CN107649222A - The driving method of absolute electrode on electrowetting-on-didigitalc digitalc micro-fluidic chip - Google Patents

The driving method of absolute electrode on electrowetting-on-didigitalc digitalc micro-fluidic chip Download PDF

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CN107649222A
CN107649222A CN201710692952.8A CN201710692952A CN107649222A CN 107649222 A CN107649222 A CN 107649222A CN 201710692952 A CN201710692952 A CN 201710692952A CN 107649222 A CN107649222 A CN 107649222A
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drop
electrode
path
chip microcomputer
level
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CN107649222B (en
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李春桥
周嘉
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Fudan University
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Fudan University
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502769Containers 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
    • B01L3/502784Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/50273Containers 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 the means or forces applied to move the fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502769Containers 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
    • B01L3/502784Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0636Focussing flows, e.g. to laminate flows
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427Electrowetting

Abstract

On a kind of electrowetting-on-didigitalc digitalc micro-fluidic chip of the present invention in the driving method of absolute electrode, PC issues the first instruction to single-chip microcomputer, to control the drive system electrode on fluidic chip that declined to electrowetting-on-didigitalc digitalc to power up one by one by single-chip microcomputer;The detected value formed according to single-chip microcomputer acquisition testing circuit to the testing result of micro-fluidic chip, whether PC is to having current driving drop or its barrier to make a distinction on electrode, the size and location of current driving drop or its barrier on electrode are characterized, and current driving drop is planned and shown from specified original position to the path in specified final position;PC issues the second instruction for being accompanied with path-related information to single-chip microcomputer, controls drive system to power up the electrode on micro-fluidic chip along path profile successively by single-chip microcomputer, so that currently driving drop moves along path.The present invention can be to one or more drops driving flexibly controlled.

Description

The driving method of absolute electrode on electrowetting-on-didigitalc digitalc micro-fluidic chip
Technical field
The present invention relates to microfluidic chip technology, independent electrical on more particularly to a kind of electrowetting-on-didigitalc digitalc micro-fluidic chip The driving method of pole.
Background technology
Micro-fluidic chip is a kind of potential technology for realizing laboratory on piece (Lab-on-a-chip), can be biology, change The basic operation units such as the, sample preparation of medical analysis process, reaction, separation, detection are integrated into the core of one piece of micro-meter scale On piece, network is formed by microchannel, whole system is run through with controlled fluid, to substitute each of standard biologic or chemical laboratory Kind function, it is automatically performed the overall process of analysis.Due to being shown in integrated, automation, portability and high efficiency etc. Great potential, microfluidic chip technology turn into one of current research focus and world's frontier science and technology.
It is to be carried out quickly with the chemical-biological medicine of few dosage the advantages of laboratory on piece, reacted on the piece of automation, Detection.In the prior art, such as using the real-time acquisition chip images of CCD, integrated LED and photodiode, impedance sensing is integrated Device, harmonic analysis, quality analysis, fluorescence reaction, electrochemical analysis etc., although not needing the external equipment of complex and expensive can be real It is existing, but it is available for the site of detection very little and limited precision system.These defects obviously do not meet the integration in laboratory on piece, just The property taken and cheapness.
On the digital two-dimentional micro-fluidic chip based on medium electrowetting benefit, by external motivating force by continuous liquid Discretization, the fine droplet of formation is manipulated and researched and analysed, wherein microscale droplets are realized with accurate detection in real time, it is right Down-stream experiment and reaction result have great significance.Different zones on micro-fluidic chip can have different work( Can, such as mixing, division, heating, detection etc..As the drop of minimum operation unit on chip, it is between different zones Motion path should consider real-time, it is also contemplated that the problems such as cross pollution punctures.It is pure to arrange droplet path workload too by hand Greatly, the original intention in laboratory on development piece is not met yet.And the programmability of medium electrowetting technology is utilized, with reference to computer, collection Algorithm into circuit layout design plans that liquid drop movement path is undoubtedly very promising solution automatically.
The different driving mode of drop, the flexibility controlled it, the manufacture craft of chip, supplementary material on micro flow chip Complexity and cost performance etc. have important influence.Prior art, for example directly drive, upper bottom crown, which intersects, to be driven It is dynamic, broadcast driving, active thin film transistor (TFT) process auxiliary drive etc., more complicated external equipment, specific technique are not required to, is exactly Lack the flexibility of control.These defects obviously do not meet the integration of chip lab, portability and cheapness.Therefore, How in two-dimentional extensive electrowetting-on-didigitalc digitalc microfluidic chip liquid is driven with a kind of cheap, portable, integrated mode The problem of drop is individual urgent need to resolve.
The content of the invention
The present invention provides a kind of driving method of absolute electrode on electrowetting-on-didigitalc digitalc micro-fluidic chip, based on automatic rule The path drawn makes monolithic function control drive system flexibly have mobile on micro-fluidic chip of one or more drops The control of effect.
In order to achieve the above object, the technical scheme is that providing one kind is based on the micro-fluidic core of electrowetting-on-didigitalc digitalc The drop driving method of piece:
PC issues the first instruction to single-chip microcomputer, to control drive system to electrowetting-on-didigitalc digitalc by single-chip microcomputer Decline and be scanned on fluidic chip, all electrodes on micro-fluidic chip are powered up one by one;To detection circuit in every sub-electrode The testing result of micro-fluidic chip, single-chip microcomputer are acquired during power-up and form corresponding detected value;
According to the detected value of singlechip feedbsck, PC is to the electrode with current driving drop or its barrier or does not have The electrode for having current driving drop or its barrier makes a distinction, to the size of current driving drop or its barrier on electrode And position is characterized, and current driving drop is planned from specified original position to the path in specified final position And display;
PC issues the second instruction for being accompanied with path-related information to single-chip microcomputer, and drivetrain is controlled by single-chip microcomputer System powers up successively to the electrode on micro-fluidic chip along path profile, so that currently driving drop moves along path.
Preferably, the drive system is provided with and gate array, solid-state relay array;Included with gate array with door, with The relay quantity that solid-state relay array includes is identical and corresponding connection, the relay and the number of micro-fluidic chip Top electrode Measure identical and corresponding connection;
The m row n column of figure pins that the single-chip microcomputer is set by it, correspondingly provide m row signal, n column signal to Each and door;Each row signal accesses the first input end with door of all row corresponding with the row, each column signal access and The second input with door of all rows corresponding to the row;
When be simultaneously each the first level with the first input end of door and the second input, the first level of output extremely with this with The input of relay corresponding to door, it is corresponding to connect the path between corresponding with the relay electrode and driving voltage Electrode powers up;Or each first input end and the second input difference with door when when being the first level, export second electrical level It is logical between corresponding with the relay electrode and driving voltage to cut off to the input with the relay corresponding with door Road, make respective electrode dead electricity;
First level is high level and second electrical level is low level;Or first level be low level and Two level are high level.
Preferably, the detection circuit includes detection resistance, voltage follower, multiplier, low pass filter;Drive system The power-up of electrode is often changed, detection resistance is just to flowing through the extraction of the current signal on micro-fluidic chip once, and by current signal Voltage signal feeding voltage follower is converted into be followed;The output of voltage follower divides two-way to be sent into multiplier progress signal Involution;Output to multiplier carries out LPF;The direct current output of low pass filter is entered by the analog-digital converter of single-chip microcomputer Row collection, and corresponding detected value is fed back to PC.
Preferably, the detected value that more all electrodes collect after powering up respectively, there is current driving drop or barrier Electrode detected value, higher than the detected value without the electrode for currently driving drop or barrier;
Current driving drop is one or more drops;
The barrier, it is the material or location point that current driving liquid drop movement is hindered on micro-fluidic chip, includes residual Any one among other drops beyond reagent, breakdown point, current driving drop or its any combination.
Preferably, all electrodes are powered up one by one according to the first instruction received, the single-chip microcomputer control drive system;And And an electrode power-up is often changed, single-chip microcomputer gathers one-time detection value at detection circuit, for being compared with the threshold value of setting Right, will be above threshold value is designated as the first comparison value, and the detected value equal to or less than threshold value is designated as into the second comparison value;
After single-chip microcomputer integrates detected value corresponding to all electrodes, PC is delivered to by serial ports;The detected value of integration In be the distribution of each electrode data bit, to record the first comparison value corresponding to the numbering of the electrode and the electrode or the second ratio To value;
PC parses to the detected value of integration, is the position where each electrode of the first comparison value by detected value Put and be identified in display, and these positions are recorded to obstacle position information storehouse.
Preferably, single-chip microcomputer receive with the second path-related information for issuing of instruction, obtain the path cooked up and by its It is deposited into the array of path;In the path-related information, the data bit of each electrode, the row comprising the electrode in respective path Address and column address;
Single-chip microcomputer parses the path, and the ranks digital pin for obtaining single-chip microcomputer corresponding with the electrode along path profile is come Level adjustment is carried out, and then is to be powered up successively along the electrode of path profile by drive system, to drive drop from original position Reach home position;
The level adjustment, comprising one by one by each electrode on path on single-chip microcomputer in corresponding ranks digital pin Level, while go to the first level from second electrical level and return to second electrical level after continuing setting time;Second electrical level is monolithic The level that machine is initially set to each ranks digital pin.
Preferably, if what single-chip microcomputer judged that PC issues it is the first instruction, and judge to store in the array of path When having the array element related to last time path planning, the detected value corresponding with last time path planning is sent to PC;
What if single-chip microcomputer judged that PC issues to it is the first instruction, and judges do not have array element in the array of path When, the ranks digital pin that single-chip microcomputer is provided with to it carries out level adjustment, and then all electrodes are added one by one by drive system Electricity;
The level adjustment, the second electricity is returned to comprising the level of each row digital pin is set to after the first level successively Flat, where each row digital pin makes the level of each column of figure pin be returned to after being set to the first level successively when being the first level Second electrical level;Second electrical level is the level that single-chip microcomputer is initially set to each ranks digital pin.
Lee algorithms are preferably based on, to current driving drop from specified original position to the road in specified final position Footpath is planned, includes procedure below:
The first step, gives the original position of current driving drop, final position, Obstacle Position, and with micro-fluidic core Footpath scope is sought corresponding to piece Top electrode array, carries out number completion:
The drop step number for seeking all positions in the range of footpath is set to " 0 ";
The drop step number of the cross adjacent position of original position is set to " 1 ";
If i initial value is 1, when the cross adjacent position for the position that any one drop step number is " i " is not terminal position When putting, circulation carries out number completion:Drop step number of each drop step number for the cross adjacent position of the position of " i " is set to " i respectively + 1 ", i=i+1 is made;
When it is final position that any one drop step number, which is the cross adjacent position of the position of " i ", stops number completion, jump Go out circulation;Start second step;
Second step, original position is refunded step by step from final position, is traced to the source:
If first " wavefront-position " is the final position specified, its drop step number is the j that the first step obtains;
If p initial value is j, it is iterated:By " wavefront-position " that the drop step number found every time is p, walked with drop Number is replaced for p-1 position, makes p=p-1;
Until p=0, when what current " wavefront-position " was replaced is the original position of drop, stops tracing to the source, iteration will be passed through The ordered queue that all " wavefront-positions " obtained are formed in turn, the path cooked up.
Preferably, the graphic user interface that the PC is set, generation are relative with micro-fluidic chip Top electrode array The array of buttons answered, by showing that the button of different patterns carries out presentation of information in array of buttons, shown packet contains: The size and location of current driving drop or its barrier on electrode, original position and terminal currently to drive drop to specify Position, the path cooked up.
Preferably, after being completed to micro-fluidic chip, single-chip microcomputer, drive system, detection circuit, PC, one is entered Step includes the following calibration process converted to drop detection result:
S1, driven threshold value is set as can be driving optional position on micro-fluidic chip first drop in phase The driving voltage applied when being moved between adjacent electrode;
S2, the first drop is removed, driving voltage is down to below driven threshold value;
S3, to optional position on micro-fluidic chip, one or more drops to be measured of arbitrary dimension, carry out and drop to be measured The related parametric measurement of state, obtains initial parameter;
S4, any one 100% electrode covered by drop to be measured on micro-fluidic chip is powered up, and it is anti-to record single-chip microcomputer Feed the value data1 of PC;
S5, to observe single-chip microcomputer while driving voltage to be recovered, to driven threshold value, to adjust to the resistance of detection resistance anti- Feed the value data2 of PC;When the value data2 of feedback is equal to data1, stops adjustment detection resistance, complete demarcation, will The initial parameter of drop to be measured is as testing result corresponding with driven threshold value.
In summary, on electrowetting-on-didigitalc digitalc micro-fluidic chip provided by the invention absolute electrode driving method, use Simple and convenient cheap method build can DIY circuit system, to drive the extensive electrowetting-on-didigitalc digitalc microfluidic chip of two dimension On drop.Because being the direct drive based on cross-over control, the special work needed for current facture of microchip can be saved Skill.The present invention can drive one or more drop simultaneously;The travel path of each drop is carried out after reasonably planning automatically, Single-chip microcomputer controls driving hardware according to path, realizes the control flow to drop movement.
Brief description of the drawings
Fig. 1 is drive signal schematic flow sheet in drop drive system;
Fig. 2 is the structural representation of drop detection and drive system;
Fig. 3 a, Fig. 3 b, Fig. 3 c, Fig. 3 d are the schematic diagram of three layers of PCB and PC respectively;
Fig. 4 is the structural representation of micro-fluidic chip;
Fig. 5 is the schematic flow sheet of drop detection result method for transformation;
Fig. 6 c1-c4 is the path and the effect diagram of drop driving planned automatically;
Fig. 7 a are the design sketch for driving a drop;
Fig. 7 b are the design sketch for driving multiple drops simultaneously;
Fig. 8 is the testing result sectional drawing shown on PC;
Fig. 9 is the control flow schematic diagram of single-chip microcomputer;
The procedure operation flow chart of Figure 10 PCs;
Figure 11 is Lee algorithmic descriptions and graphic user interface schematic diagram.
Embodiment
As shown in Figure 1 to 4, the drop drive system based on electrowetting-on-didigitalc digitalc micro-fluidic chip in the present invention, it is main Comprising:Electrowetting-on-didigitalc digitalc micro-fluidic chip (hereinafter referred to as micro-fluidic chip 4), single-chip microcomputer 7 and gate array 15, consolidate State relay array 10, PC 18.
Described micro-fluidic chip 4 (Fig. 4), is made based on PCB consent substrates, can be independently controlled comprising 100 above Electrode, be carry out electrowetting-on-didigitalc digitalc miniflow experiment critical piece;The through hole of electrod-array surrounding is lead areas, is used Absolute electrode is connected with the control circuit of outside.Described single-chip microcomputer 7, e.g. ATmega2560 types micro-control making sheet, use To drive the drop on micro-fluidic chip 4, communicated with PC 18.Described PC 18, it is corresponding by running Software program, control instruction is sent to the single-chip microcomputer 7, receive the feedack of single-chip microcomputer 7, carry out data processing, and carry Man-machine interaction etc. is carried out for graphic user interface.It is described with gate array 15, for producing the signal of ranks cross-over control.It is described Solid-state relay array 10, for the absolute electrode for delivering to driving voltage on micro-fluidic chip 4.
Illustratively, the PCB consent substrates where micro-fluidic chip 4, successively with 800 mesh, 1000 mesh, 2000 mesh, 5000 mesh, 7000 mesh carry out sand paper mechanical grinding;PCB consent substrates after cleaning polishing with deionized water, drying;The growth PVD of aluminium film Method (physical vapour deposition (PVD));Photoetching electrode pattern;Spin coating SU-8 is as dielectric layer, natural cooling;Spin coating Teflon (Teflon) As hydrophobic layer, natural cooling.
As shown in Fig. 3 a- Fig. 3 d, there is the pcb board that interval stacks in the vertical by three pieces to install corresponding component, and carry For signal path (lead, connector module etc.) appropriate between each part;PC 18 is set in addition independently of these pcb boards Put.Wherein, described micro-fluidic chip 4 is attached to first pcb board 8 on upper strata by row's pin of PCB consent substrate surroundings;Coordinate The drop detection circuit that the micro-fluidic chip 4 is set, includes detection resistance 2, voltage follower 3, multiplier 5, LPF Device 6;The single-chip microcomputer 7 is arranged on first pcb board 8 simultaneously, and is connected with the signal of PC 18;It is provided with the plate straight Dual-power module 1 is flowed for connected part power supply.Solid-state relay array 10 is arranged on second pcb board 13 in middle level, and is It is provided with AC high voltage source module 12, the first connector module 9 and the second connector module 11, the second connector mould Block 11 is connected unidirectionally controlled to carry out with micro-fluidic chip 4.Arrangement and gate array 15 on the 3rd pcb board 17 of lower floor, and be It is provided with the 3rd connector module 14 and the 4th connector module 16, wherein the 4th connector module 16 and the first connector mould Block 9 connects to carry out unidirectionally controlled to solid-state relay array 10, and single-chip microcomputer 7, which passes through, connects 14 pairs of the 3rd connector module and gate array Row 15 are unidirectionally controlled.
The PC 18 issues control command to single-chip microcomputer 7, and single-chip microcomputer 7 is according to the order control issued and gate array 15 produce cross-over control signal, pass through cross-over control signal and control solid-state relay array 10;When the input of solid-state relay For high level when, relay conducting, suitable driving voltage can be connected on the absolute electrode of micro-fluidic chip 4 by its output end, Drop on electrode is driven.During drop detection, the extract real-time of detection resistance 2 flows through the current signal of micro-fluidic chip 4 And the signal of extraction is sent into voltage follower 3 and followed.Divide two-way to input multiplier 5 with subsequent signal, carry out signal Involution.LPF is carried out with output of the low pass filter 6 to multiplier 5, can be obtained directly in the output end of low pass filter 6 Flow signal.This direct current signal single-chip microcomputer 7 is gathered, delivers to subsequent treatment is carried out on PC 18 afterwards.
Two inputs included with gate array 15 and door, correspond and connect with the relay that solid-state relay array 10 includes Connect, quantity matches with the absolute electrode quantity on micro-fluidic chip 4.Each two input and the output end of door pass through a current limliting Resistance, it is connected with the input of a corresponding solid-state relay.This example is using 25 and door chip (e.g., Philip The 74HC08D cake cores of semiconductor company, every containing 4 two inputs and door), and 100 solid-state relay (e.g., PANASONICs AQH2223 cake cores), corresponding to needed on micro-fluidic chip 4 driving 100 absolute electrodes with EWOD functions.These Absolute electrode, relay, two inputs and door each corresponding 10 × 10 array, then, and corresponding cross-over control signal totally 20 Road, include the tunnel of row signal 10, the tunnel of column signal 10.In theory, as long as the driving force of circuit and the digital pin of single-chip microcomputer are sufficient, Any more n path of row signal of the method can of this cross-over control, n × m independent electrodes of m roads column signal control.
The row/column signal that this example refers to, produced by single-chip microcomputer 7 and be fed directly to each and door chip input, wherein Access 10 two inputs and the input of door simultaneously per road row/column signal.For example the row signal of present 0th row is R0, the 0th arranges Column signal be C0, each two input and the input of door are A, B.So R0 connects and door respectively after single-chip microcomputer output AND00, AND01, AND02, AND03, AND04, AND05, AND06, AND07, AND08, AND09 input A;C0 is from monolithic Machine output after, connect respectively with door AND00, AND10, AND20, AND30, AND40, AND50, AND60, AND70, AND80, AND90 input B.(ANDnm represent line n, m row with door, 0≤n≤9,0≤m≤9).Advised according to the computing with door Then, only when R0 and C0 are high level, the output with door AND00 can be just high level.The connection side of other row/column signals Formula is similar, does not repeat one by one.
After the completion of drive system and detection circuit are built, it is necessary first to demarcated, Arduino exploitation sets can be used Part carries software (but not limited to) and corresponding data is tested in calibration process.As shown in figure 5, during demarcation, definition, which can drive, appoints The driving voltage that one drop of meaning moves between adjacent electrodes is driven threshold value;Driving voltage is dropped into driven threshold Value is following (the e.g. half of driven threshold value, but not limited to this).Start the measure of parameters afterwards, can be to difference The drop of position/different sizes measures.Parameters look for one 100% electricity covered by drop after being measured Pole, the value data1 of record single-chip microcomputer passback is powered up to the electrode.Driving voltage is recovered to driven threshold value again.Then side Adjust the value data2 of the resistance size side observation single-chip microcomputer passback of detection resistance.When the value data2 of passback is again equal to data1 When, system calibrating is completed.The parameters measured before so under low driving voltage just can accordingly change into driven The parameter that can be used under voltage.
Medium electrowetting technology, when being the electrode power-up below to drop, electrowetting phenomenon, i.e. drop can occur for drop Diminish with the contact angle at interface and (be considered as drop to fall).If drop is across between two neighboring electrode, then first Powered up afterwards to the two electrodes, drop will lateral movement between the two electrodes.Based on above-mentioned principle, driving of the invention Method, one or more drop can be driven to be moved on micro-fluidic chip simultaneously.Fig. 6 (c1-c4) shows a drop along L The situation of type path movement.Fig. 7 a (a1-a9) illustrate the feelings that path of the drop along a S-shaped is moved to different grids Condition;Fig. 7 b (b1-b6) illustrate the rotary motion on Different electrodes region respectively of four drops.
By combining the use of drop detection circuit and drive system in the present invention, further droplet path can be realized Automatic planning;The automatic planning algorithm used in this example, it is to seek footpath algorithm-Lee algorithms, is also prismatic algorithm, it is only necessary to specifies The scope of original position and final position and planning (i.e. matrix) can finds out path.That is, whether detection determines certain position There is barrier;Determine whether feasible path using Lee algorithms;If there is feasible path, with iterative algorithm find out the path (under Text is described in detail).It is the information that single-chip microcomputer passback is received by serial ports, individual in a manner of figure punch wherein to the detection of drop Shown on the screen of people's computer, sign is made to information such as droplet size, positions.
As shown in figure 11, on PC of the present invention in the example of a graphic user interface, left side is array of buttons area, To show the array of buttons corresponding with electrod-array, and pass through detection of the array of buttons to drop, barrier on chip As a result it is shown, currently shows one using the example that Lee algorithms are drop automatic path planning;Right side is control zone, Step number of some operating keys, the input frame of matrix ranks, path planning etc. is shown;Downside is message area, to provide a user The function of announcement information, e.g. operating key, the summary of drop state etc., it can be provided according to practical situations.
As shown in Figure 10, after ranks number being inserted in control zone, by clicking on New grid keys, i.e., shown in array of buttons area Go out the array of buttons (this example 10*10) with corresponding line columns.By clicking on Obstacle keys, automatic detection micro-fluidic chip Drop/obstacle information in respective electrode.What legend showed is to synthesize the reality shot by video camera in array of buttons area Chip picture and program run obtained testing result picture, intuitively to show the size and location of drop/barrier in real time, Drop/barrier and its periphery one are enclosed into corresponding button with green sign (being shown as dark button in figure).
Barrier of the present invention, refer to that those hinder normal drop on the digital microcurrent-controlled chip of two-dimensional medium electrowetting The material or location point of motion, for example remaining reagent on certain position, breakdown point, the drop of other normal works are (to a certain liquid For drop, other any drops present on chip are all barrier) etc..When the first task of chip, one can be carried out Secondary full chip scanning, the path that drop has just been moved through can be scanned afterwards.Because there is the electrode of drop or breakdown point The detected value of position can be higher than the detected value of no drop and the electrode position of breakdown point, it is believed that those detected values are higher Barrier in electrode points be present.
By clicking on Obstacle keys, the data wire that PC can turn serial ports by USB assigns scanning entirely to single-chip microcomputer The order of chip, make drive system and detection circuit while start, often drive once just detection once.For example have 100 on chip Individual electrode, then just give this 100 electrodes to add drive signal one by one, obtain 100 corresponding detected values.
Specific hardware controls flow is as follows:
A1, when clicking on Obstacle keys on a graphical user interface, PC can be to the #1 that sends instructions under single-chip microcomputer, monolithic Machine adjusts 10 path of row signal (i.e. 10 digital pins) and 10 road column signals (i.e. 10 digital pins) respectively, for example first allows the 1st Path of row signal (i.e. first row digital pin) is set to high level, and remaining path of row signal is set to low level, and column signal is opened from the 1st tunnel Begin, low level (noticing that all digital pin original states are all low level), Ran Houkai are then returned to after being set to high level 10ms Begin the road column signal of the 2nd road column signal ... the 10th, and so far, the column signal on the 1st path of row signal, which converts, to be completed;Then the 2nd is started The column signal conversion of path of row signal, method is with the 1st path of row signal ... completes until the column signal of the 10th path of row signal converts.
A2, the ranks digital pin of single-chip microcomputer are directly connected to the input with gate array, each ranks signal intensity, all can Have influence on and the current potential of the output end of gate array height;100 output signals are shown with gate array, each output signal passes through one Current-limiting resistance connects the input of a solid-state relay.When the input of solid-state relay is high level, the circuit of output end is just It can turn on, ac high-voltage driving power will be connected on the bottom electrode of corresponding digital microcurrent-controlled chip.Conversely, when its input Hold for low level when, the circuit of output end may turn off, between ac high-voltage driving power and digital micro-fluidic chip bottom crown Path will disconnect.
A3, drive system change an electrode power-up per 10ms, and detecting system detects once per 10ms, i.e., micro- to flowing through numeral The electric current of fluidic chip is extracted once per 10ms with detection resistance.Drive system and detection circuit close fit, an electrode is just It is detected one time well;Current signal is converted into voltage signal feeding voltage follower and followed by detection resistance;By voltage with Divide two-way to be sent into multiplier with the output of device and carry out signal involution;Output to multiplier carries out LPF;By single-chip microcomputer Analog-digital converter is acquired to the direct current output of low pass filter.
A4, single-chip microcomputer are according to predetermined threshold value in program (data measured by calibration process determine) to each collection Data be compared, higher than threshold value is designated as 1, and 0 is designated as equal to or less than threshold value;Single-chip microcomputer collects this enough 100 electrodes Detected value after, each electrode numbering (00~99) afterwards plus the comparison value (such as 000010021030041 ... of the electrode 101111120….980990;Every three numberings and its detected value for representing an electrode), by serial ports by this 300 data The software run is sent on PC to be handled.
A5, the software of PC can parse this 300 data automatically, by the electrode that comparison value in array of buttons area is 1 Corresponding button paints green (being illustrated as dark color) and the positional information of these buttons is added into Obstacle Position Information bank.In Fig. 8 d1~d3 difference corresponding button array area, display one, two, three big drop while be present in two dimension Three testing results when on digital electrowetting micro-fluidic chip;Green (dark color) sign region in legend, corresponding to each The actually located button position of drop/barrier and the button position of the drop/8 adjacent positions in barrier periphery.
In addition to the Obstacle Position that automatic detection goes out, the positional information of barrier can also be added manually so that press Some buttons corresponding with the barrier being added at button array area, it is changed color and is labeled as E.Again tap on Obstacle keys, the information for completing automatic/hand Obstacle Position are set.
S&D adjust keys are clicked on, original position and the terminal position of the drop to be driven can be set in array of buttons area Put.In Figure 11 example, the button settings labeled as S are the original position of drop, to be arrived for drop labeled as D button settings The final position reached.S&D adjust keys are again tapped on, complete the setting of drop whole story position.
By clicking on Animation keys, program starts automatic path planning, obtains from original position S to final position D's One droplet path, and the overall length that shows paths;Button labeled as E is the position where barrier, does not allow what is currently driven Drop is moving above.
Wherein, by taking Figure 11 as an example, Lee algorithms find the process in path in two steps:
The first step:Number completion
According to given drop original position S, final position D, Obstacle Position E and footpath scope (such as 10*10 arrays are sought In the range of), first the drop step number (i.e. drop moves to the position needs how much to walk altogether from original position) of each position is set to “0”;
Since original position S, by its four adjacent ten word locations (other four end points of " ten " font, like prismatic) Drop step number be set to " 1 ", by the step number include on the button of the cross adjacent position of original position;
Respectively in the cross adjacent position (i.e. the four edges of prismatic) of each " 1 " button, drop step number is set to " 2 ";
Respectively in the cross adjacent position of each " 2 " button, drop step number is set to " 3 ";
……
When this " ripples " expand to the final position D of setting, stop number completion.Start second step.
Second step:Trace to the source
Original position S is refunded step by step from final position D;
Assuming that final position D drop step number is j, the position is arranged to " wavefront-position ";
The position that drop step number is j-1 is found, " wavefront-position " for being arranged to new (covers the position of last time, iteration is calculated Method);
The position that drop step number is j-2 is found at " wavefront-position ", is arranged to new " wavefront-position ";
……
The original position S of position, i.e. drop that drop step number is 0 is found at " wavefront-position ", stops tracing to the source.These " ripples The ordered queue of front position " composition, is exactly the droplet path cooked up in turn.
Download keys are clicked on, the routing information that PC will can be cooked up, single-chip microcomputer, Xiang Dan are issued to by serial ports Piece machine sends instruction 2#.Due to serial ports can only be one one transceiving data, so agreement:Any particular location on path, Its row address is first sent out, then sends out its column address.By taking the path in Figure 11 as an example, the path is:67-66-65-55-45-35- 34-33-32-31 (the 10*10 array ranges marked with 0-9 rows, 0-9 row);Along with instruction #2, obtain downloading to monolithic The information flow of machine is:Instruct #2 coding+67666555453534333231.Single-chip microcomputer can be according to instruction after receiving above- mentioned information Type carry out respective handling, receive instruction #2 the path of drop can be put into the array of path.
As shown in figure 9, program of the single-chip microcomputer based on internal burning, the path issued according to PC, drives by control Dynamic hardware is realized as follows to the control process of drop movement:
Single-chip microcomputer initializes each digital pin, and row digital pin and column of figure pin are all set into low level;Extraction The instruction that people's computer issues to single-chip microcomputer, is judged:
If it is determined that currently issue is instruction #1, then determine whether recorded element in the array of path:If road Footpath array does not have element, and control drive system is scanned to whole chip and scanning result is sent into (ginseng to PC See foregoing A1-A5);If path array previously has element, the testing result in last time path is sent to PC.
If it is determined that currently issue is instruction #2, then receives the droplet path that PC issues and be deposited into road In the array of footpath, parse droplet path and drive corresponding ranks digital pin, add successively for electrode corresponding with path on chip Electricity.
If not instruction #1 or #2, then judge whether there is element in the array of path, if then detecting droplet path simultaneously Testing result is stored.
In order to be driven, single-chip microcomputer receives the instruction #2+ routing informations issued, adjusts 10 path of row signal (i.e. 10 respectively Individual digital pin) and 10 road column signals (i.e. 10 digital pins).Such as to the path in Figure 11, the 7th path of row signal (i.e. is first allowed 7 row digital pins), the 8th road column signal (respective path information 67) is set to high level 100ms, then returns to low level afterwards (noticing that all digital pin original states are all low level).Then the 7th path of row signal is allowed, the 7th road column signal (believe by respective path 66) breath is set to high level 100ms, then return to low level afterwards ... and allow the 4th path of row signal, the 2nd road column signal (believe by respective path 31) breath is set to high level 100ms, then return to low level afterwards.So far, path is parsed, and then the row for passing through single-chip microcomputer Column of figure pin level changes, and changes with the current potential height of gate array output end, the circuit of output terminal of solid-state relay array On and off, (electrode i.e. below drop) leads between ac high-voltage driving power on the bottom electrode of digital microcurrent-controlled chip The on and off on road, it is possible to drive drop to be reached home position from original position.
By clicking on the Continue keys on graphic user interface, original position and the final position of drop can be interacted. Clear keys are clicked on, the information such as array of buttons, drop/barrier, whole story position, path currently shown can be removed.
Although present disclosure is discussed in detail by above preferred embodiment, but it should be appreciated that above-mentioned Description is not considered as limitation of the present invention.After those skilled in the art have read the above, for the present invention's A variety of modifications and substitutions all will be apparent.Therefore, protection scope of the present invention should be limited to the appended claims.

Claims (10)

  1. A kind of 1. driving method of absolute electrode on electrowetting-on-didigitalc digitalc micro-fluidic chip, it is characterised in that
    PC issues the first instruction to single-chip microcomputer, to control drive system to decline electrowetting-on-didigitalc digitalc by single-chip microcomputer It is scanned on fluidic chip, all electrodes on micro-fluidic chip is powered up one by one;Detection circuit is powered up in every sub-electrode When the testing result of micro-fluidic chip, single-chip microcomputer are acquired and form corresponding detected value;
    According to the detected value of singlechip feedbsck, PC is worked as to the electrode with current driving drop or its barrier or not Forerunner's hydrodynamic drips or the electrode of its barrier makes a distinction, to the size and position of current driving drop or its barrier on electrode Put and characterized, and current driving drop is planned and shown from specified original position to the path in specified final position Show;
    PC issues the second instruction for being accompanied with path-related information to single-chip microcomputer, and drive system pair is controlled by single-chip microcomputer Powered up successively along the electrode of path profile on micro-fluidic chip, so that currently driving drop moves along path.
  2. 2. driving method as claimed in claim 1, it is characterised in that
    The drive system is provided with and gate array, solid-state relay array;Included with gate array with door, with solid-state relay battle array Arrange that the relay quantity that includes is identical and corresponding connection, the relay are identical and corresponding with the quantity of micro-fluidic chip Top electrode Connection;
    The m row n column of figure pins that the single-chip microcomputer is set by it, m row signal, n column signal are correspondingly provided to each With door;Each row signal accesses the first input end with door of all row corresponding with the row, each column signal access and the row The second input with door of corresponding all rows;
    When being simultaneously each the first level with the first input end of door and the second input, the first level of output is extremely right with door with this The input for the relay answered, it is respective electrode to connect the path between corresponding with the relay electrode and driving voltage Power-up;Or each first input end and the second input difference with door when when being the first level, output second electrical level to The input of the relay corresponding with door, to cut off the path between corresponding with the relay electrode and driving voltage, make Respective electrode dead electricity;
    First level is high level and second electrical level is low level;Or first level is low level and the second electricity Flat is high level.
  3. 3. driving method as claimed in claim 1, it is characterised in that
    The detection circuit includes detection resistance, voltage follower, multiplier, low pass filter;
    Drive system often changes an electrode power-up, and detection resistance is just extracted once to flowing through the current signal on micro-fluidic chip, And current signal is converted into voltage signal feeding voltage follower and followed;The output of voltage follower divides two-way to be sent into and multiplied Musical instruments used in a Buddhist or Taoist mass carries out signal involution;Output to multiplier carries out LPF;By the analog-digital converter of single-chip microcomputer to low pass filter Direct current output be acquired, and feed back corresponding detected value to PC.
  4. 4. the driving method as described in claim 1 or 3, it is characterised in that
    Compare the detected value collected after all electrodes power up respectively, the detection with the electrode of current driving drop or barrier Value, higher than the detected value without the electrode for currently driving drop or barrier;
    Current driving drop is one or more drops;
    The barrier, be the material or location point that current driving liquid drop movement is hindered on micro-fluidic chip, comprising remaining reagent, Any one among other drops beyond breakdown point, current driving drop or its any combination.
  5. 5. the driving method as described in claim 1 or 2 or 3, it is characterised in that
    According to the first instruction received, the single-chip microcomputer control drive system powers up one by one to all electrodes;Also, often change one Electrode powers up, and single-chip microcomputer gathers one-time detection value at detection circuit, is compared for the threshold value with setting, will be above threshold value Be designated as the first comparison value, the detected value equal to or less than threshold value is designated as the second comparison value;
    After single-chip microcomputer integrates detected value corresponding to all electrodes, PC is delivered to by serial ports;It is in the detected value of integration The data bit of each electrode distribution, to record the first comparison value corresponding to the numbering of the electrode and the electrode or the second comparison Value;
    PC is parsed to the detected value of integration, and detected value is existed for the position where each electrode of the first comparison value It is identified during display, and these positions is recorded to obstacle position information storehouse.
  6. 6. driving method as claimed in claim 1 or 2, it is characterised in that
    Single-chip microcomputer receives the path-related information issued with the second instruction, obtains the path cooked up and is deposited into number of path In group;In the path-related information, the data bit of each electrode in respective path, the row address comprising the electrode and row ground Location;
    Single-chip microcomputer parses the path, obtains the ranks digital pin of single-chip microcomputer corresponding with the electrode along path profile to carry out Level adjustment, and then be to be powered up successively along the electrode of path profile by drive system, to drive drop to be reached from original position Final position;
    The level adjustment, comprising one by one by electricity of each electrode on single-chip microcomputer in corresponding ranks digital pin on path It is flat, while go to the first level from second electrical level and return to second electrical level after continuing setting time;Second electrical level is single-chip microcomputer The level initially set to each ranks digital pin.
  7. 7. driving method as claimed in claim 1 or 2, it is characterised in that
    What if single-chip microcomputer judged that PC issues to it is the first instruction, and judges to be stored with the array of path and last time is planned During the array element of path correlation, the detected value corresponding with last time path planning is sent to PC;
    What if single-chip microcomputer judged that PC issues to it is the first instruction, and when judging there is no array element in the array of path, The ranks digital pin that single-chip microcomputer is provided with to it carries out level adjustment, and then all electrodes are powered up one by one by drive system;
    The level adjustment, comprising returning to second electrical level after the level of each row digital pin is set into the first level successively, Where each row digital pin makes the level of each column of figure pin return to after being set to the first level successively when being the first level Two level;Second electrical level is the level that single-chip microcomputer is initially set to each ranks digital pin.
  8. 8. driving method as claimed in claim 1, it is characterised in that
    Based on Lee algorithms, current driving drop is planned from specified original position to the path in specified final position, Include procedure below:
    The first step, gives the original position of current driving drop, final position, Obstacle Position, and with micro-fluidic chip Footpath scope is sought corresponding to electrod-array, carries out number completion:
    The drop step number for seeking all positions in the range of footpath is set to " 0 ";
    The drop step number of the cross adjacent position of original position is set to " 1 ";
    If i initial value is 1, when any one drop step number is not final position for the cross adjacent position of the position of " i ", Circulation carries out number completion:Drop step number of each drop step number for the cross adjacent position of the position of " i " is set to " i+1 " respectively, Make i=i+1;
    When it is final position that any one drop step number, which is the cross adjacent position of the position of " i ", stops number completion, jump out and follow Ring;Start second step;
    Second step, original position is refunded step by step from final position, is traced to the source:
    If first " wavefront-position " is the final position specified, its drop step number is the j that the first step obtains;
    If p initial value is j, it is iterated:By " wavefront-position " that the drop step number found every time is p, it is with drop step number P-1 position is replaced, and makes p=p-1;
    Until p=0, when what current " wavefront-position " was replaced is the original position of drop, stops tracing to the source, will be obtained by iteration All " wavefront-positions " ordered queue for being formed in turn, the path cooked up.
  9. 9. driving method as claimed in claim 1, it is characterised in that
    The graphic user interface that the PC is set, the generation button battle array corresponding with micro-fluidic chip Top electrode array Row, by showing that the button of different patterns carries out presentation of information in array of buttons, shown packet contains:Current driving liquid Size and location on electrode of drop or its barrier, the original position specified for current driving drop and final position, planning The path gone out.
  10. 10. driving method as claimed in claim 1, it is characterised in that
    After being completed to micro-fluidic chip, single-chip microcomputer, drive system, detection circuit, PC, further include to drop The following calibration process that testing result is converted:
    S1, driven threshold value is set as can be driving optional position on micro-fluidic chip first drop in adjacent electricity The driving voltage applied when being moved between pole;
    S2, the first drop is removed, driving voltage is down to below driven threshold value;
    S3, to optional position on micro-fluidic chip, one or more drops to be measured of arbitrary dimension, carry out and droplet-like state to be measured Related parametric measurement, obtain initial parameter;
    S4, any one 100% electrode covered by drop to be measured on micro-fluidic chip is powered up, and record single-chip microcomputer and feed back to The value data1 of PC;
    S5, observe while driving voltage to be recovered, to driven threshold value, to adjust to the resistance of detection resistance singlechip feedbsck to The value data2 of PC;When the value data2 of feedback is equal to data1, stops adjustment detection resistance, complete demarcation, will be to be measured The initial parameter of drop is as testing result corresponding with driven threshold value.
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CN109164073A (en) * 2018-08-03 2019-01-08 大连大学 Digital microcurrent-controlled chip system and method for heavy metal in water ion measurement
CN109092379A (en) * 2018-09-05 2018-12-28 仲恺农业工程学院 Miniflow reaction chip and its drop positioning control system and control method
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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
CN111250178A (en) * 2018-12-03 2020-06-09 夏普生命科学(欧洲)有限公司 AM-EWOD circuit configuration with sense column detection circuit
CN110264960A (en) * 2019-04-04 2019-09-20 上海中航光电子有限公司 Driving circuit and its driving method, panel and its driving method
CN110264960B (en) * 2019-04-04 2021-01-05 上海中航光电子有限公司 Driving circuit and driving method thereof, panel and driving method thereof
CN110694701A (en) * 2019-10-14 2020-01-17 中国科学院微电子研究所 Method and device for transporting liquid drops and method for cleaning liquid drop transport path
CN113842963A (en) * 2021-10-29 2021-12-28 佛山奥素博新科技有限公司 Micro-droplet generation system and generation method
WO2023082470A1 (en) * 2021-11-12 2023-05-19 佛山奥素博新科技有限公司 Micro-fluidic chip, micro-fluidic device, and droplet real-time control method
CN114308159A (en) * 2021-12-29 2022-04-12 复旦大学 Automatic control method for liquid drops in photoinduced electrowetting chip
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