CN106018028B - A kind of method and device for realizing the control and detection of determinand aggregation in solution - Google Patents

A kind of method and device for realizing the control and detection of determinand aggregation in solution Download PDF

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Publication number
CN106018028B
CN106018028B CN201610397607.7A CN201610397607A CN106018028B CN 106018028 B CN106018028 B CN 106018028B CN 201610397607 A CN201610397607 A CN 201610397607A CN 106018028 B CN106018028 B CN 106018028B
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determinand
stationary point
solution
sensor
position
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CN201610397607.7A
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CN106018028A (en
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段学欣
庞慰
刘文朋
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段学欣
庞慰
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Abstract

The embodiment of the invention discloses it is a kind of realize determinand aggregation method, which is characterized in that be applied to include piezoelectric vibration device system in, this method includes:A, setting one acts on the solution to form the piezo-electric resonator in hydrodynamics stationary point;B, by controlling the automatically controlled parameter of the piezoelectric vibration device, so that the solution forms the hydrodynamics stationary point in a position, the determinand is assembled at the stationary point.By upper, the present invention overcomes due to the insensitive defect of detection caused by the mass transport limitation in solution and the affine power limit in Substance Interactions, be advantageously implemented the high sensitivity detection to determinand in the prior art.

Description

A kind of method and device for realizing the control and detection of determinand aggregation in solution

Technical field

The present invention relates to field of biosensors, particularly relate to a kind of control and detection for realizing that determinand is assembled in solution Method and device.

Background technology

As science and technology is constantly to the development of micro-scale, realize the monitoring of the interaction to biomolecule in medical treatment The fields such as diagnosis, medicament research and development, environmental monitoring play a crucial role.Currently, real to the micro-example under extremely low concentration Existing high sensitivity, rapidly detection has become the development trend of related field.Therefore, people develop various based on novelty successively Sensor mechanism micro-nano device, such as nanowire sensor and micro-nano mechanical sensor etc..Since these device volumes are small, Consumption sample size is few, and in addition its table body ratio is very high, has very high signal-to-noise ratio in sensing process, this is to low concentration and micro sample This detection has a very important role.

However although the senser element based on different sensor mechanisms emerges one after another, still there are two in liquid sensing A very important limitation:Affine power limit in mass transport limitation and Substance Interactions.In almost all of base In the sensing of solid liquid interface, determinand needs could be made with having modified on interface after moving to sensing interface in solution It is combined for the substance of probe.In the solution, the kinetic rate during this be limited to the convection current of determinand in the solution with And diffusivity, that is, the limitation of so-called mass transport;And on interface, the kinetic rate during this is limited to wait for The binding ability of object and probe substance on interface, that is, so-called affine power limit are surveyed, since there are above two limitation, poles The big sensitivity reduced to the analyte detection to be measured under low concentration.

Invention content

In view of this, the main purpose of the present invention is to provide a kind of controls and inspection for realizing that determinand is assembled in solution The method and device of survey, for overcome in the prior art due in solution mass transport limitation and Substance Interactions in The insensitive defect of detection caused by affine power limit, by the way that a piezo-electric resonator is arranged, and by controlling the piezoelectric resonator The automatically controlled parameter of device, so that the solution forms the hydrodynamics stationary point in a position, the determinand is at the stationary point Aggregation is advantageously implemented the high sensitivity detection to determinand.

The present invention provides a kind of control method for realizing that determinand is assembled in solution, including:

A, setting one acts on the solution to form the resonating device in hydrodynamics stationary point;

B, by controlling the automatically controlled parameter of the resonating device, so that the solution forms the fluid in an at least position Mechanics stationary point, the determinand are assembled to form accumulation regions to the stationary point.

It is existing to overcome by being set to a resonating device in solution and controlling the automatically controlled parameter of the resonating device by upper Due to the mass transport limitation in solution and the affine power limit in Substance Interactions in technology so that in the solution Determinand is assembled at stationary point, is conducive to be detected the determinand of the low concentration in solution.

The present invention also provides a kind of detection methods for realizing determinand in solution, including:

A, setting one acts on the solution to form the resonating device in hydrodynamics stationary point;

B, by controlling the automatically controlled parameter of the resonating device, so that the solution forms the fluid in an at least position Mechanics stationary point, the determinand are assembled to form accumulation regions to the stationary point;

C, the determinand is detected in the aggregation zone position.

It is existing to overcome by being set to a resonating device in solution and controlling the automatically controlled parameter of the resonating device by upper Due to the mass transport limitation in solution and the affine power limit in Substance Interactions in technology so that in the solution Determinand is assembled at stationary point, and is further detected to the determinand after aggregation, improves to the determinand of low concentration Detectable concentration.

Preferably, further include between step B and C:It determines to assemble by determining hydrodynamics stationary point position The step of zone position.

By upper, the determination of stationary point position is conducive to rapidly and effectively detect determinand.

Preferably, described the step of determining the hydrodynamics stationary point position, includes:

Microscopy, holography method, the burnt microscopic method of copolymerization, particle are passed through to the resonating device surrounding medium Hydrodynamics stationary point position is determined in method for tracing or the observation of Laser-Ultrasonic vortex measurement method.

Preferably, the method further includes:

Pre-set the expected aggregation zone position being detected to the determinand;

The automatically controlled parameter for controlling the resonating device makes expected poly- described in the hydrodynamics stationary point location matches to be formed Collect the corresponding expected stationary point position of zone position.

By upper, by controlling the automatically controlled parameter of resonating device, the position in stationary point controlled, is conducive to rapidly and effectively detect Determinand.

Preferably, step B controls the position for forming accumulation regions and/or size by one of at least following parameter:

The resonating device size, applies power, quality factor, the solution at the resonant frequency in the automatically controlled parameter Boundary, volume.

It by upper, is controlled by many kinds of parameters, is conducive to the preferably position of control accumulation regions and/or size.

Preferably, step B controls the determinand by one of at least following parameter and assembles to form accumulation regions to the stationary point Collection efficiency and/or concentration:

Resonant frequency, application power, quality factor in the automatically controlled parameter.

Preferably, determinand includes but not limited at least one in the solution:It is biochemical molecule, albumen, thin Born of the same parents organize or micro-nano nano-sphere, magnetic bead.

Also a kind of device for realizing analyte detection to be measured in solution of the present invention, including:

Resonating device, the electric-controlled parts being electrically connected with resonating device, the electric-controlled parts are used for by controlling the resonance The automatically controlled parameter of device, so that the solution forms hydrodynamics stationary point in an at least position, the determinand is poly- to the stationary point Collection forms accumulation regions;

Determinand detection part, the determinand for detecting the accumulation regions.

By upper, by controlling the automatically controlled parameter of above-mentioned resonating device, to overcome in the prior art due to the quality in solution Affine power limit in transmission limitation and Substance Interactions so that the determinand in the solution is assembled at stationary point, makes The determinand obtained in the solution is assembled at stationary point, and is further detected to the determinand after aggregation, improves to low dense The detectable concentration of the determinand of degree.

Preferably, described device further includes:Stationary point detection for observing and/or detecting generated hydrodynamics stationary point Component.

By upper, stationary point position is detected by stationary point detection part, so that it is determined that the aggregation zone of determinand aggregation, convenient for inspection Survey the setting of component locations.

Preferably, determinand detection part institute detection zone is preset;

The electric-controlled parts adjust automatically controlled parameter also according to the stationary point that the detection part is observed/detected, so that institute's shape At stationary point corresponding to accumulation regions match determinand detection part institute detection zone.

By upper, by the adjustment of automatically controlled parameter, advantageously ensure that detection part is matched with the accumulation regions corresponding to stationary point, have It is accurate and effective conducive to ensureing to detect.

Preferably, the determinand detection part includes at least one:

Surface acoustic wave sensor, acoustic wave sensor, crystal microbalance sensor, fluorescence spectrum sensor, biomembrane are dry Relate to technical sensor, Raman spectrum sensor, infrared spectrum sensor, surface plasma resonance technology sensor, enzyme linked immunological Sensor, field-effect tube sensor, electrochemical sensor, carbon nanotube field-effect sensor, semiconductor nanowires field-effect pass Sensor, graphene field effect sensor, molybdenum disulfide field effect transistor, black phosphorus field effect transistor, impedance transducer, resistance Type sensor, cantilever beam sensor, giant magneto-resistance sensor, isothermal titration calorimetric instrument.

As seen from the above, the present invention provides a kind of method for realizing control and detection that determinand in solution is assembled and Device, by being arranged a piezo-electric resonator, and the automatically controlled parameter by controlling the piezoelectric vibration device so that the solution in One position forms the hydrodynamics stationary point, and the determinand is assembled at the stationary point, and is further detected to determinand, It overcomes in the prior art since the mass transport limitation in solution and the affine power limit in Substance Interactions cause The insensitive defect of detection, realize to determinand high sensitivity detection.

Description of the drawings

In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below There is attached drawing needed in technology description to be briefly described, it should be apparent that, the accompanying drawings in the following description is this hair Some bright embodiments for those of ordinary skill in the art without having to pay creative labor, can be with Obtain other attached drawings according to these attached drawings.

Fig. 1 is a kind of control method flow diagram for realizing that determinand is assembled in solution provided in an embodiment of the present invention;

Fig. 2 is a kind of detection method structural schematic diagram for realizing determinand in solution provided in an embodiment of the present invention;

Fig. 3 is a kind of signal of the piezoelectric vibration device provided in an embodiment of the present invention to the impact analysis of testing concentration Figure;

Fig. 4 is a kind of schematic diagram assembled to human immunoglobulin(HIg) and detected provided in an embodiment of the present invention;

Fig. 5 is a kind of schematic diagram assembled to prostate-specific antigen and detected provided in an embodiment of the present invention;

Fig. 6 is the structural schematic diagram of the sectional view of the first piezoelectric vibration device provided in an embodiment of the present invention;

Fig. 7 is the structural schematic diagram of the vertical view of the first piezoelectric vibration device provided in an embodiment of the present invention;

Fig. 8 is the structural schematic diagram of the sectional view of second of piezoelectric vibration device provided in an embodiment of the present invention;

Fig. 9 is the structural schematic diagram of the vertical view of second of piezoelectric vibration device provided in an embodiment of the present invention;

Figure 10 is the structural schematic diagram of the sectional view of the third piezoelectric vibration device provided in an embodiment of the present invention;

Figure 11 is the structural schematic diagram of the vertical view of the third piezoelectric vibration device provided in an embodiment of the present invention;

Figure 12 is the structure section view that piezoelectric vibration device provided in an embodiment of the present invention realizes determinand aggregation in the solution The structural schematic diagram of figure.

Specific implementation mode

In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with the embodiment of the present invention In attached drawing, technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described embodiment is A part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art The every other embodiment obtained without creative efforts belongs to the section that the present invention protects.

To overcome defect in the prior art, the present invention provides a kind of controls and inspection for realizing that determinand is assembled in solution The method and device of survey, by the way that a piezo-electric resonator, and the automatically controlled parameter by controlling the piezoelectric vibration device is arranged, so that The solution forms hydrodynamics stationary point in a position, and the determinand is assembled at the stationary point, and further at the stationary point Determinand is detected, the high sensitivity detection to determinand is realized.

Embodiment one

As shown in Figure 1, for a kind of control method that realizing that determinand is assembled in solution provided in this embodiment of the invention Flow diagram, the method is specific as follows:

S101, setting one act on the solution to form the piezo-electric resonator in hydrodynamics stationary point.

Specifically, in order to improve the congregational rate to determinand, it is necessary first to according to the volume of the solution and boundary, if Set a corresponding size and or position act on the solution to form the piezo-electric resonator in hydrodynamics stationary point.

S102, by controlling the automatically controlled parameter of the piezoelectric vibration device so that the solution formed in a position it is described Hydrodynamics stationary point, the determinand are assembled at the stationary point.

By controlling the automatically controlled parameter of the piezoelectric vibration device, to control the effect that the determinand is assembled at the stationary point The concentration that rate and the determinand are assembled at the stationary point.Wherein, the automatically controlled parameter includes, but is not limited to following one: Resonant frequency applies power, quality factor.By control the resonant frequency in the resonating device size, the automatically controlled parameter, Apply power, quality factor, the boundary of the solution, volume, to control the accumulation regions that the determinand is assembled at the stationary point The position in domain, size and shape.Wherein, aggregation zone both can be in the center of piezoelectric vibration device, can also be in piezoelectric resonator The edge or other positions of device;The shape of aggregation zone is either spherical shape, can also be elliposoidal or other three-dimensionals Structure.

Wherein, the determinand includes but not limited to following one:Biochemical molecule, albumen, cell tissue or micro-nano Nano-sphere, magnetic bead.

Wherein, the automatically controlled parameter includes, but is not limited to following one:Resonant frequency applies power, quality factor.

Embodiment two

Conceived based on inventive embodiments same as the method for determinand aggregation in above-mentioned realization solution, the embodiment of the present invention In additionally provide a kind of detection method for realizing determinand in solution, as shown in Fig. 2, for the detection method flow illustrate Figure, the method are specific as follows:

S201, setting one act on the solution to form the piezo-electric resonator in hydrodynamics stationary point.

Specifically, according to the volume of the solution and boundary, be arranged a corresponding size and or position act on it is described molten Liquid is to form the piezo-electric resonator in hydrodynamics stationary point.

S202, by controlling the automatically controlled parameter of the piezoelectric vibration device so that the solution formed in a position it is described Hydrodynamics stationary point, the testing molecule are assembled at the stationary point.

By controlling the automatically controlled parameter of the piezoelectric vibration device, to control the effect that the determinand is assembled at the stationary point The concentration that rate and the determinand are assembled at the stationary point.Wherein, the automatically controlled parameter includes, but is not limited to following one: Resonant frequency applies power, quality factor.

Pre-set the expected aggregation zone position being detected to the determinand;Control the automatically controlled ginseng of the resonating device Number makes to be expected the corresponding expected stationary point position of aggregation zone position described in the hydrodynamics stationary point location matches to be formed.

Wherein, the three-dimensional foreign trade of the stationary point aggregation zone can by means such as holography, Confocal laser endomicroscopies Accurately to measure.

By control the resonant frequency in the piezoelectric vibration device size, the automatically controlled parameter, apply power, quality because The boundary of several, the described solution, volume, with control the position of the aggregation zone that the determinand is assembled at the stationary point, size and Shape.

Aggregation zone both can in the center of piezoelectric vibration device, can also the edge of piezoelectric vibration device or other Position;The shape of aggregation zone is either spherical shape, can also be elliposoidal or other three-dimensional structures.

Wherein, the determinand includes but not limited to following one:Biochemical molecule, cell tissue or micro-nano small Ball.The determinand includes but not limited to following one:Biochemical molecule, cell tissue or micro-nano nano-sphere.

S203 detects the determinand at the hydrodynamics stationary point.

Specifically, as collector piezoelectric vibration device simultaneously can also be used as sensor detection solution in substance between Interaction.The determinand after aggregation is detected by piezoelectric vibration device.

In order to further decrease the detectable limit of detecting system, the performance of optimizing detection system can be humorous by piezoelectricity Device shake as collector, and is combined with other sensors based on principles such as sound, light, electricity, magnetic, heat, that is, passes through sensor pair Determinand after aggregation is detected.

Wherein, the sensor includes but not limited to following one:Surface acoustic wave sensor, acoustic wave sensor, crystal Microbalance sensor, fluorescence spectrum sensor, biomembrane interference technique sensor, Raman spectrum sensor, infrared spectrum sensing Device, surface plasma resonance technology sensor, Enzyme linked immunosensor, field-effect tube sensor, electrochemical sensor, carbon nanometer Pipe field effect transistor, semiconductor nanowires field effect transistor, graphene field effect sensor, molybdenum disulfide field-effect sensing Device, black phosphorus field effect transistor, impedance transducer, resistance type sensor, cantilever beam sensor, giant magneto-resistance sensor, isothermal drop Quantitative thermal instrument.

Embodiment three

Conceived based on inventive embodiments same as the control of determinand aggregation in above-mentioned realization solution and the method for detection, A kind of equipment for realizing analyte detection to be measured in solution is additionally provided in the embodiment of the present invention, the equipment includes:

Resonating device, the electric-controlled parts being electrically connected with resonating device, the electric-controlled parts are used for by controlling the resonance The automatically controlled parameter of device, so that the solution forms hydrodynamics stationary point in an at least position, the determinand is poly- to the stationary point Collection forms accumulation regions;

Determinand detection part, the determinand for detecting the accumulation regions.

Stationary point detection part, position, size and shape for observing and/or detecting generated hydrodynamics stationary point.

Wherein, determinand detection part institute detection zone is preset;The electric-controlled parts are also according to the detection The stationary point that component is observed/detected adjusts automatically controlled parameter, so that the accumulation regions matching being formed by corresponding to stationary point is described to be measured Analyte detection component institute detection zone.

The determinand detection part includes at least one:

Surface acoustic wave sensor, acoustic wave sensor, crystal microbalance sensor, fluorescence spectrum sensor, biomembrane are dry Relate to technical sensor, Raman spectrum sensor, infrared spectrum sensor, surface plasma resonance technology sensor, enzyme linked immunological Sensor, field-effect tube sensor, electrochemical sensor, carbon nanotube field-effect sensor, semiconductor nanowires field-effect pass Sensor, graphene field effect sensor, molybdenum disulfide field effect transistor, black phosphorus field effect transistor, impedance transducer, resistance Type sensor, cantilever beam sensor, giant magneto-resistance sensor, isothermal titration calorimetric instrument.

Wherein, the resonating device, the determinand detection part, the stationary point detection part can be respectively independently arranged Or assembly is an entirety.

Wherein, it is as in Figure 3-5 the experiment effect figure of the present invention.

As shown in figure 3, being MPR (micro-fabricated piezoelectric resonator, piezo-electric resonator Part) impact analysis to testing concentration.Wherein, can be seen that using after piezoelectric vibration device by a, c in Fig. 3, with when Between variation, the concentration of aggregation zone determinand gradually rises.It can be seen that using after piezoelectric vibration device by c, d in Fig. 3, With the variation of time, the area and height of determinand aggregation zone gradually increase.B in Fig. 3 is to measure piezoelectric vibration device The schematic diagram of device of influence to testing concentration.F in Fig. 3 shows three-dimensional flow field structure.

As shown in figure 4, for the signal that human IgG (Immunoglobulin G, immunoglobulin) is assembled and detected Figure.Wherein, a in Fig. 4 shows the functionalization process on piezoelectric vibration device surface.That is, piezoelectric vibration device is poly- to determinand The schematic diagram of the facilitation of collection.(b)-(d) in Fig. 4 shows the different power and product by the way that piezoelectric vibration device is arranged Prime factor, fluorescent image and intensity in obtained liquid after human immunoglobulin(HIg) aggregation.It can be seen from this figure that different work( The influence for the effect that rate and quality factor assemble human immunoglobulin(HIg) is different, and as the effect of the growth aggregation of time is got over It is good.(e)-(f) in Fig. 4 shows the fluorescent image and intensity of the human immunoglobulin(HIg) of various concentration in liquid.In Fig. 4 (g)-(h) shows the fluorescent image and intensity of the human immunoglobulin(HIg) of the various concentration after wash buffer and drying.

As shown in figure 5, for using piezoelectric vibration device and sensor to PSA (prostate specific antigen, Prostate-specific antigen) measurement.A in wherein Fig. 5 is to drive PSA aggregations using piezoelectric vibration device and further make The schematic diagram that the PSA after aggregation is measured with sensor.(b) in Fig. 5 indicates to measure the thermokinetics of PSA, can be with by it Find out using the combination for significantly enhancing PSA and probe after piezoelectric vibration device.(c) in Fig. 4 show in conjunction with enhancing because Influence of the son to the combination of different concentration PSA and probe.(d) in Fig. 4 shows the use pressure of experiment sensor response display The curve of enhancing binding kinetics after electric resonance device, it can be seen from this figure that left using 1.2min after piezoelectric vibration device It behind the right side, tends towards stability in conjunction with effect, can select to measure at this moment.

Technical solution in order to further illustrate the present invention, the present invention provides the structure of following piezoelectric vibration device and works Make principle.

Fig. 6 is the sectional view according to the piezoelectric vibration device of the embodiment of the present invention.This piezoelectric vibration device has sandwich Structure, wherein upper layer and lower layer are the interdigital electrode being made of electrode 1 and electrode 2, and middle layer is piezoelectric layer.Electrode 1 and electrode 2 Number is but is not limited to 6 pairs.Can be wherein molybdenum or other conductor materials as the material of electrode 1 and electrode 2, as piezoelectricity The material of layer can be aluminium nitride or other piezoelectric materials.

Fig. 7 is the vertical view according to the first piezoelectric vibration device of the embodiment of the present invention.In this specific embodiment, Electrode 1 and electrode 2 have the structure being mutually parallel, but are not limited to the structure being mutually parallel, any to make this piezoelectric resonator Device works and forms the structure in hydrodynamics stationary point in a liquid within invention protection domain.

Fig. 8 is the sectional view according to second of piezoelectric vibration device of the embodiment of the present invention.This piezoelectric vibration device has Sandwich structure, wherein upper layer and lower layer are made of electrode 1 and electrode 2, and middle layer is piezoelectric layer.Material as electrode 1 and electrode 2 Material can be that either other conductor materials as the material of piezoelectric layer can be aluminium nitride or other piezoelectric materials to molybdenum.

Fig. 9 is the vertical view according to second of piezoelectric vibration device of the embodiment of the present invention.In this specific embodiment, Piezoelectricity layer material and electrode 1 and electrode 2 belong to but are not limited to regular pentagon structure, any that this piezo-electric resonator can be made to work And the structure in hydrodynamics stationary point is formed in a liquid within invention protection domain.

Figure 10 is the sectional view according to the third piezoelectric vibration device of the embodiment of the present invention.This micro-nano piezoelectric vibration device Include the interdigital electrode being made of electrode 1 and electrode 2 and the piezoelectric layer that piezoelectric material is constituted with double-layer structure.Electrode 1 with The number of electrode 2 is but is not limited to 3 pairs.As the material of electrode 1 and electrode 2 can be molybdenum or other conductor materials, as The material of piezoelectric layer can be aluminium nitride or other piezoelectric materials.

Figure 11 is the vertical view according to the third piezoelectric vibration device of the embodiment of the present invention.In this specific embodiment In, electrode 1 and electrode 2 have the structure being mutually parallel, but are not limited to the structure being mutually parallel, any that this piezoelectricity can be made humorous The device that shakes works and forms the structure in hydrodynamics stationary point in a liquid within invention protection domain.

Above-described three kinds of piezo-electric resonators, do not constitute limiting the scope of the invention.People in the art Member it is to be understood that depend on design requirement and other factors, can occur it is various modification, combination, sub-portfolio and It substitutes.It is any within the spirit and principles in the present invention made by modifications, equivalent substitutions and improvements etc., should be included in the present invention Within protection domain.

Its principle is that, when piezoelectric vibration device is operated near resonant frequency, piezoelectric layer will produce Nano grade Vibration, and then acoustic streaming effect and hydromechanical stationary point are generated in the solution, meanwhile, the power of application is bigger, piezoelectric layer Vibration is more apparent, and the collection efficiency of determinand is also higher.Position, size and the height and piezoelectric layer nanometer in hydrodynamics stationary point Flow field is related caused by vibration, and can accurately measure accumulation regions by means such as holography, Confocal laser endomicroscopies Three-dimensional appearance.

Figure 12 is the structure section view for realizing determinand aggregation in the solution according to the piezoelectric vibration device of the embodiment of the present invention Figure.By applying the alternating voltage of fixed frequency on electrode 1 and electrode 2, piezoelectric material will produce the vibration of nanoscale.This Vibration can promote the movement of fluid in the solution, formed be vortexed in a fluid, ultimately form hydrodynamics stationary point, this hydrodynamics Stationary point is located at the position near piezoelectric vibration device, and determinand can then collect around in this hydrodynamics stationary point, forms aggregation Area.The movement of fluid accelerates determinand to the convection current and diffusion positioned at the sensor senses interface of aggregation zone, thus breaks Mass transport limitation;Meanwhile in accumulation regions, the concentration of determinand locally increases, and promotes determinand and more exists with modification The combination of the probe substance of the sensing interface of sensor, thus broken the affine power limit in Substance Interactions.Here, It is emphasized that the phase when sensor being not only restricted in the present invention in present embodiment is combined with piezoelectric vibration device To position, it is any by any piezoelectric vibration device and any sensor or other devices in any way and position has been combined Come, belongs to protection scope of the present invention.The position of aggregation zone is but is not only restricted near piezoelectric vibration device, accumulation regions The space structure in domain is but is not only restricted to elliposoidal.Simultaneously because piezoelectric vibration device itself can be used as sensor, thus it is micro- Piezoelectric vibration device itself of receiving can be used as collector and sensor to use simultaneously.

Above-mentioned specific implementation mode, does not constitute limiting the scope of the invention.Those skilled in the art should be bright It is white, design requirement and other factors are depended on, various modifications, combination, sub-portfolio and replacement can occur.It is any Modifications, equivalent substitutions and improvements made by within the spirit and principles in the present invention etc., should be included in the scope of the present invention Within.

Claims (14)

1. a kind of control method for realizing that determinand is assembled in solution, which is characterized in that including:
A, setting one acts on the solution to form the resonating device in hydrodynamics stationary point;
B, by controlling the automatically controlled parameter of the resonating device, so that the solution forms the hydrodynamics in an at least position Stationary point, the determinand are assembled to form accumulation regions to the stationary point.
2. according to the method described in claim 1, it is characterized in that, step B controls the shape by one of at least following parameter Position at accumulation regions and/or size:
The side of the resonating device size, the resonant frequency in the automatically controlled parameter, application power, quality factor, the solution Boundary, volume.
3. according to the method described in claim 1, it is characterized in that, step B described in the control of one of at least following parameter by waiting for It surveys object and assembles the collection efficiency and/or concentration to form accumulation regions to the stationary point:
Resonant frequency, application power, quality factor in the automatically controlled parameter.
4. according to the method described in claim 1, it is characterized in that, determinand includes but not limited at least following in the solution One of:Biochemical molecule, albumen, cell tissue or micro-nano nano-sphere, magnetic bead.
5. a kind of method for realizing analyte detection to be measured in solution, which is characterized in that including:
A, setting one acts on the solution to form the resonating device in hydrodynamics stationary point;
B, by controlling the automatically controlled parameter of the resonating device, so that the solution forms the hydrodynamics in an at least position Stationary point, the determinand are assembled to form accumulation regions to the stationary point;
C, the determinand is detected in the aggregation zone position.
6. according to the method described in claim 5, it is characterized in that, further including between step B and C:By determining the stream Mechanics stationary point position is come the step of determining aggregation zone position.
7. according to the method described in claim 6, it is characterized in that, described the step of determining the hydrodynamics stationary point position Including:
Microscopy, holography method, the burnt microscopic method of copolymerization, particles track are passed through to the resonating device surrounding medium Hydrodynamics stationary point position is determined in method or the observation of Laser-Ultrasonic vortex measurement method.
8. the method described according to claim 6 or 7, which is characterized in that further include:
Pre-set the expected aggregation zone position being detected to the determinand;
The automatically controlled parameter for controlling the resonating device makes expected accumulation regions described in the hydrodynamics stationary point location matches to be formed The corresponding expected stationary point position in position.
9. according to the method described in claim 5, it is characterized in that, step B controls the shape by one of at least following parameter Position at accumulation regions and/or size:
The side of the resonating device size, the resonant frequency in the automatically controlled parameter, application power, quality factor, the solution Boundary, volume.
10. according to the method described in claim 5, it is characterized in that, step B described in the control of one of at least following parameter by waiting for It surveys object and assembles the collection efficiency and/or concentration to form accumulation regions to the stationary point:
Resonant frequency, application power, quality factor in the automatically controlled parameter.
11. according to the method described in claim 5, it is characterized in that, in the solution determinand include but not limited at least with It is one of lower:Biochemical molecule, albumen, cell tissue or micro-nano nano-sphere, magnetic bead.
12. a kind of device for realizing analyte detection to be measured in solution, which is characterized in that including:
Resonating device, the electric-controlled parts being electrically connected with resonating device, the electric-controlled parts are used for by controlling the resonating device Automatically controlled parameter so that the solution forms hydrodynamics stationary point in an at least position, the determinand assembles shape to the stationary point At accumulation regions;
Determinand detection part, the determinand for detecting the accumulation regions;
Wherein, described device further includes:Stationary point detection part for observing and/or detecting generated hydrodynamics stationary point.
13. device according to claim 12, which is characterized in that determinand detection part institute detection zone is set in advance It is fixed;
The electric-controlled parts adjust automatically controlled parameter also according to the stationary point that the detection part is observed/detected, so as to be formed by Accumulation regions corresponding to stationary point match determinand detection part institute detection zone.
14. device according to claim 12, which is characterized in that the determinand detection part include at least it is following it One:
Surface acoustic wave sensor, acoustic wave sensor, crystal microbalance sensor, fluorescence spectrum sensor, biomembrane interfere skill Art sensor, Raman spectrum sensor, infrared spectrum sensor, surface plasma resonance technology sensor, immunosensing Device, field-effect tube sensor, electrochemical sensor, carbon nanotube field-effect sensor, semiconductor nanowires field effect transistor, Graphene field effect sensor, molybdenum disulfide field effect transistor, black phosphorus field effect transistor, impedance transducer, resistor-type pass Sensor, cantilever beam sensor, giant magneto-resistance sensor, isothermal titration calorimetric instrument.
CN201610397607.7A 2016-06-03 2016-06-03 A kind of method and device for realizing the control and detection of determinand aggregation in solution CN106018028B (en)

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