CN107649222B - method for driving independent electrode on dielectric electrowetting digital microfluidic chip - Google Patents
method for driving independent electrode on dielectric electrowetting digital microfluidic chip Download PDFInfo
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- 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
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- 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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- 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
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Abstract
In the method for driving the independent electrodes on the dielectric electrowetting digital microfluidic chip, a personal computer issues a first instruction to a singlechip to control a driving system to electrify the electrodes on the dielectric electrowetting digital microfluidic chip one by one through the singlechip; according to a detection value formed by a detection result of the micro-fluidic chip acquired by the single chip microcomputer and detected by the detection circuit, the personal computer distinguishes whether the current driving liquid drop or the obstacle thereof exists on the electrode, represents the size and the position of the current driving liquid drop or the obstacle thereof on the electrode, and plans and displays a path from the specified initial position to the specified end position of the current driving liquid drop; and the personal computer sends a second instruction with path related information to the singlechip, and the singlechip controls the driving system to sequentially electrify the electrodes distributed along the path on the microfluidic chip so as to enable the current driving liquid drop to move along the path. The invention enables flexible control of the actuation of one or more droplets.
Description
Technical Field
The invention relates to a micro-fluidic chip technology, in particular to a method for driving an independent electrode on a dielectric electrowetting digital micro-fluidic chip.
background
The microfluidic chip is a potential technology for realizing a Lab-on-a-chip (Lab-on-a-chip), and can integrate basic operation units of sample preparation, reaction, separation, detection and the like in the processes of biological, chemical and medical analysis on a micron-scale chip, and form a network by microchannels, so that a controllable fluid penetrates through the whole system to replace various functions of a conventional biological or chemical laboratory, and the whole analysis process is automatically completed. Due to the huge potential in the aspects of integration, automation, portability, high efficiency and the like, the microfluidic chip technology has become one of the current research hotspots and the world leading-edge science and technology.
the lab-on-a-chip has the advantage of rapid and automated reaction and detection on a chip with a very small dose of chemicals and biological drugs. In the prior art, for example, a chip image is acquired in real time by using a CCD, an LED and a photodiode are integrated, an impedance sensor is integrated, resonance analysis, mass analysis, fluorescence reaction, electrochemical analysis, and the like can be realized without complex and expensive external equipment, but the number of points available for detection is too small and the accuracy is limited. These drawbacks are clearly not compatible with the integration, portability and cheapness of laboratories on chip.
On a digital two-dimensional microfluidic chip based on the medium electrowetting benefit, continuous liquid is discretized by means of an external driving force, and formed micro-droplets are controlled, researched and analyzed, wherein the micro-droplets are accurately detected in real time, and the method has important significance on 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 chip between different areas needs to consider not only real-time performance but also cross-contamination breakdown and other problems. The purely manual routing of the drop paths is too labor intensive to meet the original goals of developing lab-on-a-chip. The automatic planning of the movement path of the liquid drop by utilizing the programmability of the dielectric electrowetting technology and combining with the algorithm of computer and integrated circuit layout design is undoubtedly a promising solution.
Different driving modes of liquid drops on the microfluidic chip have important influences on the control flexibility, the chip manufacturing process, the complexity of matched materials, the cost performance and the like. In the prior art, direct drive, upper and lower polar plate cross drive, broadcast drive, active thin film transistor auxiliary drive and the like do not need more complex external equipment and specific process, or lack control flexibility. These drawbacks are clearly not compatible with lab-on-a-chip integration, portability and cheapness. Therefore, how to drive the liquid drops on the two-dimensional large-scale medium electrowetting digital microfluidic chip in an inexpensive, portable and integrated manner is a problem to be solved.
disclosure of Invention
the invention provides a method for driving independent electrodes on a dielectric electrowetting digital microfluidic chip, which enables a singlechip control driving system to flexibly and effectively control the movement of one or more liquid drops on the microfluidic chip based on an automatically planned path.
in order to achieve the above object, the technical solution of the present invention is to provide a droplet driving method based on a dielectric electrowetting digital microfluidic chip, comprising:
The personal computer sends a first instruction to the singlechip to control the drive system to scan the medium electrowetting digital microfluidic chip through the singlechip, and all electrodes on the microfluidic chip are electrified one by one; the detection circuit is used for collecting the detection result of the microfluidic chip when the electrode is powered on every time, and the single chip microcomputer is used for forming a corresponding detection value;
according to the detection value fed back by the singlechip, the personal computer distinguishes the electrode with the current driving liquid drop or the obstacle thereof or the electrode without the current driving liquid drop or the obstacle thereof, represents the size and the position of the current driving liquid drop or the obstacle thereof on the electrode, and plans and displays the path of the current driving liquid drop from the specified initial position to the specified end position;
And the personal computer sends a second instruction with path related information to the singlechip, and the singlechip controls the driving system to sequentially electrify the electrodes distributed along the path on the microfluidic chip so as to enable the current driving liquid drop to move along the path.
Preferably, the driving system is provided with an and gate array and a solid state relay array; the number of the relays is the same as that of the electrodes on the microfluidic chip, and the relays are correspondingly connected;
The single chip microcomputer correspondingly provides m row signals and n column signals to each AND gate through m rows and n columns of digital pins arranged on the single chip microcomputer; each row signal is accessed to the first input ends of the AND gates of all the columns corresponding to the row, and each column signal is accessed to the second input ends of the AND gates of all the rows corresponding to the column;
when the first input end and the second input end of each AND gate are simultaneously at the first level, outputting the first level to the input end of the relay corresponding to the AND gate so as to switch on a path between the electrode corresponding to the relay and the driving voltage and power up the corresponding electrode; or when the first input end and the second input end of each AND gate are not at the first level at the same time, outputting the second level to the input end of the relay corresponding to the AND gate so as to cut off a path between the electrode corresponding to the relay and the driving voltage and enable the corresponding electrode to lose power;
the first level is a high level and the second level is a low level; alternatively, the first level is a low level and the second level is a high level.
preferably, the detection circuit comprises a detection resistor, a voltage follower, a multiplier and a low-pass filter; when the driving system is powered on by replacing one electrode, the detection resistor extracts a current signal flowing through the microfluidic chip once, converts the current signal into a voltage signal and sends the voltage signal to the voltage follower for following; the output of the voltage follower is divided into two paths and sent to a multiplier to carry out signal squaring; low-pass filtering the output of the multiplier; the analog-to-digital converter of the single chip microcomputer collects the direct current output of the low-pass filter and feeds back a corresponding detection value to the personal computer.
Preferably, the detection values acquired after all the electrodes are respectively electrified are compared, and the detection value of the electrode with the current driving liquid drop or obstacle is higher than the detection value of the electrode without the current driving liquid drop or obstacle;
The currently actuated drop is one or more drops;
The obstacle is a substance or a position point on the microfluidic chip which obstructs the movement of the current driving droplet, and comprises any one or any combination of residual reagent, a breakdown point, other droplets except the current driving droplet.
Preferably, according to the received first instruction, the singlechip controls the driving system to electrify all the electrodes one by one; when one electrode is powered on, the single chip microcomputer collects a detection value from the detection circuit once for comparison with a set threshold value, records the detection value higher than the threshold value as a first comparison value, and records the detection value equal to or lower than the threshold value as a second comparison value;
The singlechip integrates the detection values corresponding to all the electrodes and sends the detection values to a personal computer through a serial port; the integrated detection value is used for recording the serial number of the electrode and a first comparison value or a second comparison value corresponding to the electrode;
and the personal computer analyzes the integrated detection value, marks the positions of the electrodes with the detection values as the first comparison values when displaying, and records the positions to the obstacle position information base.
preferably, the singlechip receives the path related information issued with the second instruction, obtains the planned path and stores the planned path into the path array; in the path related information, the data bit corresponding to each electrode on the path comprises the row address and the column address of the electrode;
The single chip microcomputer analyzes the path, row and column digital pins of the single chip microcomputer corresponding to the electrodes distributed along the path are obtained to carry out level adjustment, and then the electrodes distributed along the path are sequentially electrified through a driving system so as to drive liquid drops to reach an end point position from an initial position;
The level adjustment comprises the steps of gradually changing the level of each electrode on the corresponding row-column digital pins on the singlechip on the path from the second level to the first level and recovering to the second level after lasting for a set time; the second level is the level initially set by the single chip microcomputer for each row and column digital pin.
preferably, if the single chip microcomputer judges that the personal computer issues a first instruction to the single chip microcomputer, and the path array is judged to store array elements related to the path planned last time, the single chip microcomputer sends a detection value corresponding to the path planned last time to the personal computer;
if the single chip microcomputer judges that the personal computer issues a first instruction, and judges that no array element exists in the path array, the single chip microcomputer performs level adjustment on row and column digital pins arranged on the single chip microcomputer, and then all electrodes are electrified one by one through a driving system;
The level adjustment comprises the steps that the level of each row of digital pins is set to be a first level in sequence and then is restored to be a second level, and when each row of digital pins is set to be the first level, the level of each column of digital pins is set to be the first level in sequence and then is restored to be the second level; the second level is the level initially set by the single chip microcomputer for each row and column digital pin.
preferably, the path of the currently driven droplet from the specified start position to the specified end position is planned based on the Lee algorithm, comprising the following processes:
Firstly, giving the initial position, the final position and the barrier position of the current driving liquid drop and the path-finding range corresponding to the electrode array on the micro-fluidic chip, and filling:
setting the step number of the liquid drops at all positions in the path searching range to be 0;
setting the number of liquid drop steps at the position adjacent to the cross at the starting position as 1;
And if the initial value of i is 1, and the adjacent position of the cross of the position with any droplet step number being 'i' is not the end position, circularly filling: setting the number of droplet steps at the position adjacent to the cross at the position with the droplet step number of i as i +1, and setting the i as i + 1;
stopping filling until the adjacent position of the cross of any position with the droplet step number of i is the end position, and jumping out of the cycle; starting the second step;
and secondly, rewinding the initial position from the end position one step by one step, and tracing the source:
setting the first 'wavefront position' as the appointed terminal position, and the step number of the liquid drop is j obtained in the first step;
and setting the initial value of p as j, and iterating: replacing the 'wavefront position' with the step number p of the droplet found each time by the position with the step number p-1 of the droplet, and making p equal to p-1;
And stopping tracing until the current wave front position is replaced by the initial position of the liquid drop when p is 0, and reversing an ordered queue formed by all the wave front positions obtained by iteration to obtain a planned path.
preferably, the graphical user interface provided by the personal computer generates a button array corresponding to the electrode array on the microfluidic chip, and displays information by displaying buttons of different styles on the button array, wherein the displayed information includes: the size and position of the currently driven droplet or its obstacle on the electrode, the start and end positions specified for the currently driven droplet, the planned path.
preferably, after the microfluidic chip, the single chip microcomputer, the driving system, the detection circuit and the personal computer are assembled, the method further comprises the following calibration process of converting the detection result of the liquid drop:
S1, setting the normal driving threshold as the driving voltage applied to drive a first droplet at any position on the microfluidic chip to move between the adjacent electrodes;
s2, removing the first liquid drop, and reducing the driving voltage to be lower than a normal driving threshold value;
s3, performing parameter determination related to the state of the liquid drop to be detected on one or more liquid drops to be detected at any position and in any size on the microfluidic chip to obtain original parameters;
s4, electrifying any 100% of electrodes covered by the liquid drop to be detected on the micro-fluidic chip, and recording the value data1 fed back to the personal computer by the single chip microcomputer;
s5, restoring the driving voltage to a normal driving threshold value, adjusting the resistance value of the detection resistor, and observing the value data2 fed back to the personal computer by the single chip microcomputer; and when the fed-back value data2 is equal to the data1, stopping adjusting the detection resistor, completing calibration, and taking the original parameters of the liquid drop to be detected as the detection result corresponding to the normal driving threshold value.
In summary, the driving method of the independent electrode on the dielectric electrowetting digital microfluidic chip provided by the invention is used for constructing a DIY circuit system by a simple, convenient and cheap method so as to drive the liquid drop on the two-dimensional large-scale dielectric electrowetting digital microfluidic chip. Because of the direct drive based on the cross control, the special process required by the current micro-fluidic chip manufacturing can be omitted. The invention can drive one or more liquid drops simultaneously; after the reasonable automatic planning is carried out on the traveling path of each liquid drop, the singlechip controls the driving hardware according to the path, and the control flow of the liquid drop movement is realized.
drawings
FIG. 1 is a schematic diagram of a drive signal flow in a droplet drive system;
FIG. 2 is a schematic diagram of a droplet detection and drive system;
FIGS. 3a, 3b, 3c, and 3d are schematic views of a three-layer PCB and a PC, respectively;
FIG. 4 is a schematic structural diagram of a microfluidic chip;
FIG. 5 is a schematic flow diagram of a method for converting the results of droplet detection;
c1-c4 of FIG. 6 are schematic diagrams of the effects of the automatically planned path and the droplet drive;
FIG. 7a is a graph of the effect of driving one droplet;
FIG. 7b is a graph of the effect of driving multiple droplets simultaneously;
FIG. 8 is a screenshot of the test results shown on a personal computer;
FIG. 9 is a schematic control flow diagram of the single-chip microcomputer;
FIG. 10 is a flowchart of the programmed operation of the personal computer;
FIG. 11 is a Lee algorithm description and graphical user interface diagram.
Detailed Description
As shown in fig. 1 to 4, the droplet driving system based on the dielectric electrowetting digital microfluidic chip of the present invention mainly includes: a dielectric electrowetting digital microfluidic chip (hereinafter referred to as microfluidic chip 4), a singlechip 7, an AND gate array 15, a solid-state relay array 10 and a personal computer 18.
the microfluidic chip 4 (fig. 4) is made based on a PCB plug-in substrate, and comprises 100 independently controllable electrodes thereon, which are main components for performing a dielectric electrowetting digital microfluidic experiment; the through holes around the electrode array are lead areas for connecting the independent electrodes with an external control circuit. The single chip microcomputer 7 is, for example, an ATmega2560 type micro control board, and is used for driving liquid drops on the micro-fluidic chip 4, communicating with the personal computer 18 and the like. The personal computer 18 sends a control instruction to the single chip microcomputer 7 by running a corresponding software program, receives information fed back by the single chip microcomputer 7, performs data processing, provides a graphical user interface for man-machine interaction and the like. And gate array 15 is used to generate signals for controlling the intersection of rows and columns. The solid-state relay array 10 is used for transmitting the driving voltage to the independent electrode on the microfluidic chip 4.
illustratively, the PCB plug hole substrate where the microfluidic chip 4 is located is mechanically polished by using 800 meshes, 1000 meshes, 2000 meshes, 5000 meshes and 7000 meshes of sand paper in sequence; cleaning the polished PCB plug hole substrate by using deionized water, and drying; the aluminum film is grown by a PVD method (physical vapor deposition); photoetching an electrode pattern; spin-coating SU-8 as a dielectric layer, and naturally cooling; teflon (Teflon) is spin-coated as a hydrophobic layer and is naturally cooled.
as shown in fig. 3 a-3 d, the corresponding components are mounted by three longitudinally spaced-apart stacked PCB boards and appropriate signal paths (leads, connector modules, etc.) are provided between the components; the personal computer 18 is additionally provided independently of these PCB boards. The microfluidic chip 4 is mounted on a first PCB (printed circuit board) 8 on the upper layer through pin headers at the periphery of the PCB plug hole substrate; the liquid drop detection circuit matched with the microfluidic chip 4 comprises a detection resistor 2, a voltage follower 3, a multiplier 5 and a low-pass filter 6; the single chip microcomputer 7 is arranged on the first PCB board 8 at the same time and is in signal connection with the personal computer 18; the board is provided with a direct current dual power supply module 1 for supplying power to the connected components. And a solid-state relay array 10 is arranged on a second PCB 13 in the middle layer, and an alternating-current high-voltage power supply module 12, a first connector module 9 and a second connector module 11 are arranged for the solid-state relay array, wherein the second connector module 11 is connected with the microfluidic chip 4 for unidirectional control. And an and gate array 15 is arranged on a lower third PCB 17, and a third connector module 14 and a fourth connector module 16 are provided for the and gate array, wherein the fourth connector module 16 is connected with the first connector module 9 to perform unidirectional control on the solid-state relay array 10, and the single chip microcomputer 7 performs unidirectional control on the and gate array 15 by connecting the third connector module 14.
the personal computer 18 issues a control command to the singlechip 7, the singlechip 7 controls the AND gate array 15 according to the issued command to generate a cross control signal, and the solid-state relay array 10 is controlled by the cross control signal; when the input of the solid-state relay is high level, the relay is conducted, and the output end of the relay can connect a proper driving voltage to the independent electrode of the microfluidic chip 4 to drive the liquid drop on the electrode. When the liquid drop is detected, the detection resistor 2 extracts a current signal flowing through the microfluidic chip 4 in real time and sends the extracted signal to the voltage follower 3 for following. The following signal is input to a multiplier 5 in two paths to perform signal squaring. The output of the multiplier 5 is low-pass filtered by a low-pass filter 6, and a dc signal is obtained at the output of the low-pass filter 6. The direct current signal is collected by the singlechip 7 and then sent to the personal computer 18 for subsequent processing.
and the two-input AND gates contained in the AND gate array 15 are connected with the relays contained in the solid-state relay array 10 in a one-to-one correspondence mode, and the number of the two-input AND gates is matched with that of the independent electrodes on the microfluidic chip 4. The output end of each two-input AND gate is connected with the input end of a corresponding solid-state relay through a current-limiting resistor. This example uses 25 and-gates (e.g., model 74HC08D from philips semiconductors, each containing 4 two-input and-gates) and 100 solid-state relays (e.g., model AQH2223 from panasonic corporation), corresponding to 100 individual electrodes with EWOD functionality to be driven on the microfluidic chip 4. The independent electrodes, the relays, the two-input AND gates correspond to 10 × 10 arrays respectively, and20 paths of cross control signals corresponding to the independent electrodes, the relays and the two-input AND gates comprise 10 paths of row signals and10 paths of column signals. Theoretically, as long as the driving capability of the circuit and the digital pins of the single chip microcomputer are sufficient, the method of cross control can use any number of n-path row signals and m-path column signals to control n multiplied by m independent electrodes.
The row/column signals mentioned in this example are generated by the single chip 7 and directly sent to the input terminals of the respective and gates, wherein each row/column signal is simultaneously connected to the input terminals of 10 two-input and gates. For example, now the row signal of row 0 is R0, the column signal of column 0 is C0, and the input terminal of each two-input and gate is A, B. Then the R0 is respectively connected with the input ends A of an AND gate AND00, an AND01, an AND02, an AND03, an AND04, an AND05, an AND06, an AND07, an AND08 AND an AND09 after being output from the single chip microcomputer; the C0 is respectively connected with the input ends B of an AND gate AND00, an AND10, an AND20, an AND30, an AND40, an AND50, an AND60, an AND70, an AND80 AND an AND90 after being output from the single chip microcomputer. (ANDnm represents the AND gate in the nth row and the mth column, n is more than or equal to 0 and less than or equal to 9, and m is more than or equal to 0 and less than or equal to 9). According to the operation rule of the AND gate, the output of the AND gate AND00 is high only when R0 AND C0 are both high. The connection of other row/column signals is similar and not repeated.
after the driving system and the detection circuit are built, firstly, calibration is needed, and corresponding data can be tested in the calibration process by using self-contained software (but not limited to the self-contained software) of an Arduino development kit. As shown in fig. 5, in calibration, a driving voltage for driving any one of the droplets to move between the adjacent electrodes is defined as a normal driving threshold; the drive voltage is dropped below the normal drive threshold (e.g., half of the normal drive threshold, but not limited to). After which the determination of the parameters is started and the measurement can be performed for different positions/different size of the droplets. After the parameters are measured, an electrode which is 100% covered by the liquid drop is found, and the electrode is electrified to record the value data1 returned by the singlechip. And then the driving voltage is restored to the normal driving threshold. And then the value data2 returned by the single chip microcomputer is observed while the resistance value of the detection resistor is adjusted. When the returned value data2 is again equal to data1, the system calibration is complete. Thus, the parameters previously measured at low drive voltages can be correspondingly converted into parameters that can be used at normal drive voltages.
the dielectric electrowetting technology is that when an electrode below a liquid drop is electrified, the liquid drop has an electrowetting phenomenon, namely the contact angle between the liquid drop and an interface becomes smaller (the liquid drop can be regarded as falling). If a droplet spans between two adjacent electrodes, then the two electrodes are energized in sequence and the droplet moves laterally between the two electrodes. Based on the principle, the driving method can simultaneously drive one or more liquid drops to move on the microfluidic chip. FIG. 6(c1-c4) shows a droplet moving along an L-shaped path. FIG. 7a (a1-a9) shows a droplet moving along an S-shaped path to different squares; FIG. 7b (b1-b6) shows the rotational movement of four droplets on different electrode areas, respectively.
by combining the use of a liquid drop detection circuit and a driving system, the automatic planning of the liquid drop path can be further realized; the automatic planning algorithm adopted in the embodiment is a path-finding algorithm-Lee algorithm, also called prismatic algorithm, and the path can be found only by specifying the initial position, the end position and the planning range (namely a matrix). Namely, whether an obstacle exists at a certain position is detected and determined; judging whether a feasible path exists or not by applying a Lee algorithm; if a feasible path exists, an iterative algorithm is used to find the path (described in detail below). The detection of the liquid drops is realized by receiving information returned by the single chip microcomputer through a serial port, displaying the information on a screen of a personal computer in a digital printing mode, and representing the information such as the size, the position and the like of the liquid drops.
As shown in fig. 11, in an example of a graphical user interface on a personal computer according to the present invention, a button array area is on the left side for displaying a button array corresponding to an electrode array, and displaying a detection result of a droplet and an obstacle on a chip through the button array, which currently shows an example of automatically planning a path for the droplet by using a Lee algorithm; the right side is a control area which shows some control keys, an input frame of matrix rows and columns, the step number of the planned path and the like; the lower side is a message area for providing notification information to the user, such as the function of a control key, brief description of the state of the liquid drop, etc., which can be specified according to the actual application.
as shown in fig. 10, after the control area is filled with the number of rows and columns, by clicking the New grid key, the button array with the corresponding number of rows and columns (10 × 10 in this example) is displayed in the button array area. And automatically detecting the droplet/Obstacle information on the corresponding electrode of the microfluidic chip by clicking an Obstacle key. The legend shows that the actual chip picture shot by the camera and the detection result picture obtained by program operation are synthesized in the button array area to visually display the size and the position of the liquid drop/obstacle in real time, and the liquid drop/obstacle and a circle of corresponding buttons around the liquid drop/obstacle are marked by green (the buttons are shown in the dark color in the figure).
the obstacle in the invention refers to a substance or a position point on the two-dimensional dielectric electrowetting digital microfluidic chip which hinders normal droplet movement, such as a residual reagent at a certain position, a breakdown point, other normal working droplets (for a certain droplet, any other droplet existing on the chip is an obstacle), and the like. When the chip works for the first time, full-chip scanning is performed, and then the path which the liquid drop just moves is scanned. Since the detection value of the electrode position with the droplet or the breakdown point is higher than the detection value of the electrode position without the droplet or the breakdown point, it is considered that an obstacle exists at the electrode point having a higher detection value.
By clicking the Obstacle key, the personal computer can send a command for scanning the whole chip to the single chip microcomputer through the data line of the USB-to-serial port, so that the driving system and the detection circuit are started simultaneously, and the detection is carried out once every driving. For example, if there are 100 electrodes on the chip, then the driving signals are applied to the 100 electrodes one by one to obtain 100 corresponding detection values.
The specific hardware control flow is as follows:
a1, when clicking the obsacle key on the graphical user interface, the personal computer will issue an instruction #1 to the single chip, the single chip will adjust 10 rows of signals (i.e. 10 digital pins) and10 columns of signals (i.e. 10 digital pins) respectively, for example, the row signal of the 1 st channel (i.e. the first digital pin) is set to high level, the row signals of the other channels are set to low level, the columns of signals are set to high level from the 1 st channel for 10ms and then restored to low level (note that all digital pins are in low level initial state), then the column signal of the 2 nd channel … is started, and at this time, the column signal conversion of the row signal of the 1 st channel is completed; then, the column signal conversion of the 2 nd row signal is started, and the method is the same as … of the 1 st row signal until the column signal conversion of the 10 th row signal is completed.
a2, the row and column digital pins of the single chip microcomputer are directly connected to the input end of the AND gate array, and the potential level of the output end of the AND gate array is influenced by the row and column signal change every time; the AND gate array has 100 output signals, each of which is connected to the input terminal of a solid-state relay through a current-limiting resistor. When the input end of the solid-state relay is at a high level, the circuit at the output end is conducted, and the alternating-current high-voltage driving power supply is connected to the lower electrode of the corresponding digital microfluidic chip. On the contrary, when the input end of the digital micro-fluidic chip is at a low level, the circuit at the output end is closed, and the path between the alternating-current high-voltage driving power supply and the lower polar plate of the digital micro-fluidic chip is disconnected.
A3, changing one electrode to power up every 10ms by the driving system, and detecting once every 10ms by the detecting system, namely extracting the current flowing through the digital microfluidic chip once every 10ms by using the detecting resistor. The driving system is closely matched with the detection circuit, and one electrode is just detected once; the detection resistor converts the current signal into a voltage signal and sends the voltage signal to the voltage follower for following; the output of the voltage follower is divided into two paths and sent to a multiplier to carry out signal squaring; low-pass filtering the output of the multiplier; the analog-to-digital converter of the single chip microcomputer collects the direct current output of the low-pass filter.
A4, comparing each acquired data by the singlechip according to a predetermined threshold (determined by data measured in the calibration process) in the program, and recording as 1 when the comparison threshold is higher and recording as 0 when the comparison threshold is equal to or lower than the threshold; after the single chip microcomputer collects the detection values of 100 electrodes, the comparison value (such as 000010021030041 … 101111120 …, 980990; every three bits represent the number of one electrode and the detection value thereof) of each electrode is added after the number (00-99) of each electrode, and the 300 data are sent to software running on a personal computer for processing through a serial port.
The software of a5 and a personal computer automatically analyzes the 300 data, colors the buttons corresponding to the electrodes with the comparison value of 1 in the button array area in green (shown as dark colors in the figure) and adds the position information of the buttons into the obstacle position information base. D 1-d 3 in FIG. 8 correspond to the button array regions, respectively, and show three detection results when one, two, or three large droplets exist on the two-dimensional digital electrowetting microfluidic chip at the same time; the green (dark) labeled areas in the legend correspond to the button locations where each drop/obstruction is actually located and the button locations of the 8 adjacent locations around the drop/obstruction.
in addition to the automatically detected position of the obstacle, the position information of the obstacle may be manually added such that some buttons at the button array area corresponding to the added obstacle are changed in color and labeled as E. And clicking the obsacle key again to complete the information setting of the automatic/manual Obstacle position.
clicking on the S & D adjust key sets the start and end positions of the drop to be actuated in the button array region. In the example of fig. 11, the button labeled S is set to the start position of the drop and the button labeled D is set to the end position to which the drop is to reach. And clicking the S & D adjust key again to complete the setting of the start and end positions of the liquid drops.
By clicking an Animation key, the program starts to automatically plan a path, a liquid drop path from the starting position S to the end position D is obtained, and the total length of the path is displayed; the button labeled E is where the obstacle is located and does not allow the currently actuated drop to move on.
Taking fig. 11 as an example, the process of finding a path by the Lee algorithm includes two steps:
The first step is as follows: fill number
According to the given initial position S, the final position D of the liquid drop, the position E of the obstacle and the routing range (such as within the range of 10 x 10 arrays), the step number of the liquid drop at each position (namely how many steps are needed for the liquid drop to move from the initial position to the position) is set as '0';
Starting from the starting position S, setting the step number of the liquid drops at four adjacent cross positions (other four end points of the cross shape like a prism) to be 1, and displaying the step number on the button at the adjacent position of the cross at the starting position;
setting the number of liquid drop steps to be 2 at the adjacent positions (namely four edges of the prism) of the cross of each 1 button;
setting the number of liquid drop steps to be 3 at the positions adjacent to the cross of each button 2;
……
When the ripple expands to the set end position D, the filling is stopped. The second step is started.
the second step is that: tracing to source
rewinding the starting position S from the end position D step by step;
assuming that the number of drop steps at the end position D is j, this position is set as the "wavefront position";
finding the position with the number of the droplet steps being j-1, and setting the position as a new wave front position (covering the position of the last time, and adopting an iterative algorithm);
finding out the position with the droplet step number of j-2 at the wave front position, and setting the position as a new wave front position;
……
finding the position with the step number of 0 of the liquid drop at the wave front position, namely the starting position S of the liquid drop, and stopping tracing. These "wavefront locations" constitute an ordered array, which in turn is the planned drop path.
and clicking a Download key, the personal computer issues the planned path information to the singlechip through the serial port, and sends an instruction 2# to the singlechip. Since the serial port can only receive and transmit data with one bit, the following convention is adopted: any particular location on the path will have its row address sent first and its column address sent second. Taking the path in fig. 11 as an example, the path is: 67-66-65-55-45-35-34-33-32-31 (10 x 10 array range, marked by lines 0-9, columns 0-9); and adding an instruction #2 to obtain the information stream downloaded to the singlechip as follows: instruction #2 encoding + 67666555453534333231. The single chip microcomputer can perform corresponding processing according to the type of the instruction after receiving the information, and the path of the liquid drop can be placed into the path array after receiving the instruction # 2.
As shown in fig. 9, the control process of the liquid drop movement by the single chip microcomputer via the control drive hardware according to the path issued by the personal computer based on the internal burning program is as follows:
Initializing each digital pin by the singlechip, and setting the row digital pins and the column digital pins to be low levels; extracting the instruction issued by the personal computer to the singlechip, and judging:
if the current issue is judged to be the instruction #1, whether elements are recorded in the path array is further judged: if the path array has no elements, controlling the driving system to scan the whole chip and sending the scanning result to the personal computer (see the above-mentioned A1-A5); if the path array has elements stored in advance, the detection result of the last path is sent to the personal computer.
if the current issued command is judged to be the command #2, the liquid drop path issued by the personal computer is received and stored into the path array, the liquid drop path is analyzed, corresponding row-column digital pins are driven, and electrodes corresponding to the path on the chip are sequentially electrified.
If the instruction is not the instruction #1 or #2, judging whether an element exists in the path array, if so, detecting the droplet path and storing the detection result.
for driving, the single chip receives the issued command #2+ path information, and respectively adjusts 10 rows of row signals (i.e. 10 digital pins) and10 columns of signals (i.e. 10 digital pins). For the path in fig. 11, the row signal of the 7 th row (i.e., the digital pin of the 7 th row) and the column signal of the 8 th row (corresponding to the path information 67) are set to high level for 100ms, and then are restored to low level (note that all the digital pins are low in the initial state). Then, the 7 th row signal and the 7 th column signal (corresponding to the path information 66) are set to the high level for 100ms, and then restored to the low level …, and the 4 th row signal and the 2 nd column signal (corresponding to the path information 31) are set to the high level for 100ms, and then restored to the low level. The path analysis is completed, and then the liquid drop can be driven to reach the end position from the initial position through the level change of the row-column digital pins of the single chip microcomputer, the potential height change of the output end of the AND gate array, the conduction or the closing of the output end circuit of the solid-state relay array and the conduction or the closing of the path between the lower electrode of the digital micro-fluidic chip (namely the electrode below the liquid drop) and the alternating-current high-voltage driving power supply.
by clicking the Continue key on the graphical user interface, the start and end positions of the drop can be interacted. Clicking on the Clear key clears the currently displayed information such as button array, drop/obstacle, start and end position, path, etc.
while the present invention has been described in detail with reference to the preferred embodiments, it should be understood that the above description should not be taken as limiting the invention. Various modifications and alterations to this invention will become apparent to those skilled in the art upon reading the foregoing description. Accordingly, the scope of the invention should be determined from the following claims.
Claims (10)
1. A method for driving independent electrodes on a dielectric electrowetting digital microfluidic chip is characterized in that,
The personal computer sends a first instruction to the singlechip to control the drive system to scan the medium electrowetting digital microfluidic chip through the singlechip, and all electrodes on the microfluidic chip are electrified one by one; the detection circuit is used for collecting the detection result of the microfluidic chip when the electrode is powered on every time, and the single chip microcomputer is used for forming a corresponding detection value;
According to the detection value fed back by the singlechip, the personal computer distinguishes the electrode with the current driving liquid drop or the obstacle thereof or the electrode without the current driving liquid drop or the obstacle thereof, represents the size and the position of the current driving liquid drop or the obstacle thereof on the electrode, and plans and displays the path of the current driving liquid drop from the specified initial position to the specified end position; wherein the obstacle is a substance or a position point on the microfluidic chip which obstructs the movement of the current driving droplet;
And the personal computer sends a second instruction with path related information to the singlechip, and the singlechip controls the driving system to sequentially electrify the electrodes distributed along the path on the microfluidic chip so as to enable the current driving liquid drop to move along the path.
2. the driving method according to claim 1,
the driving system is provided with an AND gate array and a solid state relay array; the number of the relays is the same as that of the electrodes on the microfluidic chip, and the relays are correspondingly connected;
the single chip microcomputer correspondingly provides m row signals and n column signals to each AND gate through m rows and n columns of digital pins arranged on the single chip microcomputer; each row signal is accessed to the first input ends of the AND gates of all the columns corresponding to the row, and each column signal is accessed to the second input ends of the AND gates of all the rows corresponding to the column;
When the first input end and the second input end of each AND gate are simultaneously at the first level, outputting the first level to the input end of the relay corresponding to the AND gate so as to switch on a path between the electrode corresponding to the relay and the driving voltage and power up the corresponding electrode; or when the first input end and the second input end of each AND gate are not at the first level at the same time, outputting the second level to the input end of the relay corresponding to the AND gate so as to cut off a path between the electrode corresponding to the relay and the driving voltage and enable the corresponding electrode to lose power;
the first level is a high level and the second level is a low level; alternatively, the first level is a low level and the second level is a high level.
3. the driving method according to claim 1,
the detection circuit comprises a detection resistor, a voltage follower, a multiplier and a low-pass filter;
When the driving system is powered on by replacing one electrode, the detection resistor extracts a current signal flowing through the microfluidic chip once, converts the current signal into a voltage signal and sends the voltage signal to the voltage follower for following; the output of the voltage follower is divided into two paths and sent to a multiplier to carry out signal squaring; low-pass filtering the output of the multiplier; the analog-to-digital converter of the single chip microcomputer collects the direct current output of the low-pass filter and feeds back a corresponding detection value to the personal computer.
4. The driving method according to claim 1 or 3,
Comparing the detection values acquired after all the electrodes are respectively electrified, wherein the detection value of the electrode with the current driving liquid drop or obstacle is higher than the detection value of the electrode without the current driving liquid drop or obstacle;
The currently actuated drop is one or more drops;
The obstacle may include any one or any combination of a residual reagent, a breakdown point, a droplet other than the current driving droplet.
5. The driving method according to claim 1, 2 or 3,
according to the received first instruction, the single chip microcomputer controls the driving system to electrify all the electrodes one by one; when one electrode is powered on, the single chip microcomputer collects a detection value from the detection circuit once for comparison with a set threshold value, records the detection value higher than the threshold value as a first comparison value, and records the detection value equal to or lower than the threshold value as a second comparison value;
The singlechip integrates the detection values corresponding to all the electrodes and sends the detection values to a personal computer through a serial port; the integrated detection value is used for recording the serial number of the electrode and a first comparison value or a second comparison value corresponding to the electrode;
And the personal computer analyzes the integrated detection value, marks the positions of the electrodes with the detection values as the first comparison values when displaying, and records the positions to the obstacle position information base.
6. The driving method according to claim 1 or 2,
the singlechip receives the path related information issued along with the second instruction, acquires a planned path and stores the planned path into a path array; in the path related information, the data bit corresponding to each electrode on the path comprises the row address and the column address of the electrode;
The single chip microcomputer analyzes the path, row and column digital pins of the single chip microcomputer corresponding to the electrodes distributed along the path are obtained to carry out level adjustment, and then the electrodes distributed along the path are sequentially electrified through a driving system so as to drive liquid drops to reach an end point position from an initial position;
The level adjustment comprises the steps of gradually changing the level of each electrode on the corresponding row-column digital pins on the singlechip on the path from the second level to the first level and recovering to the second level after lasting for a set time; the second level is the level initially set by the single chip microcomputer for each row and column digital pin.
7. the driving method according to claim 1 or 2,
If the single chip microcomputer judges that the personal computer issues a first instruction to the single chip microcomputer, and the path array is judged to store array elements related to the path planned last time, a detection value corresponding to the path planned last time is sent to the personal computer;
If the single chip microcomputer judges that the personal computer issues a first instruction, and judges that no array element exists in the path array, the single chip microcomputer performs level adjustment on row and column digital pins arranged on the single chip microcomputer, and then all electrodes are electrified one by one through a driving system;
The level adjustment comprises the steps that the level of each row of digital pins is set to be a first level in sequence and then is restored to be a second level, and when each row of digital pins is set to be the first level, the level of each column of digital pins is set to be the first level in sequence and then is restored to be the second level; the second level is the level initially set by the single chip microcomputer for each row and column digital pin.
8. the driving method according to claim 1,
Planning a path of a current driving liquid drop from a specified starting position to a specified end position based on a Lee algorithm, and comprising the following processes of:
firstly, giving the initial position, the final position and the barrier position of the current driving liquid drop and the path-finding range corresponding to the electrode array on the micro-fluidic chip, and filling:
setting the step number of the liquid drops at all positions in the path searching range to be 0;
setting the number of liquid drop steps at the position adjacent to the cross at the starting position as 1;
and if the initial value of i is 1, and the adjacent position of the cross of the position with any droplet step number being 'i' is not the end position, circularly filling: setting the number of droplet steps at the position adjacent to the cross at the position with the droplet step number of i as i +1, and enabling i = i + 1;
Stopping filling until the adjacent position of the cross of any position with the droplet step number of i is the end position, and jumping out of the cycle; starting the second step;
and secondly, rewinding the initial position from the end position one step by one step, and tracing the source:
Setting the first 'wavefront position' as the appointed terminal position, and the step number of the liquid drop is j obtained in the first step;
and setting the initial value of p as j, and iterating: replacing the 'wavefront position' with the number of droplet steps p found each time by the position with the number of droplet steps p-1, and letting p = p-1;
and stopping tracing when the current wave front position is replaced by the initial position of the liquid drop until p =0, and reversing an ordered queue formed by all the wave front positions obtained by iteration to obtain a planned path.
9. The driving method according to claim 1,
the graphical user interface arranged on the personal computer generates a button array corresponding to the electrode array on the microfluidic chip, and the buttons of different styles are displayed on the button array to display information, wherein the displayed information comprises: the size and position of the currently driven droplet or its obstacle on the electrode, the start and end positions specified for the currently driven droplet, the planned path.
10. The driving method according to claim 1,
after the micro-fluidic chip, the single chip microcomputer, the driving system, the detection circuit and the personal computer are assembled, the method further comprises the following calibration process of converting the detection result of the liquid drop:
s1, setting the normal driving threshold as the driving voltage applied to drive a first droplet at any position on the microfluidic chip to move between the adjacent electrodes;
S2, removing the first liquid drop, and reducing the driving voltage to be lower than a normal driving threshold value;
S3, performing parameter determination related to the state of the liquid drop to be detected on one or more liquid drops to be detected at any position and in any size on the microfluidic chip to obtain original parameters;
s4, electrifying any 100% of electrodes covered by the liquid drop to be detected on the micro-fluidic chip, and recording the value data1 fed back to the personal computer by the single chip microcomputer;
S5, restoring the driving voltage to a normal driving threshold value, adjusting the resistance value of the detection resistor, and observing the value data2 fed back to the personal computer by the single chip microcomputer; and when the fed-back value data2 is equal to the data1, stopping adjusting the detection resistor, completing calibration, and taking the original parameters of the liquid drop to be detected as the detection result corresponding to the normal driving threshold value.
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| CN109092380A (en) * | 2018-09-19 | 2018-12-28 | 深圳先进技术研究院 | Digital microfluidic system and drop driving method |
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| 粒子群算法在微流控芯片测试中的应用;吕莹;《电子世界》;20170606(第8期);第185-186,189页 * |
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