Calibration-Free, Seconds-Resolved In Vivo Molecular Measurements using Fourier-Transform Impedance Spectroscopy Interrogation of Electrochemical Aptamer Sensors.

Electrochemical aptamer-based (EAB) sensors are capable of measuring the concentrations of specific molecules in vivo, in real time, and with a few-second time resolution. For their signal transduction mechanism, these sensors utilize a binding-induced conformational change in their target-recognizing, redox-reporter-modified aptamer to alter the rate of electron transfer between the reporter and the supporting electrode. While a variety of voltammetric techniques have been used to monitor this change in kinetics, they suffer from various drawbacks, including time resolution limited to several seconds and sensor-to-sensor variation that requires calibration to remove. Here, however, we show that the use of fast Fourier transform electrochemical impedance spectroscopy (FFT-EIS) to interrogate EAB sensors leads to improved (here better than 2 s) time resolution and calibration-free operation, even when such sensors are deployed in vivo. To showcase these benefits, we demonstrate the approach's ability to perform real-time molecular measurements in the veins of living rats.

A tight squeeze: geometric effects on the performance of three-electrode electrochemical-aptamer based sensors in constrained, in vivo placements.

Electrochemical, aptamer-based (EAB) sensors are the first molecular monitoring technology that is (1) based on receptor binding and not the reactivity of the target, rendering it fairly general, and (2) able to support high-frequency, real-time measurements in situ in the living body. To date, EAB-derived in vivo measurements have largely been performed using three electrodes (working, reference, counter) bundled together within a catheter for insertion into the rat jugular. Exploring this architecture, here we show that the placement of these electrodes inside or outside of the lumen of the catheter significantly impacts sensor performance. Specifically, we find that retaining the counter electrode within the catheter increases the resistance between it and the working electrode, increasing the capacitive background. In contrast, extending the counter electrode outside the lumen of the catheter reduces this effect, significantly enhancing the signal-to-noise of intravenous molecular measurements. Exploring counter electrode geometries further, we find that they need not be larger than the working electrode. Putting these observations together, we have developed a new intravenous EAB architecture that achieves improved performance while remaining short enough to safely emplace in the rat jugular. These findings, though explored here with EAB sensors may prove important for the design of many electrochemical biosensors.

Conjugated Polyelectrolytes: Underexplored Materials for Pseudocapacitive Energy Storage.

Conjugated polyelectrolytes (CPEs) are characterized by an electronically delocalized backbone bearing ionic functionalities. These features lead to properties relevant for use in energy-storing pseudocapacitor devices, including ionic conductivity, water processability, gel-formation, and formation of polaronic species stabilized by electrostatic interactions. In this Perspective, the basis for evaluating the figures of merit for pseudocapacitors is provided, together with the techniques used for their evaluation. The general utility and challenges encountered with neutral conjugated polymers are then discussed. Finally, recent advances on the use of CPEs in pseudocapacitor devices are reviewed. The article is concluded by discussing how their miscibility in aqueous media permits the incorporation of CPEs in living materials that are capable of switching function from extraction of energy from bacterial metabolic pathways to pseudocapacitor energy storage.

Detection and Characterization of Single Particles by Electrochemical Impedance Spectroscopy.

We present an electrochemical impedance spectroscopy (EIS) technique that can detect and characterize single particles as they collide with an electrode in solution. This extension of single-particle electrochemistry offers more information than typical amperometric single-entity measurements, as EIS can isolate concurrent capacitive, resistive, and diffusional processes on the basis of their time scales. Using a simple model system, we show that time-resolved EIS can detect individual polystyrene particles that stochastically collide with an electrode. Discrete changes are observed in various equivalent circuit elements, corresponding to the physical properties of the single particles. The advantages of EIS are leveraged to separate kinetic and diffusional processes, enabling enhanced precision in measurements of the size of the particles. In a broader context, the frequency analysis and single-object resolution afforded by this technique can provide valuable insights into single pseudocapacitive microparticles, electrocatalysts, and other energy-relevant materials.

Nanoimpacts at Active and Partially Active Electrodes: Insights and Limitations.

While the electrochemical nanoimpact technique has recently emerged as a method of studying single entities, it is limited by requirement of a catalytically active particle impacting an inert electrode. We show that an active particle-active electrode can provide mechanistic insight into electrochemical reactions. When an individual Pt electrocatalyst adsorbs to the surface of a partially active electrode, further reduction of electrode-produced species can proceed on the nanocatalyst. Current transients obtained during hydrogen evolution allow simultaneous measurement of the Pt catalyst over different length scales, size dependency suggests H atom intercalation as a catalytic deactivation mechanism. Although results show that outer-sphere redox probes are unproductive for particle characterization, the breadth of inner-sphere electrochemical reactions makes this a promising method for understanding the properties of catalytic nanomaterials, one at a time.