debug.

[0132] In some embodiments, a spectroscopic component 40 is disposed between the objective lens 10 and the image sensor 30, and the spectroscopic component 40 is used to split the optical signal collected by the objective lens 10 into a plurality of light beams of different wavelengths. There are a plurality of image sensors 30, and each image sensor 30 is used to collect a light beam of at least one wavelength and form an image.

[0133] In this way, the light from the objective lens 10 is split by the beam splitter 40 to form a plurality of light beams, and the light beams are converged to the corresponding image sensor 30 for imaging, so as to realize simultaneous detection of different optical signals emitted by the sample 200 to be inspected.

[0134] Specifically, the light splitting component 40 can reflect part of the light and transmit another part of the light according to the wavelength of the light, or can reflect part of the light and transmit another part of the light according to the flux. The number of image sensors 30 can be 2, 3 or 4, etc.

[0135] See also Figure 2 In some embodiments, the spectroscopic component 40 is used to separate the optical signal collected by the objective lens 10 into a first light beam 230 and a second light beam 240. The image sensor 30 includes a first image sensor 31 and a second image sensor 32. The first image sensor 31 is used to collect the first light beam 230 and form an image, and the second image sensor 32 is used to collect the second light beam 240 and form an image.

[0136] In this way, the light from the objective lens 10 is split into two light beams by the light splitting component 40 , and the two light beams are converged to the corresponding image sensor 30 for imaging, so as to realize simultaneous detection of different optical signals emitted by the sample 200 to be inspected.

[0137] See also Figure 2 In some embodiments, the light splitting component 40 includes a first dichroic mirror 41, a first reflector 42, and a second reflector 43;

[0138] The first dichroic mirror 41 is arranged on the optical axis of the objective lens 10 and is tilted relative to the optical axis of the objective lens 10. The first dichroic mirror 41 is used to separate the optical signal collected by the objective lens 10 into a first light beam 230 and a second light beam 240, so that the first light beam 230 is transmitted to the first reflector 42, and the second light beam 240 is reflected to the second reflector 43. The first reflector 42 is used to reflect the first light beam 230 toward the first image sensor 31, and the second reflector 43 is used to reflect the second light beam 240 toward the second image sensor 32.

[0139] In this way, the light splitting component 40 can separate optical signals of different wavelength bands and different fluxes, so that the first image sensor 31 and the second image sensor 32 can simultaneously image different optical signals.

[0140] In some embodiments, the first dichroic mirror 41 is placed at an angle of 45° with the optical axis of the objective lens 10. The first dichroic mirror 41 can reflect part of the light and transmit another part of the light according to the wavelength of the light.

[0141] Please refer again Figure 2 In some embodiments, the first dichroic mirror 41 and the first reflector 42 are vertically arranged.

[0142] In this way, the first reflector 42 can change the optical path of the first light beam 230 so that the first image sensor 31 can be arranged at a suitable position, thereby making the structure of the imaging system 100 more compact.

[0143] In some embodiments, the first dichroic mirror 41 and the first reflector 42 are arranged in parallel.

[0144] See also Figure 2In some embodiments, the first dichroic mirror 41 and the second reflecting mirror 43 are arranged in parallel.

[0145] In this way, the second reflector 43 can change the optical path of the second light beam 240 so that the second image sensor 32 can be arranged at a suitable position, thereby making the structure of the imaging system 100 more compact.

[0146] In some embodiments, the first dichroic mirror 41 and the first reflector 42 are disposed vertically.

[0147] See also Figure 2 In some embodiments, the imaging system 100 includes a first tube lens 51 and a second tube lens 52. The first tube lens 51 is disposed between the first image sensor 31 and the first reflector 42, and is used to converge the first light beam 230 onto the first image sensor 31; the second tube lens 52 is disposed between the second image sensor 32 and the second reflector 43, and is used to converge the second light beam 240 onto the second image sensor 32.

[0148] Thus, the first tube lens 51 cooperates with the objective lens 10 to converge the first light beam 230 to the first image sensor 31 for imaging, and the second tube lens 52 cooperates with the objective lens 10 to converge the second light beam 240 to the second image sensor 32 for imaging.

[0149] Specifically, the first tube lens 51 and the second tube lens 52 may be tube lenses with the same focal length, or tube lenses with different focal lengths may be designed according to imaging requirements.

[0150] Please refer again Figure 2 In some embodiments, the imaging system 100 includes a first filter 53 and a second filter 54. The first filter 53 is disposed between the first tube lens 51 and the first reflector 42, and is used to filter the first light beam 230 entering the first tube lens 51; the second filter 54 is disposed between the second tube lens 52 and the second reflector 43, and is used to filter the second light beam 240 entering the second tube lens 52.

[0151] In this way, the filter can filter light, allowing the fluorescent wavelength band to pass through and cutting off the unnecessary laser wavelength band, thereby improving the imaging quality of the image sensor 30.

[0152] Specifically, the first filter 53 and the first tube lens 51 are respectively arranged vertically on the optical path of the first light beam 230 reflected by the first reflector 42 . The first light beam 230 is filtered by the first filter 53 and then converged to the first image sensor 31 through the first tube lens 51 .

[0153] The second filter 54 and the second tube lens 52 are respectively arranged vertically on the optical path of the second light beam 240 reflected by the second reflector 43 . The second light beam 240 is filtered by the second filter 54 and then converged to the second image sensor 32 through the second tube lens 52 .

[0154] See also Figure 2 In some embodiments, the imaging system 100 includes a light source assembly 60 for emitting an excitation light beam to the sample through the objective lens 10 .

[0155] In this way, the light source assembly 60 can excite the base with an optically detectable label bound to the biomolecule to generate an optical signal, thereby realizing the base sequence determination of the biomolecule. The biomolecule is fixed on the first surface 210 and the second surface 220 of the sample 200 to be tested, and the base with an optically detectable label is combined with the base on the biomolecule in a complementary base pairing manner. The optically detectable label can be, for example, a fluorescent group. When the light source assembly 60 irradiates the first surface 210 and the second surface 220 of the sample 200 to be tested, the fluorescent group can be excited to generate a fluorescent signal.

[0156] See also Figure 2 In some embodiments, the light source assembly 60 includes a first light source 61 and a first lens 62 disposed on an illumination light path of the first light source 61 , and the first lens 62 is used to control the aperture of the light beam of the first light source 61 entering the objective lens 10 .

[0157] In this way, by adjusting the first lens 62 to control the beam aperture of the first light source 61 entering the objective lens 10, not only the structure of the imaging system 100 is simplified, the debugging difficulty of the imaging system 100 is reduced, and the transmittance is improved, but also the illumination beam can evenly illuminate the entire field of view, which is beneficial to improving the excitation efficiency and imaging quality.

[0158] Specifically, the first light source 61 is used to emit an illumination light beam. When the illumination light beam is irradiated on the sample to be tested 200 through the objective lens 10, the biological molecules on the first surface 210 and / or the second surface 220 of the sample to be tested 200 are excited to produce fluorescence. The sample to be tested 200 can be a nucleic acid sample, such as a DNA or RNA sample. The first light source 61 emits a light beam of at least one wavelength to excite fluorescent groups on multiple bases to achieve sequencing of multiple bases. Exemplarily, the first light source 61 can simultaneously excite A base fluorescence signals and C base fluorescence signals, and can also simultaneously excite G base fluorescence signals and T base fluorescence signals.

[0159] In some embodiments, the first lens 62 may be an aspheric lens. By adjusting the distance between the first lens 62 and the objective lens 10, the beam aperture of the illumination light beam entering the objective lens 10 may be controlled, so that the illumination light beam completely enters the objective lens 10 and is projected onto the sample 200 to be inspected through the objective lens 10, thereby stimulating the sample 200 to produce fluorescence.

[0160] Please refer again Figure 2 In some embodiments, a bandpass filter 55 is disposed between the first lens 62 and the objective lens 10 , and the bandpass filter 55 is used to perform bandpass filtering on the light passing through the first lens 62 .

[0161] In this way, the illumination light beam enters the objective lens 10 after the light source passing through the first lens 62 is bandpass filtered by the bandpass filter 55 arranged between the first lens 62 and the objective lens 10. Thus, stray light in the illumination light can be removed, which is beneficial to further improve the excitation efficiency and imaging quality.

[0162] In some embodiments, the bandpass filter 55 may be a single bandpass filter 55 or a dual-bandpass laser filter.

[0163] See also Figure 2 In some embodiments, the imaging system 100 includes a second dichroic mirror 56 disposed between the bandpass filter 55 and the objective lens 10. The second dichroic mirror 56 is disposed on the optical axis of the objective lens 10 and is tilted relative to the optical axis of the objective lens 10. The second dichroic mirror 56 is used to reflect the light passing through the bandpass filter 55 to the objective lens 10, and to transmit the light from the objective lens 10.

[0164] Thus, the second dichroic mirror 56 reflects the illumination light beam emitted by the first light source 61 through the bandpass filter 55 to the objective lens 10, so that the illumination light beam emitted by the first light source 61 irradiates the sample 200 after passing through the objective lens 10, so as to excite the sample 200 to generate fluorescence of multiple wavelengths.

[0165] In some embodiments, the second dichroic mirror 56 is located on the optical axis of the objective lens 10 and is placed at a 45° angle to the optical axis of the objective lens 10, and the second dichroic mirror 56 is at a 90° angle to the first dichroic mirror 41, and the objective lens 10 and the first light source 61 are located on the same side of the second dichroic mirror 56, so that the first light source 61 is incident on the objective lens 10.

[0166] See also Figure 2In some embodiments, the imaging system 100 includes an autofocus device 70, which includes a second light source 71 and a focus sensor 72. The second light source 71 is used to project a light beam emitted by the second light source 71 onto the sample to be inspected 200 through the objective lens 10; the focus sensor 72 is used to receive the light beam reflected from the sample to be inspected 200 and collimated by the objective lens 10, and convert the light signal into an electrical signal so that the objective lens 10 moves according to the electrical signal so that the sample to be inspected 200 is located on the focal plane of the objective lens 10.

[0167] In this way, the autofocus device 70 is mainly used to mark the object distance after the objective lens 10 completes focusing, and to monitor the change in object distance in real time during the gene sequencing process and correct it to ensure that the system is always in clear focus, ensure the accuracy of the image captured by the image sensor 30, and finally obtain a clear image within the focal depth range.

[0168] In some embodiments, the focus sensor 72 is located on one side of the optical axis of the objective lens 10 and is disposed between the first dichroic mirror 41 and the first reflector 42. The focus sensor 72 is used to receive the light beam reflected from the sample 200 to be tested and collimated by the objective lens 10, and the focus sensor 72 determines the distance between the plane where the sample 200 to be tested is located and the focal plane of the objective lens 10 according to the light beam, and converts the optical signal into an electrical signal, which is used to characterize the distance between the plane where the sample 200 to be tested is located and the focal plane of the objective lens 10, and adjusts the plane where the sample 200 to be tested is located through the electrical signal, so that the plane where the sample 200 to be tested is located is at the focal plane position of the objective lens 10.

[0169] Please refer again Figure 2 In some embodiments, the imaging system 100 further includes a third dichroic mirror 57, which is disposed on the optical axis of the objective lens 10. The third dichroic mirror 57 is used to reflect the light beam emitted by the second light source 71 so that the light beam emitted by the second light source 71 is projected onto the sample to be inspected 200 through the objective lens 10, and reflects the light beam reflected from the sample to be inspected 200 to the focus sensor 72. The third dichroic mirror 57 is also used to allow the light beam from the objective lens 10 to pass through.

[0170] In this way, the reflectivity and light transmittance of the third dichroic mirror 57 are fully utilized to arrange the light path, thereby improving the utilization of space and making the structure more compact.

[0171] In some embodiments, the third dichroic mirror 57 is disposed on the optical axis of the objective lens 10, and the third dichroic mirror 57 is placed parallel to the first dichroic mirror 41. The light beam emitted by the second light source 71 in the auto-focusing device 70 is reflected by the third dichroic mirror 57 to the first dichroic mirror 41, transmitted by the first dichroic mirror 41 to the second dichroic mirror 56, and then transmitted by the second dichroic mirror 56 to the objective lens 10, and after being converged by the objective lens 10 on the sample 200 to be inspected, it returns to the auto-focusing device 70 along the original optical path.

[0172] In some embodiments, the image sensor 30 is an image sensor 30 of an area array camera or an image sensor 30 of a line array camera.

[0173] In this way, area array imaging or line scan imaging can be achieved.

[0174] Specifically, the area array camera mainly uses continuous, planar scanning light to realize product inspection to obtain an intuitive two-dimensional image. The area array camera has a wide range of applications and can be applied to measurements such as area, shape, size, position, and temperature. The line array camera uses a single beam of scanning light to scan an object to obtain an image with high resolution. The sensor of the line array camera has only one row of photosensitive elements. When the imaging system 100 is working, the sample 200 to be inspected moves at a uniform speed, and one or more line array cameras are used to continuously scan line by line to achieve uniform inspection of the entire surface of the sample 200 to be inspected. The image sensor 30 of the area array camera or the image sensor 30 of the line array camera can be selected according to the imaging requirements.

[0175] See also Figure 1 In some embodiments, the driving device 80 includes a driving member 81 and a transmission assembly 82 connected to the driving member 81 , the transmission assembly 82 is connected to the optical correction device 20 , and the driving member 81 drives the optical correction device 20 to move through the transmission assembly 82 .

[0176] In this way, the optical correction device 20 can be moved into or out of the imaging light path through the driving member 81 and the transmission assembly 82 , so that the imaging system 100 can clearly image the first surface 210 and the second surface 220 of the sample 200 .

[0177] Specifically, the driving member 81 may be a motor or a cylinder. When the driving member 81 is a motor, the transmission assembly 82 is an assembly that converts the rotational motion of the motor into linear motion.

[0178] See also Figure 1 In some embodiments, the transmission assembly 82 includes a screw rod 83 and a slider 84 mounted on the screw rod 83, the screw rod 83 is connected to the driving member 81, and the slider 84 is connected to the optical correction device 20. The driving member 81 is used to drive the screw rod 83 to rotate, thereby driving the slider 84 and the optical correction device 20 to move.

[0179] In this way, the optical correction device 20 can be moved into or out of the imaging light path by rotating the lead screw 83 , so that the imaging system 100 can clearly image the first surface 210 and the second surface 220 of the sample 200 .

[0180] Specifically, the optical correction device 20 can be fixed to the slider 84 by fasteners such as bolts. When the driving member 81 drives the screw rod 83 to rotate, the slider 84 moves linearly along the length direction of the screw rod 83 to move the optical correction device 20 into or out of the imaging light path.

[0181] Of course, in other embodiments, the transmission assembly 82 may be a crank slider assembly, a gear rack assembly, or the like, which can convert rotational motion into linear motion.

[0182] Please refer again Figure 1 In some embodiments, the driving device 80 further includes a base 85 and a slide rail 86 disposed on the base 85 , the slider 84 is slidably disposed on the slide rail 86 , and the driving member 81 is installed on the base 85 .

[0183] In this way, the slide rail 86 can not only make the optical correction device 20 move more smoothly, but also make the optical correction device 20 remain in the same plane when moving into or out of the imaging light path.

[0184] Specifically, the base 85 is used to carry the driving member 81 and the slide rail 86, and the surface shape of the base 85 is not strictly limited. Exemplarily, the base 85 can be a substantially rectangular plate-shaped structure. In some embodiments, the slide rail 86 can be fixed to the base 85 by fasteners such as bolts, and the slider 84 can slide between the two ends of the slide rail 86. The screw rod 83 is located above the slide rail 86, and the length direction of the screw rod 83 is parallel to the length direction of the slide rail 86.

[0185] The driving member 81 can be installed on the base 85 through the mounting frame 87. The mounting frame 87 can be L-shaped. The driving member 81 can be fixed to the side of the mounting frame 87 by fasteners such as bolts, and the bottom surface of the mounting frame 87 can also be fixed to the base 85 by fasteners such as bolts.

[0186] See also Figure 1 In some embodiments, the optical correction device 20 includes a lens barrel 25, a lens group 21 and a bracket 26, the lens group 21 is disposed in the lens barrel 25, and the bracket 26 connects the lens barrel 25 and the transmission assembly 82.

[0187] In this way, the lens barrel 25 can carry the lens group 21, and the bracket 26 is connected to the transmission assembly 82, so that the transmission assembly 82 can drive the bracket 26 to move, thereby moving the lens group 21 into or out of the imaging light path.

[0188] Specifically, in some embodiments, the lens barrel 25 can be cylindrical, and one end of the bracket 26 can be fixedly connected to the outside of the lens barrel 25 by fasteners or welding. The bracket 26 and the lens barrel 25 can also be formed as an integral structure, and the other end of the bracket 26 can be fixedly connected to the slider 84 of the transmission assembly 82 by fasteners such as bolts.

[0189] See also Figure 1 In some embodiments, the driving device 80 further includes a detection device 90 , and the detection device 90 is used to limit the movement range of the optical correction device 20 .

[0190] In this way, the movement range of the optical correction device 20 into or out of the imaging optical path can be limited by the detection device 90 .

[0191] Please refer again Figure 1 In some embodiments, the detection device 90 includes a first detector 91 and a second detector 92, the first detector 91 is used to trigger a first signal when the optical correction device 20 moves into the imaging light path, and the second detector 92 is used to trigger a second signal when the optical correction device 20 moves out of the imaging light path, and the driving device 80 stops working according to the first signal or the second signal.

[0192] In this way, the first detector 91 and the second detector 92 can limit the movement stroke of the optical correction device 20 and serve as a zero point reset, and can also limit the movement range of the optical correction device 20.

[0193] Specifically, in some embodiments, the first detector 91 and the second detector 92 are mounted on the base 85 and are located on the same side of the slide rail 86, the optical correction device 20 is located on the other side of the slide rail 86, the first detector 91 is arranged away from the driving member 81, and the second detector 92 is arranged close to the driving member 81.

[0194] See also Figure 1 In some embodiments, the first detector 91 is disposed on a side when the optical correction device 20 moves into the imaging light path, the second detector 92 is disposed on a side when the optical correction device 20 moves out of the imaging light path, and the detection device 90 includes a trigger member 93 that moves synchronously with the optical correction device 20;

[0195] When the optical correction device 20 moves into the imaging light path, the trigger member 93 cooperates with the first detector 91 to cause the first detector 91 to trigger a first signal. When the optical correction device 20 moves out of the imaging light path, the trigger member 93 cooperates with the second detector 92 to cause the second detector 92 to trigger a second signal.

[0196] In this way, the trigger member 93 causes the first detector 91 and the second detector 92 to generate trigger signals, thereby controlling the movement of the optical correction device 20 on the slide rail 86 .

[0197] Specifically, the trigger member 93 is, for example, a sheet-like component. The trigger member 93 can be disposed on the slider 84 and located on a side close to the first detector 91 and the second detector 92. When the optical correction device 20 moves into the imaging optical path, the trigger member 93 can touch the first detector 91, the detection device 90 sends a first signal, the driving member 81 stops working, and the imaging system 100 images the first surface 210 of the sample 200 to be inspected; similarly, when the optical correction device 20 moves out of the imaging optical path, the trigger member 93 can touch the second detector 92, the detection device 90 sends a second signal, the driving member 81 stops working, and the imaging system 100 images the second surface 220 of the sample 200 to be inspected.

[0198] The first detector 91 and / or the second detector 92 include but are not limited to photoelectric induction switches, Hall sensors, micro switches, etc. For example, when the first detector 91 and the second detector 92 are photoelectric induction switches, the trigger member 91 can block the optical paths of the first detector 91 and the second detector 92, so that the first detector 91 and the second detector 92 trigger response signals.

[0199] The sequencing system according to the embodiment of the present application includes an imaging system 100 .

[0200] The imaging system 100 of the present solution corrects the aberration between the first surface 210 and the second surface 220 of the sample 200 to be inspected by the optical correction device 20, so that the imaging system 100 can clearly image the first surface 210 and the second surface 220 of the sample 200 to be inspected, thereby improving the sequencing efficiency and sequencing throughput. The sequencing system of the embodiment of the present application includes but is not limited to systems with sequencing functions such as gene sequencing and nucleic acid sequencing, and other systems manufactured using the same principle are also applicable to the embodiment of the present application.

[0201] See also Figure 2 and Fig. 9 The imaging method of the embodiment of the present application uses an imaging system 100 to image a sample 200 to be inspected. The sample 200 to be inspected includes a first surface 210 and a second surface 220. The imaging system 100 includes an objective lens 10, an optical correction device 20 and an image sensor 30. The optical correction device 20 can be moved into or out of the imaging optical path of the imaging system 100. The imaging method includes:

[0202] S10, controlling the optical correction device 20 to move into the imaging optical path so that the optical correction device 20 is located between the objective lens 10 and the image sensor 30;

[0203] S20, using the image sensor 30 to collect a first optical signal 211 generated by the first surface 210 of the sample 200 to be inspected;

[0204] S30, controlling the optical correction device 20 to move out of the imaging light path, and using the image sensor 30 to collect the second optical signal 221 generated by the second surface 220 of the sample 200 to be inspected.

[0205] In this way, the aberration between the first surface 210 and the second surface 220 of the sample 200 is corrected by the optical correction device 20, so that the imaging system 100 can clearly image the first surface 210 and the second surface 220 of the sample 200, thereby improving sequencing efficiency and sequencing throughput.

[0206] In one embodiment, when the driving member 81 is a motor, the application process of the imaging system 100 of the embodiment of the present application can be as follows: the driving member 81 drives the screw 83 to rotate, and the optical correction device 20 moves into the imaging optical path along the slide rail 86. When the trigger member 93 touches the first detector 91, the detection device 90 sends a first signal, and the driving member 81 stops working. At this time, the optical correction device 20 is located on the optical axis of the objective lens 10. The first light source 61 sends an illumination light beam, which is irradiated on the sample to be inspected 200 through the objective lens 10 to stimulate the sample to be inspected 200 to generate fluorescence. The objective lens 10 collects the first optical signal 211 generated by the first surface 210, and the first dichroic mirror 41 transmits part of the first optical signal 211 to form a first light beam 230. The first light beam 230 is reflected by the first reflector 42 to the first image sensor 31 for imaging. The first dichroic mirror 41 reflects another part of the first optical signal 211 to form a second light beam 240. The second light beam 240 is reflected by the second reflector 43 to the second image sensor 32 for imaging.

[0207] The driving member 81 works again to drive the screw rod 83 to rotate, and the optical correction device 20 moves out of the imaging optical path along the slide rail 86. When the trigger member 93 touches the second detector 92, the detection device 90 sends a second signal, and the driving member 81 stops working. At this time, the optical correction device 20 is located on the optical axis side of the objective lens 10. The first light source 61 sends an illumination light beam, which is irradiated on the sample 200 to be inspected through the objective lens 10, and excites the sample 200 to generate fluorescence. The objective lens 10 collects the second optical signal 221 generated by the second surface 220, and the first dichroic mirror 41 transmits part of the second optical signal 221 to form a first light beam 230. The first light beam 230 is reflected by the first reflector 42 to the first image sensor 31 for imaging. The first dichroic mirror 41 reflects another part of the second optical signal 221 to form a second light beam 240, and the second light beam 240 is reflected by the second reflector 43 to the second image sensor 32 for imaging.

[0208] In the description of this specification, the description with reference to the terms "one embodiment", "certain embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0209] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

Claims

1. A driving device, characterized in that: The driving device is used in an imaging system, which includes an optical correction device. The driving device is connected to the optical correction device and is used to drive the optical correction device to move so that the optical correction device moves into or out of the imaging light path of the imaging system.

2. The driving device according to claim 1, characterized in that: The driving device comprises a driving member and a transmission assembly connected to the driving member, the transmission assembly is connected to the optical correction device, and the driving member drives the optical correction device to move through the transmission assembly; Optionally, the transmission assembly includes a screw and a slider sleeved on the screw, the screw is connected to the driving member, the slider is connected to the optical correction device, and the driving member is used to drive the screw to rotate, thereby driving the slider and the optical correction device to move; Optionally, the driving device further comprises a base and a slide rail arranged on the base, the slider is slidably arranged on the slide rail, and the driving member is mounted on the base; Optionally, the optical correction device comprises a lens barrel, a lens group and a bracket, the lens group is arranged in the lens barrel, and the bracket connects the lens barrel and the transmission assembly.

3. The driving device according to claim 1 or 2, characterized in that: The driving device further comprises a detection device, and the detection device is used to limit the movement stroke of the optical correction device; Optionally, the detection device includes a first detector and a second detector, the first detector is used to trigger a first signal when the optical correction device moves into the imaging light path, and the second detector is used to trigger a second signal when the optical correction device moves out of the imaging light path, and the driving device stops working according to the first signal or the second signal; Optionally, the first detector is arranged on a side when the optical correction device moves into the imaging light path, the second detector is arranged on a side when the optical correction device moves out of the imaging light path, and the detection device includes a trigger member that moves synchronously with the optical correction device; When the optical correction device moves into the imaging light path, the trigger cooperates with the first detector so that the first detector triggers the first signal; when the optical correction device moves out of the imaging light path, the trigger cooperates with the second detector so that the second detector triggers the second signal.

4. The driving device according to any one of claims 1 to 3, characterized in that: The optical correction device includes a lens group, and the lens group is used to eliminate spherical aberration; Optionally, the lens group includes a first lens, a second lens and a third lens arranged in sequence, and the optical power of the first lens, the second lens and the third lens after being combined is substantially 0, and the allowable error is ±1%; Optionally, the first lens has negative optical power, the second lens has positive optical power, and the third lens has negative optical power; the object side surface of one lens and the image side surface of another lens in a group of adjacent lenses are arranged opposite to each other; Optionally, the object side of the first lens is a plane at the optical axis of the first lens, and the image side of the first lens is a concave surface at the optical axis of the first lens; and / or, The object side of the second lens is a convex surface at the optical axis of the second lens, and the image side of the second lens is a convex surface at the optical axis of the second lens; and / or, The object side of the third lens is a concave surface at the optical axis of the third lens, and the image side of the third lens is a flat surface at the optical axis of the third lens.

5. An imaging system, characterized in that: The invention comprises a driving device as described in any one of claims 1 to 4.

6. The imaging system according to claim 5, characterized in that: The imaging system further comprises an objective lens and an image sensor, and when the optical correction device moves into the imaging optical path, the optical correction device is located between the objective lens and the image sensor; Optionally, when the optical correction device moves into the imaging light path, the image sensor is used to collect a first optical signal generated by a first surface of the sample to be inspected; when the optical correction device moves out of the imaging light path, the image sensor is used to collect a second optical signal generated by a second surface of the sample to be inspected; Optionally, when the optical correction device is moved into the imaging optical path, the optical correction device is located on the optical axis of the objective lens; Optionally, the center deviation between the optical correction device and the objective lens does not exceed 0.5 mm; Optionally, the first surface is located between the objective lens and the second surface; Optionally, there is a fluid between the first surface and the second surface, and the optical correction device is used to reduce or eliminate the aberration caused by the fluid; Optionally, the aberration comprises spherical aberration; Optionally, a beam splitter component is arranged between the objective lens and the image sensor, the beam splitter component is used to split the optical signal collected by the objective lens into a plurality of light beams with different wavelengths, the number of the image sensors is multiple, and each of the image sensors is used to collect a light beam of at least one wavelength and form an image; Optionally, the beam splitting component is used to split the optical signal collected by the objective lens into a first light beam and a second light beam, and the image sensor includes a first image sensor and a second image sensor, the first image sensor is used to collect the first light beam and form an image, and the second image sensor is used to collect the second light beam and form an image; Optionally, the light splitting assembly includes a first dichroic mirror, a first reflector, and a second reflector; The first dichroic mirror is arranged on the optical axis of the objective lens and is tilted relative to the optical axis of the objective lens. The first dichroic mirror is used to separate the optical signal collected by the objective lens into a first light beam and a second light beam, so that the first light beam is transmitted to the first reflector and the second light beam is reflected to the second reflector. The first reflector is used to reflect the first light beam to the first image sensor, and the second reflector is used to reflect the second light beam to the second image sensor. Optionally, the first dichroic mirror and the first reflector are arranged vertically; Optionally, the first dichroic mirror and the second reflector are arranged in parallel; Optionally, the imaging system includes a first tube lens and a second tube lens, the first tube lens is arranged between the first image sensor and the first reflector, and is used to converge the first light beam to the first image sensor; the second tube lens is arranged between the second image sensor and the second reflector, and is used to converge the second light beam and the fourth light beam to the second image sensor; Optionally, the imaging system includes a first filter and a second filter, the first filter is arranged between the first tube lens and the first reflector, and is used to filter the first light beam entering the first tube lens; the second filter is arranged between the second tube lens and the second reflector, and is used to filter the second light beam entering the second tube lens.

7. The imaging system according to claim 6, characterized in that The imaging system comprises a light source assembly, and the light source assembly is used to emit an excitation light beam to the sample through the objective lens; Optionally, the light source assembly includes a first light source and a first lens disposed on an illumination light path of the first light source, the first lens being used to control an aperture of a light beam of the first light source entering the objective lens; Optionally, a bandpass filter is disposed between the first lens and the objective lens, and the bandpass filter is used to perform bandpass filtering on the light passing through the first lens; Optionally, the imaging system includes a second dichroic mirror arranged between the bandpass filter and the objective lens, the second dichroic mirror is arranged on the optical axis of the objective lens and tilted relative to the optical axis of the objective lens, and the second dichroic mirror is used to reflect the light passing through the bandpass filter to the objective lens and to transmit the light from the objective lens.

8. The imaging system according to any one of claims 6 or 7, characterized in that: The imaging system comprises an autofocus device, which comprises a second light source and a focus sensor, wherein the second light source is used to project a light beam emitted by the second light source onto a sample to be inspected through the objective lens; the focus sensor is used to receive a light beam reflected from the sample to be inspected and collimated by the objective lens, and convert an optical signal into an electrical signal, so that the objective lens moves according to the electrical signal, so that the sample to be inspected is located on a focal plane of the objective lens; Optionally, the imaging system further comprises a third dichroic mirror, which is arranged on the optical axis of the objective lens, and is used to reflect the light beam emitted by the second light source so that the light beam emitted by the second light source is projected onto the sample to be inspected through the objective lens, and reflects the light beam reflected from the sample to be inspected to the focus sensor, and the third dichroic mirror is also used to allow the light beam from the objective lens to pass through.

9. The imaging system according to any one of claims 6 to 8, characterized in that: The image sensor is an image sensor of an area array camera or an image sensor of a line array camera.

10. A sequencing system, characterized in that: An imaging system comprising any one of claims 5-9.

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