Cell microscopy fixed-point focusing heating device

By designing a cell microscopic point-focusing heating device, a point-to-point heating of cell cultures is achieved using temperature-sensitive materials and servo motors. This solves the problem of precise control of local drug release and cell differentiation in in vitro culture, and improves the accuracy of drug release and the cell regulation effect.

CN223468395UActive Publication Date: 2025-10-24SHANGHAI MAIBOXING BIOTECHNOLOGY CO LTD
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Patent Information

Application Number
CN202422721055.3
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Filing Date
2024-11-08
Publication Date
2025-10-24
Estimated Expiration
2034-11-08

AI Technical Summary

Technical Problem

Existing technologies struggle to simulate the multicellular environment of in vivo tissues in in vitro cell culture, especially to achieve precise control over localized cell differentiation and drug release.

Method used

A cell microscopy fixed-point focusing and heating device was designed, which includes a stage module, a microscopy imaging module, a fixed-point focusing and heating module, and a control module. It uses a vertical cavity surface emitting laser and a servo motor to achieve fixed-point heating of cell cultures, and combines with temperature-sensitive materials to achieve local release of drugs.

Benefits of technology

It enables targeted activation and release of drugs in cell cultures, precisely regulating cell growth, differentiation, and apoptosis processes, mimicking the local environment within organisms, and improving the accuracy and effectiveness of drug release.

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Abstract

The utility model discloses a cell microscopy fixed-point focusing heating device, relates to a biological medicine research and development device, and can activate local medicine release in a fixed-point manner in a cell culture. The device comprises an objective table module, a microscopic imaging module, a fixed-point focusing heating module and a control module, wherein the fixed-point focusing heating module comprises a constant-temperature controller, a heating light source, a focusing device, a reflecting mirror and a motor A for adjusting the angle of the reflecting mirror. Local drug release is activated at a fixed point in a cell culture in a semi-solid culture medium, so that pharmacological research of temperature-sensitive drugs or local induced differentiation of the cell culture is realized.
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Description

TECHNICAL FIELD

[0001] The utility model relates to a biological medicine research and development device more specifically, relate to a cell microfocus focusing heating device. BACKGROUND

[0002] Cytology experiment generally refers to various experimental researches using cells cultured in vitro, and is an important method of preclinical pharmacological research in the process of new drug development. By studying the response of specific types of cells cultured in vitro to test drugs, the biological activity of the drug can be evaluated, and the physiological effect can be predicted. For example, after adding test drugs under certain conditions, existing technical means can analyze and detect the gene synthesis, transcription, translation of cells within a period of time, and the proliferation, differentiation, secretion, phagocytosis, migration and apoptosis of cells.

[0003] In addition, cytology experiments are widely used in the technical fields of life science, medicine, food detection, agriculture and animal husbandry, environmental protection, etc.

[0004] In cell cultures cultured in vitro, the types of cells are uniform. However, in living organisms, tissues are often composed of multiple types of cells arranged according to certain rules. In order to better simulate the environment in the living body, local induction differentiation of cells in the cell culture is needed.

[0005] Temperature-responsive intelligent drug release technology is an emerging drug controlled release technology that can achieve intelligent control of drug release rate. This technology plays an important role in the field of drug analysis, and can monitor and control the temperature change in the drug release process in real time, thereby improving the drug treatment effect and reducing adverse reactions.

[0006] Temperature-responsive intelligent drug release technology is based on the interaction between temperature-sensitive materials and controlled release carriers, and achieves intelligent controlled release of drugs by adjusting temperature. Among them, temperature-sensitive materials are polymers with temperature-responsive properties, which change in volume at different temperatures, thereby changing the pore structure of the carrier and controlling the drug release rate. The controlled release carrier is a material used to wrap and release drugs, which has good biocompatibility and controllability.

[0007] Poly N-isopropyl acrylamide (PNIPAm) is a kind of temperature-sensitive polymer material that can be dispersed in aqueous solution and can respond to the change of ambient temperature. Its macromolecular side chain has both hydrophilic amido group (-CONH-) and hydrophobic isopropyl [-CH(CH3)2-]. At low temperature, the interaction between PNIPAm and water is mainly the hydrogen bond between amido group and water molecules, and the water molecules around the macromolecular chain will form a solvent layer connected by hydrogen bond with high degree of ordering, and the macromolecule will exhibit a stretched coil structure. With the increase of temperature, the interaction parameter of PNIPAm and water changes suddenly, part of the hydrogen bond is destroyed, and the solvent layer of the hydrophobic part of the macromolecular chain is destroyed, at this time the macromolecule changes from loose coil structure to compact colloidal structure, thereby producing temperature sensitivity.

[0008] Gold nanoparticles (AuNPs) have good optical limiting performance, and the surface plasmon resonance (SPR) of AuNPs can absorb laser energy to realize efficient and rapid photo-thermal conversion, which can induce the conformational change of the surrounding heat-sensitive polymer, resulting in the increase of light scattering and the decrease of transmittance. Therefore, the construction of heat-sensitive polymer modified AuNPs composite material can effectively enhance the optical limiting performance. SUMMARY

[0009] The utility model provides a cell micro fixed point focusing heating device can in cell culture medium fixed point activation local drug release.

[0010] The technical scheme of the utility model is as follows:

[0011] A cell micro fixed point focusing heating device, comprising a stage module, a microscopic imaging module, a fixed point focusing heating module and a control module.

[0012] The stage module comprises a moving platform 21, a guide rail 22 and a motor B 23. The moving platform 21 is fitted on the guide rail 22 and can slide on the guide rail 22 under the drive of the motor B-23. The motor B-23 is a servo motor with positioning accuracy better than 0.01 millimeter. The culture dish 24 containing cell culture 25 is placed on the moving platform 21.

[0013] The microscopic imaging module comprises a visible light source 1, a condenser lens 2, an objective lens 3, an eyepiece 4, a CCD (charge coupled device) image sensor 5, the visible light source 1 and the condenser lens 2 are located above the stage module, the objective lens 3 is located below the stage module, and the eyepiece 4 and the CCD image sensor 5 are in optical communication with the objective lens 3. The visible light emitted by the visible light source 1 passes through the condenser lens 2 and then transmits through the culture dish 24 on the moving platform 21 to enter the objective lens 3, and then enters the CCD image sensor 5 and the eyepiece 4.

[0014] The spot focusing heating module comprises a constant temperature controller 11, a heating light source 12, a focusing device 13, a mirror 14 and a motor A-15 for adjusting the angle of the mirror, the constant temperature controller 11 is connected with the heating light source 12 through a signal transmission line, and the light emitted by the heating light source 12 is focused by the focusing device 13 and then projected onto the target position of the petri dish 24 on the moving platform 21 through the mirror 14. Preferably, the heating light source 12 is a vertical cavity surface emitting laser (VCSEL), the constant temperature controller 11 is a constant temperature controller with a temperature control precision better than 0.1 DEG C, and the motor A-15 is a servo motor with a positioning precision better than 0.01 millimeter.

[0015] The control module comprises a controller 31 and a computer 32. The motor A-15, the motor B-23, the CCD image sensor 5, the constant temperature controller 11 and the focusing device 13 are connected with the controller 31 through data lines. The controller 31 is connected with the computer 32 through data lines.

[0016] The use method and working mechanism of the utility model are as follows: cells are inoculated into a semi-solid culture medium, and a temperature-controlled drug release (or cell growth factor) is added, poured into a petri dish 24, and a thin layer culture 25 is formed. After a period of culture, the petri dish 24 is placed on the moving platform 21, the visible light source 1 is turned on, the height of the objective lens 3 is adjusted, the moving platform 21 is adjusted through the motor B-23, and the specific position of the culture 25 is clearly imaged on the CCD image sensor 5. Then the constant temperature controller 11 and the heating light source 12 are turned on, the angle of the mirror 14 is adjusted through the motor A-15, the focusing device 13 is further adjusted, the heating light source 12 is focused on the specific position of the culture 25, the specific position is heated according to the temperature set by the constant temperature controller 11, the drug (or cell growth factor) is released from the temperature-sensitive material, and the growth, differentiation, secretion and apoptosis of the cells in the periphery of the semi-solid culture medium are adjusted, so that pharmacological research or regulation of local cell differentiation in the cell culture is realized. The adjustment of the motor A-15, the motor B-23, the constant temperature controller 11 and the focusing device 13 can be automatically realized through the controller 31 by combining the analysis of the image captured by the CCD image sensor 5 and the manual input of the parameters of the software of the computer 32.

[0017] The utility model has the advantages that local drug release is activated in the cell culture in the semi-solid culture medium, so that pharmacological research of temperature-sensitive drugs or local induced differentiation of the cell culture is realized. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 : a structure diagram of a cell micro-spot focusing heating device.

[0019] Reference numerals: 1 - visible light source, 2 - condenser, 3 - objective lens, 4 - eyepiece, 5 - CCD image sensor, 11 - thermostat controller, 12 - heat light source, 13 - focusing device, 14 - reflector, 15 - motor A, 21 - moving platform, 22 - guide rail, 23 - motor B, 24 - culture dish, 25 - culture, 31 - controller, 32 - computer. DETAILED DESCRIPTION

[0020] Example 1, structure of a cell micro-focal heating device

[0021] A cell micro-focal heating device comprises a stage module, a micro-imaging module, a micro-focal heating module, and a control module.

[0022] The stage module comprises a moving platform 21, a guide rail 22, and a motor B 23. The moving platform 21 is embedded on the guide rail 22 and can slide on the guide rail 22 under the drive of the motor B 23. The motor B 23 is a servo motor with a positioning accuracy better than 0.01 mm. A culture dish 24 containing a cell culture 25 is placed on the moving platform 21.

[0023] The micro-imaging module comprises a visible light source 1, a condenser 2, an objective lens 3, an eyepiece 4, and a CCD (Charge-Coupled Device) image sensor 5. The visible light source 1 and the condenser 2 are located above the stage module, the objective lens 3 is located below the stage module, and the eyepiece 4 and the CCD image sensor 5 are in optical communication with the objective lens 3. The visible light emitted by the visible light source 1 passes through the condenser 2, then penetrates the culture dish 24 on the moving platform 21, enters the objective lens 3, and then enters the CCD image sensor 5 and the eyepiece 4.

[0024] The micro-focal heating module comprises a thermostat controller 11, a heat light source 12, a focusing device 13, a reflector 14, and a motor A 15 for adjusting the angle of the reflector. The thermostat controller 11 is connected to the heat light source 12 by a signal transmission line. The light emitted by the heat light source 12 is focused by the focusing device 13 and then projected onto the target position of the culture dish 24 on the moving platform 21 through the reflector 14. Preferably, the heat light source 12 is a Vertical-Cavity Surface-Emitting Laser (VCSEL), the thermostat controller 11 is a thermostat controller with a temperature control accuracy better than 0.1°C, and the motor A 15 is a servo motor with a positioning accuracy better than 0.01 mm.

[0025] The control module comprises a controller 31 and a computer 32. The motor A-15, the motor B-23, the CCD image sensor 5, the constant temperature controller 11 and the focusing device 13 are connected with the controller 31 through data lines. The controller 31 is connected with the computer 32 through data lines.

[0026] Embodiment 2, a method for using and working mechanism of a cell micro-focusing heating device

[0027] An example of a method for using and working mechanism of the utility model is as follows:

[0028] Cells are inoculated into semi-solid medium and temperature-controlled drug (or cell growth factor) is added, poured into a culture dish 24 to form a thin layer culture 25. After a period of culture, the culture dish 24 is placed on the moving platform 21, the visible light source 1 is turned on, the height of the objective lens 3 is adjusted, the moving platform 21 is adjusted by the motor B-23, and the specific position of the culture 25 is clearly imaged on the CCD image sensor 5. Then the constant temperature controller 11 and the heating light source 12 are turned on, the angle of the reflecting mirror 14 is adjusted by the motor A-15, the focusing device 13 is further adjusted, the heating light source 12 is focused on the specific position of the culture 25, the specific position is heated according to the temperature set by the constant temperature controller 11, the drug (or cell growth factor) is released from the temperature-sensitive material, and the growth, differentiation, secretion and apoptosis of the cells in the periphery of the semi-solid medium are adjusted, so that pharmacological research or regulation of local cell differentiation in the cell culture is realized. The adjustment of the motor A-15, the motor B-23, the constant temperature controller 11 and the focusing device 13 can be automatically realized by the controller 31 through the analysis of the image captured by the CCD image sensor 5 and the manual input of the parameters of the software of the computer 32.

Claims

1. A cell micro-focal point heating device, comprising a stage module, a micro-imaging module, a focal point heating module, characterized in that, The objective table module comprises a moving platform (21), a guide rail (22) and a motor B (23), the moving platform (21) is embedded on the guide rail (22) and can slide on the guide rail (22) under the drive of the motor B (23); the microscopic imaging module comprises a visible light source (1), a condenser (2), an objective lens (3), an eyepiece (4) and a CCD image sensor (5), the visible light source (1) and the condenser (2) are located above the objective table module, the objective lens (3) is located below the objective table module, the eyepiece (4) and the CCD image sensor (5) are in optical communication with the objective lens (3); the fixed-point focusing heating module comprises a constant temperature controller (11), a heating light source (12), a focusing device (13), a reflector (14) and a motor A (15) for adjusting the angle of the reflector, the constant temperature controller (11) is connected with the heating light source (12) through a signal transmission line, and the light emitted by the heating light source (12) is focused by the focusing device (13) and then projected onto a target position on the moving platform (21) through the reflector (14).

2. The cell micro-focussing heating device according to claim 1, characterized in that, The control module comprises a controller (31) and a computer (32), the motor A (15), the motor B (23), the CCD image sensor (5), the constant temperature controller (11) and the focusing device (13) are connected with the controller (31) through data lines, and the controller (31) is connected with the computer (32) through a data line.

3. The cell micro-focussing heating device according to claim 1, wherein, The heating light source (12) is a vertical cavity surface emitting laser, and the motor A (15) and the motor B (23) are servo motors.