Brian Roehrich

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.

The ubiquity of nanomaterials in electrochemical energy conversion technologies has driven intense interest in unravelling the material’s structure- function relationships. In response, single- entity electrochemistry has been developed as a technique to study the properties of individual nanoparticles, one at a time. This approach engenders a bottom-up understanding, linking the activities of the single particles to the emergent properties of the ensemble. The “nano-impact” technique, a subset of single-entity electrochemistry, uses low-noise instrumentation to measure current transients arising from individual particles which stochastically collide with an ultramicroelectrode. These transients have been successfully used to measure the size of both insulating and redox-active nanoparticles, as well as the activity of single electrocatalysts. However, it remains challenging to study certain classes of materials on a single-entity basis. One such class is pseudocapacitors – materials which mix electronic and ionic conductivity, critical components of ion batteries and other next-generation energy storage technologies. While careful experimental design and data analysis have allowed the detection and qualitative characterization of single ion-intercalating particles, their nature as mixed conductors makes quantitative information difficult to obtain amperometrically. This hurdle is due to the measured current response being dictated by one or more possible factors: electron transfer, ion diffusion within the particle or across the particle/electrolyte interface, or ion transfer in the bulk. To overcome this, electrochemical impedance spectroscopy (EIS) is commonly used to characterize bulk pseudocapacitors. In EIS, a small-magnitude sinusoidal (AC) voltage is applied to the working electrode and the current response is recorded. Different timescales can be probed by varying the AC frequency – the high frequency response is dominated by fast processes, such as capacitance, while the low frequency response contains information on electron transfers and mass transport. In this way, EIS gives a full picture of the electroactive material and can unravel the coexisting electronic and ionic conductivity of mixed conductors. In this presentation, I will discuss our development of an EIS-based technique to detect and characterize single particles. We implemented fast-Fourier transform based EIS to rapidly acquire impedance spectra spanning several decades of frequencies. The spectra are fit to an equivalent circuit model and monitored as a function of time. Discrete changes in various equivalent circuit parameters are observed, corresponding to single particle-electrode impact events. Using a model system of polystyrene microbeads, we demonstrate that discrete increases in the charge-transfer resistance can be used to accurately measure the contact area between the individual bead and the ultramicroelectrode. I will also discuss our recent progress towards detecting single ion-intercalating nanoparticles and characterizing their charge storage ability on a single particle basis. These advances expand both the scope of single-entity electrochemistry and the depth of information gleaned from a single measurement of a single particle.

Using low noise electronics and micro-electrodes we can now detect single analytes in solution, one at a time.^1,2 In this talk, we will briefly cover recent discoveries in the field of single entity electrochemistry and show that both electroactive and electro-inactive materials can be detected using complementary approaches.^3,4 However, some strong limitations in this field persist. In the case of electroactive entities, in order to detect the single entity above the electrochemical noise level, a careful choice of the analyte that differs in its physical properties from the electrode is needed. Here, we show that an active particle-active electrode composed of the same material can provide mechanistic insight into electrochemical reactions.⁵ 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. In the case of redox-inactive materials, a different analytical problem exists. The location of the adsorbed individual material at the electrode surface influences the magnitude of the electrochemical signal being blocked during a steady-state flux of a redox probe towards the electrode.^6,7 Our recent discovery shows that coupling the electrochemical reaction to a homogeneous rate-limiting chemical reaction offers a platform for high precision measurements. Using both finite element simulations and experimental statistical analysis we provide guiding rules for sizing redox-inactive materials with high analytical precision under various conditions such as analyte and electrode size and analyte concentration. References: (1) M. Crooks, R. Concluding Remarks: Single Entity Electrochemistry One Step at a Time. Faraday Discuss. 2016, 193 (0), 533–547. https://doi.org/10.1039/C6FD00203J. (2) V. Sokolov, S.; Eloul, S.; Kätelhön, E.; Batchelor-McAuley, C.; G. Compton, R. Electrode–Particle Impacts: A Users Guide. Phys. Chem. Chem. Phys. 2017, 19 (1), 28–43. https://doi.org/10.1039/C6CP07788A. (3) Bard, A. J.; Zhou, H.; Kwon, S. J. Electrochemistry of Single Nanoparticles via Electrocatalytic Amplification. Isr. J. Chem. 2010, 50 (3), 267–276. https://doi.org/10.1002/ijch.201000014. (4) Quinn, B. M.; van’t Hof, P. G.; Lemay, S. G. Time-Resolved Electrochemical Detection of Discrete Adsorption Events. J. Am. Chem. Soc. 2004, 126 (27), 8360–8361. https://doi.org/10.1021/ja0478577. (5) Roehrich, B.; Sepunaru, L. Nanoimpacts at Active and Partially Active Electrodes: Insights and Limitations. Angew. Chem. Int. Ed. n/a (n/a). https://doi.org/10.1002/anie.202007148. (6) Fosdick, S. E.; Anderson, M. J.; Nettleton, E. G.; Crooks, R. M. Correlated Electrochemical and Optical Tracking of Discrete Collision Events. J. Am. Chem. Soc. 2013, 135 (16), 5994–5997. https://doi.org/10.1021/ja401864k. (7) Deng, Z.; Elattar, R.; Maroun, F.; Renault, C. In Situ Measurement of the Size Distribution and Concentration of Insulating Particles by Electrochemical Collision on Hemispherical Ultramicroelectrodes. Anal. Chem. 2018, 90 (21), 12923–12929. https://doi.org/10.1021/acs.analchem.8b03550.

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.

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.