Lenses and portable single-photon calcium imaging camera for studying neurons

Abstract

The present application relates to a lens for studying neurons, wherein a Cartesian coordinate system is established with the position of a light source as the origin, and a fitting curve fitted by a plurality of lens profile surface points is rotated to form a closed three-dimensional model, the closed three-dimensional model is a lens, and the coordinate positions of the plurality of lens profile surface points in the Cartesian coordinate system can be obtained by the following formula: wherein x is the X-axis coordinate value of any one of the plurality of lens profile surface points in the Cartesian coordinate system, and y is the Y-axis coordinate value of any one of the plurality of lens profile surface points in the Cartesian coordinate system. The above scheme can solve the problem in the related art that the stimulation light beam is calibrated through a focusing lens and a second focusing lens, and the stimulation light is focused into a light beam with little or no intensity change in the light beam area, thereby causing the irradiation area of ​​the stimulation light to the sample to be reduced.

Description

Technical Field

[0001] The invention relates to the field of imaging technology, and in particular to a lens for studying neurons and a portable single-photon calcium imaging camera. Background Art

[0002] Brain science is an important research direction that is currently receiving international attention. In order to explain the neural basis of human cognition as the main body and core, and also to facilitate the study of the direct interaction between the brain and the outside world, neurons in the brain establish mutual connections through collective behavior, forming a variety of neural circuits to perform different functions. The research direction of neural circuits is to find the neuronal cells that constitute each neural circuit, study how these neurons produce communication interactions to form specific circuits and the life activities of the circuits themselves in the central nervous system. Many studies have confirmed that in the process of analyzing the regulatory mechanism of neural circuits under physiological or pathological conditions, it is necessary to accurately reflect the neuronal activity in brain tissue by real-time monitoring of changes in calcium ions, an important biosensor in neurons.

[0003] To solve the above problems, in the related art, the Chinese invention with patent number 201680077967.7 provides a system and method for simultaneous imaging and stimulation using a microscope system. Compared with ordinary microscope systems, the microscope system can have a relatively small size. The microscope can partially include an imaging light source and a stimulation light source. The light from the imaged light source and the stimulation light source can be spectrally separated to reduce the crosstalk between the stimulation light and the imaging light. In the above system and method, the stimulation light beam is calibrated by a focusing lens and a second focusing lens to focus the stimulation light into a light beam with little or no intensity change in the beam area, resulting in a smaller irradiation area of ​​the stimulation light irradiated to the sample. Summary of the invention

[0004] Based on this, a lens for studying neurons is provided to solve the problem in the related art that the stimulation light beam is calibrated through a focusing lens and a second focusing lens, and the stimulation light is focused into a light beam with little or no intensity change within the beam area, thereby resulting in a smaller irradiation area of ​​the stimulation light to the sample.

[0005] A lens for studying neurons, wherein a Cartesian coordinate system is established with the position of a light source as the origin, and a fitting curve fitted by a plurality of lens profile surface points is rotated to form a closed three-dimensional model, wherein the closed three-dimensional model is the lens, and the coordinate positions of the plurality of lens profile surface points in the Cartesian coordinate system can be obtained by the following formula:

[0006]

[0007] Wherein, x is the X-axis coordinate value of any one of the plurality of lens surface points in the Cartesian coordinate system, y is the Y-axis coordinate value of any one of the plurality of lens surface points in the Cartesian coordinate system, N ix is the normal component of any one of the plurality of lens profile surface points in the X-axis direction on the Cartesian coordinate system, N iy is the normal component of any one of the plurality of lens profile surface points in the Y-axis direction on the Cartesian coordinate system, I (i+1)x is the unit vector of the incident light in the Cartesian coordinate system that matches any one of the plurality of lens profile surface points, in the X-axis direction, (i+1)y is the unit vector of the incident light in the Cartesian coordinate system that matches any one of the plurality of lens profile surface points, in the Y-axis direction, j is the position of any one of the plurality of lens profile surface points, P ix is the X-axis coordinate value of the incident point of the incident light matched with any one of the plurality of lens profile surface points on the Cartesian coordinate system, iy is the Y-axis coordinate value of the incident point of the incident light matched with any one of the plurality of lens profile surface points on the Cartesian coordinate system.

[0008] Preferably, the lens mentioned above is an acrylic lens.

[0009] Based on the above-mentioned lens, the present application also discloses a portable single-photon calcium imaging camera device, comprising the above-mentioned lens, a shell, a beam splitter, an image receiver, an excitation light source and a self-focusing lens, the shell being provided with an inner cavity, a first opening, a second opening and a third opening, the first opening, the second opening and the third opening being all connected to the inner cavity, the first opening and the second opening being opposite to each other, the image receiver, the excitation light source and the self-focusing lens being all arranged on the shell, the receiving surface of the image receiver being opposite to the first opening, the self-focusing lens being opposite to the second opening, the excitation light source being opposite to the third opening, the beam splitter and the lens being both arranged in the inner cavity, the lens comprising a light input end and a light output end opposite to each other, the light input end being opposite to the light emitting end of the excitation light source, the beam splitter being opposite to the light output end, and the beam splitter being located between the image receiver and the self-focusing lens.

[0010] Preferably, the above-mentioned portable single-photon calcium imaging camera device further comprises a fluorescent filter, wherein the fluorescent filter is arranged in the inner cavity, and the fluorescent filter is located between the beam splitter and the image receiver.

[0011] Preferably, the above-mentioned portable single-photon calcium imaging camera device further comprises an achromatic lens, wherein the achromatic lens is arranged in the inner cavity, and the achromatic lens is located between the beam splitter and the self-focusing lens.

[0012] Preferably, the above-mentioned portable single-photon calcium imaging camera device further comprises a focusing lens, wherein the focusing lens is arranged in the inner cavity, and the focusing lens is located between the beam splitter and the self-focusing lens.

[0013] Preferably, the above-mentioned portable single-photon calcium imaging camera device also includes a liquid lens and a controller, wherein the liquid lens is arranged in the inner cavity, and the controller is arranged on the shell, and the liquid lens is located between the beam splitter and the self-focusing lens. The controller is electrically connected to the liquid lens, and when the liquid lens is in a powered state, the controller controls the deformation of the liquid lens.

[0014] Preferably, the above-mentioned portable single-photon calcium imaging camera device further comprises a battery, wherein the battery is arranged on the housing, and the image receiver and the liquid lens are both electrically connected to the battery.

[0015] Preferably, in the above-mentioned portable single-photon calcium imaging camera device, a blue light filter layer is attached to the light-incoming surface of the light-incoming end.

[0016] The technical solution adopted in this application can achieve the following beneficial effects:

[0017] In the lens disclosed in the present application, a Cartesian coordinate system is established with the position of the light source as the origin, and a closed three-dimensional model is formed by rotating the fitting curve fitted by multiple lens surface points. The closed three-dimensional model is a lens, and the coordinate positions of multiple lens surface points in the Cartesian coordinate system can be obtained by the above formula. In the structure of the above lens, since the lens is a closed three-dimensional model, the closed three-dimensional model is formed by rotating the fitting curve fitted by multiple lens surface points, so that multiple light rays emitted by the stimulation light source can be refracted by the lens and emitted uniformly and diffusely, thereby increasing the irradiation area of ​​the living brain by the multiple light rays. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 An exploded diagram of a portable single-photon calcium imaging camera device disclosed in an embodiment of the present application;

[0019] Figure 2 It is a front view of the portable single-photon calcium imaging camera device disclosed in the embodiment of the present application;

[0020] Figure 3 for Figure 1 A cross-sectional view of

[0021] Figure 4 An exploded cross-sectional view of a housing disclosed in an embodiment of the present application;

[0022] Figure 5 A partial structural diagram of a portable single-photon calcium imaging camera device disclosed in an embodiment of the present application;

[0023] Figure 6 is the energy distribution diagram of the light source;

[0024] Figure 7 is the expected energy distribution diagram of the light emitted by the light source;

[0025] Figure 8 An image taken by irradiating the brain using the lens disclosed in the embodiment of the present application;

[0026] Fig. 9 This is an image taken without using the lens disclosed in the embodiments of the present application to illuminate the brain.

[0027] Among them: lens 100, light input end 110, light output end 120, blue light filter layer 130, shell 200, inner cavity 210, first opening 220, second opening 230, third opening 240, spectrometer 300, image receiver 400, excitation light source 500, self-focusing lens 600, achromatic lens 700, focusing lens 800, liquid lens 900, fluorescent filter 1000. DETAILED DESCRIPTION

[0028] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thoroughly understood.

[0029] It should be noted that when an element is referred to as being "disposed on" another element, it may be directly on the other element or there may be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. The terms "vertical", "horizontal", "left", "right", "top", "bottom", "bottom end", "top end" and similar expressions used herein are for illustrative purposes only and do not represent the only implementation method.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0031] Please refer to Figures 1 to 5 The present application discloses a lens 100 for studying neurons. A Cartesian coordinate system is established with the position of a light source as the origin. A fitting curve fitted by a plurality of lens profile surface points is rotated to form a closed three-dimensional model. The closed three-dimensional model is the lens 100. The coordinate positions of the plurality of lens profile surface points in the Cartesian coordinate system can be obtained by the following formula:

[0032]

[0033] Wherein, x is the X-axis coordinate value of any one of the plurality of lens surface points in the Cartesian coordinate system, y is the Y-axis coordinate value of any one of the plurality of lens surface points in the Cartesian coordinate system, N ix is the normal component of any one of the multiple lens surface points in the X-axis direction on the Cartesian coordinate system, N iy is the normal component of any one of the multiple lens surface points in the Y-axis direction on the Cartesian coordinate system, I (i+1)x is the unit vector of the incident light in the Cartesian coordinate system that matches any one of the multiple lens surface points, in the X-axis direction, (i+1)y is the unit vector of the Y-axis direction of the incident light in the Cartesian coordinate system that matches any one of the multiple lens surface points, θ j is the position of any one of the multiple lens surface points, P ix is the X-axis coordinate value of the incident point of the incident light matched with any one of the multiple lens surface points on the Cartesian coordinate system, P iy It is the Y-axis coordinate value of the incident point of the incident light matched with any one of the multiple lens surface points on the Cartesian coordinate system.

[0034] The radiance distribution of the light source is known, that is, the energy distribution of the light emitted by the light source is known. If the light source is regarded as a point, its energy distribution can be roughly approximated as an axisymmetric distribution, such as Figure 6 and Figure 7As shown, Ω is the energy distribution of the light source, and S is regarded as the expected energy distribution of the light emitted by the light source. Ω and S are divided into energy grids respectively. For the division of Ω, since the energy distribution is known, the energy in each grid can be guaranteed to be equal during the division; for the division of S, the area in each grid must also be guaranteed to be equal during the division.

[0035] The above grid division is used to calculate the surface of the lens 100. The light energy distribution effect that the lens 100 can achieve is the energy distribution on S. Through the above energy division, the boundaries of each grid of Ω and S are determined. Therefore, the incident light vector I i We can determine them one by one, and use Snell's law to calculate the normal vector N corresponding to the point i , normal vector N i It is the surface normal vector of the point that can refract the incident light to the specified position. Multiple lens surface points are calculated one by one through the above formula by iteratively using the normal vector.

[0036] During the use of lens 100, the stimulation light source needs to illuminate the illumination area of ​​the living brain. The multiple light rays emitted by the stimulation light source are refracted by lens 100. Since lens 100 is a closed three-dimensional model, the closed three-dimensional model is formed by rotating the fitting curve of multiple lens surface points, so that the multiple light rays emitted by the stimulation light source can be refracted by lens 100 and emitted uniformly and diffusely, thereby increasing the illumination area of ​​the living brain by the multiple light rays, and Figure 8 and Fig. 9 As shown, Figure 8 is an image of brain neurons captured through lens 100. Fig. 9 is a brain neuron image taken without illumination by lens 100, wherein: Figure 8 and Fig. 9 Images at the same magnification.

[0037] In the lens 100 disclosed in the present application, a Cartesian coordinate system is established with the position of the light source as the origin, and a fitting curve fitted by a plurality of lens profile surface points is rotated to form a closed three-dimensional model, and the closed three-dimensional model is the lens 100, and the coordinate positions of the plurality of lens profile surface points in the Cartesian coordinate system can be obtained by the above formula. In the structure of the above lens 100, since the lens 100 is a closed three-dimensional model, the closed three-dimensional model is formed by the fitting curve fitted by a plurality of lens profile surface points through rotation, so that the plurality of light rays emitted by the stimulation light source can be refracted by the lens 100 and can be emitted uniformly and diffusely, thereby increasing the irradiation area of ​​the living brain by the plurality of light rays.

[0038] In the embodiment of the present application, the lens 100 may be an acrylic lens. Specifically, the acrylic lens is made of acrylic material. The acrylic material has the advantages of light weight and high light transmittance. Meanwhile, the acrylic material has good processing performance.

[0039] Based on the lens 100 disclosed above, the present application also discloses a portable single-photon calcium imaging camera device, including the lens 100 , a housing 200 , a beam splitter 300 , an image receiver 400 , an excitation light source 500 and a self-focusing lens 600 .

[0040] The shell 200 can provide an installation base for the lens 100, the spectroscope 300, the image receiver 400, the excitation light source 500 and the self-focusing lens 600. The excitation light source 500 can emit stimulation light, which can stimulate the GCaMP virus in the living brain to cause it to emit green fluorescence. The self-focusing lens 600 has focusing and imaging functions.

[0041] Specifically, the housing 200 may be provided with an inner cavity 210, a first opening 220, a second opening 230 and a third opening 240, the first opening 220, the second opening 230 and the third opening 240 may all be connected to the inner cavity 210, the first opening 220 may be opposite to the second opening 230, the image receiver 400, the excitation light source 500 and the self-focusing lens 600 may all be arranged on the housing 200, the receiving surface of the image receiver 400 may be opposite to the first opening 220, and the self-focusing lens 600 may be opposite to the first opening 220. The focusing lens 600 can be opposite to the second opening 230, the excitation light source 500 can be opposite to the third opening 240, the beam splitter 300 and the lens 100 can both be arranged in the inner cavity 210, the lens 100 can include a light input end 110 and a light output end 120 opposite to each other, the light input end 110 can be opposite to the light emitting end of the excitation light source 500, the beam splitter 300 can be opposite to the light output end 120, and the beam splitter 300 can be located between the image receiver 400 and the self-focusing lens 600.

[0042] During the use of the portable single-photon calcium imaging camera device, the excitation light source 500 emits stimulation light to the light input end 110 of the lens 100, and the stimulation light is emitted from the light output surface of the light output end 120. As can be seen from the above, the light output surface of the light output end 120 is a convex surface formed by the rotation of multiple light output points on a Cartesian coordinate system, so that the multiple light rays emitted by the multiple light output points can be evenly and diffusely emitted to the spectroscope 300, and the spectroscope 300 reflects the stimulation light to the self-focusing lens 600. The stimulation light passes through the self-focusing lens 600 to the living brain. The GCaMP virus in the living brain is stimulated by the stimulation light and emits green fluorescence, which passes through the self-focusing lens 600 and the spectroscope 300 to the image receiver 400 in sequence, thereby generating a brain fluorescence image.

[0043] In the above structure, since the lens 100 expands the stimulation light, the irradiation area of ​​the stimulation light in the living brain is expanded, thereby expanding the light beam of green fluorescence reflected by the living brain, and thus expanding the size of the brain fluorescence image generated on the image receiver 400. At the same time, the stimulation light beam is irradiated to the living brain uniformly and expanded, that is, the GCaMP virus in the living brain is irradiated by the stimulation light beam with uniform light intensity, and the green fluorescence generated by the GCaMP virus in the living brain when stimulated is also uniform, thereby improving the clarity of the brain fluorescence image.

[0044] In an embodiment of the present application, the portable single-photon calcium imaging camera device may further include a fluorescent filter 1000. Specifically, the fluorescent filter 1000 may be disposed in the inner cavity 210, and the fluorescent filter 1000 may be located between the spectroscope 300 and the image receiver 400, wherein the fluorescent filter 1000 is used to allow only green fluorescence to pass, thereby preventing light of other colors from being transmitted to the image receiver 400 and interfering with the generation of brain fluorescent images.

[0045] In the embodiment of the present application, the portable single-photon calcium imaging camera device may further include an achromatic lens 700. Specifically, the achromatic lens 700 may be disposed in the inner cavity 210. The achromatic lens 700 may be located between the beam splitter 300 and the self-focusing lens 600. The achromatic lens 700 is used to eliminate the chromatic aberration and spherical aberration of the green fluorescence or the stimulation light. Chromatic aberration and spherical aberration will occur during the transmission of the stimulation light and the green fluorescence. The chromatic aberration is caused by the difference in dispersion and refractive index of light of different wavelengths in the glass, which results in different focal points for light of different wavelengths. The spherical aberration is that the light beam emitted by the object point on the axis, after passing through the optical system, the light beam with different angles to the optical axis intersects the optical axis at different positions, thus forming a circular diffuse spot on the image plane. The above structure can improve the resolution of the image receiver 400.

[0046] In an embodiment of the present application, the portable single-photon calcium imaging camera device may further include a focusing lens 800. Specifically, the focusing lens 800 may be disposed in the inner cavity 210. The focusing lens 800 may be located between the beam splitter 300 and the self-focusing lens 600. The focusing lens 800 may adjust small deviations such as eccentricity of the green fluorescence or stimulation light, so that most of the green fluorescence or stimulation light may pass through the focusing lens 800 and reach a designated position.

[0047] In an embodiment of the present application, the portable single-photon calcium imaging camera device may further include a liquid lens 900 and a controller. Specifically, the liquid lens 900 may be disposed in the inner cavity 210, the controller may be disposed on the housing 200, the liquid lens 900 may be located between the beam splitter 300 and the self-focusing lens 600, the controller may be electrically connected to the liquid lens 900, and when the liquid lens 900 is in a powered-on state, the controller may control the deformation of the liquid lens 900, wherein the liquid lens 900 uses the liquid as a lens 100 to change the focal length by changing the curvature of the liquid, thereby realizing automatic focusing and zooming of the portable single-photon calcium imaging camera device, thereby improving the image effect captured by the portable single-photon calcium imaging camera device.

[0048] In an embodiment of the present application, the portable single-photon calcium imaging camera device may further include a battery. Specifically, the battery may be disposed on the housing 200, and the image receiver 400 and the liquid lens 900 may be electrically connected to the battery, thereby enabling the portable single-photon calcium imaging camera device to be disconnected from the power supply connected via the electrical connector, thereby enabling the portable single-photon calcium imaging camera device to facilitate free movement of the living body.

[0049] In the embodiment of the present application, a blue light filter layer 130 may be attached to the light input surface of the light input end 110. Since the blue light band in the stimulation light can excite the GCaMP virus to produce green fluorescence, the blue light filter layer 130 can only allow the blue light in the stimulation light to pass through, thereby preventing light of other color bands from irradiating the living brain and causing adverse effects.

[0050] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0051] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A lens for studying neurons, characterized in that: A Cartesian coordinate system is established with the position of the light source as the origin, and a fitting curve fitted by multiple lens surface points is rotated to form a closed three-dimensional model, wherein the closed three-dimensional model is the lens, and the coordinate positions of the multiple lens surface points in the Cartesian coordinate system can be obtained by the following formula: Wherein, x is the X-axis coordinate value of any one of the plurality of lens surface points in the Cartesian coordinate system, y is the Y-axis coordinate value of any one of the plurality of lens surface points in the Cartesian coordinate system, N ix is the normal component of any one of the plurality of lens profile surface points in the X-axis direction on the Cartesian coordinate system, N iy is the normal component of any one of the plurality of lens profile surface points in the Y-axis direction on the Cartesian coordinate system, I (i+1)x is the unit vector of the incident light in the Cartesian coordinate system that matches any one of the plurality of lens profile surface points, in the X-axis direction, (i+1)y is the unit vector of the incident light in the Cartesian coordinate system that matches any one of the plurality of lens profile surface points, in the Y-axis direction, j is the position of any one of the plurality of lens profile surface points, P ix is the X-axis coordinate value of the incident point of the incident light matched with any one of the plurality of lens profile surface points on the Cartesian coordinate system, iy is the Y-axis coordinate value of the incident point of the incident light matched with any one of the plurality of lens profile surface points on the Cartesian coordinate system.

2. The lens according to claim 1, characterized in that The lens is an acrylic lens.

3. A portable single-photon calcium imaging camera device, comprising the lens, shell, beam splitter, image receiver, excitation light source and self-focusing lens described in claim 2, wherein the shell is provided with an inner cavity, a first opening, a second opening and a third opening, the first opening, the second opening and the third opening are all connected to the inner cavity, the first opening and the second opening are opposite to each other, the image receiver, the excitation light source and the self-focusing lens are all arranged on the shell, the receiving surface of the image receiver is opposite to the first opening, the self-focusing lens is opposite to the second opening, the excitation light source is opposite to the third opening, the beam splitter and the lens are both arranged in the inner cavity, the lens comprises a light input end and a light output end opposite to each other, the light input end is opposite to the light emitting end of the excitation light source, the beam splitter is opposite to the light output end, and the beam splitter is located between the image receiver and the self-focusing lens.

4. The portable single-photon calcium imaging camera device according to claim 3, characterized in that: The portable single-photon calcium imaging camera device further comprises a fluorescent filter, which is arranged in the inner cavity and located between the beam splitter and the image receiver.

5. The portable single-photon calcium imaging camera device according to claim 3, characterized in that: The portable single-photon calcium imaging camera device further comprises an achromatic lens, which is arranged in the inner cavity and located between the beam splitter and the self-focusing lens.

6. The portable single-photon calcium imaging camera device according to claim 3, characterized in that: The portable single-photon calcium imaging camera device further comprises a focusing lens, which is arranged in the inner cavity and located between the beam splitter and the self-focusing lens.

7. The portable single-photon calcium imaging camera device according to claim 3, characterized in that: The portable single-photon calcium imaging camera device also includes a liquid lens and a controller. The liquid lens is arranged in the inner cavity, and the controller is arranged on the shell. The liquid lens is located between the spectroscope and the self-focusing lens. The controller is electrically connected to the liquid lens. When the liquid lens is in a powered state, the controller controls the deformation of the liquid lens.

8. The portable single-photon calcium imaging camera device according to claim 7, characterized in that: The portable single-photon calcium imaging camera device further comprises a battery, which is arranged on the housing, and the image receiver and the liquid lens are both electrically connected to the battery.

9. The portable single-photon calcium imaging camera device according to claim 3, characterized in that: A blue light filter layer is attached to the light input surface of the light input end.

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