CN115452911A - MEMS detection sensor and detection method - Google Patents
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Abstract
The invention belongs to the technical field of sensors for biomolecule detection, and particularly relates to an MEMS sensor with a detection function and a detection method, wherein a molecular layer film can be assembled on the surface of a sensor sensitive unit for specifically binding a detected substance, and the signal change before and after the specific binding of the molecular layer film and the detected substance is converted into an electric signal to be output for realizing detection, so that the technical problems of complex operation and low detection efficiency caused by the adoption of fluorescent markers in the traditional PCR and ELISA detection methods are solved.
Description
Technical Field
The invention relates to the technical field of sensors for biomolecule detection, in particular to an MEMS sensor with a detection function and a detection method.
Background
Molecular detection refers to a technique for diagnosing by detecting a change in the structure or expression level of genetic material in a patient's body using molecular biological methods. Molecular detection is a main method for prediction diagnosis, and can be used for diagnosis of individual genetic diseases and prenatal diagnosis. Molecular diagnosis mainly refers to the detection of genes encoding various structural proteins, enzymes, antigens, antibodies, and immunologically active molecules associated with diseases.
The conventional detection methods for molecular detection include PCR, ELISA, electron microscopy, gene chip, etc. PCR is also called as polymeric chain reaction, and is a method for rapidly amplifying gene segments in vitro, which can amplify specific gene segments in a small amount of genomic DNA or RNA samples millions of times in a short time of several hours, and has high specificity and accuracy. ELISA is also called enzyme-linked immunosorbent assay, and refers to a qualitative and quantitative detection method for binding soluble antigen or antibody to solid phase carriers such as polystyrene and performing immunoreaction by utilizing specific binding of antigen and antibody.
PCR and ELISA are the most common means for rapidly detecting food pathogenic bacteria at present, but because both methods need to use a fluorescence labeling method, the detection function is realized through a series of complex biochemical treatment processes, the operation is more complicated, the hybridization time is long, often several hours or even several days are needed, the price of probe labeling and modification is high, the detection time of the pathogenic bacteria is not reduced fundamentally, the detection speed is not increased, and the actual rapid detection requirement is difficult to meet.
Therefore, a solution is needed to solve the problems in the prior art in order to solve the technical problems of long detection time and low sensitivity of the sensor requiring fluorescent labeling in the detection process in the current molecular detection field.
MEMS sensors, i.e. micro-electromechanical systems, are new types of sensors manufactured by using microelectronics and micromachining techniques. Compared with the traditional sensor, the sensor has the characteristics of small volume, light weight, low cost, low power consumption, high reliability, suitability for batch production, easiness in integration and realization of intellectualization. At the same time, feature sizes on the order of microns make it possible to perform functions that some conventional mechanical sensors cannot achieve. The MEMS sensor has the characteristics of high detection speed, high sensitivity, strong practicability and low-cost detection as a novel detection technology, gradually becomes the focus of attention in the fields of various molecular detection, biomedicine, chemistry, environmental engineering and the like, and receives more and more attention and research.
Disclosure of Invention
The invention provides a MEMS detection sensor which can at least solve part of problems in the prior art.
In order to solve the above technical problems, according to one aspect of the present invention, the present invention provides the following technical solutions:
a MEMS detection sensor comprises a sensor unit and a piezoelectric module, wherein the piezoelectric module is arranged on one side of the sensor unit;
the sensor unit comprises an upper conductive plate, a lower conductive plate and a supporting structure, wherein the upper conductive plate of the sensor unit is in a suspended state under the support of the supporting structure, an aptamer molecular layer membrane for specific binding is arranged on the surface of the upper conductive plate, and after the aptamer molecular layer membrane is specifically bound with a substance to be detected, the relative area and/or the relative distance between the upper conductive plate and the lower conductive plate are/is changed.
As a preferable aspect of the MEMS detection sensor according to the present invention, wherein: the sensor unit is arranged above the substrate and arranged in an array structure, and comprises a detection unit and a reference unit which are arranged on the substrate and adjacent to each other.
As a preferable aspect of the MEMS detection sensor according to the present invention, wherein: the support structure includes interconnect's pillar structure and snakelike beam structure, wherein: the both ends of snake-shaped beam structure connect respectively go up the current conducting plate with the pillar structure, the current conducting plate sets up down the substrate surface, the pillar structure sets up the outer edge of current conducting plate down, go up the current conducting plate both sides respectively with snake-shaped beam structural connection.
As a preferable aspect of the MEMS detection sensor according to the present invention, wherein: the piezoelectric module is connected with the alternating electric field.
As a preferable aspect of the MEMS detection sensor according to the present invention, wherein: the connecting line between the two ends of the snake-shaped beam structure and the connecting line of the centers of the upper conductive plate and the lower conductive plate are the same straight line.
As a preferable aspect of the MEMS detection sensor according to the present invention, wherein: and the surface of the upper conductive plate is also provided with a sensitive layer.
As a preferable aspect of the MEMS detection sensor according to the present invention, wherein: the sensitive layer is made of any one of metal and two-dimensional materials.
As a preferable aspect of the MEMS detection sensor according to the present invention, wherein: and the surface of the upper conductive plate of the reference unit is provided with an antifouling molecular layer for preventing nonspecific combination.
In order to solve the above technical problem, according to another aspect of the present invention, the present invention provides the following technical solutions:
a detection method of a MEMS detection sensor comprises the following steps:
applying an alternating electric field to a piezoelectric module of the MEMS detection sensor, and then immersing the piezoelectric module into a solution to be detected containing a substance to be detected;
setting detection temperature and detection time to fully combine the sensor unit with the substance to be detected;
and obtaining the detection limit of the substance to be detected according to the detection results of the detection unit and the reference unit.
As a preferable aspect of the detection method of the MEMS detection sensor according to the present invention, wherein: the step of obtaining the detection limit of the substance to be detected according to the detection results of the detection unit and the reference unit comprises the following steps:
and gradually increasing the concentration of the substance to be detected in the solution to be detected from zero, adding the solution to be detected to the surface area of the sensitive membrane of the detection unit, comparing the color change and the degree of the surfaces of the detection unit and the reference unit, and calculating to obtain the detection limit of the substance to be detected by the detection unit.
The invention has the following beneficial effects:
1. the invention provides a novel MEMS detection sensor structure, which utilizes an aptamer molecular layer film on the surface of a sensor to perform specific binding on a substance to be detected, converts signal change before and after detection into an electric signal to output, does not need to adopt the operation of fluorescence labeling in the traditional PCR and ELISA detection method, can greatly reduce detection operation and detection time, greatly improves detection efficiency and detection sensitivity, and can reach ng/ml.
2. The MEMS detection sensor provided by the invention comprises a detection unit and a reference unit, wherein a sensitive layer metal film and an aptamer molecular layer film are arranged on the surface of the detection unit, specific binding can be carried out on a substance to be detected, an antifouling molecular layer is modified on the surface of the reference unit, non-specific binding of the substance to be detected can be prevented, a detection signal of the reference unit can be used as noise, the detection limit of the substance to be detected can be calculated through the detection difference value of the detection unit and the reference unit, the detection operation is simple, and the detection efficiency and the detection precision are obviously improved.
3. The sensor array is driven by the piezoelectric module, and compared with other driving modes, the piezoelectric driving mode has the advantages of simple structure, low power consumption, high response speed, high temperature resistance and strong anti-jamming capability.
4. By applying an alternating electric field on the piezoelectric module, the crystal lattice of the piezoelectric crystal is changed to cause integral mechanical vibration under the action of the electric field, so that shearing force in the X-Y direction is generated on the sensor array, and the shearing force in the X-Y direction has no component in the Z-axis direction, so that the acoustic wave energy is not vertically dissipated into liquid, the acoustic wave energy is guaranteed to be limited on the surface of a chip, the minimum energy attenuation can be kept in a liquid phase detection environment, and the detection of a target substance is realized. When the substance to be detected is added to the sensor array, the shearing force can also effectively remove non-specific binding substances, thereby improving the authenticity and the accuracy of detection.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the structures shown in the drawings without creative efforts.
FIG. 1 is a schematic view of the MEMS detection sensor array structure of the present invention;
FIG. 2 is a schematic diagram of the MEMS detection sensor unit structure of the present invention;
FIG. 3 is a schematic diagram of the structure of the detection cell and the reference cell of the MEMS detection sensor cell of the present invention;
fig. 4 is a schematic diagram illustrating the detection principle of the MEMS detection sensor according to the present invention.
The reference numbers illustrate:
the sensor comprises a sensor unit 1, a piezoelectric module 2, a detection unit 3, a reference unit 4, a substrate 5, an upper conductive plate 6, a lower conductive plate 7, a pillar structure 8, a serpentine beam structure 9, an aptamer molecular layer membrane 10, an antifouling molecular layer 11, a specific binding substance 12 and a sensitive layer 13.
The implementation of the objects, functional features and advantages of the present invention will be further explained with reference to the accompanying drawings.
Detailed Description
The following will clearly and completely describe the technical solutions in the embodiments, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that, if the present invention is related to directional indications (such as up, down, left, right, front, and back \8230;), the directional indications are only used to explain the relative position relationship between the components, the motion situation, etc. in a specific posture (as shown in the attached drawings), and if the specific posture is changed, the directional indications are correspondingly changed.
In addition, if the embodiments of the present invention have been described with reference to "first", "second", etc., the descriptions of "first", "second", etc. are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In addition, technical solutions between various embodiments may be combined with each other, but must be realized by a person skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination should not be considered to exist, and is not within the protection scope of the present invention.
The invention provides an MEMS detection sensor and a detection method, which can conveniently and rapidly realize the concentration detection of a substance to be detected, and the detection method has the advantages of simple operation and excellent detection sensitivity and accuracy.
A MEMS detection sensor comprises a sensor unit and a piezoelectric module, wherein the piezoelectric module is arranged on one side of the sensor unit;
the sensor unit comprises an upper conductive plate, a lower conductive plate and a supporting structure, wherein the upper conductive plate of the sensor unit is in a suspended state under the support of the supporting structure, an aptamer molecular layer film for specific binding is arranged on the surface of the upper conductive plate, and after the aptamer molecular layer film is specifically bound with a substance to be detected, the relative area and/or relative distance between the upper conductive plate and the lower conductive plate are/is changed.
The sensor unit is arranged above the substrate and arranged in an array structure, and comprises a detection unit and a reference unit which are arranged on the substrate adjacent to each other.
The support structure includes interconnect's pillar structure and snakelike beam structure, wherein: two ends of the snake-shaped beam structure are respectively connected with an upper conductive plate and the pillar structure, the lower conductive plate is arranged on the surface of the substrate, the pillar structure sets up the outer edge of current conducting plate down, go up the current conducting plate both sides respectively with snakelike roof beam structural connection. The piezoelectric module is connected with the alternating electric field. And a connecting line between two ends of the snake-shaped beam structure and a central connecting line of the upper conductive plate and the lower conductive plate are the same straight line. And the surface of the upper conductive plate is also provided with a sensitive layer. The sensitive layer is made of any one of metal and two-dimensional materials; specifically, the sensitive layer is a metal film, and the metal film of the sensitive layer may be a gold film. And the surface of the upper conductive plate of the reference unit is provided with an antifouling molecular layer for preventing nonspecific binding.
The upper conducting plate is suspended through the supporting structure and forms a certain distance interval with the lower conducting plate, after the substance to be detected is specifically combined with the aptamer molecular layer membrane, the mass load on the surface of the detection unit is changed, the relative area between the upper conducting plate and the lower conducting plate is changed, the change of capacitance is generated, and the concentration of the substance to be detected can be calculated according to the change difference value of the substance to be detected before and after the load.
The detection sensor is provided with a piezoelectric module, and the piezoelectric module is used for driving the whole sensor array. By applying an alternating electric field on the piezoelectric module, under the action of the electric field, the crystal lattice of the piezoelectric crystal is changed to cause overall mechanical vibration, so that shearing force in the X-Y direction is generated on the sensor array, and the minimum energy attenuation can be kept in a liquid phase detection environment. When the substance to be detected is added to the sensor array, the shearing force can also effectively remove non-specific binding substances, thereby improving the authenticity and the accuracy of detection.
According to another aspect of the present invention, there is also provided a detection method of a detection sensor.
A detection method of a MEMS detection sensor comprises the following steps:
applying an alternating electric field to a piezoelectric module of the MEMS detection sensor, and then immersing the piezoelectric module into a solution to be detected containing a substance to be detected;
setting detection temperature and detection time to fully combine the sensor unit with the substance to be detected;
and obtaining the detection limit of the substance to be detected according to the detection results of the detection unit and the reference unit.
The step of obtaining the detection limit of the substance to be detected according to the detection results of the detection unit and the reference unit comprises the following steps:
and gradually increasing the concentration of the substance to be detected in the solution to be detected from zero, adding the solution to be detected to the surface area of the sensitive membrane of the detection unit, comparing the color change and degree of the surfaces of the detection unit and the reference unit, and calculating to obtain the detection limit of the substance to be detected by the detection unit.
A sensitive layer metal film or a two-dimensional material layer, such as a gold film, is arranged on the upper conductive plate, so that the surface activity of the upper conductive plate can be enhanced.
Example 1
Embodiment 1 of the present invention provides a MEMS detection sensor, as shown in fig. 1 to 4.
A MEMS detection sensor comprises a sensor unit 1 and a piezoelectric module 2, wherein the piezoelectric module 2 is arranged on one side of the sensor unit 1;
sensor unit 1 is including last current conducting plate 6, lower current conducting plate 7 and bearing structure, sensor unit 1's last current conducting plate 6 is in be in unsettled state under bearing structure's the support, 6 surfaces of going up the current conducting plate are provided with the adaptation body molecular layer membrane 10 that is used for the specificity to combine, after adaptation body molecular layer membrane 10 and the material of waiting to detect take place the specificity to combine, go up current conducting plate 6 with the relative area and/or the relative distance of current conducting plate 7 change down.
The sensor unit 1 is arranged above the substrate 5 and arranged in an array structure, the sensor unit 1 comprises a detection unit 3 and a reference unit 4, and the detection unit 3 and the reference unit 4 are arranged adjacent to each other on the substrate 5.
The support structure comprises an interconnected strut structure 8 and a serpentine beam structure 9, wherein: the both ends of snakelike beam structure 9 connect respectively go up the current conducting plate 6 with prop structure 8, the current conducting plate 7 sets up 5 surfaces of base plate, prop structure 8 sets up the outer edge of current conducting plate 7 down, go up 6 both sides of current conducting plate respectively with snakelike beam structure 9 is connected.
The piezoelectric module 2 is connected with an alternating electric field. And a connecting line between two ends of the serpentine beam structure 9 and a central connecting line of the upper conductive plate 6 and the lower conductive plate 7 are the same straight line. The surface of the upper conductive plate 6 is also provided with a sensitive layer 13, and the sensitive layer 13 is a gold film. The surface of the upper conductive plate 6 of the reference cell 4 is provided with an anti-fouling molecular layer 11 that prevents non-specific binding.
Example 2
The embodiment 2 of the invention provides a detection method of an MEMS detection sensor.
A detection method of a MEMS detection sensor comprises the following steps:
applying an alternating electric field to a piezoelectric module of the MEMS detection sensor, and then immersing the piezoelectric module into a solution to be detected containing a substance to be detected;
setting detection temperature and detection time to fully combine the sensor unit with the substance to be detected;
and obtaining the detection limit of the substance to be detected according to the detection results of the detection unit and the reference unit.
The step of obtaining the detection limit of the substance to be detected according to the detection results of the detection unit and the reference unit comprises the following steps:
and gradually increasing the concentration of the substance to be detected in the solution to be detected from zero, adding the solution to be detected to the surface area of the sensitive membrane of the detection unit, comparing the color change and the degree of the surfaces of the detection unit and the reference unit, and calculating to obtain the detection limit of the substance to be detected by the detection unit.
The detection unit is characterized in that an aptamer molecular layer film is arranged on the surface of the detection unit and comprises magnetic spheres for capturing cancer cell antibodies and can be used for specifically binding cancer cells of a substance to be detected, an antifouling molecular layer is modified on the surface of the reference unit and is serum protein, the nonspecific binding of the substance to be detected can be prevented, the measurement value of the reference electrode is used as noise, the concentration of the substance to be detected can be calculated through the detection difference value of the detection unit and the reference unit, the detection operation is simple, the detection efficiency and the detection precision are obviously improved, and the detection sensitivity can reach ng/ml.
By applying an alternating electric field on the piezoelectric module, under the action of the electric field, the crystal lattice of the piezoelectric crystal is changed to cause overall mechanical vibration, so that shearing force in the X-Y direction is generated on the sensor array, and the minimum energy attenuation can be kept in a liquid phase detection environment. When the substance to be detected is added to the sensor array, the shearing force can also effectively remove non-specific binding substances, thereby improving the authenticity and the accuracy of detection.
The above description is only a preferred embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications and equivalents of the present invention, which are made by the present specification and directly/indirectly applied to other related technical fields within the spirit of the present invention are included in the scope of the present invention.
Claims (10)
1. A MEMS detection sensor, comprising: the sensor comprises a sensor unit (1) and a piezoelectric module (2), wherein the piezoelectric module (2) is arranged on one side of the sensor unit (1);
sensor unit (1) is including last current conducting plate (6), lower current conducting plate (7) and bearing structure, last current conducting plate (6) of sensor unit (1) are in be in unsettled state under bearing structure's the support, it is provided with adaptation body molecular layer membrane (10) that are used for the specificity to combine to go up current conducting plate (6) surface, after adaptation body molecular layer membrane (10) and the material of waiting to detect take place the specificity to combine, go up current conducting plate (6) with the relative area and/or the relative distance of current conducting plate (7) change down.
2. A MEMS detection sensor as claimed in claim 1 wherein: the sensor unit (1) is arranged above the substrate (5) and is arranged in an array structure, the sensor unit (1) comprises a detection unit (3) and a reference unit (4), and the detection unit (3) and the reference unit (4) are arranged on the substrate (5) in an adjacent mode.
3. A MEMS detection sensor as claimed in claim 2 wherein: the support structure comprises an interconnected strut structure (8) and a serpentine beam structure (9), wherein: the both ends of snake-shaped beam structure (9) are connected respectively and are gone up current conducting plate (6) and pillar structure (8), current conducting plate (7) set up down base plate (5) surface, pillar structure (8) set up the outward flange department of current conducting plate (7) down, go up current conducting plate (6) both sides respectively with snake-shaped beam structure (9) are connected.
4. A MEMS detection sensor as claimed in claim 1 wherein: the piezoelectric module (2) is connected with the alternating electric field.
5. A MEMS detection sensor as claimed in claim 3 wherein: and a connecting line between two ends of the snake-shaped beam structure (9) and a central connecting line of the upper conductive plate (6) and the lower conductive plate (7) are the same straight line.
6. A MEMS detection sensor as claimed in claim 1 wherein: and the surface of the upper conductive plate (6) is also provided with a sensitive layer (13).
7. A MEMS detection sensor according to claim 5 wherein: the sensitive layer (13) is made of any one of metal and two-dimensional materials.
8. A MEMS detection sensor as claimed in claim 1 wherein: the surface of the upper conductive plate (6) of the reference unit (4) is provided with an anti-fouling molecular layer (11) for preventing non-specific binding.
9. Method of detection of a MEMS detection sensor according to any of the claims 1-8, comprising the steps of:
applying an alternating electric field to a piezoelectric module of the MEMS detection sensor, and then immersing the piezoelectric module into a solution to be detected containing a substance to be detected;
setting detection temperature and detection time to fully combine the sensor unit with the substance to be detected;
and obtaining the detection limit of the substance to be detected according to the detection results of the detection unit and the reference unit.
10. The method for detecting a MEMS detection sensor as recited in claim 9, wherein the step of deriving the detection limit of the substance to be detected based on the detection results of the detection cell and the reference cell comprises the steps of:
and gradually increasing the concentration of the substance to be detected in the solution to be detected from zero, adding the solution to be detected to the surface area of the sensitive membrane of the detection unit, comparing the color change and the degree of the surfaces of the detection unit and the reference unit, and calculating to obtain the detection limit of the substance to be detected by the detection unit.
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| CN107007287A (en) * | 2017-05-23 | 2017-08-04 | 中国科学院电子学研究所 | Biomolecule detection devices and method |
| CN114050168A (en) * | 2022-01-13 | 2022-02-15 | 中国人民解放军火箭军工程大学 | Medical imaging-oriented semiconductor silicon-based hybrid imaging chip and preparation method thereof |
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2022
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| KR20050096469A (en) * | 2004-03-30 | 2005-10-06 | 전자부품연구원 | Chemical sensor using piezoelectric microcantilever and manufacturing method thereof |
| JP2009139102A (en) * | 2007-12-03 | 2009-06-25 | Canon Inc | Detecting element, substrate for same, and manufacturing methods thereof |
| CN103919616A (en) * | 2014-05-06 | 2014-07-16 | 苏州大学 | Device and method for artificial organ surface blood coagulation detection |
| CN107007287A (en) * | 2017-05-23 | 2017-08-04 | 中国科学院电子学研究所 | Biomolecule detection devices and method |
| CN114050168A (en) * | 2022-01-13 | 2022-02-15 | 中国人民解放军火箭军工程大学 | Medical imaging-oriented semiconductor silicon-based hybrid imaging chip and preparation method thereof |
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