In this work, we develop a label-free electrochemical immunosensor for the detection of interleukin-6 (IL-6) in human cerebrospinal fluid (CSF) and serum for diagnostic and therapeutic monitoring. The IL-6 immunosensor is fabricated from gold interdigitated electrode arrays (IDEAs) that are modified with IL-6 antibodies for direct antigen recognition and capture. A rigorous surface analysis of the sensor architecture was conducted to ensure high structural fidelity and performance. Electrochemical characterization was conducted by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and sensing was performed using differential pulse voltammetry (DPV). The DPV peak current was used to quantify IL-6 in buffer, CSF, and serum in the range 1 pg mL–1 < [IL-6] < 1 μg mL–1. The IL-6 IDEA sensor achieved a limit of detection (LOD) of 1.63 pg mL–1 in PBS, 2.34 pg mL–1 in human CSF, and 11.83 pg mL–1 in human serum. The sensor response is linear in the concentration range 10 pg mL–1 < [IL-6] < 10 ng mL–1, and the sensor is selective for IL-6 over other common cytokines, including IL-10 and TNF-α. EIS measurements showed that the resistance to charge transfer, R CT, decreases upon IL-6 binding, an observation attributed to a structural change upon Ab-Ag binding that opens up the architecture so that the redox probe can more easily access the electrode surface. The IL-6 IDEA sensor can be used as a point-of-care diagnostic tool to deliver rapid results (∼3 min) in clinical settings for traumatic brain injury, and potentially address the unmet need for effective diagnostic and prognostic tools for other cytokine-related illnesses, such as sepsis and COVID-19 induced cytokine storms. Given the interdigitated electrode form factor, it is likely that the performance of the sensor can be further improved through redox cycling.

Closed bipolar electrochemistry to couple an analytical reaction to an optical readout by the reconfiguration of an optical metamaterial.

We report a closed bipolar electrode (CBE)-based sensing platform for the detection of diagnostic metabolites in undiluted whole human blood. The sensor is enabled by electrode chemistry based on: (1) a mixed layer of blood-compatible adsorption-resistant phosphorylcholine (PPC) and phenylbutyric acid (PBA), (2) ferrocene (Fc) redox mediators, and (3) immobilized redox-active enzymes. This scheme is designed to overcome nonspecific protein adsorption and amplify sensing currents in whole human fluids. The scheme also incorporates a diffusing mediator to increase electronic communication between the immobilized redox enzyme and the working electrode. The use of both bound and freely diffusing mediators is synergistic in producing the electrochemical response. The sensor is realized by linking the analyte cell, containing the specific electrode surface architecture, through a CBE to a reporter cell containing the electrochromic reporter, methyl viologen (MV). The colorless-to-purple color change accompanying the 1e– reduction of MV2+ is captured using a smartphone camera. Subsequent red-green-blue analysis is performed on the acquired images to determine cholesterol, glucose, and lactate concentrations in whole blood. The CBE blood metabolite sensor produces a linear color change at clinically relevant concentration ranges for all metabolites with good reproducibility (∼5% or better) and with limits of detection of 79 μM for cholesterol, 59 μM for glucose, and 86 μM for lactate. Finally, metabolite concentration measurements from the CBE blood metabolite sensor are compared with results from commercially available FDA-approved blood cholesterol, glucose, and lactate meters, with an average difference of ∼3.5% across all three metabolites in the ranges studied.

As the energy storage markets demand increased capacity of rechargeable batteries, Li metal anodes have regained major attention due to their high theoretical specific capacity. However, Li anodes tend to have dendritic growth and constant electrolyte consumption upon cycling, which lead to safety concerns, low Coulombic efficiency, and short cycle life of the battery. In this work, both conductive and non-conductive 3D porous hosts were coupled with a viscous (melt) polymer electrolyte. The cross-section of the hosts showed good contact between porous hosts and the melt polymer electrolyte before and after extensive cycling, indicating that the viscous electrolyte successfully refilled the space upon Li stripping. Upon deep Li deposition/stripping cycling (5 mAh cm-2), the non-conductive host with the viscous electrolyte successfully cycled, while conductive host allowed rapid short circuiting. Post-mortem cross-sectional imaging showed that the Li deposition was confined to the top layers of the host. COMSOL simulations indicated that current density was higher and more restricted to the top of the conductive host with the polymer electrolyte than the liquid electrolyte. This resulted in quicker short circuiting of the polymer electrolyte cell during deep cycling. Thus, the non-conductive 3D host is preferred for coupling with the melt polymer electrolyte.

Electrochemical immunosensors combine the advantages of electrochemical transducers such as low cost, potential for miniaturization, and quantified readout with the selective properties of immunochemical recognition elements. Here we describe a simple, label-free electrochemical immunosensor for the rapid detection of traumatic brain injury (TBI) by quanitifcation of a cytokine interleukin-6 (IL-6) in cerebrospinal fluid (CSF). The sensor system consists of gold interdigitated electrode arrays (IDEAs) that are modified with self-assembled monolayers (SAMs) and IL-6 antibodies (IL-6 mAb) for antigen recognition and capture. Electrode modification was confirmed using surface characterization (FT-IR, fluorescence) and electrochemically via EIS. The sensor performance was evaluated in IL-6 spiked PBS solution: the LOD was determined to be 1.63 pg/mL, with a linear range across 4 orders of magnitude. The sensor exhibits selectivity against non-target cytokines TNF-α and IL-10. The detection of CSF and serum IL-6 using the outlined system will be discussed for use as a point-of-care (POC) diagnostic and prognostic tool for TBI.