WO2021175163A1 - 微流控芯片的温度控制系统、检测系统及温度控制方法 - Google Patents
微流控芯片的温度控制系统、检测系统及温度控制方法 Download PDFInfo
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- WO2021175163A1 WO2021175163A1 PCT/CN2021/078127 CN2021078127W WO2021175163A1 WO 2021175163 A1 WO2021175163 A1 WO 2021175163A1 CN 2021078127 W CN2021078127 W CN 2021078127W WO 2021175163 A1 WO2021175163 A1 WO 2021175163A1
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- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
- B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
- B01L3/502792—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
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- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
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- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- G01—MEASURING; TESTING
- G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
- G01K7/00—Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements
- G01K7/16—Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements using resistive elements
- G01K7/22—Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements using resistive elements the element being a non-linear resistance, e.g. thermistor
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- G05D23/1927—Control of temperature characterised by the use of electric means using a plurality of sensors
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- G05D23/1927—Control of temperature characterised by the use of electric means using a plurality of sensors
- G05D23/193—Control of temperature characterised by the use of electric means using a plurality of sensors sensing the temperaure in different places in thermal relationship with one or more spaces
- G05D23/1931—Control of temperature characterised by the use of electric means using a plurality of sensors sensing the temperaure in different places in thermal relationship with one or more spaces to control the temperature of one space
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- G05D23/19—Control of temperature characterised by the use of electric means
- G05D23/20—Control of temperature characterised by the use of electric means with sensing elements having variation of electric or magnetic properties with change of temperature
- G05D23/24—Control of temperature characterised by the use of electric means with sensing elements having variation of electric or magnetic properties with change of temperature the sensing element having a resistance varying with temperature, e.g. a thermistor
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- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L2300/1811—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using electromagnetic induction heating
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- B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
- B01L2400/0424—Dielectrophoretic forces
Definitions
- This application relates to the field of microfluidic technology. Specifically, this application relates to a temperature control system, a detection system, and a temperature control method of a microfluidic chip.
- Microfluidic technology is a technology for precise control and manipulation of micro-scale fluids. It provides a simple device structure and packaging, a smaller volume, and the ability to process a smaller amount of reagents in parallel. Its driving methods are diverse, including mechanical, electrical, magnetic, thermal, optical, etc. Electro-Wetting On Dielectric (EWOD) has become one of the most suitable methods due to its low power consumption and simple device manufacturing. Based on the digital microfluidic technology of dielectric wetting EWOD, the operations including the generation, transportation and merging of droplets are integrated on a micron-scale chip, and multiple droplets can be manipulated at the same time, which has a more flexible control mechanism. The advantages of higher throughput and sensitivity, and lower consumption of samples and reagents.
- EWOD Electro-Wetting On Dielectric
- microfluidic technology can achieve the requirements of automation, integration and portability that are difficult to achieve by traditional analysis systems, and can achieve low reagent consumption detection and rapid automatic detection. It has a wide range of applications in biology, chemistry, medicine, environment and other fields. prospect.
- the present application provides a temperature control system of a microfluidic chip, including:
- the circuit structure is arranged in the functional layer in the microfluidic chip and corresponds to the reaction area of the microfluidic chip, the circuit structure includes at least two thermistors and a plurality of ports; the plurality of ports includes An input port and an output port, the input port and the output port are electrically connected via the thermistor to form a use circuit;
- the controller is electrically connected to each of the ports, and is configured to select the first input port and the first output port, so that the circuit structure forms a first use circuit used as a heating device, and selects the second input port and the first output port.
- the first input port and the first output port are electrically connected via a first number of thermistors
- the second input port and The second output port is electrically connected via a second number of thermistors
- controller is further configured to:
- the first input port and the first output port are selected, so that the circuit structure forms a first use circuit used as a heating device for the reaction zone Heating is performed until the temperature of the reaction zone reaches the first preset temperature.
- circuit structure is configured as at least one of the following:
- the at least two thermistors are connected in series, and the first and the last ends of the thermistors connected in series are respectively provided with a port, and a port is provided between adjacent thermistors;
- the at least two thermistors are symmetrically arranged below the reaction zone;
- the plurality of ports are bounded by the central axis of the reaction zone, the input port is located on one side of the central axis, and the output port is located on the other side of the central axis.
- the plurality of ports includes a first left port to a third left port, a first right port to a third right port, and the at least two thermistors include a first resistor to a fifth resistor,
- One end of the first resistor is connected to the third left port
- the other end of the first resistor is connected to the second left port and one end of the second resistor;
- the other end of the second resistor and one end of the third resistor are connected to the first left port;
- the other end of the third resistor and one end of the fourth resistor are connected to the first right port;
- the other end of the fourth resistor and one end of the fifth resistor are connected to the second right port;
- the other end of the fifth resistor is connected to the third right port.
- the controller is further configured to select the first left port and the first right port, so that the circuit structure forms the first use circuit used as the heating device, the The first use circuit includes the third resistor.
- the controller is further configured to select the third left port and the third right port, so that the circuit structure forms the second use circuit used as the temperature sensor, the The second use circuit includes the first resistor to the fifth resistor connected in series.
- the controller is further configured to select the second left port and the second right port, so that the circuit structure forms the second use circuit used as the temperature sensor, the The second use circuit includes the second resistor to the fourth resistor connected in series.
- the controller is further configured to select the second left port and the first left port, so that the circuit structure forms the first use circuit used as the heating device, and
- the first use circuit includes the second resistor, and the first left port and the third right port are selected so that the circuit structure forms the second use circuit used as the temperature sensor, and the first The second use circuit includes the third resistor to the fifth resistor connected in series.
- the temperature control system further includes: a cooling device electrically connected to the controller;
- the controller is also configured to control the cooling device to cool the reaction zone until the temperature of the reaction zone reaches a second preset temperature.
- the cooling device includes a liquid storage tank and a plurality of adjacently arranged first electrodes on the periphery of the liquid storage tank;
- a first electrode layer is provided under the reaction zone, and the first electrode layer includes a plurality of second electrodes arranged in a matrix;
- Both the first electrode and the second electrode are electrically connected to the controller
- the controller is further configured to drive the cooling liquid droplets in the liquid storage tank from the first electrode through some of the plurality of second electrodes to return to the first electrode according to a first path, and then Move through the first electrode into the liquid storage tank.
- the present application provides a microfluidic detection system, including a microfluidic chip and the temperature control system of the microfluidic chip according to the embodiment of the present disclosure
- the microfluidic chip includes a reaction zone and a functional layer arranged under the reaction zone;
- the circuit structure is arranged in the functional layer.
- the microfluidic chip further includes: a sample application area and a detection area;
- the sample application area and the detection area are respectively located on both sides of the reaction area;
- a second electrode layer for driving the movement of droplets is provided below the sample application area and the detection area;
- the second electrode layer is electrically connected to the controller.
- the present application provides a temperature control method of a microfluidic chip, which is applied to the temperature control system of a microfluidic chip according to an embodiment of the present disclosure, and the method includes:
- the first input port and the first output port are selected so that the circuit structure forms a first use circuit used as a heating device.
- the temperature control method further includes:
- the first input port and the first output port are selected, so that the circuit structure forms a first use circuit used as a heating device for the reaction zone Heating is performed until the temperature of the reaction zone reaches the first preset temperature.
- the method further includes:
- the output duty ratio is used to control the circuit structure to form the temperature sensor or The time of the heating device.
- the temperature control method further includes:
- the cooling device is controlled to cool the reaction zone until the temperature of the reaction zone reaches the second preset temperature.
- the cooling device includes a liquid storage tank and a plurality of adjacently arranged first electrodes located on the periphery of the liquid storage tank; a first electrode layer is provided under the reaction zone, and the first electrode layer includes A plurality of second electrodes arranged in a matrix; both the first electrode and the second electrode are electrically connected to the controller;
- the controlling the cooling device to cool the reaction zone includes: driving the cooling liquid droplets in the liquid storage tank from the first electrode through some of the plurality of second electrodes according to a first path. Return to the first electrode, and then move into the liquid storage tank through the first electrode.
- the temperature control method further includes:
- the temperature control method further includes:
- FIG. 1 is a schematic structural diagram of a temperature control system of a microfluidic chip provided by an embodiment of the application;
- FIG. 2 is a schematic structural diagram of a circuit structure provided by an embodiment of the application.
- FIG. 3 is a schematic structural diagram of another temperature control system of a microfluidic chip provided by an embodiment of the application;
- FIG. 4 is a schematic structural diagram of a cooling device corresponding to the reaction zone provided by an embodiment of the application, showing the arrangement of the first electrode and the second electrode;
- FIG. 5 is a schematic structural diagram of a microfluidic detection system provided by an embodiment of the application.
- FIG. 6 is a schematic structural diagram of a microfluidic chip provided by an embodiment of the application.
- FIG. 7 is a flowchart of a heating mode of a temperature control method of a microfluidic chip provided by an embodiment of the application;
- FIG. 8 is a flowchart of a cooling mode of a temperature control method of a microfluidic chip provided by an embodiment of the application.
- the temperature control system includes: a circuit structure 100 and a main control unit 200;
- the circuit structure 100 is used to be arranged in the functional layer 401 in the microfluidic chip 400 and corresponds to the reaction area 402 of the microfluidic chip 400.
- the orthographic projection of the circuit structure 100 on the reaction zone 402 is located in the reaction zone 402.
- the circuit structure 100 includes at least two thermistors 103 and a plurality of ports; the ports include an input port and an output port, and one input port and one output port are electrically connected through a specific number of thermistors 103 to form a circuit with a specific resistance value.
- the main control unit 200 is electrically connected to each port for selecting input ports and/or output ports to form circuits with different resistances, so that the circuit structure 100 can be switched between being the heating device 101 and the temperature sensor 102.
- the inventor of the present application considers that when the circuit structure 100 is used as the heating device 101 or the temperature sensor 102, the optimal resistance value should be different. If the circuit structure 100 is used as the temperature sensor 102, a larger resistance value should be selected to obtain higher sensitivity, so as to achieve better temperature accuracy. If the circuit structure 100 is used as the heating device 101, when the input voltage is constant, a smaller resistance value should be selected to obtain a larger heating power. Therefore, the circuit structure 100 of the present application includes at least two thermistors 103 and multiple ports.
- One input port and/or one output port is electrically connected through the thermistor 103 to form circuits with different resistance values, so that it can be used according to Actually, it is necessary to select different use circuits to realize the function of the circuit structure 100 as the heating device 101 and the temperature sensor 102.
- the circuit structure 100 of the embodiment of the present application includes at least two thermistors 103, and the thermistors 103 can heat the reaction zone 402 after being energized. At the same time, due to changes in temperature, its own resistance will also change, and it can also be used as the temperature sensor 102 to obtain the temperature of the reaction zone 402.
- the main control unit 200 selects the corresponding input port and/or output port, so that the circuit structure 100 can be used as the heating device 101 to heat the reaction zone 402, and can also be used as the temperature sensor 102 to collect the temperature of the reaction zone 402 in real time.
- a suitable combination of input ports and output ports can be selected according to the required heating power and temperature control accuracy, which can achieve precise temperature control of the reaction zone 402, and can ensure that reactions such as genetic testing need to be performed at a specific temperature.
- the embodiment of the present application multiplexes the circuit structure 100 so that it has the functions of heating and temperature monitoring at the same time, and the two functions do not interfere with each other, perform well, and can control the temperature of the reaction zone 402 in real time to ensure the reaction zone 402 is always at the required temperature.
- the microfluidic detection system of the embodiment of the present application includes a microfluidic chip 400 and a temperature control system of the microfluidic chip 400, and the circuit structure 100 is set in the functional layer 401 of the microfluidic chip 400 to realize the circuit structure 100 (that is, the heating device 101 and the temperature sensor 102) are completely integrated inside the chip.
- the main control unit 200 may be a controller.
- the main control unit 200 is built on the basis of the inherent microcontroller of the microfluidic chip 400. In this way, there is no need to add an additional temperature control system, so there is no additional volume of the temperature control system and the detection system, and the cost is low.
- the inventor of the present application considers that the multiplexing of the circuit structure 100 is the multiplexing of the functional layer 401. If the two functions are performed at the same time, the superposition of the two control signals of the main control unit 200 may cause the actual effect to be inconsistent with expectations.
- the circuit structure 100 is time-division multiplexed, and the heating is stopped when the temperature is collected. After the temperature is collected, a certain time can be allocated to the heating device 101, during which time the temperature sensor 102 stops working. In this case, the operating time ratio of the heating device 101 can be obtained from the output duty ratio calculated by the main control unit 200.
- the circuit structure 100 can pre-form the distribution pattern of the thermistor 103, form two branches of the temperature sensor 102 and the heating device 101, and select the corresponding input port and output port to form at least two different resistance values. Circuit, thereby avoiding multiplexing of the same use circuit. In practical applications, in order to ensure that the functions of the circuit structure 100 as the heating device 101 and as the temperature sensor 102 are more mutually independent, the multiplexing of the same resistor can also be avoided.
- the main control unit 200 is used to control at least one circuit-forming temperature sensor 102 to obtain the current temperature of the reaction zone 402.
- the current temperature is lower than the first preset temperature, switch the input port and/or the output port so that at least one circuit-forming heating device 101 is used to heat the reaction zone 402 until the temperature of the reaction zone 402 reaches the first preset temperature .
- the temperature sensor 102 may be at least one use circuit, and the resistance value in each use circuit is determined by measuring the current value of each use circuit. According to the preset corresponding relationship between the resistance value of the used circuit and the temperature, each used circuit acts as a temperature sensor 102 to obtain the current temperature of a reaction zone 402. If there are multiple use circuits, the average value of the multiple use circuits can be calculated. Or calculate the final current temperature according to the current temperature collected by each using circuit and the preset weighting calculation.
- the heating device 101 may also be at least one use circuit. The number of used circuits can be adjusted according to the current temperature and which circuit to use can be selected, which facilitates uniform heating of the reaction zone 402 and also facilitates accurate temperature control according to the conditions of the reaction zone 402.
- At least two thermistors 103 are connected in series, the first and the last ends of the thermistors 103 connected in series are respectively provided with a port, and the adjacent thermistors 103 are provided with a port.
- At least two thermistors 103 are symmetrically arranged below the reaction zone 402, which can ensure uniform heating of the reaction zone 402 and reduce errors.
- the resistance distribution can be symmetrical with respect to the central axis of the reaction zone 402.
- the multiple ports are bounded by the central axis of the reaction zone 402, the input port is located on one side of the central axis, and the output port is located on the other side of the central axis.
- the main control unit 200 can be used as the power supply of the circuit structure 100, or an additional power supply electrically connected to the main control unit 200 can be provided.
- the power supply is electrically connected to the port of the circuit structure 100.
- the main control unit 200 controls the power supply to be electrically connected to the use circuit, and then heats the reaction zone 402.
- a schematic diagram of a circuit structure 100 is provided.
- five thermistors 103 connected in series are provided, and the resistance of each thermistor 103 can be the same or different.
- Five thermistors 103 are located on the functional layer 401 and are symmetrically arranged under the reaction zone 402.
- a pair of first ports 1 form a first use circuit
- a pair of second ports 2 form a second use circuit
- a pair of third ports 3 form a third use circuit.
- the input port located on the left of the central axis of the reaction zone 402 is an input port
- the output port located on the right of the central axis of the reaction zone 402 is an output port.
- the circuit structure 100 provides three use circuits, each of which has a different resistance value.
- a pair of first port 1, resistor R3 forms a circuit with small resistance
- resistor R2, resistor R3, and resistor R4 form a circuit with medium resistance
- resistors R1 to The resistor R5 forms a circuit with a large resistance value.
- the third use circuit formed by a pair of third ports 3 can be used as the temperature sensor 102
- the circuit can be used as the heating device 101 to heat the reaction zone 402.
- the fourth use circuit as the heating device 101 can be formed via the resistor R2 and the first port 1 and the second port 2.
- the resistor R3, the resistor R4, the resistor R5, and the first port 1 and the third port 3 can form a fifth use circuit as the temperature sensor 102.
- the first port 1 can be used as an input port
- the second port 2 and the third port 3 can be used as output ports. In this way, it can be ensured that the functions of the circuit structure 100 as the heating device 101 and as the temperature sensor 102 are more independent of each other, and the multiplexing of the same resistor can also be avoided.
- the thermistor 103 may have an elongated shape, and a plurality of thermistors 103 are arranged in a serpentine shape under the reaction zone 402.
- the resistance of the used circuit formed by the thermistor 103 can range from several ohms to several thousand ohms.
- the resistance of the thermistor 103 can be set according to actual temperature needs.
- the temperature control system further includes: a cooling device 300 electrically connected to the main control unit 200.
- the main control unit 200 is also used to control the cooling device 300 to cool the reaction zone 402 until the temperature of the reaction zone 402 reaches the second preset temperature.
- the cooling device 300 includes a liquid storage tank 301 and a plurality of first electrodes 302 arranged adjacent to each other on the periphery of the liquid storage tank 301.
- An electrode layer is provided under the reaction area 402, and the electrode layer includes a plurality of second electrodes 303 arranged in a matrix. Both the first electrode 302 and the second electrode 303 are electrically connected to the main control unit 200.
- the main control unit 200 is used to drive the cooling liquid droplets in the liquid storage tank 301 from the first electrode 302 through some of the plurality of second electrodes 303 to the first electrode 302 according to a preset path, and then pass through the first electrode 302. Move into the liquid storage tank 301.
- the first electrode 302 and the second electrode 303 are located on the same plane, and the first electrode 302 and the second electrode 303 may be existing electrodes in the reaction zone 402 of the microfluidic chip 400.
- An electrode 302 can also be provided in the microfluidic chip 400 according to the need for cooling.
- the first electrodes 302 are arranged in sequence according to a predetermined arrangement, and the middle area surrounded by a plurality of first electrodes 302 can be used as a liquid storage tank. 301.
- the reservoir 301 can contain cooling water.
- the first electrodes 302 at both ends of the multiple first electrodes 302 are respectively adjacent to a second electrode 303, which facilitates the movement of cooling water from the first electrode 302 on one side to the second electrode.
- both the first electrode 302 and the second electrode 303 are electrically connected to a power source, and the main control unit 200 drives the electrodes to be energized in sequence according to a preset time sequence, so that the droplets can move according to a predetermined path.
- the cooling device 300 of the embodiment of the present application can cool the reaction zone 402.
- the main control unit 200 sequentially controls the on and off of the electrodes to drive the cooling liquid droplets in the reservoir 301 from the first electrode 302 through the multiple second electrodes 303 back to the first electrode according to a preset path. 302, return to the storage tank 301 again.
- the cooling of the cooling device 300 is based on the inherent electrodes of the microfluidic chip 400, and the cooled droplets may also be readily available droplets. Therefore, there is no need to add an additional cooling device, and there is no additional volume of the temperature control system and the detection system, and the cost is low.
- an embodiment of the application also provides a microfluidic detection system.
- the microfluidic detection system includes a microfluidic chip 400 and the temperature control of the microfluidic chip of the embodiment of the application system.
- the microfluidic chip 400 includes a reaction area 402 and a functional layer 401 disposed under the reaction area 402, and the circuit structure 100 is disposed in the functional layer 401.
- the reaction area 402 is not shown in the figure.
- the microfluidic chip 400 further includes: a sample application area 403 and a detection area 404; the sample application area 403 and the detection area 404 are respectively located on both sides of the reaction area 402; the sample application area 403 and An electrode layer for driving the movement of liquid droplets is provided below the detection area 404.
- the electrode layers of the sample application area 403 and the detection area 404 are not shown, the electrode layer is electrically connected to the main control unit 200, and the functional layer 401 of the microfluidic chip 400 is located below the reaction area 402.
- the main control unit 200 controls the on and off of each electrode of the electrode layer, so as to drive the movement of the droplets.
- the front end of the reaction zone 402 is connected with the sample application zone 403, and the rear end of the reaction zone 402 is connected with the detection zone 404.
- the sample and reagent are driven by the electrode to move from the sample application area 403 into the reaction area 402.
- the reaction area 402 reacts, they circulate in the reaction area 402 until the reaction is completed and are mixed. After being uniform, it leaves the reaction zone 402 and enters the detection zone 404.
- the reaction zone 402 should be kept at a certain constant temperature to obtain the maximum activity of the enzyme. Therefore, the detection system of the present application can achieve better reaction and detection. Effect.
- the detection system further includes a cooling device 300.
- the cooling device 300 includes a liquid storage tank 301 and a plurality of first electrodes arranged adjacent to each other on the periphery of the liquid storage tank 301. 302.
- An electrode layer is provided under the reaction area 402, and the electrode layer includes a plurality of second electrodes 303 arranged in a matrix. Both the first electrode 302 and the second electrode 303 are electrically connected to the main control unit 200.
- the main control unit 200 is used to drive the cooling liquid droplets in the liquid storage tank 301 from the first electrode 302 through some of the plurality of second electrodes 303 to the first electrode 302 according to a preset path, and then pass through the first electrode 302. Move into the liquid storage tank 301.
- the main control unit 200 controls the cooling liquid drop to move according to a preset path, which can better ensure the moving position of the cooling liquid drop in the reaction zone 402 and improve the cooling effect of the reaction zone 402.
- an embodiment of the present application provides a temperature control method of a microfluidic chip, which is applied to the temperature control system of the microfluidic chip of the embodiment of the present application.
- the temperature control method includes a heating mode. And cooling mode.
- the input port and/or the output port are selected to form a circuit with a specific resistance value, so that the circuit structure 100 can be switched between the heating device 101 and the temperature sensor 102.
- the input port and/or the output port are selected to form a circuit with a specific resistance value, so that the circuit structure 100 can be switched between the heating device 101 and the temperature sensor 102, including steps S701 to S704.
- Step S701 includes selecting an input port and/or an output port (for example, a pair of third ports 3) so that at least one temperature sensor 102 is formed using a circuit to obtain the current temperature of the reaction zone 402.
- the temperature sensor 102 may be at least one use circuit, and the resistance value of each use circuit is determined by the current value of each use circuit, according to the preset resistance value and temperature of the thermistor 103 of the use circuit.
- each use circuit as a temperature sensor 102 to obtain the current temperature of a reaction zone 402, if there are multiple use circuits, you can find the average value of the multiple use circuits, or according to the current temperature collected by each use circuit And the preset weighting calculation to get the final current temperature.
- step S701 after controlling at least one circuit-forming temperature sensor 102 to obtain the current temperature of the reaction zone 402, the method further includes:
- the output duty ratio of the control signal output to the circuit structure 100 is determined; the output duty ratio is used to control the time when the circuit structure 100 functions as the temperature sensor 102 or the heating device 101, respectively.
- the circuit structure 100 when used as the temperature sensor 102 for temperature collection, it stops heating. After the temperature is collected, according to the difference between the current temperature and the first preset temperature, a certain time is allocated to the heating device 101, during which time the temperature sensor 102 stops working. In this case, the operating time ratio of the heating device 101 can be obtained from the output duty ratio calculated by the main control unit 200. At the same time, the combination of the input port and the output port is calculated by the main control unit 200 according to the set parameter (the first preset temperature).
- the ratio time of the temperature sensor 102 can be selected as 0.9 seconds, and the ratio time of the heating device 101 is 0.1 seconds; there is also a ratio between the current temperature and the first preset temperature.
- the ratio time of the temperature sensor 102 can be selected to be 0.1 second, and the ratio time of the heating device 101 is 0.9 second, so as to extend the heating time.
- the embodiment of the present application can make the reaction zone 402 reach the first preset temperature as soon as possible, thereby improving heating efficiency and saving energy.
- Step S702 includes determining whether the current temperature is lower than a first preset temperature. When the current temperature is lower than the first preset temperature, perform step S703, and when the current temperature is not lower than the first preset temperature, perform step S704;
- Step S703 includes selecting an input port and/or an output port (for example, a pair of first ports 1) so that at least one use circuit (for example, a first use circuit) forms the heating device 101 to heat the reaction zone 402.
- an input port and/or an output port for example, a pair of first ports 1
- the heating device 101 may also be at least one use circuit, and the number of used circuits can be adjusted according to the current temperature and which circuit to use can be selected, which is convenient for uniform heating of the reaction zone 402, and is also convenient for performing according to the conditions of the reaction zone 402. Precise temperature control.
- Step S704 includes that the heating device 101 stops heating.
- steps S701 to S704 are a continuous cycle process when the temperature control system is in the heating mode, until the temperature of the reaction zone 402 reaches the first preset temperature.
- the first preset temperature is set according to the actual needs of the reaction, and the setting parameters, heating temperature and tolerance error are input. That is, the first preset temperature may have an error range, and as long as it is within this temperature range, it is confirmed that the first preset temperature is reached. When no temperature is entered, the parameter can take the default value.
- the temperature control method of the microfluidic chip when in the cooling mode, includes steps S801 to S804.
- Step S801 includes selecting an input port and/or an output port (for example, a pair of third ports 3) so that at least one circuit forms the temperature sensor 102 to obtain the current temperature of the reaction zone 402.
- step S801 of this embodiment The principle of obtaining the current temperature of the reaction zone 402 in step S801 of this embodiment and step S701 of the foregoing embodiment is the same.
- Step S802 includes determining whether the current temperature is higher than the second preset temperature, when the current temperature is higher than the second preset temperature, step S803 is executed, and when the current temperature is not higher than the second preset temperature, step S804 is executed.
- Step S803 includes controlling the cooling device 300 to cool the reaction zone 402.
- the cooling device 300 includes a liquid storage tank 301 and a plurality of first electrodes 302 arranged adjacent to each other on the periphery of the liquid storage tank 301; an electrode layer is provided below the reaction zone 402, and the electrode layer includes a plurality of electrodes arranged in a matrix.
- a second electrode 303; both the first electrode 302 and the second electrode 303 are electrically connected to the main control unit 200;
- controlling the cooling device 300 to cool the reaction zone 402 includes: driving the cooling liquid droplets in the liquid storage tank 301 from the first electrode 302 through some of the plurality of second electrodes 303 according to a preset path to return The first electrode 302 moves through the first electrode 302 into the liquid storage tank 301.
- both the first electrode 302 and the second electrode 303 are electrically connected to a power source, and the main control unit 200 sequentially controls the energization of the electrodes according to a preset time sequence, so that the droplets can move according to a predetermined path.
- Step S804 includes that the cooling device 300 stops cooling.
- the temperature control method of the microfluidic chip further includes: determining the position of the droplet to be reacted; before the droplet to be reacted enters the reaction zone 402, enter the heating mode.
- the heating mode is turned on before the droplets enter the reaction zone 402, so that when the droplets enter the reaction zone 402, the inside of the reaction zone 402 is at a constant temperature, which improves the reaction efficiency and ensures the reaction effect.
- the main control unit 200 controls the power on and off of each electrode of the electrode layer, so as to drive the movement of the droplet. At the same time, the main control unit 200 pre-stores the number and position of the electrode, so that the position of the drop can be determined according to the position of the electrode where the drop is located.
- the temperature control method of the microfluidic chip further includes: determining the position of the reacted droplet; after the reacted droplet leaves the reaction zone 402, enter the cooling mode. In practical applications, it can be ensured that the reaction zone 402 does not need to react, that is, the reaction droplets leave the reaction zone 402, and then the reaction zone 402 is cooled.
- the temperature control method of the present application includes a heating mode and a cooling mode.
- the temperature sensor 102 obtains the temperature of the reaction zone 402 in real time and transmits the current temperature value to the main control unit 200.
- the main control unit 200 compares the current temperature value with the preset temperature according to the current mode, that is, the heating mode or the cooling mode, and calls the heating device 101 or the cooling device 300 according to the result.
- the heating mode can be entered to start heating, so that the reaction zone 402 reaches the required constant first preset temperature in advance.
- input setting parameters including heating temperature, cooling temperature, and tolerance error, so that the main control unit 200 stores the corresponding parameters in advance.
- the parameters are all taken as default values.
- a suitable port combination under the two functions of the heating device 101 and the temperature sensor 102 can be selected according to the required temperature accuracy and the required heating power, and the port combination is calculated by the main control unit 200 according to the set parameters.
- the heating mode is entered, and the reaction zone 402 is kept at a constant temperature until the droplet leaves the reaction zone 402 and there is no need to perform the pre-heating process of the next droplet.
- the cooling process can be started until the temperature of the reaction zone 402 drops to a second preset temperature (the second preset temperature can be room temperature or other preset temperatures), and the entire temperature control process ends.
- the temperature sensor 102 collects the current temperature of the reaction zone 402 and transmits the current temperature to the main control unit 200.
- the main control unit 200 calculates the difference between the current temperature and the first preset temperature, if If the temperature accuracy is not within the allowable range, the output duty cycle is calculated by the control algorithm, so that the heating device 101 works at the required heating power. Repeat this process until the current temperature reaches the first preset temperature. If the mode conversion signal of the main control unit 200 is not received, the heating mode is at this time, and the above-mentioned cycle is continued; if the mode conversion signal is received, the heating mode ends and the cooling mode is entered.
- the temperature sensor 102 collects the current temperature of the reaction zone 402 and transmits the current temperature to the main control unit 200, and the main control unit 200 calculates the difference between the current temperature and the second preset temperature. If it is not within the allowable range of temperature accuracy, it is necessary to continue cooling.
- the first electrode 302 around the liquid storage tank 301 is driven according to the time sequence preset by the main control unit 200, and a water droplet is generated from the liquid storage tank 301, which can make it After flowing in the reaction zone 402 for a week, it returns from the first electrode 302 on the other side to the liquid storage tank 301 and enters the next cycle.
- the temperature collection of the next cycle can be performed in advance when the current water droplets are about to enter the first electrode 302 to increase the cooling rate.
- the temperature of the reaction zone 402 reaches the second preset temperature (the second preset temperature may be room temperature or other preset temperatures)
- the cooling process ends, and the entire temperature control process ends.
- the temperature control system of the embodiment of the present application includes a circuit structure 100 and a main control unit 200.
- the main control unit 200 is electrically connected to each port of the circuit structure 100 for selecting a corresponding input port and/or output port, The use of circuits with different resistance values is formed, so that the circuit structure 100 can switch between being used as the heating device 101 to heat and being used as the temperature sensor 102 to measure temperature.
- the circuit structure 100 of the embodiment of the present application is composed of at least two thermistors 103, and the thermistors 103 can heat the reaction zone 402 after being energized. At the same time, due to changes in temperature, its own resistance will also change, and it can also be used as the temperature sensor 102 to obtain the temperature of the reaction zone 402.
- the main control unit 200 selects the input port and/or output port, so that the circuit structure 100 can be used as the heating device 101 to heat the reaction zone 402, and can also be used as the temperature sensor 102 to collect the temperature of the reaction zone 402 in real time.
- a suitable combination of input ports and output ports can be selected according to the required heating power and temperature control accuracy, which can achieve precise temperature control of the reaction zone 402, and can ensure that reactions such as genetic testing need to be performed at a specific temperature.
- the embodiment of the present application reuses the circuit structure 100 so that it has the functions of heating and temperature monitoring at the same time, and the two functions do not interfere with each other, perform well, and can control the temperature of the reaction zone 402 in real time to ensure the reaction zone 402 is always at the required temperature.
- the cooling device 300 of the embodiment of the present application can cool the reaction zone 402.
- the cooling device 300 sequentially controls the on and off of the electrodes to drive the cooling liquid droplets in the liquid storage tank 301 to follow a preset path from the first
- the electrode 302 returns to the first electrode 302 after some of the plurality of second electrodes 303, and then returns to the reservoir 301.
- the cooling of the cooling device 300 is based on the inherent electrodes of the microfluidic chip 400, and the cooling liquid droplets can also be easily available water droplets. No additional cooling device is required, and no additional volume of the temperature control system and detection system is required. , The cost is lower.
- the microfluidic detection system of the embodiment of the present application includes a microfluidic chip 400 and a temperature control system of the microfluidic chip.
- the circuit structure 100 is set in the functional layer 401 of the microfluidic chip 400 to realize the circuit structure 100 (Ie the heating device 101 and the temperature sensor 102) are fully integrated inside the chip.
- the main control unit 200 is also based on the inherent microcontroller of the microfluidic chip 400. No additional temperature control system is required, so no additional temperature control is required. The volume and cost of the system and the detection system are low.
- first and second are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. Thus, the features defined with “first” and “second” may explicitly or implicitly include one or more of these features. In the description of this application, unless otherwise specified, “plurality” means two or more.
- connection should be understood in a broad sense, unless otherwise clearly specified and limited.
- it can be a fixed connection or a detachable connection.
- Connected, or integrally connected it can be directly connected, or indirectly connected through an intermediate medium, and it can be the internal communication between two components.
- connection should be understood in a broad sense, unless otherwise clearly specified and limited.
- it can be a fixed connection or a detachable connection.
- Connected, or integrally connected it can be directly connected, or indirectly connected through an intermediate medium, and it can be the internal communication between two components.
- the specific meanings of the above terms in this application can be understood under specific circumstances.
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Abstract
Description
Claims (19)
- 一种微流控芯片的温度控制系统,包括:电路结构,设于微流控芯片内的功能层内并与所述微流控芯片的反应区相对应,所述电路结构包括至少两个热敏电阻和多个端口;所述多个端口包括输入端口和输出端口,所述输入端口、所述输出端口经由所述热敏电阻电连接形成使用电路;控制器,与每个所述端口均电连接,配置为选择第一输入端口和第一输出端口,使得所述电路结构形成用作加热装置的第一使用电路,以及选择第二输入端口和第二输出端口,使得所述电路结构形成用作温度传感器的第二使用电路,其中,在所述第一使用电路中,所述第一输入端口和所述第一输出端口经由第一数量的热敏电阻电连接,所述第二使用电路中,所述第二输入端口和所述第二输出端口经由第二数量的热敏电阻电连接。
- 根据权利要求1所述的微流控芯片的温度控制系统,其中,所述控制器还被配置为:响应于所述电路结构形成用作温度传感器的第二使用电路来得到所述反应区的当前温度;在所述当前温度低于第一预设温度时,选择所述第一输入端口和所述第一输出端口,使得所述电路结构形成用作加热装置的第一使用电路以对所述反应区进行加热,直至所述反应区的温度达到所述第一预设温度。
- 根据权利要求1所述的微流控芯片的温度控制系统,其中,所述电路结构被配置为以下至少一项:所述至少两个热敏电阻串联,串联的热敏电阻的首尾端分别设有一个端口,相邻的热敏电阻之间设有一个端口;所述至少两个热敏电阻在所述反应区的下方对称设置;所述多个端口以所述反应区的中轴线为界,位于所述中轴线一侧的为输入端口,位于所述中轴线另一侧的为输出端口。
- 根据权利要求1所述的微流控芯片的温度控制系统,其中,所述多个端口包括第一左端口至第三左端口、第一右端口至第三右端口、所述至少两个热敏电阻包括第一电阻至第五电阻,所述第一电阻的一端连接至所述第三左端口,所述第一电阻的另一端连接至所述第二左端口和所述第二电阻的一端;所述第二电阻的另一端和所述第三电阻的一端连接至所述第一左端口;所述第三电阻的另一端和所述第四电阻的一端连接至所述第一右端口;所述第四电阻的另一端和所述第五电阻的一端连接至所述第二右端口;以及所述第五电阻的另一端连接至所述第三右端口。
- 根据权利要求4所述的微流控芯片的温度控制系统,其中,所述控制器还被配置为选择所述第一左端口和所述第一右端口,使得所述电路结构形成用作所述加热装置的所述第一使用电路,所述第一使用电路包括所述第三电阻。
- 根据权利要求5所述的微流控芯片的温度控制系统,其中,所述控制器还被配置为选择所述第三左端口和所述第三右端口,使得所述电路结构形成用作所述温度传感器的所述第二使用电路,所述第二使用电路包括串联连接的所述第一电阻至所述第五电阻。
- 根据权利要求5所述的微流控芯片的温度控制系统,其中,所述控 制器还被配置为选择所述第二左端口和所述第二右端口,使得所述电路结构形成用作所述加热装置的所述第一使用电路,所述第一使用电路包括串联连接的所述第二电阻至所述第四电阻。
- 根据权利要求4所述的微流控芯片的温度控制系统,其中,所述控制器还被配置为选择所述第二左端口和所述第一左端口,使得所述电路结构形成用作所述加热装置的所述第一使用电路,所述第一使用电路包括所述第二电阻,以及选择所述第一左端口和所述第三右端口,使得所述电路结构形成用作所述温度传感器的所述第二使用电路,所述第二使用电路包括串联连接的所述第三电阻至所述第五电阻。
- 根据权利要求1所述的微流控芯片的温度控制系统,其中,所述温度控制系统还包括:与所述控制器电连接的冷却装置;所述控制器还被配置为控制所述冷却装置对所述反应区进行冷却,直至所述反应区的温度达到第二预设温度。
- 根据权利要求9所述的微流控芯片的温度控制系统,其中,所述冷却装置包括储液槽和位于所述储液槽周边的多个相邻排列的第一电极;所述反应区的下方设有第一电极层,所述第一电极层包括矩阵排列的多个第二电极;所述第一电极和所述第二电极均与所述控制器电连接;所述控制器还被配置为按照第一路径驱动所述储液槽内的冷却液滴从所述第一电极经所述多个第二电极中的一些后回到所述第一电极,再经所述第一电极移动进入储液槽。
- 一种微流控检测系统,包括微流控芯片和如权利要求1-10中任一项所述的微流控芯片的温度控制系统;所述微流控芯片包括反应区和设于所述反应区下方的功能层;所述电路结构设于所述功能层内。
- 根据权利要求11所述的微流控检测系统,其中,所述微流控芯片还包括:加样区和检测区;所述加样区和所述检测区分别位于所述反应区的两侧;所述加样区和所述检测区的下方均设有用于驱动液滴移动的第二电极层;所述第二电极层与所述控制器电连接。
- 一种微流控芯片的温度控制方法,应用于如权利要求1-10中任一项所述的微流控芯片的温度控制系统,所述方法包括:当处于加热模式时,选择所述第二输入端口和所述第二输出端口,使得所述电路结构形成用作温度传感器的第二使用电路;以及选择所述第一输入端口和所述第一输出端口,使得所述电路结构形成用作加热装置的第一使用电路。
- 根据权利要求13所述的微流控芯片的温度控制方法,进一步包括:响应于所述电路结构形成用作温度传感器的第二使用电路来得到所述反应区的当前温度;以及在所述当前温度低于第一预设温度时,选择所述第一输入端口和所述第一输出端口,使得所述电路结构形成用作加热装置的第一使用电路以对所述反应区进行加热,直至所述反应区的温度达到所述第一预设温度。
- 根据权利要求14所述的微流控芯片的温度控制方法,其中,得到所述反应区的当前温度之后,还包括:根据所述当前温度和所述第一预设温度,确定输出到所述电路结构的 控制信号的输出占空比;所述输出占空比用于控制所述电路结构形成为所述温度传感器或所述加热装置的时间。
- 根据权利要求14所述的微流控芯片的温度控制方法,还包括:当处于冷却模式时,选择所述第二输入端口和所述第二输出端口,使得所述电路结构形成用作所述温度传感器的第二使用电路以得到所述反应区的当前温度;在所述当前温度高于第二预设温度时,控制所述冷却装置对所述反应区进行冷却,直至所述反应区温度达到第二预设温度。
- 根据权利要求16所述的微流控芯片的温度控制方法,其中,所述冷却装置包括储液槽和位于储液槽周边的多个相邻排列的第一电极;所述反应区的下方设有第一电极层,所述第一电极层包括矩阵排列的多个第二电极;所述第一电极和所述第二电极均与所述控制器电连接;所述控制所述冷却装置对所述反应区进行冷却,包括:按照第一路径驱动所述储液槽内的冷却液滴从所述第一电极经所述多个第二电极中的一些后回到所述第一电极,再经所述第一电极移动进入储液槽。
- 根据权利要求13所述的微流控芯片的温度控制方法,还包括:确定待反应液滴的位置;在所述待反应液滴未进入所述反应区之前,进入所述加热模式。
- 根据权利要求16所述的微流控芯片的温度控制方法,还包括:确定已反应液滴的位置;在所述已反应液滴离开所述反应区之后,进入所述冷却模式。
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US20220403306A1 (en) * | 2020-12-25 | 2022-12-22 | Beijing Boe Sensor Technology Co., Ltd. | Substrate, microfluidic device, driving method and manufacturing method |
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