Large field-of-view mesoscopic microscope objective for drug sensitivity imaging analysis

Through a combination of multiple spherical lenses arranged coaxially, including aperture, chromatic aberration and aberration lens groups, the problem of insufficient numerical aperture and object-square field of view in drug-sensitive imaging analysis is solved, and a large field of view and high resolution imaging effect is achieved.

CN115826215BActive Publication Date: 2025-07-11SUZHOU INST OF BIOMEDICAL ENG & TECH CHINESE ACADEMY OF SCI +1
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Patent Information

Application Number
CN202211696295.1
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-12-28
Publication Date
2025-07-11
Estimated Expiration
2042-12-28

AI Technical Summary

Technical Problem

In existing microscopes, numerical aperture and object-side field of view cannot meet the needs in drug-sensitive imaging analysis, and the imaging error is large, especially when using 384-well plates, there are problems of incomplete observation and reduced imaging quality.

Method used

A combination of spherical lenses is adopted in a coaxial arrangement, including an aperture lens group, a chromatic aberration lens group and an aberration lens group. The object of observation is enlarged through the aperture lens group, the chromatic aberration lens group corrects the chromatic aberration, and the aberration lens group corrects the aberration to ensure that the numerical aperture and object-square field of view meet the requirements.

Benefits of technology

Apochromatic aberration and low-field distortion within the visible light range are achieved, large field of view and high-resolution imaging under 384-well plates are ensured, the shortcomings of numerical aperture and object-square field are solved, and the imaging quality is improved.

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Abstract

The present application discloses a large-field mesoscopic microscope objective lens for drug sensitivity imaging analysis. The objective lens includes: a plurality of spherical lenses arranged coaxially, and the plurality of spherical lenses include an aperture lens group, a chromatic aberration lens group, and an aberration lens group; the aperture lens group includes a first lens and a second lens, the first lens is a plano-concave lens, and the second lens is a positive meniscus lens; the chromatic aberration lens group includes a third lens, a fourth lens, and a fifth lens, both the third lens and the fifth lens are biconvex lenses, and the fourth lens is a biconcave mirror; the aberration lens group includes a sixth lens to an eleventh lens, the sixth lens is a plano-concave lens, the seventh lens is a biconvex lens, the eighth lens is a biconvex lens, the ninth lens is a convex-concave lens, the tenth lens is a biconcave lens, and the eleventh lens is a biconvex lens. It solves the problems that in the related art, when the microscope is used for drug sensitivity imaging analysis, the numerical aperture and the object space field of view cannot meet the requirements, and the imaging error is large.
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Description

Technical Field

[0001] The present application relates to the field of optical imaging, and in particular, to a large-field mesoscopic microscope objective for drug sensitivity imaging analysis. Background Art

[0002] Rapid bacterial or fungal identification and drug susceptibility testing are crucial for determining whether antibiotics or antifungal drugs can effectively treat bacterial or fungal infectious diseases, and are key for clinically treating bacterial or fungal infections and guiding doctors in drug use. Currently, one method for analyzing the sensitivity of antibiotics or antifungal drugs acting on bacteria or fungi is to use microscopic imaging to long-term observe the change in the number of bacteria or fungi before and after drug treatment. Considering that the size of bacteria or fungi is about 1 μm, a microscope objective with a numerical aperture of not less than 0.3 needs to be selected to distinguish the bacteria or fungi with changed numbers.

[0003] Currently, rapid drug sensitivity analysis in clinical practice requires simultaneous detection of multiple indicator parameters. Usually, a mixture of bacteria or fungi and different drugs is placed in different wells of the same 96-well plate or 384-well plate. The single-well diameters of the 96-well plate and 384-well plate are 6.96 mm and 4.50 mm respectively. The magnification factors of traditional microscope objectives that can cover the single-object space imaging fields of 6.96 mm and 4.50 mm are generally 2.5 times and 5 times, and the object space numerical apertures are generally in the range of 0.1 to 0.15. According to the resolution formula (ε = 0.61λ / NA, with λ taken as 550 nm), the resolution ε ≥ 2.2 μm, which cannot meet the resolution requirements for drug sensitivity imaging analysis.

[0004] In the prior art, the microscope objective that can be found closest to meeting the real-time detection of bacterial or fungal identification and drug susceptibility testing under a 384-well plate has the following main technical parameters: the object space numerical aperture is 0.40, the single object space field of view is 4.42 mm, and the magnification factor is 5.88 times. However, there is still a situation where the surrounding circle of bacterial samples cannot be observed in real time, and the influence of the 1.50-mm-thick cover plate of the 384-well plate on the imaging quality during the imaging drug sensitivity analysis is not considered (the flat plate will cause spherical aberration, and the spherical aberration caused by a certain thickness will affect the imaging resolution). Not to mention the defect that other microscope objectives can at most meet one of the requirements in terms of resolution and single object space field of view.

[0005] Regarding the problem that the microscope in the related art has a numerical aperture and object space field of view that cannot meet the requirements and a large imaging error during drug sensitivity imaging analysis, no effective solution has been proposed yet. Summary of the Invention

[0006] The main object of the present application is to provide a large-field mesoscopic microscope objective for drug sensitivity imaging analysis, so as to solve the problems that in the related art, when the microscope is used for drug sensitivity imaging analysis, the numerical aperture and the object field of view cannot meet the requirements, and the imaging error is large.

[0007] To achieve the above object, according to one aspect of the present application, there is provided a large-field mesoscopic microscope objective for drug sensitivity imaging analysis, including: a plurality of spherical lenses arranged coaxially, the plurality of spherical lenses including an aperture lens group for magnifying an observation object to a target aperture range, a chromatic aberration lens group for correcting chromatic aberration, and an aberration lens group for correcting aberration; the aperture lens group includes a first lens and a second lens from the object side to the image side, the first lens is a plano-concave lens, and the second lens is a positive meniscus lens; the chromatic aberration lens group includes a third lens, a fourth lens, and a fifth lens from the object side to the image side, the third lens and the fifth lens are both biconvex lenses, the fourth lens is a biconcave lens, and the third lens, the fourth lens, and the fifth lens are glued together in sequence; the aberration lens group includes a sixth lens to an eleventh lens from the object side to the image side, the sixth lens is a plano-concave lens, the seventh lens is a biconvex lens, the sixth lens and the seventh lens are glued together, the eighth lens is a biconvex lens, the ninth lens is a convex-concave lens, the tenth lens is a biconcave lens, and the eleventh lens is a biconvex lens.

[0008] Optionally, for the plano-concave lens of the first lens, the first side surface close to the object side is a plane, and the second side surface close to the image side is a concave surface; for the positive meniscus lens of the second lens, the third side surface close to the object side is a concave surface, and the fourth side surface close to the image side is a convex surface.

[0009] Optionally, for the first side, R1 = ∞ mm, D1 = 1.20 - 1.60 mm, ψ1 = 6.28 - 7.25 mm, where R1 is the radius of curvature of the first side; D1 is the mirror distance of the first side; ψ1 is the effective clear aperture of the first side; for the second side, R2 = -18.22 - -16.84 mm, D2 = 1.25 - 1.65 mm, ψ2 = 7.18 - 7.82 mm, where R2 is the radius of curvature of the second side; D2 is the side distance of the second side; ψ2 is the effective clear aperture of the second side; for the third side, R3 = 26.55 - 33.41 mm, D3 = 3.07 - 3.86 mm, ψ3 = 9.22 - 11.53 mm, where R3 is the radius of curvature of the third side; D3 is the side distance of the third side; ψ3 is the effective clear aperture of the third side; for the fourth side, R4 = 15.24 - 18.11 mm, D4 = 6.23 - 7.54 mm, ψ4 = 13.35 - 14.88 mm, where R4 is the radius of curvature of the fourth side; D4 is the side distance of the fourth side; ψ4 is the effective clear aperture of the fourth side.

[0010] Optionally, the third lens is a biconvex lens. The fifth side near the object side is convex, and the sixth side glued to the fourth lens is convex; the fifth lens is a biconvex lens. The seventh side glued to the fourth lens is convex, and the eighth side near the image side is convex; the fourth lens is a biconcave lens, which cooperates with the sixth side and the seventh side respectively.

[0011] Optionally, for the fifth side, R5 = -101.52 - -90.66 mm, D5 = 9.58 - 11.21 mm, ψ5 = 24.37 - 28.60 mm, where R5 is the radius of curvature of the fifth side; D5 is the side distance of the fifth side; ψ5 is the effective clear aperture of the fifth side; for the sixth side, R6 = 32.84 - 39.29 mm, D6 = 4.85 - 5.12 mm, ψ6 = 24.37 - 28.60 mm, where R6 is the radius of curvature of the sixth side; D6 is the side distance of the sixth side; ψ6 is the effective clear aperture of the sixth side; for the seventh side, R7 = -42.35 - -37.62 mm, D7 = 1.12 - 2.15 mm, ψ7 = 24.37 - 28.60 mm, where R7 is the radius of curvature of the seventh side; D7 is the side distance of the seventh side; ψ7 is the effective clear aperture of the seventh side; for the eighth side, R8 = 19.76 - 23.27 mm, D8 = 6.76 - 7.54 mm, ψ8 = 24.37 - 28.60 mm, where R8 is the radius of curvature of the eighth side; D8 is the side distance of the eighth side; ψ8 is the effective clear aperture of the eighth side.

[0012] Optionally, the sixth lens is a plano-concave lens, the ninth side surface close to the object side is a plane, and the tenth side surface glued to the seventh lens is a concave surface; the seventh lens is a biconvex lens, the side surface glued to the sixth lens cooperates with the tenth side surface, and the eleventh side surface close to the image side is a convex surface; the eighth lens is a biconvex lens, the twelfth side surface close to the object side is a convex surface, and the thirteenth side surface close to the image side is a convex surface; the ninth lens is a convex-concave lens, the fourteenth side surface close to the object side is a convex surface, and the fifteenth side surface close to the image side is a concave surface; the tenth lens is a biconcave lens, the sixteenth side surface close to the object side is a concave surface, and the seventeenth side surface close to the image side is a concave surface; the eleventh lens is a biconvex lens, the eighteenth side surface close to the object side is a convex surface, and the nineteenth side surface close to the image side is a convex surface.

[0013] Optionally, for the ninth side surface, R9 = ∞ mm, D9 = 0.32 - 0.51 mm, ψ9 = 24.37 - 28.60 mm, where R9 is the radius of curvature of the ninth side surface; D9 is the side surface distance of the ninth side surface; ψ9 is the effective light-transmitting aperture of the ninth side surface; for the tenth side surface, R10 = -25.27 - -19.22 mm, D10 = 1.85 - 2.72 mm, ψ10 = 24.37 - 28.60 mm, where R10 is the radius of curvature of the tenth side surface; D10 is the side surface distance of the tenth side surface; ψ10 is the effective light-transmitting aperture of the tenth side surface; for the eleventh side surface, R11 = 38.06 - 46.42 mm, D11 = 5.54 - 6.85 mm, ψ11 = 24.37 - 28.60 mm, where R11 is the radius of curvature of the eleventh side surface; D11 is the side surface distance of the eleventh side surface; ψ11 is the effective light-transmitting aperture of the eleventh side surface; for the twelfth side surface, R12 = -31.45 - -19.72 mm, D12 = 0.25 - 0.85 mm, ψ12 = 24.37 - 28.60 mm, where R12 is the radius of curvature of the twelfth side surface; D12 is the side surface distance of the twelfth side surface; ψ12 is the effective light-transmitting aperture of the twelfth side surface; for the thirteenth side surface, R13 = 135.25 - 151.39 mm, D13 = 3.65 - 5.15 mm, ψ13 = 24.37 - 28.60 mm, where R13 is the radius of curvature of the thirteenth side surface; D13 is the side surface distance of the thirteenth side surface; ψ13 is the effective light-transmitting aperture of the thirteenth side surface; for the fourteenth side surface, R14 = -42.25 - -38.49 mm, D14 = 2.58 - 3.26 mm, ψ14 = 22.55 - 24.95 mm, where R14 is the radius of curvature of the fourteenth side surface; D14 is the side surface distance of the fourteenth side surface; ψ14 is the effective light-transmitting aperture of the fourteenth side surface; for the fifteenth side surface, R15 = -22.05 - -16.65 mm, D15 = 1.10 - 2.15 mm, ψ15 = 17.94 - 22.85 mm, where R15 is the radius of curvature of the fifteenth side surface; D15 is the side surface distance of the fifteenth side surface; ψ15 is the effective light-transmitting aperture of the fifteenth side surface; for the sixteenth side surface, R16 = 16.36 - 22.36 mm, D16 = 5.67 - 7.97 mm, Ψ16 = 20.85 - 24.32 mm, where R16 is the radius of curvature of the sixteenth side surface; D16 is the side surface distance of the sixteenth side surface; ψ16 is the effective light-transmitting aperture of the sixteenth side surface; for the seventeenth side surface, R17 = -90.66 - -80.04 mm, D17 = 1.84 - 2.65 mm, Ψ17 = 17.54 - 28.92 mm, where R17 is the radius of curvature of the seventeenth side surface; D17 is the side surface distance of the seventeenth side surface; ψ17 is the effective light-transmitting aperture of the seventeenth side surface; for the eighteenth side surface, R18 = -268.14 - -197.95 mm, D18 = 4.34 - 5.79 mm, Ψ18 = 8.22 - 8.75 mm, where R18 is the radius of curvature of the eighteenth side surface; D18 is the side surface distance of the eighteenth side surface; ψ18 is the effective clear aperture of the eighteenth side surface; for the nineteenth side surface, R19 = 20.52 - 33.18 mm, D19 = 4.98 - 6.34 mm, Ψ19 = 22.55 - 30.22 mm, where R19 is the radius of curvature of the nineteenth side surface; D19 is the side surface distance of the nineteenth side surface; ψ19 is the effective clear aperture of the nineteenth side surface.

[0014] Optionally, the numerical aperture of the microscope objective satisfies 0.35 ≤ NA < 0.5, where NA represents the numerical aperture of the microscope objective; the object space field diameter of the microscope objective satisfies: 4.50 ≤ FD < 5.00, where FD represents the single object space field diameter of the microscope objective; the distance between the first side surface of the first lens and the object surface cover plate satisfies: 1.5 ≤ WD < 3.7, where WD represents the distance from the upper surface of the cover plate near the image side to the first side surface of the first lens.

[0015] To achieve the above object, according to another aspect of the present application, there is provided a method for determining a lens group of a large field of view mesoscopic microscope objective for drug sensitivity imaging analysis, including: determining the numerical aperture range and object space field range of the lens group according to the imaging requirements of the lens group; determining an aperture lens group for magnifying an observation object to a target aperture range according to the numerical aperture range, where the aperture lens group includes a first lens and a second lens from the object side to the image side, the first lens is a plano - concave lens, and the second lens is a positive meniscus lens; determining the position and distance between the first lens and the second lens according to the object space field range; determining a chromatic aberration correction lens group according to the color of the image output by the aperture lens group, where the chromatic aberration correction lens group includes a third lens, a fourth lens, and a fifth lens from the object side to the image side, the third lens and the fifth lens are both biconvex lenses, the fourth lens is a biconcave lens, and the third lens, the fourth lens, and the fifth lens are glued together in sequence; determining an aberration correction lens group according to the deformation of the image output by the chromatic aberration correction lens group, where the aberration correction lens group includes a sixth lens to an eleventh lens from the object side to the image side, the sixth lens is a plano - concave lens, the seventh lens is a biconvex lens, the sixth lens and the seventh lens are glued together, the eighth lens is a biconvex lens, the ninth lens is a convex - concave lens, the tenth lens is a biconcave lens, and the eleventh lens is a biconvex lens.

[0016] Optionally, an aberration lens group for correcting aberrations is determined according to the deformation of the image output by the chromatic aberration lens group, including: initially selecting, according to the deformation of the image output by the chromatic aberration lens group, a cemented sixth lens and a seventh lens for initially correcting aberrations, a ninth lens for correcting magnification chromatic aberration, and an eleventh lens for correcting spherical aberration; determining the magnitude of the aberration according to the light angles output by the seventh lens, the ninth lens, and the eleventh lens, where the aberration includes at least one of the following: spherical aberration, coma; adding a corresponding eighth lens after the seventh lens with spherical aberration, and adding a corresponding tenth lens after the ninth lens with coma.

[0017] In this application, a plurality of spherical lenses are coaxially arranged. The plurality of spherical lenses include an aperture lens group for magnifying an observation object to a target aperture range, a chromatic aberration lens group for correcting chromatic aberration, and an aberration lens group for correcting aberrations; the aperture lens group includes a first lens and a second lens from the object side to the image side. The first lens is a plano-concave lens, and the second lens is a positive meniscus lens; the chromatic aberration lens group includes a third lens, a fourth lens, and a fifth lens from the object side to the image side. Both the third lens and the fifth lens are biconvex lenses, the fourth lens is a biconcave mirror, and the third lens, the fourth lens, and the fifth lens are cemented together in sequence; the aberration lens group includes a sixth lens to an eleventh lens from the object side to the image side. The sixth lens is a plano-concave lens, the seventh lens is a biconvex lens, the sixth lens and the seventh lens are cemented together, the eighth lens is a biconvex lens, the ninth lens is a convex-concave lens, the tenth lens is a biconcave lens, and the eleventh lens is a biconvex lens. The purpose of ensuring a large object-side field of view while ensuring a large numerical aperture is achieved, and at the same time, the technical effects of apochromatism and aberrations such as field curvature and distortion in the visible light range are realized. Furthermore, the problem that in the related art, when a microscope is used for drug sensitivity imaging analysis, the numerical aperture and the object-side field of view cannot meet the requirements, and the imaging error is large is solved. Description of the Drawings

[0018] The drawings constituting a part of this application are used to provide a further understanding of this application. The schematic embodiments of this application and their descriptions are used to explain this application and do not constitute an improper limitation to this application. In the drawings:

[0019] Figure 1 is a schematic diagram of the lens group of a large-field mesoscopic microscope objective for drug sensitivity imaging analysis provided by an embodiment of this application;

[0020] Figure 2 is a schematic diagram of the 0.0 field-of-view lateral aberration of the microscope objective provided by an embodiment of this application;

[0021] Figure 3 is a schematic diagram of the 0.5 field-of-view lateral aberration of the microscope objective provided by an embodiment of this application;

[0022] Figure 4 It is a schematic diagram of the 0.7 field-of-view lateral aberration of the microscope objective lens provided according to the embodiments of the present application;

[0023] Figure 5 It is a schematic diagram of the 1.0 field-of-view lateral aberration of the microscope objective lens provided according to the embodiments of the present application;

[0024] Figure 6 It is a schematic diagram of the full field-of-view transfer function curve of the microscope objective lens provided according to the embodiments of the present application;

[0025] Figure 7 It is a schematic diagram of the axial chromatic aberration of the microscope objective lens provided according to the embodiments of the present application;

[0026] Figure 8 It is a schematic diagram of the lateral chromatic aberration of the microscope objective lens provided according to the embodiments of the present application;

[0027] Figure 9 It is a schematic diagram of the field curvature and distortion of the microscope objective lens provided according to the embodiments of the present application;

[0028] Figure 10 It is a full field-of-view Strehl ratio diagram of the microscope objective lens provided according to the embodiments of the present application;

[0029] Figure 11 It is a flowchart of a method for determining a lens group of a large field-of-view mesoscopic microscope objective lens for drug sensitivity imaging analysis provided according to an embodiment of the present application. Detailed implementation manners

[0030] It should be noted that, without conflict, the embodiments in the present application and the features in the embodiments may be combined with each other. The present application will be described in detail below with reference to the drawings and in conjunction with the embodiments.

[0031] In order to enable those skilled in the art to better understand the solution of the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present application.

[0032] It should be noted that the terms "first", "second", etc. in the description, claims and the above-mentioned drawings of the present application are used to distinguish similar objects, and do not necessarily have to be used to describe a specific order or sequence. It should be understood that the data used in this way can be interchanged under appropriate circumstances for the embodiments of the present application described herein. In addition, the terms "comprising" and "having" and any variations thereof are intended to cover non-exclusive inclusion. For example, a process, method, system, product or device that comprises a series of steps or units does not necessarily have to be limited to those steps or units clearly listed, but may include other steps or units not clearly listed or inherent to these processes, methods, products or devices.

[0033] The technical solution of the present application will be described below in conjunction with specific embodiments. Figure 1 It is a schematic diagram of a lens group of a large field of view mesoscopic microscope objective for drug sensitivity imaging analysis according to an embodiment of the present application, as Figure 1 shown. The microscope objective includes: a plurality of spherical lenses arranged coaxially. The plurality of spherical lenses include an aperture lens group for magnifying an observation object to a target aperture range, a chromatic aberration lens group for correcting chromatic aberration, and an aberration lens group for correcting aberration.

[0034] The aperture lens group includes a first lens L1 and a second lens L2 from the object side to the image side. The first lens L1 is a plano-concave lens, and the second lens L2 is a positive meniscus lens. The chromatic aberration lens group includes a third lens L3, a fourth lens L4, and a fifth lens L5 from the object side to the image side. Both the third lens L3 and the fifth lens L5 are biconvex lenses, and the fourth lens L4 is a biconcave mirror. The third lens L3, the fourth lens L4, and the fifth lens L5 are glued together in sequence. The aberration lens group includes a sixth lens L6 to an eleventh lens L11 from the object side to the image side. The sixth lens L6 is a plano-concave lens, the seventh lens L7 is a biconvex lens, the sixth lens L6 and the seventh lens L7 are glued together, the eighth lens L8 is a biconvex lens, the ninth lens L9 is a convex-concave lens, the tenth lens L10 is a biconcave lens, and the eleventh lens L11 is a biconvex lens.

[0035] Through the combination of the above eleven lenses, arranged coaxially, the observation object located on the object plane is magnified and imaged, and the imaging output by the objective lens has a high resolution while ensuring a large field of view. And through the combination of the above lenses, the aberration caused by the cover plate on the object plane to the imaging is corrected.

[0036] It should be noted that the cover plate is a planar transparent plate, and the flat plate will cause aberrations, such as spherical aberration. When the thickness of the flat plate reaches a certain level, the spherical aberration caused will affect the imaging resolution, resulting in a decrease in resolution and failing to meet the usage requirements. The lens group of the above microscope objective can solve the aberration caused by the above cover plate, thereby improving the resolution of the object image in the case of a relatively large field of view, achieving the guarantee of a relatively large field of view while ensuring a relatively high resolution.

[0037] The above aperture lens group includes a first lens L1 and a second lens L2, which are used to magnify the observation object on the object plane to the target aperture range. By adjusting the positions and shapes of the first lens L1 and the second lens L2, a relatively large object space field of view can be achieved.

[0038] The first lens L1 is set as a plano-concave lens, which is used to avoid the interference between the objective lens and the sample surface while increasing the working distance; the second lens L2 is set as a positive meniscus lens, which is used to bear the high optical power required for a high numerical aperture and adjust the coma aberration.

[0039] The above chromatic aberration lens group includes a third lens L3, a fourth lens L4, and a fifth lens L5. L3, L4, and L5 are glued together in sequence to form a three-in-one lens group, which can be used to correct chromatic aberration. Its structure and shape can be improved and adjusted according to the existing glued lens group for correcting chromatic aberration, so as to adjust the chromatic aberration of the light rays output by the L2 lens, so that the chromatic aberration of the image output by the lens group is compensated and weakened. The above chromatic aberration lens group is mainly used to correct secondary chromatic aberration.

[0040] The above aberration lens group includes a sixth lens L6 to an eleventh lens L11. L6 and L7 are glued together to form a lens group, which is used to initially eliminate aberrations. The eighth lens L8 is a biconvex lens, which is mainly used to correct spherical aberration; the ninth lens L9 is a convex-concave lens, which is mainly used to correct magnification chromatic aberration; the tenth lens L10 is a biconcave lens, which is mainly used to correct coma aberration; the eleventh lens L11 is a biconvex lens, which is mainly used to correct spherical aberration.

[0041] In some preferred embodiments, the focal length of the first lens L1 is -22.31 mm, the focal length of the second lens L2 is 55.31 mm, the focal length of the glued lens group formed by the combination of the third lens L3, the fourth lens L4, and the fifth lens L5 is 45.58 mm, the focal length of the glued lens group formed by the combination of the sixth lens L6 and the seventh lens L7 is 423.20 mm, the focal length of the eighth lens L8 is 49.54 mm, the focal length of the ninth lens L9 is -63.57 mm, the focal length of the tenth lens L10 is -28.44 mm, and the focal length of the eleventh lens L11 is 40.66 mm.

[0042] In some preferred embodiments, the refractive index / Abbe number of the cover plate is 1.59 / 30.9, the refractive index / Abbe number of the first lens L1 is 1.77 / 49.6, the refractive index / Abbe number of the second lens L2 is 1.63 / 35.7, the refractive index / Abbe number of the third lens L3 is 1.63 / 35.7, the refractive index / Abbe number of the fourth lens L4 is 1.61 / 44.2, the refractive index / Abbe number of the fifth lens L5 is 1.44 / 94.5, the refractive index / Abbe number of the sixth lens L6 is 1.61 / 44.2, the refractive index / Abbe number of the seventh lens L7 is 1.44 / 94.5, the refractive index / Abbe number of the eighth lens L8 is 1.44 / 94.5, the refractive index / Abbe number of the ninth lens L9 is 1.65 / 39.5, the refractive index / Abbe number of the tenth lens L10 is 1.58 / 46.6, and the refractive index / Abbe number of the eleventh lens L11 is 1.58 / 40.9.

[0043] Optionally, the first lens is a plano-concave lens, the first side surface closer to the object side is a plane, and the second side surface closer to the image side is a concave surface; the second lens is a positive meniscus lens, the third side surface closer to the object side is a concave surface, and the fourth side surface closer to the image side is a convex surface.

[0044] Optionally, for the first side surface, R1 = ∞ mm, D1 = 1.20 - 1.60 mm, ψ1 = 6.28 - 7.25 mm, where R1 is the radius of curvature of the first side surface; D1 is the mirror surface distance of the first side surface; ψ1 is the effective clear aperture of the first side surface; for the second side surface, R2 = -18.22 - -16.84 mm, D2 = 1.25 - 1.65 mm, ψ2 = 7.18 - 7.82 mm, where R2 is the radius of curvature of the second side surface; D2 is the side surface distance of the second side surface; ψ2 is the effective clear aperture of the second side surface; for the third side surface, R3 = 26.55 - 33.41 mm, D3 = 3.07 - 3.86 mm, ψ3 = 9.22 - 11.53 mm, where R3 is the radius of curvature of the third side surface; D3 is the side surface distance of the third side surface; ψ3 is the effective clear aperture of the third side surface; for the fourth side surface, R4 = 15.24 - 18.11 mm, D4 = 6.23 - 7.54 mm, ψ4 = 13.35 - 14.88 mm, where R4 is the radius of curvature of the fourth side surface; D4 is the side surface distance of the fourth side surface; ψ4 is the effective clear aperture of the fourth side surface.

[0045] Only when the first lens and the second lens are set according to the above radius of curvature, mirror surface distance and effective clear aperture, can they magnify the object surface reaching the preset object-side field of view in the above lens group, ensuring that the lens group has a larger object-side field of view.

[0046] Optionally, for the biconvex lens of the third lens, the fifth side closer to the object side is convex, and the sixth side glued to the fourth lens is convex; for the biconvex lens of the fifth lens, the seventh side glued to the fourth lens is convex, and the eighth side closer to the image side is convex; for the biconcave lens of the fourth lens, it cooperates with the sixth side and the seventh side respectively.

[0047] Optionally, for the fifth side, R5 = -101.52 to -90.66 mm, D5 = 9.58 to 11.21 mm, ψ5 = 24.37 to 28.60 mm, where R5 is the radius of curvature of the fifth side; D5 is the side distance of the fifth side; ψ5 is the effective clear aperture of the fifth side; for the sixth side, R6 = 32.84 to 39.29 mm, D6 = 4.85 to 5.12 mm, ψ6 = 24.37 to 28.60 mm, where R6 is the radius of curvature of the sixth side; D6 is the side distance of the sixth side; ψ6 is the effective clear aperture of the sixth side; for the seventh side, R7 = -42.35 to -37.62 mm, D7 = 1.12 to 2.15 mm, ψ7 = 24.37 to 28.60 mm, where R7 is the radius of curvature of the seventh side; D7 is the side distance of the seventh side; ψ7 is the effective clear aperture of the seventh side; for the eighth side, R8 = 19.76 to 23.27 mm, D8 = 6.76 to 7.54 mm, ψ8 = 24.37 to 28.60 mm, where R8 is the radius of curvature of the eighth side; D8 is the side distance of the eighth side; ψ8 is the effective clear aperture of the eighth side.

[0048] Only when the third lens, the fourth lens and the fifth lens are set according to the above radius of curvature, mirror distance and effective clear aperture, can the secondary chromatic aberration be effectively corrected in the above lens group, and the image output by the lens group can have chromatic aberration that meets the requirements.

[0049] Optionally, for the plano-concave lens of the sixth lens, the ninth side closer to the object side is flat, and the tenth side glued to the seventh lens is concave; for the biconvex lens of the seventh lens, the side glued to the sixth lens cooperates with the tenth side, and the eleventh side closer to the image side is convex; for the biconvex lens of the eighth lens, the twelfth side closer to the object side is convex, and the thirteenth side closer to the image side is convex; for the convex-concave lens of the ninth lens, the fourteenth side closer to the object side is convex, and the fifteenth side closer to the image side is concave; for the biconcave lens of the tenth lens, the sixteenth side closer to the object side is concave, and the seventeenth side closer to the image side is concave; for the biconvex lens of the eleventh lens, the eighteenth side closer to the object side is convex, and the nineteenth side closer to the image side is convex.

[0050] Optionally, for the ninth side surface, R9 = ∞ mm, D9 = 0.32 - 0.51 mm, ψ9 = 24.37 - 28.60 mm, where R9 is the radius of curvature of the ninth side surface; D9 is the side surface distance of the ninth side surface; ψ9 is the effective clear aperture of the ninth side surface; for the tenth side surface, R10 = -25.27 - -19.22 mm, D10 = 1.85 - 2.72 mm, ψ10 = 24.37 - 28.60 mm, where R10 is the radius of curvature of the tenth side surface; D10 is the side surface distance of the tenth side surface; ψ10 is the effective clear aperture of the tenth side surface; for the eleventh side surface, R11 = 38.06 - 46.42 mm, D11 = 5.54 - 6.85 mm, ψ11 = 24.37 - 28.60 mm, where R11 is the radius of curvature of the eleventh side surface; D11 is the side surface distance of the eleventh side surface; ψ11 is the effective clear aperture of the eleventh side surface; for the twelfth side surface, R12 = -31.45 - -19.72 mm, D12 = 0.25 - 0.85 mm, ψ12 = 24.37 - 28.60 mm, where R12 is the radius of curvature of the twelfth side surface; D12 is the side surface distance of the twelfth side surface; ψ12 is the effective clear aperture of the twelfth side surface; for the thirteenth side surface, R13 = 135.25 - 151.39 mm, D13 = 3.65 - 5.15 mm, ψ13 = 24.37 - 28.60 mm, where R13 is the radius of curvature of the thirteenth side surface; D13 is the side surface distance of the thirteenth side surface; ψ13 is the effective clear aperture of the thirteenth side surface; for the fourteenth side surface, R14 = -42.25 - -38.49 mm, D14 = 2.58 - 3.26 mm, ψ14 = 22.55 - 24.95 mm, where R14 is the radius of curvature of the fourteenth side surface; D14 is the side surface distance of the fourteenth side surface; ψ14 is the effective clear aperture of the fourteenth side surface; for the fifteenth side surface, R15 = -22.05 - -16.65 mm, D15 = 1.10 - 2.15 mm, ψ15 = 17.94 - 22.85 mm, where R15 is the radius of curvature of the fifteenth side surface; D15 is the side surface distance of the fifteenth side surface; ψ15 is the effective clear aperture of the fifteenth side surface; for the sixteenth side surface, R16 = 16.36 - 22.36 mm, D16 = 5.67 - 7.97 mm, Ψ16 = 20.85 - 24.32 mm, where R16 is the radius of curvature of the sixteenth side surface; D16 is the side surface distance of the sixteenth side surface; ψ16 is the effective clear aperture of the sixteenth side surface; for the seventeenth side surface, R17 = -90.66 - -80.04 mm, D17 = 1.84 - 2.65 mm, Ψ17 = 17.54 - 28.92 mm, where R17 is the radius of curvature of the seventeenth side surface; D17 is the side surface distance of the seventeenth side surface; ψ17 is the effective clear aperture of the seventeenth side surface; for the eighteenth side surface, R18 = -268.14 - -197.95 mm, D18 = 4.34 - 5.79 mm, Ψ18 = 8.22 - 8.75 mm, where R18 is the radius of curvature of the eighteenth side; D18 is the side distance of the eighteenth side; ψ18 is the effective clear aperture of the eighteenth side; for the nineteenth side, R19 = 20.52 - 33.18 mm, D19 = 4.98 - 6.34 mm, Ψ19 = 22.55 - 30.22 mm, where R19 is the radius of curvature of the nineteenth side; D19 is the side distance of the nineteenth side; ψ19 is the effective clear aperture of the nineteenth side.

[0051] Only when the sixth lens to the eleventh lens are set according to the above radius of curvature, mirror distance and effective clear aperture can various aberrations, such as spherical aberration, coma aberration, etc., be effectively eliminated in the above lens group. At the same time, while correcting the aberrations, the chromatic aberration caused by the aberration correction will also be corrected to ensure that the image output by the lens group has the required aberrations, and during the aberration correction process, the influence on the corrected chromatic aberration will be avoided as much as possible.

[0052] Optionally, the numerical aperture of the microscope objective satisfies 0.35 ≤ NA < 0.5, where NA represents the numerical aperture of the microscope objective; the object space field diameter of the microscope objective satisfies: 4.50 ≤ FD < 5.00, where FD represents the single object space field diameter of the microscope objective; the distance between the first side of the first lens and the object surface cover plate satisfies: 1.5 ≤ WD < 3.7, where WD represents the distance from the upper surface of the cover plate near the image side to the first side of the first lens.

[0053] Under the imaging drug sensitivity analysis scenario that meets this application, it meets the requirements of a numerical aperture greater than 0.35 and a single object space field greater than 4.50 mm, and weakens and suppresses the imaging aberrations caused by the 1.50 mm thick 384-well plate cover plate, having a better imaging effect.

[0054] It should be noted that this application also provides an optional implementation manner, which will be described in detail below.

[0055] A mesoscopic microscope objective that takes into account both a large field of view and high resolution is provided to address the defects in the prior art. Due to the limitations of the detector target size and the Nyquist sampling frequency, priority is given to achieving full coverage imaging within a single well of a 384-well plate with a resolution of about 1 μm, that is, a numerical aperture greater than 0.35 and a single object space field greater than 4.50 mm, and taking into account the 1.50 mm thick 384-well plate cover plate.

[0056] Eleven spherical lenses arranged on the same optical axis, the eleven spherical lenses successively including from the object side to the image side: a first lens L1, a second lens L2, a third lens L3, a fourth lens L4, a fifth lens L5, a sixth lens L6, a seventh lens L7, an eighth lens L8, a ninth lens L9, a tenth lens L10, and an eleventh lens L11. It realizes that the single object-side field of view of the microscope objective is greater than 4.50 mm, and the numerical aperture is greater than 0.35, and it can be used for single-hole full-hole imaging of a 384-well plate and meet the numerical aperture requirements for the resolution of bacteria or fungi.

[0057] In addition, considering the influence of the imaging quality brought by the 1.50-mm-thick cover plate of the 384-well plate, the spherical aberration is avoided from being too large to affect the determination of bacteria or fungi. In addition, it realizes apochromatism, low field curvature and distortion in the visible light range, ensures the imaging quality in the whole visible light band and the whole field of view during the imaging drug sensitivity analysis process, avoids the imaging effect deviation caused by different chromatic aberrations and different positions, and maximally ensures the imaging requirements during the real-time detection process of the imaging drug sensitivity analysis. Using this microscope objective can be directly used for imaging drug sensitivity analysis based on 384-well plates, and can also be used for other biological imaging detection applications that need to balance the single object-side imaging field of view and high imaging resolution requirements.

[0058] The structure of a large-field mesoscopic microscope objective for drug sensitivity imaging analysis provided by this embodiment includes: eleven spherical lenses arranged on the same optical axis, and the eleven spherical lenses successively including from the object side to the image side: a first lens L1, a second lens L2, a third lens L3, a fourth lens L4, a fifth lens L5, a sixth lens L6, a seventh lens L7, an eighth lens L8, a ninth lens L9, a tenth lens L10, and an eleventh lens L11, where:

[0059] The first lens L1 is a plane facing the object side and a concave surface facing the image side; the first lens L1 is set as a plano-concave lens, which is used to avoid the interference between the objective and the sample surface while increasing the working distance;

[0060] The second lens L2 is a concave surface facing the object side and a convex surface facing the image side; the second lens L2 is set as a positive meniscus lens, which is used to bear the high optical power required for a high numerical aperture and adjust the coma;

[0061] The third lens L3, the fourth lens L4, and the fifth lens L5 form a cemented lens group. Among them, the third lens L3 has a convex surface facing the object side and a convex surface facing the image side, the fourth lens L4 has a concave surface facing the object side and a concave surface facing the image side, and the fifth lens L5 has a convex surface facing the object side and a convex surface facing the image side; the convex surface of the third lens L3 facing the image side is cemented to the concave surface of the fourth lens L4 facing the object side, and the concave surface of the fourth lens L4 facing the image side is cemented to the convex surface of the fifth lens facing the object side; the third lens L3, the fourth lens L4, and the fifth lens L5 form a cemented lens group, which is mainly used to correct the secondary chromatic aberration;

[0062] The sixth lens L6 and the seventh lens L7 form a cemented lens group. Among them, the sixth lens L6 has a flat surface facing the object side and a concave surface facing the image side, and the seventh lens L7 has a convex surface facing the object side and a convex surface facing the image side; the concave surface of the sixth lens L6 facing the image side is cemented to the convex surface of the seventh lens L7 facing the object side;

[0063] The eighth lens L8 has a convex surface facing the object side and a convex surface facing the image side, and is mainly used to correct spherical aberration;

[0064] The ninth lens L9 has a convex surface facing the object side and a concave surface facing the image side, and is mainly used to correct the magnification chromatic aberration;

[0065] The tenth lens L10 has a concave surface facing the object side and a concave surface facing the image side, and is mainly used to correct coma;

[0066] The eleventh lens L11 has a convex surface facing the object side and a convex surface facing the image side, and is mainly used to correct spherical aberration.

[0067] Regarding the surface types of the above-mentioned first lens L1 to the eleventh lens L11, they are specifically as follows:

[0068] The plane of the first lens L1 facing the object side is set as the first side surface, and the concave surface of the first lens L1 facing the image side is set as the second side surface; the concave surface of the second lens L2 facing the object side is set as the third side surface, and the convex surface of the second lens L2 facing the image side is set as the fourth side surface; the convex surface of the third lens L3 facing the object side is set as the fifth side surface, the cemented surface of the third lens L3 and the fourth lens L4 is set as the sixth side surface, the cemented surface of the fourth lens L4 and the fifth lens L5 is set as the seventh side surface, and the convex surface of the fifth lens L5 facing the image side is set as the eighth side surface; the plane of the sixth lens L6 facing the object side is set as the ninth side surface, and the sixth lens L6 and the seventh lens L7 are set as the ninth side surface. The cemented surface is the tenth side surface, the convex surface of the seventh lens L7 facing the image side is the eleventh side surface; the convex surface of the eighth lens L8 facing the object side is the twelfth side surface, and the convex surface of the eighth lens L8 facing the image side is the thirteenth side surface; the convex surface of the ninth lens L9 facing the object side is the fourteenth side surface, and the concave surface of the ninth lens L9 facing the image side is the fifteenth side surface; the concave surface of the tenth lens L10 facing the object side is the sixteenth side surface, and the concave surface of the tenth lens L10 facing the image side is the seventeenth side surface; the convex surface of the eleventh lens L11 facing the object side is the eighteenth side surface, and the convex surface of the eleventh lens L11 facing the image side is the nineteenth side surface.

[0069] Table 1 is a table of structural parameter ranges for twenty-two side surfaces. As shown in Table 1, it represents the structural parameters of the above-mentioned nineteen side surfaces, wherein R1 is the radius of curvature of the first side surface; D1 is the side distance of the first side surface; ψ1 is the effective clear aperture of the first side surface, and the meanings of R2~R19, D2~D19 and ψ2~ψ19 are deduced accordingly. Nd / Vd represents the refractive index / Abbe coefficient.

[0070] Table 1 Structural parameter ranges of twenty-two mirrors

[0071]

[0072]

[0073]

[0074] In some preferred embodiments, the focal length of the first lens L1 is -22.31 mm, the focal length of the second lens L2 is 55.31 mm, the focal length of the cemented lens group composed of the third lens L3, the fourth lens L4 and the fifth lens L5 is 45.58 mm, the focal length of the cemented lens group composed of the sixth lens L6 and the seventh lens L7 is 423.20 mm, the focal length of the eighth lens L8 is 49.54 mm, the focal length of the ninth lens L9 is -63.57 mm, the focal length of the tenth lens L10 is -28.44 mm, and the focal length of the eleventh lens L11 is 40.66 mm.

[0075] In some preferred embodiments, the refractive index / Abbe number of the cover plate is 1.59 / 30.9, the refractive index / Abbe number of the first lens L1 is 1.77 / 49.6, the refractive index / Abbe number of the second lens L2 is 1.63 / 35.7, the refractive index / Abbe number of the third lens L3 is 1.63 / 35.7, the refractive index / Abbe number of the fourth lens L4 is 1.61 / 44.2, the refractive index / Abbe number of the fifth lens L5 is 1.44 / 94.5, the refractive index / Abbe number of the sixth lens L6 is 1.61 / 44.2, the refractive index / Abbe number of the seventh lens L7 is 1.44 / 94.5, the refractive index / Abbe number of the eighth lens L8 is 1.44 / 94.5, the refractive index / Abbe number of the ninth lens L9 is 1.65 / 39.5, the refractive index / Abbe number of the tenth lens L10 is 1.58 / 46.6, and the refractive index / Abbe number of the eleventh lens L11 is 1.58 / 40.9.

[0076] In some preferred embodiments, the microscope objective lens satisfies: 0.35 ≤ NA < 0.5, where NA represents the numerical aperture of the microscope objective lens.

[0077] In some preferred embodiments, the microscope objective lens satisfies: 4.50 ≤ FD < 5.00, where FD represents the size of the single object space field of view diameter of the microscope objective lens.

[0078] In some preferred embodiments, the microscope objective lens satisfies: 1.5 ≤ WD < 3.7, where WD represents the distance from the back surface of the cover plate away from the object space to the front surface of the object space of the first lens.

[0079] Figure 2 is a schematic diagram of the 0.0 field lateral aberration of the microscope objective lens provided according to the embodiment of the present application, as Figure 2 shown, Figure 2 In the figure, the abscissas PY and PX represent the entrance pupil, and the ordinates EY and EX represent the lateral aberration, where Y represents the meridional direction and X represents the sagittal direction. The lateral aberration at each wavelength and each entrance pupil position in the wavelength band from 0.480 μm to 0.644 μm is within ±1 μm. It can be seen from the figure that the aberration balance is very good and the imaging is excellent. Figure 2 In the figure, the abscissa is the normalized entrance pupil; the maximum value of the ordinate is +1 μm and the minimum value is -1 μm.

[0080] Figure 3 is a schematic diagram of the 0.5 field lateral aberration of the microscope objective lens provided according to the embodiment of the present application, as Figure 3 shown, Figure 3In the figure, the horizontal coordinates PY and PX represent the entrance pupil, and the vertical coordinates EY and EX represent the lateral aberration. Here, Y represents the meridional direction, and X represents the sagittal direction. The wavelengths of the respective light rays are indicated by different colors. The lateral aberration at each wavelength and each entrance pupil position in the wavelength band from 0.480 μm to 0.644 μm is within ±2 μm. It can be seen from the figure that the aberration balance is very good and the imaging is excellent. Figure 3 In the figure, the horizontal coordinate is the normalized entrance pupil; the maximum value of the vertical coordinate is +2 μm, and the minimum value is -2 μm.

[0081] Figure 4 This is a schematic diagram of the 0.7 field of view lateral aberration of the microscope objective lens provided according to an embodiment of the present application, as Figure 4 shown. Figure 4 In the figure, the horizontal coordinates PY and PX represent the entrance pupil, and the vertical coordinates EY and EX represent the lateral aberration. Here, Y represents the meridional direction, and X represents the sagittal direction. The wavelengths of the respective light rays are indicated by different colors. The lateral aberration at each wavelength and each entrance pupil position in the wavelength band from 0.480 μm to 0.644 μm is within ±2 μm. It can be seen from the figure that the aberration balance is very good and the imaging is excellent. Figure 4 In the figure, the horizontal coordinate is the normalized entrance pupil; the maximum value of the vertical coordinate is +2 μm, and the minimum value is -2 μm.

[0082] Figure 5 This is a schematic diagram of the 1.0 field of view lateral aberration of the microscope objective lens provided according to an embodiment of the present application, as Figure 5 shown. Figure 5 In the figure, the horizontal coordinates PY and PX represent the entrance pupil, and the vertical coordinates EY and EX represent the lateral aberration. Here, Y represents the meridional direction, and X represents the sagittal direction. The wavelengths of the respective light rays are indicated by different colors. The lateral aberration at each wavelength and each entrance pupil position in the wavelength band from 0.480 μm to 0.644 μm is within ±3 μm. It can be seen from the figure that the aberration balance is very good and the imaging is excellent. Figure 5 In the figure, the horizontal coordinate is the normalized entrance pupil; the maximum value of the vertical coordinate is +5 μm, and the minimum value is -5 μm.

[0083] Figure 6 This is a schematic diagram of the full field of view transfer function curve of the microscope objective lens provided according to an embodiment of the present application, as Figure 6 shown. Figure 6 In the figure, the vertical coordinate is the modulus of the normalized OTF, and the horizontal coordinate is the spatial frequency, with the unit of lp / mm. The figure shows that both the on-axis field of view transfer function curve and the off-axis field of view transfer function curve are close to the diffraction limit, indicating that the imaging contrast of the optical system in the full field of view is very high and the imaging has distinct levels.

[0084] Figure 7 This is a schematic diagram of the axial chromatic aberration of the microscope objective lens provided according to an embodiment of the present application, as Figure 7 shown. Figure 7The vertical coordinate represents the entrance pupil, and the horizontal coordinate represents the longitudinal aberration, with the unit of mm. The wavelengths of each ray are indicated by different colors. The axial chromatic aberration at each entrance pupil position for any two wavelengths in the range from 0.480 μm to 0.644 μm is less than 2λ / NA2, reaching the apochromatic level. Figure 7 The vertical coordinate in the figure is the normalized entrance pupil; the horizontal coordinate represents the longitudinal aberration, with the maximum value of 0.005 mm and the minimum value of -0.005 mm.

[0085] Figure 8 It is a schematic diagram of the lateral chromatic aberration of the microscope objective lens provided according to the embodiment of the present application. As Figure 8 shown, Figure 8 In the figure, the vertical coordinate represents the field of view, and the horizontal coordinate represents the lateral aberration, with the unit of μm. The dotted line represents the size of the Airy disk of the system diffraction limit, and the solid line represents that the full field of view range of the lateral chromatic aberration in the range from 0.480 μm to 0.644 μm is within the Airy disk.

[0086] Figure 9 It is a schematic diagram of the field curvature and distortion of the microscope objective lens provided according to the embodiment of the present application. As Figure 9 shown, Figure 9 In the left figure of the figure, it is the field curvature diagram. In the figure, the vertical coordinate represents the field of view, and the horizontal coordinate represents the field curvature, with the unit of μm. The wavelengths of each ray are indicated by different grayscales. The field curvature values at each field of view position for each wavelength in the range from 0.480 μm to 0.644 μm are all within ±4 μm. The maximum field of view is 3.661 degrees, the sagittal field curvature = 0.0049 mm, and the meridional field curvature = 0.0054 mm. The axial difference between the best focus points of the edge field of view and the center field of view is less than 2λ / NA2, and the theoretical value meets the requirement of clear full field of view, reaching the requirement of a flat-field objective lens. The vertical coordinate in the figure is the normalized field of view; the horizontal coordinate represents the field curvature, with the maximum value of 5 μm and the minimum value of -5 μm. Figure 9 In the right figure of the figure, it is the distortion diagram. In the figure, the vertical coordinate represents the field of view, and the horizontal coordinate represents the distortion (percentage). The wavelengths of each ray are indicated by different grayscales. The maximum field of view is 3.661 degrees, the maximum distortion = 0.1653%, and the distortion at each field of view position for each wavelength in the range from 0.480 μm to 0.644 μm is less than 0.166%. The vertical coordinate in the figure is the normalized field of view; the horizontal coordinate represents the distortion, with the maximum value of -0.2% and the minimum value of -0.2%.

[0087] Figure 10 It is a schematic diagram of the Strehl ratio of the full field of view of the microscope objective lens provided according to the embodiment of the present application. As Figure 10As shown in the figure, the ordinate in the figure represents the Strehl ratio value, and the abscissa represents the field of view. Strehl ratio: The ratio of the peak intensity in the diffraction pattern of a point image with aberration to the peak intensity in the diffraction pattern of a point image without aberration. A high Strehl ratio indicates a high level of aberration correction. A Strehl ratio equal to 0.8 represents the diffraction limit. Each imaging field of view is indicated by a different color. The Strehl ratio is greater than the diffraction limit within the entire field of view range from 0.480 μm to 0.644 μm, approximately equal to or greater than 0.95.

[0088] It can be seen from this that the microscope objective provided by this embodiment, while ensuring a high numerical aperture and high resolution, significantly increases the object space field of view, achieves apochromatism in the wavelength range of 480 nm to 644 nm, and well corrects spherical aberration, coma, astigmatism, field curvature, distortion, lateral chromatic aberration, and axial chromatic aberration, meeting the requirements of a flat-field apochromatic objective, and achieving the technical requirements of a wide field of view (i.e., a large field number and low magnification) and a high numerical aperture.

[0089] Of course, a large-field mesoscopic microscope objective for imaging drug sensitivity analysis in this embodiment may also have various transformations and modifications, and is not limited to the specific structure of the above embodiment. In short, the protection scope of the present invention should include those transformations, substitutions, and modifications that are obvious to those of ordinary skill in the art.

[0090] To achieve the above object, according to another aspect of the present application, a method for determining a lens group of a microscope objective is provided. The present invention will be described below in conjunction with the preferred implementation steps. Figure 11 It is a flowchart of a method for determining a lens group of a large-field mesoscopic microscope objective for drug sensitivity imaging analysis according to an embodiment of the present application. As Figure 11 shown, the method includes the following steps:

[0091] Step S111, determine the numerical aperture range and the object space field of view range of the lens group according to the imaging requirements of the lens group;

[0092] Step S112, determine an aperture lens group for magnifying the observation object to the target aperture range according to the numerical aperture range. The aperture lens group includes a first lens and a second lens from the object side to the image side. The first lens is a plano-concave lens, and the second lens is a positive meniscus lens;

[0093] Step S113, determine the positions and distances of the first lens and the second lens according to the object space field of view range;

[0094] Step S114: Determine an achromatic lens group for correcting chromatic aberration according to the color of the image output by the aperture lens group. The achromatic lens group includes a third lens, a fourth lens, and a fifth lens from the object side to the image side. The third lens and the fifth lens are both biconvex lenses, and the fourth lens is a biconcave mirror. The third lens, the fourth lens, and the fifth lens are glued together in sequence;

[0095] Step S115: Determine an aberration lens group for correcting aberration according to the deformation of the image output by the achromatic lens group. The aberration lens group includes a sixth lens to an eleventh lens from the object side to the image side. The sixth lens is a plano-concave lens, the seventh lens is a biconvex lens, and the sixth lens and the seventh lens are glued together. The eighth lens is a biconvex lens, the ninth lens is a convex-concave lens, the tenth lens is a biconcave lens, and the eleventh lens is a biconvex lens.

[0096] The above steps use multiple spherical lenses arranged coaxially. The multiple spherical lenses include an aperture lens group for magnifying an observation object to a target aperture range, an achromatic lens group for correcting chromatic aberration, and an aberration lens group for correcting aberration. The aperture lens group includes a first lens and a second lens from the object side to the image side. The first lens is a plano-concave lens, and the second lens is a positive meniscus lens. The achromatic lens group includes a third lens, a fourth lens, and a fifth lens from the object side to the image side. The third lens and the fifth lens are both biconvex lenses, the fourth lens is a biconcave mirror, and the third lens, the fourth lens, and the fifth lens are glued together in sequence. The aberration lens group includes a sixth lens to an eleventh lens from the object side to the image side. The sixth lens is a plano-concave lens, the seventh lens is a biconvex lens, and the sixth lens and the seventh lens are glued together. The eighth lens is a biconvex lens, the ninth lens is a convex-concave lens, the tenth lens is a biconcave lens, and the eleventh lens is a biconvex lens. This achieves the purpose of ensuring a large numerical aperture while ensuring a large object-side field of view, realizing the technical effect of simultaneously making the numerical aperture and the object-side field of view meet high usage requirements, and further solving the problem that in the related art, when a microscope is used for drug sensitivity imaging analysis, the numerical aperture and the object-side field of view cannot meet the requirements, and the imaging error is large.

[0097] Optionally, determining the aberration lens group for correcting aberration according to the deformation of the image output by the achromatic lens group includes: preliminarily selecting the glued sixth lens and seventh lens for initially correcting aberration, the ninth lens for correcting lateral chromatic aberration, and the eleventh lens for correcting spherical aberration according to the deformation of the image output by the achromatic lens group; determining the aberration magnitude according to the ray angles output by the seventh lens, the ninth lens, and the eleventh lens, where the aberration includes at least one of the following: spherical aberration, coma; adding a corresponding eighth lens after the seventh lens with spherical aberration, and adding a corresponding tenth lens after the ninth lens with coma.

[0098] It should also be noted that the term "including", "comprising" or any other variant thereof is intended to cover non-exclusive inclusion, such that a process, method, commodity or device comprising a series of elements not only includes those elements, but also includes other elements not expressly listed, or further includes elements inherent to such process, method, commodity or device. Without further limitation, an element defined by the statement "comprising one..." does not exclude the presence of additional identical elements in the process, method, commodity or device comprising the element.

[0099] The above are only embodiments of the present application and are not intended to limit the present application. For those skilled in the art, various changes and modifications can be made to the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included within the scope of the claims of the present application.

Claims

1. A large field of view mesoscopic microscope objective lens for drug sensitivity imaging analysis, characterized in that, Comprising: A plurality of spherical lenses arranged coaxially, said plurality of spherical lenses being composed of an aperture lens group for magnifying an observation object to a target aperture range, a chromatic aberration lens group for correcting chromatic aberration, and an aberration lens group for correcting aberration; Said aperture lens group is composed of a first lens and a second lens from the object side to the image side. The first lens is a plano-concave lens, and the second lens is a positive meniscus lens; for the plano-concave lens of the first lens, the first side surface close to the object side is a plane, and the second side surface close to the image side is a concave surface; for the positive meniscus lens of the second lens, the third side surface close to the object side is a concave surface, and the fourth side surface close to the image side is a convex surface; Said chromatic aberration lens group is composed of a third lens, a fourth lens, and a fifth lens from the object side to the image side. Both the third lens and the fifth lens are double convex lenses, the fourth lens is a double concave lens, and the third lens, the fourth lens, and the fifth lens are glued together in sequence; Said aberration lens group is composed of a sixth lens to an eleventh lens from the object side to the image side. The sixth lens is a plano-concave lens, the seventh lens is a double convex lens, the sixth lens and the seventh lens are glued together, the eighth lens is a double convex lens, the ninth lens is a convex-concave lens, the tenth lens is a double concave lens, and the eleventh lens is a double convex lens; for the plano-concave lens of the sixth lens, the ninth side surface close to the object side is a plane, and the tenth side surface glued to the seventh lens is a concave surface; for the convex-concave lens of the ninth lens, the fourteenth side surface close to the object side is a convex surface, and the fifteenth side surface close to the image side is a concave surface.

2. The microscope objective according to claim 1, characterized in that, For the first side surface, R1 = ∞mm, D1 = 1.20 - 1.60mm, ψ1 = 6.28 - 7.25mm, where R1 is the radius of curvature of the first side surface; D1 is the mirror distance of the first side surface; ψ1 is the effective aperture of the first side surface; For the second side surface, R2 = -18.22 - -16.84mm, D2 = 1.25 - 1.65mm, ψ2 = 7.18 - 7.82mm, where R2 is the radius of curvature of the second side surface; D2 is the side distance of the second side surface; ψ2 is the effective aperture of the second side surface; For the third side surface, R3 = 26.55 - 33.41mm, D3 = 3.07 - 3.86mm, ψ3 = 9.22 - 11.53mm, where R3 is the radius of curvature of the third side surface; D3 is the side distance of the third side surface; ψ3 is the effective aperture of the third side surface; For the fourth side surface, R4 = 15.24 - 18.11mm, D4 = 6.23 - 7.54mm, ψ4 = 13.35 - 14.88mm, where R4 is the radius of curvature of the fourth side surface; D4 is the side distance of the fourth side surface; ψ4 is the effective aperture of the fourth side surface.

3. The microscope objective according to claim 2, characterized in that, For the double convex lens of the third lens, the fifth side surface close to the object side is a convex surface, and the sixth side surface glued to the fourth lens is a convex surface; For the double convex lens of the fifth lens, the seventh side surface glued to the fourth lens is a convex surface, and the eighth side surface close to the image side is a convex surface; For the double concave lens of the fourth lens, it cooperates with the sixth side surface and the seventh side surface respectively.

4. The microscope objective according to claim 3, characterized in that, For the fifth side, R5 = -101.52 to -90.66 mm, D5 = 9.58 to 11.21 mm, ψ5 = 24.37 to 28.60 mm, where R5 is the radius of curvature of the fifth side; D5 is the side distance of the fifth side; ψ5 is the effective clear aperture of the fifth side; For the sixth side, R6 = 32.84 to 39.29 mm, D6 = 4.85 to 5.12 mm, ψ6 = 24.37 to 28.60 mm, where R6 is the radius of curvature of the sixth side; D6 is the side distance of the sixth side; ψ6 is the effective clear aperture of the sixth side; For the seventh side, R7 = -42.35 to -37.62 mm, D7 = 1.12 to 2.15 mm, ψ7 = 24.37 to 28.60 mm, where R7 is the radius of curvature of the seventh side; D7 is the side distance of the seventh side; ψ7 is the effective clear aperture of the seventh side; For the eighth side, R8 = 19.76 to 23.27 mm, D8 = 6.76 to 7.54 mm, ψ8 = 24.37 to 28.60 mm, where R8 is the radius of curvature of the eighth side; D8 is the side distance of the eighth side; ψ8 is the effective clear aperture of the eighth side.

5. The microscope objective according to claim 4, wherein the biconvex lens of the seventh lens, the side surface glued to the sixth lens cooperates with the tenth side surface, and the eleventh side surface closer to the image side is a convex surface; the biconvex lens of the eighth lens, the twelfth side surface closer to the object side is a convex surface, and the thirteenth side surface closer to the image side is a convex surface; the biconcave lens of the tenth lens, the sixteenth side surface closer to the object side is a concave surface, and the seventeenth side surface closer to the image side is a concave surface; the biconvex lens of the eleventh lens, the eighteenth side surface closer to the object side is a convex surface, and the nineteenth side surface closer to the image side is a convex surface.

6. The microscope objective according to claim 5, characterized in that, For the ninth side, R9 = ∞ mm, D9 = 0.32 to 0.51 mm, ψ9 = 24.37 to 28.60 mm, where R9 is the radius of curvature of the ninth side; D9 is the side distance of the ninth side; ψ9 is the effective clear aperture of the ninth side; For the tenth side, R10 = -25.27 to -19.22 mm, D10 = 1.85 to 2.72 mm, ψ10 = 24.37 to 28.60 mm, where R10 is the radius of curvature of the tenth side; D10 is the side distance of the tenth side; ψ10 is the effective clear aperture of the tenth side; For the eleventh side, R11 = 38.06 to 46.42 mm, D11 = 5.54 to 6.85 mm, ψ11 = 24.37 to 28.60 mm, where R11 is the radius of curvature of the eleventh side; D11 is the side distance of the eleventh side; ψ11 is the effective clear aperture of the eleventh side; For the twelfth side surface, R12 = -31.45 to -19.72 mm, D12 = 0.25 to 0.85 mm, ψ12 = 24.37 to 28.60 mm, where R12 is the radius of curvature of the twelfth side surface; D12 is the side distance of the twelfth side surface; ψ12 is the effective clear aperture of the twelfth side surface; For the thirteenth side surface, R13 = 135.25 to 151.39 mm, D13 = 3.65 to 5.15 mm, ψ13 = 24.37 to 28.60 mm, where R13 is the radius of curvature of the thirteenth side surface; D13 is the side distance of the thirteenth side surface; ψ13 is the effective clear aperture of the thirteenth side surface; For the fourteenth side surface, R14 = -42.25 to -38.49 mm, D14 = 2.58 to 3.26 mm, ψ14 = 22.55 to 24.95 mm, where R14 is the radius of curvature of the fourteenth side surface; D14 is the side distance of the fourteenth side surface; ψ14 is the effective clear aperture of the fourteenth side surface; For the fifteenth side surface, R15 = -22.05 to -16.65 mm, D15 = 1.10 to 2.15 mm, ψ15 = 17.94 to 22.85 mm, where R15 is the radius of curvature of the fifteenth side surface; D15 is the side distance of the fifteenth side surface; ψ15 is the effective clear aperture of the fifteenth side surface; For the sixteenth side surface, R16 = 16.36 to 22.36 mm, D16 = 5.67 to 7.97 mm, Ψ16 = 20.85 to 24.32 mm, where R16 is the radius of curvature of the sixteenth side surface; D16 is the side distance of the sixteenth side surface; ψ16 is the effective clear aperture of the sixteenth side surface; For the seventeenth side surface, R17 = -90.66 to -80.04 mm, D17 = 1.84 to 2.65 mm, Ψ17 = 17.54 to 28.92 mm, where R17 is the radius of curvature of the seventeenth side surface; D17 is the side distance of the seventeenth side surface; ψ17 is the effective clear aperture of the seventeenth side surface; For the eighteenth side surface, R18 = -268.14 to -197.95 mm, D18 = 4.34 to 5.79 mm, Ψ18 = 8.22 to 8.75 mm, where R18 is the radius of curvature of the eighteenth side surface; D18 is the side distance of the eighteenth side surface; ψ18 is the effective clear aperture of the eighteenth side surface; For the nineteenth side surface, R19 = 20.52 to 33.18 mm, D19 = 4.98 to 6.34 mm, Ψ19 = 22.55 to 30.22 mm, where R19 is the radius of curvature of the nineteenth side surface; D19 is the side distance of the nineteenth side surface; ψ19 is the effective clear aperture of the nineteenth side surface.

7. The microscope objective according to any one of claims 1 to 6, characterized in that, The numerical aperture of the microscope objective satisfies 0.35 ≤ NA < 0.5, where NA represents the numerical aperture of the microscope objective; The object space field diameter of the microscope objective satisfies 4.50 ≤ FD < 5.00, where FD represents the single object space field diameter of the microscope objective; The distance between the first side of the first lens and the object surface cover plate satisfies: 1.5 ≤ WD < 3.7, where WD represents the distance from the upper surface of the cover plate on the image side to the first side of the first lens.

8. A method for determining a lens group of a large-field mesoscopic microscope objective for drug sensitivity imaging analysis, characterized in that, Comprising: Determine the numerical aperture range and the object space field of view range of the lens group according to the imaging requirements of the lens group; Determine an aperture lens group for magnifying an observation object to a target aperture range according to the numerical aperture range, wherein the aperture lens group is composed of a first lens and a second lens from the object side to the image side, the first lens is a plano-concave lens, and the second lens is a positive meniscus lens; for the plano-concave first lens, the first side near the object side is a plane, and the second side near the image side is a concave surface; for the positive meniscus second lens, the third side near the object side is a concave surface, and the fourth side near the image side is a convex surface; Determine the positions and distances of the first lens and the second lens according to the object space field of view range; Determine a chromatic aberration lens group for correcting chromatic aberration according to the color of the image output by the aperture lens group, wherein the chromatic aberration lens group is composed of a third lens, a fourth lens, and a fifth lens from the object side to the image side, the third lens and the fifth lens are both biconvex lenses, the fourth lens is a biconcave lens, and the third lens, the fourth lens, and the fifth lens are glued together in sequence; Determine an aberration lens group for correcting aberration according to the deformation of the image output by the chromatic aberration lens group, wherein the aberration lens group is composed of a sixth lens to an eleventh lens from the object side to the image side, the sixth lens is a plano-concave lens, the seventh lens is a biconvex lens, the sixth lens and the seventh lens are glued together, the eighth lens is a biconvex lens, the ninth lens is a convex-concave lens, the tenth lens is a biconcave lens, and the eleventh lens is a biconvex lens; for the plano-concave sixth lens, the ninth side near the object side is a plane, and the tenth side glued to the seventh lens is a concave surface; for the convex-concave ninth lens, the fourteenth side near the object side is a convex surface, and the fifteenth side near the image side is a concave surface.

9. The method according to claim 8, wherein Determine an aberration lens group for correcting aberration according to the deformation of the image output by the chromatic aberration lens group, including: Preliminarily select the glued sixth lens and seventh lens for initially correcting aberration, the ninth lens for correcting magnification chromatic aberration, and the eleventh lens for correcting spherical aberration according to the deformation of the image output by the chromatic aberration lens group; Determine the aberration magnitude according to the ray angles output by the seventh lens, the ninth lens, and the eleventh lens, wherein the aberration includes at least one of the following: spherical aberration, coma; Add the corresponding eighth lens after the seventh lens with spherical aberration, and add the corresponding tenth lens after the ninth lens with coma.

Citation Information

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