Toward the Rapid Diagnosis of Sepsis: Detecting Interleukin-6 in Blood Plasma Using Functionalized Screen-Printed Electrodes with a Thermal Detection Methodology

Abstract

This paper reports the detection of the inflammatory and sepsis-related biomarker, interleukin-6 (IL-6), in human blood plasma using functionalized screen-printed electrodes (SPEs) in conjunction with a thermal detection methodology, termed heat-transfer method (HTM). SPEs are functionalized with antibodies specific for IL-6 through electrodeposition of a diazonium linking group and N′-ethylcarbodiimide hydrochloride (EDC) coupling, which was tracked through the use of cyclic voltammetry and Raman spectroscopy. The functionalized SPEs are mounted inside an additively manufactured flow cell and connected to the HTM device. We demonstrate the ability to detect IL-6 at clinically relevant concentrations in PBS buffer (pH = 7.4) with no significant interference from the similarly sized sepsis-related biomarker procalcitonin (PCT). The limit of detection (3σ) of the system is calculated to correspond to 3.4 ± 0.2 pg mL–1 with a working range spanning the physiologically relevant concentration levels in both healthy individuals and patients with sepsis, indicating the sensitivity of the sensor is suitable for the application. Further experiments helped provide a proof-of-application through the detection of IL-6 in blood plasma with no significant interference observed from PCT or the constituents of the medium. Due to the selectivity, sensitivity, straightforward operation, and low cost of production, this sensor platform has the potential for use as a traffic light sensor for the multidetection of inflammatory biomarkers for the diagnosis of sepsis and other conditions in which the rapid testing of blood biomarkers has vital clinical application.

Electroanalytical overview: utilising micro- and nano-dimensional sized materials in electrochemical-based biosensing platforms

“…Typically, AuNPs would be used in this way to help increase the surface area of the electrode, aid in electron transfer, and allow for facile coupling of biological reagents. The improved electron transfer performance of the electrode is key here, as simply using the AuNPs as a linking group is not cost-effective; facile binding of biorecognition elements has been shown directly to the surface of SPEs [107]. The nanoparticles do not always need to be deposited onto the electrode surface though Han et al [108] utilised their binding ability from solution to the sensor after attachment of the target to produce a successful electrochemical biosensor for the detection of DNA.…”

Electrochemical Improvements Can Be Realized via Shortening the Length of Screen-Printed Electrochemical Platforms

“…In the former case, a range of geometries have been realized such as microbands, − dual-microbands, microband electrode arrays, microdisc arrays, microelectrodes and microelectrode arrays, and back-to-back configurations, highlighting the versatility of the SPE production methodology. SPEs are used extensively in the production of sensing platforms, with examples ranging from ions − and small molecules ,, to larger biological analytes such as proteins. − They have even been utilized outside of electrochemical sensing platforms due to their large surface area, ease of modification, disposability, and low cost. − As such, it is critical that SPEs can be reliably compared between different reported works.…”

Understanding Microbeads Stacking in Deformable Nano-Sieve for Efficient Plasma Separation and Blood Cell Retrieval

“…The efficient plasma separation [30,31] is critical for numerous down-stream molecular analysis and diagnosis [7,[32][33][34]. The microbeads packed nano-sieve device is capable of plasma separation without using bulky and complicated instruments such as a centrifuge.…”