CN102735564A - High-sensitive biochemical sensor based on resonance oscillation type micro cantilever beam structure - Google Patents
High-sensitive biochemical sensor based on resonance oscillation type micro cantilever beam structure Download PDFInfo
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- CN102735564A CN102735564A CN2012102435136A CN201210243513A CN102735564A CN 102735564 A CN102735564 A CN 102735564A CN 2012102435136 A CN2012102435136 A CN 2012102435136A CN 201210243513 A CN201210243513 A CN 201210243513A CN 102735564 A CN102735564 A CN 102735564A
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Abstract
The invention discloses a high sensitive biochemical sensor based on a resonance oscillation type micro cantilever beam structure. The biochemical sensor comprises a resonance oscillation chamber, a cantilever beam and a Whist bridge type detection circuit, wherein a micro column structure (3), a liquid storage tank (4) and a liquid leakage hole (5) through which biochemical solution flows are etched at the free end of the cantilever beam; the support end of the cantilever beam is connected with the Whist bridge type detection circuit; the Whist bridge type detection circuit is composed four U-shaped piezoresistance bars (1), three input electrodes (8, 9, 10) and two output electrodes (7, 11); and the four piezoresistance bars (1) are connected with the input electrodes (8, 9, 10) and the output electrodes (7, 11) through a signal transmission line (2). With the adoption of the biochemical sensor, micro biochemical molecules can be sensed with a high sensitivity by detecting the frequency change after an object to be tested is absorbed; biochemical molecules with micromass can be detected; and the biochemical sensor can be widely used in engineering fields such as medicine and chemistry.
Description
Technical field
The present invention relates to MEMS field, biomedicine and field of chemical engineering, relate in particular to a kind of highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure.
Background technology
Resonant transducer develops rapidly on the basis of electronic technology, measuring technology, computing technique and SIC (semiconductor integrated circuit) technology since the seventies
[1]Fast development along with MEMS science and technology; The size of resonant transducer has been reduced to micron; Sub-micron even nanometer scale; Can carry out high-acruracy survey to multiple physical quantitys such as temperature, heat energy, magnetic field and quality, therefore be widely used in every field such as chemical analysis, biological test, medicine screening and environmental monitoring.
In recent years, become the research focus to highly sensitive biochemistry detection research based on micro cantilever structure
[2]2000, the people such as H.G..Craighead of Cornell university delivered the article that detects cell about the resonance type micromechanical semi-girder
[3]The Si for preparing 100 μ m * 20 μ m * 0.32 μ m with PECVD
3N
4Semi-girder; After its leading portion applies O157:H7 antibody; E.coli cell that can selective adsorption, semi-girder is encouraged by thermonoise, detects the vibration frequency of semi-girder with laser PSD detection system; The minimum detectable change of frequency is about 10Hz, and detectable minimum mass is about 1.5pg in air accordingly.2004; The human soi wafers such as R.Bashir of U.S. Purdure university have been made the single-crystal silicon cantilever beam of the littler 3.6 μ m * 1.7 μ m * 0.03 μ m of size; Resonance frequency is about 1.2MHz, and detection sensitivity is about 6.3Hz/ag, adopts the thermonoise excitation; Laser PSD detects, and in air, has detected a smallpox virus (9fg).
But, still existing many technical matterss based on the sensor of cantilever beam structure, absorption causes that the semi-girder elastic constant changes like: large tracts of land, produces frequency shift (FS) and the measuring error that causes; Beam semi-girder quality factor in the biochemical environment of liquid significantly reduces
[4], cause detection sensitivity to reduce or the like.In addition, for portable device, high-sensitive most important from detection architecture.Though optical detection commonly used has highly sensitive advantage, optical element can increase the volume and the cost of system.Therefore, press for exploitation portable based on novel cantilever beam structure, highly sensitive biochemical sensor.
List of references:
【1】R.T.Howe，R.S.Muller，K.J.Gabriel?and?W.S.N.Trimme?r，Silicon?micro-mechanics：sensor?and?actuators?on?a?chip，IEEE?Spectrum，7，29-35，1990.
【2】A.Hierlemann，O.Brand，C.Hagleiter?and?H.Baltes，Micro-fabrication?techniques?for?chemical/biosensor，proceedings?of?the?IEEE，6，839-863，2003.
【3】B.Ilic，D.Czaplewski，H.G.Craighead，P.Neuzil，C.Campagnolo?and?C.Batt，Mechanical?resonant?immunospecific?biological?detector，Applied?Physics?Letter，77，450-452，2000.
【4】Ekrem?Bayraktar，Deniz?Eroglu，Ata?Tuna?Cifilik，A?MEMS?based?grabimetric?resonator?for?mass?sensing?applications，IEEE?24
th?International?Conference，817-820，2011.
Summary of the invention
The technical matters that (one) will solve
In order to realize to the highly sensitive detection of the real-time on-site of testing molecule; Need be in high-sensitive frequency detecting technology, eliminate frequency error measurement that absorption causes, reduce testing environment technological breakthrough is carried out in the aspects such as influence of device stability, the present invention proposes a kind of highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure.Designed local decorated structure at the semi-girder free end, can eliminate the frequency error measurement that large tracts of land absorption produces, reduced the influence of solution simultaneously the semi-girder quality factor; Use from integrated pressure drag bar and whist bridge circuit and detect the semi-girder change of frequency, finely satisfy the portable use demand.
(2) technical scheme
In order to realize that testing molecule is carried out real-time highly sensitive detection; The invention provides a kind of highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure; This biochemical sensor comprises resonator cavity, semi-girder and whist bridge detection circuit; Wherein the free end at this semi-girder is etched with microtrabeculae structure (3) and reservoir (4), and is etched with the liquid-leaking nozzle (5) that is used to flow out bio-chemical solution; The support end of this semi-girder is connected in this whist bridge detection circuit; This whist bridge detection circuit is made up of pressure drag bar (1), three input electrodes (8,9,10) and two output electrodes (7,11) of four U type structures, and four pressure drag bars (1) are connected in input electrode (8,9,10) and output electrode (7,11) through signal transmssion line (2).
In the such scheme; This biochemical sensor is that the frequency response through semi-girder comes biochemical molecular is carried out highly sensitive detection; The finishing of semi-girder has the detection unimolecular layer structure (12) to the enough specificly-responses of molecular energy to be measured; Change the quality of semi-girder behind the absorption testing molecule (13), finally caused the resonance frequency of semi-girder to change; Utilize the whist bridge detection circuit to detect the change of frequency of adsorbing the biochemical molecular front and back, obtain the quality of biochemical molecular.
In the such scheme, said reservoir (4) is used for local the modification and surveys unimolecular layer, reduces the frequency shift that large tracts of land absorption causes the influence of semi-girder elastic constant.
In the such scheme, said microtrabeculae structure (3) is used to increase adsorption area, improves detection limit.
In the such scheme, said liquid-leaking nozzle (5) is made in the said reservoir (4), be used for guaranteeing that the reservoir adsorption reaction is accomplished after, waste liquid is discharged from through hole, does not remain in the semi-girder.
In the such scheme, the type of drive of said semi-girder is any one or more in piezoelectricity, static, electromagnetism, thermoelectricity or the optical drive.
In the such scheme, in this whist bridge detection circuit, input electrode (9) connects power supply signal, and output electrode (7,11) is as output electrode, electric input electrode (8,10) ground signalling.
In the such scheme; One of resistance in the said whist bridge detection circuit is the U type pressure drag bar (1) of semi-girder support end; The resonance frequency measurement of semi-girder is accomplished through the whist bridge detection circuit, and U type pressure drag bar (1) is used to improve the constraint ability to electric current.
In the such scheme; Four pressure drag bars (1) in the said whist bridge detection circuit are " U " type pressure drag bar; Four pressure drag bars (1) carry out ion simultaneously and inject formation; Guaranteed the consistance of resistance to greatest extent, effectively improved measuring accuracy, and effective resistance of each pressure drag bar (1) is more than or equal to 1k Ω.
In the such scheme, between the transmission line of said whist bridge detection circuit, etch isolation moat structure, be used to reduce crosstalking of signal between the transmission line, guarantee the measuring accuracy of whist bridge detection circuit.
(3) beneficial effect
Can find out from technique scheme, the invention has the beneficial effects as follows:
1, the highly sensitive biochemical sensor based on the resonant mode cantilever beam structure provided by the invention; When semi-girder at the resonance frequency place during resonance; Change in displacement will cause the resistance variations of the terminal pressure drag bar of semi-girder, thereby the output voltage that causes whist bridge circuit on the semi-girder substrate changes.Designed the reservoir structure of band microtrabeculae at the semi-girder free end; Be used for local absorption testing molecule; Eliminated the semi-girder elastic constant change that large tracts of land absorption causes, thereby the measuring error that the change of frequency that produces causes has reduced the influence of solution to the semi-girder quality factor simultaneously; And, improve detection limit through microtrabeculae design increase adsorption area.In the reservoir structure, made micro through hole, after adsorption reaction was accomplished in the assurance reservoir, waste liquid was discharged from through hole, does not remain on the semi-girder.The sensor of resonant-type tiny cantilever beam structure has higher sensitivity, may detect the biochemical molecular of small quality, can be widely used in engineering fields such as medical science, chemical industry.
2, the highly sensitive biochemical sensor based on the resonant mode cantilever beam structure provided by the invention; Through on substrate, making testing circuit; Make this sensor can realize self-checking function, and then can give up huge optical detection apparatus, reduced the volume of detector; Realized the portability of detecting devices, this also is advantage of the present invention place.
3, the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure provided by the invention through etch microtrabeculae structure and reservoir structure at the semi-girder front end, has improved the useful area of modified region and to the adsorptive power of testing molecule.
4, the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure provided by the invention; In the whist bridge detection circuit; " U " type of employing pressure drag bar is bound current preferably; And four pressure drag bars adopt ion implantation technology to form simultaneously in the whist bridge detection circuit, have guaranteed the consistance of its initial resistance.
5, the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure provided by the invention, highly doped ion inject and form the lead that connects four pressure drag bars, and between lead, carve isolation channel, reduce the signal cross-talk between lead.Effective resistance minimum of each pressure drag can not guarantee the noise of the output signal of wheatstone bridge greater than external treatment circuit less than 1k Ω.
6, the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure provided by the invention forms the cantilever array formula and arranges, and measures when can realize a plurality of determinand
7, the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure provided by the invention can adopt the different driving mode, like piezoelectricity, electromagnetism or optical drive etc., realizes portable use.
Description of drawings
Fig. 1 is the structural representation based on the highly sensitive biochemical sensor of resonant-type tiny cantilever beam structure according to the embodiment of the invention;
Fig. 2 is the diagrammatic cross-section of the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure shown in Figure 1
Fig. 3 is whist bridge detection circuit measuring principle figure;
Fig. 4 is the synoptic diagram of the biochemical sensor array that is made up of two biochemical sensors shown in Figure 1 behind the absorption biochemical molecular according to the embodiment of the invention;
Fig. 5 is the structural representation according to the biochemical sensor array that is made up of a plurality of biochemical sensors shown in Figure 1 of the embodiment of the invention;
Description of reference numerals:
1. pressure drag bar; 2. signal transmssion line; 3. microtrabeculae structure; 4. reservoir; 5. liquid-leaking nozzle; 6. resonator cavity; 7.11. output electrode; 8.9.10. input electrode; 12. detection unimolecular layer; 13. biochemical molecular to be measured; 14. with reference to beam.
Embodiment
For making the object of the invention, technical scheme and advantage clearer, below in conjunction with specific embodiment, and with reference to accompanying drawing, to further explain of the present invention.
The invention provides a kind of highly sensitive biochemical sensor, realize HIGH SENSITIVITY AND HIGH PRECISION measurement biochemical molecular through the micro cantilever structure that adopts front end to have microtrabeculae structure 3, reservoir 4 and liquid-leaking nozzle 5 based on the resonant-type tiny cantilever beam structure.
As shown in Figure 1, Fig. 1 is the structural representation based on the highly sensitive biochemical sensor of resonant-type tiny cantilever beam structure according to the embodiment of the invention, and Fig. 2 is the sectional view of Fig. 1.This single cantilever beam senser element comprises resonator cavity, semi-girder and whist bridge detection circuit.Wherein the front end at this semi-girder etches microtrabeculae structure 3 and reservoir 4, and etching flows out the liquid-leaking nozzle 5 of bio-chemical solution; The rear end of this semi-girder is connected in this whist bridge detection circuit; This whist bridge detection circuit is made up of pressure drag bar 1, input electrode 8,9,10 and the output electrode 7,11 of four U type structures; Four pressure drag bars 1 are connected in input electrode 8,9,10 and output electrode 7,11 through signal transmssion line 2; In one embodiment of the invention, electrode 9 connects power supply signal, and electrode 7 and electrode 11 are as output electrode; Electrode 8 and electrode 10 ground signallings, thus the whist bridge detection circuit obtained.
The pressure drag bar 1 of semi-girder rear end changes along with semi-girder resonance amplitude, converts resistance variations to the voltage signal of same frequency, R through the whist bridge detection circuit
1Be voltage dependent resistor, R
2, R
3, R
4Be fixed resistance, their the identical R that is of resistance when initial, stressed back voltage dependent resistor be changed to Δ R, then export signal and be:
Signal transmssion line 2, output electrode 7,11 measuring-signal output the most at last through pressure drag bar rear end.Utilize the change of frequency of semi-girder to detect the biochemical molecular 13 that the semi-girder front end adsorbs.The detection unimolecular layer structure 12 to the enough specificly-responses of molecular energy to be measured has been modified on the surface of semi-girder; Behind the absorption testing molecule; Make its resonance frequency change, through characterizing out to the detection of resonance frequency and then with biochemical molecular to be measured, beam basic mode resonant frequency is:
Wherein, k is the stiffness factor of beam, m
*Effective mass for beam.
If think that its stiffness factor does not change with institute's loading, then the skew of frequency can be expressed as
The detectable quality of semi-girder being changed to then with frequency
Can obtain the absorption quality of biochemical molecular to be measured according to this principle.
In order to improve the characteristic molecule ability that absorbs, etch microtrabeculae structure 3 at the front end of semi-girder, increase the useful area of beam front end modified region, and produced reservoir 4, biochemical molecular to be measured is fully reacted.Simultaneously, produce the fluid hole 5 of bio-chemical solution at the cantilever front end, bio-chemical solution is residual to cause damage to semi-girder to avoid.
In order to guarantee consistance, four pressure drag bars 1 formation of ion injection simultaneously in this whist bridge detection circuit and " U " type of employing structure be bound current preferably.
For the signal that guarantees the output of this whist bridge detection circuit can satisfy the noise resolution problems of external treatment circuit, effective resistance minimum of each pressure drag bar 1 can not be less than 1k Ω.
The signal transmssion line 2 that connects four pressure drag bars 1 is to be formed by highly doped B ion, and between signal transmssion line, carves isolation channel, the signal cross-talk between the reduce signal transmission line.
During practical application; Adopt the mode of Piezoelectric Driving to drive under the resonance mode of operation; Measure the resonance frequency of absorption biochemical molecular front and back respectively; Thereby through the quality that the difference of two frequencies obtains adsorbing biochemical molecular, its frequency draws from the ac voltage signal frequency measurement of 11 at the terminal output electrode 7 of whist bridge detection circuit and electrode.
As shown in Figure 3, Fig. 3 is whist bridge detection circuit measuring principle figure, and wherein the pressure drag bar 1 of semi-girder root is equivalent to the R in the circuit
4Resistance, corresponding its excess-three pressure drag bar 1 is respectively R
1, R
2, R
3, and four pressure drag bars 1 have same size and B ion doping concentration is identical, have guaranteed that its initial resistance is R.
In order to realize measuring multiple biochemical molecular simultaneously, a plurality of biochemical sensors as shown in Figure 1 are integrated made the biochemical sensor array, and choose one of them biochemical sensor for reference to beam 14.
As shown in Figure 4, Fig. 4 is the synoptic diagram of the biochemical sensor array that is made up of two biochemical sensors shown in Figure 1 behind the absorption biochemical molecular according to the embodiment of the invention.The semi-girder surface of biochemical sensor modified can specificly-response to molecule 13 to be measured detection unimolecular layer structure 12, absorption testing molecule 13 has changed the quality of semi-girder, has finally caused the change of frequency of semi-girder.Utilize the whist bridge detection circuit to detect the change of frequency before and after the absorption biochemical molecular, can obtain the quality of biochemical molecular to be measured.
As shown in Figure 5; Fig. 5 is the structural representation according to the biochemical sensor array that is made up of a plurality of biochemical sensors shown in Figure 1 of the embodiment of the invention; A biochemical sensor in the biochemical sensor array is beam 14 as a reference; The semi-girder modified surface of all the other each biochemical sensors is to the detection unimolecular layer 12 of different testing molecule 13 specificly-responses, and array structure can be measured multiple biochemical molecular simultaneously.
Above-described specific embodiment; The object of the invention, technical scheme and beneficial effect have been carried out further explain, and institute it should be understood that the above is merely specific embodiment of the present invention; Be not limited to the present invention; All within spirit of the present invention and principle, any modification of being made, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure; It is characterized in that; This biochemical sensor comprises resonator cavity, semi-girder and whist bridge detection circuit; Wherein the free end at this semi-girder is etched with microtrabeculae structure (3) and reservoir (4), and is etched with the liquid-leaking nozzle (5) that is used to flow out bio-chemical solution; The support end of this semi-girder is connected in this whist bridge detection circuit; This whist bridge detection circuit is made up of pressure drag bar (1), three input electrodes (8,9,10) and two output electrodes (7,11) of four U type structures, and four pressure drag bars (1) are connected in input electrode (8,9,10) and output electrode (7,11) through signal transmssion line (2).
2. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1; It is characterized in that; This biochemical sensor is that the frequency response through semi-girder comes biochemical molecular is carried out highly sensitive detection; The finishing of semi-girder has the detection unimolecular layer structure (12) to the enough specificly-responses of molecular energy to be measured, has changed the quality of semi-girder behind the absorption testing molecule (13), has finally caused the resonance frequency of semi-girder to change; Utilize the whist bridge detection circuit to detect the change of frequency of adsorbing the biochemical molecular front and back, obtain the quality of biochemical molecular.
3. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1; It is characterized in that; Said reservoir (4) is used for local the modification and surveys unimolecular layer, reduces the frequency shift that large tracts of land absorption causes the influence of semi-girder elastic constant.
4. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1 is characterized in that said microtrabeculae structure (3) is used to increase adsorption area, improves detection limit.
5. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1; It is characterized in that said liquid-leaking nozzle (5) is made in the said reservoir (4), be used for guaranteeing that the reservoir adsorption reaction is accomplished after; Waste liquid is discharged from through hole, does not remain in the semi-girder.
6. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1 is characterized in that the type of drive of said semi-girder is any one or more in piezoelectricity, static, electromagnetism, thermoelectricity or the optical drive.
7. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1; It is characterized in that in this whist bridge detection circuit, input electrode (9) connects power supply signal; Output electrode (7,11) is as output electrode, electric input electrode (8,10) ground signalling.
8. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1; It is characterized in that; One of resistance in the said whist bridge detection circuit is the U type pressure drag bar (1) of semi-girder support end; The resonance frequency measurement of semi-girder is accomplished through the whist bridge detection circuit, and U type pressure drag bar (1) is used to improve the constraint ability to electric current.
9. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1; It is characterized in that; Four pressure drag bars (1) in the said whist bridge detection circuit are " U " type pressure drag bar, and four pressure drag bars (1) carry out ion simultaneously and inject formation, have guaranteed the consistance of resistance to greatest extent; Effectively improved measuring accuracy, and effective resistance of each pressure drag bar (1) is more than or equal to 1k Ω.
10. the highly sensitive biochemical sensor based on the resonant-type tiny cantilever beam structure according to claim 1; It is characterized in that; Between the transmission line of said whist bridge detection circuit, etch isolation moat structure; Be used to reduce crosstalking of signal between the transmission line, guarantee the measuring accuracy of whist bridge detection circuit.
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| CN111024194A (en) * | 2019-11-26 | 2020-04-17 | 东南大学 | Coupled double-end clamped beam resonator for micro-quality detection and quality detection method |
| CN111024194B (en) * | 2019-11-26 | 2021-05-11 | 东南大学 | Quality detection method of resonance system |
| CN115178313A (en) * | 2022-08-05 | 2022-10-14 | 天津工业大学 | Design method of hollow micro-nano composite beam for biochemical molecule detection |
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