Monitoring with In Vivo Electrochemical Sensors: Navigating the Complexities of Blood and Tissue Reactivity

Abstract

The disruptive action of an acute or critical illness is frequently manifest through rapid biochemical changes that may require continuous monitoring. Within these changes, resides trend information of predictive value, including responsiveness to therapy. In contrast to physical variables, biochemical parameters monitored on a continuous basis are a largely untapped resource because of the lack of clinically usable monitoring systems. This is despite the huge testing repertoire opening up in recent years in relation to discrete biochemical measurements. Electrochemical sensors offer one of the few routes to obtaining continuous readout and, moreover, as implantable devices information referable to specific tissue locations. This review focuses on new biological insights that have been secured through in vivo electrochemical sensors. In addition, the challenges of operating in a reactive, biological, sample matrix are highlighted. Specific attention is given to the choreographed host rejection response, as evidenced in blood and tissue, and how this limits both sensor life time and reliability of operation. Examples will be based around ion, O2, glucose, and lactate sensors, because of the fundamental importance of this group to acute health care.

Towards Multiplexed and Multimodal Biosensor Platforms in Real-Time Monitoring of Metabolic Disorders

“…Although electrochemical sensors are relatively simple to use and easy to miniaturize, several instances, such as real-time monitoring of critically ill patients in an ICU (intensive care unit) setting, require the use of minimally invasive sensors that can be inserted inside the body with ease. Research demonstrates the development of implantable electrochemical sensors for in vivo monitoring [ 175 , 176 , 177 , 178 ]. However, such in vivo detection strategies require invasive surgery, which is often not feasible for neonates, seniors, or critically ill patients.…”

Assessing the triad of biocompatibility, medical device functionality and biological safety

“…Rong et al (2017) and Cho et al (2020) have summarized the current status of in vivo biosensors in general, and Cai et al (2020) have discussed the methods of characterization, cytotoxicity and animal studies with respect to glucose monitoring. Vadgama (2020) has just published an elegant analysis of the present day issues with in vivo electrochemical sensors; to quote from this paper with respect to the generic problem of biocompatibility, ‘ it has been an inappropriate quest to search for the single material or surface that absolves us from this problem (of developing tools for examining the separate entities at different locations in the reactive, hostile, environment)— the result has simply been more model systems. The quest needs to be more deeply rooted in the study of reactive biology—it is the biological control of the implant site that remains to be resolved ’.…”

“…Rong et al (2017) andCho et al (2020) have summarized the current status of in vivo biosensors in general, andCai et al (2020) have discussed the methods of characterization, cytotoxicity and animal studies with respect to glucose monitoring Vadgama (2020). has just…”

Oil-Membrane Protection of Electrochemical Sensors for Fouling- and pH-Insensitive Detection of Lipophilic Analytes

“…Generalizing the problematic solutes as hydrophilic presents a significant opportunity for more robust sensing of hydrophobic solutes since hydrophilic/hydrophobic selective protection could theoretically be added to sensors. Implementing such a hydrophilic/hydrophobic filter would provide protection even beyond the widely deployed size-selective protective membranes such as those used for in vivo glucose sensors − and other EAB sensors . Furthermore, this membrane should filter out redox-active interfering agents such as the negatively charged FAD/FADH2 and NAD+/NADH coenzymes.…”