CN115452901B - A sensor with detection function and detection method - Google Patents
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- 238000001514 detection method Methods 0.000 title claims abstract description 143
- 239000000126 substance Substances 0.000 claims abstract description 23
- 239000002052 molecular layer Substances 0.000 claims abstract description 16
- 239000000758 substrate Substances 0.000 claims description 31
- 108091023037 Aptamer Proteins 0.000 claims description 9
- 230000005684 electric field Effects 0.000 claims description 7
- 230000003373 anti-fouling effect Effects 0.000 claims description 6
- 238000004364 calculation method Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000012528 membrane Substances 0.000 abstract description 4
- 230000009870 specific binding Effects 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 3
- 239000000463 material Substances 0.000 description 13
- 239000010408 film Substances 0.000 description 10
- 238000010008 shearing Methods 0.000 description 10
- 238000010586 diagram Methods 0.000 description 5
- 238000011895 specific detection Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 230000027455 binding Effects 0.000 description 2
- 238000011898 label-free detection Methods 0.000 description 2
- 239000002077 nanosphere Substances 0.000 description 2
- 238000011897 real-time detection Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000013077 target material Substances 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
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- G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
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Abstract
本发明属于MEMS生物传感检测技术领域，具体涉及一种具有检测功能的传感器及检测方法，包括检测单元，所述检测单元的质量负载变化发生在所述检测单元平面的垂直方向，所述检测单元的质量负载变化引起所述检测单元内部的电容变化，根据电容变化计算得到检测待检测物的浓度。在传感器敏感单元表面组装分子层膜用来特异性结合被检测物质，并将二者特异性结合前后的信号变化转化为电信号输出，实现待检测物质的实时、无标记、高灵敏度检测功能；同时设计参比检测单元去除噪音信号的影响，参比单元的设计提高了检测的准确性。
The present invention belongs to the field of MEMS biosensor detection technology, and specifically relates to a sensor with detection function and a detection method, including a detection unit, wherein the mass load change of the detection unit occurs in the vertical direction of the plane of the detection unit, and the mass load change of the detection unit causes the capacitance change inside the detection unit, and the concentration of the detected object is calculated based on the capacitance change. A molecular layer membrane is assembled on the surface of the sensor sensitive unit to specifically bind to the detected substance, and the signal change before and after the specific binding of the two is converted into an electrical signal output, so as to realize the real-time, label-free, and high-sensitivity detection function of the detected substance; at the same time, a reference detection unit is designed to remove the influence of noise signals, and the design of the reference unit improves the accuracy of detection.
Description
Technical Field
The invention relates to the technical field of MEMS biosensing detection, in particular to a sensor with a detection function and a detection method.
Background
At present, the traditional means such as PCR, ELISA, kit and the like are mainly adopted to detect the substances such as biomolecules. The rapid detection kit disclosed in patent application CN 114778838A is based on pathogen detection of near infrared fluorescent nanoparticles, and needs to observe the morphology and combination condition of bacteria captured by near infrared fluorescent nanospheres and superparamagnetic nanospheres through a transmission electron microscope or a fluorescence microscope to obtain a detection result, and the detection process has more interference factors and higher cost.
The existing sensor detection means still need fluorescent labeling, and have long detection time, complex operation and low sensitivity.
Thus, there is a need for a solution to the problems of the prior art.
Disclosure of Invention
In order to solve the above technical problems, according to one aspect of the present invention, the present invention provides a technical solution: the invention aims to provide a sensor with a detection function and an array which are used for realizing specific detection of a substance to be detected by using a shearing mode of a material in a liquid phase or gas phase environment based on MEMS process processing, and at least can solve part of problems in the prior art.
The sensor with the detection function comprises a detection unit, wherein the mass load change of the detection unit occurs in the vertical direction of the plane of the detection unit, the mass load change of the detection unit causes the capacitance change inside the detection unit, and the concentration of an object to be detected is obtained through calculation according to the capacitance change.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the sensor comprises a substrate, wherein the detection unit comprises an aptamer molecular layer film, a first upper conductive plate, a first substrate, a first support structure and two first lower conductive plates which are sequentially arranged from top to bottom; the two first lower conducting plates are arranged on the base plate at intervals, and the first supporting structure is connected between the first upper conducting plates and the first lower conducting plates, so that the first upper conducting plates are in a suspended state.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the first upper conductive plate and the first lower conductive plate are parallel to each other and are arranged at intervals.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the sensor further comprises a reference unit, wherein the reference unit comprises an antifouling molecular layer film, a second upper conductive plate, a second substrate, a second supporting structure and two second lower conductive plates which are sequentially arranged from top to bottom; the two second lower conductive plates are arranged on the substrate at intervals, the second supporting structure is connected between the second upper conductive plate and the second lower conductive plate, and the second upper conductive plate and the second lower conductive plate are parallel to each other and are arranged at intervals.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: and a sensitive film is arranged on the second upper conductive plate.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the first supporting structure and the second supporting structure comprise a support column and a supporting plate, the upper end of the support column is connected with the upper conducting plate, the lower end of the support column is connected with the upper end face of the supporting plate, and the lower end face of the supporting plate is connected with the lower conducting plate.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the first supporting structure and the second supporting structure are respectively connected with the lower conducting plate and symmetrically arranged at two ends of the bottom surface of the upper conducting plate.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the detection unit and the reference unit are adjacently arranged on the substrate.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the detection units and the reference units are adjacently arranged on the substrate to form sensor units, and the sensor units are distributed on the substrate along the axis of the substrate in an array manner.
As a preferable embodiment of the sensor with a detection function according to the present invention, wherein: the sensor also comprises a piezoelectric module, wherein the piezoelectric module drives the sensing unit array, and an alternating electric field is applied to the piezoelectric module.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects:
(1) According to the sensor with the detection function, after the mass load of the upper conductive plate and the lower conductive plate is changed, the relative area of the upper conductive plate and the lower conductive plate is changed, so that the capacitance value between the upper conductive plate and the lower conductive plate is changed, and the capacitance value is converted into an electric signal to be output, and further real-time and label-free detection of a substance to be detected is realized.
(2) According to the sensor with the detection function, the material to be detected is sheared by utilizing the shearing mode of the material, so that the detection sensitivity is improved, and the detection of the material to be detected is realized by realizing the specific detection and horizontal shearing to realize the minimum attenuation of signal energy.
(3) The sensor with the detection function can be used for subtracting the signal detected by the designed reference unit from the signal detected by the detection unit as the noise signal, so that an accurate detection signal is obtained, and the accuracy of detection is improved by the design of the reference unit.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to the structures shown in these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a sensor with detection function according to the present invention;
FIG. 2 is a schematic diagram of a sensor unit with detection function according to the present invention;
FIG. 3 is a schematic diagram of a sensor with detection function according to the present invention;
Fig. 4 is a schematic diagram of a sensor detection unit with detection function according to the present invention.
Reference numerals illustrate:
1-a detection unit, 2-a reference unit, 3-a piezoelectric module and 4-a substrate;
11-first upper conductive plate, 12-aptamer molecular layer membrane, 13-first substrate, 14-first support structure, 15-first lower conductive plate, 16-specific binding substance;
21-second upper conductive plate, 22-sensitive film, 23-second substrate, 24-second support structure, 25-second lower conductive plate, 26-antifouling molecular layer film.
The achievement of the objects, functional features and advantages of the present invention will be further described with reference to the accompanying drawings, in conjunction with the embodiments.
Detailed Description
The following description will be made clearly and fully with reference to the technical solutions in the embodiments, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that, if directional indications (such as up, down, left, right, front, and rear … …) are included in the embodiments of the present invention, the directional indications are merely used to explain the relative positional relationship, movement conditions, etc. between the components in a specific posture (as shown in the drawings), and if the specific posture is changed, the directional indications are correspondingly changed.
In addition, if there is a description of "first", "second", etc. in the embodiments of the present invention, the description of "first", "second", etc. is for descriptive purposes only and is not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In addition, the technical solutions of the embodiments may be combined with each other, but it is necessary to base that the technical solutions can be realized by those skilled in the art, and when the technical solutions are contradictory or cannot be realized, the combination of the technical solutions should be considered to be absent and not within the scope of protection claimed in the present invention.
The invention aims to provide an array sensor with a detection function, which is processed based on MEMS technology and uses the shearing mode of materials in a liquid phase or gas phase environment to realize specific detection of substances to be detected.
In order to achieve the above function, a technical solution of a sensor with a detection function is provided, which includes a detection unit 1, wherein a mass load change of the detection unit 1 occurs in a vertical direction of a plane of the detection unit 1, the mass load change of the detection unit 1 causes a capacitance change inside the detection unit 1, and a concentration of an object to be detected is obtained by calculating according to the capacitance change.
Example 1
The sensor with the detection function comprises a detection unit 1, wherein the mass load change of the detection unit 1 occurs in the vertical direction of the plane of the detection unit 1, the mass load change of the detection unit 1 causes the capacitance change inside the detection unit 1, and the concentration of an object to be detected is calculated according to the capacitance change. The detection unit 1 and the reference unit 2 are arranged adjacently on a substrate 4. The detection units 1 and the reference units 2 are adjacently arranged on the substrate 4 to form sensor units, and the sensor units are distributed on the substrate 4 along the axis of the substrate 4 in an array manner; the sensor further comprises a piezoelectric module 3, the piezoelectric module 3 drives the sensing unit array, and an alternating electric field is applied to the piezoelectric module 3.
As shown in fig. 1, the whole array is driven by a piezoelectric module 3, an alternating electric field is applied to the piezoelectric module 3, and under the action of the electric field, the crystal lattice of the piezoelectric crystal is changed to cause the whole piezoelectric crystal to vibrate mechanically, so that shearing force in the X-Y direction is generated on the sensing array, and the minimum energy attenuation can be kept in a liquid phase or gas phase detection environment.
As shown in the schematic structural diagram of fig. 1, the detection unit 1 and the reference unit 2 are adjacently arranged, and simultaneously shear horizontally in the X-Y direction under the action of the inverse piezoelectric effect of the piezoelectric crystal, and both adopt conductive materials to deposit a conductive layer with a certain thickness on the surface of the substrate, and an aptamer molecular layer 12 and an anti-fouling molecular layer 26 for binding the specific binding substance 12 are assembled on the surface of the upper conductive layer. The upper conductive layer and the lower conductive plate are separated by a pillar structure, the upper conductive plate is connected by a supporting structure to be in a suspended state, the upper conductive plate is horizontally sheared in a detection environment, and after substances to be detected are added to the surface of the array, non-specific binding substances can be removed by the shearing force, and a real detection signal is obtained after noise signals of the reference unit 2 are removed. The shearing mode of the material is utilized to realize the specific detection of the substances to be detected, the horizontal shearing is realized to realize the minimum attenuation of signal energy, the high-sensitivity detection of the substances to be detected is realized, and the detection sensitivity is improved.
Example 2
The sensor with the detection function comprises a detection unit 1, wherein the mass load change of the detection unit 1 occurs in the vertical direction of the plane of the detection unit 1, the mass load change of the detection unit 1 causes the capacitance change inside the detection unit 1, and the concentration of an object to be detected is obtained through calculation according to the capacitance change. The detection unit 1 and the reference unit 2 are arranged adjacently on a substrate 4.
The detection unit 1 comprises an aptamer molecular layer membrane 12, a first upper conductive plate 11, a first substrate 13, a first support structure 14 and two first lower conductive plates 15 which are sequentially arranged from top to bottom; two first lower conductive plates 15 are disposed on the substrate 4 at intervals, and a first supporting structure 14 is connected between the first upper conductive plate 11 and the first lower conductive plate 15, so that the first upper conductive plate 11 is in a suspended state. The first upper conductive plate 11 and the first lower conductive plate 15 are parallel to each other and spaced apart from each other.
As shown in fig. 2, a supporting structure is adopted on the surface of the substrate 4 of the detection unit 1 to enable the detection unit 1 to be in a suspended state, after a substance to be detected is combined with the aptamer molecular layer film 12, the surface quality load of the detection unit 1 is changed, and under a shearing state, the relative area and/or the relative distance between the first upper conductive plate 11 and the first lower conductive plate 15 is changed, so that the capacitance is changed, and as shown in fig. 4, the detection is finally realized. After the mass load of the first upper conductive plate 11 changes, the relative area of the first upper conductive plate and the second upper conductive plate changes, so that the capacitance value between the first upper conductive plate and the second upper conductive plate changes, and the capacitance value is converted into an electric signal to be output, thereby realizing real-time and label-free detection of a substance to be detected.
It should be noted that, when the relative areas of the first upper conductive plate 11, the aptamer molecular layer 12, the specific binding material 26 and the first lower conductive plate 15 are all changed, the difference between the relative area when the first conductive plate is not moved and the relative area when the second conductive plate is finally moved is the difference, wherein Δd1 represents the change in length of the relative coincidence of the upper and lower electrode plates when the surface of the sensitive layer is only increased by the weight of the aptamer; Δd2 represents the change in length of the relative coincidence of the upper and lower electrode plates as the weight of the aptamer and target material after binding increases on the surface of the sensitive layer.
Example 3
The sensor with the detection function comprises a detection unit 1, wherein the mass load change of the detection unit 1 occurs in the vertical direction of the plane of the detection unit 1, the mass load change of the detection unit 1 causes the capacitance change inside the detection unit 1, and the concentration of an object to be detected is obtained through calculation according to the capacitance change. The detection unit 1 and the reference unit 2 are arranged adjacently on a substrate 4.
The sensor further comprises a reference unit 2, wherein the reference unit 2 comprises an antifouling molecular layer film 26, a second upper conductive plate 21, a second substrate 23, a second supporting structure 24 and two second lower conductive plates 25 which are arranged in sequence from top to bottom; two second lower conductive plates 25 are disposed on the substrate 4 at intervals, and a second supporting structure 24 is connected between the second upper conductive plate 21 and the second lower conductive plate 25, and the second upper conductive plate 21 and the second lower conductive plate 25 are disposed parallel to each other and at intervals. The second upper conductive plate 21 is provided with a sensitive film 22.
The first support structure 14 and the second support structure 24 each comprise a pillar and a support plate, the upper ends of the pillars are connected with the upper conductive plates, the lower ends of the pillars are connected with the upper end surfaces of the support plates, and the lower end surfaces of the support plates are connected with the lower conductive plates. The first support structure 14 and the second support structure 24 are respectively connected with the lower conductive plate, and symmetrically arranged at two ends of the bottom surface of the upper conductive plate.
It should be noted that the first support structure 14 and the second support structure 24 should meet the telescopic deformation along their longitudinal direction but not generate significant deformation in the lateral direction to increase the sensitivity of detection; it should be understood that the choice of material and the choice of support strength will vary with the object to be tested.
As shown in fig. 3, the surface of the reference unit 2 is provided with an antifouling molecular layer film 26, so that the nonspecific combination of the substance to be detected and the unit structure can be effectively prevented, and the signal detected by the reference unit 2 can be used as a noise signal to be subtracted from the signal of the detection unit 1, thereby obtaining an accurate detection signal. The design of the reference cell 2 improves the accuracy of the detection.
Example 4
The embodiment 4 of the invention provides a detection method of a sensor with a detection function, which specifically comprises the following steps:
Applying an alternating electric field to a piezoelectric module in the sensor, and immersing the sensor into a solution to be detected containing an object to be detected;
Setting detection temperature and detection time to enable the sensor unit to be fully combined with the substance to be detected;
gradually increasing the concentration of the substance to be detected in the solution to be detected, comparing the color change and the degree of the detection surfaces of the detection unit and the reference unit, and obtaining the detection limit of the substance to be detected by the detection unit through calculation.
In summary, compared with the prior art, the invention provides a sensor with detection function and an array which are processed based on MEMS technology and are used for realizing specific detection of substances to be detected in a liquid phase or gas phase environment by using a shearing mode of materials. After the mass load of the upper conductive plate and the lower conductive plate is changed, the relative area of the upper conductive plate and the lower conductive plate is changed, so that the capacitance value between the upper conductive plate and the lower conductive plate is changed, and the capacitance value is converted into an electric signal to be output, thereby realizing real-time, label-free and high-sensitivity detection of a substance to be detected. Meanwhile, the whole array comprises a detection unit 1 and a reference unit 2, and the signal of the detection unit 1 can be accurately read by subtracting the noise signal of the reference unit 2.
Furthermore, the detection unit 1 may be an optical and/or piezoresistive detection unit 1 and/or a surface stress detection unit 1 to realize a detection function, and the present application is not limited to the structure thereof. Those skilled in the art will appreciate that any known detection technique may be used. The basic technique in MEMS fabrication involves depositing a thin film of material onto a substrate, applying a pattern to the film by photolithographic imaging, and any type of known material may be used to construct a MEMS device. The choice of materials for the aptamer molecular layer 12, the sensing membrane 22 and the anti-fouling molecular layer 26 may be any type of known materials for performing the detection process.
The foregoing description is only of the preferred embodiments of the present invention and is not intended to limit the scope of the invention, and all equivalent structural changes made by the content of the present invention or direct/indirect application in other related technical fields are included in the scope of the present invention.
Claims (9)
1. A sensor with detection function, characterized in that: the device comprises a detection unit, wherein the mass load change of the detection unit occurs in the vertical direction of the plane of the detection unit, the mass load change of the detection unit causes the capacitance change in the detection unit, and the concentration of an object to be detected is obtained through calculation according to the capacitance change; the sensor comprises a substrate, wherein the detection unit comprises an aptamer molecular layer film, a first upper conductive plate, a first substrate, a first support structure and two first lower conductive plates which are sequentially arranged from top to bottom; the two first lower conducting plates are arranged on the base plate at intervals, and the first supporting structure is connected between the first upper conducting plates and the first lower conducting plates, so that the first upper conducting plates are in a suspended state.
2. A sensor with detection function according to claim 1, characterized in that: the first upper conductive plate and the first lower conductive plate are parallel to each other and are arranged at intervals.
3. A sensor with detection function according to claim 2, characterized in that: the sensor further comprises a reference unit, wherein the reference unit comprises an antifouling molecular layer film, a second upper conductive plate, a second substrate, a second supporting structure and two second lower conductive plates which are sequentially arranged from top to bottom; the two second lower conductive plates are arranged on the substrate at intervals, the second supporting structure is connected between the second upper conductive plate and the second lower conductive plate, and the second upper conductive plate and the second lower conductive plate are parallel to each other and are arranged at intervals.
4. A sensor with detection function according to claim 3, characterized in that: and a sensitive film is arranged on the second upper conductive plate.
5. A sensor with detection function according to claim 3, characterized in that: the first supporting structure and the second supporting structure comprise a support column and a supporting plate, the upper end of the support column is connected with the upper conducting plate, the lower end of the support column is connected with the upper end face of the supporting plate, and the lower end face of the supporting plate is connected with the lower conducting plate.
6. A sensor with detection function according to claim 3, characterized in that: the first supporting structure and the second supporting structure are respectively provided with two groups, and are symmetrically arranged at two ends of the bottom surface of the upper conducting plate after being connected with the lower conducting plate.
7. A sensor with detection function according to claim 3, characterized in that: the detection units and the reference units are adjacently arranged on the substrate to form sensor units, and the sensor units are distributed on the substrate along the axis of the substrate in an array manner.
8. A sensor with detection function according to claim 3, characterized in that: the sensor also comprises a piezoelectric module, the piezoelectric module drives the sensing unit array, an alternating electric field is applied to the piezoelectric module, and the detection unit moves back and forth on a plane in a preset direction.
9. A detection method using the sensor having a detection function according to any one of claims 1 to 8, the specific method comprising:
Applying an alternating electric field to a piezoelectric module in the sensor, and immersing the sensor into a solution to be detected containing an object to be detected;
Setting detection temperature and detection time to enable the sensor unit to be fully combined with the substance to be detected;
gradually increasing the concentration of the substance to be detected in the solution to be detected, comparing the color change and the degree of the detection surfaces of the detection unit and the reference unit, and obtaining the detection limit of the substance to be detected by the detection unit through calculation.
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| US6864692B1 (en) * | 2002-06-20 | 2005-03-08 | Xsilogy, Inc. | Sensor having improved selectivity |
| US7340941B1 (en) * | 2002-10-01 | 2008-03-11 | Xsilogy, Inc. | Dense thin film-based chemical sensors and methods for making and using same |
| AU2003287560A1 (en) * | 2002-11-06 | 2004-06-03 | Carnegie Mellon University | Mems membrane based sensor |
| CN101514990B (en) * | 2008-02-21 | 2014-01-29 | 天津先阳科技发展有限公司 | Sensor for sensing contents of components to be measured in human tissue fluid, fluid channel unit and method for measuring contents of components to be measured in human tissue fluid |
| GB2489504A (en) * | 2011-03-31 | 2012-10-03 | Sapient Sensors | A device for identifying the presence of a specific target molecule or biomarker by sensing an electrical property |
| CN203786076U (en) * | 2014-04-24 | 2014-08-20 | 西安科技大学 | Differential capacitive methane concentration sensing structure |
| CN104891418B (en) * | 2015-05-29 | 2016-09-21 | 歌尔股份有限公司 | MEMS pressure sensor, MEMS inertial sensor integrated structure |
| KR101842350B1 (en) * | 2016-05-17 | 2018-05-14 | 박주성 | The measurement apparatus for capacitive membrane sensor using mechanical resonance characteristics of membrane and the method thereof |
| CN105823749B (en) * | 2016-05-18 | 2019-04-23 | 南京信息工程大学 | A MEMS-based capacitive infrared gas sensor |
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