Dual-view objective

The dual-view microscope objective addresses the limitation of current objectives by integrating wide-FOV imaging capability using a waveguide with a reflective region, enabling simultaneous high-resolution and wide-FOV imaging, thus improving imaging efficiency and reducing the need for image stitching.

WO2025076458A1PCT designated stage expired Publication Date: 2025-04-10THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
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Patent Information

Application Number
PCT/US2024/050104
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-10-05
Filing Date
2024-10-04
Publication Date
2025-04-10

AI Technical Summary

Technical Problem

Current microscope objectives lack integrated low-resolution, wide field-of-view (FOV) imaging capability, making it difficult to locate regions of interest for imaging, especially in clinical environments where changing objectives can disrupt the imaging environment.

Method used

A dual-view microscope objective configuration that includes a rear lens group, a front lens group, and a waveguide with a reflective region, allowing for co-axis images with two distinct fields of view: a high-resolution mode and a wide-FOV mode, without the need for changing objectives.

Benefits of technology

Enables simultaneous high-resolution and wide-FOV imaging, improving the efficiency of locating regions of interest and reducing the need for image stitching, while maintaining high light efficiency and minimal impact on image contrast.

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Abstract

Objective lens configurations are described that can be used to implement dual-view microscopes with two fields of view (FOVs). An example dual-view microscope objective includes a rear lens group, a front lens group, and a waveguide positioned between the rear and front lens groups. The waveguide includes a reflective region that receives light from the front lens group and partially reflects the light in a lateral direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group. The front and rear lens groups allow viewing or imaging of a sample in a first viewing or imaging mode having a first FOV. The front lens group and the reflective region of the waveguide allow viewing or imaging of the sample in a second viewing or imaging mode having a larger FOV compared to the first FOV.
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Description

DUAL- VIEW OBJECTIVECROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims priority to the provisional application with serial number 63 / 588,074 titled “Dual-View Objective,” filed October 5, 2023. The entire contents of the above noted provisional application are incorporated by reference as part of the disclosure of this document.TECHNICAL FIELD

[0002] The technology described in this patent document relates to improved objective lens configurations.BACKGROUND

[0003] Optical microscopy is a key tool in modern biomedical and cancer imaging. It has several features that make it ideally suited for imaging cells and tissue structure: the resolution is well-matched to the sizes of subcellular structures; a diverse range of available fluorescent probes makes it possible to mark proteins, organelles, and other structures for imaging; the relatively nonperturbing nature of light means that living cells can be imaged for long periods of time to follow their dynamics; and a wide spectral range that enables various imaging modalities to investigate cell structural, molecular, and chemical characteristics, as well as cellular processes. Microscopy is also essential tool in clinical cancer imaging. A number of clinical microscopes have been developed and commercialized for cancer imaging, including reflectance confocal microscopy and multiphoton microscopy for skin cancer imaging. But there is still a need to improve imaging capabilities of microscopes for various applications.SUMMARY

[0004] The disclosed embodiments, among other features and benefits, relate to configurations and associated methods that can be used to implement dual-view microscopes that include two fields of view and can produce co-axis images of a sample.

[0005] An example dual -view microscope objective includes a rear lens group, a front lens group, and a waveguide positioned between the rear lens group and the front lens group. The waveguide includes a reflective region configured to receive light that is collected by the front lensgroup and to partially reflect the received light in a lateral direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group. The front lens group and rear lens group allow viewing or imaging of a sample in a first viewing or imaging mode having a first field of view (FOV), and the front lens group and the reflective region of the waveguide allow viewing or imaging of the sample in a second viewing or imaging mode having a second FOV that is wider than the first FOV.BRIEF DESCRIPTION OF THE DRAWINGS

[0006] FIG. 1 is a schematic diagram of a dual-view microscope objective in accordance with an example embodiment.

[0007] FIG. 2 illustrates an example waveguide plate configuration for combining a see- through mode and a virtual display mode for augmented reality devices.

[0008] FIG. 3 illustrates a configuration of the dual -view objective a in confocal imaging mode in accordance with an example embodiment.

[0009] FIG. 4 illustrates a a dual -view microscope objective that includes a laterally movable waveguide in accordance with an example embodiment.DETAILED DESCRIPTION

[0010] For microscopy both in fundamental research in the laboratory and clinical applications, the objective is the most important component as it determines the resolution and throughput. While there are significant efforts in developing new objectives for various applications, the state-of-the-art microscope objectives still have some major limitations.

[0011] One limitation of the current state-of-the-art microscope objectives is that they are designed without consideration of integrating low-resolution, wide field-of-view (FOV) imaging capability. Since the FOV in typical microscope objectives is small, it is difficult to locate region of interest (ROI) for imaging. In the laboratory environment, this bottleneck can be partially addressed by first using an objective with a relatively large FOV to locate the ROI first, and then changing to the objective with a high NA and small FOV. In clinical environments, typically only one high-resolution objective is installed in the system, and it is not easy to change to other objectives without disturbing the imaging environment. Therefore, it becomes necessary to scan the tissue and stitch the images together to obtain a sufficiently large field for analysis or diagnosis. However, without the surface information to locate the high-resolution scan, it is difficult toaccurately stitch those images together.

[0012] One approach to integrate wide-FOV imaging is to use a beamsplitter in front of the objective (i.e., between the objective and the sample), but the working distance of a microscope is often not sufficient to add a beamsplitter. Additionally, the beamsplitter can introduce aberrations in the convergent beam space, which is not desirable. There are some efforts in solving this limitation by developing a special objective with dual-FOV by, for example, adding a compact wide-FOV imaging modality to the central region of the objective. The major issue of these approaches is that the central portion of the high-resolution channel is blocked for wide-field imaging. For clinical applications, the surface color and texture information are very important for clinician to make accurate diagnosis.

[0013] The disclosed embodiments, among other features and benefits, address the abovenoted limitations of the existing objectives, and describe to a new type of microscope objective which has an integrated wide-FOV imaging capability.

[0014] FIG. 1 is a schematic diagram of a dual-view microscope objective in accordance with an example embodiment. The objective has three groups: a front group close to the object, a waveguide, and a rear group close to the tube lens (not shown). Unlike a traditional microscope objective, the disclosed objective includes a waveguide to obtain co-axis wide-FOV imaging. The function of waveguide is to relay the pupil of wide-FOV imaging system to the axis of the objective. The high-resolution microscope view and wide-FOV view share the front group. It should be noted that while the example configuration of FIG. 1 shows a single lens in the rear group and three lensed in the front group, it is understood that the front or rear groups can be designed to have one or more lenses.

[0015] Waveguide plates have been developed to combine the see-through mode and virtual display mode in augmented reality (AR), as shown in FIG 2. Waveguide is an optical combiner, pupil expander made of a thin piece of clear glass or plastic with specific structures or surface features, which helps guide electromagnetic waves in particular directions, shapes, or patterns. In AR, the waveguide is used to guide the light from the micro-display source (e.g., LCoS, DMD, MicroLED, laser, etc.) to the pupil of the human eye. The core of a waveguide consists of an input coupling section, a propagating section, and a combining section. The input coupling section couples the light from the micro-display (received via a projection lens) to the waveguide, and the light then propagates in the propagating section through total internal reflection (TIR). Thecombining section couples the light out of the waveguide and delivers to the eye pupil; it also transmits the environmental light to the eye pupil. Therefore, the eye can see both environmental information and virtual information at the same time.

[0016] Different from AR application, the waveguide in the disclosed dual-view objective combines the high-resolution microscope imaging mode and the wide-FOV imaging mode. Referring back to FIG. 1, this configuration can be used with a variety of different microscopes, including confocal, reflectance, multiphoton and others. In the high-resolution microscope imaging mode, the illumination or excitation light travels through the rear group of the objective, the waveguide, the front group of the objective, and then focuses onto the object plane. The scattered light or fluorescence light is collected by the front group of the objective, passes the waveguide and the rear group of the objective, and then focuses onto the detector by the tube lens or the scanning system (not shown). In the wide-FOV imaging mode, the front group captures the light with a large FOV and then couples the light into the waveguide. The light then propagates inside the waveguide and exits the waveguide at an output surface. An imaging system then focuses the light onto a detector (e.g., a digital sensor).

[0017] Since the aperture for wide-FOV imaging mode is small, only very small portion (e.g., less than 5%) of the light from small microscope FOV is directed to the wide-FOV imaging channel through the waveguide. Therefore, the impact on light efficiency of the high-resolution imaging is very limited.

[0018] FIG. 3 shows an implementation of the dual -view objective a in confocal imaging mode. The illumination light passes through the rear group of the objective, the waveguide, and the front group of the objective, which focuses the light at different depths inside the tissue. In the widefield imaging mode, the front group of the objective captures light from a large field and couples it into the waveguide. The light then propagates inside the waveguide and exits at the output coupling region of the waveguide. An imaging system then focuses the light onto a digital sensor to capture the widefield image. Due to the relatively small aperture (e.g., ~lmm) of the wide-field imaging mode, only a small portion of the light (e.g., less than 5%) from the high- resolution microscope FOV is directed to the widefield imaging channel through the waveguide.

[0019] In FIG. 3, the region identified as the combining region of the waveguide (sometimes referred to as the coupler) operates to receive the light collected from the sample via the front group, and to partially reflect it laterally (e.g., to the right as shown in the example configurationof FIG. 3), while allowing the remaining portion of the collected light to pass through in the direction of the rear lens group. This region is generally referred to as the reflective region of the waveguide, but it is understood that the associated functionality can be implemented using a wide range of technologies, including geometrical (refractive / reflective) and diffractive / holographic techniques. One example is a prism that relies on partially reflective coatings to efficiently couple the light to the waveguide. Cascaded embedded mirrors with partially reflective coatings provide another example. The mirrors can be positioned at a particular angle, and each mirror can be used to partially reflect one portion of the spectrum. A curved mirror and an embedded microprism array are other examples. Surface-relief gratings (SRGs) are other examples with the ability to diffract rays in any desired angle, and their wavelength and angular selectivity allow the creation of optical elements that are more compact and lighter than traditional designs. Several types of surface-relief gratings include blazed, slanted, binary, multilevel, and analog. Transparent volume holograms working in reflection mode are examples that can be used as combining couplers in waveguides. Full-color hologram based on three phase-multiplexed single-color holograms provide other examples.

[0020] In some embodiments, to minimize the stray light caused by the coupling structures of the waveguide, such as surface relief grating (SRG), volume holographic grating, or other periodical geometric structures, various design techniques can be used to reduce or minimize the impact on image contrast to be very small. For example, in some embodiments, the coupling structure can be moved out of the imaging path of the high-resolution objective when a wide-FOV view is no longer needed, thus making the impact on the light efficiency and image contrast neglectable. For instance, FIG. 4 illustrates an example configuration, where the waveguide is laterally movable to position the coupling structure out of the high-resolution imaging path. As shown in FIG. 4, the coupling structure (combining region) is moved laterally to the right. The waveguide / coupling structure can be moved, for example, via a translation stage that operates manually or by an electric motor. With anti-reflection (AR) coating positioned on the surfaces of the waveguide, the impact on the light efficiency can be less than 1%.

[0021] In some embodiments, aspherical surfaces are utilized to further increase the FOV. To achieve a large FOV with a small form factor, aspherical surfaces with large deviation from the spherical surface are needed. It is beneficial to produce such aspherical surfaces with large deviations from the spherical shape using glass material, which is needed for high-performanceobjective.

[0022] One aspect of the disclosed embodiments relates to a dual-view microscope objective that includes a rear lens group, a front lens group, and a waveguide positioned between the rear lens group and the front lens group. The waveguide includes a reflective region configured to receive light that is collected by the front lens group and to partially reflect the received light in a lateral direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group. The front lens group and rear lens group of the dual-view microscope objective allow viewing or imaging of a sample in a first viewing or imaging mode having a first field of view (FOV), and the front lens group and the reflective region of the waveguide allow viewing or imaging of the sample in a second viewing or imaging mode having a second FOV that is wider than the first FOV.

[0023] In one example embodiment, the waveguide includes an output coupling region that allows light that has traveled in the lateral direction through the waveguide to exit the waveguide. In another example embodiment, the dual-view microscope objective is part of an imaging system that further includes an imaging lens and a detector, and the imaging lens is positioned to receive the light that exits the waveguide and direct the light received thereon to the detector. In yet another example embodiment, the reflective region of the waveguide is configured to reflect less than 50 percent of the light received thereon. In still another example embodiment, the reflective region of the waveguide is configured to reflect less than 10 percent of the light received thereon.

[0024] According to another example embodiment, the reflective region of the waveguide is less than 2 mm in diameter. In another example embodiment, the first viewing or imaging mode allows viewing or imaging of the sample with a higher resolution compared to the second viewing or imaging mode. In still another example embodiment, the reflective region of the waveguide includes a geometric coupler. In yet another example embodiment, the reflective region of the waveguide includes a diffractive or a holographic coupler. In one example embodiment, the waveguide includes an antireflection coating to reduce or eliminate reflection of light that is incident onto the waveguide from outside of the waveguide.

[0025] In another example embodiment, the reflective region of the waveguide in configured to partially reflect the received light in the lateral direction that is substantially perpendicular to a direction of the light transmitted through the waveguide toward the rear lens group. In one example embodiment, the reflective region of the waveguide comprises one or more of: a prism ordichroic mirror. In still another example embodiment, images obtained in the first and the second imaging modes are co-axis. In yet another example embodiment, the images are obtained simultaneously without moving the components of the dual -view microscope objective.

[0026] In one example embodiment, the waveguide is movable, and when the dual-view microscope is operating in the first viewing or imaging mode, the reflective region is positioned out of an optical path of the first viewing or imaging mode. In another example embodiment, the dual-view microscope objective is part of an imaging system that further includes a detector positioned to receive the light after transmission through the waveguide and the rear lens group. In still another example embodiment, the dual-view microscope objective is part of an imaging system that includes a light source, the dual-view microscope objective is positioned to receive illumination light from the light source at the rear lens group configured to allow the received illumination light to pass through the rear lens group, through the waveguide and through the front lens group in a direction of a sample. In yet another example embodiment, the dual-view microscope objective is part of one of the following microscopes: a confocal microscope, a reflectance microscope, or a multiphoton microscope.

[0027] Another aspect of the disclosed embodiments relates to a dual-view microscope that includes an objective comprising a rear lens group, a front lens group, and a waveguide positioned between the rear lens group and the front lens group. The dual-view microscope also includes a light source operable to produce illumination light for illuminating a sample, and one or more detectors positioned to receive light collected by the front lens group from the sample and to produce two co-axial images of the sample. The waveguide includes a reflective region configured to receive the light that is collected by the front lens group and to partially reflect the received light in a direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group. The front lens group and rear lens group allow production of a first of the two co-axial images with a first field of view (FOV), and the front lens group and the reflective region of the waveguide allow production of a second of the two co-axial images with a second FOV that is wider than the first FOV.

[0028] In one example embodiment of the dual-view microscope, the waveguide includes an output coupling region that allows the light traveling in the waveguide to exit the waveguide, the dual-view microscope further includes an imaging lens positioned to receive the light that exits the waveguide and direct the exited light to one of the one or more detectors. Further, another one ofthe one or more detectors is positioned to receive the light collected by the front lens group after transmission through the waveguide and the rear lens group.

[0029] Another aspect of the disclosed embodiments relates to a dual-view microscope that includes an objective comprising a rear lens group, a front lens group, and a waveguide positioned between the rear lens group and the front lens group. The dual-view microscope further includes a light source operable to produce illumination light for illuminating a sample, and one or more detectors positioned to receive light collected by the front lens group from the sample and to produce two co-axial images of the sample. The waveguide includes a diffractive region configured to receive the light that is collected by the front lens group and to partially direct the received light in a direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group. The front lens group and rear lens group allow production of a first of the two co-axial images with a first field of view (FOV), and the front lens group and the reflective region of the waveguide allow production of a second of the two co-axial images with a second FOV that is wider than the first FOV.

[0030] In some embodiments, the disclosed systems include a processor / controller that is configured to include, or be coupled to, a memory that stores processor executable code that causes the processor / controller carry out various computations and processing of information. The processor / controller can further generate and transmit / receive suitable information to / from the various system components, as well as suitable input / output (IO) capabilities (e.g., wired or wireless) to transmit and receive commands and / or data. The processor / controller may, for example, provide signals to control the operation of various components such as light sources and detectors that are disclosed herein, or to provide signals to a translation stage for moving the described components. Only a few implementations and examples are described and other implementations, enhancements and variations can be made based on what is described and illustrated in this patent document.

Claims

CLAIMSWhat is claimed is:

1. A dual-view microscope objective, comprising: a rear lens group; a front lens group; and a waveguide positioned between the rear lens group and the front lens group, wherein: the waveguide includes a reflective region configured to receive light that is collected by the front lens group and to partially reflect the received light in a lateral direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group, the front lens group and rear lens group allow viewing or imaging of a sample in a first viewing or imaging mode having a first field of view (FOV), and the front lens group and the reflective region of the waveguide allow viewing or imaging of the sample in a second viewing or imaging mode having a second FOV that is wider than the first FOV.

2. The dual-view microscope objective of claim 1 , wherein the waveguide includes an output coupling region that allows light that has traveled in the lateral direction inside the waveguide through total internal reflection (TIR) to exit the waveguide.

3. The dual-view microscope objective of claim 2, wherein: the dual-view microscope objective is part of an imaging system that further includes an imaging lens and a detector, and the imaging lens is positioned to receive the light that exits the waveguide and direct the light received thereon to the detector.

4. The dual-view microscope objective of claim 1, wherein: the reflective region of the waveguide is configured to reflect less than 50 percent of the light received thereon.

5. The dual-view microscope objective of claim 4, wherein the reflective region of the waveguide is configured to reflect less than 10 percent of the light received thereon.

6. The dual-view microscope objective of claim 1, wherein the reflective region of the waveguide is less than 5 mm in diameter.

7. The dual-view microscope objective of claim 1 , wherein the first viewing or imaging mode allows viewing or imaging of the sample with a higher resolution compared to the second viewing or imaging mode.

8. The dual- view microscope objective of claim 1, wherein the reflective region of the waveguide includes a geometric coupler.

9. The dual-view microscope objective of claim 1, wherein the reflective region of the waveguide includes a diffractive or a holographic coupler.

10. The dual-view microscope objective of claim 1, wherein the waveguide includes an antireflection coating to reduce or eliminate reflection of light that is incident onto the waveguide from outside of the waveguide.

11. The dual-view microscope objective of claim 1, wherein the reflective region of the waveguide in configured to partially reflect the received light in the lateral direction that is substantially perpendicular to a direction of the light transmitted through the waveguide toward the rear lens group.

12. The dual-view microscope objective of claim 1, wherein the reflective region of the waveguide comprises one or more of: a prism or dichroic mirror.

13. The dual-view microscope objective of claim 1, wherein images obtained in the first and the second imaging modes are co-axis.

14. The dual-view microscope objective of claim 13, wherein the images are obtained simultaneously without moving the components of the dual-view microscope objective.

15. The dual-view microscope objective of claim 13, wherein the waveguide is movable, and when the dual-view microscope is operating in the first viewing or imaging mode, the reflective region is positioned out of an optical path of the first viewing or imaging mode.

16. The dual-view microscope objective of claim 1, wherein: the dual-view microscope objective is part of an imaging system that further includes a detector positioned to receive the light after transmission through the waveguide and the rear lens group.

17. The dual-view microscope objective of claim 1, wherein: the dual-view microscope objective is part of an imaging system that includes a light source, the dual-view microscope objective is positioned to receive illumination light from the light source at the rear lens group configured to allow the received illumination light to pass through the rear lens group, through the waveguide and through the front lens group in a direction of a sample.

18. The dual-view microscope objective of claim 1, wherein the dual-view microscope objective is part of one of the following microscopes: a confocal microscope, a reflectance microscope, or a multiphoton microscope.

19. A dual-view microscope, comprising: an objective comprising a rear lens group, a front lens group, and a waveguide positioned between the rear lens group and the front lens group; a light source operable to produce illumination light for illuminating a sample; and one or more detectors positioned to receive light collected by the front lens group from the sample and to produce two co-axial images of the sample, wherein: the waveguide includes a reflective region configured to receive the light that is collectedby the front lens group and to partially reflect the received light in a direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group, the front lens group and rear lens group allow production of a first of the two co-axial images with a first field of view (FOV), and the front lens group and the reflective region of the waveguide allow production of a second of the two co-axial images with a second FOV that is wider than the first FOV.

20. The dual-view microscope of claim 19, wherein the waveguide includes an output coupling region that allows the light traveling in the waveguide to exit the waveguide, the dual-view microscope further includes an imaging lens positioned to receive the light that exits the waveguide and direct the exited light to one of the one or more detectors, another one of the one or more detectors is positioned to receive the light collected by the front lens group after transmission through the waveguide and the rear lens group.

21. A dual-view microscope, comprising: an objective comprising a rear lens group, a front lens group, and a waveguide positioned between the rear lens group and the front lens group; a light source operable to produce illumination light for illuminating a sample; and one or more detectors positioned to receive light collected by the front lens group from the sample and to produce two co-axial images of the sample, wherein: the waveguide includes a diffractive region configured to receive the light that is collected by the front lens group and to partially direct the received light in a direction away from the rear lens group while allowing a portion of the received light to be transmitted through the waveguide toward the rear lens group, the front lens group and rear lens group allow production of a first of the two co-axial images with a first field of view (FOV), and the front lens group and the reflective region of the waveguide allow production of a second of the two co-axial images with a second FOV that is wider than the first FOV.

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