Method of manufacturing three-dimensional porous microfoam for biomaterial sensing for healthcare, biochemical sensor including three-dimensional porous microfoam for biomaterial sensing for healthcare manufactured thereby, and operation method thereof

Abstract

Provided is a method of manufacturing a three-dimensional porous microfoam for biomaterial sensing for health care. The method of manufacturing a three-dimensional porous microfoam for biomaterial sensing for health care may comprise the steps of: preparing a substrate provided with an electrode layer; and depositing, on the electrode layer, at least one metal sensitive to a target biomaterial, wherein in a process of forming the deposition layer on the electrode layer by the at least one metal to be deposited, deposition conditions are controlled such that bubble generation and detachment occur simultaneously in the formed deposited layer, thereby converting the formed deposited layer into a three-dimensional porous microfoam.

Description

Method for manufacturing a three-dimensional porous microfoam for sensing biomaterials for healthcare, a biochemical sensor comprising the three-dimensional porous microfoam for sensing biomaterials for healthcare manufactured thereby, and an operating method thereof

[0001] The present invention relates to a method for manufacturing a three-dimensional porous microfoam for sensing biomaterials for healthcare, a biochemical sensor comprising the three-dimensional porous microfoam for sensing biomaterials for healthcare manufactured thereby, and an operating method thereof. More specifically, the present invention relates to a method for manufacturing a three-dimensional porous microfoam for sensing biomaterials for healthcare, which can easily manufacture a three-dimensional porous microfoam for sensing biomaterials for healthcare, a biochemical sensor comprising the three-dimensional porous microfoam for sensing biomaterials for healthcare manufactured thereby, and an operating method thereof.

[0002] Diabetes is a chronic disease that is rapidly increasing worldwide, and accurate monitoring of blood sugar levels is essential to maintaining patient health.

[0003] Accurate blood sugar monitoring is essential for people with diabetes, as excessively high or low blood sugar levels can lead to serious complications such as myocardial infarction, stroke, retinopathy, and kidney failure.

[0004] Photosensors have been developed to meet these needs, measuring blood sugar levels and relaying this information to healthcare professionals for immediate action, while also enabling monitoring at the individual level.

[0005] Types of these monitoring sensors include quantum dot-based fluorescent sensors, electrochemical sensors, and optical sensors. Among these, electrochemical sensors offer advantages such as high sensitivity, stability, and selectivity for detecting glucose within electrodes in various samples.

[0006] Previously, enzyme-based sensors with excellent sensitivity and selectivity were mainly used as glucose detection sensors, but their continuous use was difficult due to problems such as instability due to the environment, cost, and invasiveness. In addition, they had the disadvantage of being economical because they were synthesized through multiple steps.

[0007] The technical problem to be solved by the present invention is to provide a method for manufacturing a three-dimensional porous microfoam for sensing biomaterials for healthcare, which can easily manufacture a three-dimensional porous microfoam for sensing biomaterials for healthcare.

[0008] Another technical problem to be solved by the present invention is to provide a biochemical sensor having a three-dimensional porous microfoam for sensing biomaterials for healthcare, which has high sensitivity, stability, reliability and selectivity, and an operating method thereof.

[0009] Another technical problem that the present invention seeks to solve is to provide a non-enzyme-based biochemical sensor and its operating method.

[0010] The technical problems to be solved by the present invention are not limited to those described above.

[0011] To solve the above technical problem, the present invention provides a method for manufacturing a three-dimensional porous micro foam for sensing biomaterials for healthcare.

[0012] According to one embodiment, the method for manufacturing a three-dimensional porous microfoam for sensing a biomaterial for healthcare may include the steps of: preparing a substrate having an electrode layer; and depositing at least one metal sensitive to a target biomaterial on the electrode layer, wherein, in the process of forming a deposition layer on the electrode layer by the at least one metal to be deposited, controlling deposition conditions so that bubbles are generated and desorbed simultaneously in the formed deposition layer, thereby converting the formed deposition layer into a three-dimensional porous microfoam.

[0013] According to one embodiment, in the step of converting the formed deposition layer into a three-dimensional porous micro-foam, at least one metal may be deposited through an electrochemical deposition method.

[0014] According to one embodiment, in the electrochemical deposition method, the voltage range depending on the applied current may be -4.5 V to -3.0 V.

[0015] According to one embodiment, in the step of converting the formed deposition layer into a three-dimensional porous micro-foam, at least one metal may be selectively deposited on the electrode layer.

[0016] In one embodiment, when the target biomaterial is glucose, the at least one metal may be any one of copper, nickel, and an alloy of copper and nickel.

[0017] Meanwhile, the present invention provides a biochemical sensor.

[0018] According to one embodiment, the biochemical sensor may include: a substrate; an electrode layer provided on the substrate; and a sensor layer provided on the electrode layer and made of at least one metal that is sensitive to a target biological material, and provided as a three-dimensional porous micro-foam.

[0019] According to one embodiment, the three-dimensional porous micro-foam can be formed by simultaneously generating and desorbing bubbles in the formed deposition layer during the process of forming a deposition layer by depositing at least one metal on the electrode layer.

[0020] According to one embodiment, the sensor layer may be optionally provided on the electrode layer.

[0021] In one embodiment, when the target biomaterial is glucose, the at least one metal may be any one of copper, nickel, and an alloy of copper and nickel.

[0022] In one embodiment, when the at least one metal is an alloy of copper and nickel, the specific surface area of ​​the three-dimensional porous micro-foam may be relatively larger than when the at least one metal is copper or nickel.

[0023] The present invention also provides a method for operating a biochemical sensor.

[0024] According to one embodiment, the method for operating the biochemical sensor comprises the steps of preparing the biochemical sensor described above; and the step of sensing a target biological substance with the prepared biochemical sensor, wherein in the step of sensing the target biological substance, a voltage of less than 6 V may be applied to the prepared biochemical sensor.

[0025] According to one embodiment, in the step of sensing the target biomaterial, a voltage of more than 4 V and less than 6 V may be applied to the prepared biochemical sensor.

[0026] According to an embodiment of the present invention, the method may include the steps of: preparing a substrate having an electrode layer; and depositing at least one metal sensitive to a target biomaterial on the electrode layer, wherein, in the process of forming a deposition layer on the electrode layer by the at least one metal deposited, the step of controlling deposition conditions so that bubbles are generated and desorbed simultaneously in the formed deposition layer, thereby converting the formed deposition layer into a three-dimensional porous microfoam may be included.

[0027] Accordingly, a method for manufacturing a three-dimensional porous microfoam for biomaterial sensing for healthcare can be provided, which can easily manufacture a three-dimensional porous microfoam for biomaterial sensing for healthcare.

[0028] In addition, according to an embodiment of the present invention, since inexpensive transition metals as well as precious metals can be used in the production of three-dimensional porous micro-foam, cost-effectiveness can be secured and it can be applied universally according to the needs of users.

[0029] And according to an embodiment of the present invention, a three-dimensional porous micro-foam can be selectively formed in a conductive region, i.e., a specific location of the electrode layer.

[0030] Through this, according to an embodiment of the present invention, a biochemical sensor having a three-dimensional porous microfoam for sensing biomaterials for healthcare with high sensitivity, stability, reliability and selectivity, and an operating method thereof can be provided.

[0031] Accordingly, it can be widely applied to invasive, minimally invasive, non-invasive diagnostic test sensors, high-cost, low-cost, extracorporeal, wearable, implantable, monitoring, and glucose sensors in cell culture environments.

[0032] In this way, according to an embodiment of the present invention, a biochemical sensor can be provided as, for example, a non-enzyme-based glucose sensor, thereby replacing conventional enzyme-based glucose sensors that are expensive and vulnerable to environmental changes.

[0033] According to an embodiment of the present invention, a biochemical sensor that acts as a glucose sensor with high sensitivity, stability, reliability and selectivity is provided, thereby greatly helping in the health management of diabetic patients.

[0034] FIG. 1 is a flowchart illustrating a method for manufacturing a three-dimensional porous micro foam for sensing biomaterials for healthcare according to one embodiment of the present invention.

[0035] Figure 2 is a schematic diagram for explaining step S110 of Figure 1.

[0036] Figures 3 and 4 are schematic diagrams for explaining step S120 of Figure 1.

[0037] FIGS. 5 and 6 are scanning electron microscope photographs of a three-dimensional porous microfoam made of an alloy of copper and nickel manufactured according to Example 1.

[0038] Figures 7 and 8 are photographs taken with a scanning electron microscope of a three-dimensional porous microfoam made of copper manufactured according to Example 2.

[0039] FIGS. 9 and 10 are scanning electron microscope photographs of a three-dimensional porous microfoam made of nickel manufactured according to Example 3.

[0040] Figures 11 and 12 are EDS analysis results for a three-dimensional porous micro-foam made of an alloy of copper and nickel manufactured according to Example 1.

[0041] FIG. 13 is a flowchart illustrating a method of operating a biochemical sensor having a three-dimensional porous microfoam manufactured through a method of manufacturing a three-dimensional porous microfoam for sensing a biomaterial for healthcare according to an embodiment of the present invention.

[0042] Figure 14 is a schematic diagram for explaining step S220 of Figure 13.

[0043] Figure 15 shows the results of CV (cyclic voltammetry) analysis according to scan speed for a three-dimensional porous micro-foam made of an alloy of copper and nickel manufactured according to Example 1.

[0044] Figure 16 shows the CV analysis results according to the presence or absence of glucose in copper nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3.

[0045] Figures 17 and 18 show the results of CV and CA (chronoamperometry) analysis according to glucose concentration for a three-dimensional porous microfoam made of an alloy of copper and nickel manufactured according to Example 1.

[0046] Figure 19 shows the CA analysis results for glucose sensitivity characteristics of copper nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3.

[0047] Figure 20 shows the CA analysis results for glucose sensitivity characteristics of a three-dimensional porous microfoam made of an alloy of copper and nickel manufactured according to Example 1.

[0048] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings. However, the technical concept of the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the embodiments introduced herein are provided to ensure that the disclosed content is thorough and complete and to sufficiently convey the spirit of the present invention to those skilled in the art.

[0049] In this specification, when a component is referred to as being on another component, it means that it can be formed directly on the other component, or a third component may be interposed between them. In addition, in the drawings, shapes and sizes are exaggerated for the purpose of effectively explaining the technical contents.

[0050] Additionally, although terms such as first, second, and third have been used to describe various components in various embodiments of this specification, these components should not be limited by these terms. These terms are only used to distinguish one component from another. Thus, what is referred to as a first component in one embodiment may be referred to as a second component in another embodiment. Each embodiment described and illustrated herein also includes its complementary embodiments. Additionally, the term "and / or" has been used herein to mean including at least one of the components listed before and after.

[0051] In the specification, singular expressions include plural expressions unless the context clearly dictates otherwise. In addition, terms such as "comprise" or "have" are intended to specify the presence of a feature, number, step, component, or combination thereof described in the specification, and should not be construed as excluding the presence or addition of one or more other features, numbers, steps, components, or combinations thereof. In addition, the term "connection" is used in the present specification to mean both indirectly connecting multiple components and directly connecting them.

[0052] Additionally, terms such as “part,” “unit,” and “module” described in the specification mean a unit that processes at least one function or operation, which may be implemented by hardware, software, or a combination of hardware and software.

[0053] In addition, when describing the present invention below, if it is determined that a detailed description of a related known function or configuration may unnecessarily obscure the gist of the present invention, the detailed description will be omitted.

[0054]

[0055] FIG. 1 is a flowchart illustrating a method for manufacturing a three-dimensional porous micro foam for sensing biomaterials for healthcare according to an embodiment of the present invention, FIG. 2 is a schematic diagram for explaining step S110 of FIG. 1, and FIGS. 3 and 4 are schematic diagrams for explaining step S120 of FIG. 1.

[0056]

[0057] As illustrated in FIG. 1, a method for manufacturing a three-dimensional porous micro-foam for sensing biomaterials for healthcare according to an embodiment of the present invention may include steps S110 and S120.

[0058]

[0059] S110 stage

[0060] Referring to FIG. 2, the step S110 is a step of preparing a substrate (110) on which an electrode layer (120) is provided.

[0061] In the above step S110, a metal may be deposited on one surface of the substrate (110) to form an electrode layer (120) that forms a conductive region. At this time, a silicon substrate may be used as the substrate (110), for example. In addition, gold (Au) may be used as the metal forming the electrode layer (120).

[0062] In the above step S110, gold (Au) can be formed as an electrode layer (120) by electron beam deposition or sputtering deposition on one surface of a substrate (110) made of a silicon substrate.

[0063] However, this is only an example, and the metal forming the electrode layer (120) in the present invention is not necessarily limited to gold (Au).

[0064] Meanwhile, in the step S110, the substrate (110) on which the electrode layer (120) is provided may be washed. In the step S110, for example, the substrate (110) on which the electrode layer (120) is provided may be washed with an HCl solution and distilled water, sterilized in 99.99% ethyl alcohol anhydrous, and then washed with distilled water.

[0065] Through this, the surface contamination of the electrode layer (120) provided on one side of the substrate (110) is reduced, and it can be maintained in a more stable state in the long term.

[0066] In addition, in the above step S110, the substrate (110) on which the electrode layer (120) is provided can be washed and then dried.

[0067]

[0068] S120 stage

[0069] Referring to FIGS. 3 and 4, the step S120 is a step of forming a deposition layer by depositing at least one metal (M) sensitive to a target biomaterial on an electrode layer (120) forming a conductive area provided on one surface of a substrate (110).

[0070] In addition, the above step S120 is a step of converting the formed deposition layer into a three-dimensional porous micro foam (130).

[0071] To this end, in the step S120, at least one metal (M) sensitive to the target biomaterial can be deposited on the electrode layer (120) provided on one surface of the substrate (110).

[0072] Accordingly, a deposition layer made of at least one metal (M) sensitive to a target biomaterial can be formed on the electrode layer (120) provided on one side of the substrate (110).

[0073] At this time, according to one embodiment of the present invention, in the step S120, at least one metal (M) sensitive to the target biomaterial can be selectively deposited on the electrode layer (120) provided on one surface of the substrate (110) to form a deposition layer.

[0074] That is, in the above step S120, at least one metal (M) sensitive to the target biomaterial can be deposited at a desired location and size on the electrode layer (120) provided on one surface of the substrate (110) to form a deposition layer.

[0075] In this way, according to one embodiment of the present invention, a biochemical sensor (100) having a three-dimensional porous micro-foam (130) manufactured by selectively depositing at least one metal (M) sensitive to a target biomaterial on an electrode layer (120) forming a conductive region can be utilized in wearable devices, in vitro diagnostic devices, etc.

[0076] Here, at least one metal (M) forming the deposition layer may vary depending on the target biomaterial.

[0077] For example, the target biomaterial may be glucose. If the target biomaterial is glucose, the at least one metal sensitive thereto may be any one of copper (Cu), nickel (Ni), and an alloy of copper (Cu) and nickel (Ni).

[0078] As shown in Table 1 below, according to one embodiment of the present invention, when the target biomaterial is any one of TNF-α (Tumor Necrosis Factor-alpha), IL-6 (Interleukin-6), IFN-γ (Interferon-gamma), SARS-CoV-2 nucleocapsid protein, Spike protein, IgG / IgM antibodies, and Cortisol, at least one metal (M) sensitive to the target biomaterial may be used.

[0079]

[0080] Disease Target Biomaterial Remarks Cancer-related biomarkersTNF-α(Tumor Necrosis Factor-alpha)Inflammatory marker in cancerIL-6(Interleukin-6)Inflammatory cytokine in cancerIFN-γ(Interferon-gamma)Immune response marker in cancerCOVID-19-related biomarkersSARS-CoV-2 nucleocapsid proteinViral protein for COVID-19 detectionSpike proteinAnother viral protein for COVID-19 detectionIgG / IgM antibodiesImmune response markers to SARS-CoV-2Sports / exercise-related biomarkersCortisolStress hormoneInflammation-related cytokinesIL-6 (Interleukin-6)Pro-inflammatory cytokines

[0081] Continuing, according to one embodiment of the present invention, in the step S120, while at least one metal (M) sensitive to a target biomaterial is deposited on an electrode layer (120) provided on one surface of a substrate (110), a deposition layer is formed on the electrode layer (120), and deposition conditions can be controlled so that the generation and desorption of bubbles (H) occur simultaneously in the formed deposition layer.

[0082] Through this, the deposition layer formed in the above step S120 can be converted into a three-dimensional porous micro foam (130).

[0083] According to one embodiment of the present invention, in step S120, at least one metal (M) sensitive to a target biomaterial can be deposited on an electrode layer (120) provided on one surface of a substrate (110) through an electrochemical deposition method.

[0084] More specifically, in step S120, at least one metal (M) precursor sensitive to the target biomaterial can be prepared. In step S120, a working electrode, a counter electrode, and a reference electrode can be installed.

[0085] Here, the electrode layer (120) provided on one side of the substrate (110) serves as a working electrode, and a platinum (Pt) electrode, for example, can be used as a counter electrode. And a silver (Ag) / silver chloride (AgCl) electrode can be used as a reference electrode.

[0086] In the above step S120, after installing the working electrode, counter electrode, and reference electrode, a galvanostatic method can be performed using electrochemical equipment. Accordingly, at least one metal (M) sensitive to the target biomaterial can be deposited on the electrode layer (120) provided on one surface of the substrate (110) to form a deposition layer.

[0087] According to one embodiment of the present invention, in the step S120, the voltage range according to the applied current can be controlled to -4.5 V to -3.0 V during electrochemical deposition, i.e., when performing the constant current method.

[0088] At this time, according to one embodiment of the present invention, when performing the constant current method, the applied current may be -1 A, the time may be 120 seconds, and the speed may be 100 rpm.

[0089] Through such constant current method condition control, when at least one metal (M) sensitive to a target biomaterial is deposited on an electrode layer (120) provided on one surface of a substrate (110), and a deposition layer is formed on the electrode layer (120), the generation and desorption of bubbles (H) in the formed deposition layer can occur simultaneously. Here, the generated bubbles (H) may be hydrogen bubbles.

[0090] According to one embodiment of the present invention, through constant current method condition control, the generation and detachment of bubbles (H) in the deposition layer occur simultaneously, so that the location where bubbles (H) are generated and detached remains as pores (P).

[0091] Accordingly, when the deposition of at least one metal (M) sensitive to the target biomaterial is completed through the galvanostatic method, the deposition layer formed by the deposition of the metal (M) can be converted into a three-dimensional porous microfoam (130).

[0092] In this way, the method for manufacturing a three-dimensional porous micro-foam for sensing biomaterials for healthcare according to one embodiment of the present invention can easily and quickly manufacture a three-dimensional porous micro-foam (130) through a single process, electrochemical deposition.

[0093] A three-dimensional porous microfoam (130) manufactured through a method for manufacturing a three-dimensional porous microfoam for sensing biomaterials for healthcare according to an embodiment of the present invention can simultaneously have a physically large specific surface area and an electrochemically active surface.

[0094] At this time, when the target biomaterial is glucose and, accordingly, at least one metal (M) sensitive thereto is an alloy of copper (Cu) and nickel (Ni), the specific surface area of ​​the three-dimensional porous microfoam (130) may be relatively larger than when at least one metal (M) sensitive to glucose is copper (Cu) or nickel (Ni).

[0095] A three-dimensional porous microfoam (130) manufactured through a method for manufacturing a three-dimensional porous microfoam for sensing biomaterials for healthcare according to an embodiment of the present invention can be applied to sensing biomaterials for healthcare.

[0096] That is, the three-dimensional porous microfoam (130) manufactured through the method for manufacturing a three-dimensional porous microfoam for sensing a biomaterial for healthcare according to one embodiment of the present invention can be applied to a biochemical sensor (100) that senses a biomaterial for healthcare.

[0097] According to one embodiment of the present invention, such a biochemical sensor (100) may include a substrate (110), an electrode layer (120), and a sensor layer.

[0098] The above substrate (110) can provide a formation surface for the electrode layer (120) and the sensor layer. Accordingly, the substrate (110) can support the electrode layer (120) and the sensor layer.

[0099] This substrate (110) may be, for example, provided as a silicon substrate. However, in the present invention, the substrate (110) is not limited to a silicon substrate.

[0100] The above electrode layer (120) may be provided on one surface of the substrate (110). At this time, the electrode layer (120) may be formed on one surface of the substrate (110) through electron beam deposition or sputtering deposition.

[0101] This electrode layer (120) may be made of gold (Au), but of course it may also be made of other metals with excellent conductivity.

[0102] The sensor layer may be provided on the electrode layer (120). At this time, the sensor layer may be selectively provided on the electrode layer (120). That is, the sensor layer may be provided at a desired location on the electrode layer (120) forming a conductive area with a desired area or width.

[0103] According to one embodiment of the present invention, the sensor layer may be provided as a three-dimensional porous micro-foam (130) made of at least one metal that is sensitive to a target biomaterial.

[0104] At this time, the three-dimensional porous micro-foam (130) can be formed by simultaneously generating and desorbing hydrogen bubbles (H) in the formed deposition layer during the process of forming a deposition layer by depositing at least one metal (M) that is sensitive to the target biomaterial on the electrode layer (120) through an electrochemical deposition method, for example, a constant current method.

[0105] That is, the three-dimensional porous micro foam (130) can be formed as the hydrogen bubbles (H) generated in the deposition layer are released and remain as pores (P). Accordingly, the three-dimensional porous micro foam (130) can form a soft template.

[0106] These three-dimensional porous microfoams (130) can simultaneously form a physically large surface area and an electrochemically active surface.

[0107] For example, if the target biomaterial is glucose, at least one metal sensitive thereto may be any one of copper (Cu), nickel (Ni), and an alloy of copper (Cu) and nickel (Ni).

[0108] At this time, when at least one metal sensitive to glucose is an alloy of copper (Cu) and nickel (Ni), the specific surface area of ​​the three-dimensional porous microfoam (130) may be relatively larger than when at least one metal (M) sensitive to glucose is copper (Cu) or nickel (Ni).

[0109] A biochemical sensor (100) according to one embodiment of the present invention can be provided as a non-enzyme-based glucose sensor that can replace a conventional enzyme-based glucose sensor that is expensive and vulnerable to environmental changes.

[0110] In addition, a biochemical sensor (100) according to an embodiment of the present invention, which comprises a three-dimensional porous microfoam (130) having a physically large surface area and an electrochemically active surface at the same time as a sensor layer, can be provided as a glucose sensor, thereby being of great help in managing the health of diabetic patients.

[0111] In addition, a biochemical sensor (100) according to an embodiment of the present invention, which comprises a three-dimensional porous micro-foam (130) having a large physical surface area and an electrochemically active surface at the same time as a sensor layer, can be widely applied to invasive, minimally invasive, and non-invasive diagnostic test sensors, high-cost, low-cost, extracorporeal, wearable, implantable, monitoring, and cell culture environment glucose sensors.

[0112]

[0113] Example 1

[0114] A gold-deposited silicon substrate was selected as the working electrode. The selected working electrode was immersed in a 0.1 M HCl solution, stirred approximately 30 times, rinsed with distilled water, sterilized in 99.99% anhydrous ethyl alcohol, and rinsed with distilled water. This process reduced surface contamination and ensured long-term stability.

[0115] A solution containing 0.02 M Copper(II) sulfate pentahydrate, 0.3 M Nickel(II) sulfate hexahydrate, 1 M sulfuric acid, 0.1 M Acetic acid, 0.05 M Hydrochloric acid, and 0.2 M sodium citrate tribasic dihydrate was used to prepare a three-dimensional porous microfoam (hereinafter referred to as copper-nickel foam) made of an alloy of copper and nickel.

[0116] Next, the prepared solution was placed in a beaker, and the selected working electrode was installed, and a platinum electrode was installed as a counter electrode and an Ag / AgCl electrode was installed as a reference electrode.

[0117] Next, a galvanostatic method was performed using electrochemical equipment to form a copper nickel foam with an area of ​​1 cm × 1 cm on the working electrode.

[0118] The conditions of the galvanostatic method for forming copper nickel foam are -1 A, 120 seconds, and 100 rpm, and the voltage range according to the applied current is -4.5 V to -0.3 V.

[0119]

[0120] Example 2

[0121] A gold-deposited silicon substrate was selected as the working electrode. The selected working electrode was immersed in a 0.1 M HCl solution, stirred approximately 30 times, rinsed with distilled water, sterilized in 99.99% anhydrous ethyl alcohol, and rinsed with distilled water. This process reduced surface contamination and ensured long-term stability.

[0122] 0.02 M Copper(II) sulfate pentahydrate, 1 M sulfuric acid, 0.1 M Acetic acid, 0.05 M Hydrochloric acid, and 0.2 M sodium citrate tribasic dihydrate were used to prepare a solution for forming a three-dimensional porous microfoam made of copper (hereinafter referred to as copper foam).

[0123] Next, the prepared solution was placed in a beaker, and the selected working electrode was installed, and a platinum electrode was installed as a counter electrode and an Ag / AgCl electrode was installed as a reference electrode.

[0124] Next, a galvanostatic method was performed using electrochemical equipment to form a copper foam with an area of ​​1 cm × 1 cm on the working electrode.

[0125] The conditions of the constant current method for forming copper foam were controlled in the same manner as in Example 1.

[0126]

[0127] Example 3

[0128] A gold-deposited silicon substrate was selected as the working electrode. The selected working electrode was immersed in a 0.1 M HCl solution, stirred approximately 30 times, rinsed with distilled water, sterilized in 99.99% anhydrous ethyl alcohol, and rinsed with distilled water. This process reduced surface contamination and ensured long-term stability.

[0129] 2 M Ammonium chloride and 0.1 M Nickel(II) chloride were used to prepare a solution for forming a three-dimensional porous microfoam made of nickel (hereinafter referred to as nickel foam).

[0130] Next, the prepared solution was placed in a beaker, and the selected working electrode was installed, and a platinum electrode was installed as a counter electrode and an Ag / AgCl electrode was installed as a reference electrode.

[0131] Next, a galvanostatic method was performed using electrochemical equipment to form a nickel foam with an area of ​​1 cm × 1 cm on the working electrode.

[0132] The conditions of the galvanostatic method for nickel foam formation were controlled in the same manner as in Example 1.

[0133]

[0134] FIGS. 5 and 6 are scanning electron microscope photographs of a three-dimensional porous microfoam (copper-nickel foam) made of an alloy of copper and nickel manufactured according to Example 1, FIGS. 7 and 8 are scanning electron microscope photographs of a three-dimensional porous microfoam (copper foam) made of copper manufactured according to Example 2, and FIGS. 9 and 10 are scanning electron microscope photographs of a three-dimensional porous microfoam (nickel foam) made of nickel manufactured according to Example 3.

[0135] Referring to FIGS. 5 to 10, the copper-nickel foam manufactured according to Example 1, the copper foam manufactured according to Example 2, and the nickel foam manufactured according to Example 3 were confirmed to have a dendritic structure at high magnification.

[0136] At this time, the pore size of the copper-nickel foam manufactured according to Example 1 was confirmed to be 13.94 ± 2.29 μm, the pore size of the copper foam was 15.9 ± 4.78 μm, and the pore size of the nickel foam was 10.8 6 ± 2.93 μm. In addition, the pore volume was 3291 ± 1220 μm for the copper-nickel foam. 3 , for copper foam, 1928 ± 864㎛ 3 , for nickel foam, 2760 ± 1497㎛ 3 It was confirmed as .

[0137] Through this, it can be expected that among copper-nickel foam, copper foam and nickel foam, the specific surface area of ​​copper-nickel foam is the largest.

[0138] Meanwhile, FIGS. 11 and 12 are EDS analysis results for a three-dimensional porous micro-foam made of an alloy of copper and nickel manufactured according to Example 1.

[0139] Referring to FIGS. 11 and 12, it can be seen that copper and nickel are deposited together in the copper-nickel foam.

[0140]

[0141] Hereinafter, a biochemical sensor operation method according to an embodiment of the present invention will be described with reference to FIGS. 13 and 14.

[0142]

[0143] FIG. 13 is a flowchart illustrating a method of operating a biochemical sensor having a three-dimensional porous microfoam manufactured through a method of manufacturing a three-dimensional porous microfoam for sensing a biomaterial for healthcare according to an embodiment of the present invention, and FIG. 14 is a schematic diagram illustrating step S220 of FIG. 13.

[0144]

[0145] A method for operating a biochemical sensor is a method for operating a biochemical sensor (100 in FIG. 14) having a three-dimensional porous microfoam (130 in FIG. 14) manufactured through a three-dimensional porous microfoam manufacturing method for sensing biological substances for healthcare according to an embodiment of the present invention.

[0146] Referring to FIG. 13, a biochemical sensor operating method according to one embodiment of the present invention may include steps S210 and S220.

[0147]

[0148] Step S210

[0149] Referring further to Fig. 14, the above step S210 is a step of preparing a biochemical sensor (100).

[0150] According to one embodiment of the present invention, in the step S210, a biochemical sensor (100) can be prepared that includes a three-dimensional porous microfoam (130) as a sensor layer that simultaneously has a physically large surface area and an electrochemically active surface.

[0151] The above three-dimensional porous micro-foam (130) can be formed by simultaneously generating and desorbing hydrogen bubbles (H) in the formed deposition layer during the process of forming a deposition layer by depositing at least one metal (M) sensitive to a target biomaterial on an electrode layer (120) provided on one surface of a substrate (110) through an electrochemical deposition method, for example, a constant current method.

[0152] At this time, the biochemical sensor (100) may be, for example, a sensor that detects glucose, and in this case, the three-dimensional porous micro-foam (130) may be made of any one of copper (Cu), nickel (Ni), and an alloy of copper (Cu) and nickel (Ni) that is sensitive to glucose.

[0153]

[0154] Step S220

[0155] Continuing, referring to FIG. 14, the step S220 is a step of sensing a target biological material using a prepared biochemical sensor (100).

[0156] In the above step S220, for example, glucose can be sensed using the prepared biochemical sensor (100).

[0157] According to one embodiment of the present invention, in step S220, a target biological substance can be sensed by applying a voltage of less than 6 V to the biochemical sensor (100). Preferably, in step S220, a voltage of more than 4 V and less than 6 V can be applied to the biochemical sensor (100) to sense the target biological substance.

[0158] At this time, when sensing glucose with the biochemical sensor (100), the biochemical sensor (100) can exhibit the best sensitivity when a voltage of 0.5 V is applied to the biochemical sensor (100).

[0159] When a voltage of 0.6 V is applied to the biochemical sensor (100), the signal intensity increases, but this may be due to an increase in noise (signals that do not specifically react with glucose). Therefore, from the perspective of stable sensing inherent in the biochemical sensor (100), it may be most desirable to apply a voltage of 0.5 V when sensing glucose.

[0160]

[0161] Hereinafter, the glucose sensing performance of copper nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3 will be described.

[0162]

[0163] To evaluate the glucose sensing performance of biochemical sensors comprising copper-nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3, a 0.1 M NaOH solution and 0 mM to 5 mM glucose were used. Then, the sensing performance and the presence or absence of electrochemical catalytic activity were evaluated through cyclic voltammetry (CV) and chronoamperometry (CA).

[0164]

[0165] Figure 15 shows the results of CV (cyclic voltammetry) analysis according to scan rates for a three-dimensional porous micro-foam (copper-nickel foam) made of an alloy of copper and nickel manufactured according to Example 1. To confirm whether the copper-nickel foam formed through an electrochemical deposition method acts as an electrochemically active catalyst, CV according to scan rates was performed from 0 V to 0.8 V in a 0.1 M NaOH solution.

[0166] Referring to Figure 15, diffusion plays a crucial role in electrochemical measurements between substances formed on the electrode surface and the solution. A faster scan rate can resolve diffusion constraints at the electrode surface. This means that the movement of substances between the electrode surface and the NaOH solution can occur more quickly.

[0167] Therefore, since the chemical reaction proceeds more rapidly at a fast scan rate, a high electrochemical activity indicates that there is a large amount of active sites participating in the chemical reaction on the electrode surface.

[0168] As the amount of material reaching the electrode surface increases, the reaction rate also increases, resulting in a higher maximum current. Current measures the amount of electron movement resulting from the chemical reaction occurring at the electrode surface, and electrochemical activity is related to the magnitude of the current.

[0169] Through this, it can be confirmed that the electrochemically active catalyst is well activated in the case of the copper nickel foam manufactured according to Example 1.

[0170] Figure 16 shows the CV analysis results according to the presence or absence of glucose in copper nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3.

[0171] Referring to Fig. 16, a 0.1 M NaOH solution with glucose concentrations of 0 mM and 1 mM was used for each of the copper-nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3, to confirm the change in reaction current depending on the presence or absence of glucose, and the difference in surface activity of the copper-nickel foam, copper foam, and nickel foam could be confirmed. Through this, it can be confirmed that the reactivity is relatively greater under the conditions of the copper-nickel foam, which is a heterogeneous metal alloy, compared to the single metal foam.

[0172] Figures 17 and 18 show the results of CV and CA (chronoamperometry) analysis according to glucose concentration for a three-dimensional porous microfoam (copper nickel foam) made of an alloy of copper and nickel manufactured according to Example 1.

[0173] First, referring to Figure 17, it can be confirmed that the current value due to the chemical reaction increases in the voltage ranges of 0.5 V and 0.7 V.

[0174] In addition, referring to FIG. 18, in order to indirectly confirm the chemical reaction contributing to each current increase, a constant voltage of 0.3 V, 0.4 V, 0.5 V, 0.6 V, and 0.7 V was sequentially applied to the copper nickel foam manufactured according to Example 1, and the glucose concentration was added starting from 0.5 mM and increasing by 1 mM, and the current increase was measured.

[0175] The measurement results show that as the concentration increases, the current value increases in a stepwise manner, and the largest increase in the current value is observed when a voltage of 0.5 V is applied. Accordingly, the voltage applied to the biochemical sensor was specified as 0.5 V.

[0176] Figure 19 shows the CA analysis results for glucose sensitivity characteristics of copper nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3.

[0177] Referring to Figure 19, the sensitivity according to the concentration of glucose from 0 mM to 5 mM was confirmed through CA. While applying a voltage of 0.5 V to the copper nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3, the current according to the change in the concentration of glucose was measured.

[0178] Here, it can be confirmed that the gold thin film (Bare Au) manufactured as a comparative example, which is stable and has a small surface area, exhibits insufficient surface activity to be used as a glucose sensor material due to minimal current change.

[0179] On the other hand, in the case of copper-nickel foam, copper foam, and nickel foam manufactured according to Examples 1, 2, and 3, it can be confirmed that the sensitivity current increases depending on the glucose concentration. At this time, it can be confirmed that the sensitivity increases in the order of nickel foam, copper foam, and copper-nickel foam.

[0180] As a result, it can be confirmed that the electrochemical activity of the catalyst in the copper nickel foam is the highest.

[0181] Figure 20 shows the CA analysis results for glucose sensitivity characteristics of a three-dimensional porous microfoam made of an alloy of copper and nickel manufactured according to Example 1.

[0182] Referring to Figure 20, a reactivity experiment was conducted by increasing the concentration of glucose from 0 mM to 5 mM by small increments of 0.2 mM, 0.3 mM, 0.5 mM, and 1 mM. Through this, it can be confirmed that the copper nickel foam manufactured according to Example 1 has excellent glucose reactivity.

[0183] At this time, the sensitivity of the copper nickel foam manufactured according to Example 1 was 805 ㎂·mM -1 ·cm -2 It was measured as follows. Table 2 below shows a comparison of the sensitivity of the copper nickel foam manufactured according to Example 1 with that of other studies, and it can be confirmed that the sensitivity of the copper nickel foam manufactured according to Example 1 is the best.

[0184]

[0185] Material nameSurfaceSensitivity (μA·mM -1 ·cm -2)Linear range (mM)Ref1CuNi foamFoam803-8050.5-5Present invention2Core-shell gold-nickel nanostructuresCore-shell23.170.5-10Xuejin Gao, et al. 20203Cu@Ni core-shell nanoparticles / reduced graphene oxide nanocompositesCore-shell7800.05-1Kong-Lin Wu, et al. 20174Cu-MOF / SWCNTs / GCENanotube5730.0002-0.008P. Arul, et al. 20205Polyaniline / CuNi nanocompositeNanoparticles2000.1, 0.3, 0.5Salma Bilal, et al. 20186CuNi / graphene Oxide NanocompositeNanoparticles160.370.015-1.03Xuming Zhuang, et al. 2017

[0186]

[0187] While the present invention has been described in detail using preferred embodiments, the scope of the present invention is not limited to the specific embodiments described above, and should be interpreted in accordance with the appended claims. Furthermore, those skilled in the art will appreciate that numerous modifications and variations are possible without departing from the scope of the present invention.

Claims

1. A step of preparing a substrate having an electrode layer; and A method for manufacturing a three-dimensional porous microfoam for sensing biomaterials for healthcare, comprising: depositing at least one metal sensitive to a target biomaterial on the electrode layer, and controlling deposition conditions so that bubbles occur simultaneously in the formed deposition layer during the process of forming a deposition layer on the electrode layer by the at least one metal deposited, thereby converting the formed deposition layer into a three-dimensional porous microfoam.

2. In paragraph 1, A method for manufacturing a three-dimensional porous micro-foam for biomaterial sensing for healthcare, wherein in the step of converting the formed deposition layer into a three-dimensional porous micro-foam, at least one metal is deposited through an electrochemical deposition method.

3. In paragraph 2, A method for manufacturing a three-dimensional porous micro-foam for sensing biomaterials for healthcare, wherein the voltage range according to the applied current in the above electrochemical deposition method is -4.5 V to -3.0 V.

4. In paragraph 1, A method for manufacturing a three-dimensional porous micro-foam for biomaterial sensing for healthcare, wherein in the step of converting the formed deposition layer into a three-dimensional porous micro-foam, at least one metal is selectively deposited on the electrode layer.

5. In paragraph 1, A method for manufacturing a three-dimensional porous microfoam for sensing a biomaterial for healthcare, wherein the target biomaterial is glucose, and the at least one metal is any one of copper, nickel, and an alloy of copper and nickel.

6. Description; An electrode layer provided on the above substrate; and A biochemical sensor comprising a sensor layer provided on the electrode layer and made of at least one metal that is sensitive to a target biomaterial, and provided as a three-dimensional porous micro-form.

7. In paragraph 6, The above three-dimensional porous micro-foam is a biochemical sensor formed by simultaneously generating and desorbing bubbles in the formed deposition layer during the process of forming a deposition layer by depositing at least one metal on the electrode layer.

8. In paragraph 6, A biochemical sensor, wherein the sensor layer is selectively provided on the electrode layer.

9. In paragraph 6, A biochemical sensor, wherein the at least one metal is any one of copper, nickel, and an alloy of copper and nickel, when the target biological material is glucose.

10. In paragraph 9, A biochemical sensor wherein the specific surface area of ​​the three-dimensional porous micro-foam is relatively larger when the at least one metal is an alloy of copper and nickel than when the at least one metal is copper or nickel.

11. A step of preparing a biochemical sensor according to Article 6; and A step of sensing a target biological material using the above-mentioned prepared biochemical sensor; including, A biochemical sensor operating method, wherein in the step of sensing the target biological material, a voltage of less than 6 V is applied to the prepared biochemical sensor.

12. In paragraph 11, A biochemical sensor operating method, wherein, in the step of sensing the target biological material, a voltage of more than 4 V and less than 6 V is applied to the prepared biochemical sensor.

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