CN104849322B - A kind of impedance biosensor and bio-impedance determination method - Google Patents
A kind of impedance biosensor and bio-impedance determination method Download PDFInfo
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Abstract
The present invention relates to a kind of impedance biosensor and bioimpedance analysis method, impedance biosensor of the invention includes microprocessor, impedance measurement module and microelectrode module；The microprocessor controls acquisition and the Treatment Analysis of the impedance of the impedance measurement module completion microelectrode module；The impedance measurement module is by setting impedance measurement chip, high-pass filter, voltage follower, I V buffers and range adjuster, realization is fast, accurately measured, while the biology sensor of the present invention has the advantages that cost is relatively low, frequency band is wider, precision is higher, quantitative analysis and Site Detection.
Description
Technical field
The present invention relates to bio-impedance detection technique field, more particularly to a kind of impedance biosensor and bio-impedance inspection
Survey analysis method.
Background technology
Food security and animal epidemic are most one of outstanding problems that China faces.Currently, food security accident is in many
Hair phase, highly pathogenic animal epidemic also happens occasionally.Pathogenic microorganism examination is food security and the key of Field of Animal Epidemic Disease Control,
Because existing common detection methods can not generally realize field quick detection, therefore in the urgent need to development pathogenic microorganism is quick
Detection technique.
Impedance biosensor is a kind of new bio detection technique, with detection speed is very fast, sensitivity is higher and grasps
The advantages of making simpler, has obtained the concern of the field researcher such as agricultural, food, environment and health and enterprise.Forefathers grind
Study carefully and show：Its accuracy of detection is generally between large-scale experiment room analytical instrument (such as real-time fluorescence quantitative PCR) and conventional quick detection
Between method (such as colloidal gold strip), it is expected to realize simple, the quick and inexpensive detection of pathogenic microorganism.At present, hinder
Antibiont sensor is generally made up of impedance biochip and electric impedance analyzer, and impedance analysis is typically by large-scale impedance analysis instrument
To complete, U.S. Agilent, Solartron companies of Britain, Zahner companies of Germany all have been developed for impedance analysis instrument
Or electrochemical workstation；In addition, also studies have reported that some small-sized impedance detection devices, such as (authorize public number in Ying Yibin
The U of CN 203310795), the impedance detection device of Hu Yaohua (authorize public CN 203241371 U) et al. independent development.Should
The refined hand-held impedance detection device of justice adds preposition processing between analog signal and detecting electrode, improves impedance detection
Precision and stability.Hu Yaohua hand-held impedance detection device can realize that multiple target is determined, and have warning function.
But existing small-sized impedance detection device there is narrow frequency band, detection speed and precision is relatively low, function is simpler
The problems such as.
The content of the invention
The technical problem to be solved in the present invention is to provide a kind of impedance biosensor, realize raw in the range of broad frequency band
The quick and precisely measurement and analysis of thing impedance.
In order to solve the above technical problems, the invention discloses a kind of impedance biosensor, the impedance biosensor
Including microprocessor, impedance measurement module and microelectrode module, objective microbe be adsorbed in the microelectrode module so as to
Change the impedance of the microelectrode module；The microprocessor controls the impedance measurement module to complete the microelectrode module
The acquisition of impedance, and objective microbe concentration is obtained to impedance progress Treatment Analysis；
The impedance measurement module includes：
Impedance measurement chip, the impedance for measuring the microelectrode module, the impedance measurement chip and micro- place
Device connection is managed, the microprocessor provides control signal for the impedance measurement chip；
High-pass filter, its input is connected with the pumping signal output end of the impedance measurement chip, low for filtering
Frequency interference signal；
Voltage follower, its input connects the output end of the high-pass filter, and its output end connects the microelectrode
The input of module, the DC offset voltage of the pumping signal for adjusting the impedance measurement chip output, so as to eliminate institute
State the DC component difference between the output end and input of microelectrode module；
I-V buffers, its input connects the output end of the microelectrode module, and its output end is connected by feedback resistance
The input pin VIN and RFB of the impedance measurement chip, the current signal for the microelectrode module to be exported are converted into electricity
Pressure signal is simultaneously input to the impedance measurement chip, and handled the voltage signal of reception by the impedance measurement chip
The microprocessor is passed to the impedance of the microelectrode module, then by the impedance of the microelectrode module；
And range adjuster, the output end of its input connection microelectrode module, its output end connection I-V
The output end of buffer, for providing multiple measurement shelves for the impedance measurement chip.
Preferably, the microprocessor uses ARM9 processors, and the ARM9 processors and the impedance measurement core
The connected mode of piece is：
The timer internal T0 of ARM9 processors pin TOUT0 and the impedance measurement chip external clock draw
Pin MCLK connections, clock signal is provided for the impedance measurement chip；The I of the ARM9 processors2C interface clock pins
I2CSCL and I2C interface data pin I2The I of CSDA respectively with the impedance measurement chip2C interface clock pins SCL and I2C
The SDA connections of interface data pin.
Preferably, the microprocessor includes analysis computing unit, and it is obtained according to the impedance measurement chip measurement
The impedance of the microelectrode module obtains the electro transfer resistance of the now microelectrode module, and calculates the now microelectrode
The difference of electro transfer resistance when the electro transfer resistance of module is with the microelectrode module unadsorbed objective microbe, as
Electro transfer increased resistance value, utilizes the electro transfer increased resistance value and the relational model of objective microbe concentration, analysis
Obtain corresponding objective microbe concentration；
The analysis computing unit includes model construction subelement, and it turns the detection architecture of the microelectrode module composition
Equivalent circuit is turned to, and calculates the impedance of the equivalent circuit, its real part is asked in the impedance further according to the equivalent circuit, afterwards
With reference to the real part and corresponding angular frequency of the impedance of measurement, electro transfer resistance is asked for using newton higher education park；Ask for now
The electro transfer resistance and the microelectrode module unadsorbed objective microbe when electro transfer resistance difference, as
Electro transfer increased resistance value, sets up the relational model of the electro transfer increased resistance value and objective microbe concentration.
In this step, the impedance measurement chip measurement obtains the real and imaginary parts (hexadecimal) of impedance, and will measurement
Value is transferred to the microprocessor, and the microprocessor is first according in the corresponding product description of the impedance measurement chip
Conversion formula obtains the actual real and imaginary parts of the impedance of microprocessor module, asks for electro transfer using formula below afterwards
Resistance,
In formula, R is that measurement obtains value of real part, R under specific angular frequencyetFor the electro transfer resistance of equivalent circuit, Rs
For the solution resistance of equivalent circuit, CdlFor the electric double layer capacitance of equivalent circuit.
Preferably, the range adjuster connects including four signal relays and respectively with four signal relays
The feedback resistance of the four different resistances connect, the signal relay is connected with four I/O mouthfuls of the microprocessor respectively, real
The existing microprocessor is automatically selected to the range of the range adjuster.
Preferably, the impedance measurement module also includes：
Voltage-stablizer, it is connected with the impedance measurement chip, for providing stable voltage for the impedance measurement chip；
Touch display module, shows and parameter setting for testing result, wherein the parameter set in the parameter setting
Including sample number, measurement frequency, time of repose, threshold value.
Preferably, the connected mode of the I-V buffers and the impedance measurement chip is：
The output end of the I-V buffers is connected to the input of the impedance measurement chip by feedback resistance RFB1
VIN pins, the output end of the I-V buffers is connected to the impedance measurement by feedback resistance RFB1 and feedback resistance RFB2
The RFB pins of chip.
Preferably, the microelectrode module includes substrate and the first gold electrode, the second gold medal electricity in the substrate
Pole, the first pad and the second pad；
First gold electrode is connected with first pad, and second gold electrode is connected with second pad；Institute
The first gold electrode and the second gold electrode is stated to combine to be formed with identical spacing parallel connection by the finger electrode of multiple identical sizes,
And the finger electrode of first gold electrode and the second gold electrode intersects；
The biological knowledge of objective microbe is modified with the surface of the finger electrode of first gold electrode and the second gold electrode
Other material.
Preferably, the impedance biosensor also includes：
USB module, is connected with the microprocessor, for carrying out Information Access operation with the microprocessor；
Serial port module, is connected with the microprocessor, for being communicated with the microprocessor；
JTAG modules, are connected with the microprocessor, for testing the processor；
Reservoir module, is connected with the microprocessor, for storing the data in the microprocessor；
Power module, is connected with the microprocessor, impedance measurement module and reservoir module, for for micro- place
Reason device, impedance measurement module and reservoir module are powered.
A kind of bio-impedance determination method, the described method comprises the following steps：
Build electro transfer increased resistance value and the relational model of objective microbe concentration：By the inspection of microelectrode module composition
Survey system is converted into equivalent circuit, and calculates the impedance of the equivalent circuit, and the impedance further according to the equivalent circuit asks for it
Real part, is combined the real part and corresponding angular frequency of the impedance of the microelectrode module of measurement, is asked for using newton higher education park afterwards
Electro transfer resistance, and calculate the now electro transfer resistance of the microelectrode module and the unadsorbed target of microelectrode module
The difference of electro transfer resistance during microorganism, as electro transfer increased resistance value, sets up the electro transfer resistance variations
The relational model of value and objective microbe concentration；
The electro transfer increased resistance value of the microelectrode module, and profit are obtained using above-mentioned impedance biosensor measurement
The relational model is used, corresponding objective microbe concentration is found.
Preferably, the impedance of the equivalent circuit is：
Wherein RetFor the electro transfer resistance of the equivalent circuit, XcFor the appearance of the electric double layer capacitance of the equivalent circuit
It is anti-, RsFor the solution resistance of equivalent circuit.
The above-mentioned structure electro transfer increased resistance value and the relational model of objective microbe concentration are specifically included
Following steps：
S1, the detection architecture that microelectrode is constituted is converted into the equivalent circuit, and calculates the impedance of the equivalent circuit,
And as shown by the equation：
Wherein RetFor the electro transfer resistance of the equivalent circuit, XcFor the appearance of the electric double layer capacitance of the equivalent circuit
It is anti-, RsFor the solution resistance of the equivalent circuit.
S2, the capacitive reactance of the calculating electric double layer capacitance are：
Wherein, CdlFor the capacitance of the electric double layer capacitance, f is frequency, and ω is angular frequency.
S3, ask for the equivalent circuit impedance real part R：
Real part is converted into：
(Rs-R)(1+ω2Cdl 2Ret 2)+Ret=0
S4, measurement obtain the value of value of real part R and frequency values ω described in three groups, and (R is designated as respectively1,ω1), (R2,ω2) and
(R3,ω3), it can obtain equation group：
S5, introducing vector
Formula in the step S4 is expressed as
F (m)=0
S6, introduce go down the hill factor lambda, draw following calculation formula：
Wherein：
λ=2-n, n=0,1,2......
According to newton higher education park, the electro transfer resistance R is solvedet, the electric double layer capacitance CdlAnd the solution
Resistance RsApproximation；
S7, the calculating now electro transfer resistance of the microelectrode module and the micro- life of the unadsorbed target of microelectrode module
The difference of electro transfer resistance during thing, as electro transfer increased resistance value, according to objective microbe concentration now, sets up
The electro transfer increased resistance value and the relational model of objective microbe concentration.
The above-mentioned technical proposal of the present invention has the following advantages that：The present invention is produced by ARM9 processor timer internals T0
One low-frequency clock, broad frequency band is expanded to by the unifrequency in existing small-sized impedance detection device or narrow-band detection
(100Hz-100kHz), for electrode polarization and impedance measurement are inaccurate as caused by DC offset voltage difference in existing apparatus
The problems such as, the present invention eliminates microelectrode module by a high-pass filter, a voltage follower and an I-V buffer
Direct current biasing difference between input signal and output signal, makes the DC offset voltage in whole signal chains constant in VDD/2,
Automatically adjusted by Stepwise calibration and range by the accurate extended detection range of impedance to 100 Ω -100k Ω, and by using equivalent
Circuit is asked for and the very positively related electro transfer resistance of objective microbe concentration, the impedance magnitude used instead of forefathers, to set up
With the relational model of objective microbe concentration, the quantitative analysis of objective microbe is carried out.In addition, existing apparatus is mostly to utilize monolithic
Machine is developed, fairly simple on interpersonal interactive interface, and it is simpler and aobvious that the present invention develops operation using ARM9 processors
Show more intuitive touch display screen human-computer interaction interface；In a word, impedance biosensor of the invention have detection speed it is very fast,
Cost is relatively low, precision is higher, frequency band is wider, quantitative analysis and the advantages of Site Detection.
Brief description of the drawings
Fig. 1 is a kind of structural representation of impedance biosensor of the present invention；
Fig. 2 is the circuit diagram of electrical equivalent of the present invention；
Fig. 3 is the circuit diagram of middle impedance measurement module of the present invention；
Fig. 4 is the structural representation of microelectrode module in the present invention；
Fig. 5 is the flow chart that biological detection is carried out using the device of the present invention.
Embodiment
The embodiment to the present invention is described in further detail with reference to the accompanying drawings and examples.Following examples
For illustrating the present invention, but it is not limited to the scope of the present invention.
The invention discloses a kind of impedance biosensor, as shown in figure 1, the impedance biosensor includes microelectrode
Module 1, microprocessor 2 and impedance measurement module 3, biological adsorption in the microelectrode module 1 so as to changing micro- electricity
The impedance of pole module 1；The impedance that the microprocessor 2 controls the impedance measurement module 3 to complete the microelectrode module 1 is obtained
Take and Treatment Analysis.
As shown in figure 3, the impedance measurement module 3 includes：Impedance measurement chip 3.2, for measuring the microelectrode mould
The impedance (real and imaginary parts for obtaining impedance under different frequency) of block 1, the impedance measurement chip 3.2 and the microprocessor 2
Connection, the microprocessor 2 is that the impedance measurement chip 3.2 provides control signal；High-pass filter 3.4, its input with
The pumping signal output end connection of the impedance measurement chip 3.2, for filtering low interference signal；Voltage follower 3.5, its
Input connects the output end of the high-pass filter 3.4, and its output end connects the input of the microelectrode module 1, is used for
The DC offset voltage of the pumping signal of the impedance measurement chip output is adjusted, so as to eliminate the output of the microelectrode module
DC component difference between end and input；I-V buffers 3.6, its input connects the output of the microelectrode module 1
End, its output end is by the feedback resistance RFB1 and RFB2 connection impedance measurement chip 3.2, for by the microelectrode module
The current signal of output is converted into voltage signal and is input to the impedance measurement chip 3.2, and by the impedance measurement chip
3.2 processing obtain the impedance of the microelectrode module, pass to the microprocessor；And range adjuster 3.1, its input
The output end of the microelectrode module 1 is connected, its output end connects the output end of the I-V buffers 3.6, for for the resistance
Anti- measurement chip 3.2 automatically selects suitable measurement shelves.
The connected mode of the I-V buffers 3.6 and the impedance measurement chip 3.2 is：The I-V buffers 3.6
Output end is connected to the VIN pins of the impedance measurement chip 3.2 by feedback resistance RFB1, the I-V buffers 3.6 it is defeated
Go out the RFB pins that end is connected to the impedance measurement chip 3.2 by feedback resistance RFB1 and feedback resistance RFB2.
The range adjuster 3.1 includes four signal relays (3.1.1,3.1.2,3.1.3,3.1.4) and difference
From four signal relays connect four different resistances feedback resistance (RF1, RF2, RF3, RF4), the signal after
Electrical equipment is connected with the microprocessor four I/O mouthfuls (GPA1, GPA2, GPA3, GPA4) respectively, realizes 2 pairs of the microprocessor
The range of the range adjuster 3.1 is automatically adjusted.
The impedance measurement module also includes：Voltage-stablizer 3.3, it is connected with the impedance measurement chip 3.2, for for institute
State impedance measurement chip 3.2 and stable 3V voltages are provided；Touch display module, shows (i.e. with the electronics for testing result
The corresponding microorganism concn of transfer resistance) and parameter setting, including sample number, measurement frequency are set, time of repose is set, threshold
Value setting etc..
The microprocessor 2 uses and is integrated with an ARM9 processor chips S3C2440 on TQ2440 core boards, plate, and
And the connected mode of the microprocessor 2 and the impedance measurement chip 3.2 is：The timer internal T0 of the microprocessor 2
Pin TOUT0 is connected with the external clock pin MCLK of the impedance measurement chip 3.2；The I of the microprocessor 22C interface leads to
Believe clock pins I2CSCL and I2C interface communication data pin I2The I of CSDA respectively with 3.2, the impedance measurement core2C interface
Clock pins SCL and I2The SDA connections of C interface data pin.
The microprocessor 2 includes analysis computing unit, and it obtains electronics according to the impedance of the microprocessor module and turned
Resistance is moved, the relational model of the electro transfer increased resistance value and corresponding objective microbe concentration, and root is built and store
According to the relational model, with reference to the impedance of measurement, corresponding objective microbe concentration is obtained；The analysis computing unit includes mould
Type builds subelement, and the detection architecture of microelectrode module composition is converted into equivalent circuit by it, as shown in Fig. 2 and calculating described
The impedance of equivalent circuit, its real part is asked for according to the impedance of the equivalent circuit, afterwards with reference to measurement obtain the value of real part and
Corresponding frequency values, electro transfer impedance is asked for using the newton higher education park, and calculates the now microelectrode module
The difference of electro transfer resistance when electro transfer resistance is with the microelectrode module unadsorbed objective microbe, turns as electronics
Increased resistance value is moved, using the relational model of the electro transfer increased resistance value and objective microbe concentration, analysis is obtained pair
The objective microbe concentration answered.
As shown in figure 4, the microelectrode module 1 includes substrate 1.1 and the first gold medal electricity in the substrate 1.1
Pole 1.2, the second gold electrode 1.3, the first pad 1.4 and the second pad 1.5；First gold electrode 1.2 and first pad
1.4 connections, second gold electrode 1.3 is connected with second pad 1.5；The gold electrode of first gold electrode 1.2 and second
1.3 combine to be formed by the finger electrode of multiple identical sizes with identical spacing parallel connection, and first gold electrode 1.2
Intersected with the finger electrode of the second gold electrode 1.3；The table of the finger electrode of the gold electrode 1.3 of first gold electrode 1.2 and second
The bio-identification material of objective microbe is modified with face.The pad 1.5 of first pad 1.4 and second is respectively as described
The input and output end of microelectrode module.
The impedance biosensor also includes：USB module, is connected with the microprocessor, for the microprocessor
Device carries out Information Access operation；Serial port module, is connected with the microprocessor, for being communicated with the microprocessor；
JTAG modules, are connected with the microprocessor, for testing the microprocessor；Reservoir module, connects with the microprocessor
Connect, for storing the data in the microprocessor；Power module, with the microprocessor, impedance measurement module and storage
Device module is connected, for being powered for the microprocessor, impedance measurement module and reservoir module；PC, for it is described
USB module, serial port module and the connection of JTAG modules, realize communication and debugging.
The invention also discloses a kind of bio-impedance determination method, electro transfer increased resistance value and mesh are built first
The relational model of microorganism concn is marked, is comprised the following steps：The detection architecture of microelectrode module composition is converted into equivalent circuit,
And the impedance of the equivalent circuit is calculated, its real part is asked in the impedance further according to the equivalent circuit, and the resistance of measurement is combined afterwards
The real part of antinoise signal and corresponding angular frequency, ask for electro transfer resistance, and calculate now described micro- using newton higher education park
The difference of electro transfer resistance when the electro transfer resistance of electrode module is with the microelectrode module unadsorbed objective microbe,
As electro transfer increased resistance value, using the electro transfer increased resistance value and the relational model of objective microbe concentration,
Analysis obtains corresponding objective microbe concentration；Afterwards, using the relational model, with reference to the electro transfer electricity of measurement
Resistance, finds corresponding objective microbe concentration.
Further, build the electro transfer increased resistance value and the relational model of objective microbe concentration is specific
Comprise the following steps：
S1, the detection architecture that microelectrode is constituted is converted into the equivalent circuit, and calculates the impedance of the equivalent circuit,
And as shown by the equation：
Wherein RetFor the electro transfer resistance of the equivalent circuit, XcFor the appearance of the electric double layer capacitance of the equivalent circuit
It is anti-, RsFor the solution resistance of equivalent circuit.
S2, the capacitive reactance of the calculating electric double layer capacitance are：
Wherein, CdlFor the capacitance of the electric double layer capacitance, f is frequency, and ω is angular frequency.
S3, the real part R for asking for the equivalent circuit：
Real part can be converted into：
(Rs-R)(1+ω2Cdl 2Ret 2)+Ret=0
S4, measurement obtain the value of value of real part R and frequency values ω described in three groups, and (R is designated as respectively1,ω1), (R2,ω2) and
(R3,ω3), it can obtain equation group：
S5, introducing vector
Formula in the step S4 is expressed as
F (m)=0
S6, introduce go down the hill factor lambda, obtain following calculation formula：
Wherein：
λ=2-n, n=0,1,2......
According to newton higher education park, the electro transfer resistance R is solvedet, the electric double layer capacitance CdlAnd the solution
Resistance RsApproximation；
S7, the calculating now electro transfer resistance of the microelectrode module and the micro- life of the unadsorbed target of microelectrode module
The difference of electro transfer resistance during thing, as electro transfer increased resistance value, according to objective microbe concentration now, sets up
The electro transfer increased resistance value and the relational model of objective microbe concentration.
Further, the microprocessor 2 is the microprocessor based on ARM9 kernels, is integrated with abundant Resources on Chip,
Including memory portion, clock part and power unit.
Further, a kind of high-precision integrated electricity of impedance transformation that the impedance measurement chip 3.2 is released using AD companies
Frequency generator and analog-digital converter are integrated with road AD5933 or AD5934, piece.
Further, the model AD5933 or AD5934 of impedance measurement chip 3.2, the model of voltage-stablizer 3.3
ADR433, the model 1/2AD8606 of model 1/2AD8606, the I-V buffer 3.6 of voltage follower 3.5, four signals
Relay 3.1.1,3.1.2,3.1.3 and 3.1.4 model are G6E-134P-US, six feedback resistances (RFB1, RFB2,
RF1, RF2, RF3 and RF4) and four biasing resistors (R1, R2, R3 and R4) service precision 0.1% precision resistance, by Wei Chu
Manage four I/O mouthfuls of GPA1, GPA2, GPA3 and GPA4 control of device 2.
Fig. 5 is a kind of flow chart of impedance biosensor biological detection of the preferred embodiment of the present invention.It is described
The bio-identification material of objective microbe is modified with first electrode 1.2, the surface of second electrode 1.3 (by taking antibody as an example)：First
Albumin A is adsorbed on the first electrode 1.2, the surface of second electrode 1.3 by electrostatic and hydrophobic effect, albumen is recycled
The Fc sections of the immunoglobulin of A and antibody occur specific binding and antibody are fixed on into the first electrode 1.2, second electrode
On 1.3, the binding site for finally closing residual using bovine serum albumin avoids nonspecific reaction.During implementation, hindered first
Anti- measurement, the electro transfer resistance R compareed by the Analysis of Equivalent Circuit of the electrodeetc, afterwards including the micro- life of target
The sample drop of thing adds on the electrodes, and the objective microbe will be captured by the antibody on the electrode 1.2,1.3 surfaces,
Recycle after PBS, redox probe ([Fe (CN) is added dropwise6]3-/4-) measuring electrode impedance, pass through the equivalent of the electrode
Circuit analysis obtains the electro transfer resistance R of sampleets, ask for RetsWith RetcDifference △ Ret, then pass through △ RetIt is micro- with target
The relational model of biological concentration, is quantitatively detected to objective microbe.
Table 1 is the electro transfer resistance R obtained using the bioimpedance analysis method of the present inventionetValue and existing impedance spectrum point
The electro transfer resistance ZR that analysis software Zsimpwin is obtainedetThe comparison of value.The present invention respectively to the electrode in bio-modification and
The reality of objective microbe detection process (albumin A is fixed, the closing of antibody coupling, bovine serum albumin BSA and object are captured) collection
Test data to be analyzed, Zsimpwin softwares carry out simulation process to experimental data using identical equivalent circuit and obtain electricity
Sub- transfger impedance ZRet, the present invention from experimental data at different frequency extract 15 data, i.e., low frequency (100,100 ± 5Hz
With 100 ± 10Hz), intermediate frequency (5kHz, 5 ± 0.25kHz and 5 ± 0.5kHz) and high frequency (85kHz, 85 ± 1kHz and 85 ±
2kHz), each then from low, medium and high frequency to choose a composition be one group of data, and the frequency and real part of every group of data are according to above-mentioned
Method is handled, i.e., solved using Newton-decline method, can obtain 5 electro transfer resistance values；Finally carry out bubbling method
Sequence, takes middle 3 values to average as electro transfer resistance Ret.It can be seen that, bioimpedance analysis method of the invention with
Zsimpwin result has preferable uniformity.
The bioimpedance analysis method and the results contrast of existing impedance analysis software of the present invention of table 1
The problems such as frequency band that exists for existing small-sized impedance detection device is narrow, accuracy of detection is relatively low, function is simpler,
The present invention using ARM9 processors (S3C2440) timer internal produce 125kHz low-frequency clocks, solve AD5933 or
AD5934 LF-response problem.For the electrode polarization as caused by DC offset voltage difference in existing impedance detection device and
The problems such as impedance measurement is inaccurate, the present invention is disappeared by a high-pass filter, a voltage follower and an I-V buffer
Except the direct current biasing difference between the input signal and output signal of microelectrode module, make the direct current biasing in whole signal chains
Voltage constant is automatically adjusted by Stepwise calibration and range impedance detection scope extending to 100 Ω -100k Ω, institute in VDD/2
There is the resistance of biasing resistor and the equal service precision 0.1% of feedback resistance to reduce inaccuracy, be effectively improved measurement accuracy,
And asked for by using equivalent circuit with the very positively related electro transfer resistance of objective microbe concentration, the resistance used instead of forefathers
Anti- amplitude, to set up the relational model with objective microbe concentration, carries out the quantitative analysis of objective microbe.In addition, existing dress
Putting mostly is developed using single-chip microcomputer, fairly simple on interpersonal interactive interface, and the present invention is developed using ARM9 processors
Operation is simpler and shows more intuitive touch-screen human-computer interaction interface.
Finally it should be noted that：The above embodiments are merely illustrative of the technical solutions of the present invention, rather than its limitations；Although
The present invention is described in detail with reference to the foregoing embodiments, it will be understood by those within the art that：It still may be used
To be modified to the technical scheme described in foregoing embodiments, or equivalent substitution is carried out to which part technical characteristic；
And these modification or replace, do not make appropriate technical solution essence depart from various embodiments of the present invention technical scheme spirit and
Scope.
Claims (9)
1. a kind of impedance biosensor, it is characterised in that the impedance biosensor includes microprocessor, impedance measurement mould
Block and microelectrode module, objective microbe are adsorbed in the microelectrode module to change the resistance of the microelectrode module
It is anti-；The microprocessor controls the acquisition of the impedance of the impedance measurement module completion microelectrode module, and to the resistance
Anti- progress Treatment Analysis obtains objective microbe concentration；
The impedance measurement module includes：
Impedance measurement chip, the impedance for measuring the microelectrode module, the impedance measurement chip and the microprocessor
Connection, the microprocessor provides control signal for the impedance measurement chip；
High-pass filter, its input is connected with the pumping signal output end of the impedance measurement chip, dry for filtering low
Disturb signal；
Voltage follower, its input connects the output end of the high-pass filter, and its output end connects the microelectrode module
Input, the DC offset voltage of the pumping signal for adjusting impedance measurement chip output, so as to eliminate described micro-
DC component difference between the output end and input of electrode module；
I-V buffers, its input connects the output end of the microelectrode module, and its output end connects described by feedback resistance
The input pin VIN and RFB of impedance measurement chip, the current signal for the microelectrode module to be exported are converted into voltage letter
Number and be input to the impedance measurement chip, and the voltage signal processing of reception is obtained into institute by the impedance measurement chip
The impedance of microelectrode module is stated, then the impedance of the microelectrode module is passed into the microprocessor；
And range adjuster, the output end of its input connection microelectrode module, its output end connection I-V bufferings
The output end of device, for providing multiple measurement shelves for the impedance measurement chip；
The microprocessor includes analysis computing unit, its microelectrode mould obtained according to the impedance measurement chip measurement
The impedance of block obtains the electro transfer resistance of the now microelectrode module, and calculates the electronics turn of the now microelectrode module
The difference of electro transfer resistance when moving resistance with the unadsorbed objective microbe of the microelectrode module, is used as electro transfer resistance
Changing value, using the electro transfer increased resistance value and the relational model of objective microbe concentration, analysis obtains corresponding mesh
Mark microorganism concn；
The analysis computing unit includes model construction subelement, and the detection architecture of the microelectrode module composition is converted into by it
Equivalent circuit, and the impedance of the equivalent circuit is calculated, the impedance further according to the equivalent circuit is asked for its real part, combined afterwards
The real part of the impedance of measurement and corresponding angular frequency, electro transfer resistance is asked for using newton higher education park；Ask for institute now
The difference of electro transfer resistance when stating electro transfer resistance with the unadsorbed objective microbe of the microelectrode module, is used as electronics
Transfer resistance changing value, sets up the relational model of the electro transfer increased resistance value and objective microbe concentration.
2. impedance biosensor according to claim 1, it is characterised in that the microprocessor uses ARM9 processing
Device, and the connected mode of the ARM9 processors and the impedance measurement chip is：
The timer internal T0 of ARM9 processors pin TOUT0 and the impedance measurement chip external clock pin
MCLK connections, clock signal is provided for the impedance measurement chip；The I of the ARM9 processors2C interface clock pins I2CSCL
And I2C interface data pin I2The I of CSDA respectively with the impedance measurement chip2C interface clock pins SCL and I2C interface number
According to pin SDA connections.
3. impedance biosensor according to claim 1, it is characterised in that
The range adjuster includes four signal relays and be connected respectively with four signal relays four not
With the feedback resistance of resistance, the signal relay is connected with four I/O mouthfuls of the microprocessor respectively, realizes micro- place
Reason device is automatically selected to the range of the range adjuster.
4. impedance biosensor according to claim 3, it is characterised in that the impedance measurement module also includes：
Voltage-stablizer, it is connected with the impedance measurement chip, for providing stable voltage for the impedance measurement chip；
Touch display module, shows and parameter setting for testing result, wherein the parameter set in the parameter setting includes
Sample number, measurement frequency, time of repose, threshold value.
5. impedance biosensor according to claim 4, it is characterised in that the I-V buffers are surveyed with the impedance
Amount chip connected mode be：
The output end of the I-V buffers is drawn by the feedback resistance RFB1 input VIN for being connected to the impedance measurement chip
Pin, the output end of the I-V buffers is connected to the impedance measurement chip by feedback resistance RFB1 and feedback resistance RFB2
RFB pins.
6. impedance biosensor according to claim 5, it is characterised in that the microelectrode module include substrate, with
And the first gold electrode, the second gold electrode, the first pad and the second pad in the substrate；
First gold electrode is connected with first pad, and second gold electrode is connected with second pad；Described
One gold electrode and the second gold electrode combine to be formed by the finger electrode of multiple identical sizes with identical spacing parallel connection, and
The finger electrode of first gold electrode and the second gold electrode intersects；
The bio-identification material of objective microbe is modified with the surface of the finger electrode of first gold electrode and the second gold electrode
Material.
7. impedance biosensor according to claim 6, it is characterised in that the impedance biosensor also includes：
USB module, is connected with the microprocessor, for carrying out Information Access operation with the microprocessor；
Serial port module, is connected with the microprocessor, for being communicated with the microprocessor；
JTAG modules, are connected with the microprocessor, for testing the microprocessor；
Reservoir module, is connected with the microprocessor, for storing the data in the microprocessor；
Power module, is connected with the microprocessor, impedance measurement module and reservoir module, for for the microprocessor
Device, impedance measurement module and reservoir module are powered.
8. a kind of bio-impedance determination method, it is characterised in that the described method comprises the following steps：
Build electro transfer increased resistance value and the relational model of objective microbe concentration：By the detection body of microelectrode module composition
System is converted into equivalent circuit, and calculates the impedance of the equivalent circuit, and its real part is asked in the impedance further according to the equivalent circuit,
The real part and corresponding angular frequency of the impedance of the microelectrode module of measurement are combined afterwards, and asking for electronics using newton higher education park turns
Resistance is moved, and calculates the now electro transfer resistance of the microelectrode module and the unadsorbed objective microbe of microelectrode module
When electro transfer resistance difference, as electro transfer increased resistance value, set up the electro transfer increased resistance value and mesh
Mark the relational model of microorganism concn；
The electronics for obtaining the microelectrode module using the impedance biosensor measurement described in any one of claim 1 to 7 turns
Increased resistance value is moved, and utilizes the relational model, corresponding objective microbe concentration is found.
9. method according to claim 8, it is characterised in that the impedance of the equivalent circuit is：
<mrow>
<mi>Z</mi>
<mo>=</mo>
<msub>
<mi>R</mi>
<mi>s</mi>
</msub>
<mo>+</mo>
<mfrac>
<mrow>
<msub>
<mi>R</mi>
<mrow>
<mi>e</mi>
<mi>t</mi>
</mrow>
</msub>
<msub>
<mi>X</mi>
<mi>c</mi>
</msub>
</mrow>
<mrow>
<msub>
<mi>R</mi>
<mrow>
<mi>e</mi>
<mi>t</mi>
</mrow>
</msub>
<mo>+</mo>
<msub>
<mi>X</mi>
<mi>c</mi>
</msub>
</mrow>
</mfrac>
</mrow>
Wherein RetFor the electro transfer resistance of the equivalent circuit, XcFor the capacitive reactance of the electric double layer capacitance of the equivalent circuit, RsFor
The solution resistance of equivalent circuit.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102680683A (en) * | 2012-05-30 | 2012-09-19 | 中国人民解放军第306医院 | Periodontal bacteria impedance immunosensor based on conductive polymer |
| CN203241371U (en) * | 2013-01-11 | 2013-10-16 | 西北农林科技大学 | Portable multi-index impedance biosensor device |
| CN203310795U (en) * | 2013-06-03 | 2013-11-27 | 浙江大学 | Portable impedance biosensing detector |
| CN203772786U (en) * | 2014-04-14 | 2014-08-13 | 西南大学 | Chip type interdigital array electrode impedance sensor |
| WO2014164654A1 (en) * | 2013-03-11 | 2014-10-09 | The University Of Toledo | A biosensor device to target analytes in situ, in vivo, and/or in real time, and methods of making and using the same |
| CN204536250U (en) * | 2015-04-22 | 2015-08-05 | 中国农业大学 | A kind of impedance biosensor |
-
2015
- 2015-04-22 CN CN201510192591.1A patent/CN104849322B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102680683A (en) * | 2012-05-30 | 2012-09-19 | 中国人民解放军第306医院 | Periodontal bacteria impedance immunosensor based on conductive polymer |
| CN203241371U (en) * | 2013-01-11 | 2013-10-16 | 西北农林科技大学 | Portable multi-index impedance biosensor device |
| WO2014164654A1 (en) * | 2013-03-11 | 2014-10-09 | The University Of Toledo | A biosensor device to target analytes in situ, in vivo, and/or in real time, and methods of making and using the same |
| CN203310795U (en) * | 2013-06-03 | 2013-11-27 | 浙江大学 | Portable impedance biosensing detector |
| CN203772786U (en) * | 2014-04-14 | 2014-08-13 | 西南大学 | Chip type interdigital array electrode impedance sensor |
| CN204536250U (en) * | 2015-04-22 | 2015-08-05 | 中国农业大学 | A kind of impedance biosensor |
Non-Patent Citations (3)
| Title |
|---|
| ELECTRIC IMPEDANCE OF SUSPENSIONS OF SPHERES;KENNETH S. COLE;《The Journal of General Physiology》;19280920;第29-36页 * |
| 基于AD5933的便携式阻抗仪研制;温新华等;《计算机测量与控制》;20131231;第21卷(第4期);第1090-1092页、第1108页 * |
| 基于叉指阵列微电极的阻抗免疫传感器研究进展;颜小飞等;《分析化学》;20111031;第39卷(第10期);第1601-1610页 * |
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