CN111678423A - Liquid drop detection system and detection method based on dielectric wetting digital microfluidics - Google Patents
Liquid drop detection system and detection method based on dielectric wetting digital microfluidics Download PDFInfo
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Abstract
The invention discloses a liquid drop detection system and a detection method based on dielectric wetting digital microfluidics, which comprises a microfluidic chip provided with a liquid drop moving channel, a driving electrode embedded in the bottom wall of the liquid drop moving channel and a detection electrode embedded in the top wall of the liquid drop moving channel; the detection electrode signal is output to the microprocessor through the detection module and the signal amplification and filtering module; the microprocessor control signal output interface is respectively connected with the liquid drop driving module, the power supply switching module and the control input interface of the adjustable driving power supply; the liquid drop driving module is used for outputting set driving voltage or detection voltage to the appointed driving electrode; the power supply switching module is used for selecting a driving power supply or a detection power supply for the liquid drop driving module; the adjustable driving power supply is used for providing power for the liquid drop driving module to drive the liquid drops to move; the detection power supply is used for generating an excitation pulse voltage for the liquid drop driving module. The invention judges whether the current driving electrode position has liquid drops and the size and the components of the liquid drops according to the acquired voltage value, and the detection precision of the liquid drop position is high.
Description
Technical Field
The invention relates to a liquid drop detection system, in particular to a liquid drop detection system and a detection method based on dielectric wetting digital microfluidics.
Background
Digital microfluidics (DMF, an acronym for digital microfluidics) has become a powerful liquid processing technology, widely used in miniaturized biological and chemical fields, and is capable of real-time, accurate, and highly flexible manipulation of a variety of samples and reagents without the need for pumps, valves, moving parts, or cumbersome tube assemblies.
Discrete droplets of nanoliter to microliter volumes 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 electrical potentials to an embedded electrode array. For example, on a digital two-dimensional microfluidic chip based on the electrowetting effect of a medium, continuous liquid is discretized by means of an external driving force, and the formed micro-droplets are controlled, researched and analyzed, wherein the micro-droplets are accurately detected in real time, and the method has important significance for subsequent programming experiments and reaction results. Different regions on the microfluidic chip may have different functions such as mixing, splitting, heating, detecting, etc. The movement path of the liquid drop serving as the minimum operation unit on the microfluidic chip between different areas needs to consider real-time property. At present, the problems of the prior art are as follows: in the existing electrowetting panel, although a control circuit can be used for transferring liquid drops from a starting electrode to an end electrode, the position of the liquid drops cannot be monitored; individual or environmental differences may occur for individual droplets, for example: the size of the liquid drop is too large or too small, bringing abnormal charge, introducing impurities or static electricity into the environment, changing temperature and humidity, etc., which may cause the liquid drop not to move normally. Without a position monitoring system, the driving circuit cannot detect the position or perform control according to a normal timing sequence, which results in that not only the droplet cannot reach the end point, but also normal movement of all the subsequent droplets is affected, and thus the reliability of the device is low.
Chinese patent application No.: 201810003124.3 discloses a feedback control system based on a sensor, which is used to detect the AC signal of the microfluidic chip and then compare with the applied driving voltage signal to achieve the purpose of feedback control, but the technical proposal has larger dependence on the characteristics of the liquid drop and poor universality. Chinese patent application No.: 201710105878.5 discloses a liquid drop positioning system based on capacitance value detection of equivalent capacitance, which regards the liquid drop to be detected in the micro-fluidic chip and the hydrophobic insulating layer under the liquid drop as the capacitance connected in series; the main control chip sends a command to the liquid drop driving module, and the liquid drop driving module drives the liquid drop to be detected to move; the liquid drop positioning module acquires the current capacitance value of the liquid drop and determines whether the relative position of the liquid drop is positioned at a target position; however, in the technical scheme, when the number of driving electrodes of the digital microfluidic control system is large, the number of required capacitive sensors is large, in order to improve the operation speed, the FPGA is required to specially process the acquired data, and the complexity of a peripheral detection circuit is increased due to more driving electrodes, which is not beneficial to miniaturization integration and cost reduction. Chinese patent application No.: 201710692529.8 discloses a method for extracting current signal flowing through a microfluidic chip by a detection resistor and sending the current signal to a voltage follower for following; the signal is input into a multiplier in two paths along with the subsequent signal to carry out signal squaring; the low-pass filter performs low-pass filtering on the signal output by the multiplier, and a direct current signal is obtained at the output end of the low-pass filter; the singlechip acquires the direct current signal output by the low-pass filter and sends the direct current signal to a personal computer for processing so as to display information related to the state of the liquid drops; the technical scheme has the advantages that the detection circuit is simple, easy to integrate and low in cost; but the defects are that different chip driving voltages are different, the detection value of the liquid drop position is influenced by the driving voltage, the chip needs to be calibrated again (calibrated by adjusting the detection resistance value and combining with a program) after each time of chip replacement, manual intervention is needed, and the automation degree is not high.
Disclosure of Invention
The invention aims to provide a liquid drop detection system based on dielectric wetting digital microfluidics, which has high working reliability and automation degree, and the invention also aims to provide a detection method of the liquid drop detection system.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention relates to a liquid drop detection system based on dielectric wetting digital microfluidics, which comprises a microfluidic chip provided with a liquid drop moving channel, a plurality of driving electrodes embedded in the bottom wall of the liquid drop moving channel and used for driving liquid drops to move, and a detection electrode embedded in the top wall and used for detecting the positions of the liquid drops; the detection signal of the detection electrode is output to the microprocessor through the detection module and the signal amplification and filtering module; the control signal output interface of the microprocessor is respectively connected with the liquid drop driving module, the power supply switching module and the control signal input interface of the adjustable driving power supply; the liquid drop driving module is used for receiving a control instruction from the microprocessor and outputting a set driving voltage or a set detection voltage to a specified driving electrode; the power supply switching module is used for receiving a control instruction from the microprocessor and selecting a driving power supply or a detection power supply for the liquid drop driving module; the adjustable driving power supply is used for receiving a control instruction from the microprocessor and providing a power supply for the liquid drop driving module to drive the liquid drops to move; the detection power supply is used for providing power for the liquid drop driving module to generate the excitation pulse voltage.
The microfluidic chip comprises an upper substrate and a lower substrate which are arranged at intervals, and a left vertical plate and a right vertical plate are respectively arranged on two sides of the upper substrate and the lower substrate so as to form the liquid drop moving channel; the detection electrode is embedded in the lower surface of the upper substrate and coated with an upper lyophobic layer; the upper surface of the lower substrate is sequentially provided with a lower lyophobic layer and a dielectric layer from top to bottom, and the driving electrode is embedded in the dielectric layer.
The number of the detection electrodes is one, two or more, and the detection signal of each detection electrode is output to the microprocessor through the detection module and the signal amplification and filtering module respectively.
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 with the detection electrode, the low potential end of the resistor R1 is connected with the input end of the signal amplification and filtering module, and the low potential end of the resistor R1 is connected with logic ground through a parallel circuit consisting of the resistor R2 and a capacitor C1.
The detection method of the liquid drop detection system of the invention is characterized in that during detection, liquid drop movement and liquid drop detection are carried out in a time-sharing manner, namely: the driving power supply and the detection power supply power to the driving module in a time-sharing manner according to a set time sequence;
droplet movement: the microprocessor controls the power supply switching module to apply the driving power supply to each driving electrode on the lower substrate to the liquid drop driving module, and one or more liquid drops in the liquid drop moving channel are controlled to move through the driving electrodes;
droplet detection: microprocessor control power switching module applys to liquid drop drive module and comes from detect each drive electrode of power to infrabasal plate, provides detection pulse voltage for every drive electrode one by one in proper order, detection module is to last base plate detection electrode signal draws in proper order in real time, through signal amplification filtering module exports for microprocessor, and microprocessor's AD collection module or outside AD collection module judge the position of liquid drop and liquid drop size, composition according to the magnitude of voltage after detection module handles.
The invention has the advantages that the driving power supply and the detection power supply are adopted to supply power to the liquid drop driving module in a time-sharing manner according to the set time sequence, the liquid drop is driven to move, and the liquid drop position acquisition is carried out in a time-sharing manner, so that the detection voltage is fixed and is not influenced by the driving voltage, the detection signal amplitude of the detection electrode is also determined, thus different micro-fluidic chips do not need to be calibrated independently, and the use is simpler and more convenient. When the liquid drop is detected, the liquid drop driving module applies detection pulse voltage to a certain driving electrode of the lower substrate, AD acquisition is carried out on signals of the detection electrode in real time, whether the liquid drop exists at the current driving electrode position or not and the size and the components of the liquid drop are judged according to the acquired voltage value, and the liquid drop position detection precision is high.
Drawings
FIG. 1 is a block diagram of a droplet detection system according to the present invention.
Fig. 2 is a schematic structural diagram of a microfluidic chip according to the present invention.
FIG. 3 is a schematic diagram of the equivalent circuit principle of the droplet detection system (one detection electrode) according to the present invention.
Fig. 4 is a schematic diagram of the equivalent circuit principle of the droplet detection system (three detection electrodes) according to the present invention.
Fig. 5 is a timing diagram of the driving power supply and the detection power supply of the present invention supplying power to the driving module in a time-sharing manner.
Fig. 6 is a schematic plan view of the driving electrodes according to the present invention.
FIG. 7 is a flow chart of a droplet detection method according to the present invention.
Detailed Description
The following describes embodiments of the present invention in detail with reference to the drawings, which are implemented on the premise of the technical solution of the present invention, and detailed embodiments and specific operation procedures are provided, but the scope of the present invention is not limited to the following embodiments.
As shown in fig. 1, 2, 3, 5 and 6, the droplet detection system based on dielectric wetting digital microfluidics of the present invention comprises a microfluidic chip provided with a droplet moving channel 1, a plurality of driving electrodes 3 embedded in the bottom wall of the droplet moving channel 1 for driving the droplet 2 to move, 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 through the detection module 4.1 and the signal amplification and filtering module; a control signal output interface of the microprocessor is respectively connected with the liquid drop driving module, the power supply switching module and a control signal input interface of the adjustable driving power supply; the liquid drop driving module is used for receiving a control instruction from the microprocessor and outputting a set driving voltage or a set detection voltage to a specified driving electrode; the power supply switching module is used for receiving a control instruction from the microprocessor and selecting a driving power supply or a detection power supply for the liquid drop driving module; the adjustable driving power supply is used for receiving a control instruction from the microprocessor and providing a power supply for the liquid drop driving module to drive the liquid drops to move; the detection power supply is used for providing power for the liquid drop driving module to generate the excitation pulse voltage.
The micro-fluidic chip comprises an upper substrate 5 and a lower substrate 6 which are arranged at intervals, and a left vertical plate 7 and a right vertical plate 8 are respectively arranged on two sides of the upper substrate 5 and the lower substrate 6 so as to form a liquid drop moving channel 1; the detection electrode 4 is embedded in the lower surface of the upper substrate 5 and coated with an upper lyophobic layer 9; the upper surface of the lower substrate 6 is sequentially provided with a lower lyophobic layer 10 and a dielectric layer 11 from top to bottom, and the driving electrodes 3 are embedded in the dielectric layer 11 to insulate the driving electrodes 3.
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 with the detection electrode, the low potential end of the resistor R1 is connected with the input end of the signal amplification filtering module, and the low potential end of the resistor R1 is connected with logic ground through a parallel circuit consisting of a resistor R2 and a capacitor C1.
As shown in fig. 4, which is a schematic diagram of a liquid drop detection system of three detection electrodes 4, a detection signal of each detection electrode 4 is output to a microprocessor through a respective detection module 4.1 and a signal amplification and filtering module.
As shown in fig. 3 and 7, the detection method of the droplet detection system according to the present invention is a method in which droplet movement and droplet detection are performed in a time-division manner during detection, that is, the method includes: the driving power supply and the detection power supply provide the droplet driving voltage Vq and the detection voltage Vj to the driving module in a time-sharing manner according to a set time sequence (as shown in fig. 5).
Droplet movement: the microprocessor controls the power supply switching module to apply driving power to each driving electrode 3 on the lower substrate 6 from the liquid drop driving module, and one or more liquid drops 2 in the liquid drop moving channel 1 are controlled to move through the driving electrodes 3;
droplet detection: the microprocessor controls the power supply switching module to apply the driving electrodes 3 from the detection power supply to the lower substrate 6 to the liquid drop driving module, detection pulse voltage is sequentially provided for each driving electrode 3 one by one, the detection module sequentially extracts signals of the detection electrodes 4 on the upper substrate 5 in real time and outputs the signals to the microprocessor through the signal amplification and filtering module, and the AD acquisition module of the microprocessor or the external AD acquisition module judges the position of the liquid drop 2 and the size and the components of the liquid drop according to the voltage value processed by the detection module 4.1.
The driving principle of the liquid drop is briefly described as follows:
the dielectric wetting effect is a mode of electrically controlling the surface tension of liquid, and changes the wettability of liquid drops and the surface of a solid by controlling an external potential to cause the internal pressure difference of the liquid drops so as to drive micro liquid drops to move.
The droplet detection principle of the present invention is as follows:
the capacitance and the capacitive reactance are calculated according to the formula that the capacitance C is C = ×0×S/d；
In the formula: capacitance C, unit F;
a relative dielectric constant;
0vacuum dielectric constant =8.86 × 10-12The unit F/m;
area S, unit square meter;
the distance d between the polar plates is unit meter.
The capacitance capacitive reactance Xc is calculated by the formula: xc = 1/(ω × C) = 1/(2 π f × C), units, ohms.
Referring to fig. 3, the principle of droplet detection based on dielectric wetting digital microfluidics according to the present invention is as follows:
the driving electrode 3 and the detection electrode 4 of the micro-fluidic chip are equivalent to two poles of a plate capacitor; after the micro-fluidic 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 plate capacitor is determined; the height of the left vertical plate 7 and the right vertical plate 8 is fixed, and the equivalent plate capacitor inter-polar distance d is determined.
After the electrode area and the electrode distance of the equivalent plate capacitor are determined, the equivalent capacitance value is only related to the dielectric constant of a medium between two electrodes of the equivalent plate capacitor, the dielectric constant of the liquid drop 2 is different from the dielectric constant of the surrounding air or other substances, the capacitance value difference between the liquid drop position and other positions is deduced, the capacitance difference between the liquid drop 2 position and other positions is known according to a capacitance formula, the component of the liquid drop 2 is determined, the dielectric constant is also determined, and the dielectric constant determined by the surrounding air or other medium components is also a determined value; therefore, the capacitive reactance value of the driving electrode 3 at the position of the liquid drop 2 and the capacitive reactance values of other driving electrodes can be calculated.
When the position of the liquid drop is detected, detection pulse voltage with fixed voltage value is sequentially provided for the driving electrode 3 of the micro-fluidic chip one by one, the detection pulse voltage passes through the driving electrode 3 of the micro-fluidic chip, the detection electrode 4, the resistor R1 and the resistor R2 to reach a logic ground, and the microprocessor collects the voltage value of the detection module 4.1 in real time, so that the position and the component of the liquid drop 2 are judged.
The invention improves the robustness of the liquid drop detection system:
during droplet detection, the microprocessor controls the power switching module to apply a detection power to each driving electrode 3 of the lower substrate 6 to the droplet driving module, detection pulse voltage is sequentially provided for each driving electrode 3 one by one, the detection module sequentially extracts signals of the detection electrodes 4 on the upper substrate 5 in real time, the signals are output to the microprocessor through the signal amplifying and filtering module, the AD acquisition module of the microprocessor or an external AD acquisition module acquires detection voltage values of the detection electrodes 4 at equal time intervals from the beginning to the end of a period of time of the detection voltage signals of the detection electrodes 4, the data acquired at equal time intervals are subjected to integral summation, and the position of the droplet 2, the size of the droplet and the components are judged by using the data subjected to the integral summation.
Claims (5)
1. A liquid drop detection system based on dielectric wetting digital microfluidics is characterized in that: the micro-fluidic chip comprises a micro-fluidic chip provided with a liquid drop moving channel, a plurality of driving electrodes embedded in the bottom wall of the liquid drop moving channel and used for driving liquid drops to move, and a detection electrode embedded in the top wall and used for detecting the positions of the liquid drops; the detection signal of the detection electrode is output to the microprocessor through the detection module and the signal amplification and filtering module; the control signal output interface of the microprocessor is respectively connected with the liquid drop driving module, the power supply switching module and the control signal input interface of the adjustable driving power supply; the liquid drop driving module is used for receiving a control instruction from the microprocessor and outputting a set driving voltage or a set detection voltage to a specified driving electrode; the power supply switching module is used for receiving a control instruction from the microprocessor and selecting a driving power supply or a detection power supply for the liquid drop driving module; the adjustable driving power supply is used for receiving a control instruction from the microprocessor and providing a power supply for the liquid drop driving module to drive the liquid drops to move; the detection power supply is used for providing power for the liquid drop driving module to generate the excitation pulse voltage.
2. A dielectric wetting digital microfluidics-based droplet detection system according to claim 1, wherein: the microfluidic chip comprises an upper substrate and a lower substrate which are arranged at intervals, and a left vertical plate and a right vertical plate are respectively arranged on two sides of the upper substrate and the lower substrate so as to form the liquid drop moving channel; the detection electrode is embedded in the lower surface of the upper substrate and coated with an upper lyophobic layer; the upper surface of the lower substrate is sequentially provided with a lower lyophobic layer and a dielectric layer from top to bottom, and the driving electrode is embedded in the dielectric layer.
3. A dielectric wetting digital microfluidics-based droplet detection system according to claim 1 or 2, wherein: the number of the detection electrodes is one, two or more, and the detection signal of each detection electrode is output to the microprocessor through the detection module and the signal amplification and filtering module respectively.
4. A dielectric wetting digital microfluidics-based droplet detection system according to claim 1 or 2, wherein: 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 with the detection electrode, the low potential end of the resistor R1 is connected with the input end of the signal amplification and filtering module, and the low potential end of the resistor R1 is connected with logic ground through a parallel circuit consisting of the resistor R2 and a capacitor C1.
5. A method of testing a droplet testing system according to claim 1, wherein: during detection, liquid drop movement and liquid drop detection are carried out in a time-sharing mode, namely: the driving power supply and the detection power supply power to the driving module in a time-sharing manner according to a set time sequence;
droplet movement: the microprocessor controls the power supply switching module to apply the driving power supply to each driving electrode on the lower substrate to the liquid drop driving module, and one or more liquid drops in the liquid drop moving channel are controlled to move through the driving electrodes;
droplet detection: microprocessor control power switching module applys to liquid drop drive module and comes from detect each drive electrode of power to infrabasal plate, provides detection pulse voltage for every drive electrode one by one in proper order, detection module is to last base plate detection electrode signal draws in proper order in real time, through signal amplification filtering module exports for microprocessor, and microprocessor's AD collection module or outside AD collection module judge the position of liquid drop and liquid drop size, composition according to the magnitude of voltage after detection module handles.
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| CN115739222B (en) * | 2022-12-14 | 2024-05-28 | 上海天马微电子有限公司 | Microfluidic device and control method thereof |
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