CN103033542B - High-sensitivity environmental compensation type capacitive surface stress biosensor - Google Patents
High-sensitivity environmental compensation type capacitive surface stress biosensor Download PDFInfo
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- CN103033542B CN103033542B CN201210405929.3A CN201210405929A CN103033542B CN 103033542 B CN103033542 B CN 103033542B CN 201210405929 A CN201210405929 A CN 201210405929A CN 103033542 B CN103033542 B CN 103033542B
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Abstract
The invention relates to a biosensor, and in particular relates to a high-sensitivity environmental compensation type capacitive surface stress biosensor. The problem that the conventional surface stress biosensor has low signal to noise ratio and low sensitivity is solved. The high-sensitivity environmental compensation type capacitive surface stress biosensor comprises a substrate, wherein an active supporting film and a reference supporting film are respectively fixed on the upper surface of the substrate; a first bottom electrode is arranged in the inner cavity of the active supporting film; the first bottom electrode is fixedly attached to the upper surface of the substrate; a first top electrode is fixedly attached to the outer top surface of the active supporting film; the first bottom electrode is dead against the first top electrode; a second bottom electrode is arranged in the inner cavity of the reference supporting film; the second bottom electrode is fixedly attached to the upper surface of the substrate; a second top electrode is fixedly attached to the outer top surface of the reference supporting film; and the second bottom electrode is dead against the second top electrode. The high-sensitivity environmental compensation type capacitive surface stress biosensor is suitable for detection and monitoring of living matters and chemical substances.
Description
Technical field
The present invention relates to biology sensor, specifically a kind of High-sensitivity environmental compensation type capacitive surface stress biology sensor.
Background technology
Biology sensor refers to and utilizes biological substance (as enzyme, protein, DNA, antibody, antigen, biological membrane, microorganism, cell etc.) as recognition component, biochemical reaction is transformed into can be quantitative physics, chemical signal, thus the device of living matter and chemical substance examination and controlling can be carried out.Surface stress biology sensor is the one of biology sensor, and it is widely used in the field such as clinical diagnose, biochemical detection, novel drugs discovery, is mainly used in the detection of cell surface STRESS VARIATION, to realize the monitoring of Cell Health.Along with the development of bio-microelectromechanical technology, increasing microstructure is used widely at biochemistry.Therefore under prior art conditions, surface stress biology sensor is mainly divided into micro cantilever structure surface stress biology sensor and mems thin film body structure surface to answer power biological sensor two kinds by structure.Wherein, micro cantilever structure surface stress biology sensor adopts the mode sensing of optics, piezoelectricity or pressure drag usually.Mems thin film body structure surface answers power biological sensor usually to adopt the mode sensing of capacitance signal.Micro cantilever structure surface stress biology sensor has highly sensitive advantage, but it is in actual applications easily by the impact of environmental factor (as temperature variation, turbulent flow, laminar flow etc.), the problem that thus its ubiquity signal to noise ratio (S/N ratio) is low.And though mems thin film body structure surface answers power biological sensor effectively can avoid the impact of environmental factor (as temperature variation, turbulent flow, laminar flow etc.), it limit due to self structure, the problem that ubiquity sensitivity is low.Be necessary to invent a kind of brand-new surface stress biology sensor, to solve the problem that existing surface stress biology sensor signal to noise ratio (S/N ratio) is low and sensitivity is low for this reason.
Summary of the invention
The present invention, in order to solve the problem that existing surface stress biology sensor signal to noise ratio (S/N ratio) is low and sensitivity is low, provides a kind of High-sensitivity environmental compensation type capacitive surface stress biology sensor.
The present invention adopts following technical scheme to realize: a kind of High-sensitivity environmental compensation type capacitive surface stress biology sensor, comprises substrate; The upper surface of substrate is fixed with active support film and reference support film respectively; The inner chamber of active support film is provided with the first hearth electrode; First hearth electrode attaches the upper surface being fixed on substrate; The outer end face of active support film attaches and is fixed with the first top electrode; First hearth electrode and the first top electrode position just right; Inner chamber with reference to support film is provided with the second hearth electrode; Second hearth electrode attaches the upper surface being fixed on substrate; Outer end face with reference to support film attaches and is fixed with the second top electrode; Second hearth electrode and the second top electrode position just right; The outer end face of active support film is modified with biochemical sensitive layer.
During work, the first hearth electrode, the first top electrode, the second hearth electrode, the second top electrode are connected with external difference circuit respectively.The chamber wall of the first hearth electrode, the first top electrode, active support film, the inner chamber of active support film form the first capacitance structure jointly.Second hearth electrode, the second top electrode, the chamber wall with reference to support film, the inner chamber with reference to support film form the second capacitance structure jointly.Specific works process comprises: the outer end face one, to active support film drips the solution containing determinand, determinand in solution and biochemical sensitive layer carry out specific binding, the outer end face of active support film is made to produce surface stress, outside active support film, between inner top surface, produce surface stress difference, cause active support film to deflect.Meanwhile, under the factor such as non-specific binding, environmental factor (as temperature variation, turbulent flow, laminar flow etc.) of the gravity of solution, solution and film affects, active support film generation deformation.Under the acting in conjunction of above-mentioned deflection and deformation, active support film drives the first top electrode motion, distance between first hearth electrode and the first top electrode is changed, the capacitance of the first capacitance structure is caused to change, the capacitance variation amount of the first capacitance structure, then by the first hearth electrode and the first top electrode input external difference circuit, realizes the detection of the surface stress to determinand thus.Two, drip not containing the same strength solution of determinand to the outer end face equivalent with reference to support film.Under the factor such as non-specific binding, environmental factor (as temperature variation, turbulent flow, laminar flow etc.) of the gravity of solution, solution and film affects, with reference to support film generation deformation.Under the effect of above-mentioned deformation, the second top electrode motion is driven with reference to support film, distance between second hearth electrode and the second top electrode is changed, the capacitance of the second capacitance structure is caused to change, the capacitance variation amount of the second capacitance structure, then by the second hearth electrode and the second top electrode input external difference circuit, realizes the detection to environmental factor (as temperature variation, turbulent flow, laminar flow etc.) thus.Three, external difference circuit calculates differential capacitance according to the capacitance variation amount of the first capacitance structure and the capacitance variation gauge of the second capacitance structure, and obtains the surface stress signal of determinand by reading differential capacitance.Based on said process, compared with micro cantilever structure surface stress biology sensor, a kind of High-sensitivity environmental compensation type capacitive surface stress biology sensor of the present invention adopts the structural design of two thin walls (active support film and reference support film), the surface stress signal of determinand is obtained by reading differential capacitance, effectively eliminate sensor by environmental factor (as temperature variation, turbulent flow, laminar flow etc.) impact, farthest achieve ambient compensation, thus effectively improve signal to noise ratio (S/N ratio), efficiently solve the problem that existing surface stress biology sensor signal to noise ratio (S/N ratio) is low.
Further, described active support film, reference support film are circular support film; Described first hearth electrode, the first top electrode, the second hearth electrode, the second top electrode are circular electrode.Compare with electrode with the support film of other shape (as square), circular support film and circular electrode can make sensor have higher sensitivity and less electric capacity edge effect.
Further, the area ratio of described first top electrode and active support film, the second top electrode are 0.9 with the area ratio with reference to support film.When the area ratio of the first top electrode and active support film is 0.9, active support film can realize maximum deflection, and the capacitance of the first capacitance structure can realize maximum change.When the second top electrode is 0.9 with the area ratio with reference to support film, can realize maximum deflection with reference to support film, the capacitance of the second capacitance structure can realize maximum change.Now sensor can obtain maximum sensitivity.
In addition, described active support film, reference support film are the support film adopting dimethyl silicone polymer to make; Described first hearth electrode, the first top electrode, the second hearth electrode, the second top electrode are the electrode adopted and be made of gold.Dimethyl silicone polymer has good biocompatibility and the low advantage of Young modulus because of it, makes active support film and is all provided with good biocompatibility and the low advantage of Young modulus with reference to support film.Jin Yinqi has excellent conductivity and is convenient to carry out biochemical responsive advantage of modifying, and makes the first hearth electrode, the first top electrode, the second hearth electrode, the second top electrode all be provided with excellent conductivity and is convenient to carry out biochemical responsive advantage of modifying.
By following experiment, can verify that circular support film and circular electrode can make sensor have higher sensitivity and less electric capacity edge effect further: as shown in Figure 3, Figure 4, utilize ANSYS software respectively to same homalographic, same parameter (at 10mJ/m
2under surface stress effect) quadrate support film and circular support film carry out finite element simulation.As shown in Figure 5, by same homalographic, same parameter (at 10mJ/m
2under surface stress effect) quadrate support film and the FEM Numerical Simulation of circular support film compare after draw: same to homalographic, same parameter are (at 10mJ/m
2under surface stress effect) circular support film maximum deflection can than square support film maximum deflection improve 20%.By following experiment, can verify when the area ratio of the first top electrode and active support film, the second top electrode are 0.9 with the area ratio with reference to support film further, sensor can obtain maximum sensitivity: as shown in Figure 6, Figure 7, utilizes ANSYS software to carry out finite element simulation to different area than the circular support film in situation.According to Fig. 6, when the area ratio of circular electrode and circular support film is 0.9, no matter the radius of circular support film is 200 μm or 250 μm, and circular support film all can realize maximum deflection.According to Fig. 7, when the area ratio of circular electrode and circular support film is 0.9, no matter the radius of circular support film is 200 μm or 250 μm, and the capacitance of electric capacity all can realize maximum change.Thus now sensor can obtain maximum sensitivity.Material properties, structural parameters and finite element model used in above-mentioned finite element simulation see the following form:
。
In sum, compared with answering power biological sensor with mems thin film body structure surface, a kind of High-sensitivity environmental compensation type capacitive surface stress biology sensor of the present invention is by optimizing the area ratio of the shape of film, material, electrode and film, effectively improve sensitivity, efficiently solve the problem that the sensitivity of existing surface stress biology sensor is low thus.
The present invention efficiently solves the problem that existing surface stress biology sensor signal to noise ratio (S/N ratio) is low and sensitivity is low, it can not only realize the detection of multiple atomic weak surface stress, and there is sensitivity, degree of accuracy is high, noise is little, good biocompatibility, simple to operate, be convenient to the series of advantages such as low cost production in enormous quantities, be applicable to the examination and controlling carrying out living matter and chemical substance.
Accompanying drawing explanation
Fig. 1 is structural representation of the present invention.
Fig. 2 is the structural representation of active support film of the present invention and the first top electrode.
Fig. 3 is the result figure utilizing the quadrate support film of ANSYS software to same homalographic, same parameter to carry out finite element simulation in the present invention.
Fig. 4 is the result figure utilizing the circular support film of ANSYS software to same homalographic, same parameter to carry out finite element simulation in the present invention.
Fig. 5 utilizes ANSYS software to carry out the results contrast statistical graph of finite element simulation to the quadrate support film of same homalographic, same parameter and circular support film in the present invention.
Fig. 6 is the result statistical graph of film deflection when utilizing ANSYS software to carry out finite element simulation to different area than the circular support film in situation in the present invention.
Fig. 7 is the result statistical graph of capacitance variations when utilizing ANSYS software to carry out finite element simulation to different area than the circular support film in situation in the present invention.
In figure: 1-substrate, the active support film of 2-, 3-reference support film, 4-first hearth electrode, 5-first top electrode, 6-second hearth electrode, 7-second top electrode, the biochemical sensitive layer of 8-.
Embodiment
A kind of High-sensitivity environmental compensation type capacitive surface stress biology sensor, comprises substrate 1; The upper surface of substrate 1 is fixed with active support film 2 and reference support film 3 respectively; The inner chamber of active support film 2 is provided with the first hearth electrode 4; First hearth electrode 4 attaches the upper surface being fixed on substrate 1; The outer end face of active support film 2 attaches and is fixed with the first top electrode 5; First hearth electrode 4 and the first top electrode 5 position just right; Inner chamber with reference to support film 3 is provided with the second hearth electrode 6; Second hearth electrode 6 attaches the upper surface being fixed on substrate 1; Outer end face with reference to support film 3 attaches and is fixed with the second top electrode 7; Second hearth electrode 6 and the second top electrode 7 position just right; The outer end face of active support film 2 is modified with biochemical sensitive layer 8;
Described active support film 2, reference support film 3 are circular support film; Described first hearth electrode 4, first top electrode 5, second hearth electrode 6, second top electrode 7 is circular electrode;
Area ratio, second top electrode 7 of described first top electrode 5 and active support film 2 are 0.9 with the area ratio with reference to support film 3;
Described active support film 2, reference support film 3 are the support film adopting dimethyl silicone polymer to make; Described first hearth electrode 4, first top electrode 5, second hearth electrode 6, second top electrode 7 is the electrode adopted and be made of gold;
During concrete enforcement, described substrate 1 adopts quartz or glass or silicon chip to make.
Claims (1)
1. a High-sensitivity environmental compensation type capacitive surface stress biology sensor, is characterized in that: comprise substrate (1); The upper surface of substrate (1) is fixed with active support film (2) and reference support film (3) respectively; The inner chamber of active support film (2) is provided with the first hearth electrode (4); First hearth electrode (4) attaches the upper surface being fixed on substrate (1); The outer end face of active support film (2) attaches and is fixed with the first top electrode (5); First hearth electrode (4) is just right with the first top electrode (5) position; Inner chamber with reference to support film (3) is provided with the second hearth electrode (6); Second hearth electrode (6) attaches the upper surface being fixed on substrate (1); Outer end face with reference to support film (3) attaches and is fixed with the second top electrode (7); Second hearth electrode (6) is just right with the second top electrode (7) position; The outer end face of active support film (2) is modified with biochemical sensitive layer (8);
Described active support film (2), reference support film (3) are circular support film; Described first hearth electrode (4), the first top electrode (5), the second hearth electrode (6), the second top electrode (7) are circular electrode;
Area ratio, second top electrode (7) of described first top electrode (5) and active support film (2) are 0.9 with the area ratio with reference to support film (3);
Described active support film (2), reference support film (3) are the support film adopting dimethyl silicone polymer to make; Described first hearth electrode (4), the first top electrode (5), the second hearth electrode (6), the second top electrode (7) are the electrode adopted and be made of gold.
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| CN202159037U (en) * | 2011-06-28 | 2012-03-07 | 陈英忠 | Film bulk acoustic wave resonance type biological sensor |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2007292564A (en) * | 2006-04-24 | 2007-11-08 | Hokkaido Univ | Biosensor chip |
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| US20050106570A1 (en) * | 2002-04-03 | 2005-05-19 | Japan Science And Technology Agency | Biochip sensor surface carrying polyethylene glycolated nanoparticles |
| CN1900305A (en) * | 2005-07-22 | 2007-01-24 | 中国科学院电子学研究所 | Biological sensor for detecting glutamic pyruvic transaminase |
| EP1808692A1 (en) * | 2006-01-13 | 2007-07-18 | Seiko Epson Corporation | Biochip, biosensor and inspection system |
| CN101661012A (en) * | 2009-08-11 | 2010-03-03 | 南京理工大学 | Microfilm capacitive type surface stress sensor used for biochemical detection and manufacture method thereof |
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