In-vitro cell culture platform with acoustic stimulation and accurate temperature control

Through the thermoelectric refrigeration sheet and water-cooled cycle cooling system combined with circular piezoelectric ceramic sheet, the PID controller is used to achieve accurate temperature control of 0-50℃, solving the problem of inaccurate temperature control in the existing technology, and providing stable and reliable Cell culture platform and enhance the accuracy of the experiment through sonic stimulation.

CN222119268UActive Publication Date: 2024-12-06ZHENGZHOU UNIV +1
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Patent Information

Application Number
CN202420733705.3
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Priority Date
2023-07-07
Filing Date
2024-04-10
Publication Date
2024-12-06
Estimated Expiration
2034-04-10

AI Technical Summary

Technical Problem

The existing cell culture devices have insufficient accuracy and stability in temperature control, especially the PTC ceramic sheet can only heat up but not cool down. The semiconductor refrigeration sheet cannot be used as an effective cold source and heat source within the temperature range near the room temperature, resulting in temperature control. Inaccurate.

Method used

Thermoelectric refrigeration sheet is used to combine the water-cooled cycle cooling system and the circular piezoelectric ceramic sheet to achieve accurate temperature control of 0-50°C through the PID temperature controller, and the acoustic surface waves are stimulated through the inverse piezoelectric effect for cell culture.

Benefits of technology

High-precision temperature control in the range of 0-50℃ is achieved, ensuring the stability and safety of the equipment, and providing sonic stimulation for cell culture, improving the reliability and accuracy of the experiment.

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Abstract

The utility model discloses an in-vitro cell culture platform with sound wave stimulation and accurate temperature control, which comprises a thermoelectric refrigeration sheet, a cell culture chamber, a circular piezoelectric ceramic sheet, a water-cooling circulating cooling system, a PID (proportion integration differentiation) temperature controller and a shell, the bottom surface of the thermoelectric refrigeration sheet is in contact with the water-cooling circulating cooling system; the utility model relates to the technical field of refrigeration. According to the utility model, the cell culture chamber can be cooled or heated through the thermoelectric refrigeration sheet, and an alternating current electric signal is applied to two ends of the piezoelectric ceramic sheet electrode to excite surface acoustic wave (SAW) through an inverse piezoelectric effect so as to control the movement of suspended particles in micro-droplets, so that sound wave stimulation is provided for realizing in-vitro cell culture; and meanwhile, the hot end of the thermoelectric refrigeration sheet is effectively cooled by virtue of the water-cooling circulating cooling system, so that the temperature of the thermoelectric refrigeration sheet is maintained within a normal working range.
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Description

Technical Field

[0001] The utility model relates to the technical field of cell biology, in particular to an in vitro cell culture platform with acoustic wave stimulation and precise temperature control. Background Art

[0002] As one of the basic characteristics of organisms, stress sensitivity is a normal physiological phenomenon in which organisms sense external stimuli and respond. Cells, the basic structural and functional units of organisms, are more sensitive to external environmental stimuli, which can cause various physiological reactions and lead to changes in a large number of signal pathways and protein levels. In order to study the physiological responses of cells under temperature and vibration stimulation, it is necessary to use a universal cell culture device that can provide external stimulation functions such as temperature (heat stimulation and cold stimulation) and mechanical vibration.

[0003] At present, the commonly used temperature control mainly uses PTC ceramic heating sheets to achieve temperature control, but PTC ceramic sheets can only heat up but not cool down, so the control accuracy and temperature range are limited, while semiconductor cooling sheets can not only heat up but also cool down, which can achieve high-precision and wide-range temperature control. SAW piezoelectric materials mainly include piezoelectric single crystals, piezoelectric ceramics, and piezoelectric films, but these materials cannot be used as cold sources and heat sources within the temperature range near room temperature. Therefore, when controlling the temperature, the stability of the working temperature cannot be guaranteed, so when monitoring the temperature in real time, the accuracy of the temperature cannot be guaranteed. Utility Model Content

[0004] In view of the deficiencies of the prior art, the utility model provides an in vitro cell culture platform with acoustic wave stimulation and precise temperature control, which solves the problems mentioned in the above background technology.

[0005] To achieve the above objectives, the utility model is implemented through the following technical solutions: an in vitro cell culture platform for acoustic wave stimulation and precise temperature control, including a thermoelectric cooling plate, a cell culture chamber, a circular piezoelectric ceramic plate, a water-cooled circulation cooling system, a PID temperature controller, and a shell. The top of the thermoelectric cooling plate is in contact with the cell culture chamber, the bottom of the thermoelectric cooling plate is in contact with the water-cooled circulation cooling system, and the temperature monitoring and control system are respectively connected to the cell culture chamber and the thermoelectric cooling plate.

[0006] Preferably, the thermoelectric cooling sheet includes P-type grains and N-type grains, and there are multiple P-type grains and multiple N-type grains. The multiple P-type grains and the multiple N-type grains are respectively arranged at both ends of multiple electrodes in a one-to-one correspondence, and the P-type grains on two adjacent electrodes are not at the same end.

[0007] Preferably, the PID temperature controller includes a DC power supply, a DC voltage and current regulator, a temperature sensor and a display, the temperature sensor is arranged between the cell culture chamber and the piezoelectric cooling sheet and connected to the temperature control chip, and the DC voltage and current regulator is connected to the thermoelectric cooling sheet.

[0008] Preferably, four circular piezoelectric ceramic sheets are connected to the four walls of the cell culture chamber, and the top of the circular piezoelectric ceramic sheet is in contact with the top inner wall of the shell. An alternating current signal is applied to both ends of the electrode to excite surface acoustic waves (SAW) through the inverse piezoelectric effect for controlling the movement of suspended particles inside the microdroplets, thereby providing acoustic wave stimulation for in vitro cell culture.

[0009] Preferably, the operating temperature of the in vitro cell culture platform is 0-50°C, and the temperature control accuracy is ±0.1°C.

[0010] Preferably, the operating voltage range of the thermoelectric cooling plate is 0-6V, and the operating current range is 0-2A.

[0011] Preferably, the water-cooling circulation cooling system includes a water flow control system, micro-channel heat sinks and a booster silent water pump. The water flow control system can adjust the water flow entering the heat sink according to the hot end temperature of the thermoelectric cooling plate, and can complete the heat dissipation of the semiconductor thermoelectric cooling ceramic plate efficiently and with low noise.

[0012] Preferably, the cold end at the top of the thermoelectric cooling sheet contacts the temperature sensor, and the cold end cools the cell culture chamber to reach the temperature set by the user; the hot end at the bottom of the thermoelectric cooling sheet contacts the micro-channel heat sink fins of the water-cooled circulation cooling system, and the water-cooled circulation cooling system cools the hot end of the thermoelectric cooling sheet by adjusting the water flow.

[0013] Beneficial Effects

[0014] The utility model provides an in vitro cell culture platform with acoustic wave stimulation and precise temperature control, which is suitable for an open work platform. Compared with the prior art, it has the following beneficial effects:

[0015] (1) As a special cooling source, semiconductor thermoelectric cooling chips have the advantages of not requiring any refrigerant, being able to work continuously, having no pollution source, and having no vibration or noise during operation.

[0016] (2) The water-cooling circulation cooling system is in direct contact with the hot end of the semiconductor thermoelectric refrigeration element to dissipate heat, ensuring that the entire equipment is maintained within the normal operating temperature range during operation, thereby ensuring the stability and safety of the equipment operation.

[0017] (3) Applying an alternating current signal across the electrodes of the circular piezoelectric ceramic piece stimulates surface acoustic waves (SAW) through the inverse piezoelectric effect, which is used to control the movement of suspended particles inside the microdroplets, providing acoustic wave stimulation for in vitro cell culture and ensuring the accuracy and reliability of cell culture. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 An exploded view of an embodiment of the utility model;

[0019] Figure 2 It is a front view of an embodiment of the utility model;

[0020] Figure 3 This is a schematic diagram of a thermoelectric cooling sheet according to an embodiment of the present utility model.

[0021] In the figure: 1-cell culture chamber, 2-temperature sensor, 3-thermoelectric cooling sheet, 4-circular piezoelectric ceramic sheet, 5-water cooling circulation system, 6-PID temperature controller, 7-housing, 8-display, 9-button, 10-cold end, 11-P-type grain, 12-N-type grain, 13-electrode, 14-hot end. DETAILED DESCRIPTION

[0022] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0023] Please refer to the figure Figure 1-Figure 3 The utility model provides a technical solution: an in vitro cell culture platform for acoustic wave stimulation and precise temperature control, including a thermoelectric cooling chip (TEC) 3, a cell culture chamber 1, a circular piezoelectric ceramic chip 4, a water-cooled circulation cooling system 5, a PID temperature controller 6, and a shell 7.

[0024] The bottom of the cell culture chamber 1 is connected to the temperature sensor 2, the side walls of the cell culture chamber 1 are in contact with four circular piezoelectric ceramic sheets 4, the top of the circular piezoelectric ceramic sheet 4 is attached to the inner wall of the top of the shell 7, and an alternating current signal is applied to both ends of the electrodes of the circular piezoelectric ceramic sheet 4 to excite the surface acoustic wave (SAW) through the inverse piezoelectric effect for controlling the movement of suspended particles inside the micro-droplets in the cell culture chamber 1, thereby providing acoustic wave stimulation for in vitro cell culture.

[0025] The temperature sensor 2 is arranged above the thermoelectric cooling sheet 3, at the cold end 10 of the thermoelectric cooling sheet 3 and below the cell culture chamber 1. The temperature sensor 2 is connected to the PID temperature controller 6. The temperature sensor 2 is used to monitor the real-time temperature of the cold end 10 at the top of the thermoelectric cooling sheet 3 and the cell culture chamber 1, and transmit it to the PID temperature controller 6. When the cold end 10 of the thermoelectric cooling sheet 3 is cooling, heat is transferred from the cold end 10 of the thermoelectric cooling sheet 3 to the hot end, thereby improving the cooling efficiency.

[0026] The cold end 10 at the top of the thermoelectric cooling sheet 3 is tightly connected to the temperature sensor 2, and the hot end 14 at the bottom is connected to the micro-channel heat sink of the water-cooling circulation cooling system 5. The heat generated by the hot end 14 is transferred to the heat sink of the water-cooling circulation cooling system 5 through the substrate, and then transferred to the heat sink by the heat sink. There are a large number of needle-shaped, square or round fins inside the heat sink to increase the contact area with the coolant and improve the heat exchange efficiency of the heat exchange system. The shape, size and number of the fins are determined according to the actual space limitations and heat dissipation requirements of the device. When the coolant of the water-cooling circulation cooling system 5 flows through the micro-channel composed of the heat sink and the heat dissipation fins, the heat is taken away, thereby achieving the heat dissipation effect of the hot end 14 at the bottom of the thermoelectric cooling sheet 3. The temperature control chip integrated in the PID temperature controller 6 can adjust the flow rate of the coolant in the water-cooling circulation cooling system 5 according to the temperature of the hot end 14 of the thermoelectric cooling sheet 3 to achieve the purpose of maintaining the temperature stability of the working platform. The operating voltage range of the thermoelectric cooling sheet 3 is 3-6V, and the operating current range is 0.5-2A. According to different use requirements, different working powers are used within the available power range.

[0027] The PID temperature controller 6 includes a DC power supply, a DC voltage and current regulator, a temperature sensor 2 and a display 8. The temperature sensor 2, the circular piezoelectric ceramic piece 4 and the thermoelectric cooling piece 3 are electrically connected to the PID temperature controller 6. The DC voltage and current regulator is connected to the thermoelectric cooling piece 3 to adjust the power of the thermoelectric cooling piece 3. The temperature control chip is connected to the temperature sensor 2, the hot end 14 of the thermoelectric cooling piece 3 and the flow regulating device of the water cooling cycle cooling system 5. The user can view the specific working parameters and information of the temperature control platform through the display 8, and can use the button 9 to set the working conditions so that the thermoelectric cooling piece 3 is maintained within the preset target temperature range.

[0028] The square opening on the top of the shell 7 is assembled and connected to the cell culture chamber 1, four circular piezoelectric ceramic sheets 4 are connected around the square opening on the top of the shell 7, the circular openings on both sides of the shell 7 are assembled and connected to the circular inlets and outlets of the micro-channel heat dissipation fins in the water-cooled circulation cooling system 5, and the notch at the lower end of the front side of the shell 7 cooperates with the PID temperature controller 6.

[0029] The electric cooling plate includes P-type grains 11 and N-type grains 12. There are multiple P-type grains and multiple N-type grains. The multiple P-type grains and the multiple N-type grains are respectively arranged at both ends of multiple electrodes 13 in a one-to-one correspondence, and the P-type grains on two adjacent electrodes are not at the same end.

[0030] When the temperature control platform is working, the thermoelectric cooling sheet 3 continuously cools the cell culture chamber 1, the temperature sensor 2 monitors the temperature of the cell culture chamber 1 in real time and ensures the temperature stability, the water cooling cycle cooling system 5 ensures that the entire device does not overheat during operation, and ensures the stability and safety of the equipment operation. The integrated control system can control the working state of the four circular piezoelectric ceramic pieces 4, and control the state of the suspended particles in the droplets to be detected in the cell culture chamber 1 by adjusting the working conditions of the different circular piezoelectric ceramic pieces 4 around, thereby improving the accuracy of detecting suspended particles in the droplets. The device can provide a cell culture chamber 1 with a temperature range of 0℃-20℃ that can be freely adjusted for users.

[0031] Meanwhile, the contents not described in detail in this specification belong to the prior art known to those skilled in the art.

[0032] When the thermoelectric cooling sheet 3 is working, the water cooling cycle cooling system 5 is started at the same time, and the temperature sensor 2 transmits the temperature of the cell culture chamber 1 to the temperature control chip. The user can adjust the working power of the cell culture chamber 1 through the DC voltage and current regulator. The DC voltage and current regulator has voltage and current buttons 9. The user can manually adjust the working voltage range and current range according to the use requirements, so as to achieve the purpose of controlling the working power of the thermoelectric cooling sheet 3. The temperature of the cell culture chamber 1 is controlled by the temperature control chip, and finally the temperature of the cell culture chamber 1 meets the use requirements of the user.

[0033] The DC power supply is used to power the temperature monitoring and control system. The user defines the required working temperature and temperature control accuracy of the cell culture chamber 1 through the temperature control chip, and controls the power of the thermoelectric cooling sheet 3 through the DC voltage and current regulator. The user sets the working temperature and temperature control accuracy of the thermoelectric cooling sheet 3 through the temperature control chip, and the data obtained by the temperature sensor 2 is transmitted to the temperature control chip. When the actual temperature of the cell culture chamber 1 is higher than the set temperature (the temperature difference is greater than the temperature control accuracy), the temperature control chip ensures that the thermoelectric cooling sheet 3 continues to work until the set temperature is reached. If the actual temperature of the cell culture chamber 1 is lower than the set temperature (the temperature difference is greater than the temperature control accuracy), the temperature control chip cuts off the power to the thermoelectric cooling sheet 3 until the temperature reaches the set temperature. The DC voltage and current regulator is responsible for adjusting the magnitude of the working voltage and the magnitude of the working current to ensure stable operation of the equipment. In some usage scenarios, increasing the working current and voltage to increase the power of the thermoelectric cooling sheet 3 can improve work efficiency. The integrated control system can control the working state of the four circular piezoelectric ceramic sheets 4, and control the state of the suspended particles in the droplets to be detected in the cell culture chamber 1 by adjusting the working conditions of the different circular piezoelectric ceramic sheets 4 around, thereby improving the accuracy of detecting suspended particles in the droplets.

[0034] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0035] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. An in vitro cell culture platform with acoustic wave stimulation and precise temperature control, characterized in that: The invention comprises a thermoelectric cooling sheet (3), a cell culture chamber (1), a circular piezoelectric ceramic sheet (4), a water-cooling circulation cooling system (5), a PID temperature controller (6), and a housing (7). The top of the thermoelectric cooling sheet (3) is in contact with the cell culture chamber (1), the bottom of the thermoelectric cooling sheet is in contact with the water-cooling circulation cooling system (5), and the temperature monitoring and control system are respectively connected to the cell culture chamber (1) and the thermoelectric cooling sheet.

2. The in vitro cell culture platform for acoustic wave stimulation and precise temperature control according to claim 1, characterized in that: The thermoelectric cooling sheet (3) comprises P-type crystal grains (11) and N-type crystal grains (12), wherein there are a plurality of the P-type crystal grains and a plurality of the N-type crystal grains, and the plurality of the P-type crystal grains and the plurality of the N-type crystal grains are arranged one by one at two ends of a plurality of electrodes (13), respectively, and the P-type crystal grains on two adjacent electrodes are not at the same end.

3. The in vitro cell culture platform for acoustic wave stimulation and precise temperature control according to claim 1, characterized in that: The PID temperature controller (6) comprises a direct current power supply, a DC voltage and current regulator, a temperature sensor (2) and a display (8), wherein the temperature sensor is arranged between the cell culture chamber and the piezoelectric cooling sheet and is connected to the temperature control chip, and the DC voltage and current regulator is connected to the thermoelectric cooling sheet.

4. The in vitro cell culture platform for acoustic wave stimulation and precise temperature control according to claim 1, characterized in that: Four circular piezoelectric ceramic sheets (4) are connected to four walls of a cell culture chamber (1), and the tops of the circular piezoelectric ceramic sheets are in contact with the top inner wall of the housing (7). An alternating current signal is applied to both ends of the electrode (13), which excites surface acoustic waves through the inverse piezoelectric effect for controlling the movement of suspended particles inside microdroplets, thereby providing acoustic wave stimulation for achieving in vitro cell culture.

5. The in vitro cell culture platform for acoustic wave stimulation and precise temperature control according to claim 1, characterized in that: The operating temperature of this in vitro cell culture platform is 0-50°C, and the temperature control accuracy is ±0.1°C.

6. The in vitro cell culture platform for acoustic wave stimulation and precise temperature control according to claim 1, characterized in that: The operating voltage range of the thermoelectric cooling sheet (3) is 0-6V, and the operating current range is 0-2A.

7. The in vitro cell culture platform for acoustic wave stimulation and precise temperature control according to claim 1, characterized in that: The water-cooling circulation temperature reduction system (5) comprises a water flow control system, micro-channel heat sink fins and a booster silent water pump. The water flow control system can adjust the water flow entering the heat sink fins according to the temperature of the hot end (14) of the thermoelectric cooling plate.

8. The in vitro cell culture platform for acoustic wave stimulation and precise temperature control according to claim 3, characterized in that: The cold end (10) at the top of the thermoelectric cooling sheet (3) contacts the temperature sensor, and the hot end (14) at the bottom of the thermoelectric cooling sheet contacts the micro-channel heat dissipation fins of the water-cooling circulation temperature reduction system.

Citation Information

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