This paper outlines a simple label-free sensor system for the sensitive, real time measurement of an important protein biomarker of sepsis, using a novel microelectrode integrated onto a needle shaped substrate. Sepsis is a life threatening condition with a high mortality rate, which is characterised by dysregulation of the immune response following infection, leading to organ failure and cardiovascular collapse if untreated. Currently, sepsis testing is typically carried out by taking blood samples which are sent to a central laboratory for processing. Analysis times can be between 12 and 72 h making it notoriously difficult to diagnose and treat patients in a timely manner. The pathobiology of sepsis is becoming increasingly well understood and clinically relevant biomarkers are emerging, which could be used in conjunction with a biosensor to support real time diagnosis of sepsis. In this context, microelectrodes have the analytical advantages of reduced iR drop, enhanced signal to noise ratio, simplified quantification and the ability to measure in hydrodynamic situations, such as the bloodstream. In this study, arrays of eight (r = 25 µm) microelectrodes were fabricated onto needle shaped silicon substrates and electrochemically characterised in order to confirm successful sensor production and to verify whether the observed behaviour agreed with established theory. After this, the electrodes were functionalised with an antibody for interleukin-6 (IL-6) which is a protein involved in the immune response to infection and whose levels in the blood increase during progression of sepsis. The results show that IL-6 is detectable at physiologically relevant levels (pg/mL) with incubation times as short as 2.5 min. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) measurements were taken and DPV was concluded to be the more suitable form of measurement. In contrast to the accepted view for macro electrodes that the impedance increases upon antigen bind, we report herein a decrease in the micro electrode impedance upon binding. The small size of the fabricated devices and their needle shape make them ideal for either point of care testing or insertion into blood vessels for continuous sepsis monitoring.

SARS-CoV-2 diagnostic practices broadly involve either quantitative polymerase chain reaction (qPCR)-based nucleic amplification of viral sequences or antigen-based tests such as lateral flow assays (LFAs). Reverse transcriptase-qPCR can detect viral RNA and is the gold standard for sensitivity. However, the technique is time-consuming and requires expensive laboratory infrastructure and trained staff. LFAs are lower in cost and near real time, and because they are antigen-based, they have the potential to provide a more accurate indication of a disease state. However, LFAs are reported to have low real-world sensitivity and in most cases are only qualitative. Here, an antigen-based electrochemical aptamer sensor is presented, which has the potential to address some of these shortfalls. An aptamer, raised to the SARS-CoV-2 spike protein, was immobilized on a low-cost gold-coated polyester substrate adapted from the blood glucose testing industry. Clinically relevant detection levels for SARS-CoV-2 are achieved in a simple, label-free measurement format using sample incubation times as short as 15 min on nasopharyngeal swab samples. This assay can readily be optimized for mass manufacture and is compatible with a low-cost meter.