Microfluidic linear cooling method and temperature control system based on thermoelectric refrigeration

Abstract

This invention discloses a microfluidic linear cooling method and temperature control system based on thermoelectric cooling, comprising the following steps: selecting a suitable thermoelectric cooler according to the target rate range of linear cooling of the microfluidic fluid within the microfluidic chip; installing the selected thermoelectric cooler between the microfluidic chip and the heat sink; controlling the operating current of the thermoelectric cooler through a programmable DC power supply; customizing a current curve function to control the driving current by coupling a single function current curve; analyzing the microfluidic cooling curve and verifying its linearity; iterating the current curve by changing the coupling parameters α and β to obtain the current curves corresponding to different microfluidic cooling rates; inputting the current functions corresponding to different microfluidic cooling rates obtained from simulation into the programmable DC power supply, thereby achieving linear cooling of the microfluidic fluid at different rates using thermoelectric cooling. This achieves a linear coupling response between current, cooling capacity, and microfluidic temperature within the microfluidic chip.

Description

Technical Field

[0001] This invention relates to the field of microfluidic cooling technology, and in particular to a microfluidic linear cooling method and temperature control system based on thermoelectric cooling. Background Technology

[0002] Microfluidic chips, also known as "lab-on-a-chip" devices, can simplify complex biomedical and chemical research, enable batch sample screening and processing, significantly reduce the amount of samples to be analyzed, and improve the predictability and controllability of research. They have unique advantages in the preparation of artificial biomembranes and cell analysis.

[0003] Manipulating biomicrofluidics requires not only precise control of the microfluidic component ratios but also, in certain scenarios, linear temperature regulation with a constant rate of temperature change. For cryopreservation, in addition to the cellular chemical environment, cell viability during freezing and thawing also depends on the cooling and thawing rates. To avoid intracellular freezing or freezing damage caused by high electrolyte concentrations, linear cooling or thawing of samples at the optimal rate of temperature change is necessary, which is difficult to achieve using conventional microfluidic temperature control methods. Summary of the Invention

[0004] This invention aims to at least partially solve one of the technical problems in related technologies. To this end, one objective of this invention is to propose a microfluidic linear cooling method and temperature control system based on thermoelectric cooling. This method obtains an unsteady transition current by coupling a conventional current, inputs the unsteady transition current curve to the thermoelectric cooler, and iteratively compensates for the cooling capacity gap and surplus generated by a single function current curve when cooling the microfluidic, thus ensuring the accuracy of constant-rate cooling of the microfluidic using thermoelectric cooling.

[0005] According to the present invention, a microfluidic linear cooling method based on thermoelectric refrigeration is proposed, the method steps are as follows:

[0006] S1: Inject the microfluidic fluid to be temperature controlled into the sample cell of the microfluidic chip;

[0007] S2: Select a suitable thermoelectric cooler according to the target rate range of linear cooling of the microfluidic fluid in the microfluidic chip, install the selected thermoelectric cooler between the microfluidic chip and the heat dissipation plate, and control the current on the thermoelectric cooler through a programmable DC power supply.

[0008] S3: Set the maximum cooling time t gen Target cooling rate T g,m ;

[0009] S4: Based on the maximum cooling time t gen Target cooling rate T g,mSet the initial values ​​for the parameters α and β of the unsteady transient current. The method for setting the initial values ​​of the parameters is as follows:

[0010] α=I a / (t gen ×t gen )

[0011] β=I b / t gen

[0012] Among them, I a with I b Satisfy I b +I a =I m I m To determine the optimal operating current of the thermoelectric cooler, initially, I is set. a =0;

[0013] S5: Based on the initial values ​​α and β of the unsteady transient current parameters, the conventional current is coupled to obtain the current function I = α × t² + β × t, where t represents time. This current function is then input into a thermoelectric cooler for numerical analysis and experimentation. Post-processing is used to obtain the microfluidic cooling curve under this current function, and the Rc of the cooling curve is calculated. 2 R 2 The goodness of fit between the actual cooling curve and the target linear cooling curve is calculated using the following formula:

[0014]

[0015] Among them, T i These are the temperature measurements at various times. This is the average of the temperature measurements. To achieve the target temperature value for linear cooling of the microfluidic fluid at each time step, R 2 The value is between 0 and 1; the closer it is to 1, the better the linearity of the cooling process.

[0016] S6: Determine R m 2 ≤R 2 Whether it is true or not, where R m 2 To satisfy the linear cooling condition R 2 If the minimum value is found, proceed to step S7; otherwise, make I... a =I a +I S I S To set the current iteration step size, proceed to step S4;

[0017] S7: Determine |T g -Tg,m |≤E r Whether it is true or not, where T g To calculate the microfluidic cooling rate, E r If the cooling rate error limit is met, proceed to step S9; otherwise, proceed to step S8.

[0018] S8: Determine T g -T g,m Does ≤0 hold true? If so, does it make t gen =t gen -t m If not, then t gen =t gen +t m and output the corrected t gen Proceed to step S4;

[0019] S9: Determine the values ​​of α and β, and input the current function I=α*t²+β*t into the programmable DC power supply to start the microfluidic temperature control system based on thermoelectric cooling, and record the changes in microfluidic temperature through the data acquisition instrument.

[0020] Preferably, the current function I is coupled with a single function current curve to obtain an unsteady transition current. The single function current curve refers to the relationship between current I and time t as a power of 1 or a power of 2. Changing the single function current curve involved in the coupling obtains different unsteady transition current ranges, thereby adapting to different microfluidic cooling target rates.

[0021] Preferably, the microfluidic temperature control system based on thermoelectric cooling includes a first heat dissipation plate, a perforated ring thermoelectric cooler, a microfluidic chip, and a support. The perforated ring thermoelectric cooler is disposed on the upper end of the microfluidic chip at the sample cell position. The first heat dissipation plate with a central opening is mounted on the upper end of the perforated ring thermoelectric cooler. The first heat dissipation plate, the perforated ring thermoelectric cooler, and the microfluidic chip are fixed by the support. A microscope is provided above the first heat dissipation plate directly opposite the opening. An injection pump for pumping microfluidic fluid into the sample cell is connected to the inlet. A waste liquid collection container is connected to the outlet of the sample cell. A programmable DC power supply is connected to the power input terminal of the perforated ring thermoelectric cooler. A temperature measurement channel is provided in the sample cell, and a temperature acquisition point for acquiring temperature using a temperature acquisition instrument is provided in the temperature measurement channel.

[0022] Preferably, a nitrogen nozzle is installed at the bottom of the microfluidic chip, the inlet of the nitrogen nozzle is connected to a precooling component, and the precooling component is externally connected to a nitrogen tank.

[0023] Preferably, the precooling assembly includes two sets of block thermoelectric coolers and a gas cooling plate. Each set of block thermoelectric coolers includes two block thermoelectric coolers. The gas cooling plate is installed between the two sets of block thermoelectric coolers. The cold ends of the two sets of block thermoelectric coolers are located on the side close to the gas cooling plate. A second heat dissipation plate is installed on the hot end of each set of block thermoelectric coolers away from the gas cooling plate. The second heat dissipation plate has a cooling water inlet for connecting external cooling water and a cooling water outlet for discharging cooling water. The gas cooling plate has a nitrogen inlet and a nitrogen outlet. The nitrogen inlet is connected to a nitrogen tank, and the nitrogen outlet is connected to a nitrogen nozzle.

[0024] Preferably, the first heat dissipation plate is provided with a circulating cooling water pipe inside, and the circulating cooling water pipe is connected to a constant temperature water tank outside.

[0025] Preferably, the control method steps of the microfluidic temperature control system based on thermoelectric cooling are as follows:

[0026] A1: Turn on the syringe pump, and the microfluidic fluid flows into the microfluidic chip sample cell. Turn on the microscope to observe the microfluidic chip sample cell in real time, and turn on the temperature acquisition instrument to record the temperature T of the microfluidic chip sample cell. cen Perform real-time measurements;

[0027] A2: Turn on the precooling device and simultaneously open the nitrogen cylinder valve, and set the nitrogen flow rate;

[0028] A3: The programmable DC power supply is turned on, and the current direction is controlled to power the orifice ring thermoelectric cooler in the first current direction so that it is in cooling mode. Input the current value or current curve to control the temperature of the microfluidic at room temperature. During this period, the microfluidic sample cell is observed and the temperature is measured in real time through a microscope and a data acquisition instrument.

[0029] The beneficial effects of this invention are:

[0030] This microfluidic linear cooling method achieves temperature control of the microfluidic chip at room temperature by combining the microfluidic chip with a thermoelectric cooler. The thermoelectric cooler, as a cooling device, has the advantages of simple structure, small size, fast cooling rate, and accurate temperature control, thus ensuring the temperature range requirements for microfluidic chip research.

[0031] This microfluidic linear cooling method obtains an unsteady transition current by coupling a conventional current, inputs the unsteady transition current curve to the thermoelectric cooler, and iterates the unsteady transition current to compensate for the cooling gap and cooling surplus generated by the single function current curve when cooling the microfluidic, thus ensuring the accuracy of constant-rate cooling of the microfluidic using thermoelectric cooling.

[0032] This microfluidic linear cooling method can switch the linear cooling rate range of the thermoelectric cooling microfluidic chip by switching different models of thermoelectric coolers, so as to meet different microfluidic temperature control requirements.

[0033] This system effectively avoids condensation and frost on the bottom of the microfluidic chip by using flowing nitrogen, thus ensuring the accuracy of optical observation. At the same time, the pre-cooling device avoids the influence of room temperature nitrogen on the cooling process of the microfluidic chip.

[0034] This system can switch the heating / cooling mode of the microfluidic chip by switching the direction of the current to cope with different application scenarios;

[0035] This system's programmable DC power supply can achieve diverse temperature control of microfluidics in microfluidic chips, including isothermal control, stepped temperature control, and linear cooling. Attached Figure Description

[0036] In the attached diagram:

[0037] Figure 1 This is a flowchart of a microfluidic linear cooling method based on thermoelectric refrigeration proposed in this invention;

[0038] Figure 2 This is a diagram illustrating the iterative process of the input current curve of the thermoelectric cooler proposed in this invention.

[0039] Figure 3 This is a diagram illustrating the iterative process of the temperature curve of the microfluidic sample cell proposed in this invention.

[0040] Figure 4 The present invention provides the current curve and the microfluidic temperature response curve after inputting the current curve into the model.

[0041] Figure 5 The linear cooling current waveform and temperature response curve proposed in this invention;

[0042] Figure 6 This is a flowchart of the microfluidic temperature control system based on thermoelectric cooling proposed in this invention.

[0043] Figure 7 This is a schematic diagram of the microfluidic temperature control system based on thermoelectric cooling proposed in this invention.

[0044] Figure 8 This is a schematic diagram of the heat dissipation cold plate section proposed in this invention;

[0045] Figure 9 The explosive body of the heat dissipation cold plate section proposed in this invention;

[0046] Figure 10 This is a schematic diagram of the precooling component proposed in this invention.

[0047] In the figure: 1-First heat dissipation plate, 2-Porcelain ring thermoelectric cooler, 3-Microfluidic chip, 4-Support, 5-Injection pump, 6-Waste liquid collection container, 7-Programmable DC power supply, 8-Temperature acquisition instrument, 9-Nitrogen tank, 10-Precooling component, 11-Nitrogen nozzle, 12-Microscope, 13-Block thermoelectric cooler, 14-Gas cooling plate, 15-Cooling water inlet, 16-Cooling water outlet, 17-Nitrogen inlet, 18-Nitrogen outlet, 19-Second heat dissipation plate. Detailed Implementation

[0048] Reference Figure 1 A microfluidic linear cooling method based on thermoelectric refrigeration, the method steps are as follows:

[0049] S1: Inject the microfluidic fluid to be temperature controlled into the sample cell of the microfluidic chip;

[0050] S2: Select a suitable thermoelectric cooler according to the target rate range of linear cooling of the microfluidic fluid in the microfluidic chip, install the selected thermoelectric cooler between the microfluidic chip and the heat dissipation plate, and control the current on the thermoelectric cooler through a programmable DC power supply.

[0051] S3: Set the maximum cooling time t gen Target cooling rate T g,m ;

[0052] S4: Based on the maximum cooling time t gen Target cooling rate T g,m Set the initial values ​​for the parameters α and β of the unsteady transient current. The method for setting the initial values ​​of the parameters is as follows:

[0053] α=I a / (t gen ×t gen )

[0054] β=I b / t gen

[0055] Among them, I a With Ib satisfying I b +I a =I m I m The measured value corresponding to the optimal current of the thermoelectric cooler is expressed in units of 1. Initially, I is set to... a =0;

[0056] S5: Based on the initial values ​​α and β of the unsteady transient current parameters, the conventional current is coupled to obtain the current function I = α × t² + β × t, where t represents time. This current function is then input into a thermoelectric cooler for numerical analysis and experimentation. Post-processing is used to obtain the microfluidic cooling curve under this current function, and the Rc of the cooling curve is calculated. 2 R 2 The goodness of fit between the actual cooling curve and the target linear cooling curve is calculated using the following formula:

[0057]

[0058] Among them, T i These are the temperature measurements at various times. This is the average of the temperature measurements. To achieve the target temperature value for linear cooling of the microfluidic fluid at each time step, R 2 The value is between 0 and 1; the closer it is to 1, the better the linearity of the cooling process.

[0059] S6: Determine R m 2 ≤R 2 Whether it is true or not, where R m 2 To satisfy the linear cooling condition R 2 If the minimum value is found, proceed to step S7; otherwise, make I... a =I a +I S I S To set the current iteration step size, proceed to step S4;

[0060] S7: Determine |T g -T g,m |≤E r Whether it is true or not, where T g To calculate the microfluidic cooling rate, E r If the cooling rate error limit is met, proceed to step S9; otherwise, proceed to step S8.

[0061] S8: Determine T g -T g,m Does ≤0 hold true? If so, does it make t gen =t gen -t m If not, then t gen =t gen +t m and output the corrected t gen Proceed to step S4;

[0062] S9: Determine the values ​​of α and β, and input the current function I=α*t²+β*t into the programmable DC power supply to start the microfluidic temperature control system based on thermoelectric cooling, and record the changes in microfluidic temperature through the data acquisition instrument.

[0063] Reference Figure 2 , 3 A microfluidic linear cooling method based on thermoelectric refrigeration, steps S3-S7, at the same t gen As the parameters α and β of the unsteady transition current change, the current curve changes accordingly, and the microfluidic temperature curve corresponding to different current curves also changes accordingly.

[0064] Reference Figure 4 A microfluidic linear cooling method based on thermoelectric refrigeration, steps S3-S7, at a certain t gen Below, the microfluidic linear cooling current that can be obtained by this method and the corresponding microfluidic linear cooling curve are shown.

[0065] Reference Figure 5 A microfluidic linear cooling method based on thermoelectric refrigeration, steps S3-S9, involves changing t gen Different linear cooling rates of microfluidics can be obtained. The thermoelectric cooler of model TEO1-042xx0425 is selected to achieve linear cooling of microfluidics between 26℃ ~ -19℃ and 24℃ / min ~ 42℃ / min, with a linearity of over 0.998.

[0066] Reference Figure 6-9The microfluidic temperature control system based on thermoelectric cooling includes a first heat dissipation plate 1, a perforated ring thermoelectric cooler 2, a microfluidic chip 3, and a support 4. The microfluidic chip 3 is made of polydimethylsiloxane (PDMS) and a glass slide substrate. The PDMS has microfluidic channels and a sample cell. The perforated ring thermoelectric cooler 2 is located at the upper end of the microfluidic chip 3, at the sample cell position. The first heat dissipation plate 1 with a central opening is installed on the upper end of the perforated ring thermoelectric cooler 2. The first heat dissipation plate 1, the perforated ring thermoelectric cooler 2, and the microfluidic chip 3 are fixed by the support 4. Thermal grease is applied to the contact surfaces to facilitate the transfer of heat and cold. A heat dissipation plate 1 is positioned directly above the opening. The microscope 12 has a sample cell inlet connected to a syringe pump 5 that pumps microfluidic fluid inwards, and a waste liquid collection container 6 connected to the sample cell outlet. The power input terminal of the ring-type thermoelectric cooler 2 is connected to a programmable DC power supply 7. A temperature measurement channel is set inside the sample cell, and a temperature acquisition point is set inside the temperature measurement channel to collect the temperature through a temperature acquisition instrument 8. A nitrogen nozzle 11 is installed at the bottom of the microfluidic chip 3, and a pre-cooling component 10 is connected to the inlet of the nitrogen nozzle 11. A nitrogen tank 9 is connected to the pre-cooling component 10. The first heat dissipation plate 1 is made of copper, and a circulating cooling water pipe is set inside the first heat dissipation plate 1. A constant temperature water bath is connected to the circulating cooling water pipe to ensure that its temperature is constant.

[0067] Reference Figure 10 The precooling assembly 10 includes two sets of block thermoelectric coolers 13 and a gas cooling plate 14. Each set of block thermoelectric coolers 13 includes two block thermoelectric coolers 13. The gas cooling plate 14 is installed between the two sets of block thermoelectric coolers 13. The cold end of the two sets of block thermoelectric coolers 13 is located on the side close to the gas cooling plate 14. A second heat dissipation plate 19 is installed on the hot end of each set of block thermoelectric coolers 13 away from the gas cooling plate 14. Thermal grease is applied to each contact surface. The second heat dissipation plate 19 has a cooling water inlet 15 for external cooling water connection and a cooling water outlet 16 for cooling water discharge. The gas cooling plate 14 has a nitrogen inlet 17 and a nitrogen outlet 18. The nitrogen inlet 17 is connected to a nitrogen tank 9, and the nitrogen outlet 18 is connected to a nitrogen nozzle 11. The second heat dissipation plate 19 and the gas cooling plate 14 are both made of copper. The second heat dissipation plate 19 is connected to a constant temperature water bath to dissipate heat from the hot end of the block thermoelectric cooler 13.

[0068] The control method steps of the microfluidic temperature control system based on thermoelectric refrigeration are as follows:

[0069] A1: Start the syringe pump 5, allowing microfluidic fluid to flow into the microfluidic chip sample cell. Turn on the microscope 12 to observe the microfluidic chip sample cell in real time. Turn on the temperature acquisition instrument 8 to monitor the temperature T of the microfluidic chip sample cell. cen Perform real-time measurements;

[0070] A2: Turn on the precooling component 10, and simultaneously open the nitrogen cylinder valve and set the nitrogen flow rate;

[0071] A3: The programmable DC power supply 7 is turned on, and the current direction is controlled to power the orifice ring thermoelectric cooler 2 with the current direction as one, so that it is in cooling mode. Input the current value or current curve to control the temperature of the microfluidic at room temperature. During this period, the microfluidic sample cell is observed and the temperature is measured in real time through the microscope 12 and the data acquisition instrument.

Claims

1. A microfluidic linear cooling method based on thermoelectric refrigeration, characterized in that, The method steps are as follows: S1: Inject the microfluidic fluid to be temperature controlled into the sample cell of the microfluidic chip; S2: Select a suitable thermoelectric cooler according to the target rate range of linear cooling of the microfluidic fluid in the microfluidic chip, install the selected thermoelectric cooler between the microfluidic chip and the heat dissipation plate, and control the current on the thermoelectric cooler through a programmable DC power supply. S3: Set the maximum cooling time t gen Target cooling rate T g,m ; S4: Based on the maximum cooling time t gen Target cooling rate T g,m Set the initial values ​​for the parameters α and β of the unsteady transient current. The method for setting the initial values ​​of the parameters is as follows: α=I a / (t gen ×t gen ) β=I b / t gen Among them, I a with I b Satisfy I b +I a =I m I m To determine the optimal operating current of the thermoelectric cooler, initially, I is set... a =0; S5: Based on the initial values ​​α and β of the unsteady transient current parameters, the conventional current is coupled to obtain the current function I = α × t 2 +β×t, where t represents time, and the current function is input into the thermoelectric cooler for numerical analysis and experimentation. Post-processing yields the cooling curve of the microfluidic under this current function, and the R² of the cooling curve is calculated using the following formula: ， Among them, T i These are the temperature measurements at various times. This is the average of the temperature measurements. To achieve the target temperature value for linear cooling of the microfluidic fluid at each time step, R 2 The value is between 0 and 1; the closer it is to 1, the better the linearity of the cooling process. S6: Determine R m 2 ≤R 2 Whether it is true or not, where R m 2 To satisfy the linear cooling condition R 2 If the minimum value is found, proceed to step S7; otherwise, make I... a =I a +I S I S To set the current iteration step size, proceed to step S4; S7: Determine |T g -T g,m |≤E r Whether it is true or not, where T g To calculate the microfluidic cooling rate, E r If the cooling rate error limit is met, proceed to step S9; otherwise, proceed to step S8. S8: Determine T g -T g,m Does ≤0 hold true? If so, does it make t gen =t gen -t m If not, then t gen =t gen +t m and output the corrected t gen Proceed to step S4; S9: Determine the values ​​of α and β, and assign the current function I = α × t 2 +β×t is input into the programmable DC power supply to start the microfluidic temperature control system based on thermoelectric cooling, and the changes in microfluidic temperature are recorded by the data acquisition instrument. The system applying the microfluidic linear cooling method includes a first heat dissipation plate, a perforated ring thermoelectric cooler, a microfluidic chip, and a support. The perforated ring thermoelectric cooler is positioned above the microfluidic chip at the sample cell location. The first heat dissipation plate, with a central opening, is mounted on the upper end of the perforated ring thermoelectric cooler. The first heat dissipation plate, the perforated ring thermoelectric cooler, and the microfluidic chip are fixed by the support. A microscope is positioned above the first heat dissipation plate, directly opposite the opening. An injection pump for pumping microfluidic fluid into the sample cell is connected to the inlet. A waste liquid collection container is connected to the outlet of the sample cell. A programmable DC power supply is connected to the power input terminal of the perforated ring thermoelectric cooler. A temperature measurement channel is provided within the sample cell, and temperature acquisition points for temperature acquisition via a temperature acquisition instrument are provided within the temperature measurement channel.

2. The microfluidic linear cooling method based on thermoelectric refrigeration according to claim 1, characterized in that: The unsteady transition current is obtained by coupling the current function I with a single function current curve. Different unsteady transition current ranges are obtained by changing the single function current curve involved in the coupling, thereby adapting to different microfluidic cooling target rates.

3. The microfluidic linear cooling method based on thermoelectric refrigeration according to claim 1, characterized in that: A nitrogen nozzle is installed at the bottom of the microfluidic chip, and the inlet of the nitrogen nozzle is connected to a pre-cooling component, which is externally connected to a nitrogen tank.

4. The microfluidic linear cooling method based on thermoelectric refrigeration according to claim 3, characterized in that: The precooling assembly includes two sets of block thermoelectric coolers and a gas cooling plate. Each set of block thermoelectric coolers includes two block thermoelectric coolers. The gas cooling plate is installed between the two sets of block thermoelectric coolers. The cold end of each set of block thermoelectric coolers is located on the side close to the gas cooling plate. A second heat dissipation plate is installed on the hot end of each set of block thermoelectric coolers away from the gas cooling plate. The second heat dissipation plate has a cooling water inlet for connecting external cooling water and a cooling water outlet for discharging cooling water. The gas cooling plate has a nitrogen inlet and a nitrogen outlet. The nitrogen inlet is connected to a nitrogen tank, and the nitrogen outlet is connected to a nitrogen nozzle.

5. A microfluidic linear cooling method based on thermoelectric refrigeration according to claim 1, characterized in that: The first heat dissipation plate has a circulating cooling water pipe inside, and the circulating cooling water pipe is connected to a constant temperature water tank.

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