Real-time liquid drop detection method and circuit based on digital micro-fluidic chip

Abstract

The invention discloses a real-time liquid drop detection circuit based on a digital micro-fluidic chip, and the real-time liquid drop detection circuit based on the digital micro-fluidic chip comprises a liquid drop driving control unit, a microprocessor, a capacitance calibration unit and a signal processing unit, the liquid drop driving control unit is connected to the micro-fluidic chip, the micro-processor is connected to the micro-fluidic chip, and the capacitance calibration unit is connected to the micro-fluidic chip. The microprocessor is connected to the liquid drop driving control unit and controls the liquid drop driving control unit, the capacitance calibration unit is connected to the microprocessor and the micro-fluidic chip, the microprocessor controls the capacitance calibration unit to calibrate the capacitance value of each electrode of the micro-fluidic chip, and the signal processing unit is connected to a VGND pin of the micro-fluidic chip and controls the micro-fluidic chip to calibrate the capacitance value of each electrode of the micro-fluidic chip. And the signal processing unit is used for processing the electric signal of the micro-fluidic chip and transmitting the electric signal to the microprocessor. The capacitance values on different electrodes of the micro-fluidic chip are calibrated through the capacitance calibration unit, the detection precision of the digital micro-fluidic system on real-time detection of liquid drops is improved, and the real-time positions of the liquid drops can be accurately judged by acting on the different electrodes of the micro-fluidic chip.

Description

Technical Field

[0001] The invention belongs to the technical field of microfluidics, and relates to a real-time droplet detection method and circuit based on a digital microfluidics chip. Background Art

[0002] Digital microfluidics is a microfluidic technology based on electrowetting or dielectric wetting effects, which precisely manipulates the movement, segmentation, merging and mixing of droplets on two-dimensional or three-dimensional surfaces. When there is liquid on the electrode, if a potential is applied to the electrode, the wettability of the solid-liquid interface at the corresponding position of the electrode can be changed, and the contact angle between the droplet and the electrode interface will also change accordingly. If there is a potential difference between the electrodes in the droplet area, resulting in different contact angles, a lateral driving force will be generated, causing the droplet to move horizontally on the electrode substrate.

[0003] At the same time, the microfluidic chip electrode and the upper cover are equivalent to the two plates of the capacitor. The presence or absence of the droplet will change the dielectric constant between the plates and thus change the size of the capacitor. When we power on the designated electrode, we detect the characteristics of the electrical signal output by the upper cover to determine whether the droplet exists.

[0004] Currently, in the field of digital microfluidics, there are problems such as the conflict between droplet detection and droplet control, the inability to monitor in real time, and insufficient detection accuracy in terms of droplet detection functions. Summary of the invention

[0005] In view of the above problems, the present invention proposes a real-time droplet detection method and circuit based on a digital microfluidic chip, which well solves the problems in the prior art.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] A real-time droplet detection circuit based on a digital microfluidic chip, comprising:

[0008] A droplet drive control unit, wherein the droplet drive control unit is connected to the microfluidic chip;

[0009] A microprocessor, wherein the microprocessor is connected to the droplet drive control unit and controls the droplet drive control unit;

[0010] A capacitance calibration unit, the capacitance calibration unit is connected to the microprocessor and the microfluidic chip, and the microprocessor controls the capacitance calibration unit to calibrate the capacitance value of each electrode of the microfluidic chip;

[0011] A signal processing unit is connected to the VGND pin of the microfluidic chip, and processes the electrical signal of the microfluidic chip and transmits it to the microprocessor.

[0012] Optionally, the capacitance calibration unit includes three capacitance circuits. Each capacitance circuit includes one of main capacitors C44, C45, and C46. One of the main capacitors is connected to one of opto-coupler relays U25, U26, and U27. The opto-coupler relay is also connected to a current-limiting resistor and a pull-down resistor.

[0013] Optionally, the signal processing unit includes an MCP6022-ISN dual operational amplifier. The VINA- port of the dual operational amplifier is connected to resistor R33 and capacitor C41. The VINA- port of the dual operational amplifier is connected to the upper cover plate of the microfluidic chip. The VOUTA port of the dual operational amplifier is connected to resistors R29, C39, and R30. The VOUTA port of the dual operational amplifier outputs U A11 to be connected to the microprocessor.

[0014] A real-time droplet detection method based on a digital microfluidic chip. The method is a usage method of a real-time droplet detection circuit based on a digital microfluidic chip as described in any one of the above, and includes the following steps:

[0015] S1. The microprocessor controls the switching of the capacitance of the capacitance calibration unit and the loop voltage U of the microfluidic chip, and determines the voltage conversion capacitance correction coefficient R;

[0016] S2. Close the capacitance calibration unit loop, and the signal processing unit receives the microfluidic chip voltage U in real time and transmits it to the microprocessor;

[0017] S3. The microprocessor converts the microfluidic chip voltage U in step S2 into a capacitance value C according to the capacitance correction coefficient R in step S1;

[0018] S4. When the capacitance value C is greater than the minimum capacitance value of the microfluidic chip, it is determined that there is a droplet; otherwise, there is no droplet. The larger the capacitance value C, the larger the droplet area.

[0019] Optionally, the step of determining the correction coefficient R is as follows:

[0020] S11. Individually connect each capacitance loop in sequence and test the microfluidic chip loop voltage values U1, U2, and U3;

[0021] S12. Calculate the voltage conversion capacitance correction coefficient R

[0022] C x = K * U x + R;

[0023] Wherein, substitute U1, U2 and the corresponding capacitance values into U x and C x, calculate K and R, substitute them into U3 and the corresponding capacitance value for detection. When the deviation is not less than 10%, adjust the values ​​of K and R so that after U1, U2, and U3 are brought in, the deviation is less than 10%.

[0024] Optionally, the steps of obtaining the microfluidic chip loop voltage U in step S1 and step S2 are:

[0025] S21, obtain the voltage signal of the cover plate on the microfluidic chip and process it through the operational amplifier to obtain U A11 ;

[0026] S22. Calculate the voltage U of the operational amplifier VINB+ pin according to the circuit connection conditions. + ;

[0027] S23, calculate the differential voltage value U

[0028] U=U A11 -U + .

[0029] Optionally, it also includes,

[0030] S24, measure 50 groups of differential voltage values ​​U and arrange them in ascending order;

[0031] S25, the 37th group of differential voltage values ​​U is added to the 12th group of differential voltage values ​​U and then an average value is taken as the microfluidic chip voltage U for calculating the capacitance value C.

[0032] Compared with the prior art, the present invention has the following beneficial effects: by setting up a signal processing unit, the weak analog signal VGND of the cover plate on the microfluidic chip is amplified and processed to obtain an accurate and reliable voltage signal for the microprocessor to read, and the capacitance values ​​on different electrodes of the microfluidic chip are calibrated by the capacitance calibration unit, thereby improving the detection accuracy of the digital microfluidic system for real-time detection of droplets, and by acting on different electrodes of the microfluidic chip, the real-time position of the droplets can be accurately determined. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is a schematic diagram of the overall structure of an embodiment of the present invention;

[0034] Figure 2 is a wiring diagram of a shift register of a droplet drive control unit according to an embodiment of the present invention;

[0035] Figure 3 is a circuit diagram of a high-voltage optical coupler of a droplet drive control unit according to an embodiment of the present invention;

[0036] Figure 4 is a circuit diagram of a capacitance calibration unit according to an embodiment of the present invention;

[0037] Figure 5is a circuit diagram of a signal processing unit according to an embodiment of the present invention. DETAILED DESCRIPTION

[0038] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0039] See also Figure 1 , a real-time droplet detection circuit based on a digital microfluidic chip disclosed in an embodiment of the present invention, including a real-time droplet detection circuit based on a digital microfluidic chip, including a droplet drive control unit, a microprocessor, a capacitance calibration unit and a signal processing unit, the droplet drive control unit is connected to the microfluidic chip, the microprocessor is connected to the droplet drive control unit to control the droplet drive control unit, the capacitance calibration unit is connected to the microprocessor and the microfluidic chip, the microprocessor controls the capacitance calibration unit to calibrate the capacitance value of each electrode of the microfluidic chip, the signal processing unit is connected to the VGND pin of the microfluidic chip, the signal processing unit processes the electrical signal of the microfluidic chip and transmits it to the microprocessor.

[0040] Specifically, the microprocessor controls the droplet drive control unit through the interface protocol, and the droplet drive control unit is connected to the microfluidic chip through the wiring to realize the droplet drive of the microfluidic chip. At the same time, the VGND pin on the microfluidic chip is used as the feedback pin for chip electrode droplet detection, which is connected to the signal processing unit. The signal processing circuit feeds back the obtained electrical signal to the microprocessor. The microprocessor uses the capacitance calibration unit to distinguish and calibrate the capacitance values ​​of droplets on different electrodes of the microfluidic chip to accurately determine whether there are droplets on the microfluidic chip.

[0041] In some possible ways, the microprocessor chip is selected as ESP32-S3, see Figure 2 and Figure 3The droplet drive control unit includes a shift register MM74HC595MX. The microprocessor controls the register OUT port to output high and low levels through the I2C protocol interface to control the droplets. Among them, the high and low levels are controlled by the high-voltage optocoupler AQW214EHAX. The high-voltage optocoupler HVOUT is connected to HV or HVGND, where HV represents the high voltage of the driving electrode, HVGND represents the low level, and HVOUT is connected to the electrode of the microfluidic chip. The register power supply position is connected with filter capacitors C1 and C8, and the high-voltage optocoupler is connected to the current limiting resistors R5, R11, R63, R69 and the pull-up resistors R12 and R64. Each register cascades multiple optocouplers for independent control to achieve droplet movement control of multiple electrodes.

[0042] For some possible approaches, see Figure 4 The capacitance calibration unit includes three capacitance loops, the capacitance loop includes one of the main capacitance C44, the main capacitance C45, and the main capacitance C46, ​​the main capacitance is connected to one of the optocoupler relays U25, the optocoupler relays U26, and the optocoupler relays U27, the optocoupler relays realize independent control of the capacitance loop, and the optocoupler relays are also connected to the current limiting resistors R37, R38, R39, R40, R41, R42 and the pull-down resistors R43, R44, and R45, the current limiting resistors and the pull-down resistors are used for precise adjustment and protection of the circuit. The microfluidic chip capacitor selected in this embodiment is 10-470pF, so C44, C45, and C46 are selected as 10pF, 100pF, and 470pF capacitors respectively, and the optocoupler relay is selected as AQW214EHA.

[0043] For some possible approaches, see Figure 5 The signal processing unit includes a MCP6022-ISN dual operational amplifier, a VINA- port of the dual operational amplifier is connected to a resistor R33 and a capacitor C41, a VINA- port of the dual operational amplifier is connected to a cover plate on the microfluidic chip, a VOUTA port of the dual operational amplifier is connected to a resistor R29, a resistor C39 and a resistor R30, and a VOUTA port of the dual operational amplifier outputs U A11 to connect the microprocessor.

[0044] Among them, MCP6022-ISN is used as a dual operational amplifier, including two channels A and B, for signal amplification and processing. In channel A, resistor R33 and capacitor C41 are used for input part to filter and limit the signal. Resistor R29 determines the gain setting of the operational amplifier and constitutes the filtering function together with other components. Capacitor C39 and resistor R30 filter the output signal. The input signal of channel B enters through the filtering and voltage divider circuit. The power supply part is powered by 3.3V. Resistor R35 and resistor R36 are 10kΩ and 2.2kΩ respectively. Therefore, in this embodiment,

[0045] U + =VINB+=3.3*R36 / (R36+R35)=3.3*2.2 / (10+2.2)≈0.6V.

[0046] By setting up a signal processing unit, the weak analog signal VGND of the microfluidic chip is amplified and filtered in two stages to remove noise and enhance the signal amplitude, so as to obtain an accurate and reliable voltage signal for the microprocessor to read. The limit protection part is used to prevent the signal from overloading and damaging the circuit, and the filtering is used to optimize the frequency response of the signal.

[0047] See also Figure 1 To facilitate the use of a real-time droplet detection circuit based on a digital microfluidic chip in the present application, the present application also discloses a real-time droplet detection method based on a digital microfluidic chip, comprising the following steps:

[0048] S1, the microprocessor controls the capacitance of the switching capacitance calibration unit and the microfluidic chip loop voltage U to determine the voltage conversion capacitance correction coefficient R;

[0049] S2, closing the capacitance calibration unit loop, receiving the microfluidic chip voltage U in real time through the signal processing unit, and transmitting it to the microprocessor;

[0050] S3, the microprocessor converts the microfluidic chip voltage U in step S2 into a capacitance value C according to the capacitance correction coefficient R in step S1;

[0051] S4. When the capacitance value C is greater than the minimum capacitance value of the microfluidic chip, it is determined that a droplet exists. Otherwise, no droplet exists. The larger the capacitance value C is, the larger the droplet area is.

[0052] Specifically, by setting up a signal processing unit, the weak analog signal VGND on the cover of the microfluidic chip is amplified to obtain an accurate and reliable voltage signal for the microprocessor to read, and the capacitance values ​​on different electrodes of the microfluidic chip are calibrated through the capacitance calibration unit, thereby improving the detection accuracy of the digital microfluidic system for real-time detection of droplets. By acting on different electrodes of the microfluidic chip, the real-time position of the droplets can be accurately determined.

[0053] Furthermore, the correction coefficient R is determined as follows:

[0054] S11, connect each capacitor circuit separately in turn, and test the microfluidic chip circuit voltage values ​​U1, U2, and U3;

[0055] S12. Calculate the voltage conversion capacitance correction coefficient R

[0056] C x =K*U x +R;

[0057] Substitute U1, U2 and the corresponding capacitance values ​​into U x With C x , calculate K and R, substitute them into U3 and the corresponding capacitance value for detection. When the deviation is not less than 10%, adjust the values ​​of K and R so that after U1, U2, and U3 are brought in, the deviation is less than 10%.

[0058] In general, the accuracy of the correction coefficient R is improved by providing a plurality of parallel capacitor loops.

[0059] Furthermore, the steps of obtaining the microfluidic chip loop voltage U in step S1 and step S2 are:

[0060] S21, obtain the voltage signal of the cover plate on the microfluidic chip and process it through the operational amplifier to obtain U A11 ;

[0061] S22. Calculate the voltage U of the operational amplifier VINB+ pin according to the circuit connection conditions. + ;

[0062] S23, calculate the differential voltage value U

[0063] U=U A11 -U + .

[0064] Furthermore, it also includes:

[0065] S24, measure 50 groups of differential voltage values ​​U and arrange them in ascending order;

[0066] S25, the 37th group of differential voltage values ​​U is added to the 12th group of differential voltage values ​​U and then an average value is taken as the microfluidic chip voltage U for calculating the capacitance value C.

[0067] It should be understood that the calculation accuracy of the capacitance value of the microfluidic chip is further improved by measuring multiple sets of differential voltage values ​​U. The 12th value in the 50 sets of sequence values ​​is equivalent to 1 / 4 of the 50 sets of sequence values, and the 37th value is equivalent to 3 / 4. This can eliminate the chance interference error of the minimum and maximum values, and ensure that the difference is relatively large, which has practical measurement significance.

[0068] Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A real-time droplet detection circuit based on a digital microfluidic chip, characterized in that: include: A droplet drive control unit, wherein the droplet drive control unit is connected to the microfluidic chip; A microprocessor, wherein the microprocessor is connected to the droplet drive control unit and controls the droplet drive control unit; A capacitance calibration unit, the capacitance calibration unit is connected to the microprocessor and the microfluidic chip, and the microprocessor controls the capacitance calibration unit to calibrate the capacitance value of each electrode of the microfluidic chip; A signal processing unit is connected to the VGND pin of the microfluidic chip, and processes the electrical signal of the microfluidic chip and transmits it to the microprocessor.

2. A real-time droplet detection circuit based on a digital microfluidic chip according to claim 1, characterized in that: The capacitance calibration unit includes three capacitance circuits, each of which includes a main capacitor C44, a main capacitor C45, and one of the main capacitors C46. The main capacitor is connected to one of the optocoupler relays U25, U26, and U27, and the optocoupler relay is also connected to a current limiting resistor and a pull-down resistor.

3. A real-time droplet detection circuit based on a digital microfluidic chip according to claim 1, characterized in that: The signal processing unit includes an MCP6022-ISN dual operational amplifier, a VINA- port of the dual operational amplifier is connected to a resistor R33 and a capacitor C41, the VINA- port of the dual operational amplifier is connected to the microfluidic chip cover plate, the VOUTA port of the dual operational amplifier is connected to a resistor R29, a resistor C39 and a resistor R30, and the VOUTA port of the dual operational amplifier outputs U A11 to connect the microprocessor.

4. A real-time droplet detection method based on a digital microfluidic chip, characterized in that: The method is a method for using a real-time droplet detection circuit based on a digital microfluidic chip as described in any one of claims 1 to 3, comprising the following steps: S1, the microprocessor controls the capacitance of the switching capacitance calibration unit and the microfluidic chip loop voltage U to determine the voltage conversion capacitance correction coefficient R; S2, closing the capacitance calibration unit loop, receiving the microfluidic chip voltage U in real time through the signal processing unit, and transmitting it to the microprocessor; S3, the microprocessor converts the microfluidic chip voltage U in step S2 into a capacitance value C according to the capacitance correction coefficient R in step S1; S4. When the capacitance value C is greater than the minimum capacitance value of the microfluidic chip, it is determined that a droplet exists. Otherwise, no droplet exists. The larger the capacitance value C is, the larger the droplet area is.

5. A real-time droplet detection method based on a digital microfluidic chip according to claim 4, characterized in that: The correction coefficient R is determined by: S11, connect each capacitor circuit separately in turn, and test the microfluidic chip circuit voltage values ​​U1, U2, and U3; S12. Calculate the voltage conversion capacitance correction coefficient R C x =K*U x +R; Substitute U1, U2 and the corresponding capacitance values ​​into U x With C x , calculate K and R, substitute them into U3 and the corresponding capacitance value for detection. When the deviation is not less than 10%, adjust the values ​​of K and R so that after U1, U2, and U3 are brought in, the deviation is less than 10%.

6. A real-time droplet detection method based on a digital microfluidic chip according to claim 4, characterized in that: The steps of obtaining the microfluidic chip loop voltage U in step S1 and step S2 are: S21, obtain the voltage signal of the cover plate on the microfluidic chip and process it through the operational amplifier to obtain U A11 ; S22. Calculate the voltage U of the operational amplifier VINB+ pin according to the circuit connection conditions. + ; S23, calculate the differential voltage value U U=U A11 -IN + 。 7. A real-time droplet detection method based on a digital microfluidic chip according to claim 6, characterized in that: Also includes, S24, measure 50 groups of differential voltage values ​​U and arrange them in ascending order; S25, the 37th group of differential voltage values ​​U is added to the 12th group of differential voltage values ​​U and then an average value is taken as the microfluidic chip voltage U for calculating the capacitance value C.

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