CN111263086A

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

Info

Publication number: CN111263086A
Application number: CN202010085432.2A
Authority: CN
Inventors: 李恭新
Original assignee: Jiangnan University
Current assignee: Jiangnan University
Priority date: 2020-02-10
Filing date: 2020-02-10
Publication date: 2020-06-09

Abstract

The invention discloses a cell fusion photoelectric sensor and a working method of an imaging system thereof. The invention relates to a method for manufacturing a cell fusion photoelectric sensor, which comprises the following steps: transfecting the rhodopsin channel protein (ChR2) extracted from Chlamydomonas reinhardtii cell eyespot (Eye spot) into Human embryonic kidney 293(Hek293, Human embryo kidney) cells; finally, the expression of the ChR2 plasmid in the cells is observed by a fluorescence microscope, and the cell expression result is further verified by the patch clamp technology in light stimulation; hek293 cells expressing ChR2 are used as sensitive materials of the photoelectric sensor, optical signals absorbed by the device are converted into ion current, and the signal acquisition and processing unit of the photoelectric sensor is used as a patch clamp technology; the cell is combined with a patch clamp detection device to form a cell fusion photoelectric sensor. The invention has the beneficial effects that: the bio-fused photoelectric device can fully utilize the advantages of organisms on light perception or vision, thereby generating a novel device with better performance than a pure artificial device.

Description

Method for manufacturing cell fusion photoelectric sensor and working method of imaging system thereof

Technical Field

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

Background

The evolution and development of biological systems over the years of nature has had many advantageous structural and functional properties not comparable to man-made systems. The biological cell or tissue and the electromechanical system are fused to construct the living-mechanical fusion system, so that the structural and functional advantages of the organism can be fully utilized, and a plurality of more complete structures and stronger functional characteristics are created. At present, many bioorganic fusion systems using living biological cells or tissues as driving or energy sources are reported in many publications in the world. Montemagno et al, university of california, los angeles, assembled into a muscle-driven and controlled microdevice by culturing muscle cells in a micromechanical structure to achieve free motion of the microdevice [ j.xi, j.j.schmidt, c.d.montemagno, nat. mater.2005,4,180 ]; parker et al, harvard university, assemble mammalian cardiomyocytes on micro-electro-mechanical systems (MEMS) to drive movement of a 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, university of illinois, ebana-champagne, modify skeletal muscle cells using optogenetic techniques and by photomodulation of the contractile properties of the cells to drive the motion of 3D printed micromechanical devices that can move linearly over distances of up to 310um/s or 1.3 body lengths per minute [ r.raman, c.cvettkovic, s.g.uzel, r.j.platt, p.senguta, r.d.kamm, r.bashir, proc.natl.acad.sci.usa.2016,113,3497 ]. In addition, there are also scholars who construct biosensors using fusion of olfactory cells and epithelial tissues with electromechanical devices to improve the sensitivity of the sensors [ l.du, c.wu, h.peng, l.zhao, l.huang, p.wang, biosens.bioelectrron.2013, 40,401 ]; the biological fusion sensor constructed by using taste cells and taste buds of mammals can detect various taste signals emitted by different stimulators [ Q.Liu, D.Zhang, F.Zhang, Y.ZHao, K.J.Hsia, P.Wang, Sens.Actuators, B2013,176,497 ]. These reports fully demonstrate that living cells or tissues of mammals can serve as very potential functional units for the construction of biological drivers, biological olfaction and taste, etc. However, there is currently no discussion of constructing a biosusion optoelectronic device or photosensor with living cells or tissues, although mammalian photosensitive cells or tissues have many advantages over artificial photosensitive devices or visual systems, for example, rod cells have an ultra-high light responsivity to sense single photons [ d.a.baylor, t.d.lamb, k.w.yau, j.physiol.1979,288,613 ], and the bungarus snake uses a 1mm sized buccal cavity to achieve infrared sensing capture [ e.a.newman, p.h.hartline, Science 1981,213,789 ]. The photosensitive device is constructed by using animal visual cells or photosensitive cells, so that the photosensitive characteristic of the device can be effectively improved.

In addition, even if the photovoltaics for biological fusion are constructed by using photosensitive cells, the problem that high-resolution imaging is not possible to be realized by using the photovoltaics still exists. In conventional imaging systems, high resolution imaging is achieved by means of an array of photosensitive elements, such as a CCD or CMOS, each of which corresponds to a pixel of the acquired image. However, for such bio-fused optoelectronic devices, it is difficult to fabricate an optoelectronic device array like a CCD or a CMOS by the current technology, and it is not found that the conventional imaging system can achieve high resolution imaging.

Disclosure of Invention

The invention aims to solve the technical problem of providing a cell fusion photoelectric sensor and a working method of an imaging system thereof, wherein a biological fusion photoelectric sensor is constructed by taking living cells as photosensitive units for the first time; aiming at the problem that the prior art is difficult to realize the array of novel photosensitive devices and cannot realize high-resolution imaging, the invention constructs a single-pixel imaging system based on a single biological fusion photoelectric device and realizes high-resolution imaging.

In order to solve the above technical problems, the present invention provides a method for manufacturing a cell fusion photosensor, comprising: transfecting the rhodopsin channel protein (ChR2) extracted from Chlamydomonas reinhardtii cell eyespot (Eye spot) into Human embryonic kidney 293(Hek293, Human embryo kidney) cells; observing the expression of the ChR2 plasmid in the cells, and further verifying the cell expression result by using a patch clamp technology in light stimulation; hek293 cells expressing ChR2 are used as sensitive materials of the photoelectric sensor, optical signals absorbed by the device are converted into ion current, and the signal acquisition and processing unit of the photoelectric sensor is used as a patch clamp technology; the cell is combined with a 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 embryo kidney) cell is as follows: 1) a proofreading polymerase (primers with BamHI and HindIII restriction sites) with polymerase (pfu, Promega) was used to generate a full-length cDNA template (GenBank No.: AF461397) to obtain full-length chop2-315 and C-terminally truncated chop2 mutations and make them into ChR2 plasmid; 2) hek293 cells were cultured at 9.6cm²The culture dish of (1), which contains 10% fetal bovine serum and 1% double antibody high-sugar DMEM medium, is placed at 37 ℃ and contains 5% CO₂When the cells grow to be full of 1/2 in the culture dish, the cells are ready for use; 3) the ChR2 plasmid was transfected into Hek293 cells using transfection reagent (Lipofectamine2000, Sigma) and placed in a cell incubator for 24 hours; 4) 1uM of cis-retinal (all-trans retinal, Sigma) was added to the dish and incubated for 2 hours in the incubator.

In one example, the expression of the ChR2 plasmid in cells was observed by fluorescence microscopy.

A work method of an imaging system of a photoelectric sensor based on cell fusion is characterized in that light is converged on a light space modulator (DMD) through a first lens after passing through a target image, the light intensity reflected to a second lens is controlled by controlling the overturning of each corresponding micromirror in the DMD through a random binary image, and is converged on the photoelectric sensor of the biological fusion manufactured by any manufacturing method, and meanwhile, a patch clamp is used for detecting a light response signal of a cell; and finally, reconstructing an original image by using the signals detected by the patch clamp.

In one embodiment, the imaging method of the imaging system is based on the compressed sensing principle, and high-resolution imaging is realized by a single photoelectric detector; the compressed sensing principle can be described as: for some unknown signal x ∈ R^N×1In the measurement matrix phi ∈ R^M×NThe linear observed value under (M < N) is y ∈ R^M×1Then, there are:

y＝Φx； (1)

wherein the signal x must satisfy a sparsity condition, i.e. x or x conversionOnly K (K < M) elements in the domain are nonzero values; according to the sparsity of the signal x, the most sparse is found out from the solution satisfying the formula (1), when the measurement matrix phi satisfies the Restricted Isometry Property (RIP (1-delta) | x | |₂ ²≤||Φx||₂ ²≤(1+δ)||x||₂ ²) This "sparsest" solution is then the original signal x; in this system, a spatial signal of an image is converted into a time-series signal by the DMD based on the compressed sensing principle, and then a reconstructed image is obtained.

In one embodiment, the compressed sensing principle is specifically performed as follows: 1) assuming a signal x to be obtained of length N, the measurement matrix Φ ∈ R^M×N(M < N) is designed as a Bernoulli random matrix, wherein each element is 1 or 0; 2) mapping each row of the measurement matrix into a random binary image, wherein the size of the image is consistent with the size of a target image; 3) the random binary image is used for controlling the turnover of the DMD in sequence, and the ion current signal of the cell after each turnover is detected through patch clamp, wherein the signal magnitude can be expressed as

Wherein j is 1,2_i(i 1,2, 3.., N) is 1 in the direction of the micromirror toward the diode, and vice versa is 0, and Dcoffset is a measure of the deviation of all micromirrors from the direction of the graphene device; finally, by sampling the signal v from the obtained sample_iAnd the measurement matrix phi ∈ R^M×NThe original image x is reconstructed.

In one of the embodiments, the sampled signal v obtained is reconstructed by a compressed perceptual reconstruction algorithm_iAnd the measurement matrix phi ∈ R^M×NThe original image x is reconstructed.

Based on the same inventive concept, the present application also provides a computer device comprising a memory, a processor and a computer program stored on the memory and executable on the processor, the processor implementing the steps of any of the methods when executing the program.

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

Based on the same inventive concept, the present application further provides a processor for executing a program, wherein the program executes to perform any one of the methods.

The invention has the beneficial effects that:

the sensor uses photosensitive living cells as photosensitive elements, and the biological fused photoelectric device can fully utilize the advantages of organisms on light perception or vision, thereby generating a novel device with better performance than a pure artificial device, for example, the cell fused photoelectric sensor has good light adaptability and higher saturation; in addition, the constructed imaging system realizes high-resolution imaging of a macroscopic object by using the cell-fused photoelectric sensor for the first time.

Drawings

FIG. 1 is a schematic diagram of the construction of a cell fusion photosensor according to the present invention.

FIG. 2 is a schematic diagram of an imaging system of the cell-fused photosensor of the present invention.

Fig. 3 is a schematic view of the imaging result in the present invention. A to E, target images; f to J, and imaging results of the cell fusion photoelectric detector.

FIG. 4 is a comparison of the imaging of the cell fusion photodetector of the present invention with that of a commercial photodetector.

Detailed Description

The present invention is further described below in conjunction with the following figures and specific examples so that those skilled in the art may better understand the present invention and practice it, but the examples are not intended to limit the present invention.

The invention provides a cell fusion photoelectric sensor and an imaging system thereof. The construction process of the cell fusion photoelectric sensor is shown in FIG. 1. The rhodopsin channel protein (ChR2) extracted from Chlamydomonas reinhardtii cell eyespot (Eye spot) was transfected into Human embryonic kidney 293(Hek293, Human embryo Kidney) cells, which had good photosensitizing properties and were prepared by patch clampThe technology is capable of detecting the photoresponsive properties of cells. The specific construction process of the photosensitive cell is as follows: 1) a proofreading polymerase (primers with BamHI and HindIII restriction sites) with polymerase (pfu, Promega) was used to generate a full-length cDNA template (GenBank No.: AF461397) to obtain full-length chop2-315 and C-terminally truncated chop2 mutations and make them into ChR2 plasmid; 2) hek293 cells were cultured at 9.6cm²The culture dish of (1), which contains 10% fetal bovine serum and 1% double antibody high-sugar DMEM medium, is placed at 37 ℃ and contains 5% CO₂When the cells grow to be full of 1/2 in the culture dish, the cells are ready for use; 3) the ChR2 plasmid was transfected into Hek293 cells using transfection reagent (Lipofectamine2000, Sigma) and placed in a cell incubator for 24 hours; 4) 1uM of cis-retinal (all-trans retinal, Sigma) was added to the dish and incubated for 2 hours in the incubator. Finally, the expression of the ChR2 plasmid in the cells was observed by fluorescence microscopy and the cell expression was further verified by patch-clamp technique in light stimulation. Hek293 cells expressing ChR2 are used as sensitive materials of the photoelectric sensor, optical signals absorbed by the device are converted into ion currents, and the signal acquisition and processing unit of the photoelectric sensor is used in a patch clamp technology. The cell is combined with a patch clamp detection device to form a cell fusion photoelectric sensor.

The structure of a single-pixel imaging system based on the cell fusion photodetector is shown in FIG. 2. After light penetrates through a target image, the light is converged on a light space modulator (DMD) through a first lens, the light intensity reflected to the second lens is controlled by controlling the overturning of each corresponding micromirror in the DMD through a random binary image, the light is converged on a biological fusion photoelectric sensor, and meanwhile, a light response signal of a cell is detected by using a patch clamp. And finally, reconstructing an original image by the signals detected by the patch clamp through an optimization algorithm.

The imaging method is based on the compressed sensing principle, and high-resolution imaging is realized by a single photoelectric detector. The compressed sensing principle can be described as: for some unknown signal x ∈ R^N×1In the measurement matrix phi ∈ R^M×NThe linear observed value under (M < N) is y ∈ R^M×1Then, there are:

y＝Φx。 (1)

where the signal x must satisfy the sparsity condition, i.e., only K (K < M) elements in the x or x transform domain are non-zero. As can be seen from linear algebraic theory, equation (1) has an infinite number of solutions, and the original signal x cannot be uniquely determined from the observed value y. However, according to the sparsity of the signal x, the most sparse is found from the solution satisfying equation (1), when the measurement matrix Φ satisfies the restrictive Isometry Property (RIP (1- δ) | x | |₂ ²≤||Φx||₂ ²≤(1+δ)||x||₂ ²) This "sparsest" solution is then the original signal x. In this system, a spatial signal of an image is converted into a time-series signal by a DMD based on a compressed sensing principle, and then, a reconstructed image, which can be consistent with original image information with a very high probability, is obtained by an optimization algorithm. The specific process is as follows: 1) assuming a signal x to be obtained of length N, the measurement matrix Φ ∈ R^M×N(M < N) is designed as a Bernoulli random matrix, wherein each element is 1 or 0; 2) mapping each row of the measurement matrix into a random binary image, wherein the size of the image is consistent with the size of a target image; 3) the random binary image is used for controlling the turnover of the DMD in sequence, and the ion current signal of the cell after each turnover is detected through patch clamp, wherein the signal magnitude can be expressed as

Wherein j is 1,2_i(i 1,2, 3.., N) is 1 in the direction of the micromirror toward the diode, and vice versa is 0, and Dcoffset is a measure of the deviation of all micromirrors from the direction of the graphene device; finally, the sampled signal v obtained is reconstructed by a compressed sensing reconstruction algorithm_iAnd the measurement matrix phi ∈ R^M×NThe original image x is reconstructed.

The following describes a specific application scenario of the present invention:

the fabrication of a cell fused photodetector is premised on the construction of a light sensitive cell. The ChR2 plasmid was transfected into Hek293 cells with transfection reagent (Lipofectamine 2000), where the ratio of ChR2 plasmid to medium (high-glucose DMEM) was 8 ug: 0.5mL, the ratio of Lipofectamine to medium was 20 uL: 0.5 mL. Transfected Hek293 cells were incubated at 37 ℃ for 24 hours in an incubator containing 5% CO2 concentration in a mixture of 1uL of cis-retinal: cis-retinal was added at a rate of 1mL and incubated for 2 hours for construction of a cell fusion biosensor.

The light response characteristic of the photosensitive cells is analyzed by using a patch clamp device, and the osmotic pressure inside and outside the cells needs to be ensured and the activity of the cells needs to be maintained for a long time, so that the solution inside and outside the glass tube of the patch clamp needs to be liquid simulating the physiological environment. The specific configuration of the extracellular solution is as follows: 140mM NaCl, 1mM CaCl2, 2mM MgCl2 and 10mM HEPES, and adjusting the pH of the solution to 7.4 (room temperature) with NaOH; the specific configuration of the intracellular solution is as follows: 140mM NaCl, 5mM EGTA, 2mM MgCl2, and 10mM HEPES, and the pH of the solution was adjusted to 7.4 (room temperature) with NaOH. Before the photocurrent of the cells was measured, the cells were digested and suspended, and the cells were fixed on a slide glass using polylysine, and then incubated in a cell incubator for about 2 hours. Finally, the slides were placed in petri dishes that were moved to contain extracellular solution and placed on a patch clamp station. Modulating light incident on the imaging system and detecting photoresponsive properties of the photosensitive cells. The cell ionic current detection mode by using the patch clamp is to record the whole cell current under a voltage clamp, the glass tube is a borosilicate glass capillary tube, the inner diameter of the glass tube is 0.5mm, the outer diameter of the glass tube is 1mm, and the liquid inlet resistance of the glass tube is 3.5-5 MOmega after the glass tube is drawn and manufactured. The sampling frequency was 10kHz and the sampled data was processed with 2kHz low pass filtering. The sealing resistance is higher than 1G omega, and the liquid level resistance and the capacitance are compensated to ensure the sampling accuracy and precision of the cell ionic current.

The DMD module directly uses the Discovery family of DLP chips. The DMD model is a 0.7 inch VGA family containing 1024 x 768 digital micromirrors each having a side length of 13.7 μm, which is suitable for all bands from ultraviolet to near infrared. The refresh rate of the control board can reach 290Hz at most. Each micromirror can be flipped 12 deg. to either side along the diagonal of the micromirror and controlled by the input response value. When the input at this position is 1, the micromirror is flipped 12 ° to one direction; when the input for this position is 0, the micromirror flips 12 to the other direction. All the micromirrors of the entire DMD can be simultaneously controlled by a random binary picture of 1024 × 768 pixels, and the pixel points of the picture correspond to the micromirrors of the DMD one to one.

The light source adopts a laser with the wavelength of 375nm to ensure the linearity of light. And the exit pupil diameter is increased by a factor of 10 with a beam expander to ensure that the light covers the DMD.

In the imaging process, the light is irradiated on the DMD at constant light intensity, the DMD is controlled to turn over at the speed of 100ms period by corresponding random binary pictures in sequence, wherein the dwell time of the DMD for turning over the corresponding pictures is 10 ms. For the light-sensitive cells in this example, the total time duration of the cell ion current from activation to inactivation was about 77ms under the 10ms light pulse stimulation. To ensure the stability and accuracy of each detected optical response signal, the DMD flip period should be greater than 77 ms.

The character patterns of fig. 3A to E are taken as target images, and imaging tests are sequentially performed thereon. The imaging results are shown in FIGS. 3F to J. The resolution of the reconstructed picture is 50 × 50, and the sampling rate is 30%. The measurement matrix is designed as a bernoulli matrix of 750 x 2500, where each element is randomly set to either 1 or 0. Each row of the measuring matrix is converted into a 50 × 50 mode matrix (), then the mode matrix () is scaled up to 1000 × 700matr ix () to control the central area of the DMD, the data corresponding to the remaining micromirrors at the periphery of the DMD is supplemented with 0, and finally, a corresponding 1024 × 768 random binary image is generated. Then, the data detected by the patch clamp and the measurement matrix are processed by an orthogonal matching pursuit algorithm to generate a reconstructed image (fig. 3F-J).

In order to observe the imaging effect of the cell fusion photodetector more intuitively, a commercially available photodiode is used as the photosensitive element of the imaging system, and the pattern of the character "I" is imaged, and the result is shown in fig. 4. In this embodiment, the source power was set to 0.8mW and 8mW, respectively, and the two detectors were used to image separately under the same conditions. From the results, fig. 4 shows that, under low optical power, both photoelectric devices can clearly reproduce the information of the target image; under high optical power (8mW), the photodiode cannot image, and the cell fusion photodetector can still reproduce the target shape clearly. In this embodiment, the advantages of the bio-fusion sensor over artificial devices are primarily highlighted.

The above detailed description of the cell fusion photoelectric sensor and the operation method of the imaging system thereof provided by the present invention also include the following points:

the invention provides a single-pixel imaging system based on a biological fusion photoelectric sensor, which is characterized by comprising the following components: the device comprises a light source, a target image, a first lens, a DMD (digital mirror device), a second lens, a cell fusion photoelectric sensor and a computer. After light emitted by the light source is projected through a target image, the light is converged on the DMD through the first lens, then is converged on photosensitive cells of the photoelectric sensor through the second lens after being reflected by the DMD, photoelectric signals of the photosensitive cells are collected by the patch clamp and then transmitted to a computer, and a reconstructed image is reproduced through an optimization algorithm.

The cell fusion photoelectric sensor comprises a photosensitive cell and a patch clamp tool. The photosensitive cells are constructed from human embryonic cells (Hek293) modified with rhodopsin channel protein (ChR2) using optogenetic tools.

The glass tube of the patch clamp is a borosilicate glass capillary tube, the inner diameter of the glass tube is 0.5mm, the outer diameter of the glass tube is 1mm, and the liquid inlet resistance of the glass tube is 3.5-5M omega after the glass tube is drawn and manufactured. The photocurrent of the light-sensitive cells was recorded in a whole cell recording mode to increase the response amplitude of the cells.

The single-pixel imaging is based on a compressed sensing principle, and the specific imaging process is as follows: 1) assuming a signal x to be obtained of length N, the measurement matrix Φ ∈ R^M×N(M < N) is designed as a Bernoulli random matrix, wherein each element is 1 or 0; 2) mapping each row of the measurement matrix into a random binary image, wherein the size of the image is consistent with the size of a target image; 3) the random binary image is used for controlling the turnover of the DMD in sequence, and the ion current signal of the cell after each turnover is detected through patch clamp, wherein the signal magnitude can be expressed as

Wherein j is 1,2_i(i 1,2, 3.., N) is 1 in the direction of the micromirror toward the diode, and is otherwise 0And Dcoffset is a measure of the deviation of all micromirrors from the orientation of the graphene device; finally, the sampled signal v obtained is reconstructed by a compressed sensing reconstruction algorithm_iAnd the measurement matrix phi ∈ R^M×NThe original image x is reconstructed.

The computer is used for generating a measurement matrix, a random binary image, patch clamp control software, DMD control software, storing and processing patch clamp sampling data and reconstructing an image.

The above-mentioned embodiments are merely preferred embodiments for fully illustrating the present invention, and the scope of the present invention is not limited thereto. The equivalent substitution or change made by the technical personnel in the technical field on the basis of the invention is all within the protection scope of the invention. The protection scope of the invention is subject to the claims.

Claims

1. A method for manufacturing a cell-fused photosensor, comprising: transfecting the rhodopsin channel protein (ChR2) extracted from Chlamydomonas reinhardtii cell eyespot (Eye spot) into human embryonic kidney 293(Hek293, human embryo kidney) cells; observing the expression of the ChR2 plasmid in the cells, and further verifying the cell expression result by using a patch clamp technology in light stimulation; hek293 cells expressing ChR2 are used as sensitive materials of the photoelectric sensor, optical signals absorbed by the device are converted into ion current, and the signal acquisition and processing unit of the photoelectric sensor is used as a patch clamp technology; the cell is combined with a patch clamp detection device to form a cell fusion photoelectric sensor.

2. The method of claim 1, wherein the Human embryonic kidney 293(Hek293, Human embryo kidney) cell is constructed by the following steps: 1) a proofreading polymerase (primers with BamHI and HindIII restriction sites) with polymerase (pfu, Promega) was used to generate a full-length cDNA template (GenBank No.: AF461397) to obtain full-length chop2-315 and C-terminally truncated chop2 mutations and make them into ChR2 plasmid; 2) hek293 cells were cultured at 9.6cm²The culture dish of (1) contains 10% fetal bovine serum and 1% double antibodyDMEM medium with sugar, and dishes were placed at 37 ℃ with 5% CO₂When the cells grow to be full of 1/2 in the culture dish, the cells are ready for use; 3) the ChR2 plasmid was transfected into Hek293 cells using transfection reagent (Lipofectamine2000, Sigma) and placed in a cell incubator for 24 hours; 4) 1uM of cis-retinal (all-trans retinal, Sigma) was added to the dish and incubated for 2 hours in the incubator.

3. The method for producing a cell-fused photosensor according to claim 1, wherein the expression of the ChR2 plasmid in cells is observed by a fluorescence microscope.

4. A working method of an imaging system of a photoelectric sensor based on cell fusion is characterized in that light is converged on a light space modulator (DMD) through a first lens after passing through a target image, the light intensity reflected to a second lens is controlled by controlling the overturning of each corresponding micromirror in the DMD through a random binary image, and is converged on the photoelectric sensor of the biological fusion manufactured by the manufacturing method of any one of claims 1 to 3, and meanwhile, a light response signal of a cell is detected by using a patch clamp; and finally, reconstructing an original image by using the signals detected by the patch clamp.

5. The method of claim 4, wherein the imaging method of the imaging system is based on the principle of compressed sensing and the single photodetector is used to realize high resolution imaging; the compressed sensing principle can be described as: for some unknown signal x ∈ R^N×1In the measurement matrix phi ∈ R^M×NThe linear observed value under (M < N) is y ∈ R^M×1Then, there are:

y＝Φx； (1)

wherein, the signal x must satisfy the sparsity condition, that is, only K (K < M) elements in the x or x transform domain are nonzero values; according to the sparsity of the signal x, the most sparse is found out from the solution satisfying the formula (1), and when the measurement matrix phi satisfies the restrictive isometryTexture (RIP (1-delta) | | x | | non-woven hair)₂ ²≤||Φx||₂ ²≤(1+δ)||x||₂ ²) This "sparsest" solution is then the original signal x; in this system, a spatial signal of an image is converted into a time-series signal by the DMD based on the compressed sensing principle, and then a reconstructed image is obtained.

6. The method of claim 5, wherein the compressive sensing principle is specifically performed by: 1) assuming a signal x to be obtained of length N, the measurement matrix Φ ∈ R^M×N(M < N) is designed as a Bernoulli random matrix, wherein each element is 1 or 0; 2) mapping each row of the measurement matrix into a random binary image, wherein the size of the image is consistent with the size of a target image; 3) the random binary image is used for controlling the turnover of the DMD in sequence, and the ion current signal of the cell after each turnover is detected through patch clamp, wherein the signal magnitude can be expressed as

7. The method of claim 6, wherein the sampled signal v obtained is reconstructed by a compressive sensing reconstruction algorithm_iAnd the measurement matrix phi ∈ R^M×NThe original image x is reconstructed.

8. A computer device comprising a memory, a processor and a computer program stored on the memory and executable on the processor, characterized in that the steps of the method of any of claims 1 to 7 are implemented when the program is executed by the processor.

9. A computer-readable storage medium, on which a computer program is stored which, when being executed by a processor, carries out the steps of the method according to any one of claims 1 to 7.

10. A processor, characterized in that the processor is configured to run a program, wherein the program when running performs the method of any of claims 1 to 7.