CN116008198B - Photosensitive protein-based bioimaging devices - Google Patents
Photosensitive protein-based bioimaging devicesInfo
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- CN116008198B CN116008198B CN202211445158.0A CN202211445158A CN116008198B CN 116008198 B CN116008198 B CN 116008198B CN 202211445158 A CN202211445158 A CN 202211445158A CN 116008198 B CN116008198 B CN 116008198B
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Abstract
本发明提供了一种基于光敏蛋白的生物成像装置，包括感光成像单元、图像读取单元以及图像还原单元。所述感光成像单元包括光敏蛋白膜以及两个像素网格凝胶层，所述光敏蛋白膜包括具有光驱质子泵功能的光敏蛋白，所述感光成像单元用于将外界目标图像的光强信息转变为所述像素网格凝胶层中各个网格内的凝胶材料的质子浓度信息。所述图像读取单元用于检测所述像素网格凝胶层中各个网格内的所述凝胶材料的质子浓度变化信息。所述图像还原单元将所述凝胶材料的质子浓度变化信息还原为各个所述网格处的光强信息，并把所述网格处的光强信息转变为灰度信息，得到目标图像。本发明提供的所述生物成像装置具有较高的图像分辨率。
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
The invention relates to the technical field of biological manufacturing, in particular to a biological imaging device based on photosensitive protein.
Background
Biophotosensors fabricated using photosensitive biological materials are an important class of light sensors. The traditional photoelectric sensor is usually made of semiconductor materials, has stable performance, but needs power supply for driving when in use, so that the use scene is limited, and the biocompatibility of the materials used for manufacturing is poor, so that the photoelectric sensor cannot function in organisms. The biological photoelectric sensor prepared by utilizing the photosensitive biological material, especially the photosensitive protein, simulates the photosensitive principle of the human eye vision system, has the characteristic of simulating human tissues, has excellent biocompatibility and expands the application scene.
At present, the photosensitive imaging device prepared from the photosensitive protein can acquire illumination intensity information by constructing a photocell structure, but the resolution of the photosensitive imaging device is limited due to the complexity of the photocell structure, so that the acquisition of high-resolution image information is difficult to realize.
Disclosure of Invention
Based on this, it is necessary to provide a light sensitive protein based bioimaging device with a higher image resolution.
At least one embodiment of the present invention provides a photoimaging device based on a photosensitive protein, comprising:
The photosensitive imaging unit comprises a photosensitive protein film and two pixel grid gel layers respectively positioned at two sides of the photosensitive protein film, the photosensitive protein film comprises photosensitive proteins with an optical drive proton pump function, the pixel grid gel layers are of grid structures containing gel materials, the pixel grid gel layers provide proton sources for the photosensitive protein film, and the photosensitive imaging unit is used for converting light intensity information of an external target image into proton concentration information of the gel materials in each grid in the pixel grid gel layers;
An image reading unit for detecting proton concentration variation information of the gel material in each of the pixel grid gel layers, and
The image reduction unit is used for reducing the proton concentration change information of the gel material into light intensity information at each grid according to the corresponding relation information and converting the light intensity information at the grid into gray information to obtain a target image.
In some of these embodiments, the photosensitive protein comprises bacteriorhodopsin, including at least one of wild-type bacteriorhodopsin and genetically-edited photostability-enhancing bacteriorhodopsin.
In some embodiments, the photosensitive protein film is constructed by at least one of Langmuir-Blodgett deposition and electrophoretic deposition, and the photosensitive proteins are oriented in a uniform manner.
In some embodiments, the mesh is 50 μm by 50 μm to 200 μm by 200 μm in size.
In some embodiments, the photoactive protein film further comprises a photoactive performance-enhancing material capable of enhancing the photoelectric response performance of the photoactive protein film, the photoactive performance-enhancing material being a material that enhances or modulates the intensity or wavelength band of incident light, the photoactive performance-enhancing material comprising at least one of a quantum dot material, a metal nanoparticle, and an upconverting material.
In some embodiments, the specific method for determining the correspondence information includes:
Constructing a calibrated photosensitive protein film identical to the photosensitive protein film;
Gel layers with the same thickness and proton concentration as those of the gel layers of the pixel grid are arranged on two sides of the calibration photosensitive protein film to obtain a pre-experiment calibration device;
Respectively irradiating the pre-experiment calibration device with light of different intensities, detecting the change of the proton concentration of the gel material in the gel layer, and
Recording the proton concentration change of the gel material in the gel layer under different illumination intensities to determine the corresponding relation information of the proton concentration change of the gel material in the gel layer and the different illumination intensities.
In some embodiments, the biological imaging device further comprises an encapsulation housing for encapsulating the photosensitive protein film and the pixel grid gel layer, the encapsulation housing being fabricated using additive manufacturing techniques, and/or
The fabrication technique of the grid structure in the pixel grid gel layer is an additive manufacturing technique.
At least one embodiment of the present invention provides a photoimaging device based on a photosensitive protein, comprising:
the photosensitive imaging unit comprises a photosensitive protein film and two pixel grid gel layers respectively positioned at two sides of the photosensitive protein film, the photosensitive protein film comprises photosensitive proteins with an optical drive ion channel function, the pixel grid gel layers are of grid structures containing gel materials, the pixel grid gel layers provide ion concentration differences for the photosensitive protein film, and the photosensitive imaging unit is used for converting light intensity information of an external target image into ion concentration information of the gel materials in each grid in the pixel grid gel layers;
An image reading unit for detecting ion concentration variation information of the gel material in each of the pixel grid gel layers, and
The image reduction unit is used for reducing the ion concentration change information of the gel material into light intensity information at each grid according to the corresponding relation information and converting the light intensity information at the grid into gray information to obtain a target image.
In some embodiments, the specific method for determining the correspondence information includes:
Constructing a calibrated photosensitive protein film identical to the photosensitive protein film;
gel layers with the same thickness and ion content as those of the gel layers of the pixel grid are arranged on two sides of the calibration photosensitive protein film to obtain a pre-experiment calibration device;
respectively irradiating the pre-experiment calibration device with light of different intensities, detecting the ion concentration change of the gel material in the gel layer, and
And recording the ion concentration change of the gel material in the gel layer under different illumination intensities to determine the corresponding relation information of the ion concentration change of the gel material in the gel layer and the different illumination intensities.
In some embodiments, the biological imaging device further comprises an encapsulation housing for encapsulating the photosensitive protein film and the pixel grid gel layer, the encapsulation housing being fabricated using additive manufacturing techniques, and/or
The fabrication technique of the grid structure in the pixel grid gel layer is an additive manufacturing technique.
Compared with the prior art, the biological imaging device provided by the invention has the following beneficial effects:
1. The photosensitive mode and the photosensitive material of the biological imaging device are based on natural life materials, realize the photosensitive function by simulating the multilayer structure of human retina, and can be independently used without other data acquisition equipment.
2. The biological imaging device utilizes the pixel grid gel layer as an image information storage component, and the pixels of the biological imaging device are regulated and controlled through the size of the pixel grid gel layer, so that compared with the existing biological photosensitive device, the resolution of a biological photosensitive function is greatly improved.
3. The photosensitive imaging device converts illumination information into storable proton concentration information or ion concentration information by utilizing the optical drive proton pump function or the optical drive ion channel function of photosensitive protein, realizes image storage while sensitization, and avoids the defect that the traditional artificial retina can only acquire images in real time.
4. The material used by the photosensitive imaging device has better biocompatibility, can still play a role after being implanted into human tissues, and can be used in the fields of auxiliary treatment of retina diseases and the like.
Drawings
FIG. 1 is a block diagram of a biological imaging apparatus according to an embodiment of the present invention;
Fig. 2 is a schematic structural view of a photosensitive imaging unit in the biological imaging apparatus shown in fig. 1;
FIG. 3 is a cross-sectional view of a photosensitive imaging unit in one embodiment of the biological imaging apparatus shown in FIG. 1;
FIG. 4 is a cross-sectional view of a photosensitive imaging unit in the biological imaging apparatus shown in FIG. 1 in another embodiment;
FIG. 5 is a block diagram of a biological imaging apparatus according to another embodiment of the present invention;
fig. 6 is a schematic structural view of a photosensitive imaging unit in the biological imaging apparatus shown in fig. 5;
FIG. 7 is a cross-sectional view of a photosensitive imaging unit in one embodiment of the biological imaging apparatus shown in FIG. 5;
fig. 8 is a cross-sectional view of a photosensitive imaging unit in the biological imaging apparatus shown in fig. 5 in another embodiment.
The icons are 100, 200-biological imaging device 10, 210-photosensitive imaging unit, 11, 2101-photosensitive protein film, 111, 21011-photosensitive performance enhancing material, 13, 2103-pixel grid gel layer, 131, 21031-gel material, 132, 21032-grid structure, 20, 220-image reading unit, 30, 230-image reduction unit.
Detailed Description
In order that the invention may be readily understood, a more complete description of the invention will be rendered by reference to the appended drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, 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 belongs. The terminology used herein in the description of the 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.
Referring to fig. 1, an embodiment of the present invention provides a biological imaging apparatus 100 based on a photosensitive protein, which includes a photosensitive imaging unit 10, an image reading unit 20, and an image restoring unit 30.
Referring to fig. 2 and 3, in one embodiment, the photosensitive imaging unit 10 includes a photosensitive protein film 11, two pixel grid gel layers 13, and a package housing (not shown).
Wherein the photosensitive protein film 11 comprises photosensitive protein with optical drive proton pump function. In one embodiment, the photosensitive protein comprises bacteriorhodopsin. In one embodiment, the bacteriorhodopsin includes at least one of wild-type bacteriorhodopsin and genetically engineered photosensitive performance enhancing bacteriorhodopsin.
In one embodiment, the light sensitive protein film 11 may be constructed using a Langmuir-Blodgett deposition method and an electrophoretic deposition method, and the orientation of the light sensitive proteins in the constructed light sensitive protein film 11 is uniform. Specifically, the photosensitive protein film 11 is constructed using Langmuir-Blodgett deposition and electrophoretic deposition, and the orientation of the photosensitive proteins can be made uniform by controlling the hydrophilicity and hydrophobicity or voltage. I.e. the N-terminal (N-terminal) of the photoprotein in the photoprotein film 11 is directed to one side and the C-terminal (C-terminal) is directed to the other side.
Referring to fig. 4, in another embodiment, the photosensitive protein film 11 further includes a photosensitive performance enhancing material 111 that can enhance the photoelectric response performance of the photosensitive protein film 11. In one embodiment, the photosensitive performance enhancing material 111 is a material that enhances or modulates the intensity or wavelength of incident light. In one embodiment, the photosensitive performance enhancing material 111 includes at least one of a quantum dot material, a metal nanoparticle, and an upconverting material.
In an embodiment, the photosensitive performance enhancing material 111 and the photosensitive protein may be combined layer by layer or doped. Specifically, in the layer-by-layer combination, the photosensitive protein and the photosensitive enhancement material 111 are independently formed and form a layered stack structure, and in the doping combination, the photosensitive enhancement material 111 and the photosensitive protein are mixed first and then formed. It will be appreciated that the photosensitive protein film 11 in fig. 4 is prepared by mixing the photosensitive property enhancing material 111 with the photosensitive protein and then molding.
Referring to fig. 2 to 4, two pixel grid gel layers 13 are respectively disposed on two sides of the photosensitive protein film 11. In one embodiment, the pixel grid gel layer 13 is a grid structure 132 containing gel material 131. Wherein each grid of the pixel grid gel layer 13 is one pixel of the biological imaging apparatus 100. The pixel grid gel layer 13 provides a proton source for the photosensitive protein film 11, so that the photosensitive protein film 11 can perform the function of optical drive proton pump. Wherein the photosensitive imaging unit 10 is used for converting light intensity information of an external target image into proton concentration information of the gel material 131 in each grid in the pixel grid gel layer 13. Wherein, the alignment of the photosensitive proteins can prevent the proton concentration changes of the gel material 131 at both sides of the photosensitive protein film 11 from being offset each other, thereby improving the detection sensitivity.
In one embodiment, the size of the grid in the pixel grid gel layer 13 is 50 μm by 50 μm to 200 μm by 200 μm.
In one embodiment, the grid structure 132 in the pixel grid gel layer 13 is made of biocompatible material by additive manufacturing. Specifically, the mesh structure 132 in the pixel mesh gel layer 13 may be manufactured using two-photon molding or near-field electrospinning.
In an embodiment, the packaging shell is made of a material with good biocompatibility through an additive manufacturing method. Specifically, the packaging shell is prepared by using photosensitive resin, PCL and other materials which have good biocompatibility and can be manufactured and formed in an additive mode through an additive manufacturing method. Wherein the packaging shell is used for packaging the photosensitive protein film 11 and the pixel grid gel layer 13.
Referring again to fig. 1 and 3, the image reading unit 20 is configured to detect information of changes in the proton concentration of the gel material 131 in each of the pixel grid gel layers 13.
The image reduction unit 30 stores the corresponding relation information of the proton concentration change and the illumination intensity of the gel material 131, and the image reduction unit 30 reduces the proton concentration change information of the gel material 131 to light intensity information at each grid according to the corresponding relation information, and converts the light intensity information at the grid to gray information to obtain a target image.
The information of the correspondence between the change of the proton concentration of the gel material 131 and the illumination intensity is determined through a pre-experiment, and the specific determining method includes:
(1) The same calibrated photosensitive protein film as the photosensitive protein film 11 was constructed.
(2) Gel layers with the same thickness and proton concentration as those of the gel layer 13 of the pixel grid are arranged on two sides of the calibration photosensitive protein film, so that a pre-experiment calibration device is obtained.
(3) And respectively irradiating lights with different intensities to the pre-experiment calibration device, and detecting the change of the proton concentration of the gel material in the gel layer.
(4) Recording the proton concentration change of the gel material in the gel layer under different illumination intensities, and determining the corresponding relation information of the proton concentration change of the gel material in the gel layer and the different illumination intensities through fitting.
Referring to fig. 3 and 4 again, the working principle of the biological imaging device 100 provided by the present invention is that the photosensitive protein having the function of optical drive proton pump has an N-terminal and a C-terminal, the two pixel grid gel layers 13 are respectively distributed on two sides of the photosensitive protein film 11, the photosensitive protein performs the function of optical drive proton pump under illumination, and can pump protons of 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, so that the proton concentration of the gel material 131 near the C-terminal is reduced, the pH value is increased, the proton concentration of the gel material 131 near the N-terminal is increased, and the pH value is reduced. The extent of the change in proton concentration of the gel material 131 in each of the grids on both sides of the photosensitive protein film 11 is related to the intensity of the light irradiated to the photosensitive protein film 11. That is, the photosensitive imaging unit 10 in the present invention converts the illumination intensity information into the proton concentration variation (H + concentration variation) of the gel material 131 in the pixel grid gel layer 13 on both sides of the photosensitive protein film 11, thereby realizing the storage of the image information. The image reading unit 20 reads the image information stored in the photosensitive imaging unit 10, specifically, detects the change of the proton concentration of the gel material 131 in each grid of the pixel grid gel layer 13 (which can be achieved by detecting the pH concentration with a pH probe), and then uses the corresponding relation information of the change of the proton concentration of the gel material 131 and the illumination intensity stored in the image reduction unit 30 to reduce the change of the proton concentration of the gel material 131 in each grid of the pixel grid gel layer 13 to the light intensity information at each grid, and then converts the light intensity information at the grid into gray information, thereby obtaining the target image.
In the imaging process of the biological imaging device 100 provided by the invention, the photosensitive imaging unit 10 can be assembled into an imaging device with a lens and a shutter in a dark place, an external target image is projected onto the photosensitive imaging unit 10 after passing through the lens and the shutter, and 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.
Referring to fig. 5, another embodiment of the present invention provides a bio-imaging device 200 based on a photosensitive protein, which includes a photosensitive imaging unit 210, an image reading unit 220, and an image restoring unit 230.
Referring to fig. 6 and 7, in one embodiment, the photosensitive imaging unit 210 includes a photosensitive protein film 2101, two pixel grid gel layers 2103, and a packaging housing (not shown).
Wherein the light sensitive protein film 2101 comprises light sensitive proteins with optical drive ion channel functions. In one embodiment, the photosensitive protein may be a plurality of proteins in the Channelrhodopsin family, such as ChR1, chR2, and various mutants.
In one embodiment, the light sensitive protein film 2101 may be constructed using a Langmuir-Blodgett deposition method and an electrophoretic deposition method, with the orientation of the light sensitive proteins in the constructed light sensitive protein film 2101 being uniform. Specifically, the photosensitive protein film 2101 is constructed using Langmuir-Blodgett deposition and electrophoretic deposition, and the orientation of the photosensitive protein can be made uniform by controlling the hydrophilicity and hydrophobicity or voltage. I.e., the N-terminal (N-terminal) of the photoprotein in the photoprotein film 2101 is all directed to one side and the C-terminal is directed to the other side.
Referring to fig. 8, in one embodiment, the photosensitive protein film 2101 further comprises a photosensitive performance enhancing material 21011 for enhancing the photoelectric response performance of the photosensitive protein film 2101. In one embodiment, the photosensitive performance enhancing material 21011 is a material that provides an intensity enhancement or band modulation of the incident light. In an embodiment, the photosensitive performance enhancing material 21011 comprises at least one of a quantum dot material, a metal nanoparticle, and an upconverting material.
In an embodiment, the photosensitive property enhancing material 21011 may be bonded to the photosensitive protein layer by layer or doped. Specifically, in layer-by-layer bonding, the photosensitive protein and the photosensitive enhancement material 21011 are independently molded and form a layered stack, and in doping bonding, the photosensitive enhancement material 21011 and the photosensitive protein are mixed first and then molded. It will be appreciated that the photosensitive protein film 2101 of fig. 8 is prepared by mixing the photosensitive property enhancing material 21011 with the photosensitive protein and then molding.
Referring to fig. 6 to 8, two pixel grid gel layers 2103 are respectively located at two sides of the photosensitive protein film 2101. In an embodiment, the pixel grid gel layer 2103 is a grid structure 21032 containing gel material 21031. Wherein each of the pixel grid gel layers 2103 is one pixel of the biological imaging apparatus 200. Wherein the pixel grid gel layer 2103 provides an ion concentration difference for the photosensitive protein film 2101, so that the photosensitive protein film 2101 can play a role of an ion channel of a CD-ROM. Wherein the ion species and ion concentration differences in the pixel grid gel layer 2103 are dependent on the species of the photosensitive protein. Wherein the photosensitive imaging unit 210 is configured to convert light intensity information of an external target image into ion concentration information of the gel material 21031 in each of the pixel grid gel layers 2103. Wherein the alignment of the photosensitive proteins can prevent the ion concentration changes of the gel material 21031 on both sides of the photosensitive protein film 2101 from canceling each other, thereby improving the detection sensitivity.
In one embodiment, the size of the grid in the pixel grid gel layer 2103 is 50 μm by 50 μm to 200 μm by 200 μm.
In one embodiment, the grid structure 21032 in the pixel grid gel layer 2103 is fabricated using biocompatible materials by additive manufacturing. In particular, the grid structure 21032 in the pixel grid gel layer 2103 can be made using a two-photon molding or near field electrospinning process.
In an embodiment, the packaging shell is made of a material with good biocompatibility through an additive manufacturing method. Specifically, the packaging shell is prepared by using photosensitive resin, PCL and other materials which have good biocompatibility and can be manufactured and formed in an additive mode through an additive manufacturing method. Wherein the encapsulation housing is used to encapsulate the photosensitive protein film 2101 and the pixel grid gel layer 2103.
Referring again to fig. 5 and 7, the image reading unit 220 is configured to detect ion concentration variation information of the gel material 21031 within each of the pixel grid gel layers 2103.
The image reduction unit 230 stores the correspondence information between the ion concentration change and the illumination intensity of the gel material 21031, and the image reduction unit 230 reduces the ion concentration change information of the gel material 21031 to light intensity information at each grid according to the correspondence information, and converts the light intensity information at the grid to gray scale information, so as to obtain a target image.
The correspondence information between the ion concentration change and the illumination intensity of the gel material 21031 is determined through a pre-experiment, and the specific determination method comprises the following steps:
(1) The same calibrated photosensitive protein film as the photosensitive protein film 2101 was constructed.
(2) Gel layers with the same thickness and ion concentration as those of the pixel grid gel layer 2103 are arranged on two sides of the calibration photosensitive protein film, so that a pre-experiment calibration device is obtained.
(3) And respectively irradiating the pre-experiment calibration device with light of different intensities, and detecting the ion concentration change of the gel material in the gel layer.
(4) And recording the ion concentration change of the gel material in the gel layer under different illumination intensities, and determining the corresponding relation information of the ion concentration change of the gel material in the gel layer and the different illumination intensities through fitting.
Referring to fig. 7 and 8 again, the working principle of the biological imaging device 200 provided by the present invention is that the photosensitive protein having the function of optical drive ion channel has an N-terminal and a C-terminal, the two pixel grid gel layers 2103 are respectively distributed on two sides of the photosensitive protein film 2101, the photosensitive protein performs the function of optical drive ion channel under illumination, and can transport the ions of 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, so that the ion concentration of the gel material 21031 near the C-terminal is reduced, the pH value is reduced, the ion concentration of the gel material 21031 near the N-terminal is increased, and the pH value is increased. The amplitude of the change in ion concentration of the gel material 21031 in each grid on both sides of the photosensitive protein film 2101 is correlated with the intensity of the light with which the photosensitive protein film 2101 is irradiated. That is, the photosensitive imaging unit 210 in the present invention converts illumination intensity information into ion concentration changes (Na + concentration changes) of the gel material 21031 in the pixel grid gel layer 2103 on both sides of the photosensitive protein film 2101, thereby realizing storage of image information. The image reading unit 220 reads the image information stored in the photosensitive imaging unit 210, specifically, detects the ion concentration change of the gel material 21031 in each grid of the pixel grid gel layer 2103 (which can be achieved by detecting the pH concentration with a pH probe), then uses the corresponding relation information of the ion concentration change of the gel material 21031 stored in the image reduction unit 230 and the illumination intensity to reduce the ion concentration change of the gel material 21031 in each grid of the pixel grid gel layer 2103 to the light intensity information at each grid, and then converts the light intensity information at the grid into gray information, thereby obtaining the target image.
In the imaging process of the biological imaging device 200 provided by the invention, the photosensitive imaging unit 210 can be assembled into an imaging device with a lens and a shutter in a dark place, an external target image is projected onto the photosensitive imaging unit 210 after passing through the lens and the shutter, and 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.
The invention provides two biological imaging devices based on photosensitive proteins, which respectively utilize the functions of an optical drive proton pump and an optical drive ion channel of the photosensitive proteins, realize the storage of images while the photosensitive proteins are sensitized, solve the defects of a traditional photoelectric conversion type photosensitive imaging device, can be separated from the independent use of a data acquisition device, simplify the device and widen the application scene.
Specifically, compared with the prior art, the biological imaging device provided by the invention has the following beneficial effects:
1. The photosensitive mode and the photosensitive material of the biological imaging device are based on natural life materials, realize the photosensitive function by simulating the multilayer structure of human retina, and can be independently used without other data acquisition equipment.
2. The biological imaging device utilizes the pixel grid gel layer as an image information storage component, and the pixels of the biological imaging device are regulated and controlled through the size of the pixel grid gel layer, so that compared with the existing biological photosensitive device, the resolution of a biological photosensitive function is greatly improved.
3. The photosensitive imaging device converts illumination information into storable proton concentration information or ion concentration information by utilizing the optical drive proton pump function or the optical drive ion channel function of photosensitive protein, realizes image storage while sensitization, and avoids the defect that the traditional artificial retina can only acquire images in real time.
4. The material used by the photosensitive imaging device has better biocompatibility, can still play a role after being implanted into human tissues, and can be used in the fields of auxiliary treatment of retina diseases and the like.
The invention is further illustrated by the following specific examples.
Example 1
A biological imaging apparatus based on a photosensitive protein is provided, which includes a photosensitive imaging unit, an image reading unit, and an image reduction unit.
The photosensitive imaging unit comprises a photosensitive protein film, two pixel grid gel layers and a packaging shell. The photosensitive imaging unit is used for converting the light intensity information of the external target image into proton concentration information of gel materials in each grid of the gel layer of the pixel grid.
The photosensitive protein film is constructed by photosensitive protein with the function of CD-ROM proton pump.
The pixel grid gel layer is a grid-like structure containing gel material. Each grid is one pixel in the biological imaging device. The two pixel grid gel layers are respectively arranged at two sides of the photosensitive protein film and used for providing proton sources for the photosensitive protein film so that the photosensitive protein film can play a role of a CD-ROM proton pump.
The image reading unit is used for detecting proton concentration change information generated by gel materials in each grid of the pixel grid gel layer under the light intensity information of the target image.
The image reduction unit is internally stored with a corresponding relation between the proton concentration change of the gel material and the illumination intensity, and is used for reducing the proton concentration change information of the gel material in each grid of the pixel grid gel layer detected by the image reading unit into light intensity information of each grid, and then converting the light intensity information of each grid into gray information to obtain a target image.
In the imaging process of the biological imaging device, the photosensitive imaging unit is assembled into imaging equipment with a lens and a shutter in a dark way, a target image is projected onto the upper photosensitive imaging unit after passing through the lens and the shutter, and the light intensity information of the target image is converted into proton concentration information of gel materials in each grid of the pixel grid gel layer.
The photosensitive imaging unit is prepared by printing PCL material into a grid structure by adopting a near-field electrospinning process, and injecting hydrogel material into the grid to finish the preparation of the gel layer of the pixel grid at one side. And taking the pixel grid gel layer at one side as a substrate, preparing 10 layers of bacteriorhodopsin on the substrate by adopting a Langmuir-Blodgett deposition method to form a photosensitive protein film, wherein the bacteriorhodopsin proteins in the constructed photosensitive protein film are consistent in orientation. Printing PCL material on the photosensitive protein film by adopting a near-field electrospinning process to form a grid structure, and injecting a hydrogel material into the grid to finish the preparation of the gel layer of the pixel grid on the other side. Then, the photosensitive resin is printed into a packaging shell by using a photo-curing process, namely the preparation of the photosensitive imaging unit is finished, and the packaging shell is preserved in a dark place after the preparation is finished.
The size of the individual cells in the gel layer of the pixel cell is 50 μm by 50 μm to 200 μm by 200 μm.
The corresponding relation between the proton concentration change of the gel material stored in the image reduction unit and the illumination intensity is determined through a pre-experiment, the specific determination method comprises the steps of constructing a calibrated photosensitive protein film which is the same as that of a photosensitive protein film of a biological imaging device, arranging gel layers which are the same as that of a pixel grid gel layer of the biological imaging device on two sides of the calibrated photosensitive protein film, packaging to form a pre-experiment calibration device, respectively irradiating light with different intensities to the pre-experiment calibration device, detecting the proton concentration change of the gel material in the gel layers, recording the proton concentration change of the gel material in the gel layers under different illumination intensities, and determining the corresponding relation between the two.
The packaging shell is formed by printing photosensitive resin with good biocompatibility through a photo-curing process, and the grid structure of the pixel grid gel layer is formed by printing PCL materials through a near-field electrospinning process.
Example 2
A biological imaging apparatus based on a photosensitive protein is provided, which includes a photosensitive imaging unit, an image reading unit, and an image reduction unit.
The photosensitive imaging unit comprises a photosensitive protein film, a pixel grid gel layer and a packaging shell. The photosensitive imaging unit is used for converting the light intensity information of the external target image into proton concentration information of gel materials in each grid of the gel layer of the pixel grid.
The photosensitive protein film is constructed by photosensitive protein with the function of CD-ROM proton pump. The pixel grid gel layer is a grid-like structure containing gel material, wherein each grid is one pixel in the biological imaging device. The pixel grid gel layers are arranged on two sides of the photosensitive protein film and used for providing proton sources for the photosensitive protein film and enabling the photosensitive protein film to play a role of a CD-ROM proton pump.
The image reading unit is used for detecting the proton concentration change generated by gel in each grid of the pixel grid gel layer of the photosensitive imaging unit under the light intensity information of the target image.
The image reduction unit is internally stored with a corresponding relation between the proton concentration change of the gel material and the illumination intensity, and is used for reducing the proton concentration change of the gel material in each grid of the pixel grid gel layer detected by the image reading unit into light intensity information at each grid, and then converting the light intensity information at the grid into gray information to obtain a target image.
In the imaging process of the biological imaging device, the photosensitive imaging unit is assembled into imaging equipment with a lens and a shutter in a dark way, a target image is projected onto the upper photosensitive imaging unit after passing through the lens and the shutter, and the light intensity information of the target image is converted into proton concentration information of gel materials in each grid of the pixel grid gel layer.
The photosensitive protein film also comprises a photosensitive performance enhancing material capable of enhancing the photoelectric response performance of the photosensitive protein film, wherein the photosensitive performance enhancing material is a material for enhancing the intensity or modulating the wave band of incident light and comprises a quantum dot material, a metal nanoparticle or an up-conversion material.
The photosensitive protein film is constructed by adopting an electrophoretic deposition method to prepare 10 layers of bacteriorhodopsin proteins, and the orientation of the bacteriorhodopsin proteins in the constructed photosensitive protein film is consistent.
The individual mesh sizes in the pixel mesh gel layer are 50 μm by 50 μm to 200 μm by 200 μm.
The corresponding relation between the proton concentration change of the gel material stored in the image reduction unit and the illumination intensity is determined through a pre-experiment, the specific determination method comprises the steps of constructing a calibrated photosensitive protein film which is the same as that of a photosensitive protein film of a biological imaging device, arranging gel layers which are the same as that of a pixel grid gel layer of the biological imaging device on two sides of the calibrated photosensitive protein film, packaging to form a pre-experiment calibration device, respectively irradiating light with different intensities to the pre-experiment calibration device, detecting the proton concentration change of the gel material in the gel layers, recording the proton concentration change of the gel material in the gel layers under different illumination intensities, and determining the corresponding relation between the two.
The packaging shell is formed by printing photosensitive resin with good biocompatibility through a photo-curing process, and the grid structure of the pixel grid gel layer is formed by printing PCL materials through a near-field electrospinning process.
Example 3
A biological imaging apparatus based on a photosensitive protein is provided, which includes a photosensitive imaging unit, an image reading unit, and an image reduction unit.
The photosensitive imaging unit comprises a photosensitive protein film, a pixel grid gel layer and a packaging shell. The photosensitive imaging unit is used for converting the light intensity information of the external target image into the ion concentration information of gel materials in each grid of the gel layer of the pixel grid.
The light sensitive protein film is constructed by light sensitive proteins with the function of light-driven ion channels.
The pixel grid gel layer is a grid-like structure containing gel material, wherein each grid is one pixel in the biological imaging device. The pixel grid gel layers are arranged on two sides of the photosensitive protein film and used for providing ion concentration difference for the photosensitive protein film and enabling the photosensitive protein film to play a role of an optical drive ion channel. Wherein the ion species and ion concentration differences in the pixel grid gel layer are dependent on the light sensitive protein species.
The image reading unit is used for detecting ion concentration changes generated by gel materials in each grid of the pixel grid gel layer of the photosensitive imaging unit under the light intensity information of the target image.
The image reduction unit is internally stored with a corresponding relation between the ion concentration change of the gel material and the illumination intensity, and is used for reducing the ion concentration change of the gel material in each grid of the pixel grid gel layer detected by the image reading unit into light intensity information at each grid, and then converting the light intensity information at the grid into gray information to obtain a target image.
The corresponding relation between the ion concentration change and the illumination intensity of the gel material stored in the image reduction unit is determined through a pre-experiment, the specific determination method comprises the steps of constructing a calibrated photosensitive protein film which is the same as that of a biological imaging device, arranging gel layers which are the same as that of a pixel grid gel layer of the biological imaging device in thickness and ion content on two sides of the calibrated photosensitive protein film, packaging to form a pre-experiment calibration device, respectively irradiating light with different intensities to the pre-experiment calibration device, recording the ion concentration change of the gel material in the gel layer under different illumination intensities, and determining the corresponding relation between the gel layer and the gel layer.
In the imaging process of the biological imaging device, the photosensitive imaging unit is assembled into imaging equipment with a lens and a shutter in a dark way, a target image is projected onto the upper photosensitive imaging unit after passing through the lens and the shutter, and the light intensity information of the target image is converted into the ion concentration information of gel materials in each grid of the gel layer of the pixel grid.
The construction mode of the photosensitive protein film is that 10 layers of photosensitive proteins are prepared by adopting an electrophoretic deposition method, and the orientation of the photosensitive proteins in the constructed photosensitive protein film is consistent.
The individual mesh sizes in the pixel mesh gel layer in this example are 50 μm by 50 μm to 200 μm by 200 μm.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (10)
1. A photosensitive protein-based biological imaging apparatus, comprising:
The imaging device comprises a photosensitive imaging unit, wherein the photosensitive imaging unit comprises a photosensitive protein film and two pixel grid gel layers respectively positioned at two sides of the photosensitive protein film, the photosensitive protein film comprises photosensitive proteins with an optical drive proton pump function, the pixel grid gel layers are of grid structures containing gel materials, the pixel grid gel layers provide proton sources for the photosensitive protein film, the photosensitive imaging unit is used for converting light intensity information of an external target image into proton concentration information of the gel materials in each grid of the pixel grid gel layers, each grid of the pixel grid gel layers is one pixel in the biological imaging device, the construction mode of the photosensitive protein film comprises at least one of Langmuir-Blodgett deposition method and electrophoresis deposition method, and the orientation of the photosensitive proteins is consistent;
An image reading unit for detecting proton concentration variation information of the gel material in each of the pixel grid gel layers, and
The image reduction unit is used for reducing the proton concentration change information of the gel material into light intensity information at each grid according to the corresponding relation information and converting the light intensity information at the grid into gray information to obtain a target image.
2. The photosensitive protein-based bioimaging device of claim 1, wherein said photosensitive protein comprises bacteriorhodopsin comprising at least one of wild-type bacteriorhodopsin and genetically edited photostability-enhancing bacteriorhodopsin.
3. The photosensitive protein-based bioimaging device of claim 1, wherein the mesh has a size of 50 μm by 50 μm to 200 μm by 200 μm.
4. The photoprotein-based biological imaging device of claim 1, wherein the photoprotein film further comprises a photoactive performance-enhancing material capable of enhancing the optoelectronic response properties of the photoprotein film, the photoactive performance-enhancing material being a material that intensity enhances or band modulates incident light, the photoactive performance-enhancing material comprising at least one of a quantum dot material, a metal nanoparticle, and an upconverting material.
5. The photosensitive protein-based bioimaging device of claim 4, wherein said photosensitive property enhancing material is bound to said photosensitive protein in a layer-by-layer or doped manner.
6. The photosensitive protein-based bioimaging apparatus of claim 1, wherein the specific determination method of correspondence information comprises:
Constructing a calibrated photosensitive protein film identical to the photosensitive protein film;
Gel layers with the same thickness and proton concentration as those of the gel layers of the pixel grid are arranged on two sides of the calibration photosensitive protein film to obtain a pre-experiment calibration device;
Respectively irradiating the pre-experiment calibration device with light of different intensities, detecting the change of the proton concentration of the gel material in the gel layer, and
Recording the proton concentration change of the gel material in the gel layer under different illumination intensities to determine the corresponding relation information of the proton concentration change of the gel material in the gel layer and the different illumination intensities.
7. The biological imaging apparatus of claim 1, further comprising an encapsulation housing for encapsulating the photosensitive protein film and the pixel grid gel layer, wherein the encapsulation housing is fabricated using additive manufacturing techniques, and/or
The fabrication technique of the grid structure in the pixel grid gel layer is an additive manufacturing technique.
8. A photosensitive protein-based biological imaging apparatus, comprising:
The imaging device comprises a photosensitive imaging unit, wherein the photosensitive imaging unit comprises a photosensitive protein film and two pixel grid gel layers respectively positioned at two sides of the photosensitive protein film, the photosensitive protein film comprises photosensitive proteins with an optical drive ion channel function, the pixel grid gel layers are of grid structures containing gel materials, the pixel grid gel layers provide ion concentration differences for the photosensitive protein film, the photosensitive imaging unit is used for converting light intensity information of an external target image into ion concentration information of the gel materials in each grid of the pixel grid gel layers, each grid of the pixel grid gel layers is one pixel in the biological imaging device, the construction mode of the photosensitive protein film comprises at least one of Langmuir-Blodgett deposition method and electrophoresis deposition method, and the orientation of the photosensitive proteins is consistent;
An image reading unit for detecting ion concentration variation information of the gel material in each of the pixel grid gel layers, and
The image reduction unit is used for reducing the ion concentration change information of the gel material into light intensity information at each grid according to the corresponding relation information and converting the light intensity information at the grid into gray information to obtain a target image.
9. The photosensitive protein-based bioimaging device of claim 8, wherein the specific determination method of correspondence information comprises:
Constructing a calibrated photosensitive protein film identical to the photosensitive protein film;
gel layers with the same thickness and ion content as those of the gel layers of the pixel grid are arranged on two sides of the calibration photosensitive protein film to obtain a pre-experiment calibration device;
respectively irradiating the pre-experiment calibration device with light of different intensities, detecting the ion concentration change of the gel material in the gel layer, and
And recording the ion concentration change of the gel material in the gel layer under different illumination intensities to determine the corresponding relation information of the ion concentration change of the gel material in the gel layer and the different illumination intensities.
10. The biological imaging apparatus of claim 8, further comprising an encapsulation housing for encapsulating the photosensitive protein film and the pixel grid gel layer, wherein the encapsulation housing is fabricated using additive manufacturing techniques, and/or
The fabrication technique of the grid structure in the pixel grid gel layer is an additive manufacturing technique.
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| US4965174A (en) * | 1986-10-08 | 1990-10-23 | Canon Kabushiki Kaisha | Recording medium and process for forming color image with use of the same |
| US5279932A (en) * | 1989-09-13 | 1994-01-18 | Fuji Photo Film Co., Ltd. | Optical response element |
| CN115294316A (en) * | 2022-06-15 | 2022-11-04 | 清华大学 | Photosensitive imaging device based on cell phase change and information storage method thereof |
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| JPH07117696B2 (en) * | 1987-03-20 | 1995-12-18 | キヤノン株式会社 | Recording medium and image forming method using the same |
| JP2632063B2 (en) * | 1990-03-02 | 1997-07-16 | 富士写真フイルム株式会社 | Color image light receiving element |
| CN1186688C (en) * | 2002-11-26 | 2005-01-26 | 西安交通大学 | Parallel photon logic and gate device based on bacterial rhodopsin molecular material |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4965174A (en) * | 1986-10-08 | 1990-10-23 | Canon Kabushiki Kaisha | Recording medium and process for forming color image with use of the same |
| US5279932A (en) * | 1989-09-13 | 1994-01-18 | Fuji Photo Film Co., Ltd. | Optical response element |
| CN115294316A (en) * | 2022-06-15 | 2022-11-04 | 清华大学 | Photosensitive imaging device based on cell phase change and information storage method thereof |
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