CN215218661U - Electrochemical sensor array capable of simultaneously detecting creatinine, glucose and uric acid - Google Patents
Electrochemical sensor array capable of simultaneously detecting creatinine, glucose and uric acid Download PDFInfo
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Abstract
The utility model provides an electrochemical sensor array capable of detecting creatinine, glucose and uric acid simultaneously, which comprises a bottom plate and an electrode group arranged on the surface of the bottom plate; the electrode group consists of a working electrode array, a reference electrode and a counter electrode; the working electrode array consists of a first working electrode, a second working electrode and a third working electrode which are arranged independently; the surface of the first working electrode is provided with a first enzyme layer which can react with creatinine to generate hydrogen peroxide; the surface of the second working electrode is provided with a second enzyme layer which can react with glucose to generate hydrogen peroxide; the surface of the third working electrode is provided with a third enzyme layer which can react with uric acid to generate hydrogen peroxide. The utility model discloses a sensor array has sensitivity height, interference immunity is strong, stable performance, simple structure, small, cost low grade integrated advantage, can be used for clinical or quick, the convenient detection at home.
Description
Technical Field
The utility model relates to a carry out the device of analytical test usefulness to clinical sample, concretely relates to a biosensor array that is used for electrochemical method to detect a plurality of chronic clinical indexes of disease.
Background
The prevalence of diabetes has continued to rise in recent years and has become a leading cause of death worldwide. Blood glucose levels are the main criteria for the diagnosis and treatment of diabetes, and fasting blood glucose levels should be >7.0mM or >11.1mM after 75 grams of glucose has been taken by a person diagnosed with diabetes. Diabetic patients usually need to test blood glucose levels several times a day, and POC (point-of-care) devices are the mainstream devices for blood glucose monitoring in the prior art. Creatinine is a naturally occurring metabolite in the human body that is filtered from the blood by the kidneys in relatively constant amounts each day. Blood creatinine concentration is an important indicator for assessing renal function, diagnosing Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD). Normal levels of blood creatinine were 40-150 μ M; creatinine clearance tests are required when blood creatinine levels exceed 150 μ M; blood creatinine levels greater than 500 μ M indicate severe renal damage. Uric acid is produced by purine metabolic pathways in vivo, and abnormal levels of uric acid can cause various diseases, such as gout, Lesch-Nyhan syndrome, hypertension, cardiovascular diseases and the like, and the normal level of uric acid in serum is 240-.
The accurate detection of the biomarkers related to various diseases plays a crucial role in controlling and treating the corresponding diseases. Currently, the common assay methods for these markers in the clinic are based on colorimetric methods. Although the sensitivity and specificity can be improved by introducing enzymes, these methods usually rely on large-scale equipment, complicate the detection process, and cannot be applied to convenient clinical detection or long-term monitoring at home. In recent years, the development of new biosensing platforms for complex physical samples containing multiple solutes has attracted considerable interest. The electrochemical biosensor has the advantages of less time consumption, simple experimental process, relatively low instrument requirement, high selectivity and sensitivity and the like, and is widely applied to the field of medical analysis. In the prior art, various electrochemical biosensor arrays have been developed based on different methods, including voltammetry, conductance, amperometry, etc. However, the existing electrochemical biosensor or sensor array still has the defects of portability, accuracy, sensitivity and the like.
Therefore, there is a need for an electrochemical biosensor that can detect multiple indicators in a sample quickly, accurately and conveniently, so that the electrochemical biosensor can be conveniently used for quick detection or long-term monitoring of blood sugar, creatinine, uric acid and other indicators.
SUMMERY OF THE UTILITY MODEL
In view of the above background, the present invention is directed to: the biosensor for detecting multiple indexes by an electrochemical method has the comprehensive advantages of high sensitivity, strong anti-interference performance, stable performance, simple structure, small volume, low cost and the like, and can be used for clinical or household rapid and convenient detection.
The above object of the utility model is realized through following technical scheme:
the biosensor array for simultaneously detecting creatinine, glucose and uric acid by an electrochemical method is provided, and comprises a bottom plate and an electrode group arranged on the surface of the bottom plate; the electrode group consists of a working electrode array, a reference electrode and a counter electrode; the working electrode array consists of a first working electrode, a second working electrode and a third working electrode which are arranged independently; the surface of the first working electrode is provided with a first enzyme layer which can react with creatinine to generate hydrogen peroxide; the surface of the second working electrode is provided with a second enzyme layer which can react with glucose to generate hydrogen peroxide; and a third enzyme layer which can react with uric acid to generate hydrogen peroxide is arranged on the surface of the third working electrode.
In the solution of the present invention, the shape and specification of each electrode in the electrode group are not particularly limited, and the cross section thereof may be circular, oval, rectangular or other polygonal shape.
In the embodiment of the present invention, the base material of each electrode may be any of various existing material compositions that can be used for redox electrodes, including various compositions containing inert metal materials (e.g., platinum electrode materials, gold electrode materials, or mercury electrode materials) or compositions containing carbon electrode materials, and so on. Each working electrode comprises a base layer made of the base material, and the corresponding enzyme layer is fixed on the surface of the base layer. In a preferred embodiment, the base layer of the first working electrode, the base layer of the second working electrode, the base layer of the third working electrode, and the counter electrode are made of the same material, for example, any one of graphite, carbon paste, or glassy carbon containing an electron mediator component; the reference electrode is made of Ag/AgCl electrode material.
The utility model discloses in the preferred scheme, in order to further improve each working electrode's sensitivity, the basic unit and the second enzyme layer of basic unit and the first enzyme layer of first working electrode between be equipped with first electron mediator enhancement layer, second working electrode between be equipped with second electron mediator enhancement layer, third working electrode between the basic unit and the third enzyme layer be equipped with third electron mediator enhancement layer. The electron mediator enhancement layer contains any one electron mediator selected from Prussian blue, methylene blue, ferrocene and derivatives thereof or potassium ferricyanide; prussian blue is most preferred.
In the scheme of the utility model, the basic operating principle of each working electrode is all based on the hydrogen peroxide that target object and enzyme reaction generated is by electron mediator catalytic reduction, and this process shifts the electron of enzyme activity center to electrode basic unit and produces reduction current, through reference electrode measurable quantity working electrode's electric potential. Therefore, the concentration of hydrogen peroxide generated at the working electrode has a crucial influence on the potential measurement. The utility model discloses in the preferred scheme, in order to prevent the hydrogen peroxide diffusion of high concentration around the working electrode, each the working electrode around set up respectively and prevent that the diffusion encloses the fender, prevent that the diffusion encloses the fender and be the cavity tubulose, the bottom surface with the inseparable fixed connection of bottom plate, highly be greater than working electrode thickness.
The specific shape of the diffusion barrier is not particularly limited, and the diffusion barrier may be a circular hollow tube, a square hollow tube, or a hollow tube with other shapes. The specific material of the diffusion barrier is not limited, and various existing corrosion-resistant dense materials, such as Polytetrafluoroethylene (PTFE), can be used.
In the preferred embodiment of the present invention, in order to further reduce the cross influence of the hydrogen peroxide generated by different targets in the sample on each working electrode, among the five electrodes of the electrode group, the first working electrode, the second working electrode and the third working electrode are located at positions on the bottom plate that are not adjacent to each other.
In a further preferred embodiment, among the five electrodes of the electrode group, the first working electrode, the second working electrode and the third working electrode are respectively located at three vertexes of the largest equilateral triangle at the upper half of the bottom plate, and the counter electrode and the reference electrode are respectively located between any two working electrodes.
In the scheme of the utility model, the concrete material, specification and the shape of bottom plate do not have special restriction. The bottom plate material can be various existing insulating materials, preferably insulating paper, plastic, rubber and other materials with hydrophobic surfaces; the plastic is further preferably any one of PET, PVC, PE or PP. The specification of the bottom plate can be manufactured into different thicknesses and sizes according to the requirement. The shape of the bottom plate can be any shape which is acceptable in the application scene in actual measurement.
In the preferred scheme of the utility model, the bottom plate is also provided with a metal lead which is independently connected with each electrode in the electrode group; the metal lead is used for electrically connecting each electrode with peripheral potential detection equipment.
In a further preferred scheme of the utility model, the joint department that each electrode and corresponding metal wire are connected be equipped with the fixed subassembly of reinforceing the connection.
The utility model discloses in the preferred scheme, the bottom plate on the periphery of electrode group still is equipped with the insulating material wall, the insulating material wall whole be closed frame form, the bottom with the inseparable fixed connection of bottom plate, highly do more than 2 times of electrode thickness and be higher than prevent that the diffusion encloses the height that keeps off, from this will each electrode of electrode group encloses inside it, forms the cavity that can splendid attire sample.
The insulating material wall can be made of various existing insulating materials, preferably hot melt adhesive.
In the embodiment of the present invention, the first enzyme layer on the first working electrode contains an enzyme composition that reacts with creatinine to generate hydrogen peroxide, preferably a three-enzyme composition consisting of Creatininase (CA), Creatininase (CI), and Sarcosine Oxidase (SO); a second enzyme layer on the second working electrode comprises an enzyme that reacts with glucose to produce hydrogen peroxide, preferably Glucose Oxidase (GOD); the third enzyme layer on the third working electrode contains an enzyme that reacts with uric acid to produce hydrogen peroxide, preferably urate oxidase (Uricase).
The utility model discloses an electrochemical biosensor array's application method and theory of operation are: during detection, each electrode is electrically connected with external potential detection equipment; then, a buffer solution is dripped into the electrode group, and then a sample (such as a plasma sample) is dripped, creatinine in the sample reacts with a complex enzyme fixed on the first working electrode to generate hydrogen peroxide, glucose in the sample reacts with an enzyme fixed on the second working electrode to generate hydrogen peroxide, and uric acid in the sample reacts with an enzyme fixed on the third working electrode to generate hydrogen peroxide. The hydrogen peroxide generated on each working electrode is subjected to catalytic reduction by the electron mediator on the corresponding electrode, electrons are transferred to the base layer of each working electrode to generate reduction current, and the content of creatine, glucose and uric acid in the sample can be obtained according to the relation between the current response value of each working electrode and the concentration of the corresponding target in the sample. Use sensor array detects time measuring, detects the sample and can be various forms such as whole blood, plasma, serum, urine.
The utility model discloses an electrochemistry biosensor array can selectively detect three kinds of important marker concentrations of creatinine, blood sugar and uric acid in the sample simultaneously, and each working electrode has higher sensitivity and selectivity to corresponding marker. The measurement result of the actual plasma sample shows that the detection performance of the electrochemical biosensor array is close to the standard method used in clinical practice, and is expected to provide powerful support for the clinical convenient detection and the household long-term monitoring of the markers. The utility model discloses in the preferred scheme, each working electrode has add electron mediator enhancement layer through optimizing inside component structure between enzyme layer and electrode basic unit for the detection to showing and strengthening electron transfer efficiency, finally can making the reduction potential of three working electrode reduce to-0.1V when detecting, thereby effectively got rid of the interference that non-target marker brought in detecting, showing and improving the interference killing feature. The utility model discloses an electrochemistry biosensor array can be arranged in multiple portable, swift small-size electrochemistry check out test set, is favorable to the clinical examination or the monitoring at home of creatinine, glucose and uric acid in samples such as blood, urine very much.
Drawings
FIG. 1 is a schematic structural diagram of an electrochemical biosensor array described in example 1.
FIG. 2 is a schematic diagram of the structure of the electrochemical biosensor array described in example 2.
FIG. 3 is a schematic structural view of each working electrode in the electrochemical biosensor array according to example 1 or 2.
Detailed Description
The technical solution of the present invention will be described in detail below by way of examples with reference to the accompanying drawings, but the scope of the present invention is not limited to the examples.
Example 1
A biosensor array for simultaneously detecting creatinine, glucose and uric acid by an electrochemical method comprises a base plate, an electrode group arranged on the surface of the base plate, an insulating material wall and a metal lead.
As shown in FIG. 1, the bottom plate 10 is a rectangular PET plate having a thickness of 0.2mm, a length of 14mm and a width of 10 mm. The electrode group consists of a working electrode array, a reference electrode 50 and a counter electrode 60; the working electrode array consists of a first working electrode 20, a second working electrode 30 and a third working electrode 40 which are arranged independently; all the working electrodes are in the shape of a head round handle bar, and the internal structures of all the working electrodes, as shown in fig. 3, comprise a carbon slurry layer 1 (a base layer) at the bottommost layer, a Prussian blue layer 2 (an electron mediator enhancement layer) in the middle and an enzyme layer 3 at the outermost surface. Reference electrode 50 was made of Ag/AgCl electrode material. The counter electrode 60 is the same carbon paste material as the carbon paste layer 1 of the working electrode. As shown in FIG. 1, first working electrode 20, second working electrode 30, and third working electrode 40 are each positioned at the three vertices of the largest equilateral triangle in the upper half of base plate 10, with counter electrode 60 between the first and second working electrodes and reference electrode 50 between the second and third working electrodes.
As shown in fig. 1, the electrode assembly is further provided with an insulating material wall 70 on the periphery thereof, the insulating material wall 70 is integrally formed into a closed frame shape, and the bottom thereof is tightly and fixedly connected with the bottom plate 10, so that each electrode of the electrode assembly is enclosed therein to form a cavity for containing a sample. The height of the insulating material wall 70 is more than 2 times of the thickness of each electrode inside the insulating material wall, so that the overflow loss of the sample is better limited. In addition, on the base plate 10, each electrode is individually connected with a copper wire 90, and a connection-reinforcing hot melt adhesive block 80 is provided at the joint of the connection. The copper wire 90 is used for electrically connecting the electrodes with the peripheral potential detection device.
When the electrochemical biosensor array of this embodiment is manufactured, first, on the PET substrate 10 of the above specification, according to a predetermined position, the first working electrode 20, the second working electrode 30, the third working electrode and the counter electrode 60 are printed by using carbon paste as a material in a screen printing manner, then the reference electrode 50 is printed at the set position by using Ag/AgCl paste as a material in a screen printing mode, adding Prussian blue layers on the surfaces of the first working electrode 20, the second working electrode 30 and the third working electrode 40 by an electrochemical deposition method, fixing enzyme compounds of CA, CI and SO on the surface of the first working electrode 20 in a glutaraldehyde crosslinking mode to form a first enzyme layer, GOD is fixed on the surface of the second working electrode 30 in a glutaraldehyde crosslinking mode to form a second enzyme layer, and (3) immobilizing Uricase on the surface of the third working electrode 40 in a glutaraldehyde crosslinking mode to form a third enzyme layer.
Example 2
A biosensor array for simultaneously detecting creatinine, glucose and uric acid by an electrochemical method, having a structure as shown in fig. 2, which is generally the same as the sensor array of example 1 except that: on each working electrode, only the Prussian blue layer and the enzyme layer are arranged on the surface of the round head part of each working electrode; a hollow short pipe 100 with the inner diameter larger than the diameter of the electrode head is arranged at each working electrode position, the bottom of the hollow short pipe 100 is tightly and fixedly connected with the bottom plate 10, and a diffusion-preventing enclosure structure is formed around each working electrode and is used for preventing high-concentration hydrogen peroxide around the working electrode from diffusing in the detection process; the height of each hollow stub 100 is greater than the working electrode thickness and less than the height of the insulating material wall 70.
Claims (8)
1. A biosensor array for simultaneously detecting creatinine, glucose and uric acid by an electrochemical method is characterized in that: comprises a bottom plate and an electrode group arranged on the surface of the bottom plate; the electrode group consists of a working electrode array, a reference electrode and a counter electrode; the working electrode array consists of a first working electrode, a second working electrode and a third working electrode which are arranged independently; the surface of the first working electrode is provided with a first enzyme layer which can react with creatinine to generate hydrogen peroxide; the surface of the second working electrode is provided with a second enzyme layer which can react with glucose to generate hydrogen peroxide; and a third enzyme layer which can react with uric acid to generate hydrogen peroxide is arranged on the surface of the third working electrode.
2. The sensor array of claim 1, wherein: a first electronic mediator enhancement layer is arranged between the base layer of the first working electrode and the first enzyme layer, a second electronic mediator enhancement layer is arranged between the base layer of the second working electrode and the second enzyme layer, and a third electronic mediator enhancement layer is arranged between the base layer of the third working electrode and the third enzyme layer.
3. The sensor array of claim 1, wherein: the periphery of each working electrode is respectively provided with a diffusion-proof enclosure, the diffusion-proof enclosure is in a hollow tubular shape, the bottom surface of the diffusion-proof enclosure is tightly and fixedly connected with the bottom plate, and the height of the diffusion-proof enclosure is larger than the thickness of the working electrode.
4. The sensor array of claim 1, wherein: in the five electrodes of the electrode group, the first working electrode, the second working electrode and the third working electrode are not adjacent to each other on the bottom plate.
5. The sensor array of claim 1, wherein: in the five electrodes of the electrode group, the first working electrode, the second working electrode and the third working electrode are respectively positioned at the positions of three vertexes of the maximum equilateral triangle at the upper half part of the bottom plate, and the counter electrode and the reference electrode are respectively positioned between any two working electrodes.
6. The sensor array of claim 1, wherein: the bottom plate is also provided with a metal lead which is independently connected with each electrode in the electrode group; the metal lead is used for electrically connecting each electrode with peripheral potential detection equipment.
7. The sensor array of claim 6, wherein: and the joints of the metal lead, the working electrode, the counter electrode and the reference electrode are respectively provided with fixing components for strengthening connection.
8. The sensor array of claim 3, wherein: the bottom plate is provided with an insulating material wall at the periphery of the electrode group, the insulating material wall is integrally in a closed frame shape, the bottom of the insulating material wall is tightly and fixedly connected with the bottom plate, and the height of the insulating material wall is more than 2 times of the thickness of the electrode and higher than the height of the anti-diffusion enclosure, so that each electrode of the electrode group is enclosed in the insulating material wall to form a cavity capable of containing a sample.
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