A large field of view imaging microscope for free-moving animals

Abstract

The application discloses a large field of view imaging microscopic device for free-moving animals, which comprises an objective lens assembly, a barrel lens assembly and an image sensor arranged coaxially in sequence, and a coaxial cable electrically connected with the image sensor. The objective lens assembly adopts a spherical lens for adjusting the chief ray angle and improving the illumination distribution of an image surface. The barrel lens assembly adopts an aspherical lens for comprehensively correcting the field curvature, astigmatism, coma and distortion and other aberrations in the large field of view imaging through the aspherical surface type. The coaxial cable is used for realizing stable transmission of power supply and image data and suppressing electromagnetic interference. The device is compact in structure and easy to assemble and adjust, and is suitable for behavior and neuroscientific imaging experiments of free-moving animals such as rodents, and can obtain clear large field of view imaging under free-moving conditions.

Description

Technical Field

[0001] This invention belongs to the field of in vivo microscopy and opto-mechatronics technology, and particularly relates to a large field-of-view imaging microscopy device for freely moving animals. Background Technology

[0002] In neuroscience research, understanding the activity of neurons in the cerebral cortex is crucial for revealing neural network function and cognitive processes in the brain. To enable real-time observation of brain activity without restricting the natural behavior of animals, many research teams have developed miniaturized head-mounted microscopes, making it possible to observe the dynamic changes of neurons in a free-moving state. For example, one team developed a small head-mounted microscope weighing only 1.9 grams. This breakthrough made imaging the brains of freely moving mice a reality. However, these early head-mounted microscopes typically suffered from a small field of view, preventing comprehensive observation of the activity across the entire cerebral cortex.

[0003] Achieving high-resolution, real-time imaging of the entire cerebral cortex to explore the differences and synergistic relationships between individual brain regions remains a major challenge in neuroscience. Limited by optical design and the weight of mechanical structures, these microscopes struggle to balance imaging field of view, resolution, and the animal's freedom of movement. Therefore, overcoming these technical bottlenecks to achieve comprehensive observation of neuronal activity across the entire cerebral cortex under free-movement conditions remains a pressing problem in neuroscience research. Summary of the Invention

[0004] The purpose of this invention is to provide a large field-of-view imaging microscopy device for freely moving animals. It proposes an optical structure of "spherical lens + aspherical tube lens" and uses coaxial cable transmission, which is conducive to realizing comprehensive observation of the activity of neurons in the whole cerebral cortex in a free-moving state and facilitates obtaining clear imaging of a large field of view under free-moving conditions.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a large field-of-view imaging microscope for freely moving animals, comprising: a housing, an objective lens assembly, a tube lens assembly, an image sensor, and a coaxial cable; wherein the objective lens assembly, the tube lens assembly, and the image sensor are sequentially arranged in the housing along the same optical axis;

[0006] The objective lens assembly includes a spherical lens for adjusting the principal ray angle and / or the image plane position; The telescope assembly includes an aspherical lens for correcting higher-order aberrations caused by large field-of-view imaging; One end of the coaxial cable is electrically connected to the image sensor, and the other end is used to connect to an external power supply unit for coaxial transmission of image data and electrical energy.

[0007] In a preferred embodiment, the objective lens assembly is an objective lens group composed of two or more lenses, wherein the lenses of the objective lens assembly are spherical lenses, cemented lenses, or combinations thereof, and are configured to provide a preset numerical aperture and working distance within a limited volume.

[0008] In a preferred embodiment, the telescope assembly employs an aspherical lens or a telescope group formed by a combination of an aspherical lens and a spherical lens, wherein the aspherical surface shape is used to reduce field curvature and astigmatism at the edge of the field of view and suppress distortion to improve the geometric accuracy of a large field of view.

[0009] In a preferred embodiment, the tube lens assembly includes six aspherical lenses, arranged in the order of the optical path from the first aspherical lens to the sixth aspherical lens. The aperture, thickness, and material of each lens are optimized and matched to correct large field-of-view imaging aberrations.

[0010] In a preferred embodiment, the telescope assembly includes: The first aspherical mirror has a light-transmitting aperture of 2.64mm, a thickness of 1.07mm, and is made of EP-6000 material; The second aspherical mirror has a light-transmitting aperture of 2.82mm, a thickness of 0.50mm, and is made of EP-6000 material; The third aspherical mirror has a light-transmitting aperture of 2.84mm, a thickness of 0.50mm, and is made of EP-8000 material; The fourth aspherical mirror has a light-transmitting aperture of 3.20mm, a thickness of 1.20mm, and is made of APL5014CL material; The fifth aspherical mirror has a light-transmitting aperture of 3.62mm, a thickness of 0.64mm, and is made of EP-8000 material; The sixth aspherical mirror has a light-transmitting aperture of 4.60mm, a thickness of 0.50mm, and is made of EP-6000 material.

[0011] In a preferred embodiment, the coaxial cable includes an inner conductor, a dielectric layer, a shielding layer, and an outer sheath. The shielding layer is grounded to suppress the influence of external electromagnetic noise on image data transmission, and the cable's flexibility meets the traction requirements when animals move freely.

[0012] In a preferred embodiment, the housing is provided with a positioning structure, and the objective lens assembly and the tube lens assembly are installed in the positioning structure by means of step positioning and pressure ring limiting, and the image plane position is finely adjusted by shims.

[0013] In a preferred embodiment, the aspherical lens in the telescope assembly is made of ground glass or injection molded optical plastic.

[0014] In a preferred embodiment, the housing is provided with a base interface for fixing the animal's head, and the external power acquisition unit receives image data transmitted via a coaxial cable and supplies power to the image sensor.

[0015] Compared with existing technologies, this invention proposes a large field-of-view imaging microscope for freely moving animals, which has at least the following beneficial technical effects: 1) Through the optical structure of "spherical objective lens + aspherical tube lens", large field aberrations can be corrected and edge image quality can be improved with fewer lenses in a limited volume, which helps to ensure the sharpness and geometric accuracy of the full field of view image; 2) Spherical field lenses are easy to process and adjust, which can improve illumination uniformity and reduce vignetting; 3) Coaxial cables have good shielding and flexibility, which can reduce noise and traction effects and improve imaging stability; 4) Coaxial transmission reduces the number of cabling and interfaces, lowers crosstalk, and improves reliability; 5) The overall structure is compact and lightweight, making it easy to fix the headband and quickly change it.

[0016] Other features and advantages of the invention will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the invention. The objects and other advantages of the invention may be realized and obtained by means of the structures particularly pointed out in the written description and the accompanying drawings.

[0017] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0018] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof.

[0019] Figure 1 This is a schematic cross-sectional view of the mechanical structure of the large field-of-view imaging microscopy device provided by the present invention.

[0020] Figure 2 This is a schematic diagram of the optical path of the optical system of the large field-of-view imaging microscopy device provided by the present invention.

[0021] Figure 3 This is a schematic diagram showing the connection between the coaxial cable provided by the present invention and the external power supply unit. Detailed Implementation

[0022] Exemplary embodiments of the present disclosure will now be described in more detail with reference to the accompanying drawings. While exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

[0023] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0024] See Figures 1 to 3 As shown, this invention proposes a large field-of-view imaging microscope device for freely moving animals. The device includes a front objective lens assembly, a tube lens assembly, an image sensor, and a coaxial cable. The objective lens assembly and the tube lens assembly adopt a linear coaxial imaging configuration (the objective lens assembly, tube lens assembly, and image sensor are arranged coaxially in sequence). In a preferred embodiment: The objective lens assembly is used to acquire light signals from animal tissue. It employs a cemented doublet lens with a light-transmitting aperture of 3.6 mm. The lens is cemented together with a 2.0 mm thick N-BAF10 positive lens and a 1.0 mm thick N-SF10 plano-concave lens, making the outgoing beam approximately parallel. The beam is then focused by the tube lens onto the image sensor to obtain a preset magnification and field of view within a compact volume.

[0025] In a preferred embodiment, see Figure 2 As shown, the telescope assembly uses six aspherical lenses as the telescope lens, and the aspherical surface shape compensates for higher-order aberrations caused by the large field of view, wherein: The first aspherical mirror (L1) has a light-transmitting aperture of 2.64 mm and a thickness of 1.07 mm, and is made of EP-6000 material; the second aspherical mirror (L2) has a light-transmitting aperture of 2.82 mm and a thickness of 0.50 mm, and is also made of EP-6000 material; the third aspherical mirror (L3) has a light-transmitting aperture of 2.84 mm and a thickness of 0.50 mm, and is made of EP-8000 material; the fourth aspherical mirror (L4) has a light-transmitting aperture of 3.20 mm and a thickness of 1.20 mm, and is made of APL5014CL material; the fifth aspherical mirror (L5) has a light-transmitting aperture of 3.62 mm and a thickness of 0.64 mm, and is made of EP-8000 material; and the sixth aspherical mirror (L6) has a light-transmitting aperture of 4.60 mm and a thickness of 0.50 mm, and is also made of EP-6000 material.

[0026] Coaxial cables combine the high-speed signal output from the image sensor (CMOS) with the power supply signal into the same channel and use a shielding structure to reduce electromagnetic interference and improve data reliability under motion conditions.

[0027] Furthermore, both the objective lens and the tube lens are mounted along the optical axis in the positioning structure inside the housing, and rapid assembly is achieved through step positioning and pressure ring limiting; the aspherical tube lens can be made by glass grinding or injection molding of optical plastic.

[0028] In one embodiment, the device housing is fixed to the animal's head via a replaceable base. Inside the housing, an objective lens group, an aspherical tube lens, and a CMOS image sensor are sequentially mounted along the optical axis, secured with a clamping ring, and the image plane position is finely adjusted with shims. During imaging, the spherical field lens improves edge illumination, the aspherical tube lens compensates for edge aberrations in the field of view, and the image sensor output data is transmitted to an external data acquisition and power supply unit via a coaxial cable, achieving stable imaging of a large field of view for freely moving animals. The coaxial cable can be fixed to the housing using a miniature coaxial connector, and the external data acquisition and power supply unit can be a portable recording module or a host computer data acquisition card to adapt to different experimental scenarios.

[0029] Workflow: See Figure 3 As shown, the device is fixed to the animal's head, with the objective lens aimed at the brain region. Fluorescence signals are acquired through the objective lens, and after aberration correction using an aspherical tube lens, the images are finally projected onto a CMOS sensor. The data is transmitted in real time to an external computer via a coaxial cable for recording and analysis.

[0030] As described in the above embodiments, the present invention provides a large field-of-view imaging microscopy device for freely moving animals, comprising an objective lens assembly, a tube lens assembly, an image sensor, and a coaxial cable electrically connected to the image sensor, arranged coaxially in sequence. The objective lens assembly uses a spherical lens as the field lens to control the principal ray angle and improve the illumination distribution on the image plane; the tube lens assembly uses an aspherical lens as the tube lens to comprehensively correct aberrations such as field curvature, astigmatism, coma, and distortion in large field-of-view imaging through its aspherical surface shape; the coaxial cable is used to achieve stable power supply and image data transmission and suppress electromagnetic interference; the device is compact, easy to assemble and adjust, and suitable for behavioral and neuroscience imaging experiments on freely moving animals such as rodents. Compared with the prior art, the present invention has the following significant advantages: Wide field of view and high image quality: By combining "spherical lens + aspherical tube lens", a wide field of view (such as several millimeters) imaging is achieved within a limited volume, and edge aberrations can be effectively eliminated, ensuring the clarity and geometric accuracy of the full field of view image.

[0031] Strong anti-interference capability: The use of coaxial shielded cable for transmission significantly reduces electromagnetic noise during movement and improves the signal-to-noise ratio and stability of data acquisition.

[0032] Lightweight and comfortable: The compact structure eliminates redundant wiring harnesses, significantly reducing the weight and rotational inertia of the headgear and minimizing interference with the animal's natural behavior.

[0033] Easy to manufacture and assemble: The objective lens assembly uses easily processed spherical lenses, and the tube lens can be made of injection-molded optical plastics, reducing manufacturing costs; the modular mechanical design facilitates rapid assembly and maintenance in the laboratory.

[0034] It should be noted that the word "comprising" does not exclude the presence of components or steps not listed in the claims. The words "a" or "an" preceding a component do not exclude the presence of a plurality of such components. This invention can be implemented by means of hardware comprising several different components and by means of a suitably programmed computer.

[0035] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0036] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A large field-of-view imaging microscope for freely moving animals, characterized in that, The device includes: a housing, an objective lens assembly, a tube lens assembly, an image sensor, and a coaxial cable; wherein; The objective lens assembly, the tube lens assembly, and the image sensor are sequentially arranged in the housing along the same optical axis; The objective lens assembly includes a spherical lens for adjusting the principal ray angle and / or the image plane position; The telescope assembly includes an aspherical lens for correcting aberrations caused by large field-of-view imaging; One end of the coaxial cable is electrically connected to the image sensor, and the other end is used to connect to an external power supply unit for coaxial transmission of image data and electrical energy.

2. The large field-of-view imaging microscope device for freely moving animals according to claim 1, characterized in that, The objective lens assembly is an objective lens group composed of two or more lenses. The lenses of the objective lens assembly are spherical lenses, cemented lenses, or combinations thereof, and are configured to provide a preset numerical aperture and working distance within a limited volume.

3. The large field-of-view imaging microscope device for freely moving animals according to claim 1, characterized in that, The telescope assembly is composed of multiple aspherical lenses, or a combination of aspherical and spherical lenses to form a telescope group.

4. The large field-of-view imaging microscope device for freely moving animals according to claim 3, characterized in that, The telescope assembly includes six aspherical lenses, arranged sequentially from the first to the sixth aspherical lens according to the optical path. The aperture, thickness, and material of each lens are optimized and matched to correct large field-of-view imaging aberrations.

5. A large field-of-view imaging microscope for freely moving animals according to claim 4, characterized in that, In the tube lens assembly: The first aspherical mirror has a light-transmitting aperture of 2.64mm, a thickness of 1.07mm, and is made of EP-6000 material; The second aspherical mirror has a light-transmitting aperture of 2.82mm, a thickness of 0.50mm, and is made of EP-6000 material; The third aspherical mirror has a light-transmitting aperture of 2.84mm, a thickness of 0.50mm, and is made of EP-8000 material; The fourth aspherical mirror has a light-transmitting aperture of 3.20mm, a thickness of 1.20mm, and is made of APL5014CL material; The fifth aspherical mirror has a light-transmitting aperture of 3.62mm, a thickness of 0.64mm, and is made of EP-8000 material; The sixth aspherical mirror has a light-transmitting aperture of 4.60mm, a thickness of 0.50mm, and is made of EP-6000 material.

6. The large field-of-view imaging microscope device for freely moving animals according to claim 1, characterized in that, The coaxial cable comprises, from the inside out, an inner conductor, a dielectric layer, a shielding layer, and an outer sheath; the shielding layer is grounded to suppress the influence of external electromagnetic noise on image data transmission, and the cable's flexibility is configured to accommodate the traction movement of animals during free movement.

7. A large field-of-view imaging microscope for freely moving animals according to claim 1, characterized in that, The housing is equipped with a positioning structure. The objective lens assembly and the tube lens assembly are installed in the positioning structure by means of step positioning and pressure ring limiting, and the image plane position is finely adjusted by shims.

8. A large field-of-view imaging microscope for freely moving animals according to claim 1, characterized in that, The aspherical lens in the telescope assembly is made of ground glass or injection molded optical plastic.

9. A large field-of-view imaging microscope for freely moving animals according to claim 1, characterized in that, The housing is provided with a base interface for fixing to the animal's head, and the coaxial cable is fixed to the housing and led out through a miniature coaxial connector.

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