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WO2012018777A1 - Capteurs de glucose non enzymatiques à base de nanomatériaux d'oxyde de métal - Google Patents

Capteurs de glucose non enzymatiques à base de nanomatériaux d'oxyde de métal Download PDF

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Publication number
WO2012018777A1
WO2012018777A1 PCT/US2011/046214 US2011046214W WO2012018777A1 WO 2012018777 A1 WO2012018777 A1 WO 2012018777A1 US 2011046214 W US2011046214 W US 2011046214W WO 2012018777 A1 WO2012018777 A1 WO 2012018777A1
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nanofibers
metal oxide
nio
glucose
metal
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Yu Lei
Yu Ding
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University of Connecticut
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University of Connecticut
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/403—Cells and electrode assemblies
    • G01N27/406—Cells and probes with solid electrolytes

Definitions

  • the present invention is in the field of sensors for blood glucose monitoring and, more specifically, for non-enzymatic glucose sensors.
  • Glucose detection has various applications ranging from clinical diagnosis of diabetes to fermentation and food quality control.
  • Glucose sensors can be generally classified into two categories: glucose oxidase (GOx) based sensors and non-enzymatic glucose sensors.
  • GOx-based sensors oxygen is reduced by GOx to H2O2 while glucose is oxidized to gluconolactone.
  • glucose detection by GOx-based sensors normally depends on the response from H2O2 oxidation or oxygen reduction.
  • GOx-based sensors Owing to the high selectivity and fast response of the enzymatic reaction, GOx-based sensors have been widely studied.
  • due to the intrinsic feature of enzymes GOx-based biosensors suffer from stability problems.
  • GOx-based test strips are not cost-effective for use in developing countries due the cost of the enzyme.
  • transition metals e.g. Au, Cu, Pt, Ni
  • metal oxides e.g. CuO, NiO, cobalt oxide
  • CNTs carbon nanotubes
  • Au nanoparticles-MW Ts, CU 2 O-MW TS nanocomposites, and Mn0 2 -MW Ts have been proposed.
  • non-enzymatic glucose sensors often lack good selectivity, which can greatly limit their clinical application.
  • metal oxide nanofibers and metal-doped metal oxide nanofibers can be prepared by, for example, electrospinning and subsequent calcination.
  • the as-prepared nanofibers can be applied to construct a non- enzymatic sensor for glucose detection in alkaline solution (e.g., pH 13).
  • alkaline solution e.g., pH 13
  • Such sensors can show a fast response time (less than 7 s), high sensitivity, and good reproducibility, selectivity, and detection limit.
  • the sensors herein are not poisoned by high concentrations of NaCl, are not affected by oxygen, and remain electrocatalytically active in alkaline solutions above 40 °C.
  • the present disclosure provides non-enzymatic glucose sensors comprising an electrode, one or more metal oxide nanofibers, and an alkaline solid electrolyte, wherein the metal oxide nanofibers and an alkaline solid electrolyte are each disposed over a surface of the electrode, at least a portion of the alkaline solid electrolyte is in contact with the metal oxide nanofibers, and the metal oxide nanofibers are each independently and optionally metal doped.
  • the present disclosure provides glucose detection apparatuses comprising a non-enzymatic glucose sensor of the preceding aspect.
  • the present disclosure provides methods for preparing non- enzymatic glucose sensors comprising, depositing one or more metal oxide nanofibers and an alkaline solid electrolyte on an electrode surface, wherein the metal oxide nanofibers are optionally metal doped.
  • the present disclosure provides glucose test strips comprising a support material comprising a working electrode wherein the working electrode comprises a surface coating comprising one or more metal oxide nanofibers and an alkaline solid electrolyte, and wherein the metal oxide nanofibers are optionally metal-doped.
  • the sensors of the present invention when applied for the detection of glucose in human blood serum, advantageously show excellent agreement with the results obtained from a commercial glucose meter (e.g., OneTouch UltraMini, LifeScan, Inc, CA). Further, the sensors herein have excellent selectivity against uric acid and ascorbic acid. Without being limited by any one theory of operation, under alkaline condition (e.g., pH 13), the metal oxide surfaces would be negatively charged resulting in a "repelling effect". Under the same conditions, potentially interfering compounds, such as uric acid (UA) and ascorbic acid (AA), would also be negatively charged due to the loss of proton. Consequently, the negatively charged metal oxide surface could strongly repel the negatively charged UA and AA molecules, thus greatly reducing the electrooxidation of UA and AA on the surface of metal oxides and resulting in good selectivity.
  • a commercial glucose meter e.g., OneTouch UltraMini, LifeScan, Inc, CA.
  • the sensors herein have excellent selectivity against uric
  • the non-enzymatic glucose sensors described herein have great commercial potential in clinical diagnosis of diabetes due to their excellent performance, good reproducibility, low cost, and inherent stability of the component inorganic materials.
  • Figure 1 shows (A) SEM image of polyvinylpyrrolidone(PVP)/Co( 03)2 nanofibers; (B) C0 3 O 4 nanofibers (C) C0 3 O 4 nanofibers after 1 h sonication in ethanol; and (D) TEM image of a single C0 3 O 4 nanofiber (inset: SAED patterns of C0 3 O 4 nanofibers).
  • Figure 2 shows (A) FTIR spectra of PVP/Co(N0 3 ) 2 nanofibers (a) and Co 3 0 4 nanofibers (b); and (B) Raman spectra of PVP/Co( 03) 2 nanofibers (a) and C0 3 O 4 nanofibers (b).
  • Figure 3 shows (A) XRD patterns for the standard values of JCPDS 42-1467 (a), and the as-prepared C0 3 O 4 nanofibers (b); and (B) a high resolution X-Ray photoelectron spectrum for Co 2p regions of the C0 3 O 4 nanofibers.
  • Figure 4a shows cyclic voltammograms (CVs) of the C0 3 O 4 nanofibers (NFs)-
  • Figure 4b shows CVs of the C0 3 O 4 NFs-Nafion/glassy carbon electrode(GCE) in 0.1 M NaOH solution at various scan rates of 25, 50, 75, 100, 125, 150, 175, 200 mV/s.
  • Figure 4c shows a plot of peak currents vs. scan rate for C0 3 O4 NFs-Nafion/glassy carbon electrode (GCE).
  • Figure 5a shows CVs of the Nafion/GCE (a and b) and Co 3 0 4 NFs-Nafion/GCE (c and d) in 0.1 M NaOH in the absence (a and c) and presence (b and d) of 2.8 mM glucose, respectively.
  • Figure 5b shows the amperometric response of the C0 3 O4 NFs-Nafion/GCE with successive additions of glucose to 0.1 M NaOH at an applied potential of +0.59 V.
  • Figure 5c shows a corresponding calibration curve with fitting curve and linear range for the amperometric response of Figure 5b.
  • Figure 5d shows the amperometric response of C0 3 O4 NFs-Nafion/GCE with successive 3-time additions of analytes in the sequence of 5 blood serum sample, 5 10 mM glucose in buffer, 10 blood serum sample, and 10 ⁇ ⁇ 10 mM glucose in buffer.
  • Figure 6 shows (A) a schematic illustration for the selective catalytic reaction towards glucose; (B) the response of Nafion modified bare GCE to the addition of 4 mM glucose (a), 0.125 mM ascorbic acid (AA) (b), 0.33 mM uric acid (UA) (c); (C) the response of the C0 3 O4 NFs-Nafion/GCE to the addition of 4 mM glucose (a), 4 mM glucose with 0.125 mM AA (b), 4 mM glucose with 0.33 mM UA (c), 0.125 mM AA (d), 0.33 mM UA (e) in 0.1 M NaOH.
  • Figure 7 shows SEM images of (a) AgN03-PVP nanofibers; (b) porous Ag obtained after calcination of AgN03-PVP nanofibers; (c) Ni(N03)2-PVP nanofibers; (d) NiO nanofibers; (e) Ni(N0 3 )2-AgN0 3 -PVP nanofibers; (f) NiO-Ag nanofibers.
  • Figure 8 shows TEM images of (a) a Ni(N0 3 ) 2 -AgN0 3 -PVP nanofiber; (b) a NiO nanofiber; (c) a NiO-Ag hybrid nanofiber; insets show the EDX mapping of Ag, Ni and O elements; (d) SAED pattern of NiO-Ag hybrid nanofiber; (e) EDX analysis of NiO-Ag hybrid nanofibers; inset: EDX analysis of Ni(N03)2-AgN03-PVP nanofibers.
  • C and Cu peaks come from the copper-carbon grid of TEM
  • Figure 9a shows FTIR spectra of Ni(N03)2-AgN03-PVP nanofibers, porous Ag, NiO nanofibers and NiO-Ag nanofibers.
  • Figure 9b shows XRD patterns for the standard values of JCPDS 04-0835 (NiO, solid line) and 04-0783 (Ag, dash-dot line), and the as-prepared porous Ag, NiO nanofibers and
  • NiO-Ag nanofibers NiO-Ag nanofibers.
  • Figure 9c shows high resolution X-Ray photoelectron spectra for Ni 2p region of the NiO-Ag nanofibers.
  • Figure 9d shows high resolution X-Ray photoelectron spectra for Ag 3d region of the NiO-Ag nanofibers.
  • Figure 11 shows (a) CVs of the NiO-Ag NFs/GCE in 0.1 M NaOH solution at various scan rates (10, 20, 40, 60, 80, and 100 mV/s); (b) plot of peak currents vs. scan rate.
  • Figure 12a shows hydrodynamic voltammograms of 200 ⁇ glucose at the porous Ag/GCE, NiO NFs/GCE and NiO-Ag NFs/GCE.
  • Figure 12b shows amperometric response of porous Ag/GCE and NiO-Ag NFs/GCE to successive additions of glucose at an applied potential of 0.1 V.
  • Figure 12c shows amperometric response of porous NiO NFs/GCE and NiO-Ag NFs/GCE to successive additions of glucose at an applied potential of 0.6 V.
  • Figure 12d shows a calibration curves corresponding to the amperometric response of Figure 12b and 12c.
  • Figure 13 shows (a) the response of the porous Ag/GCE and the NiO-Ag NFs/GCE to the addition of 4 mM glucose, 0.125 mM AA and 0.33 mM UA in 0.1 M NaOH at an applied potential of 0.1 V; and (b) the response of the NiO NFs/GCE and the NiO-Ag NFs/GCE to the addition of 4 mM glucose, 4 mM glucose with 0.125 mM AA, and 4 mM glucose with 0.33 mM UA in 0.1 M NaOH at an applied potential of 0.6 V.
  • Figure 14 is a schematic illustration for the selective catalytic reaction towards glucose.
  • Figure 15 shows the amperometric response of the NiO-Ag NFs/GCE at 0.6 V with successive additions of different analytes; the ratio of glucose to UA and AA in testing electrolyte solution is in the similar ratio level as that in the blood sample.
  • the non-enzymatic glucose sensors herein comprise one or more metal oxide nanofibers, wherein the metal oxide nanofibers are optionally metal doped.
  • Suitable metal oxides include, but are not limited to C0 3 O 4 , NiO, CuO, or a mixture thereof.
  • the metal oxide nanofibers comprise C0 3 O 4 or NiO.
  • the metal oxide nanofibers comprise C0 3 O 4 .
  • the metal oxide nanofibers comprise NiO.
  • the metal oxide nanofibers are not CuO nanofibers.
  • the metal oxide nanofibers comprise a mixture of two or more of metal oxides.
  • the two metal oxides are selected from the group consisting of Co 3 0 4 , NiO, CuO, ZnO, Sn0 2 , Ce0 2 , Mn0 2 , Ru0 2 , and CdO.
  • the metal oxide nanofibers comprise a mixture of two or more of metal oxides, where one metal oxide is Co30 4; NiO, or CuO (e.g., C0 3 O 4 or NiO), and the other metal oxide is ZnO, Sn0 2 , Ce0 2 , Mn0 2 , Ru0 2 , or CdO.
  • the metal oxide nanofibers can comprise NiO and CdO (i.e., NiO-CdO nanofibers).
  • the metal oxide nanofibers comprise a mixture of three or more metal oxides.
  • the three metal oxides are selected from the group consisting of Co 3 0 4 , NiO, CuO, ZnO, Sn0 2 , Ce0 2 , Mn0 2 , Ru0 2 , and CdO.
  • the metal oxide nanofibers comprise a mixture of three or more of metal oxides, where two metal oxide are selected from C0 3 O 4, NiO, and CuO (e.g., C0 3 O 4 and NiO), and the remaining metal oxide is ZnO, Sn0 2 , Ce0 2 , Mn0 2 , Ru0 2 , or CdO.
  • the metal oxide nanofibers comprise a mixture of three or more of metal oxides, where one metal oxide is Co30 4; NiO, or CuO (e.g., C0 3 O 4 or NiO), and the other two metal oxides are selected from ZnO, Sn0 2 , Ce0 2 , Mn0 2 , Ru0 2 , and CdO.
  • the metal oxide nanofibers can comprise Co30 4; NiO, and CuO (e.g., C0 3 O 4 -N1O-CUO nanofibers).
  • nanofiber as used herein means fibers comprising the referenced materials which have an average diameter of less than about 1000 nm and are can be prepared by electrospinning according to methods familiar to those skilled in the art, or according to the methods described below.
  • nanofibers comprise two or more constituent components, each of the components are separated by a dash “-” (e.g., NiO-CdO nanofibers comprise both NiO and CdO within the nanofibers).
  • the two metal oxide components can be present in the nanofibers in any suitable molar ratio (e.g., in a 1 : 1, 1 :2, 1:5, 1 : 10, 1: 15, 1:20, 1 :25, 1:30, 1 :35, 1 :40, 1 :45, 1:50, 1:55, 1 :60, 1 :65, 1:70, 1:75, 1 :80, 1 :85, 1 :90, 1:95, or 1 : 100 molar ratio of the two metal oxide components).
  • nanofibers containing two or more metal oxide constituents include all suitable molar ratios of the referenced components.
  • NiO and CdO can be present in the nanofibers in a molar ratio of 1: 1, 1:2, 1 :5, 1 : 10, 1: 15, 1:20, 1 :25, 1:30, 1 :35, 1 :40, 1:45, 1:50, 1:55, 1 :60, 1:65, 1:70, 1 :75, 1:80, 1 :85, 1 :90, 1:95, or 1 : 100 of either NiO to CdO or CdO to NiO.
  • the nanofibers are metal doped metal oxide nanofibers.
  • metal doped as used herein means that the nanofibers comprise one or more elemental metal component in addition to the metal oxide component within the nanofibers (e.g., NiO-Ag nanofibers comprise both NiO and Ag within the nanofibers).
  • elemental metal component can be identified, for example, by transmission electron microscopy (TEM).
  • TEM transmission electron microscopy
  • the metal-doped metal oxide nanofibers comprise discrete domains of the metal and the metal oxide.
  • the metal doped metal oxide nanofibers can comprise a mixture of metal oxide nanoparticles and metal nanoparticles which may be homogeneously or heterogeneously dispersed throughout the nanofibers.
  • the metal doped metal oxide nanofibers can comprise a heterogeneous mixture of metal oxide nanoparticles and metal nanoparticles.
  • Such metal doped metal oxide nanofibers herein are also referred to as “hybrid nanofibers.”
  • hybrid nanofibers comprise each of the referenced constituents (i.e., the two or more components, each separated by a dash "-").
  • the metal and metal oxide components can be present in the nanofibers in any suitable molar ratio (e.g., 1 : 1, 1 :2, 1 :5, 1 : 10, 1 : 15, 1 :20, 1 :25, 1 :30, 1 :35, 1 :40, 1 :45, 1 :50, 1 :55, 1 :60, 1 :65, 1 :70, 1 :75, 1 :80, 1 :85, 1 :90, 1 :95, or 1 : 100 molar ratio of metal to metal oxide), provided that the metal oxides maintain a suitable fiber structure (e.g., comprise 50 mol% or more of the nanofibers).
  • a suitable fiber structure e.g., comprise 50 mol% or more of the nanofibers.
  • metal-doped metal oxide nanofibers include all suitable molar ratio of the referenced components as defined above.
  • Ag and NiO can be present in the nanofibers in a molar ratio of 1 : 1, 1 :2, 1 :5, 1 : 10, 1 : 15, 1 :20, 1 :25, 1 :30, 1 :35, 1 :40, 1 :45, 1 :50, 1 :55, 1 :60, 1 :65, 1 :70, 1 :75, 1 :80, 1 :85, 1 :90, 1 :95, or 1 : 100 of Ag to NiO.
  • the metal oxide nanofibers can be doped with one or more noble metals.
  • the nanofibers are noble metal-doped metal oxide nanofibers.
  • Noble metals refers to metals selected from the group consisting of ruthenium, rhodium, palladium, silver, osmium, iridium, platinum, gold, and mixtures thereof.
  • noble metals are metals selected from the group consisting of palladium, silver, platinum, gold, and mixtures thereof.
  • the nanofibers are Ag-doped metal oxide nanofibers; or Au-doped metal oxide nanofibers; or Pt- doped metal oxide nanofibers; or Pd-doped metal oxide nanofibers.
  • suitable metal oxide nanofibers include, but are not limited to metal- doped NiO nanofibers, metal-doped C0 3 O 4 nanofibers, metal-doped CuO nanofibers, noble metal-doped NiO nanofibers, noble metal-doped C0 3 O 4 nanofibers, and noble metal-doped CuO nanofibers.
  • metal-doped metal oxide nanofibers include, but are not limited to, NiO-Ag nanofibers, Co 3 0 4 -Ag nanofibers, and CuO-Ag nanofibers or a combination thereof.
  • the metal-doped metal oxide hybrid nanofibers can comprise two or more metal oxides and one or more metal (e.g., one or more noble metal).
  • the metal-doped metal oxide nanofibers comprise a mixture of two or more of metal oxides (e.g., two of Co 3 0 4, NiO, CuO, ZnO, Sn0 2 , Ce0 2 , Mn0 2 , Ru0 2 , and CdO) and one or more noble metal, as defined above.
  • the metal-doped metal oxide nanofibers can comprise NiO, CdO, and Ag (i.e., Ag-NiO-CdO nanofibers).
  • the metal oxide nanofibers comprise a mixture of three or more metal oxides (e.g., three of Co 3 0 4, NiO, CuO, ZnO, Sn0 2 , Ce0 2 , Mn0 2 , Ru0 2 , and CdO) and one or more noble metal, as defined above.
  • the metal-doped metal oxide nanofibers can comprise Co 3 0 4; NiO, CuO, and Ag (e.g., Ag-Co30 4 -NiO-CuO nanofibers).
  • the total moles of metal component(s) and the total moles of the metal oxide components can be present in the nanofibers in any suitable molar ratio (e.g., 1 : 1, 1 :2, 1 :5, 1 : 10, 1 : 15, 1 :20, 1 :25, 1 :30, 1 :35, 1 :40, 1 :45, 1 :50, 1 :55, 1 :60, 1 :65, 1 :70, 1 :75, 1 :80, 1 :85, 1 :90, 1 :95, or 1 : 100 molar ratio of total moles of metal to total moles of metal oxide), provided that the metal oxide components maintain a suitable fiber structure (e.g., the total metal oxide component comprise 50 mol% or more of the nanofibers).
  • the total metal oxide component comprise 50 mol% or more of the nanofibers.
  • metal-doped metal oxide nanofibers comprising two or more metal oxide components and/or two or more metal components include all suitable molar ratio of the referenced components as defined above.
  • the relevant ratio is the moles of Ag to the total moles of NiO and Co 3 0 4; such that the molar ratio is Ag to [NiO+Co 3 0 4 ].
  • the relevant ratio is the total moles of Ag and Au to the moles of NiO ; such that the molar ratio is [Ag + Au] to NiO.
  • the metal oxide nanofibers and/or metal-doped metal oxide nanofibers are disposed over a surface of an electrode.
  • the electrode can be, for example, a gold, silver, platinum, copper, glassy carbon, or pyrolytic carbon electrode.
  • the electrode is a gold electrode.
  • the electrode is a silver electrode.
  • the electrode is a platinum electrode.
  • the electrode is a copper electrode.
  • the electrode is a glassy carbon electrode.
  • the electrode is a pyrolytic carbon electrode.
  • the non-enzymatic glucose sensor further comprises an alkaline solid electrolyte in contact with at least a portion of the metal oxide nanofibers and/or metal-doped metal oxide nanofibers.
  • the alkaline solid electrolyte provides an alkaline environment for glucose oxidation (similar to having an alkaline solution); and, when nanoporous, can block large particles like red cells and allows soluble materials in the blood, such as glucose, to flow through and be oxidized at the electrode surface, thus greatly improving the sensitivity and accuracy.
  • the alkaline solid electrolyte can be any solid electrolyte which can provide an alkaline pH at the location of the nanofibers (e.g., pH about 8 to about 14; in certain embodiments, a pH of about 10 to 13; in certain other embodiments, a pH of about 12 to about 13).
  • suitable alkaline solid electrolytes include, but are not limited to, a sulfonated tetrafluoroethylene polymer, sodium hydroxide, and/or potassium hydroxide.
  • Sulfonated tetrafluoroethylene polymers can include Nafion ® 1 17 [CAS No 31 175-20-9] a sulfonated tetrafluoroethylene based fluoropolymer-copolymer, ⁇ a copolymer of 2-[l- [difluoro-[(trifluoroethenyl)oxy]methyl]-l,2,2,2-tetrafluoroethoxy]-l, l,2,2,- tetrafluoroethane-1 -sulfonic acid with tetrafluoroethylene ⁇ .
  • the alkaline solid electrolytes are sodium hydroxide or potassium hydroxide.
  • the alkaline solid electrolyte may be nanoporous, as noted above, to act as a size-exclusion filter at the site of the metal oxide nanofibers and/or metal-doped metal oxide nanofibers.
  • glucose sensors made of metal-doped metal oxide nanofibers have shown higher sensitivity, lower detection limit, and wider linear range for glucose detection compared to sensors made of the individual components (e.g., NiO nanofibers or porous Ag).
  • NiO-Ag sensors displayed a synergistic effect between NiO and Ag.
  • the non-enzymatic glucose sensors can be prepared according to a method comprising, depositing one or more metal oxide nanofibers and an alkaline solid electrolyte on an electrode surface, wherein the metal oxide nanofibers are optionally metal doped.
  • the nanofibers and electrolyte can be deposited by either (i) depositing the optionally metal-doped metal oxide nanofibers over a surface of the electrode and depositing the alkaline solid electrolyte over the optionally metal-doped metal oxide nanofibers; or (ii) co- depositing the optionally metal doped metal oxide nanofibers and an alkaline solid electrolyte on the electrode surface.
  • a suspension of nanofibers (e.g., C0 3 O 4 nanofibers) can be cast onto the surface of an electrode (e.g., a glassy fiber electrodes (GCE)), and then the nanofibers can be entrapped by casting Nafion over the nanofibers to prepare a C0 3 O 4 nanofiber-modified electrode.
  • a suspension of nanofibers (e.g., C0 3 O 4 nanofibers) and an alkaline solid electrolyte can be co-cast onto the surface of an electrode (e.g., a glassy fiber electrodes (GCE)).
  • "Depositing" and “casting” can each include drop casting, spray coating, screen printing, doctor-blading, and any other methods familiar to those skilled in the art for coating a surface with a solution.
  • the nanofibers described in any of the preceding aspects of the disclosure, and any embodiment thereof, can be formed by electrospinning a solution comprising at least one metal oxide precursor, one or more optional metal precursors, and a polymer to yield polymer composite fibers and calcining the polymer composite fibers under conditions suitable for removing the polymer from the nanofibers.
  • the solvent can comprise water or an alcohol (e.g., methanol, ethanol, n-butanol, t-butanol, and the like).
  • the solvent is a water and alcohol mixture (e.g., water and ethanol).
  • Electrospinning can utilize a spinneret (typically a hypodermic syringe needle) connected to a high-voltage (5 to 50 kV, e.g., 20 kV) direct current power supply, a syringe pump, and a grounded collector.
  • a spinneret typically a hypodermic syringe needle
  • a high-voltage 5 to 50 kV, e.g., 20 kV
  • a polymer solution, sol-gel, particulate suspension or melt is loaded into the syringe and this liquid is extruded from the needle tip at a constant rate suitable for the generation of fibers (e.g., 0.3 mL/h) by a syringe pump.
  • Calcination includes heating the polymer composite fibers at a temperature greater than 500 °C in an oxygen-containing atmosphere (e.g., air), for an amount of time suitable to remove the polymer from the fibers, to provide the desired nanofibers, as described above.
  • an oxygen-containing atmosphere e.g., air
  • the polymer composite fibers are heated to a temperature of at least about 500 °C for at least 3 hours (e.g., 3 - 10 hours; or 3- 5 hours).
  • Metal oxide precursors and metal precursors may include any metal salt familiar to those skilled in the art which is suitable for preparation of the desired optionally-doped metal oxide nanofibers.
  • Suitable precursor salts include, Co(II) salts (e.g., Co(1Si0 3 ) 2 -6H 2 0, CoS0 4 -7H 2 0, CoCl 2 -6H 2 0, and/or cobalt (II) acetate), Ni(II) salts (e.g., Ni(N0 3 ) 2 -6H 2 0, S0 4 -7H 2 0, NiCl 2 -6H 2 0, and/or nickel (II) acetate), Ag(I) salts (AgN0 3 , Ag 2 S0 4 , and/or silver acetate), Cd(II) salts (Cd(N0 3 ) 2 -4H 2 0, CdCl 2 -2.5H 2 0, CdS0 4 -8/3H 2 0, and/or cadmium(II) acetate), Cu
  • the metal oxide precursor can be one or more Co(II) salt, Ni(II) salt, Cd(II), and/or Cu(II) salt; and the metal precursor can be one or more Ag(I) salt, Au(III) salt, Pt(II) salt, Pt(IV) salt, and/or Pd(II) salt.
  • the metal oxide precursor can be one or more Ni(II) salt; and the metal precursor can be one or more Ag(I) salt, Au(III) salt, Pt(II) salt, Pt(IV) salt, and/or Pd(II) salt (e.g.. Ag(I) salt for Ag-NiO nanofibers; Au(III) salt for Au-NiO nanofibers, Pt(II) or Pt(IV) salt for Pt-NiO nanofibers; and Pd(II) salt for Pd-NiO nanofibers).
  • Pd(II) salt e.g.. Ag(I) salt for Ag-NiO nanofibers
  • Pd(II) salt for Pd-NiO nanofibers
  • the metal oxide precursor can be one or more Co(II) salt; and the metal precursor can be one or more Ag(I) salt, Au(III) salt, Pt(II) salt, Pt(IV) salt, and/or Pd(II) salt (e.g,. Ag(I) salt for Ag-Co 3 0 4 nanofibers; Au(III) salt for Au-Co 3 0 4 nanofibers, Pt(II) or Pt(IV) salt for Pt-Co 3 0 4 nanofibers; and Pd(II) salt for Pd-Co 3 0 4 nanofibers).
  • Suitable polymers include, but are not limited to, poly(vinyl pyrrolidone) (PVP), poly(acrylic acid) (PAA), poly(caprolactone) (PCL), polyvinyl alcohol) (PVA), poly (vinyl acetate) (PVAc), and poly(ethylene oxide) (PEO).
  • the polymer is PVP.
  • the polymer e.g., PVP
  • Molecular weight refers to weight-averaged molecular weight as is familiar to those skilled in the art.
  • the polymer composite fibers can have average diameters between about 10 nm and about 1000 nm. In certain embodiments, the polymer composite fibers can have an average diameter between about 100 nm and about 500 nm. In other embodiments, the polymer composite fibers can have an average diameter between about 100 nm and about 350 nm.
  • nanofibers are formed having average diameters between about 50 nm and about 200 nm. In another embodiment, the nanofibers have average diameters between about 50 nm and about 150 nm. In another embodiment, the nanofibers have average diameters between about 50 nm and about 100 nm. In another embodiment, the nanofibers have average diameters between about 50 nm and about 75 nm.
  • the preceding non-enzymatic glucose sensor can be incorporated into a glucose detection apparatus (e.g. glucose meter, potentiostat).
  • the apparatus may comprise a temperature sensor positioned to detect the temperature at or near a surface of the non-enzymatic glucose sensor.
  • the glucose detection apparatus may also comprise programmed software to calibrate for a temperature effect on performance of the non-enzymatic glucose sensor. As the temperature effect on sensor performance can be calibrated using a temperature sensor and programmed software, the present sensors can be used in many places where there is no temperature control.
  • the sensor of the present invention can be fabricated as a test strip similar to glucose oxidase-based test strips, thus fabricating facilities used for the glucose oxidase based test strips can be used for the fabrication of the non-enzymatic test strips of the present invention.
  • glucose test strips are provided comprising a non-enzymatic glucose sensor of any of the preceding aspects and embodiments of the disclosure.
  • the test strips can comprise, a working electrode having a coating, wherein the coating comprises a metal oxide nanomaterial and an alkaline solid electrolyte, and wherein the metal oxide nanomaterial is optionally metal doped.
  • the test strip may further comprise a counter electrode and a reference electrode, each positioned in electrochemical communication with the working electrode. That is, the test strip can comprise a non-enzymatic glucose sensor as described above, a counter electrode, and a reference electrode.
  • the test strips also comprise a support material which is capable of conveying an aqueous test sample (e.g., blood or plasma) from a first point on the material (a sample application point) to the non-enzymatic glucose sensor at a second point on the material.
  • a support material which is capable of conveying an aqueous test sample (e.g., blood or plasma) from a first point on the material (a sample application point) to the non-enzymatic glucose sensor at a second point on the material.
  • a support material include paper, nylon, plastic, or a filter, and can be a suitable size for its intended purpose.
  • Other examples of such support materials include wicking membranes, such as cellulose membranes, nitrocellulose membranes, or microfluidic devices which convey the aqueous test sample to aqueous test sample via one or more microfluidic channels leading from the first point on the material (sample application point).
  • a conventional glucose meter can be adapted for use with the metal oxide-based non-enzymatic test strip described herein.
  • metal oxide nanofibers and alkaline solid electrolytes are applied to strips by a screen printing process.
  • metal oxide nanofibers and alkaline solid electrolytes are applied to strips by a spray coating process.
  • Cobalt nitrate hexahydrate (Co(N0 3 ) 2 -6H 2 0) and sodium hydroxide (NaOH, pellets) were purchased from Fisher Scientific.
  • Ascorbic acid, uric acid, ethanol (for HPLC, denatured) and D-(+)-glucose were supplied by Acros Organics.
  • 0.1 M pH 7.0 phosphate buffer solution was prepared using a 2 HP0 4 and aH 2 P0 4 .
  • Glucose solutions with different concentrations were diluted from stock solution (1 M). All aqueous solutions were prepared with deionized water (18.2 ⁇ -cm) generated by a Barnstead water system.
  • glassy carbon electrode (GCE, dia. 3 mm) was polished with 1 ⁇ and 0.05 ⁇ alumina slurries sequentially, and then rinsed with DI water. Finally, the electrode was sonicated in ethanol and deionized water, dried at room temperature, and ready for modification.
  • 5 mg/mL C0 3 O 4 nanofibers suspension 5 mg C0 3 O 4 nanofibers was first suspended in 1 mL ethanol and sonicated for 1 hour, and then a 5 ⁇ , suspension was dropped onto the surface of GCE.
  • a JEOL 6335F field-emission scanning electron microscope was used to examine the morphology and the size of the as-electrospun precursor nanofibers and C0 3 O 4 nanofibers. More detailed morphology and selected area electron diffraction (SAED) patterns were obtained with a Tecnai T12 transmission electron microscope operated at 120 kV. XRD patterns were obtained with an Oxford diffraction XcaliburTM PX Ultra with ONYX detector to study the crystal structure of C0 3 O 4 nanofibers. FTIR spectra were obtained on a Nicolet Magna-IR 560 spectrophotometer (Bruker, Germany). Raman spectra were recorded at ambient temperature on a Renishaw Ramanscope Micro-Raman with 514 nm wavelength laser.
  • Cyclic voltammetry (CV) measurements were performed on a Model CHI 601C Electrochemical Workstation (CH Instruments, USA). All experiments were conducted using a three-electrode electrochemical cell (working volume of 5 mL) with a working electrode, an Ag/AgCl reference electrode, and a platinum disc counter electrode. For amperometric detection, all measurements were performed by applying an appropriate potential to the working electrode and allowing the transient background current to decay to a steady-state value, before the addition of the analyte. A stirred solution was employed to provide convective transport.
  • Fig. 1A and IB The SEM images of PVP/Co(N0 3 ) 2 composite nanofibers and the C0 3 O 4 nanofibers obtained after calcination at 500 °C are shown in Fig. 1A and IB, respectively.
  • the fiber morphology was maintained after the degradation of PVP and decomposition of Co(N03)2, accompanied by a decrease of an average diameter from 302 ⁇ 25 nm to 105 ⁇ 10 nm (calculated from 50 randomly selected nanofibers under SEM images), which was attributed to the loss in total mass upon calcination.
  • the nanofibers obtained after calcination were composed of numerous nanoparticles with relatively uniform distribution and their surfaces are not smooth any more (Fig.
  • the SAED pattern indicates the crystalline structure of the as-prepared C0 3 O 4 nanofibers. After sonication in ethanol for 1 hour, long C0 3 O 4 nanofibers were exfoliated to short nanofibers with an average length of ca. 1 ⁇ and a three dimensional (3D) porous network was formed after drop-casting the sonicated sample on solid substrate (Fig. 1C).
  • Fig. 2A shows the FTIR spectra of the electrospun precursor nanofibers and the obtained C0 3 O 4 nanofibers, respectively.
  • the two sharp peaks can be assigned to Co-0 bonds existing in Co (II, III) oxide.
  • the disappearance of the characteristic peaks of PVP and Co( 0 3 ) 2 is an indication of the complete degradation of PVP and the conversion of Co( 0 3 ) 2 to C0 3 O 4 .
  • Raman spectra were employed to further examine the difference between the precursor nanofibers and the final product. As shown in Fig. 2B (curve b), four peaks located at 483, 523, 621, and 694 cm “1 , corresponds to E g , F ⁇ g , F 2 2g , and A l g modes of the crystalline C0 3 O 4 , respectively. As a comparison, the Raman spectrum of the precursor nanofibers does not show any obvious peak (curve a).
  • the crystal structure and the phase purity of the as-prepared C0 3 O 4 nanofibers were further characterized by XRD.
  • the XRD spectrum of C0 3 O 4 nanofibers matches the standard spectrum of cubic crystalline C0 3 O 4 (JCPDS 42-1467).
  • the formation of cubic crystalline C03O4 is revealed by the diffraction peaks at 2 ⁇ values of 19.00, 31.27, 36.85, 38.54, 44.81, 56.66, 59.36, 65.24, 74.12° corresponding to (1 11), (220), (331), (222), (440), (422), (511), (440), and (620) crystal planes, respectively.
  • the pair of redox peaks I/II can be assigned to the reversible transition between C0 3 O 4 and CoOOH, while another pair of redox peaks UVTV can be attributed to further conversion between CoOOH and C0O 2 .
  • These two reversible reactions can be schematically expressed as equation (1) C0 3 O 4 + OH " + H 2 0 ⁇ ->3CoOOH + e " and equation (2) CoOOH + OH " ⁇ Co0 2 + H 2 0 + e " .
  • C0 3 O 4 nanofibers with average diameter of ca. 105 nm were fabricated.
  • Raman and FTIR spectra were performed to confirm the complete decomposition of polymer matrix and decomposition cobalt salt.
  • XRD and XPS were employed to study the crystal structure and composition of the oxide.
  • the C0 3 O 4 nanofibers suspension was casted onto the surface of GCE and then entrapped with Nafion to prepare C0 3 O 4 nanofibers modified GCE.
  • the C0 3 O 4 NFs-Nafion/GCE showed two pairs of well-defined redox peaks in alkaline electrolyte but no obvious redox peaks in neutral solution.
  • the C0 3 O 4 nanofibers based non-enzymatic glucose sensor showed excellent performance towards the electrooxidation of glucose in alkaline solution. Its application to human blood serum was also demonstrated. The low detection limits, high reproducibility, and good selectivity of the as-prepared glucose sensor make C0 3 O 4 nanofibers a good candidate for the construction of non-enzymatic sensor for glucose detection. In addition, Langmuir isothermal theory was applied to fit the calibration curve. The mechanisms for glucose detection and good selectivity were also discussed.
  • Fig. 5A presents the CVs in the absence and presence of 2.8 mM glucose, recorded at the Nafion-GCE (curves a and b) and the C0 3 O 4 NFs-Nafion/GCE (curves c and d), respectively.
  • the C0 3 O 4 NFs-Nafion/GCE exhibited significant oxidation of glucose starting at ca. +0.25 V and covering the potential region where CoOOH and C0O 2 are formed. By contrast, no obvious response was found at the Nafion/GCE.
  • the obtained sensitivity is better than those of 17.8 ⁇ mM "1 cm “2 at Pt-Pb alloy nanoparticles-MWCNTs/GCE (Cui, H.F. et al, 2007. Anal. Chim. Acta 594, 175-183), 11.8 ⁇ mM "1 cm “2 at porous Au electrode ( Li, Y. et al, 2007. Electrochem. Commun.
  • the high sensitivity and low detection limit can be attributed to the excellent catalytic property of the as-prepared C0 3 O 4 nanofibers and the highly porous 3D network of C0 3 O 4 nanofibers, which provides high specific surface area and numerous active sites, and also allows the access of analytes to the active catalytic sites with minimal diffusion resistance (Jia, W.Z.
  • Fig. 5D demonstrated the amperometric response to successive three repeated additions of analytes in the sequence of 5 ⁇ . blood serum sample, 5 ⁇ . 10 mM glucose in buffer, 10 ⁇ . blood serum sample, and 10 ⁇ . 10 mM glucose in buffer.
  • concentration of glucose in human blood serum sample was calibrated by standard glucose solution and the result was presented in the inset table in Fig. 5D.
  • the same serum sample was also measured by commercial glucose meter (OneTouch UltraMini, LifeScan, Inc, CA). The good agreement between the results obtained by our proposed sensor and those read from the commercial glucose detector indicates the practical application of the as-prepared non- enzymatic glucose sensor.
  • the selectivity of the C0 3 O 4 NFs-Nafion/GCE was also investigated against normally co- existed interfering species with glucose such as ascorbic acid (AA) and uric acid (UA).
  • AA ascorbic acid
  • UA uric acid
  • the blood glucose level of a normal human body is between 4 and 7 mM, while the concentration of endogenous AA and UA is respectively about 0.125 mM and 0.33 mM in blood samples.
  • 0.125 mM AA dissolved in 4 mM glucose solution can only result in 14% increase of amperometric response compared to the response for 4 mM glucose, while 0.33 mM UA leads to 17% increase, which is not significant.
  • C0 3 O 4 has an isoelectric point (IEP) of ⁇ 8.
  • IEP isoelectric point
  • the negatively charged C0 3 O 4 nanofibers surface could strongly repel the negatively charged UA and AA molecules, thus greatly reducing the electrooxidation of UA and AA on the surface of C0 3 O 4 nanofibers at an applied potential of +0.59 V and resulting in good selectivity.
  • Ni(N0 3 ) 2 -6H 2 0 and 0.1 g AgN0 3 were dissolved in 1.6 g water and then mixed with a 2.8 g solution consisting of 0.4 g PVP and 2.4 g ethanol.
  • the Ni(N0 3 ) 2 -AgN0 3 -PVP composite nanofibers were prepared using a 23-gauge needle with a flow rate of 0.3 mL/h at an applied voltage of 20 kV over a gap distance of 15 cm and were collected on aluminum foil. The precursor was then calcined under air atmosphere at 500 °C for 3 h in order to remove the matrix polymer and generate NiO-Ag nanofibers.
  • NiO nanofibers and porous Ag were also synthesized following the similar procedure, the only difference was using 0.4 g Ni(N03) 2 -6H 2 0 or 0.1 g AgN0 3 as the only metal precursor, respectively.
  • glassy carbon electrode (GCE, dia. 3 mm) was polished with 1 ⁇ and 0.05 ⁇ alumina slurries sequentially, and then rinsed with deionized (DI) water. Finally, the electrode was sonicated in ethanol and deionized water, dried at room temperature, and ready for modification.
  • DI deionized
  • NiO-Ag NFs/GCE As-prepared electrode
  • NiO-Ag NFs/GCE As-prepared electrode
  • Similar procedure was also applied to prepare NiO nanofibers or porous Ag modified GCEs (NiO NFs/GCE and porous Ag/GCE).
  • a JEOL 6335F field-emission scanning electron microscope was used to examine the morphology and the size of the as-prepared samples. More detailed morphology and selected area electron diffraction (SAED) patterns were obtained with a Tecnai T12 transmission electron microscope operated at 120 kV. X D patterns were obtained with an Oxford diffraction XcaliburTM PX Ultra with ONYX detector to study the crystal structure of the NiO-Ag nanofibers. FTIR spectra were obtained on a Nicolet Magna-IR 560 spectrophotometer (Bruker, Germany). The surface property of the sample was analyzed by X-ray photoelectron spectroscopy (XPS) with a PHI multiprobe using Mg as the exciting source.
  • XPS X-ray photoelectron spectroscopy
  • Cyclic voltammetry (CV) measurements were performed on a Model CHI 601C Electrochemical Workstation (CH Instruments, USA). All experiments were conducted using a three-electrode electrochemical cell with a working electrode, an Ag/AgCl reference electrode, and a platinum disc counter electrode. For amperometric detection, all measurements were performed by applying an appropriate potential to the working electrode and allowing the transient background current to decay to a steady-state value, before the addition of the analyte. A stirred solution was employed to provide convective transport.
  • Fig. 7 a, c, e presents the images of three different precursors, AgN0 3 -PVP, Ni(N0 3 )2-PVP and Ni(N0 3 )2-AgN0 3 -PVP nanofibers, respectively.
  • the average diameter of each precursor nanofiber was calculated based on 50 randomly selected nanofibers and listed in Table 1.
  • the nanofibers electrospun from PVP containing two mixed metal salts had a smaller average diameter (ca. 20 nm smaller). This might be resulted from the increase of solution conductivity.
  • NiO cannot maintain the nanofiber structure after calcination of AgN0 3 -PVP nanofibers and some Ag merged together to form a porous network (Fig. 7b).
  • NiO still kept the nanofiber structure with a decrease in the average diameter from 249.4 ⁇ 42.5 nm to 72.6 ⁇ 22.6 nm, which was caused by the weight loss due to the decomposition.
  • the surfaces of NiO nanofibers were no longer as smooth as the Ni(N0 3 )2-PVP nanofibers (Fig. 7d).
  • the nanofiber structure was also maintained (Fig. 7f), but its average diameter was slightly larger than that of NiO nanofibers. This can be explained by the decrease of the percentage of PVP in the precursory electrospun nanofibers due to the introduction of AgN0 3 .
  • TEM was also employed to characterize the nanofibers before and after calcination.
  • numerous black dots with an average diameter of 5.38 ⁇ 1.84 nm (calculated from 50 randomly selected nanoparticles), are well distributed in a single Ni(N0 3 )2-AgN0 3 -PVP nanofiber.
  • These black dots are Ag nanoparticles, which may come from the reduction of partial AgN0 3 dissolved in PVP-ethanol.
  • the in-situ formation of Ag nanoparticles can be demonstrated by UV-Vis absorption spectra. An increase in the peak density located at ca.
  • Fig. 8b and 8c The comparison between TEM images of a NiO nanofiber and a NiO-Ag hybrid nanofiber was presented in Fig. 8b and 8c.
  • NiO nanofiber was composed of larger nanoparticles
  • the NiO-Ag hybrid nanofiber consists of numerous smaller nanoparticles.
  • the elemental heterogeneity of NiO-Ag nanofiber was further examined by EDX mapping.
  • the three insets in Fig. 8c represent EDX mapping of Ag, Ni and O elements, respectively, in the selected area as indicated by the red dash frame.
  • the recorded images of Ni and O mapping indicate a homogeneous distribution of NiO, while Ag shows an irregular distribution.
  • SAED Selected area electron diffraction
  • composition changes between the precursor nanofibers and the calcined products were revealed by EDX analysis (Fig. 8e).
  • the increase in the ratio of Ni and Ag elements indicates the degradation of polymer matrix and decomposition of metal salts.
  • the carbon peak presented in Fig. 8e and Cu peak in Fig. 8e and its inset can be attributed to the copper- carbon grid used for EDX.
  • composition and crystal structure were further characterized by XRD (Fig. 9b).
  • XRD Fig. 9b.
  • XRD spectrum of NiO-Ag nanofibers matches the combination of the standard spectrum of JCPDS 04-0835 (NiO) and JCPDS 04-0783 (Ag).
  • the formation of face-centered cubic crystalline NiO is revealed by the diffraction peaks at 2 ⁇ values of 37.28, 43.30, 62.92, 75.44, 79.39, 95.08° corresponding to (111), (200), (220), (311), (222), and (400) crystal planes, respectively; while the diffraction peaks at 2 ⁇ values of 38.12, 44.28, 64.43, 77.47, 81.54 and 97.89°, which correspond to (111), (200), (220), (311), (222), and (400) crystal planes respectively, indicates the formation of cubic crystalline Ag.
  • XPS measurement was carried out to further confirm the valence state of Ni and Ag element in NiO-Ag hybrid nanofibers.
  • two main peaks presented at binding energies of 853.53 eV and 871.58 eV with a separation of 18.1 eV can be assigned to Ni 2p 3 / 2 and Ni 2p 2 orbit of NiO, respectively.
  • three satellite (sat) peaks, due to final-state effects, are shown at 877.92, 860.12, and 855.68 eV, respectively.
  • Ni 2p photoelectron spectrum of NiO exhibits a very strong satellite structure.
  • the two peaks located at binding energies of 367.58 eV and 373.58 eV with a separation of 6.00 eV correspond to Ag 3ds/2 and Ag 3d 3 /2 orbit of Ag, respectively (Fig. 9d).
  • Fig. 10a, b, c presents the CVs of the three different electrodes in the absence and presence of 8 mM glucose in 0.1 M NaOH solution recorded at a scan rate of 100 mV/s, respectively.
  • a pair of well-defined quasi-reversible redox peaks was observed at the NiO NFs/GCE, with the anodic peak potential at 0.516 V and the cathodic peak at 0.442 V (Fig. 10a, trace a). These two peaks are assigned to Ni 2+ /Ni 3+ redox couple.
  • the oxidation peak (I) at ca. 0.325 V is attributed to the oxidation of Ag° to Ag 1+ while the peak (II) at ca. 0.785 V is assigned to the oxidation of Ag 1+ to Ag 2+ (Fig. 10b).
  • the reductions of Ag 2+ to Ag 1+ and Ag 1+ to Ag° appear at ca. 0.418 V and 0 V, respectively.
  • the oxidation peak (I) positively shifted to 0.362 V and the peak (II) shifted to 0.825 V.
  • the NiO-Ag NFs/GCE exhibits a greatly enhanced background current (Fig. 10c).
  • Well-defined oxidation and reduction peaks for Ag°/Ag 1+ and Ag 1+ /Ag 2+ redox couples are also presented, while the peaks for Ni 2+ /Ni 3+ redox couple can be hardly identified.
  • a shoulder peak at ca. 0.6 V may be assigned to the oxidation of Ni 2+ to Ni 3+ .
  • the reduction peak (III) becomes more obvious compared to that of the porous Ag/GCE (Fig. 10b), which may be due to the overlap of the reduction of Ni to Ni and Ag to Ag .
  • the enhanced current signal may endow the NiO-Ag NFs/GCE with higher sensitivity towards glucose detection than the NiO NFs/GCE or the porous Ag/GCE.
  • redox peak currents increased linearly with the scan rate in the range from 10 to 100 mV/s (Fig. lib), indicating a surface-controlled electrochemical process.
  • Example 10 Amperometric detection of glucose at the NiO-Ag NFs, NiO NFs, and porous Ag modified electrodes
  • the above electrocatalytic behavior study indicates that all of the three modified electrodes may have potential application in the glucose detection.
  • hydrodynamic voltammogram (HDV) behaviors of these three electrodes were investigated by measuring the amperometric responses to 200 ⁇ glucose at different applied potential (-0.2 V to 0.6 V).
  • the selection of the lowest applied potential of -0.2 V was based on the consideration of excluding the reduction of (3 ⁇ 4 while the upper potential was chosen at 0.6 V for less interferences because higher potential is favored by interferences.
  • Fig. 12a presents the HDVs of 200 ⁇ glucose at the three different electrodes.
  • the oxidation current of glucose at the NiO NFs/GCE was almost 0 when the detection potential was lower than 0.35 V.
  • the applied potential is above 0.35 V, the current rapidly increased with the increase of applied potential.
  • porous Ag/GCE exhibited glucose oxidation signal in the potential range from -0.2 to 0.3 V with the maximum response at 0.1
  • NiO-Ag NFs/GCE also showed 5.2-fold higher sensitivity, lower detection limit and wider linear range than the NiO NFs/GCE (Fig. 12c). Both the sensitivity and detection limit obtained at the NiO-Ag nanofibers modified electrode at 0.6 V are among the best reported values for non-enzymatic glucose sensors.
  • the analytical characteristics of different electrodes at different applied potentials were summarized in Table 2. The significant improvements obtained with NiO-Ag NFs may be attributed to the use of abundant nanofibers which can provide numerous electron transfer tunnels, the highly porous structure which can minimize the diffusion resistance of analytes, and the synergetic effect between NiO and Ag.
  • NiO-Ag Porous NiO-Ag
  • AA ascorbic acid
  • UA uric acid
  • the blood glucose level of a normal human body is between 4 and 7 mM, while the concentration of endogenous AA and UA is about 0.125 mM and 0.33 mM in blood samples, respectively.
  • the response of the porous Ag/GCE to 0.125 mM AA and 0.33 mM UA are 17-fold and 55-fold higher than that of 4 mM glucose at 0.1 V.
  • IEP isoelectic point
  • NiO-Ag nanofibers surface could strongly repel the negatively charged UA and AA molecules, thus reducing the electrooxidation of UA and AA on the surface of NiO-Ag nanofibers and resulting in an improved selectivity.
  • This explanation is also valid at the applied potential of +0.6 V, at which the NiO-Ag NFs/GCE and NiO NFs/GCE show excellent selectivity against AA and UA.
  • 0.125 mM AA only induces 1.98% current increase in the 4 mM glucose detection at the NiO NFs/GCE and 4.11% increase at the NiO-Ag NFs/GCE, while 0.33 mM UA only induce 5.01% increase at the NiO NFs/GCE and 6.13% increase at the NiO-Ag NFs/GCE (Fig. 13b).
  • another factor attributing to such superior selectivity at 0.6 V may be stronger enhancement for glucose oxidation than for UA and AA oxidation at the NiO-Ag NFs and NiO NFs.
  • NiO-Ag nanofibers modified electrode Reproducibility of NiO-Ag nanofibers modified electrode was also investigated at 0.6 V.
  • the good inter-electrode reproducibility was characterized by the low R.S.D of 6.64% in the response to 200 ⁇ glucose on five NiO-Ag NFs/GCEs.
  • the as-prepared NiO-Ag nanofibers based non-enzymatic glucose sensor was further applied to the detection of glucose in human blood serum sample at an applied potential of 0.6 V.
  • Fig. 15 demonstrated the amperometric response to successive additions of analytes (standard glucose solution, human serum sample, AA, and UA).
  • the concentration of glucose in serum sample was calibrated using standard glucose solution and compared with the result obtained by commercial GOx-based glucose meter (OneTouch UltraMini, Life Scan, Inc, CA).
  • GOx-based glucose meter OneTouch UltraMini, Life Scan, Inc, CA
  • NiO-Ag hybrid nanofibers (average dia. 82.1 nm), NiO nanofibers (average dia. 72.6 nm), and porous Ag were prepared by calcination of electrospun i( 0 3 )2-Ag 0 3 -PVP nanofibers, i( 0 3 )2-PVP nanofibers, and AgN0 3 -PVP nanofibers, respectively.
  • FTIR was used to confirm the degradation of PVP and the complete decomposition of metal salts.
  • XRD and XPS were performed to investigate the crystalline structure and compositions of the calcined products. SEM and TEM were employed to compare the morphology before and after calcination.
  • NiO-Ag nanofibers, NiO nanofibers, and porous Ag were applied in the non-enzymatic glucose detection and a comparative study was conducted.
  • a synergistic effect was obtained between NiO and Ag, endowing NiO-Ag nanofibers modified electrode with higher sensitivity, lower detection limit and wider linear range compared to NiO nanofibers and porous Ag modified electrodes.
  • the NiO-Ag nanofibers and NiO nanofibers based sensors have an excellent anti- interference property towards the electroactive compounds such as AA and UA.
  • the real sample detection was also conducted with the human blood serum, and the good agreement between the results obtained by our NiO-Ag nanofibers-based non-enzymatic glucose sensor and the commercial GOx-based glucose meter indicated potential practical application of our sensor in glucose detection.

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Abstract

La présente invention concerne des capteurs de glucose non enzymatiques basés sur des nanofibres d'oxyde de métal facultativement dopés pour la détection de glucose dans une solution alcaline (par exemple, pH 13). De tels capteurs peuvent présenter un temps de réponse rapide, une sensibilité élevée, de bonnes reproductibilité et sélectivité, et une bonne limite de détection. Contrairement aux capteurs de glucose non enzymatiques à base de métaux précieux, les capteurs présentement décrits ne sont pas empoisonnés par des concentrations élevées de NaCl, ne sont pas affectés par l'oxygène, et restent actifs sur le plan électrocatalytique dans des solutions alcalines au-dessus de 40 °C.
PCT/US2011/046214 2010-08-03 2011-08-02 Capteurs de glucose non enzymatiques à base de nanomatériaux d'oxyde de métal Ceased WO2012018777A1 (fr)

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