CN117092181A

CN117092181A - Electrochemical system and implantable biochemical test piece

Info

Publication number: CN117092181A
Application number: CN202310460816.1A
Authority: CN
Inventors: 杨振宇; 杨志亮
Original assignee: Apex Biotechnology Corp
Current assignee: Apex Biotechnology Corp
Priority date: 2022-05-18
Filing date: 2023-04-26
Publication date: 2023-11-21

Abstract

The present disclosure provides an electrochemical system comprising an electrode unit and a reaction unit electrically connected to the electrode unit. The electrode unit is positioned on the insulating substrate. The electrode unit includes a working electrode and a counter electrode, wherein the current density of the counter electrode is greater than the current density of the working electrode. The first insulating spacer is located on the electrode unit. An implantable biochemical test strip is also disclosed.

Description

Electrochemical system and implantable biochemical test piece

Technical Field

The present disclosure relates to an electrochemical system and an implanted biochemical test strip, and more particularly, to an electrochemical system and an implanted biochemical test strip for improving the charge neutrality of a counter electrode.

Background

In vitro medical measurement plays an extremely important role in the current medical industry, and by qualitatively and quantitatively measuring changes in body fluids of living beings, index information for rapid diagnosis of diseases and treatment can be given. The use of biochemical test strips has been a popular technique for medical or biochemical detection.

The conventional biochemical test strip has at least two electrodes, and after the sample is injected into the reaction area of the biochemical test strip, the electrochemical characteristics of the sample can be measured by the two electrodes. The electrochemical reaction of the sample produces a change in current that is linearly proportional to the concentration of the redox species in the sample. The sample concentration can thus be analyzed by measuring the current generated by the redox reaction at the electrode surface.

In recent years, as the demand for reduced sampling increases, biochemical test strips tend to reduce the electrode area thereof to reduce the amount of sample required. However, the reduction of the electrode area may cause deterioration or weakening of the electrochemical signal. Therefore, the biochemical test piece is provided with a plurality of conductive media to improve the measurement signal. However, adding conductive media increases manufacturing costs and increases dissolution drying difficulties. In addition, when measuring a high concentration sample, a bottleneck effect may be generated due to the fact that the electron flow of the reaction of the working electrode exceeds the total amount of the reaction of the counter electrode, so that the measurable concentration range of the biochemical test piece is limited.

The above description of "prior art" is provided merely as background, and is not admitted to disclose the subject matter of the present disclosure, do not constitute prior art to the present disclosure, and any description of "prior art" above should not be taken as any part of the present disclosure.

Disclosure of Invention

The disclosure provides a biochemical test piece, which comprises an insulating substrate, an electrode unit, a first insulating spacer, a reaction layer and a second insulating spacer. The electrode unit is positioned on the insulating substrate. The electrode unit includes a working electrode and a counter electrode, wherein the current density of the counter electrode is greater than the current density of the working electrode. The first insulating spacer is located on the electrode unit. The first insulating spacer has a first opening that at least partially exposes the electrode unit. The reaction layer is located in the first opening and is electrically connected with the electrode unit. The second insulating spacer is positioned on the first insulating spacer.

In some embodiments, the current density of the counter electrode is greater than or equal to twice the current density of the working electrode.

In some embodiments, the area of the counter electrode is less than or equal to the area of the working electrode.

In some embodiments, the reaction layer performs a primary reaction with the target analyte and the counter electrode is configured to perform a secondary reaction, wherein the secondary reaction does not interfere with the primary reaction and the secondary reaction provides the counter electrode with the ability to receive or release additional electrons.

In some embodiments, the counter electrode includes a first portion and a second portion, the first portion and the reaction layer not overlapping each other.

In some embodiments, the counter electrode includes a first portion and a second portion, the opening at least partially exposing the first portion.

In some embodiments, the biochemical test strip further comprises a protective layer electrically connected to the electrode unit.

In some embodiments, the electrode unit further comprises a second pair of electrodes, wherein the pair of electrodes and the second pair of electrodes are separated from each other.

In some embodiments, the standard reduction potential of the counter electrode is greater than the standard reduction potential of the second counter electrode.

In some embodiments, the sum of the area of the counter electrode and the area of the second counter electrode is less than or equal to the area of the working electrode.

In some embodiments, the counter electrode is a cathode and the standard reduction potential of the active material of the counter electrode is in accordance withWherein->Is the standard reduction potential of the active material, +.>Standard reduction potential for concentration reaction at working electrode, and E _v The measuring instrument is provided with the potential applied by the measuring reaction.

In some embodiments, the counter electrode is an anode and the standard reduction potential of the active material of the counter electrode is in accordance withWherein->Is the standard reduction potential of the active material, +.>Standard reduction potential for concentration reaction at working electrode, and E _v The measuring instrument is provided with the potential applied by the measuring reaction.

The biochemical test piece disclosed by the disclosure is provided with a counter electrode with current density larger than that of a working electrode. Therefore, the amount of electrons oxidized or reduced by the counter electrode can be made equal to the amount of electrons reduced or oxidized by the working electrode without increasing the area of the counter electrode. Therefore, the bottleneck effect can be solved, and the requirement of reducing the sampling volume is met.

The present disclosure provides an electrochemical system including an electrode unit and a reaction unit electrically connected to the electrode unit. The electrode unit comprises a working electrode and a counter electrode, wherein the current density of the counter electrode is larger than that of the working electrode.

In some embodiments, the counter electrode is a cathode and the standard potential of the active material of the counter electrode is in accordance withWherein->Is the standard reduction potential of the active material, +.>Standard reduction potential for concentration reaction at working electrode, and E _v The measuring instrument is provided with the potential applied by the measuring reaction.

In some embodiments, the counter electrode is an anode and the standard potential of the active material of the counter electrode is in accordance withWherein->Is the standard reduction potential of the active material, +.>Standard reduction potential for concentration reaction at working electrode, and E _v The measuring instrument is provided with the potential applied by the measuring reaction.

In some embodiments, the reaction unit performs a primary reaction with the target analyte, and the counter electrode is configured to perform a secondary reaction, wherein the secondary reaction does not interfere with the primary reaction, and the secondary reaction provides the counter electrode with the ability to receive or release additional electrons.

In some embodiments, the electrochemical system further comprises a protection unit electrically connected to the electrode unit, wherein the protection unit is configured to oxidize the electrode unit after the electrode unit receives electrons or to reduce the electrode unit after the electrode unit loses electrons, wherein a potential difference exists between the protection unit and the electrode unit

In some embodiments, the potential differenceGreater than 0.

The disclosure provides an implantable biochemical test strip, which comprises a substrate, a biocompatible coating, an electrode unit and a reaction layer. The biocompatible coating is disposed on the substrate. The electrode unit is arranged between the substrate and the biocompatible coating, wherein the electrode unit comprises a working electrode and a counter electrode, the counter electrode is used for receiving or releasing extra electrons through self redox secondary reaction, and the current density of the counter electrode is larger than that of the working electrode. The reaction layer is electrically connected to the electrode unit.

In some embodiments, the implantable biochemical test strip further comprises a first end connected to the measuring instrument, and a second end implantable in the sample.

In some embodiments, the second end is covered by a biocompatible coating.

In some embodiments, the reaction layer is between the working electrode and the counter electrode.

In some embodiments, the reaction layer covers the working electrode or the counter electrode.

In some embodiments, the substrate has an elongated structure and the biocompatible coating surrounds the substrate.

In some embodiments, the electrode unit further comprises a spare electrode on the substrate.

The disclosure provides an implantable biochemical test strip, which comprises a substrate, a biocompatible coating, an electrode unit and a protective layer. The substrate has a measurement end and an implantable end. The biocompatible coating is disposed on the substrate. The electrode unit is arranged between the substrate and the biocompatible coating, wherein the electrode unit comprises a working electrode and a counter electrode, and the counter electrode comprises an active material. The protective layer is electrically connected to the electrode unit and is used for stabilizing the active material of the counter electrode.

In some embodiments, the protective layer is located at the measurement end.

In some embodiments, the protective layer is disposed adjacent to the counter electrode.

In some embodiments, there is a potential difference between the passivation layer and the electrode unit

In some embodiments, the potential differenceGreater than 0.

The foregoing has outlined rather broadly the features and advantages of the present disclosure in order that the detailed description of the disclosure that follows may be better understood. Other technical features and advantages that form the subject of the claims of the present disclosure are described below. It should be appreciated by those skilled in the art that the conception and specific embodiment disclosed may be readily utilized as a basis for modifying or designing other structures or processes for carrying out the same purposes of the present disclosure. Those skilled in the art will also appreciate that such equivalent constructions do not depart from the spirit and scope of the disclosure as set forth in the appended claims.

Drawings

The disclosure of the present application may be more fully understood when the detailed description and claims are taken together with the accompanying drawings, in which like reference numerals refer to like elements.

FIG. 1 is an exploded view of a biochemical test strip according to some embodiments of the present disclosure.

FIG. 2 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure.

Fig. 3A and 3B are schematic diagrams of electrochemical reactions drawn according to some embodiments of the present disclosure.

FIG. 4 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure.

FIG. 5 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure.

FIG. 6 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure.

FIG. 7 is an exploded view of a biochemical test strip according to some embodiments of the present disclosure.

FIG. 8 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure.

Fig. 9A and 9B are graphs showing signal comparisons of the counter electrode of the present embodiment and the counter electrode of the comparative embodiment, respectively, applied at different concentrations.

FIG. 10 is a graph showing the comparison of signals when the counter electrode of the present embodiment and the counter electrode of the comparative embodiment have different areas.

Fig. 11A and 11B are graphs showing signal comparisons of different materials for the anode and cathode counter electrodes, respectively.

Fig. 12 is a schematic diagram of an electrochemical system drawn according to some embodiments of the present disclosure.

FIG. 13 is a schematic diagram of an implantable biochemical test strip according to some embodiments of the present disclosure.

Fig. 14A is a cross-sectional view along line A-A' of fig. 13, drawn according to some embodiments of the present disclosure.

Fig. 14B is a cross-sectional view along line B-B' of fig. 13, drawn in accordance with some embodiments of the present disclosure.

FIG. 15 is a schematic illustration of an electrochemical reaction of an electrochemical system or an implantable biochemical test strip according to some embodiments of the present disclosure.

FIG. 16 is a schematic diagram of an implantable biochemical test strip according to some embodiments of the present disclosure.

Fig. 17 is a cross-sectional view along line C-C' of fig. 16, drawn in accordance with some embodiments of the present disclosure.

FIG. 18 is a schematic diagram of an implantable biochemical test strip according to some embodiments of the present disclosure.

FIG. 19 is a schematic diagram of an implantable biochemical test strip according to some embodiments of the present disclosure.

Fig. 20 is a cross-sectional view along line D-D' of fig. 19, drawn in accordance with some embodiments of the present disclosure.

FIG. 21 is an exploded view of an implantable biochemical test strip according to some embodiments of the present disclosure.

FIG. 22 is a schematic diagram of an implantable biochemical test strip according to some embodiments of the present disclosure.

FIG. 23 is a schematic diagram of an implantable biochemical test strip according to some embodiments of the present disclosure.

FIG. 24 is a schematic diagram of an implantable biochemical test strip according to some embodiments of the present disclosure.

Fig. 25 shows signals detected at different concentrations on the counter electrode according to the present embodiment and the counter electrode of the comparative example.

FIG. 26 is a graph showing the signals detected over time on the electrochemical system according to the present embodiment and the electrochemical system of the comparative example.

[ symbolic description ]

10 insulating substrate

10C connecting region

20 electrode unit

22 working electrode

22X first part

22Y second part

24 counter electrode, first counter electrode

24A first part

24B second part

24C branch

24X first part

24Y second portion

26 second pair of electrodes

26A first part

26B second portion

30 first insulating spacer

30F front side

30B rear side

32 opening(s)

34 reaction zone

40 reaction layer

50 second insulating spacer

52 air vent

60 protective layer

100 biochemical test piece

200 biochemical test piece

300 biochemical test piece

400 biochemical test piece

500 biochemical test piece

600 biochemical test piece

1000 electrochemical System

1001 electrode unit

1002 reaction unit

1003 protection unit

2000, implantable biochemical test piece

2102 working electrode

2104 counter electrode

2106 reaction layer

2108 insulating layer

2110 biocompatible coating

2112 first end (or measuring end)

2114 second end (or implantable end)

2102E structure

2104E structure

3000 biochemical test piece

3102 working electrode

3103 substrate

3104 counter electrode

3106 reaction layer

3112 first end (or measuring end)

3114 a second end (or implantable end).

4000 biochemical test piece

4102 working electrode

4103 substrate

4104 counter electrode 4112 first end (or measuring end)

4114 second (or implantable) end 5000 implantable biochemical test strip

5102 working electrode

5103 substrate

5104 counter electrode

5106 reaction layer

5220 spare electrode 5112 first end (or measuring end)

5114 second end (or implantable end)

6000 implantable biochemical test piece

6102 working electrode

6103 substrate

6104 counter electrode

6112 first end (or measuring end)

6114 second end (or implantable end)

7000 implantable biochemical test piece

7102 working electrode

7104 counter electrode

7106 reaction layer

7108 insulating layer

7110 biocompatible coating

7112 first end (or measurement end)

7114 second end (or implantable end)

7122 protective layer

8000 implantable biochemical test piece

8102 working electrode

8103 substrate

8104 counter electrode

8122 protective layer

8112 first end (or measuring end)

8114 second end (or implantable end)

8220 spare electrode

9000 implantable biochemical test piece

9102 working electrode

9103 substrate

9104 counter electrode

9112 first end (or measuring end)

9114 a second end (or implantable end)

9122 protective layer

9220 spare electrode

C conductive medium and reduced conductive medium

C' oxidation state conductive medium

E, ferment

M measuring instrument

R: target analyte

R' reduced target analyte

R' oxidation state target analyte

S sample

Detailed Description

Embodiments of the present disclosure are discussed in detail below. It should be appreciated, however, that the embodiments provide many applicable inventive concepts that can be embodied in a wide variety of specific contexts. The specific embodiments discussed are merely illustrative of specific ways to make and use embodiments and do not limit the scope of the disclosure.

In the various views and illustrative embodiments, like reference numerals are configured to denote like elements. Reference will now be made in detail to exemplary embodiments that are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings and the description to refer to the same or like parts. In the drawings, the shape and thickness may be exaggerated for clarity and convenience. The description will be directed in particular to elements forming part of, or cooperating more directly with, apparatus in accordance with the disclosure. It is to be understood that elements not specifically shown or described may take various forms. Reference throughout this specification to "some embodiments" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in some embodiments" or "in embodiments" in various places throughout this specification are not necessarily referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

In the drawings, like reference numerals are configured to designate identical or similar elements throughout the various views, and illustrative embodiments of the present invention are shown and described. The figures are not necessarily to scale and in some cases, the figures have been exaggerated and/or simplified and are configured for illustrative purposes only. Many possible applications and variations of the present invention will be appreciated by those of ordinary skill in the art based on the following illustrative examples of the invention.

Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which embodiments of this disclosure belong. It will be appreciated that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure and will not be interpreted in an overly formal sense unless expressly so defined herein.

In addition, the following examples are provided to illustrate the core value of the present disclosure, but are not intended to limit the scope of the present disclosure. For clarity of illustration and ease of understanding, the same or similar functions or elements between different embodiments of the present disclosure will not be repeatedly described or illustrated in the figures. And the combination or replacement of different elements or technical features in different embodiments on the premise of not mutually conflicting still falls within the protection scope of the present disclosure.

The present disclosure relates to electrochemical systems that perform self-redox reactions on a counter electrode to provide additional electrons, and more particularly to biochemical test strips that employ electrochemical systems that perform self-redox on a counter electrode. Further, the present disclosure relates to a counter electrode including an active material capable of providing an amount of electrons generated by a self redox reaction equivalent to that of a conductive medium on a working electrode in an environment where an electrode area is limited or a concentration of a conductive medium capable of conducting electron transfer to the electrode surface in a reaction solution is insufficient. Therefore, the charge neutral balance capability of the counter electrode can be improved, and the electrochemical loop is stabilized to avoid the current bottleneck effect on the counter electrode. In some embodiments, the biochemical test strip further comprises a protective layer to help stabilize the active material of the counter electrode, thereby protecting the biochemical test strip and reducing or avoiding unexpected variation of the biochemical test strip and the environment.

Referring to fig. 1, fig. 1 is an exploded view of a biochemical test strip 100 according to some embodiments of the present disclosure. The biochemical test strip 100 may be an electrochemical test strip, and is a device capable of being electrically connected. The biochemical test strip 100 is used to collect a sample and perform an electrochemical reaction thereon to detect a target analyte therein. The sample includes any liquid or soluble solid in which the target analyte can be detected using electrochemical methods. For example, the sample may include biological acquisitions of blood, interstitial fluid, urine, sweat, tears, etc., but the disclosure is not limited thereto. Furthermore, the blood may include whole blood, plasma, serum, etc., but the disclosure is not limited thereto.

Referring to fig. 1, a biochemical test strip 100 includes an insulating substrate 10, an electrode unit 20, a first insulating spacer 30, a reaction layer 40 and a second insulating spacer 50. The insulating substrate 10 includes a substrate having electrical insulation properties. In some embodiments, the material of the insulating substrate 10 may include polyvinyl chloride (PVC), fiberglass (FR-4), polyethersulfone (PES), bakelite (bakelite), polyethylene terephthalate (PET), polycarbonate (PC), polypropylene (PP), polyethylene (PE), polystyrene (PS), polyimide (PI), glass plate, ceramic, or any combination of the above materials, but the disclosure is not limited thereto. The material of the insulating substrate 10 can be adjusted according to the system or the actual requirement.

The electrode unit 20 of the biochemical test strip 100 is disposed on the insulating substrate 10. The electrode unit 20 is disposed on the insulating substrate 10 to perform electrochemical measurement. Electrochemical measurements include analyzing the concentration of a sample using an electroreaction such as potentiometry, conductometry, voltammetry, polarography, high frequency titration, amperometry, coulometry or electrolysis. The electrode unit 20 includes a working electrode 22 and a counter electrode 24, but the disclosure is not limited thereto. The electrode unit 20 may be configured with other electrodes according to the system requirements. Working electrode 22 is the electrode on the surface of which the target analyte undergoes an electro-oxidation or electro-reduction reaction and which can be used by the meter as a concentration interpretation. In detail, the electro-oxidation reaction or electro-reduction reaction is an electrochemical reaction of the target analyte, which is a reciprocal conversion between electric energy and chemical energy performed on the surface of the working electrode 22.

The polarity of the working electrode 22 may be either anode or cathode, depending on the requirements of the measurement reaction. For example, if the target analyte is oxidized on the working electrode 22, the working electrode 22 is an anode; if the target analyte undergoes a reduction reaction at working electrode 22, working electrode 22 is the cathode. Counter electrode 24 is the electrode that undergoes an electro-reduction or electro-oxidation reaction with respect to working electrode 22 to conform the overall electrochemical system to the charge balance principle. The potential and polarity of counter electrode 24 is opposite to the potential and polarity of working electrode 22. The working electrode 22 and the counter electrode 24 are insulated from each other before being in contact with the sample. An electrical circuit is formed between the working electrode 22 and the counter electrode 24 and the meter when they are in contact with the sample. In some embodiments, working electrode 22 and counter electrode 24 may comprise carbon electrodes, silver electrodes, platinum electrodes, etc., but the disclosure is not limited thereto. The materials of working electrode 22 and counter electrode 24 may vary depending on the system requirements.

The first insulating spacer 30 is disposed on the insulating substrate 10 and is located on the electrode unit 20. The first insulating spacer 30 may have an opening 32, and the opening 32 at least partially exposes the electrode unit 20. In some embodiments, the opening 32 is located at the front side 30F of the first insulating spacer 30 and exposes a portion of the electrode unit 20. The opening 32 defines a reaction zone 34 of the biochemical test strip 100, and the reaction zone 34 is used for accommodating a sample. The portion of the electrode unit 20 exposed to the opening 32 may electrochemically react with the sample. The opening 32 may be sized or shaped according to the area of the electrode unit 20 and the amount of sample required for measurement. In some embodiments, the rear side 30B of the first insulating spacer 30 exposes a portion of the electrode unit 20 to form the connection region 10C. The electrode unit 20 exposed to the connection region 10C may be electrically connected to the meter. The meter is electrically connected to the biochemical test strip 100 to provide the energy required for the electrochemical measurement and analyze the reaction signal. In some embodiments, the material of the first insulating spacer 30 includes PVC insulating tape, PET insulating tape, thermal drying type insulating paint or uv curable insulating paint, but the disclosure is not limited thereto.

Fig. 2 is a schematic partial top view of a biochemical test strip 100 according to some embodiments of the present disclosure. Referring to fig. 2 together with fig. 1, the biochemical test strip 100 further includes a reaction layer 40. The reaction layer 40 is located in the opening 32 of the first insulating spacer 30. A reaction layer 40 is located in reaction zone 34. The reaction layer 40 is used to chemically react with the sample. The reaction layer 40 is electrically connected to the electrode unit 20. In some embodiments, the reaction layer 40 is electrically connected to the working electrode 22 of the electrode unit 20. In some embodiments, the area of the reaction layer 40 is less than the size of the opening 32. The reaction layer 40 at least partially covers the electrode unit 20 exposed by the opening 32. In the present embodiment, the reaction layer 40 only covers the working electrode 22, but the disclosure is not limited thereto. In some embodiments, the reaction layer 40 is at least partially in contact with the working electrode 22 of the electrode unit 20. In some embodiments, the reaction layer 40 is at least partially in contact with the working electrode 22 and the counter electrode 24 of the electrode unit 20.

In some embodiments, the reaction layer 40 includes enzymes and a conductive medium. For example, enzymes include immobilized or non-immobilized enzymes such as redox enzymes, antigens, antibodies, microbial cells, animal and plant cells, and components of animal and plant tissues having biological recognition capabilities. The conductive medium is used for receiving electrons generated after the enzyme reacts with the blood sample and conducting the electrons to the measuring instrument through the electrode unit 20. In some embodiments, the conductive medium may include hematite (potassium hexacyanoferrate (III)), yellow hematite (potassium hexacyanoferrate (II) trihydrate), ruthenium complex (rutheniumcomplex), ferrocene (ferrocene), sodium dithiosulfinate (sodium dithionite), nicotinamide adenine dinucleotide (nicotinamide adenine dinucleotide, nad+), nicotinamide adenine dinucleotide phosphate (nicotinamide adenine dinucleotide phosphate, nadp+), thiamine pyrophosphate (thiamin pyrophosphate, TPP), coenzyme a (coenzea, hscooa), flavin adenine dinucleotide (flavin adenine dinucleotide, FAD), or a combination thereof, but the disclosure is not limited thereto. In some embodiments, the reaction layer 40 may also add phosphate buffer and protectants, such as: proteins, dextrins, glucosan, amino acids, and the like, but the disclosure is not limited thereto.

Referring again to fig. 1, the second insulating spacer 50 is positioned on the first insulating spacer 30. In some embodiments, the second insulating spacer 50 at least partially covers the opening 32 of the first insulating spacer 30 such that the opening 32 forms a capillary structure. In some embodiments, the second insulating spacer 50 is provided with a vent 52 at the end corresponding to the opening 32. The vent 52 may have any shape, for example, the vent 52 may be circular, oval, rectangular, diamond-shaped, etc. The second insulating spacer 50 may have any shape or size. In some embodiments, the second insulating spacer 50 also exposes the electrode unit 20 on the connection region 10C.

Referring to fig. 2 together with fig. 1, the opening 32 of the first insulating spacer 30 at least partially exposes the electrode unit 20. The opening 32 at least partially exposes the working electrode 22 and the counter electrode 24. In the present embodiment, at least the working electrode 22 and the counter electrode 24 are disposed in the reaction region 34, but the disclosure is not limited thereto. In other embodiments, electrodes having other functions may be additionally disposed in the reaction zone 34. Further, the present disclosure is not limited to the configuration of the electrodes, and the working electrode 22 and the counter electrode 24 may have any shape. In some embodiments, working electrode 22 and counter electrode 24 may each have different shapes. In some embodiments, the material of working electrode 22 and the material of counter electrode 24 are different from each other or the same as each other.

In this embodiment, the working electrode 22 and the counter electrode 24 are insulated from each other before being in contact with the sample. When the sample is in contact with the working electrode 22 and the counter electrode 24, an electrical circuit is formed between the working electrode 22 and the counter electrode 24 and the meter. Fig. 3A and 3B are schematic diagrams of electrochemical reactions drawn according to some embodiments of the present disclosure. For simplicity of illustration, fig. 3A and 3B only show a portion of the biochemical test strip 100. In detail, fig. 3A and 3B only show a portion of the working electrode 22 and the counter electrode 24 within the reaction zone 34. As shown in fig. 3A and 3B, the working electrode 22 and the counter electrode 24 exposed in the reaction region 34 are in contact with the sample S and form an electrical circuit with the meter M. Fig. 3A and 3B further illustrate a portion of the enzyme E and the conductive medium C in the reaction region 34, wherein the enzyme E and the conductive medium C are part of the reaction layer 40 (shown in fig. 2). In some embodiments, the conductive medium C may be an iron ion, but the disclosure is not limited thereto.

Referring to fig. 3A, a sample S includes a target analyte R, wherein the target analyte R includes an electrochemically active material or an electrochemically reactive material. After the sample S is injected into the reaction region 34 of the biochemical test strip 100, the target analyte R in the sample S is reduced by the enzyme E of the reaction layer 40 to form a reduced target analyte R', but the disclosure is not limited thereto. In other embodiments, target analyte R in sample S may be oxidized by enzyme E of reaction layer 40 to form oxidized target analyte R'.

The conductive medium C of the reaction layer 40 is used to receive or provide electrons generated or lost by the reaction of the enzyme E with the target analyte R of the sample S and to conduct the electrons to the meter M via the working electrode 22 of the electrode unit 20. For simplicity of illustration, the conductive medium C of the present embodiment is formed by ferrous ions (Fe ²⁺ ) For illustration, the disclosure is not so limited. When target analyte R in sample S is reduced, conductive medium C of reaction layer 40 is oxidized. In the present embodiment, ferrous ions (Fe ²⁺ ) Oxidized to ferric ion (Fe ³⁺ ). In addition, the conductive medium C of the reaction layer 40 is oxidized by a corresponding amount corresponding to the reduced amount of the target analyte R.

When in opposition toConductive medium C of the stress layer 40 (e.g., fe ²⁺ ) Releasing electrons into an oxidation state conductive medium C' (e.g.: fe (Fe) ³ ⁺ ) During this time, the working electrode 22 also reacts to form an oxidation state conductive medium C' (e.g.: fe (Fe) ³⁺ ) Reduction to reduced-state conductive medium C (e.g.: fe (Fe) ²⁺ ). The measuring instrument M detects the number of electrons (e ^- ) Change, and conduct concentration analysis. When working electrode 22 undergoes a reduction reaction, counter electrode 24 must simultaneously oxidize a corresponding amount of reduced conducting medium C (e.g., fe ²⁺ ) So that the overall reaction reaches a neutral equilibrium.

In general, when the counter electrode 24 has insufficient oxidizing ability to match the working electrode 22, for example: when the counter electrode 24 oxidizes the conductive medium C in an amount smaller than the amount by which the working electrode 22 reduces the conductive medium C, the magnitude of the reduction current generated by the working electrode 22 is limited based on the charge neutral balance, thus creating a bottleneck effect. The bottleneck effect caused by the electron flow from the working electrode 22 exceeding the electron flow from the counter electrode 24 limits the range of measurable concentrations of the biochemical test strip 100.

In the prior art, the occurrence of the aforementioned bottleneck effect is related to the size of the areas of the working electrode 22 and the counter electrode 24. The electrochemical oxidation or reduction of the target analyte R in the sample S produces a change in current that is linearly proportional to the concentration of the target analyte R in the sample S. Thus, the concentration of the target analyte R in the sample S can be analyzed by measuring the oxidation or reduction current at the surface of the working electrode 22, which current versus concentration can be expressed asWherein i is the measured current, and the unit is A; n is the number of electrons generated by the oxidation-reduction reaction; f is Faraday constant 96500C/mol; a is the surface area of the working electrode in cm ² ；C ₀ The initial concentration of the sample is given in mol/cm ³ The method comprises the steps of carrying out a first treatment on the surface of the D is the diffusion coefficient in cm ² S; t is time in s. From the above, the magnitude of the current signal of the electrochemical reaction is positive to the surface area of the electrodeRatio relation.

In the prior art, the working electrode 22 and the counter electrode 24 are made of the same material in order to save the manufacturing process. In addition, inert carbon is often used for the working electrode 22 and counter electrode 24 materials in order to avoid additional background signal interference due to redox of the electrode material itself and electrode lifetime considerations. In other embodiments, the materials of the working electrode 22 and the counter electrode 24 include gold, palladium, and the like. In other prior art embodiments, the material of working electrode 22 is selected to be a material that is more reactive with target analyte R of sample S than the material of counter electrode 24. The material of working electrode 22 is selected to have a preferred electrochemical activity or reactivity over the material of counter electrode 24. For example, the material of the working electrode 22 is mostly a silver electrode or a silver oxide electrode having better reactivity with the target analyte R, while the material of the counter electrode 24 is mostly a carbon electrode or a platinum electrode having poorer reactivity with the target analyte R.

Referring to fig. 3B, in the present disclosure, the materials of working electrode 22 and counter electrode 24 are selected such that the current density of counter electrode 24 is greater than the current density of working electrode 22. In some embodiments, the material of counter electrode 24 is more electrochemically reactive than the material of working electrode 22. In particular, the material of counter electrode 24 is selected to have a good electrochemical reactivity with environmental substances. The environmental substance refers to a substance other than the target analyte R of the sample S. In some embodiments, the material of counter electrode 24 has a better electrochemical activity than the material of working electrode 22. The material of the counter electrode 24 is selected to have a preferred electrochemical activity with the environmental species. In some embodiments, the area of counter electrode 24 may be less than or equal to the area of working electrode 22. In some embodiments, the current density of counter electrode 24 is greater than or equal to twice the current density of working electrode 22.

In this embodiment, the counter electrode 24 may include an active material having conductivity. In some embodiments, the active material may be doped within the counter electrode 24. In some embodiments, the active material may be formed on the surface of the counter electrode 24. In some embodiments, counter electrode 24 is composed of an active material. The active material means that when the biochemical reaction is performed on the biochemical test strip 100, the active material of the counter electrode 24 may perform self-oxidation or reduction reaction without interfering with the main reaction. The primary reaction refers to an oxidation or reduction reaction caused by the target analyte R and the reaction layer 40, and the secondary reaction refers to an oxidation or reduction reaction not caused by the target analyte R and the reaction layer 40. In detail, the source of the reactant is not limited as long as the secondary reaction on the counter electrode 24 does not affect the primary reaction of the working electrode 22, and thus the substance required for the secondary reaction may be derived from the sample S or from the environment. The active material of the counter electrode 24 is a substance that undergoes oxidation and reduction in the operating voltage range. The operating voltage refers to the voltage supplied by the meter M that causes the electrochemical reaction between the working electrode 22 and the counter electrode 24. In some embodiments, the operating voltage is + -10 volts (V). In other embodiments, the operating voltage is + -5V. In some implementations, the operating voltage is ±2v. In some implementations, the operating voltage is ±1v.

Referring to fig. 3B, the counter electrode 24 of the present embodiment has an active material with conductive capability, and can perform a secondary reaction without disturbing the primary reaction. The aforementioned secondary reactions provide the counter electrode 24 with the ability to receive or release additional electrons. The additional electrons refer to electrons generated by the enzyme E or the conductive medium C of the non-reactive layer 40. In other words, the counter electrode 24 can be reacted secondarily from the active material to obtain electrons without breaking the neutral balance of the meter M, in addition to the electrochemical reaction with the target analyte R of the sample S.

As shown in fig. 3B, when the sample S is filled into the reaction area 34 and the measuring instrument M provides the working voltage, the target analyte R of the sample S reacts with the enzyme E of the reaction layer 40, so as to promote the reduction of the corresponding amount of the oxidation-state conductive medium C' on the working electrode 22 to the reduction-state conductive medium C. On the other hand, counter electrode 24 needs to oxidize the reduced-state conductive medium C of the reduced electron number of the corresponding working electrode 22 to the oxidized-state conductive medium C' to maintain the electric neutral balance of the entire system. Because the counter electrode 24 of the present disclosure has an active material that can undergo a secondary reaction, when the counter electrode 24 oxidizes the reduced form of the conductive medium C and receives electrons, it itself also undergoes an additional oxidation reaction to generate additional electrons. In this embodiment, the materials of working electrode 22 and counter electrode 24 are selected such that the current density of counter electrode 24 is greater than the current density of working electrode 22. The active material of the counter electrode 24 may undergo a self-oxidation or reduction reaction without interfering with the main reaction.

Referring again to fig. 1 and 2, the working electrode 22 is an electrode that analyzes the electrooxidation or electroreduction current. Thus, the working electrode 22 is composed of an inactive material that does not interfere on the electrode surface. It should be noted that the term "non-active material" as used in this disclosure means that the material does not undergo oxidation or reduction in the measurement environment of the biochemical test strip 100. In other words, the inactive materials referred to in this disclosure may have redox capabilities in other particular environments, but the inactive materials do not undergo redox reactions during the measurement process of this disclosure. The inactive material of working electrode 22 may comprise a conductive material. For example, the inactive material of the working electrode 22 may include palladium, platinum, gold, carbon, or combinations thereof, but the disclosure is not limited thereto. The inactive material of the working electrode 22 may be tailored to the system requirements.

On the other hand, the active material of the counter electrode 24 means that the material undergoes oxidation or reduction in the measurement environment of the biochemical test strip 100. The redox change of the active material of the counter electrode 24 is directly or indirectly causally related to the measuring environment of the biochemical test strip 100. In the present disclosure, the characteristics of the material of the counter electrode 24 must be matched to the working electrode 22. For example, the working electrode 22 is electrically reduced, and the active material of the counter electrode 24 is a material having self-oxidizing ability. In other embodiments, the counter electrode 24 is made of a material having self-reducing capability when the surface of the working electrode 22 undergoes an electro-oxidation reaction.

It should be noted that, to ensure that the active material of the counter electrode 24 performs a predetermined function during electrochemical measurement, it should be avoided that it excessively reacts before measurement, and the active material of the counter electrode 24 of the present disclosure is not in contact with the reaction layer 40 before measurement to avoid that the two react before measurement. However, in the electrochemical measurement of the biochemical test strip 100, the reaction layer 40 needs to react with the counter electrode 24, so that the smaller the distance between the working electrode 22 and the counter electrode 24 is, the better. In some embodiments, the active material of the counter electrode 24 may be covered with a protective film, wherein the protective film may be melted after the sample S enters.

In some embodiments, the active material of counter electrode 24 may include, but is not limited to, silver (Ag), tin (Sn), iron (Fe), zinc (Zn), cobalt (Co), nickel (Ni), lead (Pb), copper (Cu), manganese dioxide (MnO) ₂ ) Ferroferric oxide (Fe) ₃ O ₄ ) Ferric oxide (Fe) ₂ O ₃ ) Ferrous oxide (FeO), silver chloride (AgCl), cobalt sesquioxide (Co) ₂ O ₃ ) Cobalt oxide (CoO), nickel oxide (Ni) ₂ O ₃ ) Nickel oxide (NiO), copper oxide (CuO), copper oxide (Cu) ₂ O), benZoquinone (BenZoquinone), ferrocene (Ferrocene), ferrocenium (Ferrocenium), spinel structure mixed valence metal oxide (such as Fe) ₃ O4、Co ₃ O ₄ Etc.), iron ferricyanide, prussian blue (Fe) ₄ [Fe(CN) ₆ ] ₃ ) Metal salts of ferricyanic acid ([ Fe (CN)) ₆ ] ^3- ) Ferricyanic acid metal salts ([ Fe (CN)) ₆ ] ^4- ) A metal complex, or a combination thereof, but the disclosure is not limited thereto.

Referring again to fig. 3B, for simplicity of illustration, silver (Ag) is taken as an example of the active material of the counter electrode 24, but the disclosure is not limited thereto. Specifically, since the silver (Ag) of the counter electrode 24 is in direct contact with the sample S, the reaction region 34 contains water (H) in addition to the operating voltage applied by the meter M ₂ O) or hydroxide ions (OH) ^- ) And the like under which oxidation of silver (Ag) occurs. Thus, under appropriate circumstances, the silver of the counter electrode 24 can react with hydroxide ions (OH) from the sample S or from the environment ^- ) Water (H) ₂ O) or water gas generates oxidation reaction, and the reaction formula can be expressed as 2Ag+2OH ^- →Ag ₂ O+H ₂ O+2e ^- Or 2Ag+H ₂ O→Ag ₂ O+2H ⁺ +2e ^- . Silver (Ag) and sample S or hydroxide ions (OH) in the environment ^- ) Or silver oxide (Ag) is produced after oxidation-reduction reaction of water ₂ O), water (H) ₂ O) and O)And (3) electrons. Thus, for the overall reaction, the counter electrode 22 will oxidize the reduced-state conductive medium C (e.g., fe ²⁺ ) In addition, the oxide electrode (silver oxide) is formed by self-oxidation and releases electrons (e) ^- ). Thus, electrons generated by the active material of the counter electrode 24 help to promote the counter electrode 24's ability to balance overall charge neutrality while observing the principles of conservation of charge.

Thus, when working electrode 22 is subjected to a large number of electroreduction operations, counter electrode 24 may be correspondingly subjected to electrooxidation operations to satisfy the electrical neutral balance of the overall system. It is noted that although the active material (e.g., silver) of the counter electrode 24 consumes water (H) during oxidation ₂ O) or hydroxide ions (OH) ^- ) And generates hydrogen ions (H) ⁺ ) Or water (H) ₂ O) while partially changing the pH of the reaction zone 34, the resulting pH change is very small for the overall system and therefore has no effect on the main reaction and no effect on the detection results, and the change is negligible.

To ensure that the active material of the counter electrode 24 has the above-described function, the polarity of the reaction of the active material and the counter electrode 24 must be the same. In other words, although the oxidation number of the active material is not necessarily equal to that of the counter electrode 24, the active material must have oxidation capability when the counter electrode 24 is an anode; when the counter electrode 24 is a cathode, the active material must have a reducing ability. The active material is selected to match the polarity of the reaction of the counter electrode 24 and to promote the neutral balance of the counter electrode 24 while maintaining charge conservation. Therefore, when the counter electrode 24 is an anode, the standard reduction potential of the active material of the counter electrode 24 must be met Wherein (1)>Is the standard reduction potential of the active material, +.>A standard reduction potential for concentration reactions at working electrode 22; e (E) _v The measuring instrument M is provided with the potential applied by the measuring reaction.

In some embodiments, conductive medium C is ferricyanideThe measuring instrument M applies an operating voltage (E _v ) At +0.4V, the working electrode 22 undergoes an oxidation reaction, so that the reaction of the conductive medium C on the surface of the working electrode 22 isIt is->Therefore, the standard reduction potential of the active material required for the reduction reaction of the electrode 24 of this embodiment +.>Must be greater than-0.04V, so the standard reduction potential +.>A material of more than-0.04V is used as the material of the counter electrode 24, for example: fe (Fe) ₃ O ₄ (E ⁰ ＝+0.085V)、AgCl(E ⁰ ＝+0.2223V)、Ferrocenium(E ⁰ = +0.4v) or Benzoquinone (E ⁰ = + 0.6992V), etc., but the disclosure is not limited thereto.

In some embodiments, conductive medium C is ferricyanideThe measuring instrument M applies an operating voltage (E _v ) at-0.4V, the working electrode 22 undergoes a reduction reaction, so that the reaction of the conductive medium C on the surface of the working electrode 22 isIt is->Therefore, the embodiment is to perform the oxidation reaction on the electrode 24Standard reduction potential of the desired active material +.>Must be less than 0.76V, so the standard reduction potential can be chosen>A material of less than 0.76V, such as Ferrocene (E) ⁰ ＝+0.4V)、Cu(E ⁰ ＝+0.34V)、Fe(E ⁰ ＝+0.085V)、Sn(E ⁰ = -0.1V), etc., but the disclosure is not limited thereto.

The foregoing is merely an example of an active material for the counter electrode 24, and the present disclosure is not limited thereto. In addition, the standard reduction potential of the active material of the counter electrode 24 is not limited to the above. As before, the polarity of the active material of the counter electrode 24 must be considered, and the polarity of the active material must be the same as the polarity of the measurement reaction at the counter electrode 24. In addition, the standard reduction potential of the active material of the counter electrode 24 must be metOr->Is a condition of (2). In some embodiments, E _v Can be + -5V to + -2 mV. In some embodiments, E _v Can be + -2V to + -80 mV. In some embodiments, E _v Can be + -0.8V to + -0.1V.

The present disclosure is not limited to the foregoing embodiments, and may have other different embodiments. To simplify the description and facilitate comparison between each of the embodiments of the present disclosure, identical components in each of the following embodiments are labeled with identical numerals. In order to make it easier to compare differences between the embodiments, the following description will detail dissimilarities between different embodiments and identical features will not be repeated.

FIG. 4 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure. As shown in FIG. 4, the difference between the biochemical test strip 200 and the biochemical test strip 100 is that the counter electrode 24 includes a first portion 24A and a second portion 24B. In some embodiments, counter electrode 24 may include inactive materials as well as active materials. For example, in the present embodiment, the first portion 24A of the counter electrode 24 includes an active material, and the second portion 24B includes an inactive material. Thus, the first portion 24A has the ability to receive or release additional electrons.

In some embodiments, the first portion 24A and the second portion 24B of the counter electrode 24 of the present embodiment may be formed by disposing an active material on the insulating substrate 10 and then covering the inactive material on a predetermined position. In some embodiments, the first portion 24A and the second portion 24B of the counter electrode 24 of the present embodiment may be formed by disposing an inactive material on the insulating substrate 10 and then disposing an active material at predetermined positions of the opening 32. Thereby, the first portion 24A (active material) of the counter electrode 24 is exposed in the opening 32.

The method for disposing the first portion 24A and the second portion 24B of the electrode 24 may include, but is not limited to, screen printing (screen printing), imprinting (imaging), thermal transfer printing (thermal transfer printing), spin coating (spin coating), ink-jet printing (ink-jet printing), laser stripping (laser plating), deposition (deposition), electroplating (electro-deposition), and the like. In some embodiments, polymers such as polyaniline (polyaniline), polypyrrole (polypyrrole), polythiophene (polythiophene), polyvinylferrocene (polyvinylferrocene), and the like can be formed on the surface of the inactive material by plasma treatment (plasma) or other chemical bonding modification methods, and the surface of the counter electrode 24 is polymerized (polymerization) to form polymers, but the disclosure is not limited thereto. In some embodiments, a polymer chain may be grafted (graft) onto the surface of the inactive material of the counter electrode 24 and bonded to a conductive medium having a redox capability, such as ferrocenecarboxylic acid (ferrocenecarboxylic acid), to form the counter electrode 24.

FIG. 5 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure. As shown in FIG. 5, the difference between the biochemical test strip 300 and the biochemical test strip 200 is that the biochemical test strip 100 further comprises a protective layer 60. For example, the counter electrode 24 exposed to the environment may be oxidized by moisture or oxygen in the air to be changed. The biochemical test strip 300 is additionally provided with a protection layer 60 to protect the stability of the active material of the counter electrode 24. The protection layer 60 can be used to protect the counter electrode 24 in the biochemical test strip 300 to alleviate the unexpected variation of the first portion 24A of the counter electrode 24 in the environment, so as not to receive or release additional electrons, or to reduce the receiving or releasing of additional electrons.

The protective layer 60 is provided at a specific region of the electrode unit 20. In some embodiments, the protection layer 60 is electrically connected to the first portion 24A of the counter electrode 24 through the electrode unit 20. For example, in the present embodiment, the protection layer 60 is electrically connected to the first portion 24A and the second portion 24B of the counter electrode 24 through the branch 24C of the counter electrode 24. In some embodiments, the counter electrode 24 may not have the branch 24C, and the protection layer 60 may be directly disposed on the second portion 24B of the counter electrode 24 to be electrically connected to the first portion 24A of the counter electrode 24. In some embodiments, the protective layer 60 is at the same level as the first portion 24A of the counter electrode 24. In some embodiments, the protective layer 60 is at a different level than the first portion 24A of the counter electrode 24. For example, the protective layer 60 may be disposed above or below the counter electrode 24. In some embodiments, the protective layer 60 may be surrounded by the second portion 24B of the counter electrode 24.

In some embodiments, the first insulating spacer 30 may have a first opening (not shown), and the second insulating spacer 50 may have a second opening (not shown), the first opening and the second opening at least partially exposing the protective layer 60. The protection layer 60 and the counter electrode 24 may be exposed to the same environment, but the disclosure is not limited thereto. For example, the protective layer 60 may be disposed between the insulating substrate 10 and the first insulating spacer 30 and exposed to the same environment as the first portion 24A of the counter electrode 24 through the first and second openings. In other embodiments, the protective layer 60 and the counter electrode 24 may be exposed to different environments. For example, the protective layer 60 may be disposed between the insulating substrate 10 and the first insulating spacer 30, while the first insulating spacer 30 and the second insulating spacer 50 do not have the first opening and the second opening. The position of the protection layer 60 is not limited to the above, and in some embodiments, the protection layer 60 may be disposed on the second insulating spacer 50 and electrically connected to the electrode unit 20 through a wire. In other embodiments, the protection layer 60 may be disposed between the first insulating spacer 30 and the second insulating spacer 50 and electrically connected to the electrode unit 20 through wires.

The protective layer 60 may be solid, liquid, or gas in form. For example, the solid may include pure metals, alloys, metal compounds (halides, oxides, mixed valence compounds, organometallic complexes), organic redox agents, and the like. The liquid may include aqueous solutions, organic solutions, supercritical fluids, liquid elements (e.g., bromine, mercury), and the like. The gas may include gaseous elements (e.g., oxygen, ozone), gaseous compounds (e.g., ammonia, nitric oxide), and the like.

The protective layer 60 is of a different material or composition than the counter electrode 24 (or the first portion 24A of the counter electrode 24). The protective layer 60 and the counter electrode 24 can have a potential differenceIn some embodiments, the protective layer 60 has a potential difference +_ between the first portion 24A of the counter electrode 24>Potential difference->The formula of (2) is +.>Wherein E is _cathode For standard reduction potential of cathode (cathode electrode), E _anode Is the standard reduction potential of the anode (anode electrode). The protective layer 60 and the counter electrode 24 (or the first portion 24A of the counter electrode 24) may have different standard reduction potentials.

In the present disclosure, the potential difference between the protective layer 60 and the counter electrode 24Greater than 0. According to the relation of Gibbs free energy (Gibbs Free Energy), i.e，Wherein ΔG ⁰ The free energy is changed, n is the number of moles of electrons, and F is the charge per mole. When Gibbs free energy DeltaG ⁰ <At 0, the reaction is spontaneous. As can be seen from the above, when two have a potential difference +.>When the redox species in the same reaction vessel, the higher standard reduction potential tends to undergo reduction reaction, whereas oxidation reaction tends to occur. For example, when the standard reduction potential of the anode is less than the standard reduction potential of the cathode, the anode spontaneously transfers electrons to the cathode, which maintains the reduced state by continuously obtaining electrons, thus being protected from environmental oxidants (e.g., oxygen, moisture, etc.).

The protective layer 60 is in the same reaction chamber as the counter electrode 24. In some embodiments, the protective layer 60 is in contact with air simultaneously with the counter electrode 24, but the disclosure is not limited thereto. The passivation layer 60 is electrically connected to the counter electrode 24 and can be considered to be in the same reaction chamber. Due to the potential difference between the protective layer 60 and the counter electrode 24And the potential difference->Greater than 0, spontaneous electron flow in a specific direction occurs, and thus the object to be protected (the counter electrode 24 or the first portion 24A of the counter electrode 24) can maintain the original redox state. Thereby protecting the biochemical test piece 300 and reducing the unexpected variation of the biochemical test piece 300 and the environment. />

In some embodiments, the protective layer 60 has an area that is greater than the area of the counter electrode 24 (or the first portion 24A of the counter electrode 24). In some embodiments, the area of the protective layer 60 is substantially equal to the area of the counter electrode 24 (or the first portion 24A of the counter electrode 24). The areas and thicknesses of the protective layer 60 and the counter electrode 24 (or the first portion 24A of the counter electrode 24) may be adjusted according to system requirements. Depending on the materials of the protective layer 60 and the counter electrode 24 (or the first portion 24A of the counter electrode 24), the protective layer 60 and the counter electrode 24 (or the first portion 24A of the counter electrode 24) may be an anode and a cathode, respectively, and the protective layer 60 and the counter electrode 24 (or the first portion 24A of the counter electrode 24) may be a cathode and an anode, respectively.

For simplicity of illustration, silver (Ag) is taken as an example of the material of the first portion 24A of the counter electrode 24, but the disclosure is not limited thereto. In the present embodiment, the first portion 24A of the counter electrode 24 includes silver. However, silver readily reacts with oxygen and moisture in air to oxidize to silver oxide, the oxidation chemical formula of which can be expressed as 4Ag+O ₂ →2Ag ₂ O, wherein the standard reduction potential of silver/silver oxide is 1.17V. When silver is oxidized to silver oxide by contact with oxygen, the surface of the first portion 24A of the counter electrode 24 is poisoned, and thus the ability of the first portion 24A to receive or release additional electrons is reduced, and the bottleneck effect between the working electrode 22 and the counter electrode 24 is not effectively improved.

As shown in fig. 5, the biochemical test strip 300 is provided with a protection layer 60, and the protection layer 60 is electrically connected to the counter electrode 24. In some embodiments, a protective layer 60 is used to protect the first portion 24A of the counter electrode 24. In some embodiments, the protective layer 60 may include stannous oxide (SnO). Since stannous oxide easily performs oxidation reaction with water vapor in air, the reaction formula can be expressed as SnO+H ₂ O→SnO ₂ +2H ⁺ +2e ^- . The standard reduction potential for silver oxide/silver was 1.17V, while the standard reduction potential for stannous oxide/stannic oxide was-0.09V. Thus, in the present embodiment, the first portion 24A of the counter electrode 24 is a cathode, and the protective layer 40 is an anode. When the biochemical test piece 300 is exposed to the environment with moisture, the potential difference is generated 1.08V. Due to the difference in potential between the two>Greater than 0, free energy changeLess than 0, the following reaction Ag will spontaneously proceed ₂ O+SnO→2Ag+SnO ₂ . Wherein the half reaction occurring on the first portion 24A of the counter electrode 24 is Ag ₂ O+2H ⁺ +2e ^- →2Ag+H ₂ O。

Accordingly, the silver oxide in the first portion 24A of the counter electrode 24 is reduced to silver by the oxidation reaction of the stannous oxide of the protective layer 60. When the oxidation reaction of the protection layer 60 occurs, the first portion 24A of the counter electrode 24 undergoes a reduction reaction, so as to slow down the oxidation reaction of oxygen and moisture in the air. In addition, the oxidation reaction of the water vapor in the air to the stannous oxide further protects the first portion 24A of the counter electrode 24, so that the first portion 24A of the counter electrode 24 can maintain good stability. Therefore, by disposing the protective layer 60 in the biochemical test strip 300, the first portion 24A of the counter electrode 24 is effectively prevented from being degraded before the measurement of the sample. The constituent materials of the first portion 24A of the counter electrode 24 and the protective layer 60 are not limited to the above. In some embodiments, the constituent materials of the first portion 24A of the counter electrode 24 and the protective layer 60 are selected such that a potential difference between the twoGreater than 0.

The present embodiment provides a biochemical test strip 300 with a protection layer 60, wherein the protection layer 60 can maintain the stability of the active material in the counter electrode 24, thereby protecting the biochemical test strip 300 and slowing down the unexpected variation of the biochemical test strip 300 and the environment before the biochemical test strip 300 is used for measuring the sample, and further maintaining or protecting the receiving or releasing of additional electrons of the counter electrode 24 of the biochemical test strip 300.

FIG. 6 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure. As shown in FIG. 6, the biochemical test strip 400 is different from the biochemical test strip 100 in that the working electrode 22 and the counter electrode 24 are composite electrodes. The working electrode 22 includes a first portion 22X and a second portion 22Y. The counter electrode 24 includes a first portion 24X and a second portion 24Y. In some embodiments, both working electrode 22 and counter electrode 24 may be composed of inactive material together with active material. For example, in the present embodiment, the first portion 22X of the working electrode 22 and the first portion 24X of the counter electrode 24 comprise inactive materials, while the second portion 22Y of the working electrode 22 and the second portion 24Y of the counter electrode 24 comprise active materials.

In some embodiments, the inactive material may comprise carbon and the active material may comprise silver. Working electrode 22 and counter electrode 24 are composed of inactive material in combination with active material to promote overall conductivity and conductivity. The first portion 22X of the working electrode 22 completely overlaps the second portion 22Y of the working electrode 22, while the first portion 24X of the counter electrode 24 does not completely overlap the second portion 24Y of the counter electrode 24. In this embodiment, the first portion 24X of the counter electrode 24 at least partially exposes the second portion 24Y of the counter electrode 24.

In some embodiments, opening 32 at least partially exposes second portion 24Y of counter electrode 24, while opening 32 does not expose second portion 22Y of working electrode 22. Since the second portion 24Y of the counter electrode 24 includes an active material, it has the ability to receive or release additional electrons. The second portion 24Y of the counter electrode 24 is exposed through the opening 32 to receive or release additional electrons of the biochemical test strip 400 in the measurement reaction. Thereby, the ability of the counter electrode 24 to be electrically neutral balanced can be enhanced.

In some embodiments, the active material may be disposed on the insulating substrate 10 and then the inactive material may be covered on predetermined positions to form the working electrode 22 and the counter electrode 24 of the present embodiment. The method for disposing the working electrode 22 and the counter electrode 24 may include, but is not limited to, screen printing (screen printing), imprinting (imprinting), thermal transfer printing (thermal transfer printing), spin coating (spin coating), ink-jet printing (ink-jet printing), laser stripping (laser plating), deposition (deposition), and electroplating (electroplating).

FIG. 7 is an exploded view of a biochemical test strip according to some embodiments of the present disclosure. As shown in FIG. 7, the difference between the biochemical test strip 500 and the biochemical test strip 200 is that the counter electrode 24 has an interdigital structure. The counter electrode 24 includes a first portion 24A and a second portion 24B. In some embodiments, the first portion 24A and the second portion 24B are each composed of an active material and a non-active material. The opening 32 at least partially exposes the first portion 24A and the second portion 24B. In the opening 32, the counter electrode 24 is provided with both an active material (first portion 24A) and a non-active material (second portion 24B). In this embodiment, the second portion 24B of the counter electrode 24 is responsible for the conventional working of the counter electrode 24 with the working electrode 22, while the first portion 24A of the counter electrode 24 compensates for the deficiency of the second portion 24B by self-oxidation or reduction. In detail, the first portion 24A of the counter electrode 24 can receive or release the extra electrons of the biochemical test strip 500 during the measurement reaction.

FIG. 8 is a schematic partial top view of a biochemical test strip according to some embodiments of the present disclosure. As shown in fig. 8, the difference between the biochemical test strip 600 and the biochemical test strip 200 is that the biochemical test strip 600 is provided with a first pair of electrodes 24 and a second pair of electrodes 26, and the first pair of electrodes 24 and the second pair of electrodes 26 are separated from each other. The first and second pairs of electrodes 24, 26 include first and second portions 24A, 24B, 26A, 26B, respectively. The first portion 24A of the first pair of electrodes 24 and the first portion 26A of the second pair of electrodes 26 comprise an active material, while the second portion 24B of the first pair of electrodes 24 and the second portion 26B of the second pair of electrodes 26 comprise an inactive material. The opening 32 at least partially exposes the first portion 24A of the first pair of electrodes 24 and the first portion 26A of the second pair of electrodes 26.

In some embodiments, the material of the first portion 24A of the first pair of electrodes 24 may undergo a self-oxidation reaction and the material of the first portion 26A of the second pair of electrodes 26 may undergo a self-reduction reaction. In some embodiments, the standard reduction potential of the first pair of electrodes 24 is greater than the standard reduction potential of the second pair of electrodes 26. In some embodiments, the standard reduction potential of the first portion 24A of the first pair of electrodes 24 is greater than the standard reduction potential of the first portion 26A of the second pair of electrodes 26.

In some embodiments, the sum of the area of the first portion 24A of the first pair of electrodes 24 and the area of the first portion 26A of the second pair of electrodes 26 is less than or equal to the area of the working electrode 22. In some embodiments, the sum of the areas of the first portion 24A of the first pair of electrodes 24 and the first portion 26A of the second pair of electrodes 26 exposed in the opening 32 is less than or equal to the area of the working electrode 22 exposed in the opening 32.

The first portion 24A of the first pair of electrodes 24 and the first portion 26A of the second pair of electrodes 26 are exposed through the opening 32 to receive or release additional electrons of the biochemical test strip 600 in the measurement reaction. By electrically switching the first pair of electrodes 24 and the second pair of electrodes 26, the working electrode 22 is free from bottleneck effect in oxidation reaction or reduction reaction. Thus, the biochemical test piece 600 can measure the concentration of the substance under different reactions.

Fig. 9A and 9B are graphs showing signal comparisons of the counter electrode of the present embodiment and the counter electrode of the comparative embodiment applied at different concentrations, respectively, wherein fig. 9A is a graph of blood sample signals of 43% hematocrit 200mg/dL blood glucose, and fig. 9B is a graph of blood sample signals of 43% hematocrit 600mg/dL blood glucose. In detail, curve A of FIGS. 9A and 9B is 4.8mm ² 0.8mm of the working electrode of the embodiment of the present disclosure ² Is a blood sample signal plot of the counter electrode. Curve B is 4.8mm ² 2.4mm of the working electrode of the comparative example ² Is a blood sample signal plot of the counter electrode. Wherein the working electrode is a carbon electrode. 0.8mm of the examples of the present disclosure ² The counter electrode of (a) is exemplified by a silver oxide electrode, but the disclosure is not limited thereto. 2.4mm of comparative example ² Is commercially available with an area of 2.4mm ² Carbon electrodes are examples. Curve a and curve B are graphs comparing signals using the oxidation concentration measurement method under the same environmental conditions.

As shown in fig. 9A, since the counter electrode (inactive material) is generally sufficient to support the charge transfer amount of the reduction reaction on the working electrode in a low concentration environment, the signals of the counter electrode of the present embodiment and the counter electrode of the comparative embodiment are almost identical except for the difference in the subtracted impedance obtained by both the curve a and the curve B.

As shown in fig. 9B, in a high concentration environment, the counter electrode (inactive material) cannot generally match the charge transfer amount at the time of the reduction reaction of the working electrode at a high concentration, and thus a bottleneck effect occurs. On the other hand, since the counter electrode of the present embodiment has the self-redox capability, and thus can receive or release additional electrons, the counter electrode of the present embodiment can measure a higher signal with the same area or smaller area than the common electrode.

Fig. 10 is a graph showing a comparison of signals when the counter electrode of the present embodiment and the counter electrode of the comparative embodiment have different areas. FIG. 10 is a signal comparison chart of a reduction concentration measurement method performed on a sample of plasma (plasma) of 600mg/dL blood glucose tested by the counter electrode of the present example and the counter electrode of the comparative example versus a high concentration test. Wherein the working electrode is a carbon electrode with an electrode area of 4.8mm ² . The counter electrodes of the embodiment are silver electrodes with electrode areas of 0.8mm respectively ² (Curve A), 1mm ² (Curve B) and 1.2mm ² (Curve B). The counter electrode of the comparative example was a carbon electrode having electrode areas of 1.2mm, respectively ² (Curve D), 1.8mm ² (Curve E) and 2.4mm ² (curve F).

As shown in fig. 10, the counter electrode of the comparative example also continuously increased in the intensity of the reaction current with the increase in the area, representing the electrode area of the counter electrode of the comparative example, which was insufficient to support the electron flow through the working electrode and thus resulted in the bottleneck effect. However, in this embodiment, the counter electrode is not increased by the increase in the area of the counter electrode, and is still a stable value. Therefore, the counter electrode of the present embodiment can be smaller than the counter electrode of the comparative embodiment in electrode area, and is sufficient to support the electron flow flowing through the working electrode, so that no bottleneck effect is generated.

It should be noted that the counter electrode of this embodiment has a great signal difference from the counter electrode of the comparative embodiment. Because the working electrode has a large amount of ferric ions (Fe ³⁺ ) For its electroreduction, however, the counter electrode of the comparative example fails to oxidize the same amount of conductive medium at the same time, so the resulting signal is very small compared to the counter electrode of the present example. The counter electrode of the present embodiment has an oxidizable capacity itself, and electrons can be released by itself through oxidation. In addition, the counter electrode of the present embodiment can oxidize ferrous ions (Fe ²⁺ ). Thus, the electron flow flowing through the working electrode can be matched sufficiently, and no bottleneck effect is generated.

FIGS. 11A and 11B show the signals of different materials for the anode and cathode counter electrodes, respectivelyThe numbers compare the graphs. The working electrode is a carbon electrode, the counter electrode comprises three materials of silver (curve A), silver oxide (AgO) (curve B) and carbon (curve C), and the current density (A/m) of the biochemical test piece is detected by using the same chemical conditions ² )。

As shown in fig. 11A, the counter electrode of fig. 11A is an anode. Carbon itself does not have its own oxidation or reduction capability, so its signal size is related to the reaction layer and area. The silver has self-oxidation capability when the system environment accords with Silver oxidizes itself in the formula, and thus has a higher current density than carbon. Silver oxide does not have oxidizing ability, so when the counter electrode is an anode, even if the system environment satisfies +.>The formula is that the silver oxide cannot be oxidized to provide electrons, so that the current density (A/m ² ) Similar to carbon.

It is worth noting that the active material of the present disclosure refers to the active material that is positive at the counter electrode and the system satisfies the following conditionsThe equation may be formulated to undergo a secondary reaction, however the present disclosure is not limited to the current density that the secondary reaction may increase. In some embodiments, the current density of the counter electrode is 2 times higher than the current density of the working electrode. In addition, the present disclosure is not limited to the state of the counter electrode at the time of use, and the counter electrode may include an active material from the time of production or may be provided with the ability of the active material through the meter. In some embodiments, the counter electrode may be silver oxide, which is reduced to silver by application of an appropriate potential after the sample is injected into the reaction zone.

As shown in fig. 11B, the counter electrode of fig. 11B is a cathode. In the present embodiment, silver without reducing ability cannot receive additional electrons, so it cannot meet the system environmentIn the case of secondaryThe reaction, so that its current density (A/m) ² ) Similar to carbon. Conversely, silver oxide has a reducing ability, and it meets +_ in the system environment>Has sub-reactivity, and thus its current density (A/m ² ) Higher than silver.

As noted, the active materials of the present disclosure refer to materials that possess sub-reactivity under conditions of polarity in conjunction with a counter electrode. In other words, even though the active material has its own oxidation or reduction ability under a specific environment, the active material is not suitable for the counter electrode of the present disclosure if the environment of the main reaction does not allow the active material to undergo oxidation or reduction when the main reaction proceeds.

In the above description of the present disclosure, various biochemical test strips provided with counter electrodes including active materials are provided, and the counter electrodes including active materials can provide an amount of electrons equivalent to an amount of electrons generated by a reaction of a conductive medium on a working electrode when the system is applied with a proper voltage in an environment where an electrode area is limited or a concentration of the conductive medium capable of conducting electron transfer to the electrode surface in a reaction solution is not high, so as to improve a neutral balance capability of the counter electrodes and stabilize an electrochemical circuit without current bottleneck effect. In some embodiments, the biochemical test strip further comprises a protective layer to help stabilize the active material of the counter electrode, thereby protecting the biochemical test strip and reducing or avoiding unexpected variation of the biochemical test strip and the environment.

Fig. 12 is a schematic diagram of an electrochemical system 1000 drawn according to some embodiments of the present disclosure. As shown in fig. 12, the electrochemical system 1000 includes an electrode unit 1001 and a reaction unit 1002 electrically connected to the electrode unit 1001. In some embodiments, the electrode unit 1001 includes a working electrode and a counter electrode. Alternatively or additionally, the electrode unit 1001 comprises a spare electrode. As will be described in further detail below (i.e., with reference to fig. 13-15), in some embodiments, the reaction cell 1002 performs a primary reaction with a target analyte and the counter electrode is configured to perform a secondary reaction, wherein the secondary reaction does not interfere with the primary reaction and the secondary reaction provides the counter electrode with the ability to receive or release additional electrons.

As will be described in further detail below (i.e., with reference to fig. 13-15), the current density of the counter electrode is greater than the current density of the working electrode. In some embodiments, the current density of the counter electrode is greater than or equal to twice the current density of the working electrode. In some embodiments, the area of the counter electrode is less than or equal to the area of the working electrode. In some embodiments, the counter electrode is a cathode and the standard potential of the active material of the counter electrode is in accordance withWherein->Is the standard reduction potential of the active material, Standard reduction potential for concentration reaction at working electrode, and E _v Providing a potential applied by a measurement reaction to the meter. In some alternative embodiments, the counter electrode is an anode and the standard potential of the active material of the counter electrode is in accordance withWherein->Standard reduction potential for active material, +.>Standard reduction potential for concentration reaction at working electrode, and E _v Providing a potential applied by a measurement reaction to the meter.

Alternatively or additionally, the electrochemical system 1000 comprises a protection unit 1003. In some embodiments, the protection unit 1003 is electrically connected to the electrode unit 1001. As will be described in further detail below (i.e., with reference to fig. 22 to 24), the protection unit 1003 is used to oxidize the electrode unit 1001 after the electrode unit 1001 receives electrons or to reduce the electrode unit after the electrode unit 1001 loses electronsElement 1001 in which a potential difference exists between the protection unit 1003 and the electrode unit 1001In some embodiments, the potential difference +.>Greater than 0.

Fig. 13 is a schematic diagram of an implantable biochemical test strip 2000 according to some embodiments of the present disclosure. The implantable biochemical test strip 2000 can include one or more of the elements of the electrochemical system 1000 described above. As shown in FIG. 13, the implantable biochemical test strip 2000 comprises a working electrode 2102, a counter electrode 2104, a reaction layer 2106, an insulating layer 2108 and a biocompatible coating 2110. The working electrode 2102 and the counter electrode 2104 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer 2106 may be referred to as a reaction cell 1002 of the electrochemical system 1000.

The implantable biochemical test strip 2000 has a first end (or measuring end) 2112 connected to a measuring instrument and a second end (or implantable end) 2114 implantable into the sample. It should be noted that implantable end 2114 is covered by biocompatible coating 2110. To enable clear illustration, the biocompatible coating 2110 is depicted in dashed lines in fig. 13 to present the covered components (i.e., working electrode 2102, counter electrode 2104, reaction layer 2106, and insulating layer 2108). In some embodiments, the implantable biochemical test strip 2000 is an elongated structure. Alternatively or additionally, the implantable biochemical test strip 2000 is a laminated structure.

Fig. 14A is a cross-sectional view of a structure 2102E including a working electrode 2102, taken along line A-A' of fig. 13, according to some embodiments of the present disclosure. As shown in fig. 14A, structure 2102E includes a working electrode 2102, a substrate 2103, and a reaction layer 2106.

Fig. 14B is a cross-sectional view of a structure 2104E including a counter electrode 2104 along line B-B' of fig. 13, drawn according to some embodiments of the present disclosure. As shown in fig. 14B, the structure 2104E includes a working electrode 2102, a substrate 2103 counter electrode 2104, a reactive layer 2106, an insulating layer 2108, and a biocompatible coating 2110.

Referring to fig. 13, 14A and 14B, in some embodiments, the substrate 2103 serves as a support for the implantable biochemical test strip 2000. The substrate 2103 includes a material having certain mechanical strength and anti-cushioning properties. In some embodiments, substrate 2103 is electrically insulating. In some embodiments, the material 2103 of the substrate may include polyvinyl chloride (polyvinyl chloride, PVC), fiberglass (FR-4), polyester, polyethersulfone (PES), polyurethane (PU), polyether, polyamide (PA), polyimide (PI), bakelite, polyethylene terephthalate (polyethylene terephthalate, PET), polycarbonate (PC), polypropylene (PP), polyethylene (PE), polystyrene (PS), glass plates, ceramics, any combination of the above, or other suitable materials; but the disclosure is not so limited. The material of the substrate 2103 may be adjusted depending on the system or actual requirements.

In some embodiments, the electrodes include a working electrode 2102 and a counter electrode 2104, which may be positioned at any particular location using any suitable process, such as may be applied or processed in the following processes: chemical vapor deposition (chemical vapor deposition, CVD), physical vapor deposition (physical vapor deposition, PVD), sputtering, reactive sputtering, printing, ablation (e.g., laser ablation), coating, dip coating, etching, and the like. Each electrode (including working electrode 2102 and counter electrode 2104) may comprise any conductive material. Conductive materials may include, but are not limited to, one or more of the following: palladium (Pd), platinum (Pt), gold (Au), titanium (Ti), carbon (C), silver (Ag), copper (Cu), aluminum (Al), gallium (Ga), indium (In), iridium (Ir), iron (Fe), lead (Pb), magnesium (Mg), nickel (Ni), molybdenum (Mo), osmium (Os), rhodium (Rh), tin (Sn), zinc (Zn), silicon (Si), cobalt (Co), mercury (Hg), niobium (Nb), rhenium (Re), selenium (Se), tantalum (Ta), tungsten (W), uranium (U), vanadium (V), zirconium (Zr), or a combination of any of the foregoing conductive materials or elemental derivatives thereof. The present disclosure is not particularly limited to the relationship (e.g., spatial relationship) between the substrate 2103 and the working electrode 2102. In some embodiments, implantable biochemical test strip 2000 uses a conductive material with certain mechanical properties such that working electrode 2102 can replace substrate 2103 and serve as a substrate for implantable biochemical test strip 2000.

In some embodiments, the reactive layer 2106 may partially cover or completely cover the working electrode 2102, wherein the reactive layer 2106 may be used for electrochemical reactions at the implantable end 2114. The reaction layer 2106 may include enzymes and conductive media. The enzyme may be highly specific for the sample (or assay target). The enzyme may be used to electrochemically react with a sample (e.g., an analytical target, a blood sample, or the like). The enzyme may comprise an immobilized enzyme or an un-immobilized enzyme, such as a redox enzyme, an antigen, an antibody, a microbial cell, an animal or plant cell, or a biologically identifiable component of an animal or plant tissue. The conductive medium is used for receiving electrons generated by the reaction between the enzyme and the sample and transmitting the electrons to the measuring instrument through the working electrode 2102. In some embodiments, the conductive medium may be organic, organometallic, or inorganic, including but not limited to potassium (III) hexacyanoferrate, potassium (II) hexacyanoferrate trihydrate, ferric ferrocyanide, ruthenium complexes, ferrocene, sodium dithionite, nicotinamide adenine dinucleotide (nicotinamide adenine dinucleotide, NAD) ⁺ ) Nicotinamide adenine dinucleotide phosphate (nicotinamide adenine dinucleotide phosphate, NADP) ⁺ ) Thiamine pyrophosphate (thiamin pyrophosphate, TPP), coenzyme a (HSCoA), flavin adenine dinucleotide (flavin adenine dinucleotide, FAD), or a combination thereof; but the disclosure is not so limited. In some embodiments, the reaction layer 2106 may also be supplemented with a phosphate buffer and a protecting agent, such as proteins, dextrins, glucans, amino acids, and the like; but the disclosure is not so limited. In some embodiments, the portion of working electrode 2102 and the reactive layer 2106 (e.g., conductive medium) are constituent components of a composite. For example, a conductive paste is mixed with a conductive medium and then printed onto substrate 2103 to form working electrode 2102.

Referring to fig. 14B, in some embodiments, an insulating layer 2108 is used to electrically insulate the working electrode 2102 from the counter electrode 2104 prior to contacting the implantable biochemical test strip 2000 with the sample (i.e., prior to implantation). The insulating layer 2108 may be any insulating material such as, but not limited to, polyurethane, parylene, polyimide, polydimethylsiloxane (PDMS), liquid crystal polymer (liquid crystal polymer, LCP), PVC tape, PET tape, thermal dry paint, UV light curable paint, or photoresist. The counter electrode 2104 is provided on the insulating layer 2108.

In some embodiments of the present disclosure, the working electrode 2102 and the counter electrode 2104 are formed by sequentially stacking. Both counter electrode 2104 and working electrode 2102 are exposed to implantable end 2114 to form an electrical circuit with the sample. For example, the sample may include blood, tissue, body fluids, and other biological samples; but the disclosure is not so limited. In addition, both counter electrode 2104 and working electrode 2102 are exposed to measurement end 2112 and are sized to form an electrical circuit with the meter.

In some alternative embodiments, to enhance the biocompatibility of the implantable biochemical test strip 2000 and the living organism, a biocompatible coating 2110 may be provided on the implantable end 2114. Biocompatible coating 2110 is a polymeric barrier film that serves to prevent or reduce permeation of biomolecules (e.g., leukocytes, proteins, fibroblasts, blood clots, etc.) into an electrode surface (e.g., the surface of working electrode 2102 or counter electrode 2104). The biocompatible coating 2110 may also be used to prevent or reduce permeation or adhesion of biomolecules to the biocompatible coating 2110 that may alter the electrical characteristics of the implantable biochemical test strip 2000. In addition, biocompatible coating 2110 can be used for small molecule analytes to permeate and reach the electrode surface (e.g., the working electrode 2102 or counter electrode 2104 surface) and react with the electrode to generate a detectable current. The polymeric barrier film may be a hydrogel, chitin or derivative thereof, hyaluronic acid or derivative thereof, polyurethane, polyethylene-co-polytetrafluoroethylene, polypropylene, polyvinyl chloride, polyvinylidene fluoride, polybutylene terephthalate, polymethyl methacrylate, polyetheretherketone, cellulose ester, polysulfone, polyolefin, polyester, polycarbonate, silica gel, polyethylene, polypropylene, nylon, polyacrylonitrile, polytetrafluoroethylene, expanded polytetrafluoroethylene, or a combination thereof. In some embodiments, the biocompatible coating 2110 can be formed by layering hydrophilic and non-aqueous materials.

Fig. 15 is a schematic diagram of an electrochemical reaction of an electrochemical system 1000 or an implantable biochemical test strip 2000 according to some embodiments of the present disclosure. For ease of understanding, fig. 15 shows only a portion of the electrochemical system 1000 or the implantable biochemical test strip 2000. In detail, fig. 15 only shows portions of the working electrode 2102 and the counter electrode 2104 in the reaction zone (i.e., at the implantable end 2114). In addition, fig. 15 also shows a portion of the enzyme E and the conductive medium C in the conductive region, wherein the enzyme E and the conductive medium C form a portion of the reaction layer 2106.

Working electrode 2102 allows target analyte a to undergo an electro-oxidation reaction or electro-reduction reaction on the surface of working electrode 2102. Meter M may use working electrode 2102 to determine the concentration of target analyte a. In particular, the electro-oxidation or electro-reduction reaction is an electrochemical reaction in which the target analyte exchanges electrical and chemical energy on the surface of working electrode 2102. Working electrode 2102 can be an anode or cathode, depending on the requirements of the measurement reaction. For example, if target analyte a is oxidized on working electrode 2102, working electrode 2102 is an anode; if target analyte A is reduced on working electrode 2102, working electrode 2102 is a cathode. Counter electrode 2104 is the electrode corresponding to working electrode 2102 where the electro-reduction or electro-oxidation occurs such that the overall electrochemical system satisfies the principle of charge balance. The potential and polarity of counter electrode 2104 is opposite to working electrode 2102. The working electrode 2102 and the counter electrode 2104 are insulated from each other before being in contact with the sample S. After the working electrode 2102 contacts the counter electrode 2104 and the sample S, both form an electrical circuit with the meter M.

In some embodiments, the sample S comprises the target analyte a, wherein the target analyte a comprises an electrochemically active material or electrochemically reactive material. After loading sample S into the reaction zone, target analyte a in sample S is reduced by enzyme E in reaction layer 2106, thereby forming reduced target analyte a'; but the disclosure is not so limited. In other embodiments, target analyte a in sample S may be oxidized by enzyme E in reaction layer 2106, thereby forming an oxidized state target analyte. The conductive medium C of the reaction layer 2106 is configured to receive or provide electrons generated or lost by the reaction between the enzyme E and the target analyte a in the sample S, and to transmit the electrons to the meter M through the working electrode 2102.

For ease of understanding, the conductive medium C in the embodiment includes, for example, fe ²⁺ The method comprises the steps of carrying out a first treatment on the surface of the But the disclosure is not so limited. When target analyte a in sample S is reduced, conductive medium C of reaction layer 2106 is oxidized. In the present embodiment, fe ²⁺ Is oxidized to Fe ³⁺ . Furthermore, the extent to which conductive medium C of reaction layer 2106 is oxidized corresponds to the extent to which target analyte A is reduced. When the conductive medium C (e.g., fe ²⁺ ) The working electrode 2102 also performs the step of discharging the electrons to the oxidation state conductive medium C' (e.g., fe ³ ⁺ ) Reduced to a reduced form of conductive medium C (e.g., fe ²⁺ ) Is a reaction of (a). The meter M detects electrons (e ^- ) The number was varied and concentration analysis was performed. When the working electrode 2102 undergoes a reduction reaction, the counter electrode 2104 must oxidize a corresponding amount of the reduced conductive medium C (e.g., fe ²⁺ ) So that the overall reaction reaches charge balance.

In general, the oxidizing ability of counter electrode 2104 is insufficient to match the ability of working electrode 2102; for example, when the amount of oxidation of conductive medium C by counter electrode 2104 is less than the amount of reduction of conductive medium C by working electrode 2102, the amount of reduction current generated by working electrode 2102 may be limited due to the principle of electroneutrality, thus causing a bottleneck effect. This bottleneck effect, due to the higher amount of working electrode 2102 and electron flow reaction than can be reacted by counter electrode 2104, can limit the detectable concentration range of electrochemical system 1000 or implantable biochemical test strip 2000.

In some embodiments, the material of counter electrode 2104 in the reaction zone is selected to have a better electrochemical reactivity to environmental substances (i.e., substances other than target analyte a of sample S). In this embodiment, the counter electrode 2104 may include an active material (which also has conductivity). One of the purposes of using an active material is that when an electrochemical reaction occurs in the electrochemical system 1000 or the implantable biochemical test strip 2000, the active material of the counter electrode 2104 can undergo its own redox secondary reaction without interfering with the primary reaction. Such primary reaction refers to an oxidation or reduction reaction caused by target analyte a and reaction layer 2106, and secondary oxidation or reduction reaction refers to an oxidation or reduction reaction not caused by target analyte a and reaction layer 2106. In detail, the active material of the counter electrode 2104 is not limited as long as the secondary redox reaction occurring on the counter electrode 2104 does not affect the main reaction of the working electrode 2102 or the counter electrode 2104. In addition, the materials required for the secondary redox reaction may be from the sample S or the environment (e.g., human tissue).

By incorporating an active material in counter electrode 2104, counter electrode 2104 is able to provide an equivalent number of electrons to that generated by the reaction of conductive medium C on working electrode 2102 by its own secondary redox reaction. This secondary redox reaction enables the counter electrode 2104 to receive or release additional electrons. The additional electrons are electrons not generated by the enzyme E or the conductive medium C of the reaction layer 2106. In other words, in addition to performing an electrochemical reaction with the target analyte a in the sample S, the counter electrode 2104 may obtain electrons by performing a secondary redox reaction with the active material without destroying the electroneutrality of the meter M.

For example, after sample S is provided or deposited into the reaction zone and meter M supplies an operating voltage, target analyte a in sample S reacts with enzyme E of reaction layer 2106 and a corresponding amount of oxidation state conductive medium C' is reduced to reduction state conductive medium C on working electrode 2102. On the other hand, counter electrode 2104 needs to reduce reduced-state conductive medium C to oxidized-state conductive medium C', to an extent corresponding to the amount of reduced-state electrons of working electrode 2102, in order to maintain the electroneutrality of the system. Since counter electrode 2104 of the present disclosure has an active material that can undergo a secondary redox reaction, when counter electrode 2104 is in the redox state conductive medium C and receives electrons, it also undergoes oxidation at the same time to generate additional electrons. The active material of counter electrode 2104 may undergo its own oxidation or reduction reaction without interfering with the main reaction of counter electrode 2104. By incorporating an active material in counter electrode 2104, counter electrode 2104 can provide an equivalent number of electrons to that produced by the reaction of conductive medium C on working electrode 2102 by its own secondary redox reaction when the electrode area is limited or the concentration of conductive medium on the surface of counter electrode 2104 in the reaction solution is insufficient for electron transport. As such, the ability of counter electrode 2104 to achieve electroneutrality can be improved, and the electrochemical circuit can be stabilized to avoid current bottlenecks on counter electrode 2104. In some embodiments, the secondary redox reaction of the active material and the primary reaction of counter electrode 2104 are both oxidation reactions. Alternatively, the primary reaction of the secondary redox reaction of the active material to electrode 2104 is a reduction reaction.

Silver (Ag) is used as an illustration of the active material of counter electrode 2104 for simplicity; but the disclosure is not so limited. In detail, silver (Ag) in the counter electrode 2104 is in direct contact with the sample S. In addition to the operating voltage supplied by the meter M, the reaction zone also comprises water (H ₂ O) or hydroxide ions (OH) ^- ) So that silver (Ag) is oxidized. Thus, under appropriate conditions, the silver in counter electrode 2104 can react with hydroxyl ions (OH) from sample S or the environment ^- ) Water (H) ₂ O) or water vapor, said reaction being represented by the following reaction formula:

2Ag+2OH ^- →Ag ₂ O+H ₂ O+2e ^- or 2Ag+H ₂ O→Ag ₂ O+2H ⁺ +2e ^- 。

In silver and hydroxide ions (OH) from sample S or the environment ^- ) Or after oxidation reaction of water, silver oxide (Ag) ₂ O) and water (H) ₂ O) and release electrons. Thus, for the overall reaction, in addition to redox state conductive medium C (e.g., fe ² ⁺ ) In addition, the counter electrode 2104 is also oxidized by itself to form an oxidized state electrode (silver oxide) and release electrons (e ^- ). Thus, electrons generated by the active material of counter electrode 2104 help improve the overall ability (e.g., electroneutrality) of counter electrode 2104 under the principle of conservation of charge.

Thus, when electroreduction of working electrode 2102 occurs, counter electrode 2104 can correspondingly undergo electrooxidation to meet the electroneutrality of the overall system. It should be noted that although the counter electrode 2 is in the oxidation process 104 (e.g., silver) consumes water (H ₂ O) or hydroxide ions (OH) ^- ) And generates hydrogen ions (H) ⁺ ) Or water (H) ₂ O) and thus partially altering the pH of the reaction zone, the pH change resulting from such a condition is negligible for the overall system. Therefore, the pH change does not affect the main reaction and the test results, and therefore such a change can be ignored.

To ensure that the active material of counter electrode 2104 has the ability described above, the active material must have the same polarity of reaction as counter electrode 2104. In other words, although the oxidation number changes of the active material and the counter electrode 2104 may not be equal, when the counter electrode 2104 is an anode, the active material must have an oxidizing ability; when the counter electrode 2104 is a cathode, the active material must have a reducing ability. Accordingly, the choice of active material needs to be matched to the polarity of the reaction of the counter electrode 2104 and must be chosen under the principle of conservation of charge to enhance the charge neutrality capability of the counter electrode 2104. Therefore, when the counter electrode 2104 is an anode, the standard reduction potential of the active material of the counter electrode 2104 must be satisfiedHere, a->Is the standard reduction potential of the active substance, +.>Standard reduction potential for concentration reaction at working electrode 2102, and E _v The potential applied by the measuring instrument M in providing the measuring reaction is provided.

In some embodiments, conductive medium C isThe operating voltage (E) supplied by the meter M _v ) is-0.4V, working electrode 2102 undergoes a reduction reaction, and thus the reaction of conductive medium C on the surface of working electrode 2102 isWherein->Therefore, in this embodiment, the counter electrode 2104 is an anode. Standard reduction potential of active material of counter electrode 2104 for reduction reaction>Must be less than 0.76V; thus, the standard reduction potential can be selected>A material of less than 0.76V as an active material of the counter electrode 2104; the material may comprise ferrocene (E) ⁰ = +0.4v), copper (E ⁰ = +0.34V), iron (E ⁰ = +0.085V), tin (E ⁰ -0.1V) or the like; but the disclosure is not so limited.

In some embodiments, conductive medium C isThe operating voltage (E) supplied by the meter M _v ) Is +0.4V, oxidation reaction occurs to the working electrode 2102, and thus the reaction of the conductive medium C on the surface of the working electrode 2102 isWherein->Accordingly, in this embodiment, the counter electrode 2104 is a cathode. Standard reduction potential of active material of counter electrode 2104 for reduction reaction>Must be greater than-0.04V; thus, the standard reduction potential can be selected >A material of more than-0.04V as the counter electrode 2104An active material; the material may comprise ferroferric oxide (E ⁰ = +0.085V), silver chloride (E ⁰ = + 0.2223V), ferrocenium cation (ferrocenium) (E ⁰ = +0.4v), benzoquinone (benzoquinone) (E ⁰ = + 0.6992V) or the like; but the disclosure is not so limited.

The above is merely an example of the active material of the electrode 2104, and the present disclosure is not limited thereto. Further, the standard reduction potential of the active material of the counter electrode 2104 is not limited to the above-described embodiment. As described above, the polarity of the active material of the counter electrode 2104 should be considered, wherein the polarity of the active material should be the same as the polarity of the measurement reaction on the counter electrode 2104. Furthermore, the standard reduction potential of the active material of counter electrode 2104 should meet the following conditions:or (b)In some embodiments, E _v May be between + -5V and + -2 mV. In some embodiments, E _v And may be between + -2V and + -80 mV. In some embodiments, E _v And may be between + -0.8V to + -0.1V.

In this disclosure, the material of working electrode 2102 and the material of counter electrode 2104 are purposely chosen such that the current density 2104 of the counter electrode is greater than the current density 2102 of the working electrode. In some embodiments, the material of counter electrode 2104 is more electrochemically reactive than the material of working electrode 2102. In particular, a material of counter electrode 2104 is selected that is more electrochemically reactive with environmental substances (i.e., substances other than target analyte A of sample S) than working electrode 2102. In some embodiments, the area 2104 of the counter electrode may be less than or equal to the area 2102 of the working electrode. In some embodiments, the current density 2104 of the counter electrode is greater than or equal to twice the current density 2102 of the working electrode.

In the present disclosure, the counter electrode 2104 may include an active material that is also conductive. In some embodiments, the active material may be doped in the counter electrode 2104. In some embodiments, the active material may be formed on the surface of the counter electrode 2104. In some embodiments, counter electrode 2104 is composed of an active material. The active material of counter electrode 2104 refers to a substance that can undergo a redox reaction in the operating voltage range. The operating voltage refers to the voltage supplied by meter M, which enables the working electrode 2102 to electrochemically react with the counter electrode 2104. Active materials also refer to substances that are capable of promoting their own oxidation or reduction reactions in an electrochemical test environment. The material properties of counter electrode 2104 must be compatible with working electrode 2102. In some embodiments, the active material of counter electrode 2104 may include, but is not limited to, silver (Ag), tin (Sn), iron (Fe), zinc (Zn), cobalt (Co), nickel (Ni), lead (Pb), copper (Cu), magnesium (Mn), metal composites, or combinations thereof; but the disclosure is not so limited. In some alternative embodiments, the material of counter electrode 2104 may be a mixture of active material and its oxidized/reduced state, such as silver/silver chloride (Ag/AgCl), as the system or practical requirements.

The present disclosure is not limited to the above embodiments and may include other different embodiments. For simplicity and to enable comparison of various embodiments of the present disclosure, in the following embodiments, the same (or similar) elements are referred to by the same (or similar) reference numerals. For purposes of further comparison, only differences between the embodiments will be discussed, and the same (or similar) features will not be discussed for brevity.

Fig. 16 is a schematic diagram of an implantable biochemical test strip 3000 according to some embodiments of the present disclosure. The implantable biochemical test strip 3000 may include one or more of the elements of the electrochemical system 1000 described above. As shown in fig. 16, the implantable biochemical test strip 3000 includes a working electrode 3102, a substrate 3103, a counter electrode 3104, and a reaction layer 3106 (see fig. 17). The implantable biochemical test strip 3000 may further comprise a standby electrode 3220. The working electrode 3102, counter electrode 3104 and back-up electrode 3220 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer 3106 may be referred to as a reaction cell 1002 of the electrochemical system 1000.

The working electrode 3102, the counter electrode 3104, and the spare electrode 3220 are arranged on one side (i.e., on the same side) of the substrate 3103. In some embodiments, backup electrode 3220 may be a reference electrode. Alternatively, the back-up electrode 3220 may be a second working electrode or a second pair of electrodes. In some alternative embodiments, backup electrode 3220 may be a backup counter electrode or a common counter electrode. In some embodiments, backup electrode 3220 may form another electrical loop with working electrode 3102 or counter electrode 3104 to make a second measurement, e.g., to measure a second concentration. The second concentration may be independent of the first concentration (e.g., the concentration of target analyte a). Alternatively, the second concentration may be used to correct or calibrate the first concentration. In some alternative embodiments, the second measurement may be a non-concentration measurement (e.g., detecting implantation or detecting removal implantation).

The implantable biochemical test strip 3000 may have a first end (or measurement end) 3112 connected to a measurement instrument and a second end (or implantable end) 3114 implanted within the sample. In some embodiments, the biocompatible coating 3110 (see fig. 17) partially covers the implantable biochemical test strip 3000. For example, implantable end 3114 is covered by biocompatible coating 3110.

Fig. 17 is a cross-sectional view of an implantable biochemical test strip 3000 according to some embodiments of the present disclosure along line C-C' of fig. 16. As shown in fig. 17, the implantable biochemical test strip 3000 includes a working electrode 3102, a substrate 3103, a counter electrode 3104, a reaction layer 3106, a biocompatible coating 3110 and a back-up electrode 3220. Biocompatible coating 3110 and reactive layer 3106 coat working electrode 3102, backup electrode 3220 and counter electrode 3104 to provide the electrochemical environment necessary for measurements at implantable end 3114.

It should be noted that the spatial relationship between working electrode 3102, counter electrode 3104 and back-up electrode 3220 may be adjusted according to system requirements.

Fig. 18 is a schematic diagram of an implantable biochemical test strip 4000 according to some embodiments of the present disclosure. The implantable biochemical test strip 4000 may include one or more of the elements of the electrochemical system 1000 described above. As shown in fig. 18, the implantable biochemical test strip 4000 includes a working electrode 4102, a substrate 4103, and a counter electrode 4104. Additionally, the implantable biochemical test strip 4000 may further comprise a reaction layer (not shown). The working electrode 4102 and the counter electrode 4104 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer may be referred to as a reaction cell 1002 of the electrochemical system 1000. The implantable biochemical test strip 4000 may have a first end (or measurement end) 4112 connected to a measurement instrument and a second end (or implantable end) 4114 implanted in the sample.

Fig. 19 is a schematic diagram of an implantable biochemical test strip 5000 according to some embodiments of the present disclosure. The implantable biochemical test strip 5000 can include one or more elements of the electrochemical system 1000 described above. As shown in fig. 19, the implantable biochemical test strip 5000 includes a working electrode 5102, a substrate 5103, a counter electrode 5104, a reaction layer 5106 (see fig. 20) and a standby electrode 5220. The working electrode 5102, counter electrode 5104, and back electrode 5220 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer 5106 may be referred to as a reaction cell 1002 of the electrochemical system 1000.

The implantable biochemical test strip 5000 may have a first end (or measuring end) 5112 connected to the measuring instrument and a second end (or implantable end) 5114 implanted in the sample. As shown in fig. 19, the counter electrode 5104 and the working electrode 5102 are arranged on different sides of the substrate 5103. In some embodiments, the backup electrode 5220 is disposed on the same side as the counter electrode 5104. Alternatively, the reserve electrode 5220 is arranged on the same side as the working electrode 5102. In some embodiments, the biocompatible coating 5110 (see fig. 20) partially covers the implantable biochemical test strip 5000. For example, the implantable end 5114 is covered by a biocompatible coating 5110.

Fig. 20 is a cross-sectional view of an implantable biochemical test strip 5000 according to some embodiments of the present disclosure along line D-D' of fig. 19. As shown in fig. 20, the implantable biochemical test strip 5000 includes a working electrode 5102, a substrate 5103, a counter electrode 5104, a reaction layer 5106, a biocompatible coating 5110 and a standby electrode 5220. The reaction layer 5106 is disposed on at least one side of the working electrode 5102; but the disclosure is not so limited. The position of the reactive layer 5106 can be adjusted according to the system or actual requirements.

Fig. 21 is a schematic diagram of an implantable biochemical test strip 6000 according to some embodiments of the present disclosure. The implantable biochemical test strip 6000 may include one or more of the elements of the electrochemical system 1000 described above. As shown in fig. 21, the implantable biochemical test strip 6000 includes a working electrode 6102, a substrate 6103, and a counter electrode 6104. Additionally, the implantable biochemical test strip 6000 may further comprise a reaction layer (not shown). The working electrode 6102 and the counter electrode 6104 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer may be referred to as a reaction cell 1002 of the electrochemical system 1000. The implantable biochemical test strip 6000 may have a first end (or measuring end) 6112 connected to the measuring instrument and a second end (or implantable end) 6114 implanted in the sample. The counter electrode 6104 and the working electrode 6102 are arranged on different sides of the substrate 6103.

Fig. 22-24 illustrate alternative embodiments of the present disclosure. In some embodiments, as shown in fig. 22-24, a protective layer (e.g., 7122, 8122, or 9122) is provided at the measurement end (e.g., 7112, 8112, or 9112) of the counter electrode (e.g., 7104, 8104, or 9104). In some embodiments, the protective layer (e.g., 7122, 8122, or 9122) serves to further stabilize the active material on the counter electrode (e.g., 7104, 8104, or 9104), thereby protecting the implantable biochemical test strip (e.g., 7000, 8000, or 9000) and alleviating or avoiding undesirable causes in the implantable biochemical test strip (e.g., 7000, 8000, or 9000) and the surrounding environment. In some embodiments, the protective layer (e.g., 7122, 8122, or 9122) is electrically connected to the counter electrode (e.g., 7104, 8104, or 9104). In some embodiments, the protective layer (e.g., 7122, 8122, or 9122) is at the same level as the counter electrode (e.g., 7104, 8104, or 9104). In some embodiments, the protective layer (e.g., 7122, 8122, or 9122) is at a different level than the counter electrode (e.g., 7104, 8104, or 9104). For example, a protective layer (e.g., 7122, 8122, or 9122) may be disposed over or under a counter electrode (e.g., 7104, 8104, or 9104). The protective layer (e.g., 7122, 8122, or 9122) may be solid, liquid, or gaseous. For example, the solid state may include pure metals, alloys, metal compounds (halides, oxides, mixed valence compounds, organometallic complexes), organic redox agents, or the like. The liquid state may include aqueous solutions, organic solutions, superfluids, liquid elements (e.g., bromine, mercury), or the like. The gaseous state may include gaseous elements (e.g., oxygen, ozone), gaseous compounds (e.g., ammonium, nitric oxide), or the like.

Fig. 22 is a schematic diagram of an implantable biochemical test strip 7000 according to some embodiments of the present disclosure. The implantable biochemical test strip 7000 may include one or more of the elements of the electrochemical system 1000 described above. As shown in fig. 22, the implantable biochemical test strip 7000 includes a working electrode 7102, a counter electrode 7104, a reaction layer 7106, an insulating layer 7108, a biocompatible coating 7110 and a protective layer 7122. The working electrode 7102 and the counter electrode 7104 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer 7106 may be referred to as a reaction cell 1002 of the electrochemical system 1000. Furthermore, the protective layer 7122 may be referred to as a protective unit 1003 of the electrochemical system 1000.

The implantable biochemical test strip 7000 may have a first end (or measuring end) 7112 connected to the meter and a second end (or implantable end) 7114 implanted in the sample. The protective layer 7122 may be disposed on the counter electrode 7104 at the measurement end 7112. Alternatively, the protective layer 7122 is located at the same level as the counter electrode 7104.

Fig. 23 is a schematic diagram of an implantable biochemical test strip 8000 according to some embodiments of the present disclosure. The implantable biochemical test strip 8000 may include one or more of the elements of the electrochemical system 1000 described above. As shown in fig. 23, the implantable biochemical test strip 8000 includes a working electrode 8102, a substrate 8103, a counter electrode 8104, a reaction layer (not shown), a protective layer 8122, and a standby electrode 8220. The working electrode 8102, the counter electrode 8104, and the backup electrode 8220 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer may be referred to as a reaction cell 1002 of the electrochemical system 1000. Furthermore, the protective layer 8122 may be referred to as a protective unit 1003 of the electrochemical system 1000. The implantable biochemical test strip 8000 may have a first end (or measurement end) 8112 connected to a meter and a second end (or implantable end) 8114 implanted in a sample. The protective layer 8122 may be disposed adjacent to the counter electrode 8104 at the measurement end 8112.

FIG. 24 is a schematic diagram of an implantable biochemical test strip 9000 according to some embodiments of the present disclosure. The implantable biochemical test strip 9000 can comprise one or more elements of the electrochemical system 1000 described above. As shown in fig. 24, the implantable biochemical test strip 9000 comprises a working electrode 9102, a substrate 9103, a counter electrode 9104, a reaction layer (not shown), a protective layer 9122 and a backup electrode 9220. The working electrode 9102, counter electrode 9104 and backup electrode 9220 may be collectively referred to as an electrode unit 1001 of the electrochemical system 1000. Additionally, the reaction layer may be referred to as a reaction cell 1002 of the electrochemical system 1000. Furthermore, the protective layer 9122 may be referred to as a protective unit 1003 of the electrochemical system 1000. The implantable biochemical test strip 9000 can have a first end (or measurement end) 9112 connected to a measurement meter and a second end (or implantable end) 9114 implanted in a sample. The protective layer 9122 can be disposed adjacent to the counter electrode 9104 at the measurement end 9112.

In some embodiments, there may be a potential difference between the protection unit 1003 and the electrode unit 1001For example, there may be a potential difference between the protective layer 7122, 8122 or 9122 and the counter electrode 7104, 8104 or 9104>Said potential difference->Can be expressed as->Wherein E is _cathod Is the standard reduction potential of the cathode, and E _anode Is the standard reduction potential of the anode. The protective layer 7122, 8122, or 9122 may have different standard reduction electricity than the counter electrode 7104, 8104, or 9104. In the present disclosure, the potential difference between the protective layer 7122, 8122 or 9122 and the counter electrode 7104, 8104 or 9104 is +.>Greater than 0. In the present disclosure, the potential difference between the protective layer 60 and the counter electrode 24 +>Greater than 0. According to Ji clothThe Sfree energy relation, i.e.)>Wherein ΔG ⁰ The free energy is changed, n is the number of moles of electrons, and F is the charge per mole. When Gibbs free energy DeltaG ⁰ <At 0, the reaction is spontaneous. As can be seen from the above, when two have a potential difference +.>When the redox species in the same reaction vessel, the higher standard reduction potential tends to undergo reduction reaction, whereas oxidation reaction tends to occur. For example, when the standard reduction potential of the anode is less than the standard reduction potential of the cathode, the anode spontaneously transfers electrons to the cathode, which maintains the reduced state by continuously obtaining electrons, thus being protected from environmental oxidants (e.g., oxygen, moisture, etc.).

The protective layer 7122, 8122, or 9122 is in the same reaction tank as the counter electrode 7104, 8104, or 9104. In some embodiments, the protective layer 7122, 8122, or 9122 is in contact with air simultaneously with the counter electrode 7104, 8104, or 9104, but the disclosure is not limited thereto. The protective layer 7122, 8122, or 9122 is electrically connected to the counter electrode 7104, 8104, or 9104, and may be considered to be in the same reaction tank. Due to the potential difference between the protective layer 7122, 8122 or 9122 and the counter electrode 7104, 8104 or 9104 And the potential difference->Greater than 0, electrons spontaneously flow in a specific direction, and the object to be protected (counter electrode 7104, 8104, or 9104) can maintain the original redox state. Thereby protecting the biochemical test piece 7000, 8000 or 9000 and reducing the unexpected variation of the biochemical test piece 7000, 8000 or 9000 and the environment. The areas and thicknesses of the protective layers 7122, 8122, or 9122 and the counter electrode 7104, 8104, or 9104 may be adjusted according to system requirements.

As the protective layer 7122, 8122, or 9122 is different from the material of the counter electrode 7104, 8104, or 9104, it may be an anode and a cathode, respectively, or vice versa. For further explanation, silver (Ag) is taken as an example of the active material of the counter electrode 104; but the disclosure is not so limited. However, when silver is exposed to air, it reacts readily with oxygen and water vapor to produce silver oxide, where the oxidation reaction can be expressed as 4Ag+0 ₂ →2Ag ₂ O, and wherein the standard reduction potential of silver/silver oxide is 1.17V. When silver is oxidized to silver oxide after exposure to air, toxicity may occur on the surface of the counter electrode 7104, 8104, or 9104. At this time, the ability of the counter electrode 7104, 8104, or 9104 to receive or release additional electrons is weakened, and thus the bottleneck effect between the working electrode 7102, 8102, or 9102 and the counter electrode 7104, 8104, or 9104 cannot be effectively reduced.

As shown in fig. 22 to 24, the implantable biochemical test strip 7000, 8000 or 9000 is provided with a protective layer 7122, 8122 or 9122, and the protective layer 7122, 8122 or 9122 is electrically connected to the counter electrode 7104, 8104 or 9104. In some embodiments, the protective layer 7122, 8122, or 9122 serves to protect the active material of the counter electrode 7104, 8104, or 9104. In some embodiments, the protective layer 7122, 8122, or 9122 may include stannous oxide (SnO). When stannous oxide is exposed to air, oxidation reaction with water vapor readily occurs, which reaction can be expressed as SnO+H ₂ O→SnO ₂ +2H ⁺ +2e ^- . The standard reduction potential for silver oxide/silver was 1.17V, while the standard reduction potential for stannous oxide/stannic oxide was-0.09V. Thus, in the present embodiment, the active material of the counter electrode 7104, 8104, or 9104 is a cathode, and the protective layer 7122, 8122, or 9122 is an anode. When the implanted biochemical test piece 7000, 8000 or 9000 is exposed to an environment containing water vapor, the potential difference1.08V. Because of the potential difference between the twoGreater than 0, free energyLess than 0, and thus the following reaction will proceed spontaneously: ag (silver) ₂ O+SnO→2Ag+SnO ₂ . At this time, the half reaction occurring on the active material of the counter electrode 104 is Ag ₂ O+2H ⁺ +2e ^- →2Ag+H ₂ O。

Accordingly, silver oxide in the counter electrode 7104, 8104, or 9104 may be reduced to silver due to oxidation reaction of stannous oxide in the protective layer 7122, 8122, or 9122. When the protective layer 7122, 8122 or 9122 undergoes an oxidation reaction, the active material of the counter electrode 7104, 8104 or 9104 undergoes a reduction reaction, thereby slowing down the oxidation reaction caused by oxygen and water vapor in the air. Further, the active material of the counter electrode 7104, 8104, or 9104 is further protected by oxidation reaction between water vapor in the air and stannous oxide, and the active material of the counter electrode 7104, 8104, or 9104 can be kept stable. Thus, by providing the protective layer 7122, 8122, or 9122 in the implantable biochemical test strip 7000, 8000, or 9000, the active material of the counter electrode 7104, 8104, or 9104 can be prevented from being damaged before the sample measurement is performed. The composition and materials of the counter electrode 7104, 8104, or 9104 and the active material of the protective layer 7122, 8122, or 9122 are not limited to those described above. In some embodiments, the composition and materials of the active materials of the counter electrode 7104, 8104, or 9104 and the protective layer 7122, 8122, or 9122 are selected such that the potential difference therebetween Greater than 0. In some embodiments, the potential difference +.>The absolute value of (2) is greater than 0.

In this embodiment, the protective layer 7122, 8122 or 9122 is provided in the implantable biochemical test strip 7000, 8000 or 9000. The protective layer 7122, 8122 or 9122 may maintain stability of the active material in the counter electrode 7104, 8104 or 9104, while being capable of protecting the implantable biochemical test strip 7000, 8000 or 9000 and mitigating accidental damage to the implantable biochemical test strip 7000, 8000 or 9000 caused by reactions with the environment before the implantable biochemical test strip 7000, 8000 or 9000 is used for sample measurement, thereby being capable of maintaining or protecting the capability of the counter electrode 7104, 8104 or 9104 of the implantable biochemical test strip 7000, 8000 or 9000 to receive or release additional electrons.

Fig. 25 shows signals detected at different concentrations on the counter electrode according to the present embodiment and the counter electrode of the comparative example. In detail, data C and data D show signals detected on the counter electrodes 2104, 3104, 4104, 5104, 6104, 7104, 8104, or 9104 according to the present disclosure, and data a and data B show signals detected on the counter electrodes according to the comparative example. As shown in fig. 25, the difference between the counter electrode of this example and the counter electrode of the comparative example was small at a low sugar concentration. However, as the sugar concentration increases, a bottleneck occurs in the counter electrode of the comparative example.

Fig. 26 is a graph showing signals detected over time on the electrochemical system according to the present embodiment and the electrochemical system of the comparative example. Fig. 26 can be used as a long-term stability test of the counter electrode of the present embodiment and the counter electrode of the comparative example. The implanted biochemical test strip of the implanted biochemical test strip electrochemical system 1000 and the electrochemical system of the comparative example are implanted or inserted into the same chemical tank having a fixed concentration. The reaction signal was continuously detected. In detail, data M shows a signal from the electrochemical system 1000 according to the present embodiment, and data N shows a signal from the electrochemical system of the comparative example. As shown in fig. 26, the electrochemical system of the comparative example shows the same initial performance as the electrochemical system 1000 of the present example. However, at day 15 or 16 (see point Y), the counter electrode of the electrochemical system of the comparative example presents a bottleneck due to the disintegration of the conductive medium on the counter electrode. On the other hand, the electrochemical system 1000 of the present embodiment has a better stability due to its own redox ability.

Although the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the disclosure as defined by the appended claims. Furthermore, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. Those of skill in the art will appreciate from the disclosure that a process, machine, manufacture, composition of matter, means, methods, or steps, presently existing or future developed that perform the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, such processes, machines, manufacture, compositions of matter, means, methods, or steps, are included in the claims of the present application.

Claims

1. An electrochemical system, comprising:

an electrode unit including a working electrode and a pair of electrodes, wherein a current density of the pair of electrodes is greater than a current density of the working electrode; and

and a reaction unit electrically connected with the electrode unit.

2. The electrochemical system of claim 1, wherein the current density of the pair of electrodes is greater than or equal to twice the current density of the working electrode.

3. The electrochemical system of claim 1, wherein an area of the pair of electrodes is less than or equal to an area of the working electrode.

4. The electrochemical system of claim 1, wherein the pair of electrodes is a cathode and a standard reduction potential of an active material of the pair of electrodes is metWherein the->For a standard reduction potential of the active material, the +.>A standard reduction potential for a concentration reaction on the working electrode, and the E _v A measuring instrument is provided with a potential applied by a measuring reaction.

5. The electrochemical system of claim 1, wherein the pair of electrodes is an anode and a standard reduction potential of an active material of the pair of electrodes is metWherein the->Is a standard reduction potential of the active material, the A standard reduction potential for a concentration reaction on the working electrode, and the E _v A measuring instrument is provided with a potential applied by a measuring reaction.

6. The electrochemical system of claim 1, wherein the reaction unit performs a primary reaction with a target analyte and the pair of electrodes is configured to perform a secondary reaction, wherein the secondary reaction does not interfere with the primary reaction, the secondary reaction enabling the pair of electrodes to receive or release additional electrons.

7. The electrochemical system of claim 1, further comprising:

a protection unit electrically connected to the electrode unit for oxidizing the electrode unit after the electrode unit receives an electron or reducing the electrode unit after the electrode unit loses an electron, wherein a potential difference exists between the protection unit and the electrode unit

8. The electrochemical system of claim 7, wherein the potential differenceGreater than0。

9. An implantable biochemical test strip comprising:

a substrate;

a biocompatible coating disposed on the substrate;

an electrode unit between the substrate and the biocompatible coating, wherein the electrode unit comprises

A working electrode and a pair of electrodes, wherein the pair of electrodes are used for receiving or releasing additional electrons through a self redox reaction, and a current density of the pair of electrodes is larger than a current density of the working electrode; and a reaction layer electrically connected with the electrode unit.

10. The implantable biochemical test strip of claim 9, further comprising:

a first end connected to a measuring instrument; and

a second end implanted in a sample.

11. The implantable biochemical test strip of claim 10, wherein the second end is covered by the biocompatible coating.

12. The implantable biochemical test strip of claim 9, wherein the reaction layer is between the working electrode and the pair of electrodes.

13. The implantable biochemical test strip of claim 9, wherein the reaction layer covers the working electrode or the pair of electrodes.

14. The implantable biochemical test strip of claim 9, wherein the substrate has an elongated structure and the biocompatible coating surrounds the substrate.

15. The implantable biochemical test strip of claim 9, wherein the electrode unit further comprises a spare electrode disposed on the substrate.

16. An implantable biochemical test strip comprising:

a substrate having a measurement end and an implantable end;

a biocompatible coating disposed on the substrate;

an electrode unit interposed between the substrate and the biocompatible coating, wherein the electrode unit comprises a working electrode and a pair of electrodes, wherein the pair of electrodes comprises an active material; and a protection layer electrically connected to the electrode unit for stabilizing the active material of the pair of electrodes.

17. The implantable biochemical test strip of claim 16, wherein the protective layer is located at the measurement end.

18. The implantable biochemical test strip of claim 16, wherein the protective layer is disposed adjacent to the pair of electrodes.

19. The implantable biochemical test strip of claim 16, wherein a potential difference exists between the protective layer and the electrode unit

20. The implantable biochemical test strip of claim 19, wherein the potential differenceGreater than 0.