Window and microscopic imaging system

By using silica gel as an immersion medium in the microscopic imaging system, the problems of fluidity and refractive index mismatch of liquid media are solved, achieving high resolution and high quality imaging effects for live imaging, and improving the user experience and lifespan of the system.

WO2026149286A1PCT designated stage Publication Date: 2026-07-16PEKING UNIV +1

Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
PEKING UNIV
Filing Date
2025-12-31
Publication Date
2026-07-16

AI Technical Summary

Technical Problem

In existing microscopic imaging systems, the fluidity of the liquid immersion medium limits the application scenarios of live imaging when using high-NA objectives, and the refractive index mismatch leads to a decrease in image quality, making it difficult to maintain high resolution and image quality in live imaging.

Method used

Using non-fluid silica gel as the immersion medium, the refractive index of the silica gel matches that of biological tissue, and it is used as a window in the microscopic imaging system. The elastic deformation of the silica gel adapts to the movement of the objective lens, maintaining the stability of the imaging focal plane.

Benefits of technology

It achieves high-resolution and high-quality imaging in live imaging, avoids the fluidity problem of liquid media, and improves the user experience and lifespan of the imaging system.

✦ Generated by Eureka AI based on patent content.

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Abstract

Disclosed in the present invention are a window and a microscopic imaging system. The window comprises a transparent glass slide and an immersion medium, the side of the transparent glass slide away from a sample to be observed is provided with the immersion medium, and the material of the immersion medium comprises silica gel. The microscopic imaging system provided by the present invention is provided with the window. Because the non-fluid silica gel of which the refractive index matches the refractive index of biological tissues is used as the immersion medium in the window, the window can be suitable for biopsy, thereby providing an excellent in-vivo imaging effect and product use experience.
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Description

Window and Microscopic Imaging System Technical Field

[0001] This application relates to the field of optical imaging technology, and in particular to a window and a microscopic imaging system having the window. Background Technology

[0002] The microscope objective (hereinafter referred to as the objective lens) is one of the core components of a microscope imaging system. Numerical aperture (NA) is one of the key indicators of the objective lens, describing its ability to converge and collect light. Its mathematical expression is:

[0003] NA = n × sinα

[0004] Where n is the refractive index of the immersion medium and α is the aperture angle.

[0005] Common immersion media include fluids such as air (n = 1.00), water (n = 1.33–1.34), and oil (n = 1.5–1.6). The higher the refractive index of the immersion medium, the larger the numerical aperture (NA), and correspondingly, the higher the theoretical resolution and the stronger the light-gathering ability of the objective lens. However, practical imaging systems exhibit various aberrations, especially when using high-NA objectives with specific imaging requirements. Refractive index mismatch can lead to significant spherical aberration. Therefore, simply increasing the refractive index of the immersion medium does not always improve imaging performance. Maintaining refractive index matching during focusing is crucial for preserving image quality. Thus, to achieve optimal imaging results, the objective lens immersion medium must be selected based on the actual refractive index of the sample being observed.

[0006] For bioimaging, the sample to be observed is biological tissue. Biological tissue is mainly composed of water, proteins, lipids, etc., and is a complex complex with anisotropic microstructures composed of different components. Its refractive index is usually described by a statistical average. The higher the proportion of a certain component, the closer the refractive index is to that component. The average refractive index of biological tissue composed of a large number of living cells is usually around 1.40. For example, when the wavelength is in the visible to near-infrared range, the refractive index of the skin epidermis is 1.39–1.43. Therefore, water immersion lenses (objectives with water as the immersion medium) or oil immersion lenses (objectives with ordinary mineral oil as the immersion medium) are not the optimal imaging medium options.

[0007] On the other hand, in vivo microscopy mainly images various parts of a living body. Since the objective lens is not always vertically downward when imaging a living body, but may be in any position, if a liquid substance is used as the immersion medium, the fluidity of the liquid may limit the application scenarios or even affect the imaging quality. Summary of the Invention

[0008] In view of this, the purpose of the present invention is to provide a window and a microscopic imaging system provided with the window, wherein the window uses non-fluid silica gel as an immersion medium, which matches the refractive index of biological tissue, is suitable for in vivo examination, and obtains very good imaging effect and product user experience.

[0009] To achieve the above objectives, the present invention provides the following technical solution:

[0010] A window pane includes a transparent glass slide and an immersion medium, wherein:

[0011] The immersion medium is provided on the side of the transparent glass slide away from the sample to be observed;

[0012] The immersion medium is made of silicone gel.

[0013] Optionally, in the above-mentioned window, the immersion medium is bonded to the transparent glass sheet.

[0014] Optionally, in the aforementioned window, the thickness of the immersion medium gradually decreases from the central region to the periphery.

[0015] Optionally, in the above-mentioned window, the outer contour of the immersion medium in a cross section perpendicular to the transparent glass sheet is curved.

[0016] Optionally, in the above-mentioned window, the transparent glass sheet is made of any one of glass, quartz, sapphire, or plexiglass.

[0017] Optionally, the aforementioned window also includes a bracket for mounting the transparent glass sheet.

[0018] Optionally, in the aforementioned window slats, the bracket is provided with a light-transmitting hole:

[0019] The transparent glass slide is located inside the light-transmitting hole and is fixedly connected to the support. The outer surface of the transparent glass slide can contact the sample to be observed.

[0020] The immersion medium is located on the inner side of the transparent glass slide.

[0021] Optionally, in the above-mentioned window, the bracket can be fitted onto the outer side of the bottom end of the objective lens, and there is a gap distance greater than zero between the bracket and the bottom sidewall of the objective lens.

[0022] A microscopic imaging system, provided with the window described above.

[0023] Optionally, the above-mentioned microscopic imaging system further includes:

[0024] The housing, to which the transparent glass slide is connected; the housing is either a closed housing or an open housing.

[0025] An objective lens, which is movably disposed within the housing, or the objective lens is fixedly mounted within the housing.

[0026] As can be seen from the above technical solution, the microscopic imaging system and its window provided by the present invention use non-fluid silica gel as the immersion medium. Compared with the solutions using gaseous immersion media (air) and liquid immersion media (water, oil, silicone oil), the present invention uses silica gel as the immersion medium, which has advantages such as non-volatile, non-flowing, chemical inertness, wide operating temperature range, and long lifespan. Moreover, since silica gel is a colorless, transparent, highly elastic, highly viscous solid silicone with self-healing properties in the near-ultraviolet to near-infrared band, and its refractive index is 1.407 in the 780nm band, the advantages of the window and microscopic imaging system using silica gel as the immersion medium provided by the present invention are that not only is the immersion medium in a non-fluid state, but its refractive index (1.39~1.4) matches the refractive index of biological tissues (for example, the refractive index of the skin epidermis is 1.39~1.43), which is suitable for in vivo examination and achieves very good imaging results and product user experience. Attached Figure Description

[0027] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0028] Figure 1 is a half-sectional view of the window provided in an embodiment of the present invention;

[0029] Figure 2 is a schematic diagram of the structure of the objective lens body gradually approaching the window according to an embodiment of the present invention;

[0030] Figure 3 is a schematic diagram of the structure when the objective lens body and the silica gel are just in contact, according to an embodiment of the present invention;

[0031] Figures 4 and 5 are schematic diagrams of the structure of the objective lens body when extruding silicone gel according to the embodiments of the present invention;

[0032] Figure 6 is a schematic diagram of the structure of the microscopic imaging device provided in an embodiment of the present invention.

[0033] The components are: 1-support, 2-transparent glass slide, 3-immersion medium, 4-sample to be observed, 5-objective lens, 6-shell. Detailed Implementation

[0034] This invention discloses a window and a microscopic imaging system equipped with the window. The window uses non-fluid silica gel as the immersion medium, which matches the refractive index of biological tissue (such as human skin tissue), making it suitable for in vivo examination and achieving excellent imaging results and user experience.

[0035] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0036] Please refer to Figure 1. The window provided in this embodiment of the invention includes a transparent glass slide 2 and an immersion medium 3. The immersion medium 3 is disposed on the side of the transparent glass slide 2 away from the sample 4 to be observed. The immersion medium 3 is made of silica gel, which is fixed to the surface of the transparent glass slide 2. It is an elastic, non-fluid, maintenance-free, solid transparent state, naturally possessing a specific volume and shape. Specifically, the silica gel, as the immersion medium 3, is a rubber-like, non-flowing, but highly elastic solid with self-healing properties.

[0037] Compared to solutions using gaseous or liquid immersion media (air, water, silicone oil, etc.), the window using silicone (such as silicone gel) as the immersion medium 3 provided in this embodiment of the invention has advantages such as non-volatile, non-flowing, chemically inert, wide operating temperature range, and long lifespan. Furthermore, since silicone gel is a colorless, transparent, highly elastic, highly viscous solid silicone with self-healing properties in the near-ultraviolet to near-infrared band, and its refractive index is 1.407 in the working band (such as the 780nm band), the window using highly elastic silicone (such as silicone gel) as the immersion medium 3 provided in this embodiment of the invention also has the advantage that not only is the immersion medium 3 non-fluid in form, but its refractive index (1.39–1.4) matches the refractive index of biological tissues (e.g., the refractive index of skin epidermis is 1.39–1.43), making it suitable for microscopic imaging systems requiring in vivo examination, resulting in excellent imaging effects and a superior user experience.

[0038] It is understood that the silicone used in this application is preferably a silicone gel, and further, the silicone gel used in this application is preferably an organosilicon gel.

[0039] In practice, as shown in Figures 2 to 5, the window is located between the objective lens 5 of the microscopic imaging system and the sample 4 to be observed, with the sample 4 closely attached to the lower surface of the transparent slide 2. When observing the sample using the microscopic imaging system and the aforementioned window: First, the objective lens 5 is gradually moved closer to the window (see Figure 2); the bottom of the objective lens 5 contacts the immersion medium 3, at which point the imaging focal plane is located inside the immersion medium 3 or the transparent slide 2 (see Figure 3); the objective lens 5 continues to move towards the position of the sample 4, and the imaging focal plane reaches the interface between the transparent slide 2 and the sample 4. During this process, the immersion medium 3 is compressed and deformed (see Figure 4); as the objective lens 5 continues to move, the immersion medium 3 reaches its maximum designed deformation and can no longer be compressed, and the imaging focal plane reaches its maximum designed imaging depth (see Figure 5), without the need for complex mechanical focusing.

[0040] During the above process, under the pressure of objective lens 5, the immersion medium 3 gradually deforms, thereby changing the relative position between the focal plane, the window, and the sample. As the immersion medium 3 is gradually compressed, its thickness decreases, its cross-sectional diameter increases, while its overall volume remains essentially unchanged. When objective lens 5 makes a small-range triaxial translation relative to the window during observation, the immersion medium 3, due to its inherent viscosity and elasticity, ensures that the gap between the transparent slide 2 and objective lens 5 remains filled throughout the observation.

[0041] Specifically, the transparent glass slide 2 is a cover glass for bioimaging made of any material such as glass, quartz, sapphire, or plexiglass. The immersion medium 3 is adhered to one side of the transparent glass slide 2 by its own adhesiveness, or, in other specific embodiments, the immersion medium 3 can be fixed to the transparent glass slide 2 by other means such as adhesives.

[0042] In a preferred embodiment, as shown in Figures 1 and 2, in its natural state, the immersion medium 3 is fixed to the surface of the transparent glass slide 2, forming a smooth, raised shape. Its thickness gradually decreases from the central region to the periphery (i.e., h1 > h2 > h3 in Figure 1). Furthermore, the outer contour of the immersion medium 3 in a cross-section perpendicular to the transparent glass slide 2 is generally curved, resembling a Gaussian line. However, this is not a limitation. In other embodiments, the shape of the immersion medium 3 may also be a regular frustum structure, a trapezoidal block structure, a hemispherical structure, or other structures. This invention does not specifically limit this.

[0043] It should be noted that during the extrusion process, a Gaussian-shaped immersion medium facilitates gradual contact with the objective lens and guides its flow, allowing the immersion medium to flow more effectively and evenly in all directions, thus filling the gaps more stably. Furthermore, it helps reduce stress concentration in the immersion medium. Of course, the initial shape of the immersion medium can also be other continuous, smooth curves.

[0044] Furthermore, a bracket 1 is also provided in the aforementioned window. The main function of the bracket 1 is to mount the transparent slide 2, fixing it to the observation position below the objective lens 5 of the imaging system, thus serving as a positioning and fixing connection. For example, as shown in Figure 6, the transparent slide 2 is fixed to the bottom of the housing 6 by the bracket 1; the imaging system and its bottom objective lens 5 are both located inside the housing 6, and can be axially or triaxially translated within the housing 6 to adjust the imaging position. It should be noted that fixing the transparent slide 2 to the bottom of the housing 6 by the bracket 1 means that the bracket 1 can fix the transparent slide 2 to the bottom of the housing 6 without moving it. If adjustment, maintenance, or replacement of the window is required, the transparent slide 2 can be removed from the bracket 1, or the bracket 1 can be removed from the housing 6, or the distance between the transparent slide 2 and the housing 6 can be adjusted by the bracket 1.

[0045] Specifically, the bracket 1 is provided with a light-transmitting hole, and the immersion medium 3 and the transparent glass slide 2 are both located on the axis of the light-transmitting hole. Moreover, the transparent glass slide 2 is fixedly connected to the bracket 1. For example, as shown in Figure 1, the bottom opening of the light-transmitting hole of the bracket 1 is provided with a mounting groove that matches the transparent glass slide 2. The transparent glass slide 2 is fixed in the mounting groove by bonding, pressing or other means.

[0046] Specifically, as shown in Figures 2 to 6, the transparent glass slide 2 is installed in the center area of ​​the base plate of the support 1, and the annular sidewall of the support 1 is fitted on the outer side of the bottom end of the objective lens 5. The objective lens 5 can be raised, lowered, and translated within the support 1 according to the observation requirements to adjust the observation position.

[0047] In specific implementation, there is a gap distance greater than zero between the support 1 and the bottom sidewall of the objective lens 5, that is, the inner diameter of the connecting end of the support 1 is greater than the outer diameter of the bottom end of the objective lens 5. The objective lens 5, together with the rest of the microscopic imaging system, is connected to the housing 6 via a displacement stage, or directly connected to the housing 6 after the observation position is adjusted. Alternatively, in other specific embodiments, the support 1 and the housing 6 can be connected in other ways, such as sliding connection, riveting, snap-fit ​​connection, or other detachable connection, to facilitate the removal and replacement of the support 1 from the housing 6, and to facilitate the timely replacement of the immersion medium 3 and the transparent slide 2.

[0048] In addition, embodiments of the present invention also provide a microscopic imaging system, which includes conventional components such as an objective lens 5, and also includes the window described above.

[0049] This microscopic imaging system can be used for in vivo examination. Because the immersion medium is a non-fluid silica gel and its refractive index (1.39–1.4) matches the refractive index of the sample to be observed (e.g., the refractive index of the skin epidermis in biological tissue is 1.39–1.43), it can achieve very good imaging results and a good user experience.

[0050] Specifically, the microscopic imaging system can be various types of microscopes, such as wide-field microscopes, fluorescence microscopes, laser scanning microscopes (including but not limited to multiphoton microscopes, confocal microscopes, etc.), structured light microscopes, light sheet microscopes, super-resolution microscopes, etc.

[0051] In practice, the microscopic imaging system also includes a housing 6, to which the transparent slide 2 is fixedly connected. For example, as shown in Figure 1, the transparent slide 2 is fixedly connected to the housing 6 via a support 1.

[0052] Specifically, referring to Figure 6, the housing 6 can be a frame structure; the transparent glass slide 2 is fixedly mounted on the outside of the housing 6 via a bracket 1; the objective lens 5 is relatively movable within the housing 6 via a displacement stage. Alternatively, in other specific embodiments, the objective lens 5 can also be fixedly mounted within the housing 6. For example, in one possible embodiment, after adjusting the objective lens 5 and the transparent glass slide 2 of the window to a suitable relative position, the relative position may not be changed; instead, the function of changing the focal plane is achieved by changing the optical power of the beam incident on the objective lens 5.

[0053] In specific implementation, the microscopic imaging system provided in this embodiment of the invention can be applied to handheld probes or desktop microscopes. When the microscopic imaging system is applied to a handheld probe, its housing 6 is generally a closed housing; when the microscopic imaging system is applied to a desktop microscope, its housing 6 can be an open housing.

[0054] Finally, it should be noted that in this document, the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0055] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A window for use in a microscopic imaging system, characterized in that, The window comprises a transparent glass sheet (2) and an immersion medium (3), wherein: The transparent glass slide (2) is configured to contact one side of the sample (4) to be observed. The immersion medium (3) is disposed on the side away from the sample to be observed (4), and the immersion medium (3) is configured to fill the gap between the transparent glass slide (2) and the objective lens (5) of the microscopic imaging system; The immersion medium (3) is a type of silicone.

2. The window pane according to claim 1, characterized in that, The immersion medium (3) is bonded to the transparent glass sheet (2).

3. The window pane according to claim 1, characterized in that, The thickness of the immersion medium (3) gradually decreases from the center area to the periphery.

4. The window slat according to claim 3, characterized in that, The outer contour of the immersion medium (3) in a cross section perpendicular to the transparent glass sheet (2) is curved.

5. The window pane according to claim 1, characterized in that, The transparent glass sheet (2) is made of any one of glass, quartz, sapphire, or plexiglass.

6. The window pane according to any one of claims 1 to 5, characterized in that, It also includes a bracket (1) for mounting the transparent glass slide (2).

7. The window pane according to claim 6, characterized in that, The bracket (1) is provided with a light-transmitting hole: The transparent glass slide (2) is located inside the light-transmitting hole and is fixedly connected to the support (1). The outer surface of the transparent glass slide (2) can contact the sample (4) to be observed. The immersion medium (3) is located on the inner side of the transparent glass slide (2).

8. The window pane according to claim 6, characterized in that, The bracket (1) can be fitted onto the outer side of the bottom end of the objective lens (5) and has a gap between it and the bottom sidewall of the objective lens (5), the size of which is greater than zero.

9. The window pane according to claim 1, characterized in that, Furthermore, the refractive index of the immersion medium matches the refractive index of the sample to be observed. The refractive index of the immersion medium (3) in the working band is 1.39 to 1.43, and it has viscoelastic and self-healing properties.

10. The window pane according to claim 1, characterized in that, The immersion medium (3) is made of silicone gel.

11. A microscopic imaging system, characterized in that, Includes a window and an objective lens (5) as described in any one of claims 1 to 9, wherein the objective lens (5) is disposed opposite to the transparent glass slide (2) of the window, and the immersion medium (3) of the window is located between the objective lens (5) and the transparent glass slide (2).

12. The microscopic imaging system according to claim 11, characterized in that, It also includes a housing (6), to which the transparent glass sheet (2) is connected; the housing (6) is either a closed housing or an open housing; The objective lens (5) is relatively movable and disposed within the housing (6).

13. The microscopic imaging system according to claim 12, characterized in that, The objective lens (5) is configured to be axially movable relative to the window, changing the thickness of the immersion medium (3) by squeezing the immersion medium (3).

14. The microscopic imaging system according to claim 12, characterized in that, During the observation process, the gap between the transparent glass slide (2) and the objective lens (5) is filled with the immersion medium of the window throughout the entire process.

15. The microscopic imaging system according to claim 12, characterized in that, The objective lens (5) is fixedly installed inside the housing (6).