Device for high-throughput detection of transmembrane resistance by using electrical impedance sensing technology
By designing a high-throughput detection device using impedance sensing technology, and employing a microelectrode array plate and an impedance meter, the problem of low detection throughput in existing TEER devices was solved, enabling simultaneous detection of multiple cell samples and improving detection efficiency.
Patent Information
- Application Number
- CN202520256945.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-18
- Publication Date
- 2025-12-23
- Estimated Expiration
- 2035-02-18
AI Technical Summary
Existing transmembrane resistance (TEER) detection methods and devices have low throughput, making them inefficient for large-scale drug screening and cell biology research, and consuming a lot of time and resources.
A high-throughput detection device based on impedance sensing technology was designed, including a worktable, a frame, a pressure measurement component, a cell culture component, and a gas source. It employs a microelectrode array plate and an impedance meter, and uses a lifting device to drive the electrodes into the culture dish to form a current loop with the cells, enabling simultaneous detection of multiple cell samples.
It enables high-throughput screening experiments, is simple to operate, and can simultaneously and accurately measure the TEER value of multiple cell samples, thus improving detection efficiency.
Smart Images
Figure CN223705602U_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of cell detection, and in particular to a device for high-throughput detection of trans-epithelial electrical resistance (TEER) by electrical impedance sensing technology. BACKGROUND
[0002] In biomedical research, trans-epithelial electrical resistance (TEER) is one of the important indicators for evaluating the function of cell barriers. For example, in the process of drug development, it is necessary to understand the ability of drug molecules to pass through cell barriers, and the measurement of TEER can help researchers to judge the permeability and potential side effects of drugs. However, the existing TEER detection methods and devices have many limitations.
[0003] Traditional detection methods often have low throughput, and can only detect one cell sample in each culture space, which is extremely inefficient for large-scale drug screening and cell biology research, and consumes a large amount of time and resources. For example, in the early stages of new drug development, a large number of candidate drugs need to be preliminarily evaluated at the cell level. If the traditional low-throughput detection method is used, it is difficult to obtain enough data to screen out potential drug molecules in a short period of time. CONTENT OF THE INVENTION
[0004] In order to solve the problem that each time only one cell sample in each culture space can be detected, which is extremely inefficient for large-scale drug screening and cell biology research, the present application provides a device for high-throughput detection of trans-epithelial electrical resistance (TEER) by electrical impedance sensing technology.
[0005] The device for high-throughput detection of trans-epithelial electrical resistance (TEER) by electrical impedance sensing technology provided by the present application adopts the following technical solution:
[0006] A device for high-throughput detection of trans-epithelial electrical resistance (TEER) by electrical impedance sensing technology, comprising a workbench, a rack is arranged on the workbench, a pressure measuring assembly is arranged on the rack, the pressure measuring assembly comprises a plurality of electrodes arranged on the workbench, and the electrodes are movable along the Z-axis, and a detachable cell culture assembly is further arranged on the workbench, the cell culture assembly comprises a microelectrode array plate arranged on the workbench, a plurality of cell culture units are arranged on the microelectrode array plate, and microelectrodes are arranged in the cell culture units.
[0007] Preferably, a lifting device is arranged on the rack, and an air source is connected to the lifting device.
[0008] Preferably, the lower end of the lifting device is detachably connected to an electrode array plate, a plurality of electrodes are arranged in parallel on the electrode array plate, and an impedance measuring instrument is arranged on the electrode array plate.
[0009] Preferably, the cell culture unit comprises a base plate arranged on the microelectrode array plate, the microelectrodes are arranged on the top of the base plate, and the surface of the microelectrodes on the base plate is provided with a biocompatible coating.
[0010] Preferably, the threaded sleeve on the base plate is provided with a culture dish, and a sealing gasket is arranged at the connection between the base plate and the microelectrode.
[0011] Preferably, a plurality of needle rows are arranged on the workbench, the upper ends of the needle rows pass through the microelectrode array plate, and the needle rows are in sliding connection with the microelectrode array plate.
[0012] In summary, the present application has the following beneficial technical effects:
[0013] By cooperation of the pressure measuring assembly, the cell culture assembly, the gas source and the needle row, the microelectrode array plate is connected with the needle row to realize electrical connection between the microelectrode array plate and the system, and accurate positioning of the microelectrode array plate is realized. The electrode array plate is driven downward by the lifting device to insert into the inside of the culture dish, and the control system generates an accurate alternating current signal, which is applied to the cell layer through the electrode array plate and the microelectrode to form a current loop. The impedance measuring instrument measures the voltage and current signals between the microelectrodes to calculate the TEER value. Compared with the prior art, the present application has the effects of high-throughput screening experiment and simple operation. BRIEF DESCRIPTION OF DRAWINGS
[0014] Figure 1 is a first perspective view of the embodiment of the application;
[0015] Figure 2 is a second perspective view of the embodiment of the application;
[0016] Figure 3 is a third perspective view of the embodiment of the application.
[0017] BRIEF DESCRIPTION OF DRAWINGS 1, workbench; 2, rack; 3, pressure measuring assembly; 301, lifting device; 302, electrode array plate; 303, electrode; 304, impedance measuring instrument; 4, cell culture assembly; 401, microelectrode array plate; 402, base plate; 403, biocompatible coating; 404, microelectrode; 405, culture dish; 5, gas source; 6, needle row. DETAILED DESCRIPTION
[0018] The following will be described in detail with reference to the accompanying drawings Figures 1-3 The application will be further described in detail.
[0019] The embodiment of the application discloses a device for high-throughput detection of transmembrane electrical resistance (TEER) by electrical impedance sensing technology. Referring to Figures 1-3The application discloses a device for high-throughput detection of transmembrane electrical resistance (TEER) by using an electrical impedance sensing technology, which mainly comprises a workbench 1, a rack 2, a pressure measuring assembly 3, a cell culture assembly 4, an air source 5 and a needle discharge device 6, and realizes accurate detection of the transmembrane electrical resistance.
[0020] With reference to Figure 1 And Figure 2 The workbench 1 is a basic support platform of the whole device and is made of high-strength aluminum alloy. The control system is internally mounted, and an embedded microprocessor is used as a core processor to run special control and analysis software. The signal generation and acquisition process of the signal generation and measurement module can be automatically controlled, and the TEER value is calculated by using the built-in algorithm (such as based on Ohm's law and an equivalent circuit model) according to the collected signal data.
[0021] With reference to Figure 1 The rack 2 is made of aluminum alloy. The pressure measuring assembly 3 and a lifting device 301 are arranged on the rack 2. The lifting device 301 is selected from high-precision electric lifting rods, and the stroke accuracy can reach ±0.05 mm, so that the lifting height of the electrodes 303 can be accurately controlled. The lifting device 301 is firmly connected with the rack 2, so that the whole structure is stable and reliable during adjustment of the electrode position and does not shake or displace.
[0022] With reference to Figure 1 The lower end of the lifting device 301 is detachably connected with an electrode array plate 302, so that the electrode array plate 302 can be conveniently installed, maintained and replaced. The electrode array plate 302 is made of engineering plastic with good insulation performance, and the surface is specially treated to improve the installation stability of the electrodes 303. A plurality of electrodes 303 are arranged in parallel on the electrode array plate 302, and the electrode array plate 302 serves to fix and connect the electrodes 303, facilitating overall operation. The electrodes 303 are made of stainless steel and are subjected to gold plating treatment on the surface, so that the conductivity and corrosion resistance of the electrodes 303 are improved. The electrodes 303 can move along the Z axis, and this design can flexibly adjust the contact position of the electrodes and the cell sample, so that the measurement accuracy is ensured.
[0023] With reference to Figure 2 An impedance measuring instrument 304 is arranged on the electrode array plate 302. The impedance measuring instrument 304 is selected from professional high-precision measuring instruments, and is subjected to strict calibration and testing, so that the measurement accuracy is ensured to be within ±0.1%. The impedance measuring instrument 304 can accurately measure the voltage and current signals between the microelectrodes, and provides an accurate data basis for calculation of the TEER value.
[0024] With reference to Figure 1The lifting device 301 on the rack 2 is also connected with an air source 5. The air source 5 is selected as a small air compressor, which can provide stable air pressure. The connection of the air source 5 with the lifting device 301 provides air power support for the movement of the electrode 303 and some operation processes (such as cleaning the electrode, etc.). Referring to Figure 2 The workbench 1 is also provided with a detachable cell culture assembly 4. The cell culture assembly 4 includes a microelectrode array plate 401 arranged on the workbench 1. The microelectrode array plate 401 is made of silicon-based material and is manufactured by micro-nano processing technology, which ensures the layout accuracy and size accuracy of the microelectrode 404. A plurality of pin rows 6 are arranged on the workbench 1, the upper end of the pin row 6 penetrates through the microelectrode array plate 401 and is in sliding connection with the microelectrode array plate 401. The pin row 6 plays a role of electrical connection and positioning, and through the connection with the microelectrode array plate 401, the electrical connection with the system is realized, and at the same time, the microelectrode array plate 401 can be accurately positioned to ensure the accuracy of detection. The sliding fit gap between the pin row 6 and the microelectrode array plate 401 is controlled to be within ±0.05 mm, which further ensures the accuracy of connection and positioning.
[0025] Referring to Figure 3 A plurality of cell culture units are arranged on the microelectrode array plate 401. The cell culture unit includes a bottom plate 402 arranged on the microelectrode array plate 401. The bottom plate 402 is made of polycarbonate material with good biocompatibility and is manufactured by injection molding process, which provides a stable support structure for the microelectrode 404 and cell culture. The microelectrode 404 is arranged on the top of the bottom plate 402 and is a high-throughput microelectrode array manufactured by MEMS technology. The microelectrode material is gold or platinum, and a biocompatible coating 403 is arranged on the surface of the microelectrode 404. The biocompatible coating 403 can be collagen, polylysine, etc. and is formed on the surface of the microelectrode 404 by chemical plating or physical adsorption method. The thickness of the coating is controlled to be between 1-5 μm. The coating can promote the adhesion and growth of cells, and at the same time does not affect the measurement of electrical impedance.
[0026] Referring to Figure 3 A culture dish 405 is threadedly arranged on the bottom plate 402, and the threaded connection facilitates the installation and removal of the culture dish 405. A sealing gasket is arranged at the connection between the bottom plate 402 and the microelectrode 404, which ensures the sealing and stability of the cell culture environment and provides good conditions for the growth of cells. The culture dish 405 is made of transparent polystyrene material and is manufactured by injection molding process. The threaded connection between the culture dish 405 and the bottom plate 402 has high precision, which further guarantees the sealing performance.
[0027] The implementation principle of the device for detecting transmembrane electrical resistance (TEER) by the electrical impedance sensing technology according to the embodiment of the present application is as follows:
[0028] In the use of the device for TEER detection, first, the cell culture assembly 4 is installed on the workbench 1, and the electric connection is completed through the needle 6 and the system, and the needle 6 is accurately positioned to the microelectrode array plate 401. Then the cells are seeded on the microelectrode 404 in the culture dish 405, and under the action of the biocompatible coating 403, the cells gradually grow and form a cell monolayer.
[0029] When detection is needed, the lifting device 301 is started, the lifting device 301 drives the electrode array plate 302 to drive the electrode 303 to move downward, so that the electrode 303 is inserted into the inside of the culture dish 405, and the electrode 303 is electrically connected with the cell monolayer and the microelectrode 404. The control system generates an accurate alternating current signal, which is applied to the cell layer through the electrode array plate 302 and the microelectrode 404, to form a current loop.
[0030] At this time, the impedance measuring instrument 304 on the electrode array plate 302 measures the voltage and current signals between the microelectrodes, and according to Ohm's law and related resistance impedance calculation principles, the measured voltage and current data are processed to accurately calculate the TEER value. Since the device is provided with a plurality of cell culture units and corresponding electrodes, a plurality of cell samples can be detected at the same time, and high-throughput detection is realized.
[0031] Finally, it should be pointed out that: first, in the description of the present application, it should be pointed out that unless otherwise specified and limited, the terms "installation", "connection", "connection" should be understood broadly, which can be mechanical connection or electrical connection, or the communication between two elements, or direct connection, "up", "down", "left", "right" and the like are only used to indicate the relative positional relationship, when the absolute position of the described object changes, the relative positional relationship may change;
[0032] Secondly: the utility model discloses the embodiment of the drawings, only relate to the structure involved in the embodiment of the present disclosure, other structures can refer to the usual design, under the condition of no conflict, the same embodiment and different embodiments of the utility model can be combined with each other;
[0033] Finally: the above only for the preferred embodiment of the utility model, and does not limit the utility model, any modification, equivalent replacement, improvement etc. made within the spirit and principle of the utility model should be included in the protection scope of the utility model.
[0034] The above are the preferred embodiments of the present application, and do not limit the protection scope of the present application, therefore: any equivalent changes made according to the structure, shape, principle of the present application should be covered in the protection scope of the present application.
Claims
1. A device for high-throughput detection of transmembrane electrical resistance by electrical impedance sensing technology, comprising a worktable (1), characterized in that: The workbench (1) is provided with a rack (2), the rack (2) is provided with a pressure measuring assembly (3), the pressure measuring assembly (3) includes a plurality of electrodes (303) arranged on the workbench (1), and the electrode (303) can move along the Z axis, the workbench (1) is further provided with a detachable cell culture assembly (4), the cell culture assembly (4) includes a microelectrode array plate (401) arranged on the workbench (1), the microelectrode array plate (401) is provided with a plurality of cell culture units, and a microelectrode (404) is arranged in the cell culture unit.
2. The device for high-throughput detection of transmembrane resistance by electrical impedance sensing technology according to claim 1, characterized in that: The rack (2) is provided with a lifting device (301), and the lifting device (301) is connected with an air source (5).
3. The device for high-throughput detection of transmembrane resistance by electrical impedance sensing technology according to claim 2, characterized in that: The lower end of the lifting device (301) is detachably connected with an electrode array plate (302), a plurality of electrodes (303) are arranged in parallel on the electrode array plate (302), and an impedance measuring instrument (304) is arranged on the electrode array plate (302).
4. The device of claim 1, wherein the device is configured to detect the transmembrane resistance at a high throughput rate. The cell culture unit includes a bottom plate (402) arranged on the microelectrode array plate (401), the microelectrode (404) is arranged on the top of the bottom plate (402), and a biocompatible coating (403) is arranged on the surface of the microelectrode (404) on the bottom plate (402).
5. The device for high-throughput detection of transmembrane resistance by electrical impedance sensing technology according to claim 4, characterized in that: The bottom plate (402) is threadedly sleeved with a culture dish (405), and a sealing gasket is arranged at the connection between the bottom plate (402) and the microelectrode (404).
6. The device for high-throughput detection of transmembrane resistance by electrical impedance sensing technology according to claim 5, characterized in that: A plurality of needle rows (6) are arranged on the workbench (1), the upper end of the needle row (6) penetrates through the microelectrode array plate (401), and the needle row (6) is in sliding connection with the microelectrode array plate (401).