Microfluidic chip refrigeration system and temperature control method

Abstract

The application provides a micro-fluidic chip refrigeration system, belonging to the technical field of micro-fluidics, comprising a hollow transparent refrigeration box with a concave cross section, heat insulation material coated on the outer surface of the refrigeration box through bonding, a refrigeration module, a temperature sensor and a temperature controller. The application also provides a temperature control method for the micro-fluidic chip refrigeration system. The micro-fluidic chip refrigeration system and the temperature control method have the refrigeration box designed as a box with a concave cross section, the height of the two sides of the box can be matched with the size of the actual semiconductor refrigeration module, the temperature sensor can measure the temperature in the refrigeration box in real time and feed back to the temperature controller, the temperature controller can judge whether the semiconductor refrigeration module continues to work through the pre-set temperature range, so that the temperature in the refrigeration box is always kept within a certain range, the precision can reach within 1 DEG C, the precision is high, the temperature control range is large, the operation is simple, and the system can be combined with a microscope for real-time observation.

Description

Technical Field

[0001] The present invention belongs to the field of microfluidic technology and relates to a microfluidic chip refrigeration system and a temperature control method. Background Art

[0002] A microfluidic chip is a chemical or biological laboratory built on a centimeter-square chip. Basic operations can be integrated onto a very small chip, with microchannels forming a network to control the flow of fluids through the system, enabling functions such as chemical synthesis and biological detection. However, temperature control is often required during chemical synthesis and biological detection. For example, gene sequencing PCR testing requires cycling between 95°C, 65°C, and 4°C. Cultivation of marine organisms such as hydra generally requires maintaining a temperature between 8-15°C.

[0003] One existing solution involves using a commercial temperature table, where the entire microfluidic chip is placed on the temperature control console to heat or cool it. Another approach involves placing the entire microfluidic culture chip in a sufficiently large temperature-controlled chamber. This approach offers a wide temperature control range and is relatively well-established. A commonly used cooling method in engineering involves combining semiconductor refrigeration chips, heat sinks, and cooling fans, but this approach is difficult to integrate with microfluidic chips.

[0004] The commercial temperature stage used is relatively easy to quickly control the overall heating process, but the cooling process requires a long wait due to the lack of a heat dissipation device, which may also cause damage to the control console. At the same time, it cannot achieve independent temperature control of multiple units and cannot provide a suitable observation path for the microscope. Although it is simple and easy to place the entire microfluidic culture chip in a sufficiently large box that can be controlled in temperature, this does not meet the requirements of independent temperature control of multiple units in the microfluidic chip, and it also makes it difficult to observe the internal conditions of the microfluidic chip. Large volumes of water can also be cooled for standby use and input into the microfluidic chip, but the energy loss at room temperature is large, and the temperature control is unstable and imprecise. Using a combination of semiconductor refrigeration plates, heat sinks and cooling fans to directly cool the microfluidic chip will make it impossible for the microscope to observe and record the status of the microfluidic chip in real time.

[0005] Therefore, there is an urgent need to study a microfluidic chip refrigeration system and temperature control method that can solve the problem that the existing refrigeration method cannot observe the microfluidic chip in real time and the disadvantage of low precision, and provide a refrigeration system with high precision, large temperature control range, simple operation, and can be combined with a microscope, and can observe the microfluidic chip in real time. Summary of the Invention

[0006] In view of this, the present invention will provide a microfluidic chip refrigeration system and temperature control method, and the refrigeration box is designed to be a box with a "concave"-shaped cross-section. The middle position of the box can provide movable space for focusing in the vertical direction to the maximum extent. The height of both sides of the box can be matched with the actual size of the semiconductor refrigeration module. At the same time, the temperature sensor can measure the temperature in the refrigeration box in real time and feed it back to the temperature controller. The temperature controller can determine whether to continue to work in the semiconductor refrigeration module according to the preset temperature range, so that the temperature in the refrigeration box is always maintained within a certain range with an accuracy of less than 1°C. It has high precision, a large temperature control range, simple operation, and can be combined with a microscope for real-time observation.

[0007] To achieve the above objectives, the present invention provides a microfluidic chip refrigeration system, comprising a hollow, transparent refrigeration box with a concave cross-section. A microfluidic chip is placed at the center of the bottom surface of the refrigeration box by bonding an insulating material to the outer surface of the refrigeration box. No insulating material is provided in the observation path areas above and below the microfluidic chip. A refrigeration module is provided on each of the left and right sides of the refrigeration box, and the refrigeration module is used to control the temperature within the refrigeration box.

[0008] The refrigeration module is composed of a cold-end cooling fan, a cold-end heat sink, a semiconductor refrigeration fin, a hot-end heat sink, and a hot-end cooling fan from left to right. Through holes for installing the refrigeration module are provided on the left and right sides of the refrigeration box. Through holes are also provided on the insulation material at corresponding positions. The cold end of the refrigeration module extends into the interior of the refrigeration box through the through holes. The size of the through holes matches the size of the cold-end heat sink, so that a closed chamber is formed inside the refrigeration box.

[0009] It also includes a temperature sensor and a temperature controller; the temperature sensor is electrically connected to the semiconductor refrigeration plate and the temperature sensor respectively; the temperature sensor is arranged inside the refrigeration box to detect the temperature inside the refrigeration box and feed back to the temperature controller, and the temperature controller controls the operation of the semiconductor refrigeration plate according to a preset temperature range, so that the temperature inside the refrigeration box is maintained within the preset temperature range.

[0010] Furthermore, the refrigeration box is made of a double-layer vacuum PMMA board.

[0011] Furthermore, the thermal insulation material is foamed plastic with a thickness of 3 to 5 cm.

[0012] Furthermore, the cold-end heat sink and the cold-end cooling fan are consistent in size with the semiconductor refrigeration fin, and the hot-end heat sink and the hot-end cooling fan are three times the size of the semiconductor refrigeration fin; each contact surface between the cold-end cooling fan, the cold-end heat sink, the semiconductor refrigeration fin, the hot-end heat sink, and the hot-end cooling fan is evenly coated with thermal grease for bonding.

[0013] Furthermore, the semiconductor refrigeration chip is a 12706 type semiconductor refrigeration chip with an external size of 40×40×4.7 mm.

[0014] Furthermore, the temperature controller is of the XH-W1315 type, with a temperature measurement and control range of -50°C to 110°C, an input power supply of 12 / 24V DC, and an external size of 79×54×21mm.

[0015] Furthermore, the temperature sensor is a temperature sensing probe, which is any one of a thermocouple wire, a waterproof head, a water drop head, and a magnetic head. A through hole is opened in the refrigeration box so that the temperature sensing probe can be inserted into the interior thereof. One end of the temperature sensing probe is electrically connected to the temperature controller, and the other end is placed at a distance of no more than 5 cm from the microfluidic chip.

[0016] Furthermore, the concave area of ​​the refrigeration box is sufficient for a microscope to move vertically and adjust the focal length for real-time observation of the sample in the microfluidic chip, and the side height of the refrigeration box is greater than the height of the cold end of the refrigeration module.

[0017] Furthermore, a hole is opened at the bottom of the refrigeration box near the microfluidic chip for installing a liquid flow tube, one end of the liquid flow tube is connected to the microfluidic chip for introducing a sample, and a sealant is applied to the liquid flow tube for sealing.

[0018] The present invention also provides a temperature control method using the microfluidic chip refrigeration system as described above, comprising the following steps:

[0019] Debugging the microfluidic chip refrigeration system to ensure it is in normal condition;

[0020] A preset temperature range is input on the temperature controller, and the temperature controller receives the measured temperature detected by the temperature sensor. When the measured temperature is within the preset temperature range, the temperature controller controls the semiconductor refrigeration chip to stop working. When the measured temperature is greater than or less than the preset temperature range, the temperature controller controls the semiconductor refrigeration chip to restart working so that the measured temperature returns to the preset temperature range.

[0021] The advantages of the present invention using the above technical solution are:

[0022] The microfluidic chip refrigeration system and temperature control method of the present invention place the microfluidic chip in a temperature-controlled refrigeration box, use PMMA (polymethyl methacrylate) with low thermal conductivity as the refrigeration box material, and have high transparency, which can provide good observation conditions for a microscope. To reduce the influence of external temperature, the refrigeration box is made of a double-layer vacuum PMMA board, and a 3-5 cm thick foam plastic is attached to the outside of the refrigeration box. The refrigeration box is designed to have a "concave"-shaped cross-section. The middle position of the box can provide a movable space for focusing in the vertical direction to the greatest extent. The height of both sides of the box can be matched with the actual size of the semiconductor refrigeration module. At the same time, the temperature sensor can measure the temperature in the refrigeration box in real time and feed it back to the temperature controller. The temperature controller can determine whether to continue to operate the semiconductor refrigeration module according to a preset temperature range, so that the temperature in the refrigeration box is always maintained within a certain range with an accuracy of less than 1°C. The system has high accuracy, a large temperature control range, simple operation, and can be combined with a microscope for real-time observation. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0024] Figure 1 Schematic diagram of the structure of the microfluidic chip refrigeration system of the present invention;

[0025] Figure 2 This is a schematic structural diagram of a refrigeration module in the microfluidic chip refrigeration system of the present invention;

[0026] Figure 3 Schematic diagram of the electrical connection between the temperature controller, the refrigeration module and the temperature sensor in the microfluidic chip refrigeration system of the present invention;

[0027] Figure 4 This is a temperature control principle diagram of the microfluidic chip refrigeration system of the present invention. DETAILED DESCRIPTION

[0028] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0029] The present invention provides a microfluidic chip refrigeration system, such as Figure 1As shown, it includes a hollow transparent refrigeration box with a concave cross-section. The microfluidic chip is placed at the center of the bottom surface of the refrigeration box by bonding the thermal insulation material coated on the outer surface of the refrigeration box. The observation path area above and below the microfluidic chip is not provided with thermal insulation material. A refrigeration module is provided on the left and right sides of the refrigeration box respectively, and the refrigeration module is used to control the temperature inside the refrigeration box.

[0030] like Figure 2 The figure shows a schematic diagram of the refrigeration module structure. The refrigeration module consists of a cold-end cooling fan, a cold-end heat sink, a semiconductor refrigeration fin, a hot-end heat sink, and a hot-end cooling fan from left to right. Through holes for installing the refrigeration module are opened on the left and right sides of the refrigeration box, and through holes are also opened on the insulation material at the corresponding positions. The cold end of the refrigeration module extends into the interior of the refrigeration box through the through hole. The size of the through hole matches the size of the cold-end heat sink to form a closed chamber inside the refrigeration box.

[0031] like Figure 3 As shown in FIG, it is a schematic diagram of the electrical connection between the temperature controller, the refrigeration module, and the temperature sensor, which also includes a temperature sensor and a temperature controller; the temperature sensor is electrically connected to the semiconductor refrigeration chip and the temperature sensor respectively. Figure 4 As shown in the figure, it is a temperature control principle diagram of the microfluidic chip refrigeration system of the present invention. The temperature sensor is arranged inside the refrigeration box to detect the temperature inside the refrigeration box and feed back to the temperature controller. The temperature controller controls the operation of the semiconductor refrigeration chip according to a preset temperature range, so that the temperature inside the refrigeration box is maintained within the preset temperature range.

[0032] The refrigeration box is constructed from a double-layer vacuum PMMA sheet. PMMA has low thermal conductivity and high transparency, providing excellent microscope observation conditions. The double-layer vacuum PMMA sheet further reduces the impact of ambient temperature. The insulation material is a foam plastic with a thickness of 3-5 cm. The concave area within the refrigeration box allows for vertical movement and focal adjustment of the microscope for real-time observation of samples within the microfluidic chip. The side height of the refrigeration box is greater than the height of the cold end of the refrigeration module.

[0033] The cold-end heat sink and cold-end cooling fan are the same size as the semiconductor refrigeration chip, while the hot-end heat sink and hot-end cooling fan are three times the size of the semiconductor refrigeration chip. All contact surfaces between the cold-end cooling fan, cold-end heat sink, semiconductor refrigeration chip, hot-end heat sink, and hot-end cooling fan are evenly coated with thermally conductive silicone grease and bonded together. The semiconductor refrigeration chip is preferably a 12706-type semiconductor refrigeration chip with dimensions of 40×40×4.7 mm.

[0034] Among them, the role of the temperature controller in this solution is to control the temperature fluctuation range, and the fluctuation range can be set manually. The XH-type digital temperature controller is easy to install and simple to connect. The start and stop temperatures can be set. It has high precision, long life, and low price. It can completely replace mechanical temperature control and has a delayed start function. The temperature controller of the present invention is preferably XH-W1315 type, with a temperature measurement and control range of -50℃-110℃, an input power supply of 12 / 24V DC, and an external size of 79×54×21mm, which meets the requirements of occupying appropriate space. The temperature sensor is a temperature probe, which is any one of a thermocouple wire, a waterproof head, a water drop head, a magnetic head, etc. A through hole is opened in the refrigeration box so that the temperature probe can extend into it. One end of the temperature probe is electrically connected to the temperature controller, and the other end is placed at a distance of less than 5cm from the microfluidic chip. When the temperature of the refrigeration box is within the set temperature range, the temperature controller will stop the semiconductor refrigeration chip from working. When the temperature of the refrigeration box is greater than or less than the set temperature range, the temperature controller will restart the semiconductor refrigeration chip to cause the temperature to return to the set temperature range. At room temperature, the temperature control range can reach 6 to 20°C, and the temperature control accuracy can reach within 1°C.

[0035] In addition, a hole can be opened at the bottom of the refrigeration box near the microfluidic chip for installing a liquid flow tube. One end of the liquid flow tube is connected to the microfluidic chip for introducing a sample, and sealant is applied to the liquid flow tube for sealing.

[0036] The present invention also provides a temperature control method using the microfluidic chip refrigeration system as described above, comprising the following steps:

[0037] Debugging the microfluidic chip refrigeration system to ensure it is in normal condition;

[0038] A preset temperature range is input on the temperature controller, and the temperature controller receives the measured temperature detected by the temperature sensor. When the measured temperature is within the preset temperature range, the temperature controller controls the semiconductor refrigeration chip to stop working. When the measured temperature is greater than or less than the preset temperature range, the temperature controller controls the semiconductor refrigeration chip to restart working so that the measured temperature returns to the preset temperature range.

[0039] The advantages of the present invention using the above technical solution are:

[0040] The microfluidic chip refrigeration system and temperature control method of the present invention place the microfluidic chip in a temperature-controlled refrigeration box, use PMMA (polymethyl methacrylate) with low thermal conductivity as the refrigeration box material, and have high transparency, which can provide good observation conditions for a microscope. To reduce the influence of external temperature, the refrigeration box is made of a double-layer vacuum PMMA board, and a 3-5 cm thick foam plastic is attached to the outside of the refrigeration box. The refrigeration box is designed to have a "concave"-shaped cross-section. The middle position of the box can provide a movable space for focusing in the vertical direction to the greatest extent. The height of both sides of the box can be matched with the actual size of the semiconductor refrigeration module. At the same time, the temperature sensor can measure the temperature in the refrigeration box in real time and feed it back to the temperature controller. The temperature controller can determine whether to continue to operate the semiconductor refrigeration module according to a preset temperature range, so that the temperature in the refrigeration box is always maintained within a certain range with an accuracy of less than 1°C. The system has high accuracy, a large temperature control range, simple operation, and can be combined with a microscope for real-time observation.

[0041] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A microfluidic chip refrigeration system, characterized in that: The invention comprises a hollow transparent refrigeration box with a concave cross-section, a heat-insulating material bonded to the outer surface of the refrigeration box, a microfluidic chip placed at the center of the bottom surface of the refrigeration box, and an observation path area above and below the microfluidic chip without heat-insulating material. A refrigeration module is provided on each side of the refrigeration box, and the refrigeration module is used to control the temperature inside the refrigeration box. The refrigeration module is composed of a cold-end cooling fan, a cold-end heat sink, a semiconductor refrigeration fin, a hot-end heat sink, and a hot-end cooling fan from left to right. Through holes for installing the refrigeration module are provided on the left and right sides of the refrigeration box. Through holes are also provided on the insulation material at corresponding positions. The cold end of the refrigeration module extends into the interior of the refrigeration box through the through holes. The size of the through holes matches the size of the cold-end heat sink, so that a closed chamber is formed inside the refrigeration box. The device further comprises a temperature sensor and a temperature controller; the temperature sensor is electrically connected to the semiconductor refrigeration chip and the temperature controller respectively; the temperature sensor is arranged inside the refrigeration box to detect the temperature inside the refrigeration box and feed back to the temperature controller, and the temperature controller controls the operation of the semiconductor refrigeration chip according to a preset temperature range, so that the temperature inside the refrigeration box is maintained within the preset temperature range; The concave area of ​​the refrigeration box is large enough for a microscope to move vertically and adjust the focus for real-time observation of the sample in the microfluidic chip, and the side height of the refrigeration box is greater than the height of the cold end of the refrigeration module; The refrigeration box is made of double-layer vacuum PMMA board; The thermal insulation material is foamed plastic with a thickness of 3 to 5 cm.

2. The microfluidic chip refrigeration system according to claim 1, characterized in that: The cold-end heat sink and the cold-end cooling fan are consistent in size with the semiconductor refrigeration fin, and the hot-end heat sink and the hot-end cooling fan are three times the size of the semiconductor refrigeration fin; each contact surface between the cold-end heat sink fan, the cold-end heat sink, the semiconductor refrigeration fin, the hot-end heat sink, and the hot-end cooling fan is evenly coated with thermal grease for bonding.

3. The microfluidic chip refrigeration system according to claim 1, characterized in that: The semiconductor refrigeration chip is a 12706 type semiconductor refrigeration chip with an external size of 40×40×4.7 mm.

4. The microfluidic chip refrigeration system according to claim 1, characterized in that: The temperature controller is XH-W1315 model, with a temperature measurement and control range of -50°C to 110°C, an input power supply of 12 / 24V DC, and an external size of 79×54×21mm.

5. The microfluidic chip refrigeration system according to claim 1, characterized in that: The temperature sensor is a temperature sensing probe, which is a thermocouple wire. A through hole is opened in the refrigeration box so that the temperature sensing probe can extend into the interior thereof. One end of the temperature sensing probe is electrically connected to the temperature controller, and the other end is placed within 5 cm of the microfluidic chip.

6. The microfluidic chip refrigeration system according to claim 1, characterized in that: The temperature sensor is a temperature sensing probe, which has a waterproof head. A through hole is opened in the refrigeration box so that the temperature sensing probe can be inserted into the interior. One end of the temperature sensing probe is electrically connected to the temperature controller, and the other end is placed within 5 cm from the microfluidic chip.

7. The microfluidic chip refrigeration system according to claim 1, characterized in that: The temperature sensor is a temperature sensing probe, which is a water drop head. A through hole is opened in the refrigeration box so that the temperature sensing probe can extend into the interior. One end of the temperature sensing probe is electrically connected to the temperature controller, and the other end is placed within 5 cm from the microfluidic chip.

8. The microfluidic chip refrigeration system according to claim 1, characterized in that: The temperature sensor is a temperature sensing probe, which is a magnetic head. A through hole is opened in the refrigeration box so that the temperature sensing probe can extend into the interior. One end of the temperature sensing probe is electrically connected to the temperature controller, and the other end is placed within 5 cm from the microfluidic chip.

9. The microfluidic chip refrigeration system according to claim 1, characterized in that: It also includes a hole at the bottom of the refrigeration box near the microfluidic chip for installing a liquid flow tube. One end of the liquid flow tube is connected to the microfluidic chip for introducing a sample, and sealant is applied to the liquid flow tube for sealing.

10. A temperature control method using the microfluidic chip refrigeration system according to any one of claims 1 to 9, characterized in that: The following steps are involved: Debugging the microfluidic chip refrigeration system to ensure it is in normal condition; A preset temperature range is input on the temperature controller, and the temperature controller receives the measured temperature detected by the temperature sensor. When the measured temperature is within the preset temperature range, the temperature controller controls the semiconductor refrigeration chip to stop working. When the measured temperature is greater than or less than the preset temperature range, the temperature controller controls the semiconductor refrigeration chip to restart working so that the measured temperature returns to the preset temperature range.

Images