Optical components and fluorescence microscopy systems for fluorescence microscopy

Abstract

The present disclosure relates to an optical assembly for fluorescence microscopy and a fluorescence microscopy system. The optical assembly includes: an illumination module, including a light source that emits excitation light for exciting a sample; a signal collection module, including an objective lens that guides the excitation light from the illumination module to the sample and guides the emission light from the sample to an imaging module; an imaging module, including an image sensor that images the emission light from the sample and a tube lens configured to guide the emission light from the objective lens to the image sensor; and a dichroic mirror, which is arranged on an optical path between the excitation light from the light source to the objective lens and on an optical path between the emission light from the objective lens to the tube lens, and the dichroic mirror transmits one of the excitation light and the emission light and reflects the other of the excitation light and the emission light. The objective lens and the tube lens form an infinite conjugate with each other, and the illumination module, the signal collection module and the imaging module are detachably assembled together via a mechanical interface to achieve optical alignment and mechanical structure.

Description

Technical Field

[0001] The present disclosure relates to the field of fluorescence microscopy detection. More specifically, the present disclosure relates to an optical component for fluorescence microscopy detection and a fluorescence microscopy detection system comprising the optical component. Background Art

[0002] Biological sample detection and analysis systems such as fluorescence microscopy detection systems can be used in a variety of applications, such as DNA sequencing, nucleic acid detection and other gene sequencing applications. Existing biological sample detection and analysis systems are usually high-throughput, in order to meet the needs of high throughput and high sample number and flexible startup in some applications. However, for high-throughput gene sequencing applications (such as second-generation sequencing), it is usually required that the biological sample detection and analysis system use a conventional optical microscope system for large-area scanning, which makes the traditional biological sample detection and analysis system usually have defects such as bulky size, complex structure, high design cost, and high maintenance requirements.

[0003] For example, in some existing biological sample detection and analysis systems, it is necessary to use an adjustable optical lens adjustment frame in the optical platform to adjust the optical components for optical alignment, which not only leads to a complex mechanical structure design of the biological sample detection and analysis system, but also makes the optical adjustment of the biological sample detection and analysis system time-consuming and difficult.

[0004] In addition, in some other biological sample detection and analysis systems, the optical components used need to be individually designed in advance according to the throughput requirements of different customers, and in order to ensure the assembly accuracy between the various components of the optical components, the optical components are often assembled using a large-scale production line fully automatic assembly process such as whole-body bonding. This results in the optical components in the biological sample detection and analysis system often being inseparable, resulting in the need to redesign the optical components and replace them as a whole when the customer's throughput requirements change. Such defects result in time-consuming changes to the optical components in the existing biological sample detection and analysis systems (the change cycle is generally 3-5 months), high cost of changes (the entire optical component needs to be redesigned and updated), and low flexibility in changes and production (only applicable to large-scale production, not to small-scale production of biological sample detection and analysis systems with different throughput requirements).

[0005] At present, there is a strong demand for medium-low throughput miniaturized biological sample detection and analysis systems suitable for small-batch production (e.g., medium-low throughput desktop second-generation sequencers). However, the existing biological sample detection and analysis systems are difficult to simply and directly quantify and miniaturize due to the above-mentioned defects and deficiencies, and are difficult to produce in small batches at a low cost. Summary of the invention

[0006] The main purpose of the present disclosure is to provide an optical component for fluorescence microscopy detection and a biological sample detection and analysis system (e.g., a fluorescence microscopy detection system) comprising the optical component, which can overcome one or more defects in existing biological sample detection and analysis systems, is suitable for small-batch production at a lower cost, has a simple structure, and / or has design flexibility.

[0007] In a first aspect of the present disclosure, an optical assembly for fluorescence microscopy detection is provided, the optical assembly comprising: an illumination module, the illumination module comprising a light source configured to emit excitation light for exciting a sample; a signal collection module, the signal collection module comprising an objective lens configured to guide the excitation light from the illumination module to the sample and to guide the emission light from the sample to an imaging module; an imaging module, the imaging module comprising an image sensor for imaging the emission light from the sample and a tube lens configured to guide the emission light from the objective lens to the image sensor; and a dichroic mirror, the dichroic mirror being arranged The dichroic mirror is disposed on an optical path between the excitation light from the light source to the objective lens and on an optical path between the emission light from the objective lens to the tube lens, the dichroic mirror being configured to transmit one of the excitation light and the emission light and reflect the other of the excitation light and the emission light, wherein the objective lens and the tube lens form an infinite conjugate with each other, wherein the dichroic mirror is a part of one of the illumination module, the signal collection module and the imaging module, and wherein the illumination module, the signal collection module and the imaging module are detachably assembled together via a mechanical interface to achieve optical alignment and mechanical structure.

[0008] According to one embodiment of the present disclosure, the optical component meets the following conditions: Wherein, f1 is the focal length of the objective lens, NA is the numerical aperture of the objective lens, f2 is the focal length of the tube lens, and λ is the wavelength of the emitted light in μm.

[0009] According to one embodiment of the present disclosure, the focal length of the tube lens is designed to be 5mm-100mm.

[0010] According to one embodiment of the present disclosure, the lighting module includes a first light source configured to emit first excitation light in a first wavelength range and a second light source configured to emit second excitation light in a second wavelength range different from the first wavelength range. The lighting module also includes a second dichroic mirror arranged on an optical path of the first excitation light from the first light source to the dichroic mirror and on an optical path of the second excitation light from the second light source to the dichroic mirror. The second dichroic mirror is configured to transmit one of the first excitation light and the second excitation light and reflect the other of the first excitation light and the second excitation light.

[0011] According to one embodiment of the present disclosure, the lighting module also includes a converging lens for converging the first excitation light and the second excitation light and an excitation filter for filtering the first excitation light and the second excitation light, and the converging lens and the excitation filter are located on the optical path from the second dichroic mirror to the dichroic mirror.

[0012] According to one embodiment of the present disclosure, the imaging module includes a first image sensor configured to image first emitted light in a third wavelength range and a second image sensor configured to image second emitted light in a fourth wavelength range different from the third wavelength range. The imaging module also includes a third dichroic mirror arranged on an optical path of the first emitted light from the dichroic mirror to the first image sensor and on an optical path of the second emitted light from the dichroic mirror to the second image sensor. The third dichroic mirror is configured to transmit one of the first emitted light and the second emitted light and reflect the other of the first emitted light and the second emitted light.

[0013] According to one embodiment of the present disclosure, the imaging module further includes an emission filter for filtering the first emission light and the second emission light, and the tube lens and the emission filter are located on an optical path from the dichroic mirror to the third dichroic mirror.

[0014] According to one embodiment of the present disclosure, the signal collection module further includes a focus motor coupled to the objective lens, and the focus motor is configured to move the objective lens to focus on the sample.

[0015] According to an embodiment of the present disclosure, the lighting module includes one or more light source mounting seats for mounting the light source, the light source mounting seat includes a cylindrical supporting component, and the light source is detachably mounted in the supporting component.

[0016] According to an embodiment of the present disclosure, a heat sink is installed at an end of the support component opposite to an end at which the light source is installed, so as to dissipate heat from the light source.

[0017] According to an embodiment of the present disclosure, an enhanced heat conduction element is provided between the support component and the heat sink to enhance the heat dissipation effect of the heat sink.

[0018] According to an embodiment of the present disclosure, the support component is formed integrally with the heat sink.

[0019] According to an embodiment of the present disclosure, the heat sink includes a flange portion, and the support member is inserted into and fixed in the flange portion using a fastening element.

[0020] According to an embodiment of the present disclosure, the lighting module includes a collimating lens mounting seat for arranging a collimating lens, and the light source mounting seat can be detachably connected to the collimating lens mounting seat.

[0021] According to one embodiment of the present disclosure, the collimating lens mount is in the shape of a cube and is provided with a through channel suitable for light to pass through. One or more mounting flanges are provided on one or more surfaces of the collimating lens mount, and the supporting component of the light source mount can be inserted into the mounting flange to connect the light source mount to the collimating lens mount.

[0022] According to an embodiment of the present disclosure, a stop step surface is provided inside the mounting flange of the collimating lens mounting seat for positioning the supporting component of the light source mounting seat.

[0023] According to one embodiment of the present disclosure, the mounting flange of the collimating lens mounting seat and the supporting component of the light source mounting seat are locked and fixed to each other via a fastening element.

[0024] According to one embodiment of the present disclosure, the concentricity between the mounting flange of the collimating lens mounting seat and the supporting component of the light source mounting seat is maintained between 1-100 microns.

[0025] According to one embodiment of the present disclosure, a narrow groove is provided on one surface of the collimating lens mount, and the second dichroic mirror can be inserted through the narrow groove and positioned in the collimating lens mount.

[0026] According to an embodiment of the present disclosure, the lighting module further comprises a condenser lens mounting seat for arranging a condenser lens, and the condenser lens mounting seat can be detachably connected to the collimating lens mounting seat in a manner opposite to the light source mounting seat.

[0027] According to one embodiment of the present disclosure, the condenser lens mounting seat includes a cylindrical lens barrel, and the condenser lens can be detachably mounted in the lens barrel.

[0028] According to one embodiment of the present disclosure, the optical path deviation in the lens barrel is set within a range of 1-100 microns.

[0029] According to an embodiment of the present disclosure, connecting flanges are provided at both ends of the lens barrel, so that the focusing lens mounting seat can be detachably connected to the collimating lens mounting seat via the connecting flanges.

[0030] According to one embodiment of the present disclosure, a positioning element is provided on the connecting surface of the collimating lens mount, and a positioning hole for the positioning element to extend through is provided on the connecting flange of the focusing lens mount, so as to accurately position the focusing lens mount.

[0031] According to one embodiment of the present disclosure, the optical assembly includes a separate dichroic mirror mounting seat to mount the dichroic mirror.

[0032] According to one embodiment of the present disclosure, a side surface of the separate dichroic mirror mount is provided with a narrow slot, and the dichroic mirror can be inserted into the separate dichroic mirror mount through the narrow slot.

[0033] According to one embodiment of the present disclosure, a top surface of the separate dichroic mirror mount is provided with a positioning edge to facilitate accurate positioning of the imaging module.

[0034] The signal collection module is disposed below the separate dichroic mirror mounting seat in a manner that it can move up and down along a vertical direction.

[0035] According to one embodiment of the present disclosure, the signal collection module includes an objective lens mount, the objective lens mount includes an upper surface, a lower surface and a rear surface, the objective lens is mounted on the lower surface of the objective lens mount, and a focus motor is installed on the rear surface of the objective lens mount.

[0036] According to one embodiment of the present disclosure, the imaging module is disposed above the separate dichroic mirror mount and includes a tube lens mount and a reflector or dichroic mirror mount.

[0037] According to an embodiment of the present disclosure, the tube lens mounting seat includes a tube lens barrel and connecting flanges arranged at both ends of the tube lens barrel, and one connecting flange of the tube lens barrel can be detachably fixed to the separate dichroic mirror mounting seat.

[0038] According to one embodiment of the present disclosure, the reflector or dichroic mirror mounting seat is in the shape of a cube and includes an inclined surface with an opening, and the reflector or the third dichroic mirror is detachably mounted on the inclined surface.

[0039] According to one embodiment of the present disclosure, one or more image sensor interfaces are provided on one or more surfaces of the reflector or dichroic mirror mount, and the image sensor interfaces are constructed as standard industrial interfaces.

[0040] According to one embodiment of the present disclosure, the image sensor interface is a standard C-type interface for imaging devices.

[0041] According to one embodiment of the present disclosure, the sample is placed in a biochemical reaction flow cell.

[0042] In a second aspect of the present disclosure, a fluorescence microscopic detection system is provided, which comprises an optical assembly according to the present disclosure and a flow cell for placing a sample.

[0043] According to one embodiment of the present disclosure, the fluorescence microscopy detection system further includes a scanning platform for carrying the flow cell.

[0044] According to one embodiment of the present disclosure, the parallelism between the reference plane of the optical component and the reference plane of the fixing base plate is controlled within a range of 1 to 50 microns.

[0045] According to one embodiment of the present disclosure, the parallelism of the sample slide in the flow cell is controlled within a range of 2 to 20 microns, and the parallelism of the surface of the scanning platform on which the flow cell is loaded is controlled within a range of 1 to 20 microns.

[0046] According to one embodiment of the present disclosure, the parallelism between the objective lens of the optical assembly and the sample slide in the flow cell is controlled within a range of 5 to 20 microns.

[0047] Other features and advantages of the present disclosure will become more apparent from the following detailed description of exemplary embodiments of the present disclosure with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The accompanying drawings, which constitute a part of the specification, illustrate embodiments of the present disclosure and, together with the description, serve to explain the principles of the present disclosure.

[0049] The present disclosure may be more clearly understood from the following detailed description with reference to the accompanying drawings, in which:

[0050] Figure 1 Schematically illustrates an optical arrangement of an optical assembly according to an embodiment of the present disclosure;

[0051] Figure 2 The principle of the infinite conjugate optical system is schematically shown;

[0052] Figure 3 The relationship between the focal length of the tube lens and the imaging error is schematically shown;

[0053] Figure 4 schematically illustrates an optical arrangement of an optical assembly according to another embodiment of the present disclosure;

[0054] Figure 5 Schematically illustrates an optical arrangement of an optical assembly according to yet another embodiment of the present disclosure;

[0055] Figure 6 Schematically illustrates the mechanical structure of an optical assembly according to an embodiment of the present disclosure;

[0056] Figure 7 Schematically illustrates the mechanical structure of a lighting module of an optical assembly according to an embodiment of the present disclosure;

[0057] Figure 8 Schematically illustrates the mechanical structure of an imaging module of an optical assembly according to an embodiment of the present disclosure;

[0058] Fig. 9 A fluorescence microscopy detection system according to an embodiment of the present disclosure is schematically shown.

[0059] Note that in the embodiments described below, sometimes the same reference numerals are used in common between different drawings to represent the same parts or parts with the same functions, and their repeated descriptions are omitted. In some cases, similar numbers and letters are used to represent similar items, so once an item is defined in one drawing, it does not need to be further discussed in subsequent drawings.

[0060] For ease of understanding, the positions, sizes, and ranges of various structures shown in the drawings and the like sometimes do not represent actual positions, sizes, and ranges, etc. Therefore, the present disclosure is not limited to the positions, sizes, and ranges, etc. disclosed in the drawings and the like. Moreover, the drawings are not necessarily drawn to scale, and some features may be exaggerated to show details of specific components. DETAILED DESCRIPTION

[0061] Each exemplary embodiment of the present disclosure will be described in detail below with reference to the accompanying drawings. It should be noted that the following description of each exemplary embodiment is actually only illustrative and is by no means intended to limit the present disclosure and its application or use. That is, the structures and methods herein are shown in an exemplary manner to illustrate different embodiments of the structures and methods in the present disclosure. However, those skilled in the art will appreciate that they merely illustrate exemplary ways of the present disclosure that can be used to implement, rather than an exhaustive way. In addition, unless otherwise specifically stated, the relative arrangement of the components and steps, numerical expressions, and numerical values ​​described in these embodiments do not limit the scope of the present disclosure.

[0062] Technologies, methods, and apparatus known to ordinary technicians in the relevant field may not be discussed in detail, but where appropriate, such technologies, methods, and apparatus should be considered part of the authorization specification.

[0063] It should be noted that the drawings depicted in the present disclosure are merely schematic illustrations of the relative positional relationship of the components according to the embodiments of the present disclosure, and unless otherwise specified, the specific structure of the components is not particularly limited. It should also be noted that the embodiments of the present disclosure may further include additional components that are neither discussed herein nor shown in the drawings in order to avoid blurring the main points of the present disclosure.

[0064] The present disclosure provides an optical assembly for fluorescence microscopic detection and a fluorescence microscopic detection system including the optical assembly. In addition to its unique optical arrangement, the optical assembly according to the present disclosure also abandons the integrated design and assembly concept commonly used in existing optical assemblies, and forms multiple modules by appropriately grouping the components of the optical assembly, and accurately designs the basic constant mechanical structure of each module according to the grouping (that is, when used for different fluxes, the mechanical structure of each module of the optical assembly does not need to be significantly changed or redesigned), thereby achieving the design flexibility of the optical assembly and simply replacing the optical components in the corresponding modules to assemble into optical assemblies suitable for different fluxes, so that the purpose of small-scale production can be achieved with a shorter transformation cycle and low cost. In addition, the optical assembly according to the present disclosure abandons the optical lens adjustment frame required in the existing optical assembly, and ensures optical accuracy through the precise connection between the constant mechanical structures of each module, thereby avoiding the steps of manually adjusting the optical alignment and simplifying the operation. The optical assembly according to the present disclosure and the fluorescence microscopic detection system including the optical assembly will be described in detail below in conjunction with the accompanying drawings.

[0065] First refer to Figure 1 The optical arrangement of the optical assembly 100 for fluorescence microscopy detection according to the present disclosure is described below. Figure 1 As shown, the optical assembly 100 may include an illumination module 110, a signal collection module 120, and an imaging module 130. The optical assembly 100 may detect the sample 150 by irradiating the sample 150 with excitation light and collecting the emission light emitted by the excited sample 150. As a non-limiting example, the sample 150 may be, for example, a biological sample (e.g., a DNA sequence, etc.), in which the target analyte that may be contained may have fluorescent properties itself or be labeled with a fluorophore. Therefore, when excited, the sample 150 may emit light, and the wavelength of the emission light of the sample 150 is generally different from the wavelength of the excitation light. By detecting the emission light of the sample 150, the situation of the target analyte contained in the sample 150 may be analyzed. In some embodiments, the sample 150 may be placed in a biochemical reaction flow cell.

[0066] The lighting module 110 may include a light source 111 configured to emit excitation light for exciting the sample 150. The light source 111 may be any suitable light source as long as it can provide light with an excitation wavelength specific to the sample 150. The light source 111 may be, for example, a monochromatic or polychromatic light source, or a broadband light source capable of outputting light in a continuous wavelength range. Examples of the light source 111 include, but are not limited to, light emitting diodes (LEDs) or lasers. For example, the light source 111 may use a high-brightness LED light source with high power output in a small-sized light-emitting area to meet etendue design requirements, thereby ensuring sufficient output light intensity while miniaturizing the lighting module. For example, the light source 111 may be configured to provide 1-10 W / cm 2 lighting power density, or can be configured to provide 2-7W / cm 2 lighting power density, or can be configured to provide 2-4W / cm 2 lighting power density, etc.

[0067] In some embodiments, the illumination module 110 may further include a lens 112, which may be configured to collimate the excitation light emitted by the light source 111. The light source 111 is preferably located at the back focal plane of the lens 112. In some embodiments, the illumination module 110 may further include a stop 113, which may be configured to limit the excitation light from the light source 111 (collimated by the lens 112) to a predetermined beam size range. In some embodiments, the illumination module 110 may further include an excitation filter 114, which may be configured to filter the excitation light to obtain a desired excitation spectrum.

[0068] The signal collection module 120 may include an objective lens 121 configured to guide the excitation light from the illumination module 110 to the sample 150 and guide the emission light from the sample 150 to the imaging module 130 .

[0069] The imaging module 130 may include an image sensor 131 that images the emission light from the sample 150 and a tube lens 134 configured to guide the emission light from the objective lens 121 to the image sensor 131. In some embodiments, the sample 150, the objective lens 121, the tube lens 134, and the image sensor 131 may be located in a straight line. In some embodiments, the imaging module 130 may also include a reflector 133 that may deflect the emission light from the tube lens 134 onto the image sensor 131, so that the height of the imaging module 130 may be greatly reduced. In some embodiments, the imaging module 130 may also include an emission filter 132 that may be configured to filter the emission light to exclude the influence of interfering light.

[0070] In addition, the optical assembly 100 may further include a dichroic mirror 140, which is disposed on an optical path between the excitation light from the light source 111 to the objective lens 121 and on an optical path between the emission light from the objective lens 121 to the tube lens 134. The dichroic mirror 140 may transmit or reflect the received light according to the wavelength of the received light. The dichroic mirror 140 may be configured to transmit one of the excitation light and the emission light and reflect the other of the excitation light and the emission light, for example, Figure 1 In the illustrated case, the dichroic mirror 140 is configured to reflect the excitation light and transmit the emission light. Figure 1 In the embodiment, the dichroic mirror 140 is shown as a part of the imaging module 130, but this is only exemplary and not limiting. In the optical assembly according to the present disclosure, the dichroic mirror 140 can be a part of any one of the illumination module 110, the signal collection module 120 and the imaging module 130.

[0071] The objective lens 121 and the tube lens 134 of the optical assembly 100 form an infinite conjugate with each other. The magnification M of the infinite conjugate optical system formed by the objective lens 121 and the tube lens 134 satisfies the relationship M=f2 / f1=I h / O h , where f1 is the focal length of the objective lens 121, f2 is the focal length of the tube lens 134, h It is high, and I h It's like high. Figure 2The principle of the infinite conjugate optical system is schematically shown. It can be seen that the infinite conjugate design of the objective lens 121 and the tube lens 134 provides a parallel light transmission space between the objective lens 121 and the tube lens 134, so that the distance between the objective lens 121 and the tube lens 134 can be set with a large tolerance, for example, the distance can be 50mm±10mm, making the assembly of the optical component 100 easier. Moreover, the large tolerance allows the distance between the objective lens 121 and the tube lens 134 to vary within a large range, thereby allowing additional (one or more) optical elements (for example, a beam splitter, a filter and its corresponding bracket, etc.) to be inserted between the objective lens 121 and the tube lens 134, making the design of the optical component 100 more flexible. In addition, this also allows the objective lens 121 to move relative to the tube lens 134 in a direction close to or away from the tube lens 134 (that is, relative to the sample 150 in a direction away from or close to the sample 150), which can achieve better focusing without significantly affecting the imaging of the image sensor 131, ensuring that the object-side imaging accuracy is about 1-3 μm or less. In some embodiments, the signal collection module 120 may also include a focus motor 122 coupled to the objective lens 121, and the focus motor 122 may be configured to move the objective lens 121 to focus on the sample 150. In some examples, the focus motor 122 may move the objective lens 121 in a vertical direction perpendicular to the surface of the sample 150. In some examples, the focus motor 122 may be an autofocus motor, which may automatically move the objective lens 121 to a position determined based on the best focal plane information obtained by analyzing the image obtained from the imaging module 130. Additionally, in the case where the signal collection module 120 includes a focus motor 122 coupled to the objective lens 121 , the dichroic mirror 140 may be more preferably a part of one of the illumination module 110 and the imaging module 130 .

[0072] Furthermore, because the objective lens 121 and the tube lens 134 of the optical assembly 100 form an infinite conjugate with each other, the distance requirement between the objective lens 121 and the tube lens 134 is relatively loose, thereby allowing the optical assembly 100 to be split into the lighting module 110, the signal collection module 120, and the imaging module 130 described above, so that the lighting module 110, the signal collection module 120, and the imaging module 130 can each have a separate housing to accommodate their respective components in the corresponding housing, and then the lighting module 110, the signal collection module 120, and the imaging module 130 can be detachably assembled together via a mechanical interface to achieve optical alignment and mechanical structure. That is: the optical assembly 100 is assembled from a plurality of detachable modules, rather than being no longer detachable after the relative positional relationship of each component is accurately fixed during manufacturing, so that the optical assembly 100 can be easily reassembled after each split and the relative positional relationship between the components still meets the requirements.

[0073] In this way, the optical assembly 100 according to the present disclosure can have a detachable structure, which makes it easy to replace any one or more of the lighting module 110, the signal collection module 120, and the imaging module 130 based on the specific needs of different samples, and also facilitates the repair or replacement of the lighting module 110, the signal collection module 120, or the imaging module 130 separately. Such a detachable modular optical assembly 100 is easy to maintain, can also adapt to various detection requirements, and also leaves sufficient space for the subsequent development and upgrading of various components of the optical assembly 100.

[0074] In some embodiments, the image sensor 131 of the imaging module 100 of the optical assembly 100 according to the present disclosure may adopt a pixel array camera based on CMOS or CCD, etc. Preferably, the image sensor 131 may be a back-illuminated black and white CMOS image sensor. In order to enable the image sensor 131 to have a small pixel and a large array to achieve high resolution, the objective lens 121 and the tube lens 134 of the optical assembly 100 may satisfy the following expression:

[0075]

[0076] Wherein, f1 is the focal length of the objective lens 121, NA is the numerical aperture of the objective lens 121, f2 is the focal length 134 of the tube lens, and λ is the wavelength of the emitted light in μm. When the value is lower than the lower limit of expression (1), the pixel size of the image sensor 131 adapted to the objective lens 121 and the tube lens 134 will be too small, so that the same photon will be excessively divided into multiple pixels, resulting in a decrease in detection sensitivity. When the upper limit of expression (1) is exceeded, the pixel size of the image sensor 131 adapted to such an objective lens 121 and a tube lens 134 will be too large, resulting in too few pixel selections, and large-size pixels will increase costs and limit the field of view, ultimately affecting the flux requirements. The objective lens 121 and the tube lens 134 satisfying expression (1) can be adapted to an image sensor having a suitable small pixel and large array, so that the obtained optical component 100 covers a larger optical imaging area, improves the overall flux, and facilitates the realization of optimal optical resolution, sensitivity, field of view and other performance. At present, the pixel size of a mainstream typical CMOS image sensor can be in the range of about 1-4μm, and a larger pixel array such as 20-100 megabytes can be provided. The objective lens 121 and the tube lens 134 satisfying expression (1) can also be designed to be compatible with mainstream typical CMOS image sensors, thereby having a wide range of image sensor selection space, so that the imaging detection performance of the optical component 100 can have greater flexibility and versatility.

[0077] More preferably, the objective lens 121 and the tube lens 134 of the optical assembly 100 may satisfy the following expression:

[0078]

[0079] More preferably, the objective lens 121 and the tube lens 134 of the optical assembly 100 may satisfy the following expression:

[0080]

[0081] Since standard objective lenses usually have better designs and complex process flow, and are not easy to customize and modify, in order to make the cost of the optical component 100 lower, standard objective lenses can usually be used. Therefore, in order to achieve the above expression, the focal length of the tube lens can be further optimized. In some embodiments, the focal length of the tube lens can be designed to be 5mm-100mm. In some examples, the focal length of the tube lens can be designed to be 50mm-100mm, preferably 50mm-80mm, and more preferably 50mm-60mm. In some examples, the focal length of the tube lens can be designed to be 5mm-50mm, preferably 5mm-30mm, and more preferably 5mm-10mm. The reduction of the focal length of the tube lens allows the optical component 100 to have a smaller magnification, which can not only optimize the use and selection of the image sensor, but also shorten the object-image working distance (the distance from the sample 150 to the image sensor 131), for example, to 200mm or less. Thus, compared with the object-image working distance of about 400mm-500mm of conventional microscopic detection systems, the object-image working distance of the optical component 100 according to the present disclosure is greatly reduced, thereby having a greatly reduced height, so that the optical component 100 is miniaturized as a whole.

[0082] In addition, since the miniaturized optical assembly 100 has a shorter tube lens focal length, the imaging error caused by the installation error of the tube lens is also reduced. Figure 3 As shown in the figure, when the tube lens has a longer focal length f 2l When the height is O h The image of the object has a height I hl At this time, if the tube mirror tilts at an angle α due to installation errors or vibrations during transportation, use, etc., then the image dI hl When the tube lens has a shorter focal length f 2s When the height is O h The image of the object has a height I hs At this time, the tube lens tilt angle α causes the image to occur dI hs It can be seen that dI hs Less than dI hlThat is to say, the deflection error in the case of short focal length and working distance is much smaller than the deflection error in the case of long focal length and working distance. From another perspective, the shorter tube lens focal length not only makes the imaging error smaller so that no additional optical lens adjustment frame is required, but also makes the optical assembly 100 have a larger installation tolerance, reduces the difficulty of optical alignment, and significantly reduces the installation complexity and cost.

[0083] The modular design of the optical assembly according to the present disclosure may also allow the optical assembly to be expanded for detecting samples with different excitation / emission wavelengths. For example, Figure 4 Schematically illustrates an optical assembly 200 according to some embodiments of the present disclosure. The optical assembly 200 may include an illumination module 210, a signal collection module 220, and an imaging module 230. The dichroic mirror 240 is similar to the dichroic mirror 140 described above, but Figure 4 The signal collecting module 220 is used as a part of the signal collecting module 220. The signal collecting module 220 includes an objective lens 221 similar to the objective lens 121, which will not be described in detail here. In some embodiments, in order to achieve automatic focusing, a focus motor can also be coupled to a support component for supporting the sample 250 so as to achieve optimal focus by moving the sample 250 up and down relative to the objective lens 221.

[0084] Unlike the lighting module 110, in some embodiments, the lighting module 210 may include a first light source 211A configured to emit a first excitation light in a first wavelength range and a second light source 211B configured to emit a second excitation light in a second wavelength range different from the first wavelength range. The lighting module 210 also includes a second dichroic mirror 216 disposed on an optical path between the first excitation light from the first light source 211A to the dichroic mirror 240 and disposed on an optical path between the second excitation light from the second light source 211B to the dichroic mirror 240. The second dichroic mirror 216 may be configured to transmit one of the first excitation light and the second excitation light and reflect the other of the first excitation light and the second excitation light. For example, as a non-limiting example, in Figure 4In the embodiment of the present invention, the second dichroic mirror 216 is configured to transmit the first excitation light emitted by the first light source 211A and reflect the second excitation light emitted by the second light source 211B. In some embodiments, the lighting module 210 may further include a lens 212A and an aperture 213A for the first excitation light and a lens 212B and an aperture 213B for the second excitation light. The first excitation light emitted by the first light source 211A is collimated by the lens 212A and limited by the aperture 213A within a predetermined beam size range before reaching the second dichroic mirror 216. The second excitation light emitted by the second light source 211B is collimated by the lens 212B and limited by the aperture 213B within a predetermined beam size range before reaching the second dichroic mirror 216. When the first light source 211A and the second light source 211B work simultaneously, the first excitation light and the second excitation light can be synthesized into a light beam by the second dichroic mirror 216. Optionally, the synthesized light beam can be further converged by the focusing lens 215. In some embodiments, the illumination module 210 may further include an excitation filter 214, which may be configured to filter the first excitation light and the second excitation light to obtain a desired excitation spectrum. In some embodiments, each light source in the illumination module 210 may each have a separate excitation filter.

[0085] The dual-channel illumination of the illumination module 210 can be designed based on the Kohler illumination principle. Preferably, the first light source 211A and the second light source 211B can be located at the rear focal plane of the lens 212A and the lens 212B, respectively, and the apertures 213A and 213B can be located in front of the lens 212A and the lens 212B, respectively. Preferably, the distances from the second dichroic mirror 216 to the first light source 211A and the second light source 211B are the same. Preferably, the apertures 213A and 213B can be located at the rear focal plane of the lens 215. Preferably, the front focal plane of the lens 215 can coincide with the rear focal plane of the objective lens 221.

[0086] The illumination module 210 can be further modularly split into a plurality of submodules, for example, wherein the first submodule can include a first light source 211A, a lens 212A, and an aperture 213A, the second submodule can include a second light source 211B, a lens 212B, and an aperture 213B, the third submodule can include a second dichroic mirror 216, and the fourth submodule can include a lens 215 and an excitation filter 214. The first submodule, the second submodule, and the fourth submodule can be detachably coupled to the third submodule via a mechanical interface, respectively. In some embodiments, the lens 215 and the excitation filter 214 and the second dichroic mirror 216 can belong to one submodule. In some embodiments, the illumination module 210 can also include more submodules to include more different light sources, thereby supporting the excitation requirements of more different samples.

[0087] Unlike the imaging module 130, in some embodiments, the imaging module 230 may include a first image sensor 231A configured to image the first emission light in a third wavelength range and a second image sensor 231B configured to image the second emission light in a fourth wavelength range different from the third wavelength range. The imaging module 230 also includes a third dichroic mirror 235 that may be disposed on an optical path between the first emission light from the dichroic mirror 240 to the first image sensor 231A and on an optical path between the second emission light from the dichroic mirror 240 to the second image sensor 231B. The third dichroic mirror 235 may be configured to transmit one of the first emission light and the second emission light and reflect the other of the first emission light and the second emission light. For example, in Figure 4 , as a non-limiting example, the third dichroic mirror 235 transmits the first emission light so that the first emission light is received by the first image sensor 231A, and reflects the second emission light so that the second emission light is received by the second image sensor 231B. In some embodiments, the imaging module 230 may also include an emission filter 232 for filtering the first emission light and the second emission light, and the tube lens 234 and the emission filter 232 may be located on the optical path from the dichroic mirror 240 to the third dichroic mirror 235. Alternatively, each image sensor 231A, 231B may each have a separate emission filter, and each emission filter is located on the optical path from the third dichroic mirror 235 to the corresponding image sensor. Alternatively, the imaging module 230 may also include two tube lenses, so that each tube lens is located on the optical path from the third dichroic mirror 235 to the corresponding image sensor.

[0088] The imaging module 230 can be further modularly split into a plurality of submodules, for example, wherein the first submodule can include a first image sensor 231A, the second submodule can include a second image sensor 231B, the third submodule can include a third dichroic mirror 235, and the fourth submodule can include a tube lens 234 and an emission filter 232. The first submodule, the second submodule, and the fourth submodule can be detachably coupled to the third submodule via a mechanical interface, respectively. In some embodiments, the tube lens 234 and the emission filter 232 and the third dichroic mirror 235 can belong to one submodule. In some embodiments, the imaging module 230 can also include more submodules to include more different image sensors, thereby supporting the detection requirements of more different samples.

[0089] also, Figure 5The optical assembly 300 according to other embodiments of the present disclosure is also schematically shown. The optical assembly 300 may include an illumination module 310, a signal collection module 320, and an imaging module 330. Except that the dichroic mirror 240 is included as a part of the illumination module 310, the illumination module 310 is the same as the aforementioned illumination module 210, and the signal collection module 320 and the imaging module 330 are the same as the aforementioned signal collection module 120 and the imaging module 130, and their specific components are not repeated here.

[0090] like Figure 1 , Figure 4 and Figure 5 As exemplarily shown, the dichroic mirrors 140, 240 can be part of any of the lighting module, the signal collection module and the imaging module, and the optical component can be expanded to include one or more light sources and one or more image sensors, wherein the number of light sources and image sensors does not need to be the same, but can be specifically set according to actual needs.

[0091] Next, the specific mechanical structure of the optical assembly according to the embodiment of the present disclosure will be described in detail. As an example, Figure 6 Schematically shows Figure 5 The mechanical structure of the optical assembly 300 shown in FIG. 1 is a schematic diagram showing the mechanical structure of the illumination module 310, the signal collection module 320 and the imaging module 330 according to an embodiment of the present disclosure. However, it should be noted that Figure 6 The mechanical structure shown is non-limiting, and the mechanical structure of the optical assembly may be different depending on different optical arrangements of the optical assembly.

[0092] like Figure 7As more clearly shown, the lighting module 310 of the optical assembly 300 may include one or more light source mounting seats 3101 for mounting corresponding light sources. The light source mounting seat 3101 may include a generally cylindrical support member 3102, and the light source may be detachably mounted in the support member 3102. In one example, a heat sink 3103 may be mounted at the end of the support member 3102 opposite to the end where the light source is mounted to dissipate heat for the light source. The heat sink 3103 may be configured to include a substantially quadrilateral (such as a square or a rectangle) base 3104 and a plurality of substantially parallel heat sink fins 3105 extending outward from one side of the base 3104. The length and height of the heat sink fins 3105 and the gaps between them may be selected to achieve the desired heat dissipation effect. The heat sink 3103 may also include a substantially cylindrical flange portion 3106 extending outward from the other side of the base 3104. One end of the support member 3102 can be inserted into the flange portion 3106 concentrically with the flange portion 3106 for fixing, and the other end of the support member 3102 can extend a certain length from the flange portion 3106. For the accuracy of the optical path, at least the support member 3102 and the flange portion 3106 of the heat sink 3103 can be finely processed so that the concentricity of the support member 3102 and the flange portion 3106 is maintained between 1-10 microns. In one example, the support member 3102 can be fixed in the flange portion 3106 using a fastening element (such as a set screw). In another example, the support member 3102 can be formed integrally with the heat sink 3103, in which example, the heat sink 3105 may not include the flange portion 3106. In order to enhance the heat dissipation effect of the radiator 3103, an enhanced heat conductive element 3107 may be provided between the support component 3102 and the radiator 3103, so as to quickly conduct the heat generated by the light source to the radiator 3103 and its heat dissipation fins 3105 via the support component 3102 and the enhanced heat conductive element 3107. In one example, the enhanced heat conductive element 3107 may be made of thermally conductive graphene. The support component 3102 and the radiator 3103 of the light source mounting seat 3101 may be made of aluminum or aluminum alloy material, which can ensure good heat dissipation effect while meeting the requirements of strength and low weight. However, the present disclosure is not limited thereto, and the support component 3102 and the radiator 3103 of the light source mounting seat 3101 may be made of any appropriate material.

[0093] The lighting module 310 of the optical assembly 300 may further include a collimating lens mounting seat 3110 for arranging a collimating lens. Figure 7As shown, the collimating lens mount 3110 can be in the shape of a general cube, and a through passage suitable for light to pass through is provided inside the collimating lens mount 3110. One or more substantially cylindrical mounting flanges 3111 can be provided on one or more surfaces of the collimating lens mount 3110. The collimating lens can be detachably positioned in the mounting flange 3111 in an appropriate manner, so that the collimating lens can be easily replaced according to demand. In addition, the light source mount 3101 can also be detachably connected to the collimating lens mount 3110 via the mounting flange 3111. In one example, the light source mount 3101 can be connected to the collimating lens mount 3110 by inserting the support member 3102 of the light source mount 3101 into the mounting flange 3111 of the collimating lens mount 3110. After the support component 3102 of the light source mounting seat 3101 is inserted into the mounting flange 3111 of the collimating lens mounting seat 3110, the support component 3102 and the mounting flange 3111 can be locked and fixed to each other via a fastening element (such as a set screw), so that the light source mounting seat 3101 is fixedly connected to the collimating lens mounting seat 3110. To this end, one or more threaded holes corresponding to each other can be provided on the circumferential surfaces of the support component 3102 of the light source mounting seat 3101 and the mounting flange 3111 of the collimating lens mounting seat 3110 (for example, Figure 7 In order to facilitate positioning, a stop step surface 3113 can be provided in the mounting flange 3111 of the collimating lens mounting seat 3110. When the supporting component 3102 of the light source mounting seat 3101 is inserted into the mounting flange 3111 of the collimating lens mounting seat 3110, the front end surface of the supporting component 3102 can abut against the stop step surface 3113, thereby achieving the positioning of the supporting component 3102. In the case where the optical component 300 is used for a long time without replacing the light source, in order to ensure the connection stability between the light source mounting seat 3101 and the collimating lens mounting seat 3110, glue can be poured into the threaded hole 3112 to ensure a reliable fixed connection between the light source mounting seat 3101 and the mounting flange 3111 of the collimating lens mounting seat 3110. In addition, in order to ensure the accuracy of the optical path, at least the mounting flange 3111 of the collimating lens mount 3110 can be finely processed so that the concentricity of the supporting part 3102 of the light source mount 3101 and the mounting flange 3111 of the collimating lens mount 3110 is maintained between 1-100 microns, preferably between 1-50 microns, more preferably between 1-20 microns, and most preferably between 1-10 microns.

[0094] In the case where the optical assembly includes the second dichroic mirror 216, a surface (e.g., the top surface) of the collimating lens mount 3110 may be provided with a slot 3114, and the second dichroic mirror 216 may be inserted and positioned in the collimating lens mount 3110 through the slot 3114. The slot 3114 may have an appropriate angle so as to orient the second dichroic mirror 216 at a predetermined angle. In one embodiment, the collimating lens mount 3110 may be made of aluminum or an aluminum alloy material, and the weight of the collimating lens mount may be reduced while satisfying strength.

[0095] The lighting module 310 of the optical assembly 300 may further include a condenser lens mounting seat 3115 for arranging a condenser lens. Figure 7 As shown, the condenser lens mounting seat 3115 can include a substantially cylindrical lens barrel 3116, and the condenser lens can be detachably mounted in the lens barrel 3116 in an appropriate manner. In one example, the condenser lens can be rotated into the lens barrel 3116 by means of a tool and fixed with a pressure ring, so that the installation and splitting of the condenser lens are very convenient. The length of the lens barrel 3116 is designed to meet the required optical path length. The lens barrel 3116 can be finely processed to ensure that the optical path deviation in the lens barrel 3116 is controlled within the range of 1-100 microns, preferably within the range of 1-50 microns, and more preferably within the range of 1-20 microns. In order to facilitate the connection of the condenser lens mounting seat 3115 with other components, a connecting flange 3117 is respectively provided at the two ends of the lens barrel 3116. The connecting flange 3117 can be configured into a quadrilateral (such as a square or a rectangle) shape. When connected to the collimating lens mount 3110, the connecting flange 3117 of the condensing lens mount 3115 can abut against a connecting surface 3118 of the collimating lens mount 3110, and then be fixedly connected to the connecting surface 3118 by means of a fastening element (such as a set screw). In order to facilitate the proper positioning of the connecting flange 3117 relative to the connecting surface 3118 of the collimating lens mount 3110, a positioning element 3119 (such as a positioning pin) can be provided on the connecting surface 3118 of the collimating lens mount 3110. Accordingly, a positioning hole 3120 for the positioning element 3119 to extend through can be provided on the connecting flange 3117 of the condensing lens mount 3115. In this way, the condensing lens mount 3115 can be conveniently and accurately positioned by extending the positioning element 3119 through the positioning hole 3120, so that the accuracy of the optical path can be ensured in the process of repeatedly disassembling and installing the condensing lens mount 3115.

[0096] exist Figure 7 In the example shown, the illumination module 310 of the optical assembly 300 may also include a separate dichroic mirror mount 3121. Figure 7As shown, the dichroic mirror mount 3121 has a similar structure to the collimating lens mount 3110, except that it does not include the mounting flange 3111. A surface (e.g., the side surface 3122) of the dichroic mirror mount 3121 may be provided with a narrow groove 3123, and the dichroic mirror 240 may be inserted into the dichroic mirror mount 3121 through the narrow groove 3123. The narrow groove 3123 may have an appropriate angle so as to orient the dichroic mirror 240 at a predetermined angle. The dichroic mirror mount 3121 may be fixed to another connecting flange 3117 of the focusing lens mount 3115 via a fastening element, which will not be described in detail herein. It should be noted that although in Figure 7 In the example shown, the dichroic mirror mount 3121 is shown as a part of the illumination module 310 , however, the disclosure is not limited thereto. The dichroic mirror mount 3121 may be a part of any one of the illumination module 310 , the signal collection module 320 , and the imaging module 330 .

[0097] return Figure 6 , the specific mechanical structure of the signal collection module 320 according to an embodiment of the present disclosure will be described. Figure 6 As shown, the signal collection module 320 may include an objective lens mount 3201. The objective lens mount 3201 may include an upper surface 3202, a lower surface 3203, and a rear surface 3204. The objective lens 121 may be mounted on the lower surface 3203 of the objective lens mount 3201. The objective lens mount 3201 is configured to be able to move up and down in the vertical direction under the drive of the focus motor 122, so as to move the objective lens to the best focal plane. The focus motor 122 may be mounted to the rear surface 3204 of the objective lens mount 3201, so as to move the objective lens 121 up and down in the vertical direction via the objective lens mount 3201. In one example, the displacement speed of the focus motor 122 may be in the range of 5-50 mm / s, and the displacement accuracy thereof may be in the range of 0.1-1 μm. When assembled into the optical assembly 300, the objective lens mount 3201 of the signal collection module 320 is disposed below the dichroic mirror mount 3121.

[0098] Next, refer to Figure 8 , the specific mechanical structure of the imaging module 330 according to an embodiment of the present disclosure will be described. The imaging module 330 may include a tube lens mount 3301. The tube lens mount 3301 may have a structure similar to that of a condenser lens mount, including a tube lens barrel 3302 and connection flanges 3303 disposed at both ends of the tube lens barrel 3302. The tube lens barrel 3302 may be configured in a cylindrical shape, and the tube lens 134 may be detachably disposed in the tube lens barrel 3302. The connection flange 3303 may be configured in a quadrilateral (such as a square or a rectangle) shape, for connecting to the dichroic mirror mount 3121 and other components of the imaging module 330, respectively.

[0099] The imaging module 330 may further include a reflector or dichroic mirror mount 3304. The reflector or dichroic mirror mount 3304 is substantially in the shape of a cube and has a through passage for light to pass through. In one example, the reflector or dichroic mirror mount 3304 may include an inclined surface 3305 with an opening. Figure 1 and Figure 5 Mirror 133 shown) or dichroic mirror (such as Figure 4 The third dichroic mirror 235 shown in the figure can be detachably mounted on the inclined surface 3305. The inclination angle of the inclined surface 3305 can be selected to orient the reflector or dichroic mirror at a desired angle. In the case where the imaging module 330 includes an emission filter, the emission filter can also be detachably mounted in the reflector or dichroic mirror mount 3304. In one example, one or more image sensor interfaces 3306 are provided on one or more surfaces of the reflector or dichroic mirror mount 3304. In an embodiment according to the present disclosure, the image sensor interface 3306 is configured as a standard industrial interface, such as a standard C-type interface for imaging devices, so that an image sensor 131 with any industrial standard interface can be directly detachably mounted on the reflector or dichroic mirror mount 3304 without using an adapter, thereby greatly improving the design and modification flexibility and versatility of optical components. The reflector or dichroic mirror mount 3304 can be detachably mounted on another connecting flange 3303 of the tube lens mount 3301 via a fastening element (such as a set screw).

[0100] In addition, if Figure 8 As shown, the assembled imaging module 330 can be detachably mounted on the dichroic mirror mounting seat 3121 by means of a fastening element (such as a set screw) above the dichroic mirror mounting seat 3121. When the imaging module 330 is mounted on the dichroic mirror mounting seat 3121, since a certain size of optical path offset needs to be ensured in the optical path design, a positioning edge 3124 can be provided on one side of the top surface of the dichroic mirror mounting seat 3121. When the imaging module 330 is mounted on the dichroic mirror mounting seat 3121, it is only necessary to make one edge of the connecting flange 3303 of the tube lens mounting seat 3301 of the imaging module 330 abut against the positioning edge 3124 of the dichroic mirror mounting seat 3121 to ensure the desired optical path offset, so that the imaging module 330 can be positioned quickly and accurately. The positioning edge 3124 can be milled out by fine machining.

[0101] Referenced above Figures 6 to 8The mechanical structure of the optical assembly shown can greatly improve the flexibility of design, modification, maintenance and assembly of the optical assembly according to the present disclosure by dividing the optical assembly into corresponding modules and fixing and assembling various modules in a detachable manner. In response to different customer needs, if it is necessary to produce optical assemblies suitable for different fluxes, in some cases, it is sufficient to replace the optical components on each mounting seat without replacing the entire set of optical assemblies. In addition, even if it is necessary to re-invent new optical assemblies, it is only necessary to proportionally enlarge the size of all or part of the mounting seats without changing the mechanical structure of each mounting seat, which can greatly reduce the design cycle and design cost of the optical assembly according to the present disclosure, and makes the optical assembly according to the present disclosure particularly suitable for small-batch production for different needs of different users.

[0102] In addition, it can be seen from the above description that the optical assembly according to the present invention does not have the optical lens adjustment frame required in the existing optical assembly, and it accurately positions the components of the optical assembly by utilizing the design of positioning elements (such as positioning pins and positioning edges) and the precision of fine processing, thereby relying on the precision of the mechanical structure of each mounting seat to ensure the optical path accuracy of the optical assembly without using the optical lens adjustment frame. This can not only simplify the structure of the optical assembly and save material costs, but also omit the step of using the optical lens adjustment frame to adjust the optical path, thereby greatly simplifying the operation of the optical assembly according to the present invention.

[0103] The optical assembly according to the present disclosure is also particularly suitable for miniaturization, which can greatly reduce the size of medium and low-throughput fluorescence microscopy detection systems. In one example according to the present disclosure, the size of the illumination module of the optical assembly can be around 40×40×150 mm, the size of the signal collection module (including the focus motor) can be around 50×80×110 mm, and the size of the imaging module can be around 40×80×100 mm, which is significantly smaller than the existing optical assembly. In addition, in order to adapt to the miniaturized mounting seat, some optical lenses of the optical assembly can use smaller aspherical lenses, which helps to further miniaturize the optical assembly.

[0104] Fig. 9An exemplary embodiment of a fluorescence microscopic detection system 400 including an optical assembly according to the present disclosure is shown. The fluorescence microscopic detection system 400 may include an optical assembly 401 according to the present disclosure, a flow cell 402 (e.g., a biochemical reaction flow cell) for placing a sample, and / or a scanning platform 403 for loading the flow cell 402. The optical assembly 401 may be disposed above the flow cell 402. In order to ensure the detection accuracy, when assembling the fluorescence microscopic detection system 400, the parallelism between the components is very important. For this reason, the parallelism between the reference plane 404 of the optical component 401 and the reference plane 405 of the fixed bottom plate thereof is required to be controlled within the range of 1-50 microns, preferably within the range of 1-20 microns, and more preferably within the range of 1-5 microns. The parallelism of the sample glass slide in the flow cell 402 itself is controlled within the range of 2-20 microns, preferably within the range of 2-10 microns. The parallelism of the surface 406 of the scanning platform 403 on which the flow cell 402 is loaded is controlled within the range of 1-20 microns, preferably within the range of 1-10 microns, and more preferably within the range of 1-5 microns. The parallelism between the objective lens of the optical component 401 and the sample glass slide in the flow cell 402 is controlled within the range of 5-20 microns, preferably within the range of 5-10 microns. When the above requirements are met, the fluorescence microscopic detection system 400 according to the present disclosure can meet the desired optical accuracy.

[0105] The words "front", "rear", "top", "bottom", "above", "below", etc. in the specification and claims are used for descriptive purposes only and are not necessarily used to describe invariant relative positions. It should be understood that the words so used are interchangeable under appropriate circumstances, such that the embodiments of the disclosure described herein, for example, are capable of operation in other orientations than those illustrated or otherwise described herein.

[0106] The word "exemplary" as used herein means "serving as an example, instance or illustration" rather than as a "model" to be exactly copied. Any implementation described as an example herein is not necessarily to be construed as preferred or advantageous over other implementations. Moreover, the present disclosure is not limited by any expressed or implied theory given in the above technical field, background technology, summary of the invention or detailed description.

[0107] As used herein, the term "substantially" is intended to include any minor variations due to design or manufacturing imperfections, device or component tolerances, environmental influences, and / or other factors. The term "substantially" also allows for deviations from a perfect or ideal situation due to parasitic effects, noise, and other practical considerations that may exist in actual implementations.

[0108] In addition, the foregoing description may have referred to elements or nodes or features that are "connected" or "coupled" together. As used herein, unless otherwise expressly stated, "connection" means that one element / node / feature is directly connected (or directly communicates) with another element / node / feature electrically, mechanically, logically or otherwise. Similarly, unless otherwise expressly stated, "coupling" means that one element / node / feature can be mechanically, electrically, logically or otherwise connected to another element / node / feature in a direct or indirect manner to allow interaction, even if the two features may not be directly connected. In other words, "coupling" is intended to include direct and indirect connections of elements or other features, including connections using one or more intermediate elements.

[0109] In addition, the terms "first", "second" and the like may also be used herein for reference purposes only, and thus are not intended to be limiting. For example, the terms "first", "second" and other such numerical terms referring to structures or elements do not imply a sequence or order unless the context clearly indicates otherwise.

[0110] In this disclosure, the term "provide" is used in a broad sense to cover all ways of obtaining an object, and thus "providing an object" includes but is not limited to "purchasing", "preparing / manufacturing", "arranging / setting up", "installing / assembling", and / or "ordering" an object, etc.

[0111] Those skilled in the art will appreciate that the boundaries between the above operations are merely illustrative. For example, multiple operations may be combined into a single operation, and a single operation may be distributed among multiple operations, and each operation may be performed at least partially overlapping in time. Moreover, other embodiments may include multiple instances of specific operations, and the order of operations may be changed in other various embodiments. Moreover, other modifications, variations, and replacements are possible as well. In addition, the various embodiments and examples described above may be combined arbitrarily as needed, for example, the specific operations or details described in a certain embodiment may also be applied to other embodiments or examples.

[0112] Although some specific embodiments of the present disclosure have been described in detail by way of example, it should be understood by those skilled in the art that the above examples are for illustration only and are not intended to limit the scope of the present disclosure. The various embodiments disclosed herein may be combined in any manner without departing from the spirit and scope of the present disclosure. It should also be understood by those skilled in the art that various modifications may be made to the embodiments without departing from the scope and spirit of the present disclosure. The scope of the present disclosure is defined by the appended claims.

Claims

1. An optical component for fluorescence microscopy, characterized in that: The optical assembly comprises: an illumination module, the illumination module comprising a light source configured to emit excitation light for exciting the sample and a collimating lens for collimating the excitation light emitted by the light source; a signal collection module, the signal collection module comprising an objective lens configured to direct the excitation light from the illumination module to the sample and direct the emission light from the sample to an imaging module; an imaging module, the imaging module comprising an image sensor that images the emission light from the sample and a tube lens configured to guide the emission light from the objective lens to the image sensor; and a dichroic mirror, the dichroic mirror being arranged on an optical path between the excitation light from the light source to the objective lens and on an optical path between the emission light from the objective lens to the tube lens, the dichroic mirror being configured to transmit one of the excitation light and the emission light and reflect the other of the excitation light and the emission light, The objective lens and the tube lens form an infinite conjugate with each other. wherein the dichroic mirror is a part of one of the illumination module, the signal collection module and the imaging module, The lighting module includes one or more light source mounting seats for mounting the light source and a collimating lens mounting seat for setting the collimating lens, the signal collection module includes an objective lens mounting seat, and the imaging module includes a tube lens mounting seat and a reflector or a dichroic mirror mounting seat, so that the lighting module, the signal collection module and the imaging module can be detachably assembled together via a mechanical interface to achieve optical alignment and mechanical structure. Wherein, the light source mounting seat comprises a cylindrical supporting component, the light source is detachably mounted in the supporting component, and a heat sink is mounted on the end of the supporting component opposite to the end on which the light source is mounted, so as to dissipate heat from the light source; The collimating lens mounting seat is in the shape of a cube and is provided with a through channel suitable for light to pass through, one or more surfaces of the collimating lens mounting seat are provided with one or more mounting flanges, and the collimating lens can be detachably positioned in the mounting flanges; Wherein, the supporting component of the light source mounting seat can be inserted into the mounting flange of the collimating lens mounting seat to detachably connect the light source mounting seat to the collimating lens mounting seat, and a stop step surface is provided in the mounting flange of the collimating lens mounting seat for positioning the supporting component of the light source mounting seat; and Wherein, the concentricity between the mounting flange of the collimating lens mounting seat and the supporting component of the light source mounting seat is maintained between 1-100 microns.

2. The optical component according to claim 1, characterized in that The optical components meet the following conditions: Wherein, f1 is the focal length of the objective lens, NA is the numerical aperture of the objective lens, f2 is the focal length of the tube lens, and λ is the wavelength of the emitted light in μm.

3. The optical component according to claim 1, characterized in that The focal length of the tube lens is designed to be 5mm-100mm.

4. The optical component according to claim 1, characterized in that The lighting module includes a first light source configured to emit a first excitation light in a first wavelength range and a second light source configured to emit a second excitation light in a second wavelength range different from the first wavelength range. The lighting module also includes a second dichroic mirror arranged on an optical path of the first excitation light from the first light source to the dichroic mirror and on an optical path of the second excitation light from the second light source to the dichroic mirror. The second dichroic mirror is configured to transmit one of the first excitation light and the second excitation light and reflect the other of the first excitation light and the second excitation light.

5. The optical component according to claim 4, characterized in that The illumination module further includes a converging lens for converging the first excitation light and the second excitation light and an excitation filter for filtering the first excitation light and the second excitation light, wherein the converging lens and the excitation filter are located on an optical path from the second dichroic mirror to the dichroic mirror.

6. The optical component according to claim 1, characterized in that The imaging module includes a first image sensor configured to image first emitted light in a third wavelength range and a second image sensor configured to image second emitted light in a fourth wavelength range different from the third wavelength range. The imaging module also includes a third dichroic mirror arranged on an optical path of the first emitted light from the dichroic mirror to the first image sensor and on an optical path of the second emitted light from the dichroic mirror to the second image sensor, the third dichroic mirror being configured to transmit one of the first emitted light and the second emitted light and to reflect the other of the first emitted light and the second emitted light.

7. The optical component according to claim 6, characterized in that The imaging module further includes an emission filter for filtering the first emission light and the second emission light, and the tube lens and the emission filter are located on an optical path from the dichroic mirror to the third dichroic mirror.

8. The optical component according to claim 1, characterized in that The signal collection module also includes a focus motor coupled to the objective lens, and the focus motor is configured to move the objective lens to focus on the sample.

9. The optical component according to claim 1, characterized in that: An enhanced heat conduction element is arranged between the support component and the heat sink to enhance the heat dissipation effect of the heat sink.

10. The optical component according to claim 1, characterized in that The supporting member is formed integrally with the heat sink.

11. The optical component according to claim 1, characterized in that The heat sink includes a flange portion in which the support member is inserted and fixed with a fastening element.

12. The optical component according to claim 1, characterized in that The mounting flange of the collimating lens mounting seat and the supporting member of the light source mounting seat are locked and fixed to each other via a fastening element.

13. The optical component according to claim 1, characterized in that A narrow slot is provided on one surface of the collimating lens mount, and the second dichroic mirror can be inserted through the narrow slot and positioned in the collimating lens mount.

14. The optical component according to claim 1, characterized in that The lighting module further comprises a condenser lens mounting seat for arranging a condenser lens, and the condenser lens mounting seat can be detachably connected to the collimating lens mounting seat in a manner opposite to the light source mounting seat.

15. The optical component according to claim 14, characterized in that The condenser lens mounting seat comprises a cylindrical lens barrel, in which the condenser lens can be detachably mounted.

16. The optical component according to claim 15, characterized in that The optical path deviation in the lens barrel is set within the range of 1-100 microns.

17. The optical component according to claim 15, characterized in that Both ends of the lens barrel are provided with connecting flanges, so that the condensing lens mounting seat can be detachably connected to the collimating lens mounting seat via the connecting flanges.

18. The optical component according to claim 17, characterized in that A positioning element is arranged on the connection surface of the collimating lens mounting seat, and a positioning hole for the positioning element to extend through is arranged on the connection flange of the condensing lens mounting seat, so as to accurately position the condensing lens mounting seat.

19. The optical component according to claim 4, characterized in that The optical assembly includes a separate dichroic mirror mount to mount the dichroic mirror.

20. The optical component according to claim 19, characterized in that A side surface of the separate dichroic mirror mount is provided with a slot through which the dichroic mirror can be inserted into the separate dichroic mirror mount.

21. The optical assembly according to claim 19, wherein: The top surface of the separate dichroic mirror mount is provided with a positioning edge to facilitate accurate positioning of the imaging module.

22. The optical assembly according to claim 19, wherein: The signal collection module is disposed below the separate dichroic mirror mounting seat in a manner that it can move up and down along a vertical direction.

23. The optical component according to claim 22, characterized in that The objective lens mounting seat of the signal collection module comprises an upper surface, a lower surface and a rear surface, the objective lens is mounted on the lower surface of the objective lens mounting seat, and a focus motor is mounted on the rear surface of the objective lens mounting seat.

24. The optical assembly according to claim 19, wherein: The imaging module is disposed above the separate dichroic mirror mount.

25. The optical component according to claim 24, characterized in that The tube lens mounting seat comprises a tube lens barrel and connecting flanges arranged at two ends of the tube lens barrel, and one connecting flange of the tube lens barrel is detachably fixed on the separate dichroic mirror mounting seat.

26. The optical component according to claim 24, characterized in that The reflector or dichroic mirror mount is in the shape of a cube and includes an inclined surface with an opening, and the reflector or the third dichroic mirror is detachably mounted on the inclined surface.

27. The optical component according to claim 24, characterized in that One or more image sensor interfaces are disposed on one or more surfaces of the reflector or dichroic mirror mount, and the image sensor interfaces are constructed as standard industrial interfaces.

28. The optical component according to claim 27, characterized in that The image sensor interface is a standard C-type interface for imaging devices.

29. The optical assembly according to claim 1, wherein: The sample is placed in a biochemical reaction flow cell.

30. A fluorescence microscopy detection system, characterized in that: The fluorescence microscopy detection system comprises the optical assembly according to any one of claims 1 to 29, and a flow cell for placing a sample.

31. The fluorescence microscopy detection system according to claim 30, characterized in that: The fluorescence microscopy detection system also includes a scanning platform for carrying the flow cell.

32. The fluorescence microscopy detection system according to claim 31, characterized in that: The parallelism between the reference plane of the optical component and the reference plane of the fixing base plate is controlled within the range of 1 to 50 microns.

33. The fluorescence microscopy detection system according to claim 32, characterized in that: The parallelism of the sample slide in the flow cell is controlled within a range of 2 to 20 micrometers, and the parallelism of the surface of the scanning platform on which the flow cell is mounted is controlled within a range of 1 to 20 micrometers.

34. The fluorescence microscopy detection system according to claim 33, characterized in that: The parallelism between the objective lens of the optical assembly and the sample glass slide in the flow cell is controlled within a range of 5 to 20 microns.

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