Droplet detection system and detection method based on dielectric wetting digital microfluidics

Abstract

The present invention discloses a droplet detection system and method based on dielectric wetting digital microfluidics, comprising a microfluidic chip provided with a droplet movement channel, a drive electrode embedded in the bottom wall of the droplet movement channel, and a detection electrode embedded in the top wall; the detection electrode signal is output to a microprocessor via a detection module and a signal amplification and filtering module; the microprocessor control signal output interface is respectively connected to a droplet drive module, a power switching module, and a control input interface of an adjustable drive power supply; the droplet drive module is used to output a set drive voltage or detection voltage to a specified drive electrode; the power switching module is used to select a drive power supply or a detection power supply for the droplet drive module; the adjustable drive power supply is used to provide power for the droplet drive module to drive droplet motion; and the detection power supply is used to generate an excitation pulse voltage for the droplet drive module. The present invention uses the collected voltage value to determine whether there are droplets at the current drive electrode position, as well as the droplet size and composition, and has high droplet position detection accuracy.

Description

Technical Field

[0001] The present invention relates to a droplet detection system, and in particular to a droplet detection system and a detection method based on dielectric wetting digital microfluidics. Background Art

[0002] Digital microfluidics (DMF) has become a powerful liquid handling technology, widely used in miniaturized biology and chemistry, enabling real-time, precise, and highly flexible manipulation of a variety of samples and reagents without the need for pumps, valves, moving parts, or bulky tubing.

[0003] Discrete droplets of nanoliter to microliter volume are dispensed from a reservoir onto a flat surface coated with a hydrophobic insulator, where they are manipulated (transported, split, merged, mixed) by applying a series of electric potentials to an embedded electrode array. For example, on a digital two-dimensional microfluidic chip based on dielectric electrowetting, a continuous liquid is discretized with the help of an external driving force, and the formed tiny droplets are manipulated and analyzed. The real-time and accurate detection of microscale droplets is of great significance to subsequent programmed experiments and reaction results. Different areas on a microfluidic chip can have different functions, such as mixing, splitting, heating, detection, etc. As the smallest operating unit on a microfluidic chip, the movement path of the droplet between different areas needs to be considered in real time. The current problem with existing technology is that, while existing electrowetting panels can use control circuits to transport droplets from the starting electrode to the ending electrode, they cannot monitor the droplet's position. Individual droplets can exhibit individual or environmental variations, such as being too large or too small, carrying an abnormal charge, introducing impurities or static electricity into the environment, or experiencing temperature and humidity fluctuations. These factors can potentially prevent the droplet from moving properly. Without a position monitoring system, the drive circuit remains unaware of this and continues to control the device according to normal timing. This can prevent the droplet from reaching its destination and affect the normal movement of all subsequent droplets, resulting in low device reliability.

[0004] Chinese Patent Application No. 201810003124.3 discloses a sensor-based feedback control system that detects an AC signal from a microfluidic chip and compares it with an applied drive voltage signal to achieve feedback control. However, this technical solution is highly dependent on the characteristics of the droplet and has poor versatility. Chinese Patent Application No. 201710105878.5 discloses a droplet positioning system based on equivalent capacitance detection. This system treats a droplet to be tested within a microfluidic chip and a hydrophobic insulating layer beneath the droplet as a series capacitor. A main control chip issues a command to a droplet drive module, which drives the droplet to be tested. The droplet positioning module collects the current capacitance value of the droplet and determines whether the droplet is at the target position relative to the target. However, this technical solution requires a large number of capacitance sensors for digital microfluidic systems with a large number of drive electrodes. To increase computing speed, an FPGA is required to process the collected data. The large number of drive electrodes increases the complexity of the peripheral detection circuitry, hindering miniaturization and cost reduction. Chinese patent application number: 201710692529.8 discloses a method of extracting the current signal flowing through a microfluidic chip through a detection resistor and sending it to a voltage follower for following; the followed signal is divided into two paths and input into a multiplier for self-multiplication; a low-pass filter performs low-pass filtering on the signal output by the multiplier, and a DC signal is obtained at the output end of the low-pass filter; a single-chip microcomputer collects the DC signal output by the low-pass filter and sends it to a personal computer for processing to display information related to the droplet state; the advantages of this technical solution are simple detection circuit, easy integration and low cost; but the disadvantages are that different chips have different driving voltages, and the detection value of the droplet position is affected by the driving voltage. Each time the chip is replaced, it needs to be recalibrated (by adjusting the detection resistor value and then combining it with program calibration), which requires manual intervention and the degree of automation is not high. Summary of the Invention

[0005] The present invention aims to provide a droplet detection system based on dielectric wetting digital microfluidics with high working reliability and automation. Another object of the present invention is to provide a detection method for the droplet detection system.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] The droplet detection system based on dielectric wetting digital microfluidics described in the present invention includes a microfluidic chip provided with a droplet movement channel, a plurality of drive electrodes embedded in the bottom wall of the droplet movement channel for driving droplet movement, and a detection electrode embedded in the top wall for detecting the position of the droplet; the detection signal of the detection electrode is output to the microprocessor via the detection module and the signal amplification and filtering module; the control signal output interface of the microprocessor is respectively connected to the control signal input interface of the droplet driving module, the power switching module and the adjustable driving power supply; the droplet driving module is used to receive control instructions from the microprocessor and output the set driving voltage or detection voltage to the designated driving electrode; the power switching module is used to receive control instructions from the microprocessor and select the driving power supply or the detection power supply for the droplet driving module; the adjustable driving power supply is used to receive control instructions from the microprocessor and provide power for the droplet driving module to drive the droplet movement; the detection power supply is used to provide power for the droplet driving module to generate an excitation pulse voltage.

[0008] The microfluidic chip includes upper and lower substrates arranged at intervals, and left and right vertical plates are respectively arranged on both sides of the upper and lower substrates to form the droplet movement channel; the detection electrode is embedded in the lower surface of the upper substrate and coated with an upper liquid-repellent layer; the upper surface of the lower substrate is sequentially provided with a lower liquid-repellent layer and a dielectric layer from top to bottom, and the driving electrode is embedded in the dielectric layer.

[0009] There are one, two or more detection electrodes, and the detection signal of each detection electrode is output to the microprocessor via the respective detection module and signal amplification and filtering module.

[0010] The detection module consists of a resistor R1, a resistor R2 and a capacitor C1; the high potential end of the resistor R1 is connected to the detection electrode, the low potential end of the resistor R1 is connected to the input end of the signal amplification and filtering module, and is connected to the logic ground through a parallel circuit composed of the resistor R2 and the capacitor C1.

[0011] In the detection method of the droplet detection system of the present invention, during detection, droplet movement and droplet detection are performed in a time-sharing manner, that is, the driving power supply and the detection power supply supply power to the driving module in a time-sharing manner according to a set timing sequence;

[0012] Droplet movement: the microprocessor controls the power switching module to apply the driving power from the droplet driving module to each of the driving electrodes on the lower substrate, thereby controlling the movement of one or more droplets in the droplet movement channel through the driving electrodes;

[0013] Droplet detection: The microprocessor controls the power switching module to apply the detection power supply from the detection power supply to each driving electrode on the lower substrate to the droplet driving module, and provides a detection pulse voltage to each driving electrode one by one. The detection module extracts the detection electrode signals on the upper substrate in real time and outputs them to the microprocessor through the signal amplification and filtering module. The AD acquisition module of the microprocessor or the external AD acquisition module determines the position, size and composition of the droplet based on the voltage value processed by the detection module.

[0014] The advantage of the present invention lies in the use of a drive power supply and a detection power supply to power the droplet drive module in a time-sharing manner according to a set timing. The drive droplet movement and droplet position collection are carried out in a time-sharing manner. Therefore, the detection voltage is fixed and is not affected by the drive voltage. The amplitude of the detection signal of the detection electrode is also determined accordingly. This eliminates the need for individual calibration of different microfluidic chips, making it easier to use. During droplet detection, the droplet drive module applies a detection pulse voltage to a drive electrode on the lower substrate and performs AD acquisition on the detection electrode signal in real time. The collected voltage value is used to determine the presence of droplets at the current drive electrode position and the droplet size and composition. The droplet position detection is highly accurate. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 1 is a block diagram of the droplet detection system described in the present invention.

[0016] Figure 2 It is a schematic diagram of the structure of the microfluidic chip described in the present invention.

[0017] Figure 3 Schematic diagram of the equivalent circuit principle of the droplet detection system (one detection electrode) of the present invention.

[0018] Figure 4 Schematic diagram of the equivalent circuit principle of the droplet detection system (three detection electrodes) of the present invention.

[0019] Figure 5 This is a timing diagram of the driving power supply and the detection power supply of the present invention providing power to the driving module in a time-sharing manner.

[0020] Figure 6 It is a schematic diagram of the planar layout of the driving electrodes of the present invention.

[0021] Figure 7 4 is a flow chart of the droplet detection method of the present invention. DETAILED DESCRIPTION

[0022] The following describes an embodiment of the present invention in detail with reference to the accompanying drawings. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process. However, the protection scope of the present invention is not limited to the following embodiment.

[0023] like Figure 1 、 2 As shown in Figures 3, 5, and 6, the droplet detection system based on dielectric wetting digital microfluidics of the present invention includes a microfluidic chip provided with a droplet movement channel 1, a plurality of drive electrodes 3 embedded in the bottom wall of the droplet movement channel 1 for driving the movement of droplets 2, and a detection electrode 4 embedded in the top wall for detecting the position of the droplet 2; the detection signal of the detection electrode 4 is output to the microprocessor via the detection module 4.1 and the signal amplification and filtering module; the control signal output interface of the microprocessor is respectively connected to the control signal input interface of the droplet driving module, the power switching module and the adjustable driving power supply; the droplet driving module is used to receive control instructions from the microprocessor and output the set driving voltage or detection voltage to the designated driving electrode; the power switching module is used to receive control instructions from the microprocessor and select the driving power supply or the detection power supply for the droplet driving module; the adjustable driving power supply is used to receive control instructions from the microprocessor and provide power for the droplet driving module to drive the droplet movement; the detection power supply is used to provide power for the droplet driving module to generate an excitation pulse voltage.

[0024] The microfluidic chip includes upper and lower substrates 5 and 6 arranged at intervals, with left and right vertical plates 7 and 8 respectively arranged on both sides of the upper and lower substrates 5 and 6 to form a droplet movement channel 1; the detection electrode 4 is embedded in the lower surface of the upper substrate 5 and coated with an upper liquid-repellent layer 9; the upper surface of the lower substrate 6 is provided with a lower liquid-repellent layer 10 and a dielectric layer 11 from top to bottom, and the driving electrode 3 is embedded in the dielectric layer 11 to serve as insulation between each driving electrode 3.

[0025] The detection module 4.1 consists of a resistor R1, a resistor R2 and a capacitor C1; the high potential end of the resistor R1 is connected to the detection electrode, the low potential end of the resistor R1 is connected to the input end of the signal amplification and filtering module, and is connected to the logic ground through a parallel circuit consisting of the resistor R2 and the capacitor C1.

[0026] like Figure 4 As shown, it is a schematic diagram of the circuit principle of the droplet detection system with three detection electrodes 4. The detection signal of each detection electrode 4 is output to the microprocessor through its own detection module 4.1 and signal amplification and filtering module.

[0027] like Figure 3 、 7 As shown, the detection method of the droplet detection system of the present invention is that during detection, the droplet movement and droplet detection are performed in a time-sharing manner, that is, the driving power supply and the detection power supply are set according to the time sequence (such as Figure 5 As shown) provides the droplet driving voltage Vq and the detection voltage Vj to the driving module in a time-sharing manner.

[0028] Droplet movement: The microprocessor controls the power switching module to apply driving power from the droplet driving module to each driving electrode 3 on the lower substrate 6, thereby controlling the movement of one or more droplets 2 located in the droplet movement channel 1 through the driving electrodes 3;

[0029] Droplet detection: The microprocessor controls the power switching module to apply the detection power supply from the detection power supply to each driving electrode 3 on the lower substrate 6 to the droplet driving module, and provides a detection pulse voltage to each driving electrode 3 one by one. The detection module extracts the signal of the detection electrode 4 on the upper substrate 5 in real time, and outputs it to the microprocessor through the signal amplification and filtering module. The AD acquisition module of the microprocessor or the external AD acquisition module determines the position, size and composition of the droplet 2 based on the voltage value processed by the detection module 4.1.

[0030] The droplet driving principle of the present invention is briefly described as follows:

[0031] The dielectric wetting effect is a method of using electricity to control the surface tension of liquids. By controlling the applied electric potential, the wettability of the droplets and the solid surface is changed, causing a pressure difference inside the droplets, thereby driving the movement of microdroplets.

[0032] The droplet detection principle of the present invention is as follows:

[0033] Capacitance and capacitive reactance calculation formula: The calculation formula for capacitance C is: C=ε×ε0×S / d;

[0034] Where: capacitance C, unit F;

[0035] ε relative dielectric constant;

[0036] ε0 vacuum dielectric constant = 8.86×10 -12 , unit F / m;

[0037] Area S, in square meters;

[0038] The plate distance d is in meters.

[0039] The calculation formula for the capacitive reactance Xc is: Xc = 1 / (ω×C) = 1 / (2πf×C), unit: ohm.

[0040] like Figure 3 The principle of droplet detection based on dielectric wetting digital microfluidics of the present invention is as follows:

[0041] The driving electrode 3 and the detection electrode 4 of the microfluidic chip are equivalent to the two poles of a flat plate capacitor; after the microfluidic chip is manufactured, the areas of the driving electrode 3 and the detection electrode 4 are fixed, and the electrode area S of the equivalent flat plate capacitor is determined; the heights of the left and right vertical plates 7 and 8 are fixed, and the equivalent flat plate capacitor pole spacing d is determined.

[0042] After the electrode area and electrode spacing of the equivalent flat-plate capacitor are determined, the equivalent capacitance value is only related to the dielectric constant of the medium between the two electrodes of the equivalent flat-plate capacitor. The dielectric constant of the droplet 2 is different from the dielectric constant of the air or other substances around it. It is deduced that the capacitance value at the droplet position is different from that at other positions. According to the capacitive reactance formula, it is known that the capacitive reactance at the droplet 2 position and other positions is different. The composition of the droplet 2 is determined, and the dielectric constant is also determined. The dielectric constant determined by the composition of the surrounding air or other medium is also a certain value; therefore, the capacitive reactance value of the driving electrode 3 at the position of the droplet 2 and the capacitive reactance values of other driving electrodes can be calculated.

[0043] When detecting the position of the droplet, a detection pulse voltage with a fixed voltage value is provided to the drive electrode 3 of the microfluidic chip one by one. The detection pulse voltage passes through the microfluidic chip drive electrode 3, the detection electrode 4 and the resistor R1 and the resistor R2 to the logic ground. The microprocessor collects the voltage value of the detection module 4.1 in real time, thereby determining the position and composition of the droplet 2.

[0044] Examples of the present invention improving the robustness of the droplet detection system:

[0045] During droplet detection, the microprocessor controls the power switching module to apply the detection power supply from the droplet driving module to each driving electrode 3 on the lower substrate 6, and provides a detection pulse voltage to each driving electrode 3 one by one. The detection module extracts the detection electrode 4 signal on the upper substrate 5 in real time, and outputs it to the microprocessor through the signal amplification and filtering module. The AD acquisition module of the microprocessor or the external AD acquisition module collects the detection voltage value of the detection electrode 4 at equal time intervals from the start to the end of the detection voltage signal of the detection electrode 4, and integrates and sums the data collected at equal time intervals. The data after integration and summation are used to determine the position, size and composition of the droplet 2.

Claims

1. A droplet detection system based on dielectric wetting digital microfluidics, characterized by: The invention relates to a microfluidic chip provided with a droplet movement channel, wherein the microfluidic chip comprises an upper and a lower substrate arranged at intervals, and a left and a right vertical plate are respectively provided on both sides of the upper and lower substrates to form the droplet movement channel; a plurality of driving electrodes for driving the movement of droplets embedded in the bottom wall of the droplet movement channel and a detection electrode for detecting the position of droplets embedded in the top wall; the detection signal of the detection electrode is output to the microprocessor via the detection module and the signal amplification and filtering module; the control signal output interface of the microprocessor is respectively connected to the control signal input interface of the droplet driving module, the power switching module and the adjustable driving power supply; the droplet driving module is used to receive control instructions from the microprocessor and output a set driving voltage or detection voltage to the designated driving electrode; the power switching module is used to receive control instructions from the microprocessor and select a driving power supply or a detection power supply for the droplet driving module; the adjustable driving power supply is used to receive control instructions from the microprocessor and provide power for the droplet driving module to drive the droplet movement; the detection power supply is used to provide power for the droplet driving module to generate an excitation pulse voltage; During detection, the droplet movement and the droplet detection are performed in a time-sharing manner, that is, the driving power supply and the detection power supply supply power to the driving module in a time-sharing manner according to a set timing sequence; Droplet movement: the microprocessor controls the power switching module to apply the driving power to the droplet driving module to each of the driving electrodes on the lower substrate, thereby controlling the movement of one or more droplets in the droplet movement channel through the driving electrodes; Droplet detection: The microprocessor controls the power switching module to apply the detection power supply to the droplet driving module to each driving electrode of the lower substrate, and provides a detection pulse voltage to each driving electrode one by one. The detection module extracts the detection electrode signals on the upper substrate in real time, and outputs them to the microprocessor through the signal amplification and filtering module. The AD acquisition module of the microprocessor or the external AD acquisition module collects the detection voltage values of the detection electrodes at equal time intervals from the start to the end of the time period based on the detection voltage signal of the detection electrodes, and integrates and sums the data collected at equal time intervals, and uses the integrated and summed data to determine the position, size and composition of the droplets.

2. The droplet detection system based on dielectric wetting digital microfluidics according to claim 1, characterized in that: The detection electrode is embedded in the lower surface of the upper substrate and coated with an upper liquid-repellent layer; the upper surface of the lower substrate is sequentially provided with a lower liquid-repellent layer and a dielectric layer from top to bottom, and the driving electrode is embedded in the dielectric layer.

3. The droplet detection system based on dielectric wetting digital microfluidics according to claim 1 or 2, characterized in that: There are one, two or more detection electrodes, and the detection signal of each detection electrode is output to the microprocessor via the respective detection module and signal amplification and filtering module.

4. The droplet detection system based on dielectric wetting digital microfluidics according to claim 1 or 2, characterized in that: The detection module is composed of a resistor R1, a resistor R2 and a capacitor C1; the high potential end of the resistor R1 is connected to the detection electrode, The low potential end of the resistor R1 is connected to the input end of the signal amplification and filtering module, and is connected to the logic ground through a parallel circuit composed of the resistor R2 and the capacitor C1.

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