CN2795853Y - Micro suspension arm biological sensor for quick detecting biological molecule - Google Patents
Micro suspension arm biological sensor for quick detecting biological molecule Download PDFInfo
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- CN2795853Y CN2795853Y CN 200520040958 CN200520040958U CN2795853Y CN 2795853 Y CN2795853 Y CN 2795853Y CN 200520040958 CN200520040958 CN 200520040958 CN 200520040958 U CN200520040958 U CN 200520040958U CN 2795853 Y CN2795853 Y CN 2795853Y
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Abstract
The utility model relates to a micro suspension arm biosensor for the quick detection of biological molecule, which comprises a liquid sample chamber with an electric field. A micro suspension arm fixed with a bioprobe or a micro suspension arm array is positioned at the upper part in the liquid sample chamber, and a bottom electrode is positioned at the bottom in the liquid sample chamber. The micro suspension arm or the micro suspension arm array as a positive electrode (or a negative electrode) and the bottom electrode as a negative electrode (or a positive electrode) form an electrostatic field or an alternating electric field in the liquid sample chamber. The macromolecules of the sample to be measured placed in the liquid sample chamber quickly swim towards the positive or the negative electrode driven by the electric field, and the concentration of target molecules on the micro suspension arm increases so as to cause the resonant frequency of the micro suspension arm to be changed rapidly. The utility model has the advantages of high measurement speed, high sensitivity and high accuracy. Compared with the prior art that the electric field is not added, the detection sensitivity of the biosensor of the utility model can be increased by 100 to 1000 times.
Description
Technical field
The utility model relates to a kind of biosensor of micro cantilever, relates in particular to a kind of biosensor of micro cantilever of fast detecting biomolecule.
Background technology
Biosensor of micro cantilever is meant the sensor that utilizes the micro-cantilever surface that is fixed with bioprobe (molecule that combines with the target molecule selectivity) to come in conjunction with the principle of winding degree that causes micro-cantilever behind the bio-target molecule to be measured or frequency change the bio-target molecule in testing environment and the body.Mode of operation based on biosensor of micro cantilever can be divided into static state and dynamic operation mode.Static mode of operation is meant the mode of operation of the crooked deformation of micro-cantilever generation under the effect of measuring bio-target molecule to be measured as measurement parameter.This pattern such as auspicious on the University of Basel and the patent (patent No. is US5807758) of U.S.'s digital implementation (DI) company application described in.Dynamic operation mode is meant under the effect of measuring bio-target molecule to be measured, causes the variation of micro-cantilever quality, stress, and then the mode of operation that causes the resonant frequency characteristic of micro-cantilever to change.Can carry out qualitative and quantitative analysis to bio-target molecule to be measured by detecting change of resonance frequency.This pattern is convenient, accurate, reliable and be convenient to integrated.In the biology sensor of clinical diagnosis, environment measuring and portable instrument, vast potential for future development is being arranged.Nanogen (nano gene, www.nanogen.com/products) company is incorporated into electric field in the biochip first, improved the speed that DNA (DNA (deoxyribonucleic acid)) detects, reduce the background of DNA detection, though increased the speed that detects, but the degree of accuracy of measuring is desirable not enough, also needs to improve.
Summary of the invention
The purpose of this utility model is to solve the following shortcoming that the biosensor of micro cantilever in the technology formerly exists in detection of biological sample process: because under the situation of micro-cantilever at no electric field, intermolecular reaction is mainly collided generation by the bioprobe on the thermal motion of molecule and micro-cantilever surface.The efficient that bioprobe is caught target molecule except with binding constant mutually outside the Pass, also the concentration of the target molecule that is comprised in the solution with biology to be measured is correlated with.Under the lower situation of concentration, the micro-cantilever response is little, even does not have.Simultaneously, also because the interference of the association reaction of incomplete coupling etc. can cause testing result false positive and false-negative phenomenon to occur.At these shortcomings, detect at micro-cantilever on the basis of target molecule, the utility model provide a kind of novel can be sensitive under the low concentration situation, detection of biological sample fast and exactly, with the biosensor of micro cantilever of electric field driven.
To achieve the above object, the technical solution adopted in the utility model is: adopt dynamic operation mode.Introduce electric field driven testing sample target molecule and accumulate in rapidly on the bioprobe on micro-cantilever surface, cause the variation of micro-cantilever quality and stress.By detecting the change of resonance frequency of micro-cantilever, and then to the qualitative and quantitative analysis of testing sample target molecule.
Make it comprise the fluid sample chamber that has electric field, be positioned at the micro-cantilever that is fixed with bioprobe on the indoor top of fluid sample, be positioned at the bottom electrode of the indoor bottom of fluid sample; Described micro-cantilever is the micro-cantilever electrode as positive electrode or negative electrode; Described bottom electrode then is as negative electrode or positive electrode; Constitute between micro-cantilever electrode and the bottom electrode and be positioned at indoor electrostatic field of fluid sample or alternating electric field.
The described micro-cantilever that is fixed with bioprobe is the single micro-cantilever that is fixed with bioprobe, or is fixed with the micro-cantilever array of bioprobe.
As above-mentioned structure, when after micro-cantilever electrode and bottom electrode add voltage, the bioprobe on the micro-cantilever can be caught the target molecule that is seated in the indoor testing sample of fluid sample quickly under effect of electric field.In the process of bioprobe and target molecule hybridization reaction, at first be with the micro-cantilever electrode as positive electrode, bottom electrode is as negative electrode, electronegative target molecule is towards the positive electrode direction swimming, collide the bioprobe on the micro-cantilever apace, and be enriched on the bioprobe.Measure the variation that its resonance frequency takes place thus.And then apply reversed electric field, that is, make the micro-cantilever electrode become negative electrode by positive electrode, bottom electrode becomes positive electrode by negative electrode.Under the effect of reversed electric field, make attached to the target molecule of the lip-deep non-specific responding of micro-cantilever bioprobe by throwing off to the swimming of bottom electrode direction on the bioprobe surface.This moment the resonance frequency measured by the micro-cantilever resonance frequency that to be exactly wash-out do not wish to mix the target molecule of the non-specific responding in the measurement data.Therefore, biology sensor of the present utility model has not only improved measuring speed under the driving of electric field, and has improved sensitivity and the degree of accuracy measured.
Biology sensor effect of the present utility model is remarkable.
As above-mentioned structure, biology sensor of the present utility model is compared with technology formerly, and biology sensor of the present utility model uses the electric field driven target molecule to produce biochemical reaction fast on the bioprobe of micro-cantilever.Not only improved measuring speed, and made its detection sensitivity can improve 100～1000 times.When the target molecule of testing sample was DNA, the detectability of biosensor of micro cantilever of the present utility model can reach 300pg/ml.
The utility model adopts the biosensor of micro cantilever of electric field driven, not only can improve sensitivity, speed and the accuracy of detection, and relatively simple for structure, easy to use, can be further integrated.
Description of drawings
Fig. 1 is the structural representation of the utility model biosensor of micro cantilever.
Fig. 2 is an embodiment of the utility model biosensor of micro cantilever, when adding electric field driven, and the swimming view of DNA target molecule.
Fig. 3 is the measured resonance frequency spectrogram of the embodiment of Fig. 2.
Embodiment
Further specify the architectural feature of the utility model biosensor of micro cantilever below in conjunction with accompanying drawing.
Fig. 1 is the structure of the utility model biology sensor.As shown in Figure 1, the utility model biology sensor comprises base plate 7, is positioned at filling opening 1 and liquid outlet 5 on the base plate 7.Place in the seal groove (not shown) on the base plate 7, comprise filling opening 1 and liquid outlet 5 at interior O-ring seal 6.Be positioned at the fluid sample chamber 3 of the band filling opening 1 and the liquid outlet 5 of O-ring seal 6.Be positioned at the firm banking spring 9 of fluid sample chamber 3, place the micro-cantilever base 8 above the firm banking spring 9, place the micro-cantilever that has bioprobe (or micro-cantilever array) 2 on the micro-cantilever base 8.Be positioned at the bottom electrode 4 of fluid sample chamber 3 inner bottom parts.
The above-mentioned member that comprises constitutes one all integratedly.Also just say that biosensor of micro cantilever of the present utility model is integrated biosensor of micro cantilever.
Fig. 2 is the embodiment of the utility model biology sensor of application drawing 1 structure.
Embodiment 1
At the indoor adding electrostatic field of fluid sample (as shown in Figure 2).At first the solution with biomacromolecule to be measured (DNA target molecule) is injected in the fluid sample chamber 3 by filling opening 1, and what fix on the micro-cantilever is and the single-minded big molecule that combines of biomacromolecule to be measured (DNA target molecule) (with the dna probe of DNA target molecule complementation) bioprobe.Direct supply 10 will be inserted between micro-cantilever electrode 5 in the fluid sample chamber 3 and the bottom electrode 4.Micro-cantilever electrode 5 is a positive electrode, and bottom electrode 4 is a negative electrode.Between two electrodes, add 0.5 volt of DC voltage.After adding voltage on two electrodes, formed electric field between two electrodes in fluid sample chamber 3, under the driving of electric field, the electronegative DNA target molecule swimming promptly in the testing sample is to the micro-cantilever electrode as positive electrode.For the time 5 minutes, caught a certain amount of DNA target molecule on the bioprobe on the micro-cantilever.Measure the resonance frequency of its micro-cantilever, as shown in table 1.Under the situation of added electric field and added electric field not, before and after the hybridization reaction, from the change in displacement of the resonance frequency main peak of micro-cantilever seen the utility model biology sensor add electric field and technology formerly not added electric field compare, the sensitivity of biology sensor reaction of the present utility model can improve 2-3 the order of magnitude, and the DNA concentration of target molecules that can measure reaches 300pg/ml (every milliliter of pik).
Table 1 biosensor of micro cantilever has electric field driven and does not have the variation of resonance frequency main peak before and after the hybridization reaction under the electric field driven situation in different DNA concentration of target molecules solution.
At the indoor adding alternating electric field of fluid sample.As shown in Figure 2, on micro-cantilever (or micro-cantilever array) surface, fixed under the situation of dna probe, under effect of electric field, fixing dna probe is caught the DNA target molecule in the solution on the micro-cantilever, be in the DNA hybridization reaction process, make the positive electrode of electric field with the micro-cantilever electrode, as negative electrode, apply the voltage of 0.5V at the bottom electrode of bottom, fluid sample chamber.Under effect of electric field, dna molecular (molecule of DNA peripheral zone negative charge) makes electronegative DNA target molecule be enriched to micro-cantilever (or micro-cantilever array) surface towards the positive electrode direction swimming, collides micro-cantilever surface dna probe apace.The resonance frequency of micro-cantilever (or micro-cantilever array) promptly changes.Therefore the sensitivity and the speed that detect have been improved.Change the direction of DC voltage again, make the positive electrode of micro-cantilever electrode become negative electrode, and the negative electrode of bottom electrode becomes positive electrode.In fluid sample chamber 5, form alternating electric field.At this moment,, reduce non-specific material, and then improved the accuracy of analyzing by the absorption of bioprobe on the micro-cantilever by applying the biomolecule that reversed electric field washes away the non-specific responding of swimming to the micro-cantilever bioprobe.In the present embodiment, use the vibration mode atomic force microscope that the resonance frequency of micro-cantilever is scanned, obtain the frequency spectrum (shown in Figure 3) of micro-cantilever.
When the resonance frequency in being taken at 200～400kHz interval was analyzed, under the situation of electric field driven, the DNA concentration of target molecules was when 30ng/ml, and the displacement of resonance frequency main peak reaches 1.2kHz behind the hybridization reaction; The DNA concentration of target molecules is low to moderate under the 300pg/ml situation, and the displacement of resonance frequency main peak is 0.3kHz (table 1).Compare under the situation of added electric field not, the DNA concentration of target molecules is when 3 μ g/ml, and the resonance frequency displacement is 1.2kHz, and the DNA concentration of target molecules is when 300ng/ml, and the resonance frequency displacement is 0.2kHz (seeing Table 1) only.Because it is 0.1kHz that the vibration mode atomic force microscope detects background fluctuations to resonance frequency, calculate as detectability by the background fluctuations of 3 times of resonance frequencies, under the situation of added electric field, biosensor of micro cantilever can reach 300pg/ml to the detectability of DNA.Therefore think that under the situation that added electric field drives, detection sensitivity can improve 100～1000 times.
Fig. 3 is the frequency spectrum that micro-cantilever among the embodiment 2 is recorded with the vibration mode atomic force microscope.Curve 01 is that secondary peak is 179.65kHz; Curve 02 is that main peak is 270.77kHz, (frequency sweeping scope be 0 to 600KHz).Be that displacement with main peak frequency is as the criterion in the above-described embodiment.
Claims (6)
1. the biosensor of micro cantilever of a fast detecting biomolecule, it comprises the fluid sample chamber that has electric field, is positioned at the micro-cantilever that is fixed with bioprobe on the indoor top of fluid sample, it is characterized in that comprising the bottom electrode that is positioned at the indoor bottom of fluid sample; Described micro-cantilever is the micro-cantilever electrode as positive electrode or negative electrode; Described bottom electrode then is negative electrode or positive electrode; Constitute between micro-cantilever electrode and the bottom electrode and be positioned at indoor electrostatic field of fluid sample or alternating electric field.
2. the biosensor of micro cantilever of fast detecting biomolecule according to claim 1 is characterized in that the described micro-cantilever that is fixed with bioprobe is the single micro-cantilever that is fixed with bioprobe, or is fixed with the micro-cantilever array of bioprobe.
3. the biosensor of micro cantilever of fast detecting biomolecule according to claim 2 is characterized in that the described bioprobe that is fixed on the micro-cantilever is the probe that has the molecule that combines with testing sample target molecule selectivity.
4. the biosensor of micro cantilever of fast detecting biomolecule according to claim 1, it is characterized in that described fluid sample chamber comprises the base plate of band filling opening and liquid outlet, be positioned at comprise on the base plate filling opening and liquid outlet seal groove, place O-ring seal in the seal groove to constitute the fluid sample chamber of the band filling opening and the liquid outlet that are positioned at O-ring seal.
5. the biosensor of micro cantilever of fast detecting biomolecule according to claim 1 is characterized in that the described micro-cantilever that is fixed with bioprobe places indoor being positioned at of fluid sample to be fixed on the firm banking on the base spring.
6. the biosensor of micro cantilever of fast detecting biomolecule according to claim 1 is characterized in that described biosensor of micro cantilever is integrated biosensor of micro cantilever.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200520040958 CN2795853Y (en) | 2005-04-19 | 2005-04-19 | Micro suspension arm biological sensor for quick detecting biological molecule |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200520040958 CN2795853Y (en) | 2005-04-19 | 2005-04-19 | Micro suspension arm biological sensor for quick detecting biological molecule |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104160275A (en) * | 2012-02-16 | 2014-11-19 | 麦克罗威斯克有限公司 | Micro-sensor based test apparatus |
| CN107515297A (en) * | 2017-08-17 | 2017-12-26 | 扬州大学 | It is a kind of self-driven from sensing microcantilever sensors, preparation method and its application |
| CN109142657A (en) * | 2017-06-28 | 2019-01-04 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | A kind of detection analysis instrument |
| US11333661B2 (en) | 2017-06-28 | 2022-05-17 | Cixi Institute Of Biomedical Engineering Ningbo Institute Of Industrial Technology, Chinese Academy Of Sciences | Detection analyzer |
-
2005
- 2005-04-19 CN CN 200520040958 patent/CN2795853Y/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104160275A (en) * | 2012-02-16 | 2014-11-19 | 麦克罗威斯克有限公司 | Micro-sensor based test apparatus |
| CN109142657A (en) * | 2017-06-28 | 2019-01-04 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | A kind of detection analysis instrument |
| US11333661B2 (en) | 2017-06-28 | 2022-05-17 | Cixi Institute Of Biomedical Engineering Ningbo Institute Of Industrial Technology, Chinese Academy Of Sciences | Detection analyzer |
| CN107515297A (en) * | 2017-08-17 | 2017-12-26 | 扬州大学 | It is a kind of self-driven from sensing microcantilever sensors, preparation method and its application |
| CN107515297B (en) * | 2017-08-17 | 2019-08-27 | 扬州大学 | It is a kind of to drive autobiography sense microcantilever sensors, production method and its application certainly |
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060712 Termination date: 20100419 |