CN107238790A - Digital microcurrent-controlled biochip in situ rest structure and method based on coding and decoding - Google Patents
Digital microcurrent-controlled biochip in situ rest structure and method based on coding and decoding Download PDFInfo
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- CN107238790A CN107238790A CN201710388109.0A CN201710388109A CN107238790A CN 107238790 A CN107238790 A CN 107238790A CN 201710388109 A CN201710388109 A CN 201710388109A CN 107238790 A CN107238790 A CN 107238790A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R31/00—Arrangements for testing electric properties; Arrangements for locating electric faults; Arrangements for electrical testing characterised by what is being tested not provided for elsewhere
- G01R31/28—Testing of electronic circuits, e.g. by signal tracer
- G01R31/282—Testing of electronic circuits specially adapted for particular applications not provided for elsewhere
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R31/00—Arrangements for testing electric properties; Arrangements for locating electric faults; Arrangements for electrical testing characterised by what is being tested not provided for elsewhere
- G01R31/28—Testing of electronic circuits, e.g. by signal tracer
- G01R31/2801—Testing of printed circuits, backplanes, motherboards, hybrid circuits or carriers for multichip packages [MCP]
- G01R31/281—Specific types of tests or tests for a specific type of fault, e.g. thermal mapping, shorts testing
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R31/00—Arrangements for testing electric properties; Arrangements for locating electric faults; Arrangements for electrical testing characterised by what is being tested not provided for elsewhere
- G01R31/28—Testing of electronic circuits, e.g. by signal tracer
- G01R31/2851—Testing of integrated circuits [IC]
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Abstract
The invention provides a kind of digital microcurrent-controlled biochip in situ rest structure based on coding and decoding and method, which solve in 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.Including decoder, input is connected with controller, and output end is connected with electrode, for voltage signal to be converted into electrode drive sequence according to decoding rule, is acted on each electrode;Encoder, input is connected with electrode, and output end is connected with controller, for passing the actual voltage signal of each electrode back controller by data/address bus after circuit code;And controller, for the voltage signal for passing voltage signal back with exporting to be contrasted, judge whether electrode breaks down, if so, be then failure by corresponding electrode designations, and the drop scheduling to after is adjusted.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 coding 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 decoding.
Background technology
Digital microcurrent-controlled biochip is mainly made up of a two-dimensional array of electrodes, and top crown is one and covered in array
The large electrode of all units, is used as common ground end;Bottom crown applies different control voltages as needed in use, can
Bibliography 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. Griffin,V.Srinivasan,V.K.Pamula,
M.G.Pollack,J.Zhou,Chemical and biological applications of digital-micro
fluidic devices.IEEE Des.Test Comput.24,10–24(2007)).Experimental procedure is translated into one by controller
Series voltage sequence, is loaded on each electrode by pin, realizes all behaviour such as droplets mixing, separation, dilution, injection
Make.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 cause the mistake of result of the test, not only it can consume the plenty of time
With the resource 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 of document 3
Optimize [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 that is being currently used
Failure in region is invalid, and the consumption of test droplets is larger.Some on-line testings pass through the test to choosing in advance
Drop state at point 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.) in reads and analyzes test result using capacitance sensing circuit, this method needs extra steps is divided
Pulse train is analysed to determine that microfluidic arrays to be measured whether there is failure.Read test result and analyze the process of pulse train
The testing time is added, the process of analysis pulse train is particularly susceptible because sensor scale inaccurately introduces error, therefore not enough
It is practical.
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 and entered
Row detection finds, beyond error allowed band, just to judge that an error has occurred, and this result only shows the institute of operating area
There is unit to be likely to failure, it is impossible to obtain correct time and the position of failure generation, the generation that can not fix a breakdown exists
As a result the possibility that drop is moved in detector processes.If being obstacle by suspected malfunctions region all mark, cause a large amount of
The waste of electrode 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, do not apply to
In 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 biographies
There are some problem and shortage in sensor, it is often more important that, this method of testing detected for drop state can only
It can be just detected after failure causes fluid operating mistake to occur, and in order to obtain correct result, in addition it is also necessary to enter again
Row occur the operation of mistake it is even more many before operation, waste time and drop.Moreover, in order that subsequent operation is avoided
Trouble unit to it, it is necessary to carry out resource allocation and droplet path is recombined, and this will change and apply in controlling switch
The voltage driving sequence corresponding with advance scheme, and pin constrain chip in, controlling switch it is corresponding with electrode pass
System is obtained by the voltage driving sequence of advance scheme, therefore the numeral that this on-line testing method can not be constrained in pin
Used on microflow controlled biochip, but the design of electrode direct addressin can make chip-scale excessive again.The present invention is by chip
Electrod-array is as 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, errors repair when
Between it is long and resource consumption is more, and controlling switch it is excessive caused by the excessive technical problem of chip-scale sent out there is provided a kind of failure
Now in time, repair time is short and resource consumption is few, and pin introduces the few digital microcurrent-controlled biological core based on coding and decoding
Piece in situ rest structure and method.
Therefore, the present invention includes decoder, input is connected with controller, and output end is connected with electrode, for by voltage
Signal is converted to the voltage driving sequence of electrode according to decoding rule, acts on each electrode;
Encoder, input is connected with electrode, and output end is connected with controller, for the virtual voltage of each electrode to be believed
Controller is passed back by data/address bus number after circuit code;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 controller, decoder, the voltage letter for latching input
Number, data/address bus is discharged, the time-sharing multiplex of input/output signal is realized.
Preferably, decoder is the line decoder of 2 lines -4, and encoder is the line coding device of 4 lines -2.
Preferably, decoder, encoder number it is identical, and be at least 1.
The present invention also provides a kind of digital microcurrent-controlled biochip on-line testing method based on coding and decoding, including with
Lower step:
(1) application of electrode drive sequence:Controller regard the voltage drive signals in same period as sequence, input
To the line decoder of 2 lines -4, latch is then output to, contact potential series is output on corresponding electrode, made by latch simultaneously
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
The row input line coding device of 4 lines -2, then pass controller back by data/address bus, controller is by the contact potential series passed back and same period
The sequence of application is compared, and the particular location of failure generation and failure is determined whether, by the counter electrode of failure labeled as event
Hinder, and the drop scheduling to after is adjusted.
Preferably, while step (1) chips carry out relevant work, the electrode sequence in next cycle inputs 2 by turn
The line decoder of line -4, is then output to the latch, waits after current period terminates, is output in parallel to the electrode.
The beneficial effects of the invention are as follows its controllable electric number of poles is increased in the form of index, is ensureing that each electrode is separate
Under conditions of reduce the use of pin, efficiently solve fault discovery in digital microcurrent-controlled biochip on-line testing too late
When the problem of so that failure adjusts follow-up relevant operation it is evaded once occur to be positioned at once, it is to avoid
Cause fluid operating mistake, realize the real-time monitoring to electrod-array, reduce the complete of faulty biochemical reaction when occurring
Into the time, testing cost is reduced.
Brief description of the drawings
Fig. 1 is digital microcurrent-controlled biochip interface structure schematic diagram;
Fig. 2 is 4x4 electrod-arrays packet schematic diagram;
Fig. 3 is one group of electrode input/output structure schematic diagram.
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, the line coding device group of 4 lines -2 and
The line decoder group of 2 lines -4, latch, the line decoder of 2 lines -4 group, electrode sequence are sequentially connected with the line coding device group of 4 lines -2,
Controller is connected by data/address bus with latch, the line coding device group of 4 lines -2, and input/output signal is realized by latch
Time-sharing multiplex.
As shown in figure 3, the line decoder of 2 lines -4 each output end correspondence one electrode, each electrode simultaneously connect 4 lines -
The input of 2 line coding devices.That is the number of the line coding of 4 lines -2 device and the line decoder of 2 lines -4 is identical, and is electrode number
A quarter.
Test process is broadly divided into two stages:(1) application of voltage driving sequence;(2) virtual voltage is obtained on electrode
Take and breakdown judge.
(1) application of electrode drive sequence:
Because every kind of signal is by there was only one effectively in the output signal after decoding, that is, in synchronization one 2
The line of line -4 decoder can only choose an electrode, which limits the controllable electrode number of the line decoder of 2 lines -4, otherwise can
What influence fluid was operated is normally carried out.And same Prescribed Properties, i.e. two drops can not be in being directly adjacent in fluid operation
Or diagonal neighbouring array element, it otherwise can cause droplet coalescence, so having certain spacing distance between drop need to be ensured.
In summary two constraints, of the invention to be translated using the line decoder of 2 lines -4, i.e. two pins by the line of 2 lines -4
Code device controls four electrodes.As shown in Fig. 2 four adjacent up and down electrodes are controlled by the same line of 2 line -4 decoder,
An electrode is up in four electrodes of synchronization effectively, that is, there is liquid on a be up to electrode in four electrodes
Drop, this meets the distance limitation of fluid operation to a certain extent just, nor affects on synchronization other fluids operation
It is synchronous to carry out.The voltage signal inputted on data/address bus first will be temporarily stored in latch, and this is in order in detecting electrode voltage
When, data/address bus can free out test result sending back controller.
According to the decoding rule of the line decoder of 2 lines -4, the voltage driving sequence that can apply on each electrode is counter to be released
Actually it is added in the voltage signal of the line decoder input of 2 lines -4.The truth table of the line decoder of 2 lines -4 is shown in Table 1, wherein X1,X2,
C represents three inputs of the line decoder of 2 lines -4, i.e. the three of chip controlling switch, and pin C controls are that the line of 2 lines -4 is translated
The Enable Pin of code device, when C is high, no matter X1And X2Input how, the line of 2 lines -4 decoder output be all low;When C is low
When, the output of the line decoder of 2 lines -4 depends on X1And X2State.E1, E2, E3, E4 represent the line decoder of 2 lines -4 respectively
Four output ends, i.e., four electrodes controlled in electrod-array by the same line of 2 line -4 decoder.
The line decoder truth table of line -4 of table 12
C X1X2 | E1E2E3E4 |
000 | 0001 |
001 | 0010 |
010 | 0100 |
011 | 1000 |
1xx | 0000 |
According to truth table, it can obtain voltage signal and the corresponding relation formula of electrode drive sequence be:
As shown in figure 3, one group of electrode input structure includes four electrodes of the same line of 2 line -4 decoder control, is used for
Apply three pins of voltage signal, the voltage driving sequence such as table 2 of electrode.Each in voltage driving sequence represents this
Electrode is in the state of a certain particular point in time, and " 1 " represents effectively, i.e., applies high voltage on electrode;It is invalid that " 0 " is represented, i.e. electrode
Upper application low-voltage;It is 0 or be 1 all without on the mobile generation of drop influence that " * ", which represents input signal,.Because applying for a long time
High voltage may result in electrode and produce irreversible charge buildup, so when calculating voltage signal, " * " is all regarded
For " 0 ".After the voltage driving sequence for obtaining each electrode, corresponding voltage letter on pin can be obtained by formula (1) (2) (3)
Number, voltage signal table is shown in Table 3.
The voltage driving sequence of the electrode of table 2
Corresponding voltage signal table on the pin of table 3
(2) acquisition of virtual voltage and breakdown judge on electrode:
During chip operation, the voltage in electrod-array on each electrode is detected in real time, according to passing back
The signal of controller determines whether the position of electrode failure and fault electrode.The acquisition of electrode voltage is that voltage signal applies
Inverse process, therefore, it is possible to use the voltage code on electrod-array is output to control by the line coding of 4 lines -2 device by pin
In device, if the voltage signal that the voltage signal after coding is applied to synchronization on electrod-array is identical, illustrate that electrode works
Normally;If differing, show there is electrode to break down, the binary digit differed in two sequences is found by contrast, after
And determine it is that the output signal of which or which line coding device of 4 lines -2 exists abnormal, then it is by its corresponding electrode designations
Failure, and drop scheduling is adjusted to after, it is to avoid use them in subsequent fluid operation.The formula of coding is same
For (1) (2) (3).
Assuming that in second clock cycle, because the residual of liquid causes electrode E1 and E2 short circuit, it can be seen from table 2,
The electrode signal that contact potential series now should be on E1E2E3E4=1000, pin is CX1X2=011.But occur after short circuit,
Low level on E2 will become high level, and the voltage signal that the line coding of 4 lines -2 device is obtained is E1E2E3E4=1100, and 4
The input of the line coding device of line -2 only allows a bit to be 1, therefore its coding output will produce exception.Control
Device rapid drop scheduling to after the 3rd clock cycle after discovery is adjusted, and will in subsequent operation
E1E2E3E4 is labeled as obstacle.
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, it all should still belong to the present invention
The category that claims are covered.
Claims (6)
1. a kind of digital microcurrent-controlled biochip in situ rest structure based on coding and decoding, it is characterized in that, including
Decoder, input is connected with controller, and output end is connected with electrode, for voltage signal to be changed according to decoding rule
For the voltage driving sequence of electrode, act on each electrode;
Encoder, input is connected with electrode, and output end is connected with controller, for by the actual voltage signal of each electrode through electricity
Controller is passed back by data/address bus after the coding of road;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 coding and decoding, its feature
It is, in addition to latch, the latch is located between the controller, decoder, for latching the voltage signal inputted,
Data/address bus is discharged, the time-sharing multiplex of input/output signal is realized.
3. the digital microcurrent-controlled biochip in situ rest structure according to claim 1 or 2 based on coding and decoding, it is special
Levy and be, the decoder is the line decoder of 2 lines -4, the encoder is the line coding device of 4 lines -2.
4. the digital microcurrent-controlled biochip in situ rest structure according to claim 3 based on coding and decoding, its feature
Be, the decoder, encoder number it is identical, and be at least 1.
5. a kind of digital microcurrent-controlled biochip on-line testing method based on coding and decoding, it is characterised in that including following step
Suddenly:
(1) application of electrode drive sequence:Voltage drive signals in same period as sequence, are input to 2 by controller
The line decoder of line -4, is then output to latch, and contact potential series is output on corresponding electrode by latch simultaneously, makes chip
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 the line coding device of 4 lines -2, then controller is passed back by data/address bus, controller applies the contact potential series passed back and same period
Sequence be compared, determine whether failure occur and failure particular location, by the counter electrode of failure be labeled as failure, and
Drop scheduling to after is 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 inputs described 2 by turn
The line decoder of line -4, is then output to the latch, waits after current period terminates, is output in parallel to the electrode.
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