A device for monitoring and electric field intervention of cells

Abstract

The present application relates to the field of biotechnology, and more specifically, to a device for monitoring and intervening in electric fields for cells, which, to a certain extent, can overcome the technical challenges of existing cell monitoring and electric field intervention devices, and solve the problems of insufficient spatial resolution of traditional impedance spectroscopy in cell culture monitoring and low flexibility in electric field intervention spatial settings. The device includes a main control unit, an electric field intervention unit, an electrical impedance scanning unit, a temperature monitoring and adjustment unit, an energy supply unit, a communication unit, and an integrated monitoring and intervention electrode; by multiplexing the electrical impedance measurement electrode with the electric field intervention electrode, the accuracy of three-dimensional electrical impedance imaging of cells can be improved, and at the same time, a flexible electric field intervention mode setting is provided. The device also integrates cell electrical impedance monitoring, electric field intervention function, and temperature monitoring and control function, which can monitor and adjust the growth state of cells under electric field intervention and the temperature change of the device in real time to ensure safety.

Description

Technical Field

[0001] The present application relates to the field of biotechnology, and in particular to a device for monitoring and intervening in electric fields of cells. Background Art

[0002] Cell culture is widely used in the biotechnology and pharmaceutical industries, as well as in scientific research. Given the highly complex production or research processes of cells, real-time perception of key processes and, when necessary, intervention are crucial for improving product quality or scientific research efficiency. At the same time, electric field manipulation of cells has been proposed. For example, TTFields (Tumor-treating Fields) is a novel, non-invasive physical therapy for cancer treatment. It inhibits tumor cell proliferation by applying a low-intensity (1-3 V / cm) medium-frequency alternating electric field (100-500 kHz) to tumor cells, disrupting the mitotic process. Alternatively, transcranial magnetic stimulation (TMS) stimulates the brain through alternating magnetic fields, generating an induced electric field within the brain and thereby regulating neural activity. Therefore, monitoring the cell culture process and intervening with electric fields are of great significance.

[0003] In recent years, various sensing and imaging technologies for cell monitoring have been proposed and studied. Existing bioprocess sensing and imaging technologies are mainly electrical methods (impedance spectroscopy) and optical methods (Raman spectroscopy and microscopy imaging). Compared with optical methods, impedance spectroscopy can provide better characterization of cell characteristics. However, the commonly used impedance spectroscopy method usually uses two electrodes for measurement and lacks spatial resolution. EIT allows non-destructive, real-time, continuous, label-free, qualitative and even quantitative visualization of spatiotemporal resolution. These characteristics make EIT a very promising cell imaging and bioprocess monitoring technology.

[0004] However, current devices for electric field intervention on cells usually only have electric field intervention functions, and it is difficult to monitor the actual distribution of the applied electric field in the cell culture device in real time. The design of cell devices that can implement monitoring and spatial electric field regulation is challenging. Summary of the Invention

[0005] In order to overcome the technical challenges of existing cell monitoring and electric field intervention devices, and solve the problems of insufficient spatial resolution of traditional impedance spectroscopy in cell culture monitoring and low flexibility in spatial setting of electric field intervention, the present application provides a cell monitoring and electric field intervention device.

[0006] The embodiment of the present application is implemented as follows:

[0007] In a first aspect, the present application provides a device for monitoring and intervening in electric fields of cells, comprising:

[0008] Main control unit: used for data processing and control device operation;

[0009] Electric field intervention unit: used to generate electric field excitation;

[0010] Electrical impedance scanning unit: used to measure the electrical impedance of cells and culture fluid in the device and reconstruct the electrical impedance image;

[0011] Temperature monitoring and regulation unit: used for multi-point temperature monitoring and regulation within the device;

[0012] Energy supply unit: used to supply electrical energy for the overall operation of the device;

[0013] Communication unit: used for external communication of the entire device, including wireless communication and limited communication;

[0014] Integrated monitoring and intervention electrode: used for electric field intervention output, electrical impedance signal measurement, and temperature monitoring and adjustment within the device, with a multiplexing design.

[0015] In a possible implementation, the electric field intervention unit includes an electric field generation and conversion module, an electric field output parameter measurement module, and an electric field conditioning output module;

[0016] The electric field conversion module is used to generate relevant electric field intervention waveforms;

[0017] The electric field conditioning output module is used to distribute the electric field waveform generated by the electric field generation and conversion module to the corresponding monitoring and intervention integrated electrode for signal output.

[0018] In a possible implementation, the electrical impedance scanning unit includes a cell electrical impedance information reconstruction module and an electrical impedance measurement module;

[0019] The electrical impedance measurement module is used to generate electrical impedance measurement excitation signals and measure electrical impedance signals.

[0020] The cell electrical impedance information reconstruction module is used to reconstruct the electrical impedance information based on the electrical impedance signal acquisition results.

[0021] In one possible implementation, the cell electrical impedance information reconstruction module obtains the electrical impedance information from the monitoring and intervention integrated electrode, and then performs three-dimensional cell electrical impedance reconstruction using the Laplace and sparse joint regularization algorithm. The Laplace and sparse joint regularization algorithm uses a measurement signal of a single frequency, and then measurement signals of different frequencies can be applied through the electrical impedance measurement module to measure the bioimpedance at different frequencies, and use them to reconstruct multi-frequency conductivity distribution images related to the characteristics of biological tissues.

[0022] In one possible implementation, in the device, the monitoring and intervention integrated electrode can be a pure metal electrode, a ceramic and metal composite electrode, or a ceramic coil electrode, and the monitoring and intervention integrated electrode is placed at the bottom and inner side of the device.

[0023] In a possible implementation, in the device, electric field excitation or electrical impedance measurement can be performed using any of the inner bottom and inner side electrodes.

[0024] In a possible implementation, in the device, the bottom of the device is a light-transmitting sheet, and the light-transmitting sheet is replaceable.

[0025] In one possible implementation, the main control unit uses an FPGA or MCU chip, which can set the device operating parameters between the electric field output and the electrical impedance measurement, monitor the temperature inside the cell culture device, control the temperature inside the feedback regulation device, and determine whether this information is normal. If it is abnormal, the main control unit controls the operation of the system.

[0026] In one possible implementation, the energy supply unit needs to supply power to multiple other units. The power supply source of the energy supply unit is 220V AC power, which is converted into DC through a rectifier bridge, and the voltage is converted into a specific value through some power conversion chips or DC-DC chips. At the same time, the energy supply unit has an industrial frequency filtering function to reduce industrial frequency interference.

[0027] In one possible implementation, the temperature monitoring includes a temperature signal monitoring module and a temperature regulation module. Based on the temperature change of the cell culture fluid caused by the ambient temperature or the heating of the electrode, the conductivity changes. In order to keep the temperature of the culture fluid constant during operation or to perform temperature / conductivity compensation, temperature monitoring and control are required. Temperature monitoring can be performed through a temperature sensor to comprehensively evaluate the temperature distribution of each area in the culture dish, arrange a temperature sensor array, and integrate the temperature sensor into each electrode, including the side electrode and the bottom electrode.

[0028] The technical solution provided by this application can achieve at least the following beneficial effects:

[0029] The cell monitoring and electric field intervention device provided in this application integrates cell electrical impedance monitoring and electric field intervention functions to monitor the growth status of cells under electric field intervention in real time. The bottom of the device is transparent and replaceable, allowing for convenient and real-time observation of cell status in combination with optical electron microscopy and other means during the electric field intervention process. The entire device is reusable, requiring only the replacement of the bottom transparent sheet, and is easy to install.

[0030] This application also improves the accuracy of three-dimensional impedance imaging of cells by multiplexing impedance measurement electrodes and electric field intervention electrodes. It also provides flexible electric field intervention mode settings and integrates temperature monitoring and control functions, which can monitor and adjust the temperature changes of the device in real time to ensure safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, a brief introduction will be given below to the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0032] Figure 1 This is a principle block diagram of a device for monitoring and intervening in electric fields of cells, shown in an exemplary embodiment of the present application;

[0033] Figure 2 is a structural block diagram of a cell monitoring and electric field intervention device shown in an exemplary embodiment of the present application;

[0034] Figure 3 This is a schematic diagram of a space configuration shown in an exemplary embodiment of the present application;

[0035] Figure 4 is another spatial configuration schematic diagram shown in an exemplary embodiment of the present application;

[0036] Figure 5 This is a schematic diagram of a preferred embodiment shown in an exemplary embodiment of the present application;

[0037] Figure 6 It is a schematic diagram of another preferred embodiment shown in an exemplary embodiment of the present application. DETAILED DESCRIPTION

[0038] In order to make the purpose, implementation methods and advantages of the present application clearer, the exemplary implementation methods of the present application will be clearly and completely described below in conjunction with the drawings in the exemplary embodiments of the present application. Obviously, the described exemplary embodiments are only part of the embodiments of the present application, not all of the embodiments. It should be understood that the specific embodiments described here are only used to explain the present application and are not used to limit the present application.

[0039] It should be noted that the brief descriptions of terms in this application are only for the purpose of facilitating the understanding of the embodiments described below, and are not intended to limit the embodiments of this application. Unless otherwise specified, these terms should be understood according to their ordinary and usual meanings.

[0040] In the specification and claims of this application and the accompanying drawings, the terms "first," "second," "third," etc. are used to distinguish similar or similar objects or entities, and are not necessarily intended to limit a particular order or sequence, unless otherwise noted. It should be understood that the terms used in this manner are interchangeable under appropriate circumstances.

[0041] The terms "comprise," "include," and "have," and any variations thereof, are intended to cover but not exclude inclusion; for example, a product or device comprising a list of components is not necessarily limited to all the components expressly listed but may include other components not expressly listed or inherent to such product or device.

[0042] Before explaining the cell monitoring and electric field intervention device provided in the embodiment of the present application, the application scenario and implementation environment of the embodiment of the present application are first introduced.

[0043] Cell culture is widely used in the biotechnology and pharmaceutical industries, as well as in scientific research. Given the highly complex production or research processes of cells, real-time perception of key processes and, when necessary, intervention are crucial for improving product quality or scientific research efficiency. At the same time, electric field manipulation of cells has been proposed. For example, TTFields (Tumor-treating Fields) is a novel, non-invasive physical therapy for cancer treatment. It inhibits tumor cell proliferation by applying a low-intensity (1-3 V / cm) medium-frequency alternating electric field (100-500 kHz) to tumor cells, disrupting the mitotic process. Alternatively, transcranial magnetic stimulation (TMS) stimulates the brain through alternating magnetic fields, generating an induced electric field within the brain and thereby regulating neural activity. Therefore, monitoring the cell culture process and intervening with electric fields are of great significance.

[0044] In recent years, various sensing and imaging technologies for cell monitoring have been proposed and studied. Existing bioprocess sensing and imaging technologies primarily rely on electrical methods (impedance spectroscopy) and optical methods (Raman spectroscopy and microscopy). Compared to optical methods, impedance spectroscopy can provide better characterization of cellular properties. However, commonly used impedance spectroscopy methods typically use two electrodes for measurement and lack spatial resolution. EIT allows for non-destructive, real-time, continuous, label-free, qualitative, and even quantitative visualization with spatiotemporal resolution. These characteristics make EIT a promising technology for cell imaging and bioprocess monitoring.

[0045] However, current devices for electric field intervention on cells usually only have electric field intervention functions, and it is difficult to monitor the actual distribution of the applied electric field in the cell culture device in real time. The design of cell devices that can implement monitoring and spatial electric field regulation is challenging.

[0046] Based on this, the present application provides a cell monitoring and electric field intervention device, which realizes real-time electrical impedance state monitoring of cells, and integrates electric field intervention function through electrode multiplexing. The electrical impedance monitoring method through electrode multiplexing improves the electrical impedance imaging quality of cells, and can monitor and explore the response of cells to electric field interventions of different frequencies and intensities in real time.

[0047] Next, the technical solution of the present application and how the technical solution of the present application solves the above-mentioned technical problems will be described in detail through embodiments and in conjunction with the accompanying drawings. The various embodiments can be combined with each other, and the same or similar concepts or processes may not be repeated in some embodiments. Obviously, the described embodiments are only part of the embodiments of the present application, not all of them.

[0048] Figure 1 This is a principle block diagram of a device for monitoring and intervening in electric fields of cells, shown in an exemplary embodiment of the present application;

[0049] In an exemplary embodiment, Figure 1 As shown, a cell monitoring and electric field intervention device is provided. In this embodiment, the device includes a main control unit, an electric field intervention unit, an electrical impedance scanning unit, a temperature monitoring and adjustment unit, a power supply unit, a communication unit and an integrated monitoring and intervention electrode.

[0050] The main control unit is used for data processing and controlling the operation of the device.

[0051] The electric field intervention unit is used to generate electric field excitation and is composed of an electric field generation and conversion module, an electric field output parameter measurement module and an electric field conditioning output module; the electric field generation and conversion module is used to generate relevant electric field intervention waveforms, and the electric field conditioning output module is used to distribute the electric field waveforms generated by the electric field generation and conversion module to the corresponding monitoring and intervention integrated electrodes for signal output.

[0052] The impedance scanning unit is used to perform impedance measurement and impedance image reconstruction on the cells and culture fluid in the device. It consists of a cell impedance information reconstruction module and an impedance measurement module. The impedance measurement module is used to generate impedance measurement excitation signals and measure impedance signals, and the cell impedance information reconstruction module is used to reconstruct impedance information based on the impedance signal acquisition results.

[0053] The temperature monitoring and regulation unit is used for multi-point temperature monitoring and regulation in the device, and consists of a temperature signal monitoring module and a temperature regulation module.

[0054] The energy supply unit is used to supply electrical energy for the overall operation of the device.

[0055] The communication unit is used for external communication of the entire device, including wireless communication and wired communication.

[0056] The integrated monitoring and intervention electrode is used for electric field intervention output, electrical impedance signal measurement, and temperature monitoring and adjustment within the device, and adopts a multiplexing design.

[0057] Specifically, in the above system, the main control unit generally adopts FPGA or MCU chip.

[0058] The main control unit is responsible for controlling the operation of the entire device, such as setting the device operating parameters between the electric field output and the electrical impedance measurement. In addition, the central control unit can also monitor the temperature inside the cell culture device, and at the same time control the temperature inside the feedback regulation device and determine whether this information is normal. If it is abnormal, it will control the operation of the system.

[0059] The energy supply unit needs to supply power to multiple other units. In this embodiment, the power supply source of the energy supply unit is 220V AC power, which is converted into DC through a rectifier bridge, and the voltage is converted into specific values ​​such as ±12V, 5V, 3.3V, etc. through some power conversion chips or DC-DC chips. At the same time, the energy supply unit has an industrial frequency filtering function to reduce industrial frequency interference.

[0060] The electric field intervention unit is used to generate electric field excitation and is composed of an electric field generation and conversion module, an electric field output parameter measurement module and an electric field conditioning output module; the electric field generation and conversion module is used to generate relevant electric field intervention waveforms, and the electric field conditioning output module is used to distribute the electric field waveforms generated by the electric field generation and conversion module to the corresponding integrated monitoring and intervention electrodes for signal output; the electric field frequency generated by the electric field generation and conversion module needs to completely cover the medium frequency band, that is, the electric field frequency is DC to 500kHz, and the load capacity needs to reach an electric field strength of 0-3V / cm.

[0061] Figure 2 is a structural block diagram of a cell monitoring and electric field intervention device shown in an exemplary embodiment of the present application. Figure 3 This is a schematic diagram of a space configuration shown in an exemplary embodiment of the present application. Figure 4 This is another spatial configuration diagram shown in an exemplary embodiment of the present application.

[0062] The monitoring and intervention integrated electrode is used for electric field intervention output, electrical impedance signal measurement and temperature monitoring and regulation in the device. It needs to have relatively low impedance, improve load capacity and reduce conversion loss. It can be made of biocompatible materials such as titanium, tungsten, nickel titanium, platinum wire, etc. Figure 2 or Figure 3 or Figure 4 As shown, there are many ways to configure the electrodes (electrode position, shape, number), for example, Figure 2The electrodes shown are evenly distributed on the curved inner wall of the cylindrical cell culture device, using rectangular electrodes, and other electrodes are distributed in a ring shape at the bottom, using cylindrical electrodes.

[0063] Select different electrode combinations, including the number of electrodes, electrode position, and current intensity. By applying a constant intensity current to a certain electrode or a certain electrode group, the electrode couples the electric field to the cell culture environment, which can induce different electric field distributions in the cell culture fluid. By changing the electrode combination, the electric field intensity and the focusing of the electric field distribution in the stimulation target area can be improved.

[0064] The temperature monitoring and regulation unit is used for multi-point temperature monitoring and regulation within the device, and is composed of a temperature signal monitoring module and a temperature regulation module. Since the ambient temperature or heating of the electrode can cause the temperature of the cell culture fluid to change, thereby changing the conductivity, temperature monitoring and control are required to maintain a constant temperature of the culture fluid during operation or to perform temperature / conductivity compensation. The present invention uses a temperature sensor for temperature monitoring, which can comprehensively evaluate the temperature distribution in each area of ​​the culture dish. The temperature sensor array is arranged and the temperature sensor is integrated into each electrode, including the side electrode and the bottom electrode.

[0065] The bottom of the device is designed with a removable and replaceable circular transparent window. Figure 3 As shown, light-transmitting materials are used to enable cell monitoring and the electric field intervention device to be used in conjunction with an optical microscope.

[0066] The impedance scanning unit is used to perform impedance measurement and impedance image reconstruction on the cells and culture fluid in the device. It consists of a cell impedance information reconstruction module and an impedance measurement module. The impedance measurement module is used to generate impedance measurement excitation signals and measure impedance signals. The cell impedance information reconstruction module is used to reconstruct impedance information based on the impedance signal acquisition results.

[0067] In one possible implementation, in the device, the cell electrical impedance information reconstruction module obtains the electrical impedance information from the monitoring and intervention integrated electrode, and then performs three-dimensional cell electrical impedance reconstruction using the Laplace and sparse joint regularization algorithm. The Laplace and sparse joint regularization algorithm uses a measurement signal of a single frequency, and then measurement signals of different frequencies can be applied through the electrical impedance measurement module to measure the bioimpedance at different frequencies, and use them to reconstruct multi-frequency conductivity distribution images related to the characteristics of biological tissues.

[0068] By applying an AC excitation signal to one electrode, an induced potential is generated in the area to be measured, and the induced voltage is detected on the remaining electrodes. By cyclically exciting N electrodes, N*(N-1) / 2 impedance values ​​can be obtained. The dielectric property distribution in the area to be measured is obtained using an image reconstruction algorithm, thereby obtaining a conductivity distribution image of the material distribution in the cell culture device and displaying it on a computer.

[0069] Based on the voltage measurements and the three-dimensional Jacobian matrix obtained by the measurement and data acquisition unit, the conductivity distribution of the sensing area can be estimated using an image reconstruction algorithm.

[0070] The present invention is described by taking a three-dimensional image reconstruction algorithm of a Laplace and sparse joint regularization algorithm as an example. The Laplace and sparse joint regularization algorithm uses a measurement signal of a single frequency.

[0071] In electrical impedance, the relationship between the conductivity distribution σ of the sensing domain and the measured boundary voltage difference V is expressed as:

[0072] V=F(σ)+e (1)

[0073] Where F is the nonlinear forward operator and e is the measurement noise. In practice, formula (1) can be linearized and expressed as:

[0074] y≈Jx+e (2)

[0075] Where y is the normalized voltage measurement, J is the Jacobian matrix or sensitivity matrix, and X is the conductivity vector.

[0076] The three-dimensional Jacobian matrix J can be expressed as:

[0077]

[0078] Among them, J dm (t, z, q) is the sensitivity value of the electrode pair composed of electrode d and electrode m at voxel (t, z, q) when used as current excitation and measurement, U tzq (I d ) and U tzq (I m ) are the potentials in the three-dimensional sensing area of ​​the electrode pair consisting of electrode d and electrode m when used as current excitation and measurement.

[0079] In order to estimate the conductivity distribution from the boundary voltage measurements, an inverse problem needs to be solved. This process is image reconstruction, which can be generally formulated as an optimization problem:

[0080]

[0081] in, is the reconstructed conductivity distribution, H is the regularization function containing prior information, and λ is the regularization factor.

[0082] Figure 5 This is a schematic diagram of a preferred embodiment shown in an exemplary embodiment of the present application. Figure 6 It is a schematic diagram of another preferred embodiment shown in an exemplary embodiment of the present application.

[0083] In a possible implementation, in the device, the monitoring and intervention integrated electrode can be a pure metal electrode, such as Figure 5 As shown in the figure, ceramic and metal composite electrodes can also be used, such as Figure 6 As shown, ceramic coil electrodes can also be used, and the monitoring and intervention integrated electrodes are placed at the bottom and inner side of the device.

[0084] It should be understood that, although the various steps in the flowcharts involved in the above-described embodiments are displayed in sequence according to the instructions, these steps are not necessarily executed in the order indicated. Unless otherwise specified herein, there is no strict order restriction on the execution of these steps, and these steps can be executed in other orders. Moreover, at least a portion of the steps in the flowcharts involved in the above-described embodiments may include multiple steps or multiple stages, and these steps or stages are not necessarily executed at the same time, but can be executed at different times. The execution order of these steps or stages is not necessarily to be carried out in sequence, but can be executed in turn or alternately with other steps or at least a portion of steps or stages in other steps.

[0085] The technical features of the above embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0086] The embodiments described above merely represent several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art could make various modifications and improvements without departing from the spirit of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of the present patent application shall be determined by the appended claims.

Claims

1. A device for monitoring and electric field intervention of cells, characterized in that: include: Main control unit: used for data processing and control device operation; Electric field intervention unit: used to generate electric field excitation; Electrical impedance scanning unit: used to measure the electrical impedance of cells and culture fluid in the device and reconstruct the electrical impedance image; Temperature monitoring and regulation unit: used for multi-point temperature monitoring and regulation within the device; Energy supply unit: used to supply electrical energy for the overall operation of the device; Communication unit: used for external communication of the entire device, including wireless communication and wired communication; Monitoring and intervention integrated electrode: used for electric field intervention output, electrical impedance signal measurement, and temperature monitoring and adjustment within the device, with a multiplexing design; The electric field intervention unit includes an electric field generation and conversion module, an electric field output parameter measurement module and an electric field conditioning output module; The electric field conversion module is used to generate relevant electric field intervention waveforms; The electric field conditioning output module is used to distribute the electric field waveform generated by the electric field generation and conversion module to the corresponding monitoring and intervention integrated electrode for signal output; The electrical impedance scanning unit includes a cell electrical impedance information reconstruction module and an electrical impedance measurement module; The electrical impedance measurement module is used to generate electrical impedance measurement excitation signals and measure electrical impedance signals. The cell electrical impedance information reconstruction module is used to reconstruct the electrical impedance information based on the electrical impedance signal acquisition results; After obtaining the electrical impedance information from the integrated monitoring and intervention electrode, the cell electrical impedance information reconstruction module performs three-dimensional cell electrical impedance reconstruction using the Laplace and sparse joint regularization algorithm. The Laplace and sparse joint regularization algorithm uses a single-frequency measurement signal, and then applies measurement signals of different frequencies through the electrical impedance measurement module to measure the bioimpedance at different frequencies, and uses them to reconstruct a multi-frequency conductivity distribution image related to the characteristics of biological tissue.

2. The cell monitoring and electric field intervention device according to claim 1, characterized in that: In the device, the monitoring and intervention integrated electrode adopts one of a pure metal electrode, a ceramic and metal composite electrode, and a ceramic coil electrode, and the monitoring and intervention integrated electrode is placed on the bottom and inner side of the device.

3. The cell monitoring and electric field intervention device according to claim 1, characterized in that: In the device, the inner bottom and inner side electrodes are arbitrarily selected to perform electric field excitation or electrical impedance measurement.

4. The cell monitoring and electric field intervention device according to claim 1, characterized in that: In the device, the bottom of the device is a light-transmitting sheet.

5. The cell monitoring and electric field intervention device according to claim 1, characterized in that: The main control unit uses an FPGA or MCU chip. The main control unit can set the device operating parameters between the electric field output and the electrical impedance measurement, monitor the temperature inside the cell culture device, control the temperature inside the feedback regulation device, and determine whether this information is normal. If it is abnormal, the main control unit will control the operation of the system.

6. The cell monitoring and electric field intervention device according to claim 1, characterized in that: The energy supply unit needs to supply power to multiple other units. The power supply source of the energy supply unit is 220V AC power, which is converted into DC through a rectifier bridge, and the voltage is converted into a specific value through some power conversion chips or DC-DC chips. At the same time, the energy supply unit has an industrial frequency filtering function to reduce industrial frequency interference.

7. The cell monitoring and electric field intervention device according to claim 1, characterized in that: The temperature monitoring includes a temperature signal monitoring module and a temperature regulation module. The temperature of the cell culture fluid will change due to the ambient temperature or heating of the electrode, thereby changing the conductivity. In order to keep the temperature of the culture fluid constant during operation or to perform temperature / conductivity compensation, temperature monitoring and control are required. Temperature monitoring can be performed through a temperature sensor to comprehensively evaluate the temperature distribution in each area of ​​the culture dish. A temperature sensor array is arranged and the temperature sensor is integrated into each electrode, including the side electrode and the bottom electrode.

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