Micro-fluidic chip and temperature control system based on micro-fluidic chip
By introducing the synchronous use of electric heating wire and semiconductor refrigeration sheet in the microfluidic chip, the problems of slow heating speed and inaccurate temperature control in the prior art are solved, rapid heating and real-time temperature detection are achieved, and the microfluidic chip is improved temperature control performance.
Patent Information
- Application Number
- CN202420523261.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-03-18
- Publication Date
- 2025-01-07
- Estimated Expiration
- 2034-03-18
AI Technical Summary
The existing microfluidic chips are slow to heat up when they need to increase the temperature and cannot detect the temperature of the reaction chamber in real time, resulting in insufficient temperature control.
The electric heating wire is introduced into the microfluidic chip for heating, and the temperature of the reaction chamber is directly detected through the first temperature sensor, combined with the synchronous vertical lifting and lowering of the semiconductor refrigeration sheet and the thermal block, to achieve rapid heating and real-time temperature feedback.
It realizes rapid temperature increase and real-time temperature detection of microfluidic chips, improving the accuracy and efficiency of temperature control.
Smart Images
Figure CN222305840U_ABST
Abstract
Description
Technical Field
[0001] The utility model relates to the technical field of microfluidic chips, in particular to a microfluidic chip and a temperature control system based on the microfluidic chip. Background Art
[0002] Digital microfluidics is a technology for precisely controlling and manipulating microscale fluids. It has received widespread attention in the fields of biomedical testing, chemical analysis, drug screening, etc., and has gradually been industrialized.
[0003] It mainly uses microfluidic chips (also called digital microfluidic chips) for operation, and specifically the electrode layer drives the droplets to move and react in the reaction chamber of the microfluidic chip.
[0004] In biomedical testing, specific reaction system reagents need to achieve reaction goals at different temperatures. For example, the three basic reaction steps of denaturation, annealing, and extension in PCR (polymerase chain reaction) need to be completed in cycles at different temperatures.
[0005] However, the existing microfluidic chip itself does not have a heating function. When the temperature needs to be increased, a heating device is mainly used to heat the heat conductive block to increase the temperature of the heat conductive block. Then, the heated heat conductive block quickly contacts the bottom of the chip to heat the chip, thereby achieving the temperature increase of the chip. This method of using the heat conductive block as an intermediate heat conduction component to heat the chip has a relatively slow heating speed.
[0006] In addition, the existing chip cannot directly detect the real-time temperature of the reaction chamber through the temperature sensor. It mainly uses the temperature sensor to detect the temperature of the heat conductive block to obtain the temperature of the chip. Since the temperature sensor does not directly detect the temperature of the chip itself, but detects the temperature of the heat conductive block, this will cause a slight hysteresis in the detection result, and thus the chip temperature cannot be fed back in real time. Utility Model Content
[0007] In order to solve at least one of the technical problems mentioned in the background technology, the purpose of the present utility model is to provide a microfluidic chip and a temperature control system based on the microfluidic chip.
[0008] In order to achieve the above purpose, the utility model provides the following technical solutions:
[0009] A microfluidic chip comprises a base layer and a top layer, wherein the base layer and the top layer are spaced apart to form a reaction chamber; the base layer is provided with a driving electrode layer for driving droplets to move in the reaction chamber, and the base layer is provided with a heat conductive member and a heating wire for heating the reaction chamber; the microfluidic chip further comprises a first temperature sensor for detecting the temperature of the reaction chamber, and the temperature of the reaction chamber is conducted to the first temperature sensor through the heat conductive member to detect the temperature of the reaction chamber.
[0010] Preferably, a copper block is provided in the driving electrode layer; one end of the heat conductor contacts the copper block, and the other end contacts the detection end of the temperature sensor.
[0011] Preferably, the heat conducting member is made of copper.
[0012] Preferably, the base layer comprises a base layer and a first functional coating layer disposed above the base layer; and the heating wire is embedded in the base layer.
[0013] Preferably, the top layer includes an upper substrate and a second functional coating disposed on the bottom wall of the upper substrate.
[0014] The utility model also provides a temperature control system based on a microfluidic chip, comprising the above-mentioned microfluidic chip and a temperature control module, wherein the temperature control module comprises a second temperature sensor, and a semiconductor refrigeration plate and a heat-conducting block which are arranged below the microfluidic chip and can be synchronously lifted and lowered vertically; the heat-conducting block is arranged on the working surface of the semiconductor refrigeration plate, and the second temperature sensor is used to detect the temperature value of the heat-conducting block.
[0015] Preferably, the semiconductor cooling plate and the heat conducting block are driven by a driving mechanism to rise and fall vertically synchronously.
[0016] Preferably, the driving mechanism is a screw linear module; the screw linear module is provided with a frame driven by the screw linear module to vertically lift and lower, and the semiconductor cooling plate and the heat conductive block are both fixed on the frame.
[0017] Compared with the prior art, the advantages of adopting this solution are:
[0018] The microfluidic chip provided in the present solution is provided with a heating wire. When the temperature of the microfluidic chip needs to be increased, the heating wire can be energized to generate heat to heat the reaction chamber, which is equivalent to the microfluidic chip having a built-in heating function. Compared with the traditional method of heating the heat conductive block through a heating device and then indirectly heating the microfluidic chip through the heat conductive block, the heating wire in the present solution can make the reaction chamber heat up more quickly.
[0019] In addition, in the present solution, the temperature detection of the microfluidic chip is realized by the first temperature sensor, and the temperature in the reaction chamber is transmitted to the first temperature sensor by the heat conductor for detection by the first temperature sensor; at this time, the first temperature sensor is basically equivalent to directly detecting the temperature of the reaction chamber, and the detection result has almost no hysteresis, so that the temperature in the reaction chamber can be fed back in real time to achieve better temperature control and rapid heating. BRIEF DESCRIPTION OF THE DRAWINGS
[0020] Figure 1 This is a schematic diagram of the structure of the microfluidic chip of the utility model;
[0021] Figure 2 for Figure 1 A partial schematic diagram of the location of the heating wire in the middle;
[0022] Figure 3 It is a structural schematic diagram of the utility model. DETAILED DESCRIPTION
[0023] The following is an explanation and description of the technical scheme of the embodiment of the utility model in conjunction with the drawings of the embodiment of the utility model, but the following embodiment is only a preferred embodiment of the utility model, not all. Based on the embodiment in the implementation mode, other embodiments obtained by those skilled in the art without creative work are all within the protection scope of the utility model.
[0024] In the following description, terms such as "inside", "outside", "up", "down", "left", "right", etc. that indicate directions or positional relationships are only used to facilitate the description of the embodiments and simplify the description, and do not indicate or imply that the referred device or element must have a specific direction, be constructed and operate in a specific direction. Therefore, it should not be understood as a limitation on the present invention.
[0025] Example 1
[0026] See also Figure 1-Figure 2 As shown, this embodiment provides a microfluidic chip, including a base layer 1 and a top layer 2, wherein the base layer 1 and the top layer 2 are spaced apart to form a reaction chamber 3; a driving electrode layer 4 for driving droplets to flow in the reaction chamber 3 is provided in the base layer 1.
[0027] The base layer 1 includes a base layer 11 and a first functional coating layer 12 disposed on the base layer 11 .
[0028] The top layer 2 includes an upper substrate 21 and a second functional coating 22 disposed on the bottom wall of the upper substrate 21; the reaction chamber 3 is located between the first functional coating 12 and the second functional coating 22. The reagent droplets flow and react in the reaction chamber 3.
[0029] The first functional coating 12 and the second functional coating 22 are mainly used to ensure the normal driving of the reagent droplets. They have specific applications and descriptions in existing microfluidic chips, and will not be described in detail here.
[0030] The driving electrode layer 4 is mainly composed of copper foil and is mainly used to drive the droplets to move in the reaction chamber 3 . In this embodiment, the driving electrode layer 4 is disposed between the base layer 11 and the first functional coating layer 12 .
[0031] The base layer 1 is provided with a heat conducting member 61 and a heating wire 5 for heating the reaction chamber 3; the microfluidic chip further includes a first temperature sensor 6 for detecting the temperature of the reaction chamber 3. The temperature of the reaction chamber 3 is conducted to the first temperature sensor 6 through the heat conducting member 61 to detect the temperature of the reaction chamber 3. Specifically:
[0032] A copper block 62 for heat conduction is also provided in the driving electrode layer 4. It is worth noting that the copper block 62 is not used as an electrode in the driving electrode layer 4, but as a heat conducting component. Specifically, one end of the heat conducting member 61 contacts the copper block 62, and the other end contacts the detection end of the first temperature sensor 6. In this way, the temperature in the reaction chamber can be sequentially conducted to the first temperature sensor 6 through the copper block 62 and the heat conducting member 61 to realize temperature detection.
[0033] As an optional implementation, the heating wire 5 is embedded in the base layer 11 for heating the reaction chamber 3. The heating wire 5 can be copper foil, graphite, etc., or a high resistivity alloy material, such as iron-chromium-aluminum alloy series and nickel-chromium, etc.
[0034] When the microfluidic chip needs to be heated (it can also be understood as heating the reaction chamber 3), it can be directly heated by the heating wire 5 built into the microfluidic chip. This is equivalent to directly heating the microfluidic chip itself. Compared with the traditional method of heating the heat conductive block 73 through a heating device and then indirectly heating the microfluidic chip through the heat conductive block 73, the heating wire 5 of this solution can make the microfluidic chip heat up more quickly.
[0035] The first temperature sensor 6 may be buried in the base layer 1 or installed on the bottom wall of the base layer 11 , and may be an NTC thermistor.
[0036] The heat conductor 61 is mainly used to conduct the temperature of the reaction chamber 3 to the first temperature sensor 6 so that the first temperature sensor 6 can perform temperature detection, wherein the heat conductor 61 is preferably copper, and can also be graphite / aluminum / chromium / alloy and other heat-conducting materials; since copper has excellent thermal conductivity and a short thermal conduction distance, and the first functional coating 12 has a thickness of 50nm-50μm, which is thin and has good thermal conductivity, the temperature of the heat conductor 61 detected by the first temperature sensor 6 is basically equivalent to the real-time temperature of the reaction chamber 3. It can be seen that the first temperature sensor 6 is equivalent to directly detecting the real-time temperature in the reaction chamber 3, and there is basically no hysteresis.
[0037] Example 2
[0038] Combination Figure 1-Figure 3 As shown, this embodiment further provides a temperature control system based on a microfluidic chip on the basis of Embodiment 1, including a temperature control module and the microfluidic chip described in Embodiment 1.
[0039] like Figure 3 As shown, the temperature control module includes a second temperature sensor 731 and a microfluidic chip (such as Figure 3 Specifically, the semiconductor refrigeration plate 72 and the heat-conducting block 73 are driven to be vertically lifted synchronously by a driving mechanism 71, wherein the driving mechanism 71 is preferably a lead screw linear module, which relies on the lead screw linear module to drive the semiconductor refrigeration plate 72 and the heat-conducting block 73 to be vertically lifted synchronously.
[0040] During specific installation, a frame 70 driven by the lead screw linear module for vertical lifting can be connected to the lead screw linear module, the semiconductor cooling sheet 72 and the heat conductive block 73 are both fixed on the frame 70, and the heat conductive block 73 is located at the top of the frame 70; in this way, by driving the frame 70 to rise and fall vertically through the lead screw linear module, the heat conductive block 73 and the semiconductor cooling sheet 72 can be driven to rise and fall vertically synchronously.
[0041] It is worth mentioning that the semiconductor refrigeration sheet 72 is also called TEC. The working surface of the semiconductor refrigeration sheet 72 can be used for both heating and cooling. Whether the working surface is cooled or heated depends on the direction of the voltage input to the semiconductor refrigeration sheet 72. There are many explanations and applications about the working principle of the semiconductor refrigeration sheet 72 in the prior art, so no further elaboration will be made here.
[0042] In this embodiment, the working surface of the semiconductor refrigeration sheet 72 is its top surface; it can be understood that because the working surface of the semiconductor refrigeration sheet 72 needs to dissipate heat when cooling, a radiator for dissipating heat for the semiconductor refrigeration sheet 72 is also provided at the bottom of the semiconductor refrigeration sheet 72, and the radiator can be an air-cooled or water-cooled radiator.
[0043] The semiconductor cooling sheet 72 is selected as part of the temperature control module, so that the temperature control module can not only assist the heating wire 5 to heat the reaction chamber 3, but also enable the temperature control module to cool the reaction chamber 3.
[0044] In this embodiment, the heat conductive block 73 is disposed on the working surface of the semiconductor cooling sheet 72 , that is, on the top surface of the semiconductor cooling sheet 72 , and the second temperature sensor 731 is used to detect the temperature value of the heat conductive block 73 .
[0045] There are two specific methods for heating the reaction chamber 3 using this embodiment, namely heating method 1 and heating method 2, which are described below respectively; for better understanding, this embodiment takes the case where the reaction chamber 3 needs to be heated from temperature T2 to T1 (T2<T1) as an example for specific description:
[0046] Heating method 1:
[0047] The reaction chamber 3 is completely heated by the heating wire 5, that is, the heating wire 5 is energized to heat the reaction chamber 3. When the temperature value detected by the first temperature sensor 6 reaches T1, the controller controls the heating wire 5 to work so that the temperature value of the reaction chamber 3 is maintained at T1. The specific control method is to set T1 as the detection threshold of the first temperature sensor 6. In this way, when the first temperature sensor 6 detects that the temperature value in the reaction chamber 3 reaches T1, the controller controls the heating wire 5 to adjust the power so that the temperature of the reaction chamber 3 is maintained at T1 under the action of the heating wire 5. That is, the power of the heating wire 55 should basically ensure that the heating of the heating wire 5 can basically be balanced with the natural cooling of the reaction chamber 3, so that the temperature of the reaction chamber 3 is maintained at T1.
[0048] Heating method 2:
[0049] The heating wire 5 and the heat conducting block 73 heat the reaction chamber 3 together. Specifically:
[0050] First, before the reaction chamber 3 needs to be heated up, the working surface (i.e., the top surface) of the semiconductor cooling plate 72 is controlled to generate heat to heat the heat conductive block 73, and the heat conductive block 73 is heated up; it can be understood that during this process, the heat conductive block 73 is separated from the bottom of the chip.
[0051] During the heating process of the heat-conducting block 73, the second temperature sensor 731 detects the temperature of the heat-conducting block 73 in real time. When the temperature value detected by the temperature sensor reaches T3 on the second day, the controller controls the semiconductor cooling sheet 72 to keep the temperature of the heat-conducting block 73 at T3, and the driving mechanism 71 drives the heat-conducting block 73 to rise and contact the bottom of the base layer 1. In this way, the heat-conducting block 73 at the temperature of T3 contacts the bottom of the base layer 1 and heats the bottom of the base layer 1, thereby heating the reaction chamber 3. Here, T3 refers to a detection threshold set for the second temperature sensor 731, where T3>T1, or 0℃≤T1-T3≤10℃.
[0052] The controller controls the semiconductor refrigeration plate 72 to keep the temperature of the heat conductive block 73 at T3. It mainly controls the semiconductor refrigeration plate 72 to heat with a set power. The set power can satisfy the balance between the natural cooling and heating of the heat conductive block 73, so that the temperature of the heat conductive block 73 is basically maintained at T3.
[0053] Then, the heating wire 5 starts to be powered on and heats the reaction chamber 3. When the detection value of the first temperature sensor 6 reaches T1, the heat-conducting block 73 is controlled to descend and separate from the bottom of the base layer 1, and the heating wire 5 is controlled to work so that the temperature of the reaction chamber 3 is maintained at T1, that is, the temperature of the reaction chamber 3 is maintained at T1 under the heating action of the heating wire 5.
[0054] In addition, when the heat conductive block 73 descends and leaves the bottom of the base layer 1, the controller also controls the cooling surface of the semiconductor refrigeration plate 72 to start cooling to cool the heat conductive block 73; during the cooling process, when the temperature value detected by the second temperature sensor 731 reaches T4, the controller controls the semiconductor refrigeration plate 72 to work so that the temperature value of the heat conductive block 73 is maintained at T4; T4 here refers to a detection threshold set for the second temperature sensor 731, wherein T4≤T2, and T2 here refers to the target temperature value to which the reaction chamber 3 needs to be cooled when the temperature is subsequently cooled.
[0055] Through the above-mentioned configuration, the heat conductive block 73 can be placed in a low temperature state, i.e., T2, after being separated from the bottom of the chip, so as to prepare for the subsequent cooling step. During the subsequent cooling, the heat conductive block 73 that has risen to a low temperature can directly contact the bottom of the chip and start cooling. Such a configuration is conducive to saving time for the subsequent cooling step and improving efficiency.
[0056] The difference between the above two heating methods is that in heating method one, the reaction chamber 3 is heated entirely by the electric heating wire 5, while in heating method two, the electric heating block heats the reaction chamber 3 while the heat conducting block 73 assists in heating the reaction chamber 3. Therefore, the reaction chamber 3 heats up faster using heating method two than using heating method one.
[0057] When the reaction chamber 3 needs to be cooled from temperature T1 to T2, the cooling method is:
[0058] First, turn off the heating wire 5, and control the heat-conducting block 73 that has been cooled to the temperature T4 in the above-mentioned heating method 2 to rise and contact the bottom wall of the base layer 1 to cool the reaction chamber 3; when the temperature value detected by the first temperature sensor 6 reaches T5, control the heat-conducting block 73 to descend and leave the bottom of the base layer 1; wherein T5 refers to a detection threshold set for the first temperature sensor 6, wherein T4≤T5≤T2.
[0059] When the temperature value detected by the first temperature sensor 6 reaches T2, the heating wire 5 starts to heat the reaction chamber 3, and the controller controls the heating power of the heating wire 5 to keep the temperature of the reaction chamber 3 at T2.
[0060] The following specifically describes the temperature increase control method and the temperature decrease control method of this embodiment by taking T1=95°C and T2=65°C as an example:
[0061] When the temperature of reaction chamber 3 is required to rise to 95°C:
[0062] The aforementioned heating method 1 is used for heating and temperature increase: 95°C is set as a detection threshold of the first temperature sensor 6. When the temperature detected by the first temperature sensor 6 reaches 95°C, the power of the heating wire 5 is controlled to keep the temperature of the reaction chamber 3 at 95°C, which can also be understood as keeping the temperature value detected by the first temperature sensor 6 at 95°C.
[0063] The aforementioned heating method 2 is used for heating: before the temperature needs to be raised, the temperature of the heat-conducting block 73 is controlled to be above 95°C, such as 100°C, by the semiconductor cooling sheet 72; then, while the heating wire is powered on, the driving mechanism 71 drives the heat-conducting block 73 to rise and contact the bottom of the chip to assist in heating. Finally, the temperature of the reaction chamber 3 is controlled at 95°C by the heating wire.
[0064] After testing, it takes 4 seconds to heat up to 95°C using heating method 1, and 3 seconds to heat up to 95°C using heating method 2.
[0065] When the temperature of the reaction chamber 3 needs to be reduced from 95°C to 65°C, the temperature of the heat-conducting block 73 is controlled at 0°C in advance (performed in the second heating method, equivalent to T4=0°C). When the temperature needs to be lowered, the heat-conducting block 73 is controlled by the driving mechanism 71 to rise and contact the bottom of the chip to absorb the heat of the chip so that the temperature of the reaction chamber 3 reaches 65°C. According to the test, it takes 7 seconds to reach the required temperature.
[0066] In addition, in the temperature increase control method, when the temperature of the reaction chamber 3 rises to T1, a heat preservation block 8 is covered on the top of the top layer 2; and / or in the temperature decrease control method, when the temperature of the reaction chamber 3 drops to T2, a heat preservation block 8 is covered on the top of the top layer 2. The heat loss of the microfluidic chip is reduced by the heat preservation block 8, so as to play a certain heat preservation role.
[0067] It is obvious to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or basic features of the present invention. Therefore, no matter from which point of view, the embodiments should be regarded as exemplary and non-restrictive, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims are included in the present invention.
Claims
1. A microfluidic chip, comprising a base layer and a top layer, wherein the base layer and the top layer are spaced apart to form a reaction chamber; a driving electrode layer for driving droplets to move in the reaction chamber is provided in the base layer, characterized in that: The base layer is provided with a heat conducting member and a heating wire for heating the reaction chamber; the microfluidic chip also includes a first temperature sensor for detecting the temperature of the reaction chamber, and the temperature of the reaction chamber is conducted to the first temperature sensor through the heat conducting member to realize the temperature detection of the reaction chamber.
2. A microfluidic chip according to claim 1, characterized in that: A copper block is arranged in the driving electrode layer; one end of the heat conducting member contacts the copper block, and the other end contacts the detection end of the temperature sensor.
3. A microfluidic chip according to claim 1, characterized in that: The heat conducting member is made of copper.
4. A microfluidic chip according to claim 1, characterized in that: The base layer comprises a base layer and a first functional coating layer arranged above the base layer; the heating wire is embedded in the base layer.
5. The microfluidic chip according to claim 1, characterized in that: The top layer includes an upper substrate and a second functional coating arranged on the bottom wall of the upper substrate.
6. A temperature control system based on a microfluidic chip, characterized in that: It comprises a microfluidic chip and a temperature control module as described in any one of claims 1 to 5, wherein the temperature control module comprises a second temperature sensor, and a semiconductor refrigeration plate and a heat-conducting block which are arranged below the microfluidic chip and can be synchronously lifted and lowered vertically; the heat-conducting block is arranged on the working surface of the semiconductor refrigeration plate, and the second temperature sensor is used to detect the temperature value of the heat-conducting block.
7. A temperature control system based on a microfluidic chip according to claim 6, characterized in that: The semiconductor refrigeration plate and the heat-conducting block are driven by a driving mechanism to rise and fall vertically synchronously.
8. The temperature control system based on a microfluidic chip according to claim 7, characterized in that: The driving mechanism is a lead screw linear module; a frame driven by the lead screw linear module to vertically lift is arranged on the lead screw linear module, and the semiconductor cooling sheet and the heat conducting block are both fixed on the frame.