Miniaturized differential interference phase contrast microscopic imaging system based on gradient refractive index lens

Abstract

The invention discloses a miniaturized differential interferometric phase contrast (DIC) microscopic imaging system and method based on a gradient index lens (GRIN), light emitted by a white light LED light source is changed into parallel light after passing through a hemispherical lens, the parallel light is incident to a Wollaston prism through a polarizer and a beam splitter for difference, and then the parallel light is converged to a sample through the GRIN lens. And the reflected signal light is differentiated again through the wollaston prism, and then the differential signal is focused on the CMOS through the polarization analyzer and the tube lens, so that the imaging process is completed. The differential interference phase contrast microscopic imaging system is very sensitive to gradient due to the differential characteristic, so that compared with a common bright field microscope, the differential interference phase contrast microscopic imaging system can further highlight edge information, which is very important for industrial detection and biological sample observation. The miniaturized DIC microscopic imaging system is designed by combining a series of miniaturized optical elements and CMOS through the characteristics of small size and high imaging quality of the GRIN lens, so that the quality and the cost of the system are greatly reduced, the application range of the system is expanded, and edge microscopic detection can be applied to more fields.

Description

Technical Field

[0001] The present invention relates to a miniaturized differential interference contrast microscopy imaging system and method, and in particular to a miniaturized edge information enhancement system and method based on a gradient refractive index lens. Currently, miniaturized microscopy imaging technology has the advantages of small size and large imaging field of view. By combining the core component gradient refractive index lens with the miniaturized differential interference contrast element and changing the image transmission mode, edge enhancement detection can be achieved under various application conditions. Background Art

[0002] The original intention of the miniaturized microscope (Miniscope) was to better image and observe the brain of freely moving mice. Since the invention of the optical microscope, the pursuit of multifunctional in vivo microscopes has been continuous. Living cell observations such as culture dishes are already very mature, but in vivo imaging of mammals still faces great challenges. Among mammalian species, mice are an excellent and tenacious genetic model for targeted manipulation of cell characteristics, but when using an optical microscope to observe their brains, their limbs and heads still need to be fixed, and the objective lens is fixed above the head for observation. This restriction on their normal behavior and activities will greatly affect the universality of obtaining information. The improvement of manufacturing technology is the most critical progress in miniaturization integration. Gradient refractive index lenses (GRIN lenses) replace traditional objective lenses, small-sized optical components replace conventional-sized optical components, and all optical components are integrated in a 3D-printed housing. A miniaturized microscope that can be worn on the head came into being. However, it is only used in fluorescence microscopy imaging systems, and other imaging methods have not been developed. Miniscope is not only small in size, but also has micron-level resolution and millimeter-level field of view. Through adaptive improvements, it can be applied to biological or industrial detection under special conditions. Summary of the invention

[0003] A brief overview of the present invention is provided below in order to provide a basic understanding of certain aspects of the present invention. It should be understood that this overview is not an exhaustive overview of the present invention. It is not intended to identify key or important parts of the present invention, nor is it intended to limit the scope of the present invention. Its purpose is merely to present certain concepts in a simplified form as a prelude to a more detailed description discussed later.

[0004] In view of this, in order to overcome the above-mentioned technical problems, the present invention provides a miniaturized differential interference contrast microscopy system and method based on a gradient refractive index lens. By using a gradient refractive index lens instead of a single objective lens, optical elements can be highly integrated while ensuring resolution and field of view, thereby reducing the volume of the edge-enhanced microscopy system.

[0005] In order to achieve the above object, the present invention adopts the following technical solution:

[0006] Solution 1: The present invention provides a miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens, characterized in that it includes an illumination module, a differential module, and a miniaturized imaging acquisition module;

[0007] The illumination module comprises, in order of light propagation direction: a white light source, a hemispherical lens, a polarizer, a beam splitter, a Wollaston prism, a GRIN lens, a Wollaston prism, a beam splitter, an analyzer, a tube lens and a CMOS;

[0008] The miniaturized differential module is composed of a polarizer, a beam splitter, a Wollaston prism, a GRIN lens, a Wollaston prism, a beam splitter, and an analyzer according to the light propagation direction;

[0009] The miniaturized acquisition modules are, in order of light propagation direction: tube lens and CMOS;

[0010] Furthermore: the white light source is closely attached to the hemispherical lens, ensuring that the volume is compressed to the maximum extent while the light source is transformed from a spherical wave into parallel light.

[0011] Furthermore: the size of the polarizer is 4mm×4mm×2mm, the size of the analyzer is 4mm×4mm×2mm, the size of the beam splitter is 4mm×4mm×2mm, and the size of the Wollaston prism is 4mm×4mm×3mm.

[0012] Furthermore: the gradient refractive index lens has NA (numerical aperture) = 0.5, f = 0.2 mm, a diameter of 2 mm, and a length of 10 mm.

[0013] Furthermore: the miniaturized differential interference contrast microscopy system based on gradient refractive index lens is characterized in that the GRIN lens, polarizer, hemispherical lens, white light source, CMOS, tube lens, analyzer, beam splitter and Wollaston prism are all integrated in the shell of the miniaturized microscopy system made of 3D printed optical resin.

[0014] Furthermore: the tube has a focal length of f=6 mm and a diameter of D=5 mm, and is used to converge the differentiated light emitted by the sample onto the CMOS photosensitive surface.

[0015] Furthermore: the miniaturized differential interference contrast microscopy imaging system based on the gradient refractive index lens is characterized in that the CMOS pixel size is 6 μm and the field of view can reach 700×700 μm.

[0016] Furthermore: the device has a total length of 25 mm, a width of 15 mm×15 mm, and a mass of only 4 g, and can be easily fixed on a multi-axis robotic arm to achieve lateral movement, axial movement, and coaxial rotation.

[0017] Beneficial Effects

[0018] The miniaturized differential interference contrast microscopy imaging system and method based on the gradient refractive index lens of the present invention has the advantages of small size, large imaging field of view, high resolution and enhanced edge information. Different from the large mass and volume characteristics of the traditional desktop differential interference contrast microscope, the present invention is very suitable as an integrated scientific research payload with its excellent volume-mass characteristics, and is used in various biological detection or industrial detection fields. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The schematic diagram is a structural diagram of a miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to the present invention.

[0020] In the figure: 1 gradient refractive index lens, 2 polarizer, 3 hemispherical lens, 4 white light source, 5 housing, 6 CMOS, 7 tube lens, 8 analyzer, 9 beam splitter, 10 wollaston prism. DETAILED DESCRIPTION

[0021] Exemplary embodiments of the present invention will be described below in conjunction with the accompanying drawings. For the sake of clarity and conciseness, not all features of the actual implementation are described in the specification. However, it should be understood that many implementation-specific decisions must be made in the process of developing any such actual implementation in order to achieve the developer's specific goals, such as meeting those constraints related to the system and business, and these constraints may vary from implementation to implementation. In addition, it should be understood that although the development work may be very complex and time-consuming, it is only a routine task for those skilled in the art who benefit from the disclosure of the present invention.

[0022] It is also necessary to explain here that, in order to avoid obscuring the present invention due to unnecessary details, only the system structure and / or processing steps closely related to the solution according to the present invention are shown in the accompanying drawings, while other details that are not very relevant to the present invention are omitted.

[0023] Embodiment 1: As attached Figure 1 The embodiment shown provides a miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens, which is used to achieve edge enhancement detection.

[0024] A miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens is characterized by comprising an illumination module, a differential module, and a miniaturized imaging acquisition module;

[0025] The illumination module is composed of a white light source 4, a hemispherical lens 3, a polarizer 2, a beam splitter 9, a wollaston prism 10, a GRIN lens 1, a wollaston prism 10, a beam splitter 9, an analyzer 8, a tube lens 7 and a CMOS 6 in order according to the light propagation direction;

[0026] The miniaturized differential module is sequentially: polarizer 2, beam splitter 9, wollaston prism 10, GRIN lens 1, wollaston prism 10, beam splitter 9, analyzer 8 according to the light propagation direction;

[0027] The miniaturized acquisition modules are, in order according to the light propagation direction: tube lens 7 and CMOS 6;

[0028] More specifically: the white light source 4 is closely attached to the hemispherical lens 3, ensuring that the volume is compressed to the maximum extent while the light source is transformed from a spherical wave into parallel light.

[0029] More specifically: the size of the polarizer 2 is 4mm×4mm×2mm, the size of the analyzer 8 is 4mm×4mm×2mm, the size of the beam splitter 9 is 4mm×4mm×2mm, and the size of the Wollaston prism 9 is 4mm×4mm×3mm.

[0030] More specifically: the gradient refractive index lens has 1NA (numerical aperture) = 0.5, f = 0.2 mm, a diameter of 2 mm, and a length of 10 mm.

[0031] More specifically: the GRIN lens 1, polarizer 2, hemispherical lens 3, white light source 4, CMOS 6, tube lens 7, analyzer 8, beam splitter 9 and Wollaston prism 10 are all integrated in a housing 5 of a miniaturized microscopic imaging system made of 3D-printed optical resin.

[0032] More specifically: the tube lens 7 has a focal length of f=6 mm and a diameter of D=5 mm, and is used to converge the differentiated light emitted by the sample onto the photosensitive surface of the CMOS 6 .

[0033] More specifically: the CMOS 6 has a pixel size of 6 μm and a field of view of up to 700×700 μm.

[0034] More specifically: the device has a total length of 25 mm, a width of 15 mm×15 mm, and a mass of only 4 g. It can be easily fixed on a multi-axis robotic arm to achieve lateral movement, axial movement, and coaxial rotation.

[0035] Although the embodiments disclosed in the present invention are as above, the contents are only embodiments adopted for facilitating understanding of the technical solution of the present invention, and are not used to limit the present invention. Any technician in the technical field to which the present invention belongs can make any modifications and changes in the form and details of the implementation without departing from the core technical solution disclosed in the present invention, but the protection scope defined by the present invention shall still be subject to the scope defined in the attached claims.

Claims

1. A miniaturized differential interference contrast (DIC) microscopy system based on a gradient refractive index lens (GRIN lens), characterized by: Including lighting module, differential module, miniaturized imaging acquisition module; The illumination module comprises, in order of light propagation direction: a white light source (4), a hemispherical lens (3), a polarizer (2), a beam splitter (9), a Wollaston prism (10), a GRIN lens (1), a Wollaston prism (10), a beam splitter (9), an analyzer (8), a tube lens (7) and a CMOS (6); The miniaturized differential module comprises, in order according to the light propagation direction: a polarizer (2), a beam splitter (9), a Wollaston prism (10), a GRIN lens (1), a Wollaston prism (10), a beam splitter (9), and an analyzer (8); The miniaturized collection modules are, in order of light propagation direction, tube lens (7) and CMOS (6).

2. The miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to claim 1, characterized in that: The white light source (4) is closely attached to the hemispherical lens (3), ensuring that the volume is compressed to the maximum extent possible while the light source is transformed from a spherical wave into parallel light.

3. The miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to claim 1, characterized in that: The size of the polarizer (2) is 4mm×4mm×2mm, the size of the analyzer (8) is 4mm×4mm×2mm, the size of the beam splitter (9) is 4mm×4mm×2mm, and the size of the Wollaston prism (9) is 4mm×4mm×3mm.

4. The miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to claim 1, characterized in that: The gradient refractive index lens (1) has NA (numerical aperture) = 0.5, f = 0.2 mm, a diameter of 2 mm, and a length of 10 mm.

5. The miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to claim 1, characterized in that: The GRIN lens (1), polarizer (2), hemispherical lens (3), white light source (4), CMOS (6), tube lens (7), analyzer (8), beam splitter (9) and Wollaston prism (10) are all integrated in a housing (5) of a miniaturized microscopic imaging system made of 3D-printed optical resin.

6. The miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to claim 1, characterized in that: The tube lens (7) has a focal length of f=6 mm and a diameter of D=5 mm, and is used to converge the light emitted by the sample after differentiation onto the photosensitive surface of the CMOS (6).

7. The miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to claim 1, characterized in that: The pixel size of the CMOS (6) is 6 μm, and the field of view can reach 700×700 μm.

8. The miniaturized differential interference contrast microscopy imaging system based on a gradient refractive index lens according to claim 7, characterized in that: The device has a total length of 25 mm, a width of 15 mm×15 mm, and a mass of only 4 g. It can be easily fixed on a multi-axis robotic arm to achieve lateral movement, axial movement, and coaxial rotation.

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