CN111263086A - Method for manufacturing cell fusion photoelectric sensor and working method of imaging system thereof - Google Patents

Abstract

The invention discloses a cell fusion photoelectric sensor and a working method of its imaging system. The manufacturing method of the cell-fused photoelectric sensor of the present invention includes: transfecting channelrhodopsin (ChR2) extracted from the eye spot of Chlamydomonas reinhardtii cells into human embryonic kidney 293 (Hek293, Human embryonic kidney) cells Finally, the expression of ChR2 plasmid in cells was observed by fluorescence microscope, and the results of cell expression were further verified by light stimulation with patch clamp technology; Hek293 cells expressing ChR2 were used as the sensitive material of the photoelectric sensor, which absorbed the light absorbed by the device. The signal is converted into ionic current, and the patch clamp technology is used as the signal acquisition and processing unit of the photoelectric sensor; the cell is combined with the patch clamp detection device to form a cell fusion photoelectric sensor. Beneficial effects of the present invention: The bio-integrated optoelectronic device can make full use of the organism's advantages in light perception or vision, thereby producing a new type of device with better performance than pure artificial devices.

Description

Fabrication method of cell fusion photoelectric sensor and working method of imaging system

technical field

The invention relates to the field of photoelectric sensors, in particular to a cell fusion photoelectric sensor and a working method of an imaging system thereof.

Background technique

Biological systems have evolved and developed over hundreds of millions of years in nature, and have many superior structural and functional characteristics that are unmatched by man-made systems. Integrating biological cells or tissues with electromechanical systems to construct bio-integrated systems can make full use of the structural and functional advantages of organisms, thereby creating some more complete structures and more powerful functional properties. At present, many biological fusion systems using living cells or tissues as driving or energy sources have been reported in many top international journals. Montemagno et al. at the University of California, Los Angeles, achieved free movement of the microdevice by culturing muscle cells in a micromechanical structure and assembling it into a microdevice driven and controlled by muscles [J.Xi, J.J.Schmidt, C.D.Montemagno, Nat.Mater. 2005, 4, 180.]; Parker et al. of Harvard University assembled mammalian cardiomyocytes on a microelectromechanical system (MEMS) to drive the motion of the micromechanical device [A.W.Feinberg, A.Feigel, S.S.Shevkoplyas, S.Sheehy, G.M. Whitesides, K.K. Parker, Science 2007, 317, 1366.]; Bashir et al. of the University of Illinois at Urbana-Champaign modified skeletal muscle cells with optogenetics and modulated the cell's telescopic properties by light to drive 3D-printed Movement of a micromechanical device that can move linearly at a distance of 310 um/s or 1.3 body lengths per minute [R.Raman,C.Cvetkovic,S.G.Uzel,R.J.Platt,P.Sengupta,R.D.Kamm,R. Bashir, Proc. Natl. Acad. Sci. USA. 2016, 113, 3497.]. In addition, some scholars have used the fusion of olfactory cells and epithelial tissues with electromechanical devices to construct biosensors to improve the sensitivity of the sensors [L.Du,C.Wu,H.Peng,L.Zhao,L.Huang,P.Wang,Biosens. Bioelectron. 2013, 40, 401.]; A bio-fusion sensor constructed with mammalian taste cells and taste buds can detect a variety of taste signals emitted by different stimuli [Q.Liu, D. Zhang, F. Zhang, Y. Zhao, K. J. Hsia, P. Wang, Sens. Actuators, B2013, 176, 497.]. These reports fully demonstrate that mammalian living cells or tissues can be used as very potential functional units to construct biological drives, biological sense of smell and taste. However, there is currently nothing about constructing bio-fused optoelectronic devices or photosensors with living cells or tissues, although mammalian photosensitive cells or tissues have many advantages over artificial photosensors or visual systems. For example, rod cells have sensory Ultra-high photoresponsivity of a single photon [D.A.Baylor, T.D.Lamb, K.W.Yau, J.Physiol.1979,288,613.], Rattlesnake achieves infrared perception with 1mm-sized cheek socket to capture prey [E.A.Newman,P.H.Hartline,Science 1981,213,789 .]. Using animal visual cells or photosensitive cells to construct photosensitive devices can effectively improve the photosensitive properties of the devices.

In addition, even if photosensitive cells are used to construct bio-fused optoelectronic devices, however, there is still an insurmountable problem to achieve high-resolution imaging with this device. In traditional imaging systems, high-resolution imaging is achieved by means of photosensitive element arrays such as CCD or CMOS, wherein each photosensitive element of the CCD or CMOS corresponds to one pixel of the obtained image. However, for this kind of bio-integrated optoelectronic device, the current technology is still difficult to manufacture the same optoelectronic device array as CCD or CMOS, and it has not been found that the traditional imaging system can achieve high-resolution imaging.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a cell-fused photoelectric sensor and a working method of its imaging system. For the first time, a living cell is used as a photosensitive unit to construct a biologically fused photoelectric sensor; for the current technology is difficult to realize the array of new photosensitive devices and For the problem that high-resolution imaging cannot be achieved, the present invention constructs a single-pixel imaging system based on a single bio-fusion photoelectric device to achieve high-resolution imaging.

In order to solve the above-mentioned technical problems, the present invention provides a method for manufacturing a photoelectric sensor of cell fusion, comprising: transfecting channelrhodopsin (ChR2) extracted from the eye spot of Chlamydomonas reinhardtii cells into human embryos Kidney 293 (Hek293, Human embryonic kidney) cells; observe the expression of ChR2 plasmid in cells, and use patch clamp technology to further verify the results of cell expression under light stimulation; Hek293 cells expressing ChR2 are used as sensitive materials for photoelectric sensors. The light signal absorbed by the device is converted into ionic current, and the patch clamp technology is used as the signal acquisition and processing unit of the photoelectric sensor; the cell is combined with the patch clamp detection device to form a cell fusion photoelectric sensor.

In one embodiment, the specific construction process of the human embryonic kidney 293 (Hek293, Human embryonic kidney) cells is: 1) using a proofreading polymerase (with BamHI and HindIII restriction enzymes) with a polymerase (pfu, Promega) The primers for the cut site), the full-length chop2-315 and the C-terminal truncated chop2 mutation were obtained from the full-length cDNA template (GenBank No.: AF461397) by PCR and made into a ChR2 plasmid; 2) Hek293 cells were cultured in In a ^9.6cm2 petri dish containing high glucose DMEM medium containing 10% fetal bovine serum and 1% double antibody, the petri dish was placed in an incubator at 37°C with 5% _CO2 , and the cells were 3) Use transfection reagent (Lipofectamine2000, Sigma) to transfect the ChR2 plasmid into Hek293 cells, and place them in a cell incubator for 24 hours; 4) Add to the culture dish 1 uM of cis-retinal (all-trans retinal, Sigma) and incubated in the incubator for 2 hours.

In one embodiment, the expression of the ChR2 plasmid in the cells is observed by fluorescence microscopy.

A working method of an imaging system based on a photoelectric sensor based on cell fusion. After the light passes through the target image, it is concentrated on the optical spatial modulator DMD through a first lens, and the corresponding micromirror in the DMD is controlled by a random binary image. Flip to control the light intensity reflected on the second lens, and focus on the bio-fused photoelectric sensor fabricated by any of the fabrication methods, and use patch clamp to detect the light response signal of the cell; finally, use the patch clamp to detect the signal The original image is reconstructed.

In one of the embodiments, the imaging method of the imaging system is based on the principle of compressed sensing, and a single photodetector realizes high-resolution imaging; the principle of compressed sensing can be described as: for an unknown signal x∈R ^N×1 , The linear observation value under the measurement matrix Φ∈R ^M×N (M<N) is y∈R ^M×1 , then:

y=Φx; (1)

Among them, the signal x must meet the sparsity condition, that is, only K (K<M) elements in the transformation domain of x or x are non-zero values; according to the sparsity of the signal x, find the most sparse solution from the solution satisfying Eq. , when the measurement matrix Φ satisfies the Restricted Isometric Property (RIP: (1-δ)||x|| ₂ ² ≤||Φx|| ₂ ² ≤(1+δ)||x|| ₂ ² ), the "sparsest" solution is the original signal x; in this system, based on the principle of compressed sensing, the spatial signal of the image is converted into a time series signal through DMD, and then the reconstructed image is obtained.

其中，j＝1,2,...,M，I_i(i＝1,2,3,...,N)在该微镜偏向二极管方向是为1,反之为0，而Dcoffset是所有微镜都偏离石墨烯器件方向的测量值；最后，通过从获得的采样信号v_i和测量矩阵Φ∈R^M×N重构出原始图像x。In one of the embodiments, the specific process of the compressed sensing principle is: 1) Assuming that the signal x to be obtained has a length of N, the measurement matrix Φ∈R ^M×N (M<N) is designed as a Bernoulli random matrix, where Each element is 1 or 0; 2) Map each row of the measurement matrix into a random binary image whose size is consistent with the size of the target image; 3) Control the inversion of the DMD with the random binary image in turn, and pass the film Patch clamp detects the ion current signal of cells after each flip, and the signal size can be expressed as

Among them, j=1,2,...,M, I _i (i=1,2,3,...,N) is 1 when the micromirror is deflected to the diode direction, otherwise it is 0, and Dcoffset is all The micromirrors are all deviated from the measured values of the graphene device orientation; finally, the original image x is reconstructed from the obtained sampled signal vi and the measurement matrix _Φ∈R ^M×N .

In one of the embodiments, the original image x is reconstructed from the obtained sampled signal v _i and the measurement matrix Φ∈R ^M×N by a compressive sensing reconstruction algorithm.

Based on the same inventive concept, the present application also provides a computer device, including a memory, a processor, and a computer program stored in the memory and running on the processor, the processor implements any one of the above when executing the program. steps of the method described.

Based on the same inventive concept, the present application also provides a computer-readable storage medium on which a computer program is stored, and when the program is executed by a processor, implements the steps of any one of the methods.

Based on the same inventive concept, the present application also provides a processor for running a program, wherein the program executes any one of the methods when the program runs.

Beneficial effects of the present invention:

The sensor uses photosensitive living cells as photosensitive elements. This bio-fused optoelectronic device can make full use of the organism's advantages in light perception or vision, resulting in new devices with better performance than pure artificial devices. For example, the cell fusion The photosensors have good light adaptability and higher saturation; in addition, the constructed imaging system realizes high-resolution imaging of macroscopic objects for the first time with cell-fused photosensors.

Description of drawings

FIG. 1 is a schematic diagram of the construction of the photoelectric sensor for cell fusion of the present invention.

FIG. 2 is a schematic structural diagram of the imaging system of the photoelectric sensor for cell fusion of the present invention.

FIG. 3 is a schematic diagram of the imaging result in the present invention. Among them, A～E, target image; F～J, cell fusion photodetector imaging result.

FIG. 4 is a comparison between the imaging results of the cell fusion photodetector in the present invention and the imaging results of a commercial photodetector.

Detailed ways

The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

The invention provides a photoelectric sensor for cell fusion and an imaging system thereof. The photoelectric sensor construction process for cell fusion is shown in Figure 1. The channelrhodopsin protein (ChR2) extracted from the eye spot of Chlamydomonas reinhardtii cells was transfected into human embryonic kidney 293 (Hek293, Human embryonic kidney) cells, which have good photosensitivity and can pass through the membrane. The patch-clamp technique can detect the light-responsive properties of cells. The specific construction process of the photosensitive cell is: 1) Using a proofreading polymerase with a polymerase (pfu, Promega) (primers with BamHI and HindIII restriction sites), a full-length cDNA template (GenBank No. : AF461397) to obtain full-length chop2-315 and C-terminal truncated chop2 mutation and make it into a ChR2 plasmid; ² ) to culture Hek293 cells in a 9.6 cm dish containing 10% fetal bovine serum and 1 % double-antibody high-glucose DMEM medium, and place the culture dish in an incubator at 37°C with 5% CO ₂ until the cells reach 1/2 of the culture dish; 3) Use transfection reagent (Lipofectamine 2000, Sigma) The ChR2 plasmid was transfected into Hek293 cells and placed in a cell incubator for 24 hours; 4) 1uM cis-retinal (all-trans retinal, Sigma) was added to the culture dish, and incubated in the incubator for 2 hours. Finally, the expression of ChR2 plasmid in cells was observed by fluorescence microscope, and the results of cell expression were further verified by light stimulation with patch clamp technique. Hek293 cells expressing ChR2 are used as the sensitive material of the photoelectric sensor, which converts the light signal absorbed by the device into ionic current, and the patch clamp technology is used as the signal acquisition and processing unit of the photoelectric sensor. The cells were combined with a patch-clamp detection device to form a photoelectric sensor for cell fusion.

The structure of the single-pixel imaging system based on the cell fusion photodetector is shown in Figure 2. After the light passes through the target image, it converges on the optical spatial modulator DMD through the first lens, and controls the flip of each corresponding micromirror in the DMD through the random binary image to control the light intensity reflected on the second lens, and converges Photoelectric sensors for biofusion, while using patch clamp to detect the light response signal of cells. Finally, the signal detected by the patch clamp is reconstructed from the original image by an optimized algorithm.

The imaging method is based on the principle of compressed sensing to achieve high-resolution imaging with a single photodetector. The principle of compressed sensing can be described as: for an unknown signal x∈R ^N×1 , the linear observation value under the measurement matrix Φ∈R ^M×N (M<N) is y∈R ^M×1 , then:

y=Φx. (1)

其中，j＝1,2,...,M，I_i(i＝1,2,3,...,N)在该微镜偏向二极管方向是为1,反之为0，而Dcoffset是所有微镜都偏离石墨烯器件方向的测量值；最后，通过压缩感知重构算法从获得的采样信号v_i和测量矩阵Φ∈R^M×N重构出原始图像x。Among them, the signal x must satisfy the sparsity condition, that is, only K (K<M) elements in the transformation domain of x or x are non-zero values. According to linear algebra theory, equation (1) has infinitely many solutions, and the original signal x cannot be uniquely determined from the observed value y. However, according to the sparsity of the signal x, find the most sparse solution from the solutions satisfying Eq. (1), when the measurement matrix Φ satisfies the Restricted Isometric Property (RIP: (1-δ)||x| | ₂ ² ≤||Φx|| ₂ ² ≤(1+δ)||x|| ₂ ² ), the “sparsest” solution is the original signal x. In this system, based on the principle of compressed sensing, the spatial signal of the image is converted into a time series signal by DMD, and then the reconstructed image is obtained through the optimization algorithm, and the image can be consistent with the original image information with a very high probability. The specific process is: 1) Assuming that the signal x to be obtained is of length N, the measurement matrix Φ∈R ^M×N (M<N) is designed as a Bernoulli random matrix, in which each element is 1 or 0; 2 ) Map each row of the measurement matrix into a random binary image whose size is consistent with the size of the target image; 3) Control the inversion of the DMD with the random binary image in turn, and detect the ions of the cells after each inversion by patch clamp The current signal, its signal size can be expressed as

Among them, j=1,2,...,M, I _i (i=1,2,3,...,N) is 1 when the micromirror is deflected to the diode direction, otherwise it is 0, and Dcoffset is all The micromirrors are all deviated from the measured value of the graphene device direction; finally, the original image x is reconstructed from the obtained sampled signal vi and the measurement matrix _Φ∈R ^M×N by the compressive sensing reconstruction algorithm.

A specific application scenario of the present invention is introduced below:

The premise of making photodetectors for cell fusion lies in the construction of light-sensitive cells. The ChR2 plasmid was transfected into Hek293 cells with transfection reagent (Lipofectamine 2000), wherein the ratio of ChR2 plasmid to medium (high glucose DMEM) was 8ug:0.5mL, and the ratio of Lipofectamine to medium was 20uL:0.5mL. The transfected Hek293 cells were placed at 37°C in an incubator with a concentration of 5% CO2 for 24 hours, and cis-retinal was added according to the ratio of cis-retinal and medium to 1uL: 1mL, and incubated for 2 hours. Used to build cell fusion biosensors as a child.

To analyze the light response characteristics of photosensitive cells with a patch clamp device, it is necessary to ensure the osmotic pressure inside and outside the cells and maintain the cell activity for a long time. Therefore, the solution inside and outside the glass tube of the patch clamp needs to use a liquid that simulates the physiological environment. The specific configuration of the extracellular solution is: 140 mM NaCl, 1 mM CaCl2, 2 mM MgCl2 and 10 mM HEPES, and the pH of the solution is adjusted to 7.4 (room temperature) with NaOH; the specific configuration of the intracellular solution is: 140 mM NaCl , 5mM EGTA, 2mM MgCl2 and 10mM HEPES, and adjusted the pH of the solution to 7.4 (room temperature) with NaOH. In addition, before measuring the cell photocurrent, the cells were digested and made into a suspension, and the cells were fixed on a glass slide with polylysine, and then incubated in a cell incubator for about 2 hours. Finally, place the slide in a petri dish containing the extracellular solution and place it on the patch clamp stage. The incident light of the imaging system is adjusted, and the photoresponse characteristics of the photosensitive cells are detected. Using patch clamp to detect cell ion current mode is to record whole cell current under voltage clamp, glass tube is borosilicate glass capillary, inner diameter is 0.5mm and outer diameter is 1mm. . The sampling frequency is 10kHz, and the sampled data is processed with 2kHz low-pass filtering. The sealing resistance must be higher than 1GΩ, while compensating for liquid level resistance and capacitance to ensure the accuracy and precision of cell ion current sampling.

The DMD module directly uses the Discovery series of DLP chips. The DMD type is a 0.7-inch VGA series, including 1024×768 digital micromirrors, each with a side length of 13.7μm, suitable for all wavelengths from ultraviolet to near-infrared. The control board refresh rate can be up to 290Hz. Each micromirror can be flipped 12° to both sides along the diagonal of the micromirror, and is controlled by the input response value. When the input at this position is 1, the micromirror is flipped 12° in one direction; when the input at this position is 0, the micromirror is flipped 12° in the other direction. All the micromirrors of the entire DMD can be controlled simultaneously with a random binary image of 1024×768 pixels, and the pixels of the image correspond to the micromirrors of the DMD one-to-one.

The light source uses a laser with a wavelength of 375 nm to ensure the linearity of the light. And use a 10x beam expander to increase the diameter of the exit pupil to ensure that the light can cover the DMD.

During the imaging process, the DMD is irradiated with a constant light intensity, and the corresponding random binary images are used to control the DMD to flip at a speed of 100ms period, wherein the DMD is flipped according to the corresponding image for a dwell time of 10ms. For the photosensitive cells in this example, under the stimulation of 10ms light pulses, the entire process duration of the cell ion current from being activated to inactivating is about 77ms. In order to ensure the stability and accuracy of the optical response signal detected each time, the DMD turnover period should be greater than 77ms.

Taking the character patterns in Figs. 3A to E as target images, imaging tests were performed on them in turn. The imaging results are shown in Figures 3F–J. The reconstructed graphics have a resolution of 50×50 and a sampling rate of 30%. The measurement matrix is designed as a 750×2500 Bernoulli matrix, in which each element is randomly set to 1 or 0. Each row of the measurement matrix is converted into a 50 × 50 pattern matrix ( ), which is then scaled up to 1000 × 700 matr i x ( ) to control the central area of the DMD, and the data corresponding to the remaining micromirrors around the DMD are supplemented with 0 , and finally, generate the corresponding 1024×768 random binary image. Then, the patch-clamped data and measurement matrix are used to generate reconstructed images through the orthogonal matching pursuit algorithm (Fig. 3F-J).

In order to observe the imaging effect of the cell fusion photodetector more intuitively, a commercial photodiode was used as the photosensitive element of the imaging system to image the pattern of the character "I". The results are shown in Figure 4. In this example, the light source powers were set to 0.8 mW and 8 mW, respectively, and two kinds of detectors were used to image separately under the same conditions. From the results in Figure 4, it can be seen that at low optical power, both optoelectronic devices can clearly reproduce the information of the target image; while at high optical power (8mW), the photodiode can no longer image, and the cell fusion The photodetector can still reproduce the target shape relatively clearly. In this embodiment, the advantages of bio-fusion sensors over artificial devices are preliminarily highlighted.

The working method of the photoelectric sensor for cell fusion and its imaging system provided by the present invention has been described in detail above, and the following points need to be explained:

The invention provides a single-pixel imaging system based on a bio-fusion photoelectric sensor, which is characterized by comprising: a light source, a target image, a first lens, a DMD, a second lens, a cell fusion photoelectric sensor and a computer. After the light emitted by the light source is projected through the target image, it is concentrated on the DMD through the first lens, and then reflected by the DMD and then concentrated on the photosensitive cells of the photoelectric sensor through the second lens. The photoelectric signals of the photosensitive cells are collected by the patch clamp and transmitted to The computer reproduces the reconstructed image through an optimized algorithm.

Cell fusion photosensors include photosensitive cells and patch clamp tools. The photosensitive cells are composed of human embryonic cells (Hek293) modified with channelrhodopsin (ChR2) using optogenetic tools.

The glass tube of the patch clamp is a borosilicate glass capillary with an inner diameter of 0.5 mm and an outer diameter of 1 mm. After the glass tube is drawn and manufactured, the resistance of the glass tube into liquid is 3.5-5MΩ. The photocurrent of photosensitive cells was recorded in whole-cell mode to increase the cell's response amplitude.

其中，j＝1,2,...,M，I_i(i＝1,2,3,...,N)在该微镜偏向二极管方向是为1,反之为0，而Dcoffset是所有微镜都偏离石墨烯器件方向的测量值；最后，通过压缩感知重构算法从获得的采样信号v_i和测量矩阵Φ∈R^M×N重构出原始图像x。Single-pixel imaging is based on the principle of compressed sensing. The specific imaging process is as follows: 1) Assuming that the signal x to be obtained is of length N, the measurement matrix Φ∈R ^M×N (M<N) is designed as a Bernoulli random matrix, in which each The bit elements are all 1 or 0; 2) Map each row of the measurement matrix into a random binary image whose size is consistent with the size of the target image; 3) Use the random binary image to control the inversion of the DMD in turn, and pass the diaphragm The clamp detects the ionic current signal of the cells after each flip, and the signal size can be expressed as

Among them, j=1,2,...,M, I _i (i=1,2,3,...,N) is 1 when the micromirror is deflected to the diode direction, otherwise it is 0, and Dcoffset is all The micromirrors are all deviated from the measured value of the graphene device direction; finally, the original image x is reconstructed from the obtained sampled signal vi and the measurement matrix _Φ∈R ^M×N by the compressive sensing reconstruction algorithm.

The computer is used to generate measurement matrices, random binary images, patch clamp control software, DMD control software, store and process patch clamp sampling data and reconstruct images.

The above-mentioned embodiments are only preferred embodiments for fully illustrating the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or transformations made by those skilled in the art on the basis of the present invention are all within the protection scope of the present invention. The protection scope of the present invention is subject to the claims.

Claims (10)

1. the manufacture method of the photoelectric sensor of a kind of cell fusion, is characterized in that, comprises: the channelrhodopsin (ChR2) extracted at Chlamydomonas reinhardtii cell eye spot (Eye spot) place is transfected into human embryonic kidney 293 (Hek293 , Humanembryonic kidney) cells; observed the expression of ChR2 plasmid in cells, and further verified the results of cell expression by light stimulation with patch clamp technology; Hek293 cells expressing ChR2 were used as sensitive materials for photoelectric sensors, which absorbed the light absorbed by the device. The signal is converted into ionic current, and the patch clamp technology is used as the signal acquisition and processing unit of the photoelectric sensor; the cell is combined with the patch clamp detection device to form a cell fusion photoelectric sensor. 2. the manufacture method of the photoelectric sensor of cell fusion as claimed in claim 1, is characterized in that, the concrete construction process of this human embryonic kidney 293 (Hek293, Human embryonic kidney) cell is: 1) use with polymerase (pfu, Promega) proofreading polymerase (primers with BamHI and HindIII restriction sites), full-length chop2-315 and C-terminal truncated chop2 mutations were obtained by PCR from a full-length cDNA template (GenBank No.: AF461397), And make it into a ChR2 plasmid; 2) Culture Hek293 cells in a 9.6cm ² petri dish containing 10% fetal bovine serum and 1% double antibody in high glucose DMEM medium, and place the petri dish at 37°C , in an incubator containing 5% CO ₂ , wait until the cells reach 1/2 of the culture dish; 3) Use transfection reagent (Lipofectamine 2000, Sigma) to transfect the ChR2 plasmid into Hek293 cells, and place Incubate for 24 hours in a cell culture incubator; 4) Add 1 uM of cis-retinal (all-trans retinal, Sigma) to the dish and incubate for 2 hours in the incubator. 3 . The method for producing a cell-fused photoelectric sensor according to claim 1 , wherein the expression of the ChR2 plasmid in the cells is observed by a fluorescence microscope. 4 . 4. A working method of an imaging system based on a photoelectric sensor based on cell fusion, characterized in that, after the light passes through the target image, it is converged on the optical spatial modulator DMD through the first lens, and the corresponding images in the DMD are controlled by random binary images. Each micromirror is flipped to control the light intensity reflected on the second lens, and converges on the bio-fused photoelectric sensor fabricated by the fabrication method of any one of claims 1 to 3, while using patch clamps to detect the light response of cells signal; finally, the original image is reconstructed using the signal detected by the patch clamp. 5. The working method of an imaging system based on a photoelectric sensor based on cell fusion according to claim 4, wherein, the imaging method of the imaging system is based on the principle of compressed sensing, and realizes high-resolution imaging with a single photodetector ; The principle of compressed sensing can be described as: for an unknown signal x∈R ^N×1 , the linear observation value under the measurement matrix Φ∈R ^M×N (M<N) is y∈R ^M×1 , then: y=Φx; (1) Among them, the signal x must meet the sparsity condition, that is, only K (K<M) elements in the transformation domain of x or x are non-zero values; according to the sparsity of the signal x, find the most sparse solution from the solution satisfying Eq. , when the measurement matrix Φ satisfies the Restricted Isometric Property (RIP: (1-δ)||x|| ₂ ² ≤||Φx|| ₂ ² ≤(1+δ)||x|| ₂ ² ), the "sparsest" solution is the original signal x; in this system, based on the principle of compressed sensing, the spatial signal of the image is converted into a time series signal through DMD, and then the reconstructed image is obtained. 6. the working method of the imaging system of the photoelectric sensor based on cell fusion as claimed in claim 5, is characterized in that, the concrete process of compressed sensing principle is: 1) suppose the signal x to be obtained, the length is N, the measurement matrix Φ ∈R ^M×N (M<N) is designed as a Bernoulli random matrix, in which each element is 1 or 0; 2) Map each row of the measurement matrix into a random binary image whose size is the same as that of the target image. 3) Control the inversion of the DMD with random binary images in turn, and detect the ionic current signal of the cells after each inversion by patch clamp, and the signal size can be expressed as

Among them, j=1,2,...,M, I _i (i=1,2,3,...,N) is 1 when the micromirror is deflected to the diode direction, otherwise it is 0, and Dcoffset is all The micromirrors are all deviated from the measured values of the graphene device orientation; finally, the original image x is reconstructed from the obtained sampled signal vi and the measurement matrix _Φ∈R ^M×N . 7. The working method of the photoelectric sensor imaging system based on cell fusion as claimed in claim 6, characterized in that, reconstructed from the obtained sampling signal v _i and the measurement matrix Φ∈R ^M×N by the compressive sensing reconstruction algorithm out the original image x. 8. A computer device comprising a memory, a processor and a computer program stored on the memory and running on the processor, wherein the processor implements any one of claims 1 to 7 when executing the program the steps of the method. 9. A computer-readable storage medium on which a computer program is stored, characterized in that, when the program is executed by a processor, the steps of the method according to any one of claims 1 to 7 are implemented. 10. A processor, wherein the processor is used to run a program, wherein the method of any one of claims 1 to 7 is executed when the program is run.

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