Kaiyu Fu

Electrochemistry at single molecule occupancy in nanopore-confined recessed ring-disk electrode arrays

Electrochemical reactions at nanoscale structures possess unique characteristics, e.g. fast mass transport, high signal-to-noise ratio at low concentration, and insignificant ohmic losses even at low electrolyte concentrations. These properties motivate the fabrication of high density, laterally ordered arrays of nanopores, embedding vertically stacked metal-insulator-metal electrode structures and exhibiting precisely controlled pore size and interpore spacing for use in redox cycling. These nanoscale recessed ring-disk electrode (RRDE) arrays exhibit current amplification factors, AFRC, as large as 55-fold with Ru(NH3)62/3+, indicative of capture efficiencies at the top and bottom electrodes, Φt,b, exceeding 99%. Finite element simulations performed to investigate the concentration distribution of redox species and to assess operating characteristics are in excellent agreement with experiment. AFRC increases as the pore diameter, at constant pore spacing, increases in the range 200-500 nm and as the pore spacing, at constant pore diameter, decreases in the range 1000-460 nm. Optimized nanoscale RRDE arrays exhibit a linear current response with concentration ranging from 0.1 μM to 10 mM and a small capacitive current with scan rate up to 100 V s-1. At the lowest concentrations, the average pore occupancy is 〈n〉 ∼ 0.13 molecule establishing productive electrochemical signals at occupancies at and below the single molecule level in these nanoscale RRDE arrays.

Nanochannel Arrays for Molecular Sieving and Electrochemical Analysis by Nanosphere Lithography Templated Graphoepitaxy of Block Copolymers

The ability to design, fabricate, and manipulate materials at the nanoscale is fundamental to the quest to develop technologies to assemble nanometer-scale pieces into larger-scale components and materials, thereby transferring unique nanometer-scale properties to macroscopic objects. In this work, we describe a new approach to the fabrication of highly ordered, ultrahigh density nanochannel arrays that employs nanosphere lithography to template the graphoepitaxy of polystyrene-polydimethylsiloxane, diblock copolymers. By optimizing the well-controlled solvent vapor annealing, overcoating conditions, and the subsequent reactive ion etching processes, silica nanochannel (SNC) arrays with areal densities, ρA, approaching 1000 elements μm-2, are obtained over macroscopic scales. The integrity and functionality of the SNC arrays was tested by using them as permselective ion barriers to nanopore-confined disk electrodes. The nanochannels allow cations to pass to the disk electrode but reject anions, as demonstrated by cyclic voltammetry. This ion gating behavior can be reversed from cation-permselective to anion-permselective by chemically inverting the surface charge from negative to positive. Furthermore, the conformal SNC array structures obtained could easily be lifted, detached, and transferred to another substrate, preserving the hierarchical organization while transferring the nanostructure-derived properties to a different substrate. These results demonstrate how nanoscale behavior can be replicated over macroscale distances, using electrochemical analysis as a model.

Closed bipolar electrode-enabled dual-cell electrochromic detectors for chemical sensing

Bipolar electrodes (BPE) are electrically floating metallic elements placed in electrified fluids that enable the coupling of anodic and cathodic redox reactions at the opposite ends by electron transfer through the electrode. One particularly compelling application allows electron transfer reactions at one end of a closed BPE to be read out optically by inducing a redox-initiated change in the optical response function of a reporter system at the other end. Here, a BPE-enabled method for electrochemical sensing based on the electrochromic response of a methyl viologen (MV) reporter is developed, characterized, and rendered in a field-deployable format. BPE-enabled devices based on two thin-layer-cells of ITO and Pt were fabricated to couple an analytical reaction in one cell with an MV reporter reaction, producing a color change in the complementary cell. Using Fe(CN)63/4- as a model analyte, the electrochemically induced color change of MV was determined initially by measuring its absorbance via a CCD camera coupled to a microscope. Then, smartphone-based detection and RGB analysis were employed to further simplify the sensing scheme. Both methods produced a linear relationship between the analyte concentration, the quantity of MV generated, and the colorimetric response, yielding a limit of detection of 1.0 μM. Similar responses were observed in the detection of dopamine and acetaminophen. Further evolution of the device replaced the potentiostat with batteries to control potential, demonstrating the simplicity and portability of the device. Finally, the physical separation of the reporter and analytical cells renders the device competent to detect analytes in different (e.g. non-aqueous) phases, as demonstrated by using the electrochromic behavior of aqueous MV to detect ferrocene in acetonitrile in the analytical cell.

Electrochromic Sensor for Multiplex Detection of Metabolites Enabled by Closed Bipolar Electrode Coupling

Biosensors based on converting electrochemical signals into optical readouts are attractive candidates as low-cost, high-throughput sensor platforms. Here, we described a closed bipolar electrode (CBE)-based two-cell electrochromic device for sensing multiple metabolites, using the simultaneous detection of lactate, glucose, and uric acid as a model system. In the two-cell configuration, an analytical cell contains a redox mediator combined with a specific oxidase, e.g., lactate oxidase, glucose oxidase, or uricase, to form an electrochemical mediator-electrocatalyst pair that supports redox cycling. A closed bipolar electrode couples the electron transfer event in the analytical cell to an electrochromic reaction in a separate reporter cell, such that the magnitude of the color change is related to the concentration of metabolites in the analytical cell. To demonstrate multiplex operation, the CBE-based electrochromic detector is modified by integrating three sets of detection chemistries into a single device, in which simultaneous determination of glucose, lactate, and uric acid is demonstrated. Device sensitivity can be tuned by using reporter cells with different volumes. Furthermore, the analytical cell of this device can be fabricated as a disposable, paper-based carbon electrode without any pretreatment, demonstrating the potential to screen phenotypes that require multiple biomarkers in a point-of-care format.

Voltage‐Gated Nanoparticle Transport and Collisions in Attoliter‐Volume Nanopore Electrode Arrays

Single nanoparticle analysis can reveal how particle-to-particle heterogeneity affects ensemble properties derived from traditional bulk measurements. High-bandwidth, low noise electrochemical measurements are needed to examine the fast heterogeneous electron-transfer behavior of single nanoparticles with sufficient fidelity to resolve the behavior of individual nanoparticles. Herein, nanopore electrode arrays (NEAs) are fabricated in which each pore supports two vertically spaced, individually addressable electrodes. The top ring electrode serves as a particle gate to control the transport of silver nanoparticles (AgNPs) within individual attoliter volume NEAs nanopores, as shown by redox collisions of AgNPs collisions at the bottom disk electrode. The AgNP-nanoporeis system has wide-ranging technological applications as well as fundamental interest, since the transport of AgNPs within the NEA mimics the transport of ions through cell membranes via voltage-gated ion channels. A voltage threshold is observed above which AgNPs are able to access the bottom electrode of the NEAs, i.e., a minimum potential at the gate electrode is required to switch between few and many observed collision events on the collector electrode. It is further shown that this threshold voltage is strongly dependent on the applied voltage at both electrodes as well as the size of AgNPs, as shown both experimentally and through finite-element modeling. Overall, this study provides a precise method of monitoring nanoparticle transport and in situ redox reactions within nanoconfined spaces at the single particle level.

Nanopore Electrochemistry: A Nexus for Molecular Control of Electron Transfer Reactions

Pore-based structures occur widely in living organisms. Ion channels embedded in cell membranes, for example, provide pathways, where electron and proton transfer are coupled to the exchange of vital molecules. Learning from mother nature, a recent surge in activity has focused on artificial nanopore architectures to effect electrochemical transformations not accessible in larger structures. Here, we highlight these exciting advances. Starting with a brief overview of nanopore electrodes, including the early history and development of nanopore sensing based on nanopore-confined electrochemistry, we address the core concepts and special characteristics of nanopores in electron transfer. We describe nanopore-based electrochemical sensing and processing, discuss performance limits and challenges, and conclude with an outlook for next-generation nanopore electrode sensing platforms and the opportunities they present.

Microscale and Nanoscale Electrophotonic Diagnostic Devices

Detecting and identifying infectious agents and potential pathogens in complex environments and characterizing their mode of action is a critical need. Traditional diagnostics have targeted a single characteristic (e.g., spectral response, surface receptor, mass, intrinsic conductivity, etc.). However, advances in detection technologies have identified emerging approaches in which multiple modes of action are combined to obtain enhanced performance characteristics. Particularly appealing in this regard, electrophotonic devices capable of coupling light to electron translocation have experienced rapid recent growth and offer significant advantages for diagnostics. In this review, we explore three specific promising approaches that combine electronics and photonics: (1) assays based on closed bipolar electrochemistry coupling electron transfer to color or fluorescence, (2) sensors based on localized surface plasmon resonances, and (3) emerging nanophotonics approaches, such as those based on zero-mode waveguides and metamaterials.

Whole-Cell Pseudomonas aeruginosa Localized Surface Plasmon Resonance Aptasensor

The detection of whole-cell Pseudomonas aeruginosa presents an intriguing challenge with direct applications in health care and the prevention of nosocomial infection. To address this problem, a localized surface plasmon resonance (LSPR) based sensing platform was developed to detect whole-cell Pseudomonas aeruginosa strain PAO1 using a surface-confined aptamer as an affinity reagent. Nanosphere lithography (NSL) was used to fabricate a sensor surface containing a hexagonal array of Au nanotriangles. The sensor surface was subsequently modified with biotinylated polyethylene glycol (Bt-PEG) thiol/PEG thiol (1:3), neutravidin, and biotinylated aptamer in a sandwich format. The 1:3 (v/v) ratio of Bt-PEG thiol/PEG thiol was specifically chosen to maximize PAO1 binding while minimizing nonspecific adsorption and steric hindrance. In contrast to prior whole-cell LSPR work, the LSPR wavelength shift was shown to be linearly related to bacterial concentration over the range of 10-103 cfu mL-1. This LSPR sensing platform is rapid (∼3 h for detection), sensitive (down to the level of a single bacterium), selective for detection of Pseudomonas strain PAO1 over other strains, and exhibits a clinically relevant dynamic range and excellent shelf life (≥2 months) when stored at ambient conditions. This versatile LSPR sensing platform should be extendable to a wide range of supermolecular analytes, including both bacteria and viruses, by switching affinity reagents, and it has potential to be used in point-of-care and field-based applications.

Asymmetric Nafion-Coated Nanopore Electrode Arrays as Redox-Cycling-Based Electrochemical Diodes

Inspired by the functioning of cellular ion channels, pore-based structures with nanoscale openings have been fabricated and integrated into ionic circuits, for example, ionic diodes and transistors, for signal processing and detection. In these systems, the nonlinear current responses arise either because asymmetric nanopore geometries break the symmetry of the ion distribution, creating unequal surface charge across the nanopore, or by coupling unidirectional electron transfer within a nanopore electrode. Here we develop a high-performance redox-cycling-based electrochemical diode by coating an asymmetric ion-exchange membrane, that is, Nafion, on the top surface of a nanopore electrode array (Nafion@NEA), in which each pore in the array exhibits one or more annular electrodes. Nafion@NEAs exhibit highly sensitive and charge-selective electroanalytical measurements due to efficient redox-cycling reaction, the permselectivity of Nafion, and the strong confinement of redox species in the nanopore array. In addition, the top electrode of dual-electrode Nafion@NEAs can serve as a voltage-controlled switch to gate ion transport within the nanopore. Thus Nafion@NEAs can be operated as a diode by switching voltages applied to the top and bottom electrodes of the NEA, leading to a large rectification ratio, fast response times, and simplified circuitry without the need for external electrodes. By taking advantage of closely spaced and individually addressable electrodes, the redox-cycling electrochemical diode has the potential for application to large-scale production and electrochemically controlled circuit operations, which go well beyond conventional electronic diodes or transistors.