Photosensitive protein-based bioimaging devices

Abstract

This invention provides a bioimaging device based on photosensitive proteins, comprising a photosensitive imaging unit, an image reading unit, and an image reconstruction unit. The photosensitive imaging unit includes a photosensitive protein membrane and two pixel grid gel layers. The photosensitive protein membrane includes a photosensitive protein with a light-driven proton pump function. The photosensitive imaging unit converts the light intensity information of an external target image into proton concentration information of the gel material within each grid of the pixel grid gel layers. The image reading unit detects the proton concentration change information of the gel material within each grid of the pixel grid gel layers. The image reconstruction unit restores the proton concentration change information of the gel material to the light intensity information at each grid, and converts the light intensity information at the grid into grayscale information to obtain the target image. The bioimaging device provided by this invention has high image resolution.

Description

Technical Field

[0001] This invention relates to the field of biomanufacturing technology, and in particular to a bioimaging device based on photosensitive proteins. Background Technology

[0002] Bio-optoelectronic sensors, fabricated using photosensitive biomaterials, represent an important category of light sensors. Traditional optoelectronic sensors are typically made of semiconductor materials, offering relatively stable performance, but require a power source, limiting their applications. Furthermore, the materials used in their fabrication often have poor biocompatibility, preventing them from functioning effectively within living organisms. Bio-optoelectronic sensors, utilizing photosensitive biomaterials, particularly photosensitive proteins, mimic the photosensitivity of the human visual system, exhibiting characteristics similar to human tissue. Moreover, the photosensitive materials possess excellent biocompatibility, expanding their application scenarios.

[0003] Currently, although photosensitive imaging devices made from photosensitive proteins can acquire light intensity information by constructing photovoltaic cell structures, the complexity of the photovoltaic cell structure itself limits the resolution of these photosensitive imaging devices, making it difficult to acquire high-resolution image information. Summary of the Invention

[0004] Therefore, it is necessary to provide a photosensitive protein-based bioimaging device with high image resolution.

[0005] At least one embodiment of the present invention provides a bioimaging device based on a photosensitive protein, comprising:

[0006] A photosensitive imaging unit includes a photosensitive protein membrane and two pixel grid gel layers located on both sides of the photosensitive protein membrane. The photosensitive protein membrane includes a photosensitive protein with a light-driven proton pump function. The pixel grid gel layers are a grid structure containing gel material and provide a proton source for the photosensitive protein membrane. The photosensitive imaging unit is used to convert the light intensity information of an external target image into proton concentration information of the gel material in each grid of the pixel grid gel layer.

[0007] An image reading unit is used to detect changes in the proton concentration of the gel material within each grid of the pixel grid gel layer; and

[0008] An image restoration unit stores information on the correspondence between the proton concentration change of the gel material and the light intensity. The image restoration unit restores the proton concentration change information of the gel material into light intensity information at each of the grids based on the correspondence information, and converts the light intensity information at the grids into grayscale information to obtain the target image.

[0009] In some embodiments, the photosensitive protein includes bacterial rhodopsin, which includes at least one of wild-type bacterial rhodopsin and gene-edited photosensitivity-enhancing bacterial rhodopsin.

[0010] In some embodiments, the photosensitive protein membrane is constructed using at least one of Langmuir-Blodgett deposition and electrophoretic deposition, wherein the photosensitive proteins are oriented in a consistent manner.

[0011] In some embodiments, the size of the mesh is 50μm*50μm to 200μm*200μm.

[0012] In some embodiments, the photosensitive protein film further includes a photosensitive performance enhancement material capable of improving the photoelectric response performance of the photosensitive protein film. The photosensitive performance enhancement material is a material that enhances the intensity or modulates the wavelength of incident light, and the photosensitive performance enhancement material includes at least one of quantum dot materials, metal nanoparticles, and upconversion materials.

[0013] In some embodiments, the specific method for determining the correspondence information includes:

[0014] Construct a calibration photosensitive protein membrane identical to the aforementioned photosensitive protein membrane;

[0015] A gel layer with the same thickness and proton concentration as the pixel grid gel layer is disposed on both sides of the calibration photosensitive protein membrane to obtain a pre-experimental calibration device;

[0016] The pre-experiment calibration device was irradiated with light of different intensities to detect changes in the proton concentration of the gel material in the gel layer; and

[0017] Record the changes in proton concentration of the gel material in the gel layer under different light intensities to determine the correspondence between the changes in proton concentration of the gel material in the gel layer and the different light intensities.

[0018] In some embodiments, the bioimaging device further includes an encapsulation shell for encapsulating the photosensitive protein membrane and the pixel grid gel layer, the encapsulation shell being fabricated using additive manufacturing technology; and / or

[0019] The mesh structure in the pixel mesh gel layer is prepared using additive manufacturing technology.

[0020] At least one embodiment of the present invention provides a bioimaging device based on a photosensitive protein, comprising:

[0021] A photosensitive imaging unit includes a photosensitive protein membrane and two pixel grid gel layers located on both sides of the photosensitive protein membrane. The photosensitive protein membrane includes a photosensitive protein with a photodriven ion channel function. The pixel grid gel layers are a grid structure containing gel material. The pixel grid gel layers provide an ion concentration difference for the photosensitive protein membrane. The photosensitive imaging unit is used to convert the light intensity information of an external target image into ion concentration information of the gel material in each grid of the pixel grid gel layers.

[0022] An image reading unit is used to detect changes in the ion concentration of the gel material within each grid of the pixel grid gel layer; and

[0023] An image restoration unit stores information on the correspondence between the ion concentration change of the gel material and the light intensity. The image restoration unit restores the ion concentration change information of the gel material into light intensity information at each of the grids based on the correspondence information, and converts the light intensity information at the grids into grayscale information to obtain the target image.

[0024] In some embodiments, the specific method for determining the correspondence information includes:

[0025] Construct a calibration photosensitive protein membrane identical to the aforementioned photosensitive protein membrane;

[0026] A gel layer with the same thickness and ion content as the pixel grid gel layer is disposed on both sides of the calibration photosensitive protein membrane to obtain a pre-experimental calibration device.

[0027] The pre-experiment calibration device was irradiated with light of different intensities to detect changes in the ion concentration of the gel material in the gel layer; and

[0028] Record the changes in ion concentration of the gel material in the gel layer under different light intensities to determine the correspondence between the changes in ion concentration of the gel material in the gel layer and the different light intensities.

[0029] In some embodiments, the bioimaging device further includes an encapsulation shell for encapsulating the photosensitive protein membrane and the pixel grid gel layer, the encapsulation shell being fabricated using additive manufacturing technology; and / or

[0030] The mesh structure in the pixel mesh gel layer is prepared using additive manufacturing technology.

[0031] Compared with the prior art, the bioimaging device provided by the present invention has the following beneficial effects:

[0032] I. The photosensitive method and photosensitive material of the bioimaging device of the present invention are based on natural biological materials. The photosensitive function is achieved by simulating the multi-layer structure of the human retina, and it can be used independently without other data acquisition equipment.

[0033] Second, the bioimaging device of the present invention utilizes the pixel grid gel layer as a component for image information storage, and adjusts the pixels of the bioimaging device by controlling the size of the pixel grid gel layer, which significantly improves the resolution of the bio-photosensing function compared with existing bio-photosensing devices.

[0034] Third, the photosensitive imaging device of the present invention utilizes the light-driven proton pump function or the light-driven ion channel function of photosensitive protein to convert light information into storable proton concentration information or ion concentration information, thereby realizing image storage while sensing light, avoiding the shortcomings of traditional artificial retinas that can only acquire images in real time.

[0035] Fourth, the materials used in the photosensitive imaging device of the present invention have good biocompatibility and can still function after being implanted into human tissue, and can be used in the field of adjuvant treatment of retinal diseases. Attached Figure Description

[0036] Figure 1 This is a modular composition diagram of a bioimaging device provided in an embodiment of the present invention;

[0037] Figure 2 for Figure 1 A schematic diagram of the structure of the photosensitive imaging unit in the bio-imaging device shown in the figure;

[0038] Figure 3 for Figure 1 A cross-sectional view of a photosensitive imaging unit in a bioimaging device shown in the figure, in one embodiment;

[0039] Figure 4 for Figure 1 A cross-sectional view of the photosensitive imaging unit in the bioimaging device shown in the figure in another embodiment;

[0040] Figure 5 A modular composition diagram of a bioimaging device provided in another embodiment of the present invention;

[0041] Figure 6 for Figure 5 A schematic diagram of the structure of the photosensitive imaging unit in the bio-imaging device shown in the figure;

[0042] Figure 7 for Figure 5 A cross-sectional view of a photosensitive imaging unit in a bioimaging device shown in the figure, in one embodiment;

[0043] Figure 8 for Figure 5 A cross-sectional view of the photosensitive imaging unit in the bioimaging device shown in the figure in another embodiment.

[0044] Icons: 100, 200 - Bioimaging device; 10, 210 - Photosensitive imaging unit; 11, 2101 - Photosensitive protein membrane; 111, 21011 - Photosensitive performance enhancement material; 13, 2103 - Pixel grid gel layer; 131, 21031 - Gel material; 132, 21032 - Grid structure; 20, 220 - Image reading unit; 30, 230 - Image restoration unit. Detailed Implementation

[0045] To facilitate understanding of the present invention, a more complete description will be given below with reference to the accompanying drawings. Preferred embodiments of the invention are shown in the drawings. However, the invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the invention.

[0046] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0047] Please see Figure 1 An embodiment of the present invention provides a bioimaging device 100 based on photosensitive proteins, including a photosensitive imaging unit 10, an image reading unit 20, and an image restoration unit 30.

[0048] Please see Figure 2 and Figure 3 In one embodiment, the photosensitive imaging unit 10 includes a photosensitive protein film 11, two pixel grid gel layers 13, and an encapsulation shell (not shown).

[0049] The photosensitive protein membrane 11 includes a photosensitive protein with a light-driven proton pump function. In one embodiment, the photosensitive protein includes bacterial rhodopsin. In another embodiment, the bacterial rhodopsin includes at least one of wild-type bacterial rhodopsin and gene-edited photosensitivity-enhancing bacterial rhodopsin.

[0050] In one embodiment, the photosensitive protein membrane 11 can be constructed using Langmuir-Blodgett deposition and electrophoretic deposition, wherein the photosensitive proteins in the constructed photosensitive protein membrane 11 have a consistent orientation. Specifically, when constructing the photosensitive protein membrane 11 using Langmuir-Blodgett deposition and electrophoretic deposition, the consistent orientation of the photosensitive proteins can be achieved by controlling hydrophilicity / hydrophobicity or voltage. That is, the N-terminals of the photosensitive proteins in the photosensitive protein membrane 11 all face to one side, and the C-terminals all face to the other side.

[0051] Please see Figure 4 In another embodiment, the photosensitive protein film 11 further includes a photosensitizing material 111 that can enhance the photoelectric response performance of the photosensitive protein film 11. In one embodiment, the photosensitizing material 111 is a material that enhances the intensity or modulates the wavelength of incident light. In one embodiment, the photosensitizing material 111 includes at least one of quantum dot materials, metal nanoparticles, and upconversion materials.

[0052] In one embodiment, the binding method between the photosensitizing material 111 and the photosensitive protein can be layer-by-layer binding or doping binding. Specifically, in layer-by-layer binding, the photosensitive protein and the photosensitizing material 111 are independently formed and form a layered stacked structure; in doping binding, the photosensitizing material 111 and the photosensitive protein are first mixed and then formed. It can be understood that... Figure 4 The photosensitive protein film 11 is prepared by first mixing the photosensitizing material 111 with the photosensitive protein, and then molding it.

[0053] Please see Figures 2 to 4 Two pixel grid gel layers 13 are respectively located on both sides of the photosensitive protein membrane 11. In one embodiment, the pixel grid gel layer 13 is a grid structure 132 containing gel material 131. Each grid in the pixel grid gel layer 13 is a pixel in the bioimaging device 100. The pixel grid gel layer 13 provides a proton source for the photosensitive protein membrane 11, enabling the photosensitive protein membrane 11 to function as a light-driven proton pump. The photosensitive imaging unit 10 is used to convert the light intensity information of the external target image into proton concentration information of the gel material 131 in each grid of the pixel grid gel layer 13. The consistent orientation of the photosensitive protein can prevent the proton concentration changes of the gel material 131 on both sides of the photosensitive protein membrane 11 from canceling each other out, thereby improving the detection sensitivity.

[0054] In one embodiment, the size of the grid in the pixel grid gel layer 13 is 50μm*50μm to 200μm*200μm.

[0055] In one embodiment, the mesh structure 132 in the pixel mesh gel layer 13 is prepared by additive manufacturing using a biocompatible material. Specifically, the mesh structure 132 in the pixel mesh gel layer 13 can be fabricated using two-photon molding or near-field electrospinning processes.

[0056] In one embodiment, the encapsulation shell is prepared using a biocompatible material via additive manufacturing. Specifically, the encapsulation shell is prepared using biocompatible materials such as photosensitive resin and PCL, which can be additively manufactured. The encapsulation shell is used to encapsulate the photosensitive protein film 11 and the pixel grid gel layer 13.

[0057] Please refer to it again. Figure 1 and Figure 3 The image reading unit 20 is used to detect the proton concentration change information of the gel material 131 in each grid of the pixel grid gel layer 13.

[0058] The image restoration unit 30 stores the correspondence information between the proton concentration change of the gel material 131 and the light intensity. The image restoration unit 30 restores the proton concentration change information of the gel material 131 into the light intensity information at each of the grids according to the correspondence information, and converts the light intensity information at the grids into grayscale information to obtain the target image.

[0059] The relationship between the proton concentration change of the gel material 131 and the light intensity was determined through preliminary experiments. The specific determination method included:

[0060] (1) Construct a calibration photosensitive protein membrane identical to the photosensitive protein membrane 11.

[0061] (2) A gel layer with the same thickness and proton concentration as the pixel grid gel layer 13 is set on both sides of the calibration photosensitive protein membrane to obtain a pre-experiment calibration device.

[0062] (3) Irradiate the pre-experiment calibration device with light of different intensities and detect the change in proton concentration of the gel material in the gel layer.

[0063] (4) Record the changes in proton concentration of the gel material in the gel layer under different light intensities, and determine the correspondence between the changes in proton concentration of the gel material in the gel layer and the different light intensities by fitting.

[0064] Please refer to it again. Figure 3and Figure 4 The working principle of the bioimaging device 100 provided by the present invention is as follows: The photosensitive protein with light-driven proton pump function has an N-terminal and a C-terminal. Two pixel grid gel layers 13 are respectively distributed on both sides of the photosensitive protein membrane 11. Under illumination, the photosensitive protein exerts its light-driven proton pump function, pumping protons from the gel material 131 in the pixel grid gel layer 13 near the C-terminal to the gel material 131 in the pixel grid gel layer 13 near the N-terminal. This results in a decrease in the proton concentration and increase in the pH value of the gel material 131 near the C-terminal, and an increase in the proton concentration and decrease in the pH value of the gel material 131 near the N-terminal. The change in proton concentration of the gel material 131 in each grid on both sides of the photosensitive protein membrane 11 is related to the light intensity irradiated to the photosensitive protein membrane 11 at that location. That is, the photosensitive imaging unit 10 in this invention converts light intensity information into the proton concentration change (H) of the gel material 131 in the pixel grid gel layer 13 on both sides of the photosensitive protein film 11. + The image information is stored by detecting changes in the concentration of the gel material 131 in each grid of the pixel grid gel layer 13 (which can be achieved by detecting pH concentration using a pH probe). Then, using the correspondence between the changes in the proton concentration of the gel material 131 and the light intensity stored in the image restoration unit 30, the changes in the proton concentration of the gel material 131 in each grid of the pixel grid gel layer 13 are restored to the light intensity information at each grid. Finally, the light intensity information at the grid is converted into grayscale information to obtain the target image.

[0065] During the imaging process, the bioimaging device 100 provided by the present invention can assemble the photosensitive imaging unit 10 into an imaging device with a lens and shutter in a light-proof manner. The external target image is projected onto the photosensitive imaging unit 10 after passing through the lens and shutter. The light intensity information of the external target image is converted into the proton concentration information of the gel material 131 in each grid of the pixel grid gel layer 13.

[0066] Please see Figure 5 Another embodiment of the present invention provides a bioimaging device 200 based on photosensitive proteins, including a photosensitive imaging unit 210, an image reading unit 220 and an image restoration unit 230.

[0067] Please see Figure 6 and Figure 7 In one embodiment, the photosensitive imaging unit 210 includes a photosensitive protein film 2101, two pixel grid gel layers 2103, and an encapsulation shell (not shown).

[0068] The photosensitive protein membrane 2101 includes a photosensitive protein with photo-driven ion channel function. In one embodiment, the photosensitive protein may be one of many proteins in the Channelrhodopsin family, such as ChR1, ChR2, and various mutants.

[0069] In one embodiment, the photosensitive protein membrane 2101 can be constructed using Langmuir-Blodgett deposition and electrophoretic deposition, wherein the photosensitive proteins in the constructed photosensitive protein membrane 2101 have a consistent orientation. Specifically, when constructing the photosensitive protein membrane 2101 using Langmuir-Blodgett deposition and electrophoretic deposition, the consistent orientation of the photosensitive proteins can be achieved by controlling hydrophilicity / hydrophobicity or voltage. That is, the N-terminals of the photosensitive proteins in the photosensitive protein membrane 2101 all face to one side, and the C-terminals face to the other side.

[0070] Please see Figure 8 In one embodiment, the photosensitive protein film 2101 further includes a photosensitizing material 21011 that can enhance the photoelectric response performance of the photosensitive protein film 2101. In one embodiment, the photosensitizing material 21011 is a material that enhances the intensity or modulates the wavelength of incident light. In one embodiment, the photosensitizing material 21011 includes at least one of quantum dot materials, metal nanoparticles, and upconversion materials.

[0071] In one embodiment, the binding method between the photosensitizing material 21011 and the photosensitive protein can be layer-by-layer binding or doping binding. Specifically, in layer-by-layer binding, the photosensitive protein and the photosensitizing material 21011 are independently formed and form a layered stacked structure; in doping binding, the photosensitizing material 21011 and the photosensitive protein are first mixed and then formed. It can be understood that... Figure 8 The photosensitive protein film 2101 mentioned above is prepared by first mixing the photosensitive performance enhancement material 21011 with the photosensitive protein, and then molding it.

[0072] Please see Figures 6 to 8Two pixel grid gel layers 2103 are respectively located on both sides of the photosensitive protein membrane 2101. In one embodiment, the pixel grid gel layer 2103 is a grid structure 21032 containing gel material 21031. Each grid in the pixel grid gel layer 2103 is a pixel in the bioimaging device 200. The pixel grid gel layer 2103 provides an ion concentration difference for the photosensitive protein membrane 2101, allowing the photosensitive protein membrane 2101 to function as a light-driven ion channel. The type of ions and the ion concentration difference in the pixel grid gel layer 2103 depend on the type of photosensitive protein. The photosensitive imaging unit 210 is used to convert the light intensity information of the external target image into ion concentration information of the gel material 21031 in each grid of the pixel grid gel layer 2103. The consistent orientation of the photosensitive protein can prevent the ion concentration changes of the gel material 21031 on both sides of the photosensitive protein membrane 2101 from canceling each other out, thereby improving the detection sensitivity.

[0073] In one embodiment, the size of the grid in the pixel grid gel layer 2103 is 50μm*50μm to 200μm*200μm.

[0074] In one embodiment, the mesh structure 21032 in the pixel mesh gel layer 2103 is prepared by additive manufacturing using a biocompatible material. Specifically, the mesh structure 21032 in the pixel mesh gel layer 2103 can be fabricated using two-photon molding or near-field electrospinning processes.

[0075] In one embodiment, the encapsulation shell is prepared using a biocompatible material via additive manufacturing. Specifically, the encapsulation shell is prepared using biocompatible materials such as photosensitive resin and PCL, which can be additively manufactured. The encapsulation shell is used to encapsulate the photosensitive protein film 2101 and the pixel grid gel layer 2103.

[0076] Please refer to it again. Figure 5 and Figure 7 The image reading unit 220 is used to detect the ion concentration change information of the gel material 21031 in each grid of the pixel grid gel layer 2103.

[0077] The image restoration unit 230 stores the correspondence information between the ion concentration change of the gel material 21031 and the light intensity. The image restoration unit 230 restores the ion concentration change information of the gel material 21031 into the light intensity information at each of the grids according to the correspondence information, and converts the light intensity information at the grids into grayscale information to obtain the target image.

[0078] The relationship between the ion concentration change of the gel material 21031 and the light intensity was determined through preliminary experiments. The specific determination method included:

[0079] (1) Construct a calibration photosensitive protein membrane identical to the photosensitive protein membrane 2101.

[0080] (2) A gel layer with the same thickness and ion concentration as the pixel grid gel layer 2103 is set on both sides of the calibration photosensitive protein membrane to obtain a pre-experiment calibration device.

[0081] (3) Irradiate the pre-experiment calibration device with light of different intensities and detect the change in ion concentration of the gel material in the gel layer.

[0082] (4) Record the changes in ion concentration of the gel material in the gel layer under different light intensities, and determine the correspondence between the changes in ion concentration of the gel material in the gel layer and the different light intensities by fitting.

[0083] Please refer to it again. Figure 7 and Figure 8 The working principle of the bioimaging device 200 provided by the present invention is as follows: The photosensitive protein with photo-driven ion channel function has an N-terminal and a C-terminal. Two pixel grid gel layers 2103 are respectively distributed on both sides of the photosensitive protein membrane 2101. Under illumination, the photosensitive protein exerts its photo-driven ion channel function, which can transport ions from the gel material 21031 in the pixel grid gel layer 2103 near the C-terminal to the gel material 21031 in the pixel grid gel layer 2103 near the N-terminal. This results in a decrease in the ion concentration and pH value of the gel material 21031 near the C-terminal, and an increase in the ion concentration and pH value of the gel material 21031 near the N-terminal. The variation in the ion concentration of the gel material 21031 in each grid on both sides of the photosensitive protein membrane 2101 is related to the light intensity irradiated to the photosensitive protein membrane 2101 at that location. That is, the photosensitive imaging unit 210 in this invention converts light intensity information into changes in the ion concentration (Na+) of the gel material 21031 in the pixel grid gel layer 2103 on both sides of the photosensitive protein film 2101. +The image information is stored by detecting changes in the concentration of gel material 21031 in each grid of the pixel grid gel layer 2103 (which can be achieved by detecting pH concentration using a pH probe). Then, using the correspondence between the changes in the ion concentration of gel material 21031 and the light intensity stored in the image restoration unit 230, the changes in the ion concentration of gel material 21031 in each grid of the pixel grid gel layer 2103 are restored to the light intensity information at each grid. Finally, the light intensity information at the grid is converted into grayscale information to obtain the target image.

[0084] During the imaging process, the bioimaging device 200 provided by the present invention can assemble the photosensitive imaging unit 210 into an imaging device with a lens and shutter in a light-proof manner. The external target image is projected onto the photosensitive imaging unit 210 after passing through the lens and shutter. The light intensity information of the external target image is converted into the ion concentration information of the gel material 21031 in each grid of the pixel grid gel layer 2103.

[0085] This invention provides two bioimaging devices based on photosensitive proteins, which respectively utilize the photo-driven proton pump function and the photo-driven ion channel function of photosensitive proteins. The devices achieve image storage while the photosensitive proteins are photosensitive, which solves the shortcomings of traditional photoelectric conversion type photosensitive imaging devices. They can be used independently without data acquisition devices, simplifying the devices and expanding the application scenarios.

[0086] Specifically, compared with the prior art, the bioimaging device provided by the present invention has the following beneficial effects:

[0087] I. The photosensitive method and photosensitive material of the bioimaging device of the present invention are based on natural biological materials. The photosensitive function is achieved by simulating the multi-layer structure of the human retina, and it can be used independently without other data acquisition equipment.

[0088] Second, the bioimaging device of the present invention utilizes the pixel grid gel layer as a component for image information storage, and adjusts the pixels of the bioimaging device by controlling the size of the pixel grid gel layer, which significantly improves the resolution of the bio-photosensing function compared with existing bio-photosensing devices.

[0089] Third, the photosensitive imaging device of the present invention utilizes the light-driven proton pump function or the light-driven ion channel function of photosensitive protein to convert light information into storable proton concentration information or ion concentration information, thereby realizing image storage while sensing light, avoiding the shortcomings of traditional artificial retinas that can only acquire images in real time.

[0090] Fourth, the materials used in the photosensitive imaging device of the present invention have good biocompatibility and can still function after being implanted into human tissue, and can be used in the field of adjuvant treatment of retinal diseases.

[0091] The present invention will be further illustrated by specific embodiments below.

[0092] Example 1

[0093] A bioimaging device based on photosensitive proteins is provided, including a photosensitive imaging unit, an image reading unit, and an image reconstruction unit.

[0094] The photosensitive imaging unit comprises a photosensitive protein membrane, two pixel grid gel layers, and an encapsulation shell. The photosensitive imaging unit is used to convert the light intensity information of an external target image into proton concentration information of the gel material in each grid of the pixel grid gel layer.

[0095] The photosensitive protein membrane is constructed using a photosensitive protein that has a light-driven proton pump function.

[0096] The pixel grid gel layer is a grid-like structure containing gel material. Each grid represents a pixel in the bioimaging device. Two pixel grid gel layers are respectively disposed on both sides of the photosensitive protein membrane to provide a proton source for the photosensitive protein membrane, enabling the photosensitive protein membrane to perform the function of a light-driven proton pump.

[0097] The image reading unit is used to detect the changes in proton concentration of the gel material in each grid of the pixel grid gel layer under the light intensity information of the target image.

[0098] The image restoration unit stores the correspondence between the proton concentration change of the gel material and the light intensity. It is used to restore the proton concentration change information of the gel material in each grid of the pixel grid gel layer detected by the image reading unit to the light intensity information at each grid. Then, the light intensity information at each grid is converted into grayscale information to obtain the target image.

[0099] During the imaging process, the photosensitive imaging unit is assembled into an imaging device with a lens and shutter in a light-proof manner. The target image is projected onto the upper photosensitive imaging unit after passing through the lens and shutter. The light intensity information of the target image is converted into the proton concentration information of the gel material in each grid of the pixel grid gel layer.

[0100] The fabrication method of the photosensitive imaging unit is as follows: First, PCL material is printed into a grid structure using a near-field electrospinning process. Hydrogel material is then injected into the grid to complete the fabrication of one side of the pixel grid gel layer. Using this pixel grid gel layer as a substrate, 10 layers of bacterial rhodopsin are deposited on it using the Langmuir-Blodgett deposition method to form a photosensitive protein film. The bacterial rhodopsin proteins in the constructed photosensitive protein film are uniformly oriented. Next, PCL material is printed into a grid structure on the photosensitive protein film using a near-field electrospinning process, and hydrogel material is injected into the grid to complete the fabrication of the other side of the pixel grid gel layer. Finally, photosensitive resin is printed into an encapsulation shell using a photocuring process, thus completing the fabrication of the photosensitive imaging unit. After fabrication, it is stored in the dark.

[0101] The size of a single grid in the pixel grid gel layer is 50μm*50μm-200μm*200μm.

[0102] The correspondence between the proton concentration change of the gel material stored in the image reconstruction unit and the light intensity was determined through a preliminary experiment. The specific method was as follows: a calibration photosensitive protein membrane identical to that of the bioimaging device was constructed. A gel layer with the same thickness as the pixel grid gel layer of the bioimaging device was set on both sides of the calibration photosensitive protein membrane. After encapsulation, a preliminary calibration device was formed. Light of different intensities was irradiated onto the preliminary calibration device, and the proton concentration change of the gel material in the gel layer was detected. The proton concentration change of the gel material in the gel layer under different light intensities was recorded, and the correspondence between the two was determined.

[0103] The outer shell is printed using a biocompatible photosensitive resin through a photocuring process, while the grid structure of the pixel grid gel layer is printed using PCL material through a near-field electrospinning process.

[0104] Example 2

[0105] A bioimaging device based on photosensitive proteins is provided, including a photosensitive imaging unit, an image reading unit, and an image reconstruction unit.

[0106] The photosensitive imaging unit comprises a photosensitive protein membrane, a pixel grid gel layer, and an encapsulation shell. The photosensitive imaging unit is used to convert the light intensity information of an external target image into proton concentration information of the gel material in each grid of the pixel grid gel layer.

[0107] The photosensitive protein membrane is constructed from photosensitive proteins that function as light-driven proton pumps. The pixel grid gel layer is a grid-like structure containing gel material, where each grid represents a pixel in the bioimaging device. The pixel grid gel layer is positioned on both sides of the photosensitive protein membrane to provide a proton source for the membrane, enabling it to perform its light-driven proton pump function.

[0108] The image reading unit is used to detect the changes in proton concentration in each grid of the pixel grid gel layer of the photosensitive imaging unit under the light intensity information of the target image.

[0109] The image restoration unit stores the correspondence between the proton concentration change of the gel material and the light intensity. It is used to restore the proton concentration change of the gel material in each grid of the pixel grid gel layer detected by the image reading unit to the light intensity information at each grid. Then, the light intensity information at the grid is converted into grayscale information to obtain the target image.

[0110] During the imaging process, the photosensitive imaging unit is assembled into an imaging device with a lens and shutter in a light-proof manner. The target image is projected onto the upper photosensitive imaging unit after passing through the lens and shutter. The light intensity information of the target image is converted into the proton concentration information of the gel material in each grid of the pixel grid gel layer.

[0111] The photosensitive protein film also includes photosensitive performance enhancement materials that can improve the photoelectric response performance of the photosensitive protein film. The photosensitive performance enhancement materials are materials that enhance the intensity or modulate the wavelength of incident light, including quantum dot materials, metal nanoparticles or upconversion materials.

[0112] The photosensitive protein membrane was constructed by preparing 10 layers of bacterial rhodopsin using an electrophoretic deposition method. The bacterial rhodopsin in the constructed photosensitive protein membrane had a consistent orientation.

[0113] The individual grid size in the pixel grid gel layer is 50μm*50μm-200μm*200μm.

[0114] The correspondence between the proton concentration change of the gel material stored in the image reconstruction unit and the light intensity was determined through a preliminary experiment. The specific method was as follows: a calibration photosensitive protein membrane identical to that of the bioimaging device was constructed. A gel layer with the same thickness as the pixel grid gel layer of the bioimaging device was set on both sides of the calibration photosensitive protein membrane. After encapsulation, a preliminary calibration device was formed. Light of different intensities was irradiated onto the preliminary calibration device, and the proton concentration change of the gel material in the gel layer was detected. The proton concentration change of the gel material in the gel layer under different light intensities was recorded, and the correspondence between the two was determined.

[0115] The outer shell is printed using a biocompatible photosensitive resin through a photocuring process, while the grid structure of the pixel grid gel layer is printed using PCL material through a near-field electrospinning process.

[0116] Example 3

[0117] A bioimaging device based on photosensitive proteins is provided, including a photosensitive imaging unit, an image reading unit, and an image reconstruction unit.

[0118] The photosensitive imaging unit comprises a photosensitive protein membrane, a pixel grid gel layer, and an encapsulation shell. The photosensitive imaging unit is used to convert the light intensity information of an external target image into ion concentration information of the gel material in each grid of the pixel grid gel layer.

[0119] The photosensitive protein membrane is constructed using a photosensitive protein that has a photodriven ion channel function.

[0120] The pixel grid gel layer is a grid-like structure containing gel material, where each grid represents a pixel in a bioimaging device. The pixel grid gel layer is positioned on both sides of the photosensitive protein membrane to provide an ion concentration gradient, enabling the photosensitive protein membrane to function as a photo-driven ion channel. The types of ions and the ion concentration differences within the pixel grid gel layer depend on the type of photosensitive protein.

[0121] The image reading unit is used to detect the changes in ion concentration of the gel material in each grid of the pixel grid gel layer of the photosensitive imaging unit under the light intensity information of the target image.

[0122] The image restoration unit stores the correspondence between the ion concentration change of the gel material and the light intensity. It is used to restore the ion concentration change of the gel material in each grid of the pixel grid gel layer detected by the image reading unit to the light intensity information at each grid. Then, the light intensity information at the grid is converted into grayscale information to obtain the target image.

[0123] The correspondence between the changes in ion concentration of the gel material stored in the image reconstruction unit and the light intensity was determined through a preliminary experiment. The specific method was as follows: a calibration photosensitive protein membrane identical to that of the bioimaging device was constructed. Gel layers with the same thickness and ion content as the pixel grid gel layer of the bioimaging device were set on both sides of the calibration photosensitive protein membrane. After encapsulation, a preliminary calibration device was formed. Light of different intensities was irradiated onto the preliminary calibration device, and the changes in ion concentration of the gel material in the gel layer under different light intensities were recorded. The correspondence between the two was then determined.

[0124] During the imaging process, the photosensitive imaging unit is assembled into an imaging device with a lens and shutter in a light-proof manner. The target image is projected onto the upper photosensitive imaging unit after passing through the lens and shutter. The light intensity information of the target image is converted into the ion concentration information of the gel material in each grid of the pixel grid gel layer.

[0125] The photosensitive protein membrane was constructed by preparing 10 layers of photosensitive proteins using electrophoretic deposition, and the photosensitive proteins in the constructed membrane were oriented in a consistent manner.

[0126] In this example, the size of a single grid in the pixel grid gel layer is 50μm*50μm-200μm*200μm.

[0127] The technical features of the above embodiments can be combined in any way. For the sake of brevity, 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.

[0128] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A bioimaging device based on photosensitive proteins, characterized in that, include: A photosensitive imaging unit includes a photosensitive protein membrane and two pixel grid gel layers located on both sides of the photosensitive protein membrane. The photosensitive protein membrane includes a photosensitive protein with a light-driven proton pump function. The pixel grid gel layers are a grid structure containing gel material and provide a proton source for the photosensitive protein membrane. The photosensitive imaging unit is used to convert the light intensity information of an external target image into proton concentration information of the gel material in each grid of the pixel grid gel layer. Each grid in the pixel grid gel layer is a pixel in the bioimaging device. The photosensitive protein membrane is constructed by at least one of Langmuir-Blodgett deposition and electrophoretic deposition methods, and the photosensitive protein is oriented in a consistent manner. An image reading unit is used to detect the proton concentration change information of the gel material in each grid of the pixel grid gel layer; as well as An image restoration unit stores information on the correspondence between the proton concentration change of the gel material and the light intensity. The image restoration unit restores the proton concentration change information of the gel material into light intensity information at each of the grids based on the correspondence information, and converts the light intensity information at the grids into grayscale information to obtain the target image.

2. The bioimaging device based on photosensitive proteins as described in claim 1, characterized in that, The photosensitive protein includes bacterial rhodopsin, which includes at least one of wild-type bacterial rhodopsin and gene-edited photosensitivity-enhancing bacterial rhodopsin.

3. The bioimaging device based on photosensitive proteins as described in claim 1, characterized in that, The size of the mesh is 50μm*50μm to 200μm*200μm.

4. The bioimaging device based on photosensitive proteins as described in claim 1, characterized in that, The photosensitive protein film also includes a photosensitive performance enhancement material that can improve the photoelectric response performance of the photosensitive protein film. The photosensitive performance enhancement material is a material that enhances the intensity or modulates the wavelength of the incident light. The photosensitive performance enhancement material includes at least one of quantum dot materials, metal nanoparticles, and upconversion materials.

5. The bioimaging device based on photosensitive proteins as described in claim 4, characterized in that, The photosensitive material is bonded to the photosensitive protein via layer-by-layer bonding or doping bonding.

6. The bioimaging device based on photosensitive proteins as described in claim 1, characterized in that, The specific methods for determining the correspondence information include: Construct a calibration photosensitive protein membrane identical to the aforementioned photosensitive protein membrane; A gel layer with the same thickness and proton concentration as the pixel grid gel layer is disposed on both sides of the calibration photosensitive protein membrane to obtain a pre-experimental calibration device; The pre-experiment calibration device was irradiated with light of different intensities to detect changes in the proton concentration of the gel material in the gel layer; and Record the changes in proton concentration of the gel material in the gel layer under different light intensities to determine the correspondence between the changes in proton concentration of the gel material in the gel layer and the different light intensities.

7. The bioimaging device based on photosensitive proteins as described in claim 1, characterized in that, The bioimaging device also includes a packaging shell, which is used to encapsulate the photosensitive protein membrane and the pixel grid gel layer. The packaging shell is manufactured using additive manufacturing technology. and / or The mesh structure in the pixel mesh gel layer is prepared using additive manufacturing technology.

8. A bioimaging device based on photosensitive proteins, characterized in that, include: A photosensitive imaging unit includes a photosensitive protein membrane and two pixel grid gel layers located on opposite sides of the photosensitive protein membrane. The photosensitive protein membrane includes a photosensitive protein with photo-driven ion channel function. The pixel grid gel layers are a grid structure containing gel material and provide an ion concentration difference for the photosensitive protein membrane. The photosensitive imaging unit is used to convert the light intensity information of an external target image into ion concentration information of the gel material in each grid of the pixel grid gel layer. Each grid in the pixel grid gel layer is a pixel in the bioimaging device. The photosensitive protein membrane is constructed by at least one of Langmuir-Blodgett deposition and electrophoretic deposition methods, and the photosensitive protein is oriented in a consistent manner. An image reading unit is used to detect the change information of ion concentration of the gel material in each grid of the pixel grid gel layer; as well as An image restoration unit stores information on the correspondence between the ion concentration change of the gel material and the light intensity. The image restoration unit restores the ion concentration change information of the gel material into light intensity information at each of the grids based on the correspondence information, and converts the light intensity information at the grids into grayscale information to obtain the target image.

9. The bioimaging device based on photosensitive proteins as described in claim 8, characterized in that, The specific methods for determining the correspondence information include: Construct a calibration photosensitive protein membrane identical to the aforementioned photosensitive protein membrane; A gel layer with the same thickness and ion content as the pixel grid gel layer is disposed on both sides of the calibration photosensitive protein membrane to obtain a pre-experimental calibration device. The pre-experiment calibration device was irradiated with light of different intensities to detect changes in the ion concentration of the gel material in the gel layer; and Record the changes in ion concentration of the gel material in the gel layer under different light intensities to determine the correspondence between the changes in ion concentration of the gel material in the gel layer and the different light intensities.

10. The bioimaging device based on photosensitive proteins as described in claim 8, characterized in that, The bioimaging device also includes a packaging shell, which is used to encapsulate the photosensitive protein membrane and the pixel grid gel layer. The packaging shell is manufactured using additive manufacturing technology. and / or The mesh structure in the pixel mesh gel layer is prepared using additive manufacturing technology.

Images