Patent Publication Number: US-2023141805-A1

Title: Coated electrode, electrochemical sensor and method for detection of hydrogen peroxide

Description:
RELATED APPLICATION 
     The present patent document claims the benefit of priority to U.S. Provisional Patent Application No. 63/278,313, which was filed on Nov. 11, 2021, and is hereby incorporated by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     The present disclosure is related generally to electrochemistry, and more particularly to an electrochemical sensor for detection of hydrogen peroxide. 
     BACKGROUND 
     Hydrogen peroxide (H 2 O 2 ) is an important chemical not only for industrial and everyday use as bleaches and disinfectants, but also for regulating various metabolisms in biological systems such as cellular signaling, oxidative stress, aging, and cancer growth. All of these biological functions depend sensitively on the intracellular concentration of H 2 O 2 , which typically ranges from 10 nM to 1 μM. Therefore, sensitive detection of H 2 O 2  in the nano- to micro-molar range is critical for health monitoring and disease diagnosis. While enzyme-based electrochemical sensors have been developed and clinically used for H 2 O 2  detection, their high cost and low thermal and chemical stability limit their large-scale production and diagnostic applications. Therefore, tremendous efforts have been devoted to developing inorganic electrocatalysts for H 2 O 2  detection in the past few years. However, existing enzyme-free electrochemical sensors either require expensive precious metals or have limited sensitivity. Therefore, development of a low-cost and highly sensitive H 2 O 2  electrochemical sensor would be beneficial. 
     BRIEF SUMMARY 
     A coated electrode for in vitro detection of hydrogen peroxide includes a conductive substrate and a coating comprising a topological insulator on the conductive substrate. 
     An electrochemical method for detecting hydrogen peroxide includes providing an electrochemical sensor comprising: a container holding an electrolyte; a coated electrode positioned in the container; and a counter electrode spaced apart from the coated electrode in the container, where the coated electrode includes a conductive substrate and a coating comprising a topological insulator on the conductive substrate. A voltage is applied to the coated electrode and the counter electrode, and a biological specimen is added to the electrolyte to form an analyte solution. Current density is measured. An increase in the current density upon forming the analyte solution indicates presence of hydrogen peroxide in the biological specimen. 
     A method of making a coated electrode for electrochemical detection of hydrogen peroxide includes: depositing a coating solution comprising flakes dispersed in a liquid onto a conductive substrate, the flakes comprising a topological insulator; and drying the conductive substrate to evaporate the liquid, whereby the flakes form a coating on the conductive substrate. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1 A  shows a coated electrode that includes a coating comprising a topological insulator on a conductive substrate. 
         FIG.  1 B  shows a scanning electron microscopy (SEM) image of synthesized Bi 2 Te 3  flakes drop-casted onto a substrate; scale bar is 10 microns. 
         FIG.  1 C  shows atomic force microscopy (AFM) images of different Bi 2 Te 3  flakes in 3D view. 
         FIG.  2    is a schematic of an electrochemical sensor for in vitro detection of hydrogen peroxide. 
         FIG.  3    is a schematic of a solution coating process to form the coated electrode of  FIG.  1 A . 
         FIG.  4 A  shows linear sweep voltammetry (LSV) curves at different H 2 O 2  concentrations (from 0.3 to 34.3 μM), obtained at a scan rate of 5 mV/s. 
         FIG.  4 B  shows current density as a function of H 2 O 2  concentration. The square dots and the line show the raw data and linear fit, respectively 
         FIG.  4 C  shows chronoamperometry (CA) response upon adding different amount of H 2 O 2 , at a potential of 0.022 V vs RHE. 
         FIG.  4 D  shows an expanded view of the step increase in current density when 0.1 μM H 2 O 2  was added to different batches of sensor devices. The addition of H 2 O 2  occurred at time=0 s. 
         FIG.  4 E  shows results of selectivity testing of an exemplary Bi 2 Te 3 -based electrochemical sensor. 
         FIG.  5 A  shows cyclic voltammetry (CV) curves at different scan rates, with a H 2 O 2  concentration of 81 μM. 
         FIG.  5 B  shows cathodic peak current as a function of the square root of scan rate, including the raw data and linear fit. 
         FIG.  5 C  shows linear regression of the cathodic peak position (relative to the half-wave potential) as a function of the natural logarithm of scan rate (with a unit of V/s). 
         FIG.  5 D  shows a Nyquist plot of the EIS measurement of 100 μM H 2 O 2  in 0.1 M K 2 SO 4  solution, at a potential of 0.066 V vs RHE; the obtained values of the equivalent circuit elements are R ct =3.3 kΩ 12 cm 2 , Q=737.7 μF/cm 2  and phase factor n=0.724 in. 
         FIG.  5 E  shows EIS result of 5.0 mM K 3 Fe(CN) 6  and 5.0 mM K 4 Fe(CN) 6  in an aqueous solution containing 0.1 M K 2 SO 4 , at the standard potential of 0.764 V vs RHE; the obtained values of the equivalent circuit elements are R ct =1.2 Ωcm 2 , solution resistance R s =0.83 Ωcm 2 , double layer capacitance C dl =188.7 μF/cm 2  and Warburg coefficient σ=19.1 ΩS −1/2  cm 2 . 
         FIG.  6 A  shows CV at different H 2 O 2  concentrations and a scan rate of 5 mV/s. 
         FIG.  6 B  shows CV at different scan rates, with a H 2 O 2  concentration of 1 μM. 
     
    
    
     DETAILED DESCRIPTION 
     Described in this disclosure is the application of topological materials to electrochemical sensing. Topological materials, including topological insulators and topological semimetals, are systems where strong spin-orbit coupling induces band inversion in the bulk and delocalized, topologically protected states on the surface. The inventors have recognized that attributes of these materials previously exploited for catalysis, such as highly mobile surface states that can facilitate interfacial charge transfer, and topological protection that can minimize current noise induced by parasitic surface modifications, may be beneficial in electrochemical sensing, e.g., by enhancing the signal-to-noise ratio of the sensing current. Given this recognition, a coated electrode for in vitro detection of hydrogen peroxide, an electrochemical sensor, and a method of detecting H 2 O 2  that utilize topological materials have been developed. 
     Referring to  FIG.  1 A , the coated electrode  102  includes a conductive substrate  104  and a coating  106  comprising a topological insulator on the conductive substrate  104 . The topological insulator may exhibit van der Waals bonding. The coating  106  does not include (is devoid of) a precious metal or an enzyme. As indicated above, the topological insulator exhibits band inversion in the bulk due to strong spin-orbit coupling and includes delocalized, topologically protected states on the surface. Topological insulators may be described as having electrically conducting surface states and an electrically insulating bulk (interior). The topological insulator of the coating  106  may comprise a bismuth and/or antimony chalcogenide having a chemical formula of Bi 2 Se 3 , Bi 2 Te 3 , Sb 2 Te 3 , Bi 2-x Sb x Te 3 , or Bi 2-x Sb x Se 3 , where 0≤x≤2. A bismuth chalcogenide, in particular, Bi 2 Te 3 , is employed in experiments described below. 
     Advantageously, the coating  106  on the conductive substrate  104  may be formed from flakes  108  comprising the topological insulator. The flakes  108  may have a desirable crystalline structure as well as a morphology advantageous for sensing. To achieve both high crystalline quality and exposed surfaces, edges, and corners as potential active sites for H 2 O 2  reduction, a liquid-phase exfoliation method (e.g., sonication) may be employed to produce the flakes  108 . As described below, commercially available powders comprising the topological insulator may undergo sonication to form nano- and microscale flakes having lateral dimensions ranging from a few nanometers to a few microns. The flakes  108  may include a homogeneous distribution of the elemental components (e.g., Bi, Te and/or Sb) of the topological insulator and/or a stoichiometric composition of the topological insulator. Electron microscopy and atomic force microscopy investigations reveal that exposed facets of the flakes  108  may have different orientations, crystalline domains, and/or surface roughness. The nanoscale thickness and rich surface structure of the flakes  108  may promote both high conductivity and exposure of various possible active sites, thus facilitating electrochemical sensing. A scanning electron microscope (SEM) image of flakes  108  prepared by drop-casting onto a silicon substrate is shown in  FIG.  1 B  (10 μm scale bar) and atomic force microscopy (AFM) images showing the morphology of different flakes  108  are shown in  FIG.  1 C . 
     An electrochemical sensor for in vitro detection of hydrogen peroxide has been developed based on the coated electrode  102 , as illustrated in  FIG.  2   . The electrochemical sensor  200  includes a container  202  for holding an electrolyte  204  and receiving a biological specimen  206 . The electrochemical sensor  200  also includes the coated electrode  102  positioned in the container  202 , and a counter electrode  208  spaced apart from the coated electrode  102  in the container  202 .  FIG.  3    shows the electrochemical sensor  200  prior to immersion of the coated electrode  102  and the counter electrode  208  into the electrolyte  204  for use in hydrogen peroxide detection. The coated electrode  102  may have any of the characteristics described in this disclosure and may be fabricated as described below. The coated electrode  102  and the counter electrode  208  are configured for electrical connection  210  to a voltage source and an ammeter. An electrochemical method for in vitro detection of hydrogen peroxide utilizing the electrochemical sensor  200  is discussed below. 
     To form the coating  106  comprising the topological insulator, which is essential to the coated electrode  102 , a coating solution  110  including the flakes  108  may be deposited onto the conductive substrate  104 , as illustrated in  FIG.  3   . In addition to the flakes  108  comprising the topological insulator, the coating solution  110  may include a liquid  112 , which is typically water, such as deionized (DI) water. The conductive substrate  104  may be dried to evaporate the liquid  112  while the flakes  108  remain, forming the coating  106 , as illustrated in  FIG.  1 A . In some examples, the coating  106  may directly adhere to the conductive substrate  104 . In other examples, the coating  106  may further include an organic binder to promote adhesion (e.g., of the flakes  108 ) to the conductive substrate  104 . To effect drying or evaporation of the liquid in the coating solution  112 , the conductive substrate  104  may be exposed to a nitrogen atmosphere after the coating solution is deposited. Drying may be carried out for a time duration from 30 minutes to about 12 hours. Thus, a coated electrode  102  for use in hydrogen peroxide detection may be formed. 
     Surface coverage of the flakes  108  may be at least about 8%, at least about 20%, at least about 40%, and/or as high as 100% of the conductive substrate, in terms of area. To optimize exposure of surfaces, edges, and corners as potential active sites for H 2 O 2  reduction, the coating  106  may include no more than three layers of the flakes  108 , and in some cases no more than two layers of the flakes  108 , or no more than a single layer of the flakes  108 . Also or alternatively, a loading level of the topological insulator on the conductive substrate  104  may be at least about 0.005 mg/cm 2 , or at least about 0.01 mg/cm 2 . Typically, the loading level is no greater than about 1 mg/cm 2 , or no greater than about 0.5 mg/cm 2 . 
     Deposition of the coating solution  110  onto the conductive substrate  104 , as illustrated in  FIG.  3   , may entail drop casting, spray coating, spin coating, dip coating, or another solution coating technique. The method may further include forming the coating solution  110  prior to deposition on the conductive substrate  104 . Powders comprising the topological insulator may be added to the liquid  112  to form a mixture, and the mixture may be sonicated to exfoliate the powders, forming the flakes  108 , and dispersing them into the liquid  112 . The powders may be dispersed into the liquid at a weight ratio in a range from about 1:500 to about 1:1500, such as 1:1000. Sonication of the mixture may take place for a time duration from about 2 hours to about 48 hours to form the coating solution  110 . 
     Individually, the flakes  108  formed via sonication or another exfoliation method may have a nanoscale thickness. For example, the thickness may be at least about 1 nm, at least about 10 nm, at least about 30 nm, at least about 50 nm, at least about 100 nm, or at least about 200 nm. Typically, the thickness is no greater than about 700 nm, no greater than about 500 nm, no greater than about 300 nm, or no greater than 100 nm. 
     Individually, the flakes  108  may have a lateral dimension, e.g., length and/or width, that falls within the nanoscale or microscale range. For example, the lateral dimension may be at least about 0.02 micron (20 nm), at least about 0.05 micron (50 nm), at least about 0.1 micron (100 nm), at least about 0.2 micron (200 nm), or at least about 0.5 micron (500 nm). Typically, the lateral dimension is no greater than about 20 microns, no greater than about 10 microns, or no greater than about 5 microns. 
     The conductive substrate  104  may comprise or be formed from an electrically conductive material which is nonreactive in an aqueous solution. The electrically conductive material may be a metal, an alloy, or carbon. A suitable conductive substrate  104  may include carbon paper, graphite, graphite powder, glassy carbon, carbon particles, carbon black, carbon fibers, carbon nanotubes, and/or carbon fullerenes. 
     An electrochemical method for detecting hydrogen peroxide may include the electrochemical sensor  200  shown schematically in  FIG.  2   , once the coated electrode  102  and the counter electrode  208  are immersed in the electrolyte  204 . As described above, the electrochemical sensor  200  includes a container  202  holding an electrolyte  204 , the coated electrode  102  described above positioned in the container  202 , and a counter electrode  208  spaced apart from the coated electrode  102  in the container  202 . A voltage or potential is applied to the coated electrode  102  and the counter electrode  208 , and a biological specimen (e.g., a blood sample)  206  is added to the electrolyte  204  to form an analyte solution  212 . The electrolyte  204  may comprise an aqueous solution, which may in some examples may include a salt species, such as 0.1 M K 2 SO 4 . The method may further include purging the electrolyte  204  with argon gas to remove dissolved oxygen. Also or alternatively, the electrolyte  204  may be stirred and/or the coated electrode  102  may be rotated while the voltage is applied. The voltage applied to the coated and counter electrodes  102 , 208  may be in a range from about −0.5 V to about 0.5 V. 
     Typically, no more than one or two droplets of the biological specimen  206  is/are added to the electrolyte  204 . Current density is measured while the voltage is applied before the biological specimen  206  is added and after the analyte solution  212  is formed. An increase in the current density upon forming the analyte solution  212  indicates the presence of hydrogen peroxide in the biological specimen  206 . More specifically, the increase in current density may occur due to reduction of hydrogen peroxide catalyzed by the topological insulator on the coated electrode  102 , as illustrated in  FIG.  1 A . For an analyte solution including hydrogen peroxide at a concentration of about 0.1 μM or greater, the increase in current density may be at least about 2.5 μA/cm 2 . The increase may occur rapidly, e.g., within about 5 s, or within about 2 s, of adding the biological specimen  206  to the electrolyte  204 . A limit of detection of the electrochemical sensor  200  may be 0.02 μM or less of the hydrogen peroxide. For analyte solutions including hydrogen peroxide at a concentration in a range from 0.016 μM to 65 μM, the sensitivity of the measurement may be in a range from about 2500 μA/mM cm 2  to 4905 μA/mM cm 2 . 
     The electrochemical sensor performance was tested experimentally using a standard three-electrode electrochemical cell. The working electrode in this example included flakes of Bi 2 Te 3  deposited on a glassy carbon electrode, as described below in the Methods section. First, linear sweep voltammetry (LSV) curves were obtained at different H 2 O 2  concentrations from 0.3 μM to more than 30 μM. As shown in  FIG.  4 A , clear reduction peaks are observed in all the curves, with a peak position between 0 V and 0.1 V versus reversible hydrogen electrode (RHE). At a concentration higher than about 20 μM, a second peak emerges around 0.2 V versus RHE, which is likely due to the reduction of oxygen produced by H 2 O 2  decomposition. Of particular interest is the main H 2 O 2  reduction peak at ˜0.05 V. Peak current density versus concentration shows a linear dependence in  FIG.  4 B , revealing a sensitivity of ˜4903 μA mM −1  cm −2  and a linear response throughout the measured range. To quantify the limit of detection (LOD), the chronoamperometry (CA) response of the sensor was measured upon adding small drops of H 2 O 2  solutions at a fixed potential of 0.022 V versus RHE, which is close to the reduction peaks in the measured concentration range. As shown in  FIG.  4 C , the device shows clear step increases of current density when 0.1 μM H 2 O 2  was added, and the step height becomes larger when the amount of added H 2 O 2  increases. Tests on different batches of sensors show similar responses upon the addition of 0.1 μM H 2 O 2  (see  FIG.  4 D ), revealing the reproducibility of these devices. Based on the CA results of different batches of samples, the change of current density was plotted as a function of H 2 O 2  concentration a linear response was obtained down to 0.1 μM. From the signal to noise (S/N) ratio of the step response, it was possible to extract a LOD of 0.016 μM corresponding to S/N=3.  FIG.  4 D  shows that the response time of the sensor is typically within 2 seconds, which is mainly limited by the speed of mixing of the added H 2 O 2  solution droplet with the existing electrolyte, rather than an intrinsic response time of the sensor.  FIG.  4 E  shows results of selectivity tests of the sensor. For each chemical species, 10 μM was added at the marked time, where PA represents potassium ascorbate, PP represents potassium phosphate (a mixture of KH 2 PO 4  and K 2 HPO 4 , with pH=6.8), Glu represents glucose, and NaCl represents sodium chloride. Note the significant spike in current density with the addition of (only) H 2 O 2 . 
     LSV measurements of several different batches of sensor devices show similar performance. All of the Bi 2 Te 3  sensors exhibit a linear response over the full tested range of 0.1-60 μM, and the actual linear range of the devices is likely larger. As summarized in Table 1, the sensitivity and LOD of the sensors are both among the best in all the reported devices. In addition, both the materials and processing conditions of the demonstrated sensors are of low cost. Therefore, the demonstrated Bi 2 Te 3  electrochemical sensors are believed to be promising devices for biosensing and clinical diagnosis applications. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Comparison of the performance of various reported H 2 O 2  sensors with 
               
               
                 the Bi 2 Te 3  electrochemical sensors demonstrated in this work. 
               
            
           
           
               
               
               
            
               
                   
                 Sensitivity 
                 Limit of Detection 
               
               
                 Material 
                 (μA mM −1  cm −2 ) 
                 (LCD) (μM) 
               
               
                   
               
            
           
           
               
               
               
            
               
                 CoO—CoS/NF 
                 0.059 
                 0.89 
               
               
                 NiCo 2 O 4  NSs 
                 303.42 
                 0.596 
               
               
                 Au NPs/Cu-MOF 
                 1710 
                 1.2 
               
               
                 Ag@MOF/GO 
                 80.23 
                 0.18 
               
               
                 IE-MoS 2   
                 1706 
                 0.2 
               
               
                 ZnO/Co 3 O 4 /NiCo 2 O 4   
                 388 
                 0.163 
               
               
                 PtNi/MWCNT 
                 2123.1 
                 0.06 
               
               
                 CoO x  NPs/cholesterol oxidase 
                 43.5 
                 4.2 
               
               
                 Bi 2 Te 3   
                 4903 
                 0.016 
               
               
                   
               
            
           
         
       
     
     Kinetic Analysis 
     Previous studies of electrocatalysis using topological materials have used density functional theory (DFT) to calculate the electronic structure and adsorption energy, and attributed the high catalytic activity to coupling of atomic active sites with the topological surface states which can lead to favorable binding energies of the reactants. While these thermodynamic properties are in general relevant to all types of electrochemical reactions, for sensing applications the reaction kinetics is more critical, which directly impacts the magnitude of electrochemical current—the sensed signal in response to an analyte—at an optimized applied potential. To achieve sensitive detection of trace amounts of chemical species, it is important to have facile interfacial charge transfer, in order to generate a large redox current. However, previous work on H 2 O 2  electrochemical sensors have rarely reported analysis of the charge transfer rate constants. Therefore, a microkinetic analysis of our Bi 2 Te 3 -based electrochemical sensors may be both complementary to previous DFT simulations on the atomistic thermodynamics of the catalytic reactions, and may shed light on the kinetics of the interfacial charge transfer processes. 
     To enable a thorough kinetic analysis, cyclic voltammetry (CV) was performed at different scan rates. As shown in  FIG.  5 A , both cathodic (&lt;0 V) and anodic peaks (&gt;0.4 V) are observed. These CV results reveal that the H 2 O 2  reduction reaction is in the quasi-reversible regime, due to 1) the large anodic and cathodic peak separation and 2) the shift of peak position at different scan rates. To quantify the kinetic parameters of H 2 O 2  reduction, the peak current density and peak potential are extracted as a function of the scan rate (v), as shown in  FIGS.  5 B and  5 C . The linear dependence of the peak current as a function of v 1/2  indicates that the reaction is diffusion limited at sufficiently negative potential. The peak potential changes roughly linearly as a function of ln v, which is also expected for a quasireversible reaction as long as the scan rate is not too small. It is assumed that the reaction proceeds via a two-electron reduction of H 2 O 2 : 
       H 2 O 2 +2H + +2 e   − →2H 2 O
 
     To extract the standard rate constant, the following kinetic equation for the quasi-reversible reactions is used: 
     
       
         
           
             
               Δ 
               ⁢ 
               E 
             
             = 
             
               
                 
                   E 
                   p 
                 
                 - 
                 
                   E 
                   
                     1 
                     / 
                     2 
                   
                 
               
               = 
               
                 
                   - 
                   
                     Ξ 
                     ⁡ 
                     ( 
                     
                       Λ 
                       , 
                       α 
                     
                     ) 
                   
                 
                 ⁢ 
                 
                   ( 
                   
                     RT 
                     F 
                   
                   ) 
                 
               
             
           
         
       
     
     where E p  is the peak potential, E 1/2  is the half-wave potential (middle of the anodic and cathodic peaks), R is the ideal gas constant, T=298 K is the temperature, and F is the Faraday constant. In addition, Λ is determined by 
     
       
         
           
             
               Λ 
               = 
               
                 
                   k 
                   0 
                 
                 
                   
                     ( 
                     
                       
                         D 
                         O 
                         
                           1 
                           - 
                           α 
                         
                       
                       ⁢ 
                       
                         D 
                         R 
                         α 
                       
                       ⁢ 
                       fv 
                     
                     ) 
                   
                   
                     1 
                     / 
                     2 
                   
                 
               
             
             , 
           
         
       
     
     where k 0  is the standard rate constant of the reaction, D O =1.2×10 −9  m 2 /s and D R =2.3×10 −9  m 2 /s are the diffusion coefficients of H 2 O 2  and H 2 O molecules, respectively, and f=F/RT. The transfer coefficient α can be determined from the ratio of the Tafel slope of the measured cathodic (Slope c ) and anodic (Slope a ) waves: 
     
       
         
           
             
               
                 Slope 
                 c 
               
               
                 Slope 
                 a 
               
             
             = 
             
               
                 
                   - 
                   α 
                 
                 
                   1 
                   - 
                   α 
                 
               
               . 
             
           
         
       
     
     α=0.51 is obtained. Ξ is a parameter that has a fixed dependence on Λ and α. Substituting the experimental data and standard parameters into these formulas, one obtains k 0 ≈3×10 −5  cm/s. Note that k 0  is the rate constant at the half-wave potential. At other cathodic potentials (E), the reaction rate constant is k=k 0 e −αf(E−E     1/2     ) . For example, at a scan rate of 5 mV/s, the cathodic peak potential occurs at ΔE=E p −E 1/2 ≈−0.25 V, and the corresponding rate constant is k≈4.3×10 −3  cm/s. 
     The kinetic parameters can also be determined independently from electrochemical impedance spectroscopy (EIS). Assuming that the kinetics follows the Butler-Volmer model, at cathodic potentials 
     
       
         
           
             k 
             = 
             
               RT 
               
                 α 
                 ⁢ 
                 n 
                 ⁢ 
                 
                   F 
                   2 
                 
                 ⁢ 
                 
                   CR 
                   ct 
                 
               
             
           
         
       
     
     is obtained, where R ct  is the charge transfer resistance, n=2 is the charge transfer number, and C is the initial concentration of H 2 O 2 . EIS measurements were performed at C=100 μM and E=0.066 V, and the Nyquist plot shown in  FIG.  5 D  was obtained. Using a RQ (Parallel resistance and constant-phase element) circuit model, the EIS spectrum is fit and R ct =3.3 kΩcm 2  is obtained. Therefore, the rate constant can be obtained as k=7.9×10 −4  cm/s. The standard rate constant is thus k 0 =ke αf(E−E     1/2     ) =3.6×10 −5  cm/s. It can be seen that the k 0  values obtained using these two methods are similar, confirming the validity of the kinetic analysis algorithms. 
     Since the kinetic parameters of H 2 O 2  reduction have rarely been reported in existing literature on electrochemical sensors, a standard redox couple, ferricyanide/ferrocyanide (5 mM each in 0.1 M K 2 SO 4  solution), is used as a medium to compare the charge transfer resistance of the Bi 2 Te 3  catalyst with other reported catalysts for H 2 O 2  sensing. EIS of this redox couple is performed, and the Nyquist plot is extracted, as shown in  FIG.  5 E . Using a Randles equivalent circuit model, an R ct  of 1.2 Ωcm 2  is obtained. This is smaller than other catalyst materials typically used for H 2 O 2  sensing (measured using the same redox couple), such as noble metal nanostructures, 2D materials and heterostructures, and oxide nanomaterials. This result reveals that the Bi 2 Te 3  catalysts have intrinsically facile interfacial charge transfer kinetics, which may be due to wave function delocalization of the topological surface states. 
     To further verify the kinetic parameters and understand the reaction mechanism, microkinetics simulations based on the Butler-Volmer model were performed, as described in the Methods section below. Using the parameters extracted from experimental data, CV curves were simulated at a series of different H 2 O 2  concentration and scan rate parameters, as shown in  FIGS.  6 A and  6 B . Except for double layer capacitance and solution resistance effects that are not included in the simulation, the main features of the simulated CV curves are consistent with the experimental results, including the position, separation and asymmetry of the cathodic and anodic peaks, and the dependence of the peak intensity on H 2 O 2  concentration and scan rate. This agreement reveals that the reactions are indeed quasireversible and can be reasonably explained using the classical kinetics model. While this model does not contain the atomistic details of the interfacial charge transfer processes, it offers a general framework for understanding the electrochemical sensing properties based on the inherently sluggish redox reactions, such as the reduction of oxygen and H 2 O 2 . 
     In conclusion, an ultrasensitive electrochemical sensor for H 2 O 2  detection using nanostructured topological insulators has been demonstrated. Through microkinetic analysis and simulations, it has been found that facile interfacial charge transfer is likely the key factor leading to high sensitivity. Topological materials are therefore expected to be suitable for use in a wide variety of chemical and bio-sensors. 
     Methods 
     Materials Synthesis and Electrode Preparation. Commercial Bi 2 Te 3  powders purchased from Sigma Aldrich were dispersed in DI water with 1:1000 weight ratio. The mixture solution was then ultrasonicated in a Branson sonicator (M2800) for 24 hours, and stored as stock solution. To prepare each working electrode, 10 μL sonicated solution was drop-casted onto a glassy carbon disk electrode (Pine E5TQ) and then dried in N 2  atmosphere overnight. The geometric surface area of the electrode is 0.196 cm 2 , and the surface coverage is estimated to be 7.9% from direct SEM imaging of the glassy carbon electrodes in multiple areas. As a result, an electrochemical surface area of ˜0.0155 cm 2  is estimated. 
     Electron Microscopy Characterization. For SEM, samples were prepared by drop casting Bi 2 Te 3  flakes on Si substrates or glassy carbon electrode inserts, and imaged using Hitachi S4700 and S4800 SEM. EDS mappings were obtained with using an IXRF system integrated to the Hitachi S4700 SEM. For TEM, samples were prepared by drop casting Bi 2 Te 3  flakes on a Cu TEM grid, and then imaged using a JEOL 2100 Cryo TEM with a LaB 6  emitter at 200 kV. 
     Atomic Force Microscopy Characterization. AFM measurements were performed using a Cypher ES AFM (Asylum Research, Oxford Instruments). Tap 300 AI-G probes purchased from Budget Sensors were used for AC mode imaging. Imaging parameters were optimized to ensure that repulsive mode was reached, so that the obtained height profiles of the flakes are accurate. 
     Electrochemical Measurements. LSV, CV, CA and EIS measurements were carried out using a standard three-electrode setup with one glassy carbon working electrode (Pine E5TQ), one Ag/AgCl reference electrode (BASi MF-2052) and one Pt counter electrode (CHI 115). The electrolyte was aqueous solutions of 0.1 M K 2 SO 4 . To eliminate the dissolved oxygen in the solution, the electrolyte was purged using ultrapure argon for at least 5 hours before the electrochemical measurements, and continuously purged argon throughout all the electrochemical tests. LSV and CV were carried out using a CHI 600E potentiostat (CH Instruments). EIS was measured using either a CHI 760 potentiostat from CH Instruments or a VSP potentiostat from BioLogic. The electrolyte used in EIS measurements was either 100 μM H 2 O 2  in 0.1 M K 2 SO 4 , or a mixture of 5.0 mM K 3 Fe(CN) 6  and 5.0 mM K 4 Fe(CN) 6  dissolved in 0.1 M K 2 SO 4  solution. All the electrochemical measurements were carried out with either no electrode rotation, or with a rotation speed of 200 rpm. When the electrode was not rotated, a magnetic stir bar was used with stirring rate of 800 rpm. 
     Kinetic Simulation. The simulation of CV curves follows the finite difference method proposed by Dieter Britz. Mass transfer is determined by Fick&#39;s law and the reaction current is determined by Butler-Volmer equation. The input parameters are the rate constant, charge transfer coefficient, scan rate, and initial concentration of H 2 O 2 , all of which are the same as or close to the experimental values. 
     Although the present invention has been described in considerable detail with reference to certain embodiments thereof, other embodiments are possible without departing from the present invention. The spirit and scope of the appended claims should not be limited, therefore, to the description of the preferred embodiments contained herein. All embodiments that come within the meaning of the claims, either literally or by equivalence, are intended to be embraced therein. 
     Furthermore, the advantages described above are not necessarily the only advantages of the invention, and it is not necessarily expected that all of the described advantages will be achieved with every embodiment of the invention.