CN107153122A - Digital microcurrent-controlled biochip in situ rest structure and method based on serial communication - Google Patents
Digital microcurrent-controlled biochip in situ rest structure and method based on serial communication Download PDFInfo
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- CN107153122A CN107153122A CN201710388149.5A CN201710388149A CN107153122A CN 107153122 A CN107153122 A CN 107153122A CN 201710388149 A CN201710388149 A CN 201710388149A CN 107153122 A CN107153122 A CN 107153122A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/00594—Quality control, including calibration or testing of components of the analyser
Abstract
The invention provides a kind of digital microcurrent-controlled biochip in situ rest structure based on serial communication and method, which solve in existing digital microcurrent-controlled biochip on-line testing fault discovery not in time, errors repair time length and resource consumption is more, and controlling switch it is excessive caused by the excessive technical problem of chip-scale.Provided with SI PO shift register, parallel in serial Output Shift Register；Controller is connected by the output end of data/address bus input respectively with SI PO shift register, parallel in serial Output Shift Register, and clock end of the controller by controlling bus respectively with SI PO shift register, parallel in serial Output Shift Register is connected.The present invention is widely used in digital microcurrent-controlled biochip on-line testing technique field.
Description
Technical field
It is more particularly to a kind of based on serial logical the present invention relates to digital microcurrent-controlled biochip on-line testing technique field
The digital microcurrent-controlled biochip in situ rest structure and method of letter.
Background technology
Digital microcurrent-controlled biochip is mainly made up of a two-dimensional array of electrodes, and top crown is institute in a covering array
There is the large electrode of unit, be used as common ground end；Bottom crown applies different control voltages as needed in use, refers to
Document 1 (R.Fair, A.Khlystov, V.Srinivasan, V.Pamula, and K.Weaver, " Integrated
chemical/biochemical sample collection,pre-concentration,and analysis on a
digital microfluidic lab-on-a-chip platform”,Proceedings of SPIE,volume 5591,
Issue 8,page 113–124,2004).Based on dielectric wetness technique, the drop of nanoliter level is limited in operation
Between two-plate, by applying low level and adjacent electrode application high level to electrode where drop simultaneously, change the table of drop
Face tension force, it is achieved thereby that drop is moved from low level to high level, such as document 2 (R.B.Fair, A.Khlystov,
T.D.Tailor,V.Ivanov,R.D.Evans,P.B.Grif fin,V.Srinivasan,V.K.Pamula,
M.G.Pollack,J.Zhou,Chemical and biological applications of digital-
microfluidic devices.IEEE Des.Test Comput.24,10–24(2007)).Controller turns over experimental procedure
A series of voltage sequence is translated into, is loaded into by pin on each electrode, realizes that droplets mixing, separation, dilution, injection etc. are owned
Operation.As digital microcurrent-controlled biochip is in the extensive reference in each field, its function becomes increasingly complex, and needs in use big
Amount fluid operation repeats on an array, and electrode contacts the continuous macromolecular substances with various easy adhesions thereon, and
High level is kept for a long time or the switching of low and high level is constantly carried out, and this will make the increase of its fault rate.Once it breaks down
The mistake that can then cause drop movement and fluid to operate, and then causes the mistake of result of the test, can not only consume the plenty of time and
The resources such as drop, serious consequence can be more caused in actual applications.
Because digital microcurrent-controlled biochip is generally used in terms of health detection, drug research and development and air quality monitoring,
In order to ensure the rapidity, accuracy and reliability of operating result, just have to carry out it online during chip use
Test.
(digital microcurrent-controlled biochip on-line testing paths of Xu Chuanpei, Cai Zhen, the Hu Cong based on ant group algorithm is excellent for document 3
Change [J] Chinese journal of scientific instrument, 2014,35 (6):1417-1424.)、4(Su F,Hwang W,Mukherjee A,et
al..Testing and diagnosis of realistic defects in digital microfluidic
biochips[J].Journal of Electronic Testing:Theory and Applications,2007,23(2/
3):219-233.) with 5 (Xu T and Chakrabarty K.Paralled scan-like test and multiple-
defect diagnosis for digital microfluidic biochips[J].IEEE Transactions on
Biomedical Circuits and Systems,2007,1(2):148-158.) propose to set up test droplets on chip,
Test droplets are controlled under conditions of not influenceing fluid operation to be normally carried out, the electrode unit for making it travel through current idle passes through
Detect whether its correspondence detection zone of test droplets condition adjudgement is faulty.This method is for the array area that is being currently used
Failure in domain is invalid, and the consumption of test droplets is larger.Some on-line testings pass through the test point to choosing in advance
The drop state at place is tested, to judge whether operation is normally carried out, wherein needing additional sensor to complete detection.
(T.Xu, K.Chakrabarty, V.K.Pamula, Design and optimization of a of document 6
digital microfluidic biochip for protein crystallization.in Proceedings of
the IEEE/ACM International Conference on Computer-Aided Design,(2008),pp.297–
301.) read using capacitance sensing circuit in and analyze test result, this method needs extra step to analyze pulse sequence
Arrange to determine that microfluidic arrays to be measured whether there is failure.Read test result and analyze the process of pulse train and add test
Time, the process of analysis pulse train is particularly susceptible because sensor scale inaccurately introduces error, therefore not practical enough.
As most of on-line testings, document 7 (N.Jokerst, L.Luan, S.Palit, M.Royal, S.Dhar,
M.Brooke,and T.Tyler II,“Progress in chip-scale photonic sensing”,IEEE
Trans.Biomedical Circuits and Sys., vol.3, pp.202-211,2009.) it is middle using photoelectric detector inspection
The fluorescence of drop in the middle of surveying, so as to obtain the parameters such as its volume and content of material.It, which is disadvantageous in that, to find in time
Mistake, it is impossible to be accurately positioned failure.During chip operation, the result drop of a certain operation is sent to photoelectric detector progress
Detection finds, beyond error allowed band, just to judge that an error has occurred, and this result only shows all lists of operating area
Member is likely to break down, it is impossible to obtain correct time and the position of failure generation, the generation that can not fix a breakdown is in result
The possibility that drop is moved in detector processes.If being obstacle by suspected malfunctions region all mark, a large amount of electrodes are caused
The waste of resource.
Document 8 (Yan Luo, Krishnendu Chakrabarty, " Hardware/Software Co-Design and
Optimization for Cyberphysical Integration in Digital Microfluidic Biochips”,
2014.) propose to use the sensor based on CCD in, image real-time acquisition to liquid drop movement situation and with desired image pair
Than that can find that mistake occurs in drop in the very first time, and confirm the accurate location of failure.But CCD costs are too high, are not suitable for
This disposable chip, and if having photosensitive sample or reagent in experiment, its light can be impacted to drop.
In summary, current on-line testing method, can only be realized by additional sensor, but various types of sensings
There are some problem and shortage in device, it is often more important that, this method of testing detected for drop state can only be in event
Barrier causes fluid operating mistake to be just detected after occurring, and in order to obtain correct result, in addition it is also necessary to re-start out
Operation before more than the operation even more of existing mistake, wastes time and drop.Moreover, in order that Trouble ticket is avoided in subsequent operation
Member, it is necessary to carry out resource allocation to it and droplet path is recombined, this will change apply in controlling switch with it is advance
The corresponding voltage driving sequence of scheme, and in the chip that pin is constrained, the corresponding relation of controlling switch and electrode is to pass through
What the voltage driving sequence of advance scheme was obtained, therefore the digital microcurrent-controlled biology that this on-line testing method can not be constrained in pin
Used on chip, but the design of electrode direct addressin can make chip-scale excessive again.The present invention is by the electrod-array work of chip
For detection object, the problem of solving on-line testing from the angle of chip structure design for Measurability.
The content of the invention
The present invention be directed to existing digital microcurrent-controlled biochip on-line testing in fault discovery not in time, the errors repair time
Grow and resource consumption is more, and there is provided a kind of fault discovery for the excessive technical problem of the excessive caused chip-scale of controlling switch
In time, repair time is short and resource consumption is few, and pin introduces few digital microcurrent-controlled biochip based on serial communication
In situ rest structure and method.
Therefore, the present invention includes the first shift register, input is connected with controller, and output end is connected with electrode, is used
In moving into voltage signal by turn, act on each electrode；
Second shift register, input is connected with electrode, and output end is connected with controller, for by the reality of each electrode
Voltage signal passes controller back by data/address bus；And
Controller, for the voltage signal for passing voltage signal back with exporting to be contrasted, judges whether electrode event occurs
Barrier, if so, be then failure by corresponding electrode designations, and the drop scheduling to after is adjusted.
Preferably, in addition to latch, latch is located between the first shift register, electrode, for making in controller
With lower while output voltage signal is to electrode.
Preferably, the first shift register is SI PO shift register, and the second shift register is simultaneously
Row incoming serial Output Shift Register.
Preferably, latch count is identical with electrode number.
The present invention also provides a kind of digital microcurrent-controlled biochip on-line testing method based on serial communication, including following
Step：
(1) application of electrode drive sequence：Controller as sequence, moves the voltage drive signals in same period by turn
Enter SI PO shift register, be then output to latch, contact potential series is output to correspondence by latch simultaneously
Electrode on, chip is worked accordingly；
(2) acquisition of virtual voltage and breakdown judge on electrode：The virtual voltage of each electrode of same period is used as a sequence
Row input parallel in serial Output Shift Register, then pass controller back by data/address bus, controller is by the voltage sequence passed back
Arrange the sequence applied with same period to be compared, the particular location of failure generation and failure is determined whether, by the correspondence of failure
Electrode designations are failure, and the drop scheduling to after is adjusted.
Preferably, while step (1) chips carry out relevant work, the electrode sequence in next cycle is moved into serially by turn
Parallel output shift register is inputted, latch is then output to, waits after current period terminates, is output in parallel to electrode.
The beneficial effects of the invention are as follows provided with latch, can simultaneously act on and counter electrode, effectively reduce electrode failure
Rate, provided with controller, SI PO shift register and parallel in serial Output Shift Register, is effectively solved
In digital microcurrent-controlled biochip on-line testing fault discovery not in time the problem of so that failure once occur can at once by
Positioning, and adjust follow-up relevant operation and evade to it, it is to avoid cause fluid operating mistake, reduces faulty life when occurring
The deadline of thing chemical reaction, reduce testing cost.
Brief description of the drawings
Fig. 1 is digital microcurrent-controlled biochip interface structure schematic diagram；
Fig. 2 is 3 × 3 electrod-array serial input structural representation；
Fig. 3 is 3 × 3 electrod-array voltage signal serial input schematic diagram；
Fig. 4 is the structural representation for being grouped control signal input；
Fig. 5 is the structural representation for obtaining virtual voltage on electrode.
Embodiment
The present invention is described further with reference to embodiment.
As shown in figure 1, the I/O interfaces of digital microcurrent-controlled biochip include latch group, serial input-parallel output
The electrode number of latch count and chip in shift register and parallel in serial Output Shift Register, latch group
It is identical.SI PO shift register, latch group, electrode sequence and parallel in serial Output Shift Register
It is sequentially connected, controller is exported with SI PO shift register, parallel in serial respectively by data/address bus
Shift register is connected, and is exported respectively with SI PO shift register, parallel in serial by controlling bus
Shift register and the connection of latch group.
The on-line checking process of digital microcurrent-controlled biochip is broadly divided into two stages：(1) input of voltage signal；
(2) acquisition of virtual voltage and breakdown judge on electrode.
(1) application of electrode drive sequence：
As shown in Fig. 2 digital microcurrent-controlled biochip is provided with 3 × 3 electrod-arrays and corresponding serial input simultaneously
Row Output Shift Register, D1~D9 is the d type flip flop of nine edging triggers, is controlled by same pulse signal, each trigger
Output end Q (Q1~Q8) be connected to its right one trigger input D (D2~D9).By controlled nine electrodes (E1~
E9 nine parallel output terminal Q (Q1~Q9)) are connected on successively, and voltage signal, from D1 serial inputs, works as clock according to corresponding order
Signal is added on nine trigger D simultaneously when, what each trigger was received is original data in the trigger of one, the left side, string
Data in row input parallel output SYN register move to right one successively, and in parallel output terminal Q outputs.
Due to acting on the voltage driving sequence needs of same work period in chip while being applied on each electrode, and
The sequence of SI PO shift register input will sequentially pass through parallel defeated on the left of it in the presence of clock
Go out end and get to corresponding electrode, this can cause the frequent change of voltage on some electrodes in the short time, cause unnecessary
Fluid is operated.
Therefore, latch is set between SI PO shift register and electrod-array, to the defeated of result
Go out to be controlled by.Data/address bus connects the serial input terminal of SI PO shift register, serial input-parallel output
Each parallel output terminal of shift register is connected on each electrode successively by a latch respectively.Controller is according to voltage
The work period of drive signal, using the voltage drive signals in same period as sequence, under control of the clock signal by turn
Move into SI PO shift register；Etc. the whole end-of-shifts of sequence, after the input for being output to each latch, control
Bus processed sends control signal, the signal that serial shift is completed while being output in parallel on corresponding electrode to latch, makes
Chip is worked accordingly, at the same time, starts to move into serial input-parallel by turn in next cycling electrode sequence
Output Shift Register, is output to latch, waits after the end cycle that front electrode driving voltage is acted on, is output in parallel to
Electrode, is then repeated.
The electrod-array of one 3 × 3 as shown in Figure 3, the voltage driving sequence such as table 1 of its electrode.Voltage driving sequence
In each represent state of this electrode in a certain particular point in time, " 1 " represents effective, i.e., applies high voltage on electrode；“0”
It is invalid to represent, i.e., apply low-voltage on electrode；It is 0 or be 1 all without the mobile generation shadow to drop that " * ", which represents input signal,
Ring.Irreversible charge buildup is produced because applying high voltage for a long time and may result in electrode, voltage signal is being calculated
When, " * " is all considered as " 0 "., will be right in each work period according to sequential after the voltage driving sequence of each electrode is determined
The contact potential series answered is output in parallel to electrode, then the sequence series of next work period are inputted.For example, in second clock
In cycle, the clock cycle, corresponding sequence 000 100 010 was output in parallel to each electrode by latch, simultaneously, the
The sequence 000 100 000 of three clock cycle starts to sequentially enter from serial input terminal.
The voltage driving sequence of the electrode of table 1
In digital microcurrent-controlled biochip, the working frequency f of driving voltagebFor 18kHz, and the displacement of shift register frequency
Rate frThe order of magnitude be MHz, therefore, by all electrodes after the voltage signal serial input of synchronization the side of parallel output again
Case, the chip for being less than 103 orders of magnitude for electrode number is feasible, but for the electrod-array being on a grand scale, it is serial defeated
The total time entered, which may be more than driving voltage, needs duration.I.e. M × N electrod-array needs M × N number of shift clock
Cycle could fully enter voltage signal, ifThen chip can not normal work.
As shown in figure 4, for avoid chip can not normal work, by M × N electrod-array with from left to right, from top to bottom
Order be grouped, one SI PO shift register of every group of setting, make with group electrode voltage signal string
Row is inputted, and is inputted parallel between different groups.In grouping process, in order to ensure the electricity acted within next voltage power supply cycle
Press sequence all to shift in current operating cycle to complete, set ten times of work period as the sequential shift total time of voltage
Left and right, i.e., every group of electrode number is tentatively set to
If its electrode sum is less thanThen with the mode of the whole serial inputs of signal, otherwise also need to continue division operation.
Group numberIfIt is not integer, illustrates that electrod-array can not be averaged packet, this
When judgeRounding-off situation.IfShow the electrode number of last group less than T ', it is actualIfCalculate the electrode number F=M × N-T ' given up
×G。
If F≤G, the number of electrodes in preceding F groups is added 1, the electrode number for finally giving every group is
If F>G, then every group need to increase number of electrodes k=floor (F/G), obtain T (i)=T '+k；If also electrode is remaining,
Then the number of electrodes of preceding r=mod (F, G) group adds 1 again, F electrode is assigned in G groups, the electrode number for finally giving every group is
So M × N electrod-array, which at most only needs to clock cycle of T '+k+1 displacements, can just realize that signal is inputted.
In irregular electrod-array, whole serial inputs of voltage signal can also be realized by the above method or are divided
M × N, need to only be substituted for total number of electrodes of array by group serial input when calculating.
(2) acquisition of virtual voltage and breakdown judge on electrode：
As shown in figure 5, the real-time monitoring to each electrode virtual voltage in electrod-array is considered as voltage signal input
Inverse process, therefore, realize the acquisition stage from parallel in serial Output Shift Register, parallel in serial output
Shift register situation corresponding with electrode is consistent with the stage (1).During chip carries out fluid operation, same week
The virtual voltage of phase each electrode is as a sequence inputting parallel in serial Output Shift Register, in the control of clock signal
Lower Serial output, controller is passed back by data/address bus.The sequence for applying the contact potential series passed back and same period in controller
It is compared, you can determine whether the particular location of failure generation and failure.If the signal that controller is obtained is applied with synchronization
The voltage signal being added on electrod-array is identical, shows that electrode is working properly；If differing, show there is electrode to break down,
The binary digit differed in two sequences is found by contrast, then determine be which or which electrode output signal exist it is different
Often, by corresponding electrode designations it is then failure, and the drop scheduling to after is adjusted, it is to avoid operated in subsequent fluid
In use them.
As shown in Figure 3, it is assumed that in second clock cycle, because the residual of liquid causes electrode E1 and E2 short circuit.Root
Understand that contact potential series now should be E1E2E3E4E5E6E7E8E9=000 100 010 according to table 1.After short circuit, serial input is arrived
The voltage signal of controller is E1E2E3E4E5E6E7E8E9=000 110 010, by contrast, it is known that the low-voltage on E5 is by E4
Draw high, i.e., two electrodes there occurs short circuit.Controller rapid drop to after the 3rd clock cycle after discovery, which is dispatched, to be carried out
Adjustment, and E4, E5 are labeled as obstacle in subsequent operation.
Only above person, is only the specific embodiment of the present invention, when can not limit the scope that the present invention is implemented with this, therefore
The displacement of its equivalent assemblies, or the equivalent variations made according to scope of patent protection of the present invention and modification, all should still belong to power of the present invention
The category that sharp claim is covered.
Claims (6)
1. a kind of digital microcurrent-controlled biochip in situ rest structure based on serial communication, it is characterized in that, including
First shift register, input is connected with controller, and output end is connected with electrode, for moving into voltage signal by turn,
Act on each electrode；
Second shift register, input is connected with electrode, and output end is connected with controller, for by the virtual voltage of each electrode
Signal passes controller back by data/address bus；And
Controller, for the voltage signal for passing voltage signal back with exporting to be contrasted, judges whether electrode breaks down, if
It is then failure by corresponding electrode designations to be, and the drop scheduling to after is adjusted.
2. the digital microcurrent-controlled biochip in situ rest structure according to claim 1 based on serial communication, its feature
It is, in addition to latch, the latch is located between first shift register, electrode, in the controller
The lower output voltage signal simultaneously of effect is to electrode.
3. the digital microcurrent-controlled biochip in situ rest structure according to claim 1 or 2 based on serial communication, it is special
Levy and be, first shift register is SI PO shift register, and second shift register is simultaneously
Row incoming serial Output Shift Register.
4. the digital microcurrent-controlled biochip in situ rest structure according to claim 3 based on serial communication, its feature
It is, the latch count is identical with electrode number.
5. a kind of digital microcurrent-controlled biochip on-line testing method based on serial communication, it is characterized in that, comprise the following steps：
(1) application of electrode drive sequence：Voltage drive signals in same period as sequence, are moved into string by controller by turn
Row input parallel output shift register, is then output to latch, and contact potential series is output to corresponding electricity by latch simultaneously
On extremely, chip is set to be worked accordingly；
(2) acquisition of virtual voltage and breakdown judge on electrode：The virtual voltage of each electrode of same period is defeated as a sequence
Enter parallel in serial Output Shift Register, then controller passed back by data/address bus, controller by the contact potential series passed back with
The sequence that same period applies is compared, and the particular location of failure generation and failure is determined whether, by the counter electrode of failure
Labeled as failure, and to after drop scheduling be adjusted.
6. a kind of digital microcurrent-controlled biochip on-line testing method according to claim 5 based on serial communication, its
It is characterised by, while step (1) chips carry out relevant work, the electrode sequence in next cycle moves into the string by turn
Row input parallel output shift register, is then output to the latch, waits after current period terminates, is output in parallel to
The electrode.
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Application publication date: 20170912 |