CN103592349A - Method for measuring concentration of target molecule in solution by using biosensor array - Google Patents

Method for measuring concentration of target molecule in solution by using biosensor array Download PDF

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Publication number
CN103592349A
CN103592349A CN201310625181.2A CN201310625181A CN103592349A CN 103592349 A CN103592349 A CN 103592349A CN 201310625181 A CN201310625181 A CN 201310625181A CN 103592349 A CN103592349 A CN 103592349A
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biosensor array
biology sensor
digital signal
solution
concentration
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CN103592349B (en
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胡文闯
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ZHANGJIAGANG ONECHIP BIO-TECHNOLOGY Co.,Ltd.
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胡文闯
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Abstract

The invention relates to a method for measuring the concentration of a target molecule in a solution by using a biosensor array. The method comprises the following concrete steps: conveying an electrolyte solution to the surface of biosensors; measuring electric signal response; comparing electric signal response values with a reference value; calculating the quantity of the biosensors; and determining the concentration of the target molecule. The method for measuring the concentration of the target molecule in the solution by using the biosensor array has the following advantages: with the biosensor array, the dynamic range of detection is expanded, accuracy and repeatability of quantification of the concentration of a to-be-measured target molecule are improved, errors are substantially reduced, and accuracy and the dynamic scope of measurement are enhanced.

Description

Utilize biosensor array to measure the method for target molecular conecentration in solution
Technical field
The invention belongs to biosensor application field, be specifically related to a kind of method of utilizing biosensor array to measure target molecular conecentration in solution.
Background technology
In medical biotechnology, detect and chemical analysis field, often with biochemical sensor, carrying out the system and method for the molecule in quantified goal analyte sample is the foundation stone that modern analysis is measured.Quick detection system and method at a low price has very important application for many fields, as life science, health care, medical diagnosis on disease, drug development, environmental monitoring, food security and bioterrorism, all need to rely on biology sensor to come detection specificity, detection speed and sensitivity.
In prior art, disclosed biology sensor and biosensor array are inaccurate to the measurement of target molecular conecentration in solution, and error causes measurement result to lose efficacy through accumulative total, in order to solve the problems of the prior art, the present invention proposes a kind of method of utilizing biosensor array to measure target molecular conecentration in solution.
Summary of the invention
In order to overcome deficiency of the prior art, the present invention discloses a kind of method of utilizing biosensor array to measure target molecular conecentration in solution.
The present invention is achieved by the following technical solutions:
Utilize biosensor array to measure the method for target molecular conecentration in solution, its concrete steps are as follows:
S01: the electrolyte solution that comprises target molecules is transported to biosensor array surface;
S02: the electric response of measuring each biology sensor;
S03: the electric response value of each biology sensor and the reference value of setting are compared; If response signal is greater than reference value, digital signal output and storage digital signal " 1 "; Otherwise output and storage digital signal " 0 ";
S04: calculate the quantity that storage digital signal is the biology sensor of " 1 " and " 0 ";
S05: the concentration of result of calculation and calibration curve relatively being carried out to determine to target molecules.
Be preferably, in step S03, described reference value is the mean value of the response signal of whole biosensor array.
Be preferably, in step S04, calculate storage digital signal and account for respectively the number percent of all sensors array sum for the biology sensor of " 1 " and " 0 ".
Be preferably, the comparison of the reference value of described biology sensor electric response and setting, digital signal output, and the quantitative task of target molecules concentration is by circuit or software, or circuit and software have been combined.
Compared with prior art, the superior effect of utilizing biosensor array to measure the method for target molecular conecentration in solution of the present invention is: utilize the dynamic range of biosensor array detection and increase measured target molecular conecentration accuracy and repeatability while quantizing, can significantly reduce error and expand accuracy and the dynamic test scope of measuring.
Accompanying drawing explanation
Fig. 1 is the method flow diagram that utilizes biosensor array to measure target molecular conecentration in solution of the present invention;
Fig. 2 is the schematic diagram that reads that the method for the invention is applied to digital detection signal;
Fig. 3 is the scheme that the method for the invention is applied to digital testing circuit.
Embodiment
Below in conjunction with accompanying drawing, the specific embodiment of the invention is described in further detail.
As shown in accompanying drawing 1-3, utilize biosensor array to measure the method for target molecular conecentration in solution, its concrete steps are as follows:
S01: the surface that the electrolyte solution that comprises target molecules is transported to biosensor array;
S02: the electric response of measuring each biology sensor 1;
S03 a: reference value of the electric response value of each biology sensor 1 and setting is compared; If response signal is greater than reference value, digital signal output and storage digital signal " 1 "; Otherwise output and storage digital signal " 0 ";
S04: calculate the quantity that storage digital signal is the biology sensor 1 of " 1 " and " 0 ";
S05: the concentration of result of calculation and calibration curve relatively being carried out to quantitative target molecules.
In step S03, described reference value is the mean value of the response signal of whole biosensor array.
In step S04, calculate storage digital signal and account for respectively the number percent of all sensors array sum for the biology sensor 1 of " 1 " and " 0 ".
The comparison of the electric response of described biology sensor 1 and the reference value of setting, digital signal output, and the quantitative task of target molecules concentration is by circuit or software, or circuit and software have been combined.
The method of utilizing biosensor array to measure target molecular conecentration in solution of the present invention can realize reading of digital detection signal, thus accuracy and repeatability when the dynamic range that expansion detects and the measured target molecular conecentration that increases quantize.
Figure 2 shows that the method for the invention is applied to the schematic diagram that reads of digital detection signal, one comprises electrochemical sensor, the sensor array of quantity between 50 to 50000, and each biology sensor 1 is by row-address decoder 4 and the independent read signal of column address decoder 5; By quick timesharing, read, the signal of each biology sensor 1 in whole array is read.
When detecting, described biology sensor 1 power taking chemical sensor, the electrolyte that comprises target molecule to be measured is transported to the sensing region that chip surface covers each electrochemical sensor of whole electrochemical sensor array.Each biology sensor 1 is read, and reads rear response and is divided into two kinds:
1) there is target molecule to be attached to described electrochemical sensor and produce change in electric, producing digital signal " 1 ";
2) do not have target molecule to be attached to this sensor and there is no change in electric, thereby producing digital signal " 0 ";
The last quantity of testing result biology sensor 1 of output, or the number percent that accounts for total biosensor array exported " 1 " or " 0 ", the i.e. statistical conditions of testing molecule and biosensor array combination.When the concentration of target molecules in solution is very low, the diffusion process of molecule makes few biology sensor 1 can capture target molecule and output signal " 1 "; And concentration of target molecules in solution is when high, has a large amount of biology sensor 1 and can capture target molecule and output signal " 1 ".The quantity of the biology sensor 1 of output signal " 1 " and testing molecule concentration form unidirectional increasing function relation.By the typical curve comparison with test is set up in advance, can quantize the concentration of testing molecule.The scheme of this numeral output can significantly reduce accuracy and the dynamic test scope of error expansion measurement.
Be illustrated in figure 3 the scheme that the method for utilizing biosensor array to measure target molecular conecentration in solution is applied to digital testing circuit.
Described biosensor array comprises a plurality of biology sensors 1.When testing molecule is attached to the biology sensor 1 that scribbles probe, described biology sensor 1 has produced change in electric, as curent change; The signal of described curent change is exaggerated and converts to magnitude of voltage.The threshold value of described magnitude of voltage and setting compares.If the magnitude of voltage of biology sensor 1 response is greater than default threshold value, with regard to output digit signals " 1 ", biology sensor 1 is judged as and has successfully caught target molecule; Otherwise output " 0 ".The output valve of each biology sensor 1 is imported in a moving type register 2.These digital signals directly output in the signal processor of rear end, also can connect again and be input in a counter 3, then calculate the quantity of the biology sensor 1 that is output as " 1 " or " 0 ", also can recently quantize testing molecule concentration according to biology sensor 1 and the percentage of biosensor array sum.
Biology sensor 1 in described biosensor array adopts electrochemica biological sensor, ion-sensitive field effect transistor; Described ion-sensitive field effect transistor is nano-wire field effect transistor, fin formula field effect transistor, the winding type nanowire channel biology sensor of high sensitivity.That the raceway groove of described winding type nanowire channel biology sensor is is snakelike, serrate, spirality.
The biology sensor 1 of described biosensor array, row-address decoder 4 and column address decoder 5 are existing equipment.
The present invention is not limited to above-mentioned embodiment, and in the situation that not deviating from flesh and blood of the present invention, any distortion it may occur to persons skilled in the art that, improvement, replacement all fall into scope of the present invention.

Claims (6)

1. utilize biosensor array to measure the method for target molecular conecentration in solution, it is characterized in that, concrete steps are as follows:
S01: the electrolyte solution that comprises target molecules is transported to biosensor array surface;
S02: the electric response of measuring each biology sensor;
S03: the electric response value of each biology sensor and the reference value of setting are compared; If response signal is greater than reference value, digital signal output and storage digital signal " 1 "; Otherwise output and storage digital signal " 0 ";
S04: calculate the quantity that storage digital signal is the biology sensor of " 1 " and " 0 ";
S05: the concentration of result of calculation and calibration curve relatively being carried out to determine to target molecules.
2. the method for utilizing biosensor array to measure target molecular conecentration in solution according to claim 1, is characterized in that, in step S03, described reference value is the mean value of the response signal of whole biosensor array.
3. the method for utilizing biosensor array to measure target molecular conecentration in solution according to claim 1, it is characterized in that, in step S04, calculate storage digital signal and account for respectively the number percent of all sensors array sum for the biology sensor of " 1 " and " 0 ".
4. the method for utilizing biosensor array to measure target molecular conecentration in solution according to claim 1, it is characterized in that, the comparison of the reference value of described biology sensor electric response and setting, digital signal output, and the quantitative task of target molecules concentration is completed by circuit.
5. the method for utilizing biosensor array to measure target molecular conecentration in solution according to claim 1, it is characterized in that, the comparison of the reference value of described biology sensor electric response and setting, digital signal output, and the quantitative task of target molecules concentration is completed by software.
6. the method for utilizing biosensor array to measure target molecular conecentration in solution according to claim 1, it is characterized in that, the comparison of the reference value of described biology sensor electric response and setting, digital signal output, and the quantitative task of target molecules concentration has been combined by circuit and software.
CN201310625181.2A 2013-11-28 2013-11-28 Biosensor array is utilized to measure the method for target molecular conecentration in solution Active CN103592349B (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008070058A2 (en) * 2006-12-04 2008-06-12 Purdue Research Foundation Method and apparatus for detection of molecules using sensor array
CN101206217A (en) * 2007-12-07 2008-06-25 中国科学院理化技术研究所 Multiple sample magneto-dependent sensor array biochip tester
WO2009022246A1 (en) * 2007-08-10 2009-02-19 Koninklijke Philips Electronics N.V. Sensor array for spr-based detection.
CN101961240A (en) * 2009-07-24 2011-02-02 瑞鼎科技股份有限公司 Biosensor, probe, sensing device and biosensor manufacturing method
CN102985814A (en) * 2010-07-20 2013-03-20 Nth技术公司 Biosensor apparatuses and methods thereof
CN103308572A (en) * 2012-03-12 2013-09-18 厚美德生物科技股份有限公司 Test strip with array type contacts

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008070058A2 (en) * 2006-12-04 2008-06-12 Purdue Research Foundation Method and apparatus for detection of molecules using sensor array
WO2009022246A1 (en) * 2007-08-10 2009-02-19 Koninklijke Philips Electronics N.V. Sensor array for spr-based detection.
CN101206217A (en) * 2007-12-07 2008-06-25 中国科学院理化技术研究所 Multiple sample magneto-dependent sensor array biochip tester
CN101961240A (en) * 2009-07-24 2011-02-02 瑞鼎科技股份有限公司 Biosensor, probe, sensing device and biosensor manufacturing method
CN102985814A (en) * 2010-07-20 2013-03-20 Nth技术公司 Biosensor apparatuses and methods thereof
CN103308572A (en) * 2012-03-12 2013-09-18 厚美德生物科技股份有限公司 Test strip with array type contacts

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Address before: Room 1002, gate 3, building 19, Ding'an Dongli, Fengtai District, Beijing 100075

Patentee before: Hu Wenchuang

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