Sluggish Electron Transfer of Oxygen-Terminated Moderately Boron-Doped Diamond Electrode Induced by Large Interfacial Capacitance between a Diamond and Silicon Interface.

Boron-doped diamond (BDD) has tremendous potential for use as an electrode material with outstanding characteristics. The substrate material of BDD can affect the electrochemical properties of BDD electrodes due to the different junction structures of BDD and the substrate materials. However, the BDD/substrate interfacial properties have not been clarified. In this study, the electrochemical behavior of BDD electrodes with different boron-doping levels (0.1% and 1.0% B/C ratios) synthesized on Si, W, Nb, and Mo substrates was investigated. Potential band diagrams of the BDD/substrate interface were proposed to explain different junction structures and electrochemical behaviors. Oxygen-terminated BDD with moderate boron-doping levels exhibited sluggish electron transfer induced by the large capacitance generated at the BDD/Si interface. These findings provide a fundamental understanding of diamond electrochemistry and insight into the selection of suitable substrate materials for practical applications of BDD electrodes.

Green Synthesis of Ceria Nanoparticles from Cassava Tubers for Electrochemical Aptasensor Detection of SARS-CoV-2 on a Screen-Printed Carbon Electrode.

Green synthesis approaches for making nanosized ceria using starch from cassava as template molecules to control the particle size are reported. The results of the green synthesis of ceria with an optimum calcination temperature of 800 °C shows a size distribution of each particle of less than 30 nm with an average size of 9.68 nm, while the ratio of Ce3+ to Ce4+ was 25.6%. The green-synthesized nanoceria are applied to increase the sensitivity and attach biomolecules to the electrode surface of the electrochemical aptasensor system for coronavirus disease (COVID-19). The response of the aptasensor to the receptor binding domain of the virus was determined with the potassium ferricyanide redox system. The screen-printed carbon electrode that has been modified with green-synthesized nanoceria shows 1.43 times higher conductivity than the bare electrode, while those modified with commercial ceria increase only 1.18 times. Using an optimized parameter for preparing the aptasensors, the detection and quantification limits were 1.94 and 5.87 ng·mL-1, and the accuracy and precision values were 98.5 and 89.1%. These results show that green-synthesized ceria could be a promising approach for fabricating an electrochemical aptasensor.

Impact of gate electrode on free chlorine sensing performance in solution-gated graphene field-effect transistors.

Free chlorine is widely used to disinfect water used for drinking and food processing. This requires highly sensitive, simple, and capable continuous-measurement sensors to enable the concentration of free chlorine in water to be monitored and controlled. Free chlorine sensors based on solution-gated graphene field-effect transistors (GFETs) are a suitable platform for highly sensitive and continuous measurements. However, their sensing mechanisms require further elucidation to improve their performance. In this study, we focused on the gate electrode and investigated its influence on the sensing performance. Using the free chlorine sensor based on the solution-gate GFET, we showed that the Dirac point voltage in the transfer curve changed significantly as the free chlorine concentration changed, and the electric double-layer capacitance of the gate electrode decreased. Furthermore, we demonstrated that a solution-gated GFET using graphene or boron-doped diamond as the gate electrode could be used to detect changes in the free chlorine concentration in the concentration range of tap water. The sensing performance in the low concentration range benefits from the wide potential window of carbon-based electrodes, which do not have electrochemically active sites. Using these carbon-based materials as gate electrodes, GFETs have the potential to be used as durable sensors that are resistant to surface fouling and oxidation.

Designing Molecularly Imprinted Polymer-Modified Boron-Doped Diamond Electrodes for Highly Selective Electrochemical Drug Sensors.

Drug detection in biological solutions is essential in studying the pharmacokinetics of the body. Electrochemical detection is an accurate and rapid method, but measuring multiple drugs that react at similar potentials is challenging. Herein, we developed an electrochemical sensor using a boron-doped diamond (BDD) electrode modified with a molecularly imprinted polymer (MIP) to provide specificity in drug sensing. The MIP is a polymer material designed to recognize and capture template molecules, enabling the selective detection of target molecules. In this study, we selected the anticancer drug doxorubicin (DOX) as the template molecule. In the electrochemical measurements using an unmodified BDD, the DOX reduction was observed at approximately -0.5 V (vs Ag/AgCl). Other drugs, i.e., mitomycin C or clonazepam (CZP), also underwent a reduction reaction at a similar potential to that of DOX, when using the unmodified BDD, which rendered the accurate quantification of DOX in a mixture challenging. Similar measurements conducted in PBS using the MIP-BDD only resulted in a DOX reduction current, with no reduction reaction observed in the presence of mitomycin C and CZP. These results suggest that the MIP, whose template molecule is DOX, inhibits the reduction of other drugs on the electrode surface. Selective DOX measurement using the MIP-BDD was also possible in human plasma, and the respective limits of detection of DOX in PBS and human plasma were 32.10 and 16.61 nM. The MIP-BDD was durable for use in six repeated measurements, and MIP-BDD may be applicable as an electrochemical sensor for application in therapeutic drug monitoring.

Hydroxyapatite-Gold Modified Screen-Printed Carbon Electrode for Selective SARS-CoV-2 Antibody Immunosensor.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or coronavirus disease 2019 (COVID-19), is still spreading worldwide; therefore, the need for rapid and accurate detection methods remains relevant to maintain the spread of this infectious disease. Electrochemical immunosensors are an alternative method for the rapid detection of the SARS-CoV-2 virus. Herein, we report the development of a screen-printed carbon electrode immunosensor using a hydroxyapatite-gold nanocomposite (SPCE/HA-Au) directly spray-coated with the immobilization receptor binding domain (RBD) Spike to increase the conductivity and surface electrode area. The HA-Au composite synthesis was optimized using the Box-Behnken method, and the resulting composite was characterized by UV-vis spectrophotometry, TEM-EDX, and XRD analysis. The specific interaction of RBD Spike with immunoglobulin G (IgG) antibodies was evaluated by differential pulse voltammetry and electrochemical impedance spectroscopy methods in a [Fe(CN)6]4-/3- solution redox system. The IgG was detected with a detection limit of 0.0561 pg mL-1, and the immunosensor had selectivity and stability of 103-122% and was stable until week 7 with the influence of storage conditions. Also, the immunosensor was tested using real samples from human serum, where the results were confirmed using the chemiluminescent microparticle immunoassay (CMIA) method and showed satisfactory results. Therefore, the developed electrochemical immunosensor can rapidly and accurately detect SARS-CoV-2 antibodies.

Real-Time Measurement of Antiglaucoma Drugs in Porcine Eyes Using Boron-Doped Diamond Microelectrodes.

The primary treatment for glaucoma, the most common cause of intermediate vision impairment, involves administering ocular hypotensive drugs in the form of topical eye drops. Observing real-time changes in the drugs that pass through the cornea and reach the anterior chamber of the eye is crucial for improving and developing safe, reliable, and effective medical treatments. Traditional methods for measuring temporal changes in drug concentrations in the aqueous humor employ separation analyzers such as LC-MS/MS. However, this technique requires multiple measurements on the eyes of various test subjects to track changes over time with a high temporal resolution. To address this issue, we have developed a measurement method that employs boron-doped diamond (BDD) microelectrodes to monitor real-time drug concentrations in the anterior chamber of the eye. First, we confirmed the electrochemical reactivity of 13 antiglaucoma drugs in a phosphate buffer solution with a pH of 7.4. Next, we optimized the method for continuous measurement of timolol maleate (TIM), a sympathetic beta-receptor antagonist, and generated calibration curves for each BDD microelectrode using aqueous humor collected from enucleated porcine eyes. We successfully demonstrated the continuous ex vivo monitoring of TIM concentrations in the anterior chambers of these enucleated porcine eyes. The results indicate that changes in intracameral TIM concentrations can be monitored through electrochemical measurements using BDD microelectrodes. This technique holds promise for future advancements in optimizing glaucoma treatment and drug administration strategies.

Anode Reaction Control for a Single-Compartment Electrochemical CO2 Reduction Reactor with a Surface-Activated Diamond Cathode.

The electrochemical reaction of carbon dioxide (CO2 ) in aqueous electrolyte solutions is attracting increasing attention for sustainable chemical production. Boron-doped diamond (BDD) electrodes have been previously shown to be very effective for the stable electrochemical production of formic acid from CO2 . Typically, the electrochemical production of formic acid by CO2 reduction (CO2 R) reaction is performed with a dual-compartment flow reactor equipped with a membrane separator. The problems caused by the membrane separator, such as scaling-up, complicated operational control and materials costs can be solved using a membrane free single-compartment reactor. Here we demonstrate anode reaction control for a single-compartment CO2 R flow reactor using a surface-activated BDD cathode and achieve a Faradaic efficiency for formic acid production of over 70 %.

Electrochemical Diagnosis of Urinary Tract Infection Using Boron-Doped Diamond Electrodes.

Efficient detection of sodium nitrite in human urine could be used to diagnose urinary tract infections rapidly. Here, we demonstrate a fast and novel method for the selective detection of sodium nitrite in different human urine samples using electrolysis with a bare boron-doped diamond electrode. The measurement is performed without adding any other species, such as enzymes, and uses a simple electrochemical approach with an oxidation step followed by reduction. In the present study, we pay attention to the reduction potential range for the measurement, which is substantially different from many previous literature reports that focus on the oxidation reaction. The determination of added sodium nitrite based on cyclic voltammetry or differential pulse voltammetry is employed for two pooled urine samples and three individual urine matrices. From this, the linear response ranges for sodium nitrite detection are 0.5-10 mg/L (7.2-140 µmol/L) and 10-400 mg/L (140-5800 µmol/L). The results from these urine samples convert well to the calibration curve, with a limit of detection established as 0.82 mg/L (R2 = 0.9914), which is clinically relevant.

Urine protein quantification in human urine on boron-doped diamond electrodes based on the electrochemical reaction of Coomassie brilliant blue.

Urinalysis is attracting interest in personal healthcare management as part of a general move to improve quality of life. Urine contains various metabolites and the protein level in urine is an indicator of kidney function. In this study, a novel electrochemical sensing system based on boron-doped diamond (BDD) electrodes was developed for the detection of protein concentrations in human urine. BDD electrodes have the advantages of a wide electrochemical potential window and low non-specific adsorption, making them ideal for simple, rapid, and compact devices for home detection of bio-relevant substances. Coomassie brilliant blue (CBB), a dye that selectively and strongly binds to urine proteins, was found to be a redox-active indicator to show a decrease in its redox currents in relation to the concentration of protein in urine samples. Our detailed studies of BDD electrodes showed their limit of detection to be 2.57 µg mL-1 and that they have a linear response that ranges from 0 to 400 µg mL-1 in urine samples. We also investigated the detection of urine protein in different urine samples. Our results agreed with those obtained using conventional colorimetric analysis. We believe this to be the first study of electrochemical detection of urine protein in urine samples on BDD electrodes, which is of great significance to be able to obtain results with electrical signals rapidly compared to conventional colorimetric analysis. This CBB-BDD technique has the potential to assist healthcare management in the form of a rapid daily diagnostic test to judge whether a more detailed examination is needed.

Electrochemical reduction of carbon dioxide to acetic acid on a Cu-Au modified boron-doped diamond electrode with a flow-cell system.

Boron-doped diamond (BDD) was modified with copper and gold particles by using an electrodeposition technique to improve its catalytic effect on CO2 reduction in a flow system. The system was optimized based on the production of formic acid by the electroreduction process. At the optimum applied potential of -1.0 V (vs. Ag/AgCl) and flow rate of 50 mL min-1, the copper-gold-modified BDD produced formic acid at the highest rate of 4.88 mol m-2 s-1 and a concentration of 15.93 ppm, while acetic acid was produced with a rate of 0.11 mol m-2 s-1 and a concentration of 0.47 ppm. An advantage of the flow system using the modified BDD was that it was found to accelerate the production rate of acetic acid as well as to decrease the reduction potential of CO2. Furthermore, better stability of the metal particles was observed when using mixed copper-gold modification on the BDD surface than single modification by either metal. The results indicated that a flow system is suitable to be employed for electroreduction of CO2 using the bimetal-modified BDD electrodes, especially with copper and gold as the modifying particles.

Electrochemical investigation of hydroxyapatite-lanthanum strontium cobalt ferrite composites (HA-LSCF) for SARS-CoV-2 aptasensors.

The hydroxyapatite-lanthanum strontium cobalt ferrite (HA-LSCF) composite showed a good response on a screen-printed carbon electrode (SPCE) electrochemical aptasensor to detect SARS-CoV-2. SPCE/HA-LSCF with a thiolated aptamer has a strong affinity for the SARS-CoV-2 spike RBD protein. This occurs due to the binding of -SH to the HA-positive region. In the presence of LSCF, which is conductive, an increase in electron transfer from the redox system [Fe(CN)6]3-/4- occurs. The interaction of the aptamer with the RBD protein can be observed based on the decrease in the electron transfer process. As a result, the developed biosensor is highly sensitive to the SARS-CoV-2 spike RBD protein with a linear range of 0.125 to 2.0 ng mL-1, a detection limit of 0.012 ng mL-1, and a quantification limit of 0.040 ng mL-1. The analytical application of the aptasensor demonstrates its feasibility in the analysis of saliva or swab samples.

A strategy for low-cost portable monitoring of plasma drug concentrations using a sustainable boron-doped-diamond chip.

On-site monitoring of plasma drug concentrations is required for effective therapies. Recently developed handy biosensors are not yet popular owing to insufficient evaluation of accuracy on clinical samples and the necessity of complicated costly fabrication processes. Here, we approached these bottlenecks via a strategy involving engineeringly unmodified boron-doped diamond (BDD), a sustainable electrochemical material. A sensing system based on a ∼1 cm2 BDD chip, when analysing rat plasma spiked with a molecular-targeting anticancer drug, pazopanib, detected clinically relevant concentrations. The response was stable in 60 sequential measurements on the same chip. In a clinical study, data obtained with a BDD chip were consistent with liquid chromatography-mass spectrometry results. Finally, the portable system with a palm-sized sensor containing the chip analysed ∼40 µL of whole blood from dosed rats within ∼10 min. This approach with the 'reusable' sensor may improve point-of-monitoring systems and personalised medicine while reducing medical costs.

Electrogenerated chemiluminescence at boron-doped diamond electrodes.

Electrogenerated chemiluminescence (ECL) refers to the phenomenon of light emission from molecular species which is triggered by an electrochemical reaction. Therefore, like most electrochemical systems, the electrode material plays a pivotal role and much effort has been made in order to find the best material for ECL, in terms of light signal intensity and long-term stability, especially after the development of ECL for analytical applications. In this article, we will introduce and highlight the distinctive features of boron-doped diamond (BDD) as an electrode material for ECL which has complementary properties compared to the most common metals (e.g., Au or Pt) and carbon materials (e.g., glassy carbon, carbon nanotubes and graphene). Boron-doped diamond electrodes emerged as novel electrodes, gaining more and more interest from the electrochemical community for their peculiar characteristics such as a wide solvent window, low capacitance, resistance to fouling and mechanical robustness. Furthermore, compared to metal electrodes, BDD does not form an oxide layer in aqueous solutions, and the sp3 carbon hybridization gives BDD the ability to enable peculiar electrochemical reactions that are not possible on sp2 carbon materials. Electrogenerated chemiluminescence investigations with boron-doped diamond electrodes have been reported for common ECL systems (luminophores and co-reactants), and special ECL that is only possible on BDD which includes the in situ electrochemical generation of the co-reactant.

Spin Manipulation in a Metal-Organic Layer through Mechanical Exfoliation for Highly Selective CO2 Photoreduction.

Spin manipulation of transition-metal catalysts has great potential in mimicking enzyme electronic structures to improve activity and/or selectivity. However, it remains a great challenge to manipulate room-temperature spin state of catalytic centers. Herein, we report a mechanical exfoliation strategy to in situ induce partial spin crossover from high-spin (s=5/2) to low-spin (s=1/2) of the ferric center. Due to spin transition of catalytic center, mixed-spin catalyst exhibits a high CO yield of 19.7 mmol g-1 with selectivity of 91.6 %, much superior to that of high-spin bulk counterpart (50 % selectivity). Density functional theory calculations reveal that low-spin 3d-orbital electronic configuration performs a key function in promoting CO2 adsorption and reducing activation barrier. Hence, the spin manipulation highlights a new insight into designing highly efficient biomimetic catalysts via optimizing spin state.

Low-interference norepinephrine signal on dopamine detection using nafion-coated boron doped diamond electrodes.

The detection of dopamine in the presence of norepinephrine using nafion-coated boron doped diamond (Nafion-BDD) electrodes was presented. An increase current signal for dopamine could be observed at around 0.75 V using Nafion-BDD, while a change in the current signal of norepinephrine that appears at similar potential was not observed. This might be due to electronegativity of the norepinephrine that is not positive enough to be attracted towards the nafion membrane, albeit neutral enough to pass through the membrane and undergo electrochemical oxidation. An optimization process including accumulation time of dopamine inside the nafion layer, solution of the pH, and nafion thickness was conducted to exploit the difference electrochemical behavior between those two catecholamines at the Nafion-BDD. Using an accumulation time of 300 s, solution pH of 7, and nafion thickness of 1.1 µm, dopamine's LOD was found to be 0.966 µM. Low-interference signal of norepinephrine to the dopamine could be observed with an excellent %recovery of dopamine in 5% range when the concentration of norepinephrine was 10 times lower compared to dopamine concentration.

Boron-Doped Diamond Electrodes: Fundamentals for Electrochemical Applications.

Boron-doped diamond (BDD) electrodes have emerged as next-generation electrode materials for various applications in electrochemistry such as electrochemical sensors, electrochemical organic synthesis, CO2 reduction, ozone water generation, electrochemiluminescence, etc. An optimal BDD electrode design is necessary to realize these applications. The electrochemical properties of BDD electrodes are determined by important parameters such as (1) surface termination, (2) surface orientation, and (3) boron doping level.In this Account, we discuss how these parameters contribute to the function of BDD electrodes. First, control of the surface termination (hydrogen/oxygen) is described. The electrochemical conditions such as the solution pH and the application potential were studied precisely. It was confirmed that an acidic solution and the application of negative potential accelerate hydrogenation, and the mechanism behind this is discussed. For oxygenation, we directly observed changes in surface functional groups by in situ attenuated total reflection infrared spectroscopy and electrochemical X-ray photoelectron spectroscopy measurements.Next, the difference in surface orientation was examined. We prepared homoepitaxial single-crystal diamond electrodes comprising (100) and (111) facets with similar boron concentrations and resistivities and evaluated their electrochemical properties. Experimental results and theoretical calculations revealed that (100)-oriented single-crystal BDD has a wider space charge layer than (111)-oriented BDD, resulting in a slower response. Furthermore, isolated single-crystal microparticles of BDD with exposed (100) and (111) crystal facets were grown, and we studied the electrochemical properties of the respective facets by combination with hopping-mode scanning electrochemical cell microscopy.We also systematically investigated how the boron concentration and sp2 species affect the electrochemical properties. The results showed that the appropriate composition (boron and sp2 species level) is dependent on the application. The transmission electron microscopy images and electron energy loss spectra of highly boron-doped BDD are shown, and the relationship between the composition and electrochemical properties is discussed. Finally, we investigated in detail the effect of the sp2 component on low-doped BDD. Surprisingly, although the sp2 component is usually expected to induce a narrowing of the potential window and an increase in the charging current, low-doped BDD showed the opposite trend depending on the degree of sp2 carbon.The results and discussion presented in this Account will hopefully promote a better understanding of the fundamentals of BDD electrodes and be useful for the optimal development of electrodes for future applications.

Boron-Doped Diamond as a Quasi-Reference Electrode.

As a working electrode, boron-doped diamond (BDD) has been studied in detail in electrochemical processes because of its superior electrochemical properties. However, these characteristics have rarely been mentioned when BDD is used as a quasi-reference electrode (QRE). Herein, we conducted a systematic investigation on BDD electrodes, with different boron-doping levels (1 and 0.1%) and different surface terminations (hydrogen and oxygen) for their application as a QRE. A BDD electrode with 1% boron and a hydrogen-terminated surface achieved the best stability. Its open-circuit potential (OCP) exhibited less than 100 mV of potential drift over 6000 s and showed a minuscule half-wave potential difference (E1/2) of 0.0037 V in 0.1 mM K3[Fe(CN)6]/1 M KCl solution before and after the OCP measurement. Based on these observations, anions are found to contribute to the potential, which we preliminarily speculate as related to the capacitance caused by electrostatic adsorption on the positively charged hydrogen-terminated surface. The repeatability of measurement was verified through continuous cyclic voltammetry tests in 0.1 mM K3[Fe(CN)6]/1 M KCl, showing a maximum E1/2 difference of 0.042 V. The contribution of the redox couples was excluded, and the repeatability was considered to originate from its surface stability. Finally, a linear response of the optimized BDD as a QRE was validated (R2 > 0.99) by determination of free chlorine and dopamine concentrations, respectively. These results consolidate the existing fundamental research on BDD electrodes and promote the possibility of its application as a QRE in harsh environments or in vivo biological monitoring.

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes.

A straightforward electro-conversion of cumene into acetophenone has been reported using boron-doped diamond (BDD) electrodes. This particular conversion is driven by the addition reaction of a cathodically generated hydroperoxide anion to an anodically generated cumyl cation, where the BDD's wide potential window enables the direct anodic oxidation of cumene into the cumyl cation. Since electricity is directly employed as the oxidizing and reducing reagents, the present protocol is easy to use, suitable for scale-up, and inherently safe.

A rapid and simple electrochemical detection of the free drug concentration in human serum using boron-doped diamond electrodes.

Monitoring drug concentration in blood and reflecting this in the dosage are crucial for safe and effective drug treatment. Most drug assays are based on total concentrations of bound and unbound proteins in the serum, although only the unbound concentration causes beneficial and adverse events. Monitoring the unbound concentration alone is expected to provide a means for further optimisation of drug treatment. However, unbound concentration monitoring has not been routinely used for drug treatment due to the long analysis time and the high cost of conventional methods. Here, we have developed a rapid electrochemical method to determine the unbound concentration in ultrafiltered human serum using boron-doped diamond (BDD) electrodes. When the anticancer drug doxorubicin was used as the test drug, the catalytic doxorubicin-mediated reduction of dissolved oxygen provided a sensitive electrochemical signal, with a detection limit of 0.14 nM. In contrast, the sensitivity of glassy carbon (GC) was inferior under the same conditions due to interference from the dissolved oxygen reduction current. The signal background ratio (S/B) of BDD and GC was 11.5 (10 nM doxorubicin) and 1.1 (50 nM), respectively. The results show that a fast measurement time within ten seconds is possible in the clinical concentration range. Additionally, in the ultrafiltered human serum, the obtained values of unbound doxorubicin concentration showed good agreement with those quantified by conventional liquid chromatography-mass spectrometry. This approach has the potential for application in clinical settings where rapid and simple analysis methods would be beneficial.

Electrochemical detection of triamterene in human urine using boron-doped diamond electrodes.

Urine is one of the most used biological fluids for screening drug delivery and the resultant metabolites. In sports, the use of diuretics such as triamterene is considered a violation of anti-doping rules and is stipulated to be present at less than 79 nM in urine by the World Anti-Doping Agency (WADA). It is therefore important to develop effective rapid and low-cost tests for this diuretic. Here we apply electrochemical analysis using boron-doped diamond (BDD) electrodes, which have superior properties such as low background current, a wide potential window, and high resistance to deactivation. Since real urine samples show clear oxidation current peaks in the potential range more positive than 0.5 V (vs. Ag/AgCl) due to the presence of bio-components such as protein, uric acid, and ascorbic acid, to detect triamterene effectively, the electrochemical protocol was optimized towards a potential range where the other components have limited effect. Our results show that reduced triamterene exhibits an oxidation peak at 0.1 V (vs. Ag/AgCl) in 0.1 M phosphate buffer (PB) and at 0.2 V (vs. Ag/AgCl) in pooled human urine. The peak current value increased according to the triamterene concentration. The limit of detection (LOD) was 3.15 nM in the PB and 7.80 nM in pooled human urine. Finally, triamterene detection was attempted in individual urine samples. Triamterene was electrochemically detectable in individual urine samples, excluding urine samples containing an excess amount of ascorbic acid. The limit of detection (LOD) in individual urine samples was determined to be 20.8 nM.