CN111468198B - Detection chip - Google Patents
Detection chip Download PDFInfo
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- CN111468198B CN111468198B CN202010300377.4A CN202010300377A CN111468198B CN 111468198 B CN111468198 B CN 111468198B CN 202010300377 A CN202010300377 A CN 202010300377A CN 111468198 B CN111468198 B CN 111468198B
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
Abstract
The invention provides a detection chip, belongs to the technical field of biological medicines, and can at least partially solve the problem of unstable detection of the existing detection chip. The detection chip of the embodiment of the invention comprises: the detection device comprises a substrate, a detection area and a detection area, wherein the detection area is used for bearing a sample to be detected, interdigital electrodes and an insulating layer covering the interdigital electrodes are formed on the substrate of the detection area, the interdigital electrodes comprise first electrodes and second electrodes, the first electrodes comprise a plurality of first electrode strips which are arranged at intervals and electrically connected, the second electrodes comprise a plurality of second electrode strips which are arranged at intervals and electrically connected, and the first electrode strips and the second electrode strips are arranged in a rotating mode and are mutually spaced; and the signal unit is respectively connected with the first electrode and the second electrode of the interdigital electrode, and is used for applying a radio-frequency signal to the interdigital electrode and detecting the electromagnetic parameters of the interdigital electrode so as to determine the concentration of the substance to be detected in the sample to be detected according to the electromagnetic parameters.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a detection chip.
Background
With the increase of health importance, the detection of blood glucose concentration and other basic physical indicators in blood has become an examination item for more and more people to perform regularly. The detection chip is used for detecting the indexes simply and conveniently, and the method is a mainstream detection scheme at present.
The existing detection chip (such as a detection chip for detecting the blood sugar concentration in blood) mainly utilizes three electrodes to detect the blood sugar, and the scheme needs glucose oxidase/dehydrogenase to participate, so that the detection result is unstable.
Disclosure of Invention
The invention at least partially solves the problem of unstable detection of the existing detection chip and provides a detection chip for stable detection.
One aspect of the present invention provides a detection chip, including:
the detection device comprises a substrate, a detection area and a detection area, wherein the detection area is used for bearing a sample to be detected, interdigital electrodes and an insulating layer covering the interdigital electrodes are formed on the substrate of the detection area, the interdigital electrodes comprise first electrodes and second electrodes, the first electrodes comprise a plurality of first electrode strips which are arranged at intervals and electrically connected, the second electrodes comprise a plurality of second electrode strips which are arranged at intervals and electrically connected, and the first electrode strips and the second electrode strips are arranged in a rotating mode and are mutually spaced;
and the signal unit is respectively connected with the first electrode and the second electrode of the interdigital electrode, and is used for applying a radio-frequency signal to the interdigital electrode and detecting the electromagnetic parameters of the interdigital electrode so as to determine the concentration of the substance to be detected in the sample to be detected according to the electromagnetic parameters.
Optionally, the signal unit is connected to the first electrode through a first lead formed on the substrate, and is connected to the second electrode through a second lead formed on the substrate;
the first lead wire comprises a first spiral wire wound around at least two circles at the periphery of the detection area, the second lead wire comprises a second spiral wire wound around at least two circles at the periphery of the detection area, and the first spiral wire and the second spiral wire are arranged alternately in the outward direction of the detection area.
Optionally, the material of the first electrode and the second electrode is silver or copper.
Optionally, the line width of the first electrode is 10 to 40 microns, the line width of the second electrode is 10 to 40 microns, and the interval between the first electrode strip and the second electrode strip is 10 to 40 microns.
Optionally, the thickness of the insulating layer is 90-110 micrometers, and the insulating layer is made of silicon nitride.
Optionally, the detection chip is a microfluidic chip.
Optionally, the detection chip further includes: the detection chip further comprises:
the cover plate corresponds to the substrate and is provided with a flow channel for collecting the sample to be detected, the flow channel is positioned above the detection area and comprises a groove with a liquid inlet at the bottom, and the groove is used for allowing the sample to be detected to enter the detection area from the liquid inlet.
Further optionally, the surface of the groove has a modification layer for increasing the hydrophilicity of the groove.
Further optionally, the material of the modified layer is silicon dioxide.
Optionally, the sample to be detected is blood, and the substance to be detected is blood sugar;
the electromagnetic parameter is the S-parameter.
Drawings
FIG. 1 is a schematic top view of a substrate of a test chip according to an embodiment of the present invention;
FIG. 2 is a schematic structural diagram of an interdigital electrode of a detection chip according to an embodiment of the present invention;
FIG. 3 is a schematic structural diagram of a chip according to an embodiment of the present invention;
FIG. 4 is a diagram of a flow channel structure of a chip according to an embodiment of the present invention;
FIG. 5 is a graph showing the relationship between the center frequency of the interdigital electrode and the relative dielectric constant of the dielectric layer;
FIG. 6 is a graph showing the relationship between blood glucose concentration and the relative node constant of the dielectric layer according to the embodiment of the present invention;
wherein the reference numerals are: 1. a substrate; 2. an interdigitated electrode; 21. a first electrode; 211. a first electrode strip; 22. a second electrode; 221. a second electrode strip; 23. a first lead; 24. a second lead; 3. an insulating layer; 4. a detection zone; 5. a cover plate; 6. a flow channel; 7. a liquid inlet.
Detailed Description
In order to make the technical solutions of the present invention better understood, the present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
It is to be understood that the specific embodiments and figures described herein are merely illustrative of the invention and are not limiting of the invention.
It is to be understood that the embodiments and features of the embodiments can be combined with each other without conflict.
It is to be understood that, for the convenience of description, only parts related to the present invention are shown in the drawings of the present invention, and parts not related to the present invention are not shown in the drawings.
It should be understood that each unit and module related in the embodiments of the present invention may correspond to only one physical structure, may also be composed of multiple physical structures, or multiple units and modules may also be integrated into one physical structure.
Example 1:
as shown in fig. 1 to 4, the present embodiment provides a detection chip, which specifically includes:
a substrate 1 having a detection region 4 for carrying a sample to be detected, an interdigital electrode 2 and an insulating layer 3 covering the interdigital electrode 2 formed on the substrate 1 of the detection region 4
The electrode assembly 2 comprises a first electrode 21 and a second electrode 22, wherein the first electrode 21 comprises a plurality of first electrode strips 211 which are arranged at intervals and electrically connected, the second electrode 22 comprises a plurality of second electrode strips 221 which are arranged at intervals and electrically connected, and the first electrode strips 211 and the second electrode strips 221 are arranged in turn and are mutually spaced;
and the signal unit is respectively connected with the first electrode 21 and the second electrode 22 of the interdigital electrode 2 and is used for applying a radio-frequency signal to the interdigital electrode 2 and detecting the electromagnetic parameters of the interdigital electrode 2 so as to determine the concentration of the substance to be detected in the sample to be detected according to the electromagnetic parameters.
The detection chip of the embodiment uses glass as a substrate 1, and an interdigitated electrode 2 is integrated on the substrate, as shown in fig. 2, the interdigitated electrode 2 includes a plurality of first electrodes 21 of first electrode strips 211 arranged at intervals and electrically connected, and a plurality of second electrodes 22 of second electrode strips 221 arranged at intervals and electrically connected, and the first electrode strips 211 and the second electrode strips 221 are arranged in turn and spaced from each other.
In practical applications, the first electrode strips 211 and the second electrode strips 221 may be a plurality of wires arranged in turn and spaced apart from each other. The plurality of first electrode bars 211 are connected to each other and are finally connected to the signal units of the test chip, and similarly, the plurality of second electrode bars 221 are connected to each other and are finally connected to the signal units of the test chip. The first electrode stripes 211 and the second electrode stripes 221 are spaced apart from each other, but are not connected to each other.
The detection chip of the embodiment further comprises a signal unit for applying a radio frequency signal to the interdigitated electrodes 2, and the signal unit is respectively connected with the first electrode 21 and the second electrode 22 of the interdigitated electrodes 2 to apply a signal thereto.
Since the electromagnetic characteristics (e.g., electromagnetic parameters) of the rf component are related to the electromagnetic parameters of the medium in the vicinity thereof, the interdigital electrode 2 in this embodiment is obviously a rf component, which also has the characteristics of the rf component.
While the plurality of first electrode stripes 211 and the plurality of second electrode stripes 221 are spaced apart in this region to form a high electromagnetic density region in a manner that the electromagnetic characteristics (e.g., electromagnetic parameters) of the interdigitated electrodes 2 are amplified by the influence of the electromagnetic parameters of the medium in the vicinity thereof.
Therefore, a small change of the nearby medium can cause a significant change of the electromagnetic parameter thereof, i.e., a small change of the concentration of the substance to be detected in the sample to be detected can cause a significant change of the electromagnetic parameter of the interdigital electrode 2.
The concentration of the substance to be detected in the sample to be detected can be judged by obtaining the change of the electromagnetic parameters of the interdigital electrode 2 after the sample to be detected enters the detection area 4.
It should be noted that, because the interdigital electrode 2 is an electric wire, if the detected sample (such as blood) is conductive, the detected sample directly drops on the interdigital electrode 2 to cause a short circuit, so the insulating layer 3 is needed on the interdigital electrode 2 to separate the detected sample from the interdigital electrode 2, and it is ensured that the change of the electromagnetic parameter of the interdigital electrode 2 is caused by the sample to be detected entering the detection zone 4 instead of the short circuit, and the detection chip is also protected.
The chip of this embodiment judges the concentration of waiting to detect the material of waiting to detect sample through waiting to detect the electromagnetic parameter change of interdigital electrode behind sample entering detection zone, simple structure, and because need not to detect according to waiting to detect the result after material reacts with other materials, detect more stable and low cost.
Example 2:
as shown in fig. 1 to 4, the present embodiment provides a detection chip, which is used for detecting the concentration of a substance to be detected in a sample to be detected.
Optionally, the sample to be detected is blood, and the substance to be detected is blood sugar.
Most of the energy required for the cellular activities of tissues in the body comes from glucose, so blood glucose must be kept at a certain level to maintain the needs of organs and tissues in the body. In modern society, more and more diabetic patients have more and more requirements on blood sugar detection.
The chip of the embodiment specifically includes:
the detection device comprises a substrate 1, a detection area 4 and a detection unit, wherein the detection area 4 is used for bearing a sample to be detected, interdigital electrodes 2 and an insulating layer 3 covering the interdigital electrodes 2 are formed on the substrate 1 of the detection area 4, the interdigital electrodes 2 comprise first electrodes 21 and second electrodes 22, the first electrodes 21 comprise a plurality of first electrode strips 211 which are arranged at intervals and electrically connected, the second electrodes 22 comprise a plurality of second electrode strips 221 which are arranged at intervals and electrically connected, and the first electrode strips 211 and the second electrode strips 221 are alternately arranged and mutually spaced;
And the signal unit is respectively connected with the first electrode 21 and the second electrode 22 of the interdigital electrode 2 and is used for applying a radio-frequency signal to the interdigital electrode 2 and detecting the electromagnetic parameters of the interdigital electrode 2 so as to determine the concentration of the substance to be detected in the sample to be detected according to the electromagnetic parameters.
The detection chip of the embodiment uses glass as a substrate 1, and an interdigitated electrode 2 is integrated on the substrate, as shown in fig. 2, the interdigitated electrode 2 includes a plurality of first electrodes 21 of first electrode strips 211 arranged at intervals and electrically connected, and a plurality of second electrodes 22 of second electrode strips 221 arranged at intervals and electrically connected, and the first electrode strips 211 and the second electrode strips 221 are arranged in turn and spaced from each other.
In practical applications, the first electrode strips 211 and the second electrode strips 221 may be a plurality of wires arranged in turn and spaced apart from each other. The plurality of first electrode bars 211 are connected to each other and are finally connected to the signal units of the test chip, and similarly, the plurality of second electrode bars 221 are connected to each other and are finally connected to the signal units of the test chip. The first electrode stripes 211 and the second electrode stripes 221 are spaced apart from each other, but are not connected to each other.
The detection chip of the embodiment further comprises a signal unit for applying a radio frequency signal to the interdigitated electrodes 2, and the signal unit is respectively connected with the first electrode 21 and the second electrode 22 of the interdigitated electrodes 2 to apply a signal thereto.
Alternatively, the signal unit is connected to the first electrode 21 through a first lead 23 formed on the substrate 1, and is connected to the second electrode 22 through a second lead 24 formed on the substrate 1;
the first lead 23 comprises a first spiral wound at least two turns around the detection zone 4, and the second lead 24 comprises a second spiral wound at least two turns around the detection zone 4, the first and second spirals being arranged alternately in an outward direction from the detection zone 4.
As shown in fig. 1, the signal unit is connected to the first electrode 21 through a first lead 23, and the second lead 24 is connected to the second electrode 22. Wherein the first and second leads 23 and 24 are each a spiral line, and the spirals are alternately arranged.
Through the lead wire, can conveniently acquire interdigital electrode 2 electromagnetic parameter more, only need connect the lead wire promptly can, and do not need lug connection interdigital electrode 2, obviously the shape and the position of lead wire compare in interdigital electrode 2 more free, and the design is more convenient.
Through the design of the spiral line, the first lead 23 and the second lead 24 are located at different sides of the interdigital electrode 2, so that the mutual influence of the first lead 23 and the second lead 24 is avoided, and the space of a detection chip can be fully utilized.
Optionally, the material of the first electrode 21 and the second electrode 22 is silver or copper.
In order to ensure that the interdigital electrode 2 is sensitive to the electromagnetic parameter changes of the medium in the vicinity of the interdigital electrode, the material of which the interdigital electrode 2 is composed should be a high conductivity metal such as silver or copper as much as possible, i.e., the material of the first electrode 21 and the second electrode 22 is silver or copper.
Optionally, the line width of the first electrode 21 is 10 to 40 micrometers, the line width of the second electrode 22 is 10 to 40 micrometers, and the interval between the adjacent first electrode strips 211 and the adjacent second electrode strips 221 is 10 to 40 micrometers.
The line widths of the first electrodes 21 and the second electrodes 22 and the intervals between the first electrode stripes 211 and the second electrode stripes 221 may be adjusted according to a detection index (accuracy of detection, etc.). When the detection chip is used for detecting the blood glucose concentration in blood, the line width of the first electrode 21 is 10-40 micrometers, the line width of the second electrode 22 is 10-40 micrometers, and the interval between the adjacent first electrode strips 211 and the adjacent second electrode strips 221 is 10-40 micrometers.
Since the electromagnetic characteristics (e.g., electromagnetic parameters) of the rf component are related to the electromagnetic parameters of the medium in the vicinity thereof, the interdigital electrode 2 in the present embodiment is obviously an rf component, which also has the characteristics of an rf component.
While the plurality of first electrode stripes 211 and the plurality of second electrode stripes 221 are spaced apart in this region to form a high electromagnetic density region in the sense that the electromagnetic characteristics (e.g., electromagnetic parameters) of the interdigitated electrodes 2 are amplified by the electromagnetic parameters of the medium in the vicinity thereof.
Therefore, a small change of the nearby medium can cause a significant change of the electromagnetic parameter thereof, i.e., a small change of the concentration of the substance to be detected in the sample to be detected can cause a significant change of the electromagnetic parameter of the interdigital electrode 2.
The concentration of the substance to be detected in the sample to be detected can be judged by obtaining the change of the electromagnetic parameters of the interdigital electrode 2 after the sample to be detected enters the detection area 4.
Optionally, when the sample to be detected is blood and the substance to be detected is blood sugar, the electromagnetic parameter is an S parameter.
The S-parameter, i.e. the scattering parameter, is a network parameter based on the relationship between the incident microwave and the reflected microwave. As shown in FIG. 5, the magnitude of the S parameter, which is the center frequency, is inversely proportional to the relative dielectric constant (relative permittivity) of the dielectric layer.
By detecting the S parameter of the interdigital electrode 2 and dropping the glucose solution in the detection area 4 to perform concentration calibration, an area in which the glucose concentration and the relative permittivity of the glucose industry have a linear relationship can be determined, as shown in fig. 6, and the method can be used for detecting the blood glucose concentration in blood.
Of course, other parameters, such as Z parameter, R parameter, L parameter, C parameter, etc., may also be used, and the linear region available for detection may be determined according to the above steps to perform detection using the region parameter.
It should be noted that, because the interdigital electrode 2 is an electric wire, if the detected sample (such as blood) is conductive, the detected sample directly drops on the interdigital electrode 2 to cause a short circuit, so the insulating layer 3 is needed on the interdigital electrode 2 to separate the detected sample from the interdigital electrode 2, and it is ensured that the change of the electromagnetic parameter of the interdigital electrode 2 is caused by the sample to be detected entering the detection zone 4 instead of the short circuit, and the detection chip is also protected.
Optionally, the thickness of the insulating layer 3 is 90-110 micrometers, and the material of the insulating layer 3 is silicon nitride.
The thicker the insulating layer 3, the better the insulating effect, but the corresponding sensitivity of the interdigital electrode 2 to the change of the electromagnetic parameters of the medium nearby the interdigital electrode can be affected, so the thinner the insulating layer 3 is, the better on the basis of ensuring the insulating performance, and when the chip is used for detecting the blood glucose concentration in blood, the more suitable the chip is at 90-100 micrometers.
Optionally, the detection chip is a microfluidic chip.
Microfluidics refers to the handling and manipulation of minute quantities of fluids in channel systems on the scale of tens to hundreds of microns. The micro-scale structure of the microfluidic chip significantly increases the specific surface area of the fluid, i.e., the ratio of the surface area to the volume, resulting in a series of surface-related special effects, such as laminar flow effect, surface tension, capillary effect, rapid thermal conduction effect, diffusion effect, etc., thus providing superior performance thereto that macro-scale laboratory devices do not have.
Optionally, the detection chip further includes:
the cover plate 5 corresponding to the substrate 1 is provided with a flow channel 6 for collecting a sample to be detected, the flow channel 6 is positioned above the detection area 4 and comprises a groove with a liquid inlet 7 at the bottom for allowing the sample to be detected to enter the detection area 4 from the liquid inlet 7.
After the interdigital electrodes 2 are integrated on the substrate 1 of the detection chip, in order to protect the interdigital electrodes 2, a cover plate 5 is correspondingly added above the substrate 1, and the material of the cover plate 5 is glass as the substrate 1, so that the interdigital electrodes 2 are sealed in the chip.
Meanwhile, a flow channel 6 for collecting a sample to be detected and feeding it into the detection region 4 is directly etched on the cover plate 5 using PS glue.
The flow channel 6 should be located directly above the detection zone 4 to ensure that the sample (e.g., blood) to be detected can travel along the flow channel 6 to the detection zone 4, i.e., the area where the interdigitated electrodes 2 are located.
Specifically, the flow channel 6 may be a groove with a liquid inlet 7 at the bottom, that is, a groove is etched on the cover plate 5, and a small hole (i.e., the liquid inlet 7) is formed at the bottom of the groove, so that the sample to be detected enters the detection region 4 from the liquid inlet 7 after entering the groove.
Further optionally, the surface of the groove has a modification layer for increasing the hydrophilicity of the groove.
Further optionally, the modified layer material is silicon dioxide.
Silicon dioxide is sputtered on the surface of the flow channel 6 to increase the hydrophilicity of the surface of the flow channel 6, so that a sample to be detected (such as blood) can better enter the detection zone 4 through the liquid inlet 7.
The chip of this embodiment judges the concentration of waiting to detect the material of waiting to detect sample through waiting to detect the electromagnetic parameter change of interdigital electrode behind sample entering detection zone, simple structure, and because need not to detect according to waiting to detect the result after material reacts with other materials, detect more stable and low cost.
It will be understood that the above embodiments are merely exemplary embodiments adopted to illustrate the principles of the present invention, and the present invention is not limited thereto. It will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit and substance of the invention, and these modifications and improvements are also considered to be within the scope of the invention.
Claims (8)
1. An assay chip, comprising:
the detection device comprises a substrate, a detection area and a detection area, wherein the detection area is used for bearing a sample to be detected, interdigital electrodes and an insulating layer covering the interdigital electrodes are formed on the substrate of the detection area, the interdigital electrodes comprise first electrodes and second electrodes, the first electrodes comprise a plurality of first electrode strips which are arranged at intervals and are electrically connected, the second electrodes comprise a plurality of second electrode strips which are arranged at intervals and are electrically connected, and the first electrode strips and the second electrode strips are arranged in a rotating flow manner and are mutually spaced;
The signal unit is respectively connected with the first electrode and the second electrode of the interdigital electrode, and is used for applying a radio-frequency signal to the interdigital electrode and detecting the electromagnetic parameters of the interdigital electrode so as to determine the concentration of a substance to be detected in the sample to be detected according to the electromagnetic parameters;
the sample to be detected is blood, and the substance to be detected is blood sugar;
the electromagnetic parameter is an S parameter;
the signal unit is connected with the first electrode through a first lead formed on the substrate and is connected with the second electrode through a second lead formed on the substrate;
the first lead wire comprises a first spiral wire wound around at least two circles at the periphery of the detection area, the second lead wire comprises a second spiral wire wound around at least two circles at the periphery of the detection area, and the first spiral wire and the second spiral wire are arranged alternately in the outward direction of the detection area.
2. The detection chip according to claim 1, wherein the material of the first electrode and the second electrode is silver or copper.
3. The detection chip according to claim 1, wherein the line width of the first electrode is 10 to 40 micrometers, the line width of the second electrode is 10 to 40 micrometers, and the interval between the adjacent first electrode stripes and the adjacent second electrode stripes is 10 to 40 micrometers.
4. The detection chip according to claim 1, wherein the thickness of the insulating layer is 90-110 μm, and the material of the insulating layer is silicon nitride.
5. The detection chip according to claim 1, wherein the detection chip is a microfluidic chip.
6. The detection chip of claim 1, wherein the detection chip further comprises:
the cover plate corresponds to the substrate and is provided with a flow channel for collecting the sample to be detected, the flow channel is positioned above the detection area and comprises a groove with a liquid inlet at the bottom, and the groove is used for allowing the sample to be detected to enter the detection area from the liquid inlet.
7. The detecting chip according to claim 6, wherein the surface of the recess has a modified layer for increasing the hydrophilicity of the recess.
8. The detection chip according to claim 7, wherein the material of the modified layer is silicon dioxide.
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