The chemistry strand of IMPACT is focused on the generation of electrochemical sensors for cancer biomarkers that can be miniaturised and integrated onto the implantable silicon based chip system.
The aim of IMPACT was to "personalise" the delivery of radiotherapy and to monitor its effect. To meet this objective IMPACT’s focus was to deliver a platform consisting of a miniaturised and wireless implantable system that monitors and interprets biomarkers that are associated directly with cancer progression and cancer cell death (apoptosis) to optimise cancer treatment.
Initially we focused in the development of a system for electrochemical detection of proteases. Proteases are enzymes that catalyse the cleavage of amide bonds at specific sites in a protein or peptide. Among their many physiological roles, these enzymes are involved in many pathophysiological conditions. These include inflammation and cancer and the enzymes involved include: thrombin, human neutrophil elastase (HNE), matrix metalloproteinases (MMPs), caspases, etc. In this context, electrochemical biosensors have proved to be valuable tools - benefitting from a fast response, ease of miniaturisation (allowing the development of point-of-care devices), minimal sample preparation and high-sensitivity and selectivity.
To start with, we developed a proof-of-concept peptide-based electrochemical biosensor for the detection of protease activity using self-assembled monolayers (SAMs) on gold surfaces, using the model enzyme trypsin. This work was published in Biosensors and Bioelectronics in 2016. We then further optimised the proposed SAM system in order to enhance its analytical performance, while minimising non-specific adsorptions of other proteins and increase its stability, leading to two publications in Sensors and Actuators B in 2018. The proposed platform was subsequently successfully applied to the detection of HNE activity in blood human samples leading to a publication in Biosensors and Bioelectronics in 2018. We also worked towards the miniaturisation of these protease-based electrochemical sensors, assessing its analytical performance for trypsin detection using Pt microelectrodes, work that was published in Analyst in 2020. We finally integrated one of our sensors into an implantable silicon microfabricated device (manuscript in preparation).
The chemistry strand of the project also developed a novel in-situ electrochemical-based pro-drug activation strategy that was validated in cell culture and published in Chemical Communications in 2018.
