Towards Electrochemical Lab-on-PCB Microsystems for Sepsis Diagnosis

Abstract

Sepsis is a life-threatening condition in which the body’s immune system becomes dysregulated in response to an infection. This disruption can cause severe organ failure but can be prevented by fast diagnosis and early treatment. Early diagnosis can be achieved by immune system monitoring through quantification of multiple protein biomarkers at the point of care. Electrochemical biosensors (such as diabetes glucose sensors) are a preferred technological solution for this challenge however, protein biomarker quantification often requires multiple sample processing steps which need to be integrated into a miniaturised microsystem to provide a sample-in-answer-out device. Such electrochemical microsystems are not widely available, due to high cost and complexity of their respected manufacturing techniques.
In this thesis, this challenge is tackled by utilisation of Lab-on-PCB technology, which explores the integration of multiple sample processing steps with electrochemical biosensors constructed on the same printed circuit board (PCB) platform. The first study explores a new antifouling surface chemistry on planar gold electrodes, enabling detection of sepsis biomarker procalcitonin in whole blood which is validated using clinical samples. In the second study, sensors for two additional sepsis biomarkers were constructed and multiplexed detection was demonstrated in whole blood. In the next study, gold PCB electrodes were physically and electrochemically characterised to ensure electrochemical integrity and their capability to be coupled with biological assays. The following study explored label-free approaches for detection of protein biomarkers using PCB electrodes through redox active self-assembly monolayers as well as simplified surface chemistry. In the last study, the previously described assay, based on antifouling surface chemistry, was transferred to a PCB platform. A PCB-based procalcitonin sensor was integrated with microfluidics and detection in undiluted human serum was achieved in under 17 minutes, with the sensor’s response in the clinically relevant concentration range.
In conclusion, this thesis serves as a guide for future development of Lab-on-PCB based microsystems describing advantages, challenges, and opportunities associated with the presented technology in the specific case of sepsis diagnosis. Utilisation of this technology could enable low-cost and scalable manufacturing of such diagnostic microsystems, enabling wide adoption and accessibility of sepsis diagnostics tools.

Date of Award	16 Jun 2021
Original language	English
Awarding Institution	University of Bath
Supervisor	Despina Moschou (Supervisor), Pedro Estrela (Supervisor) & John Campbell (Supervisor)