Smart Switchable Sensors for On-demand Biosensing and Cell Therapy Monitoring

Cell and gene therapies are poised to transform medicine by providing personalized and effective treatments for patients with chronic or life-threatening diseases. However, the complexity and high costs linked with the manufacturing of cell and gene therapy products have been severely constraining market availability and patient accessibility to these life changing therapies. There is an urgent need for innovative technologies that can address current challenges facing cell and gene therapy biomanufacture. Major advances are needed to enrich process integrated analytical tools, enabling accurate, real-time measurement of cell therapy key attributes during biomanufacture. This interdisciplinary project aims to develop smart switchable biosensors for real-time monitoring of cell-secreted, or bioreactor supplemented, cytokine biomarkers. For the first time, we aim to combine this novel switchable technology with complementary metal-oxide-semiconductors (CMOS), enabling on-demand electrochemical biosensing on-chip. Conceptually different from traditional biosensors where the surface immobilised recognition elements act as passive receptors, we introduce nature inspired surfaces with the unique ability to actively manipulate single-domain antibodies ie. nanobodies, conferring antigen-nanobody binding control. Consequently, analytes can be captured in space and time for on-demand detection, supporting real-time data capture for different periods of time. The switchable biosensor platform will bring innovation to cell therapy bioprocessing, leading to the implementation of fully automated, robust cell therapy culture processes to reduce production costs, and ultimately deliver cost-effective and impactful therapeutics to patients in need.

The project will be carried out in partnership with Imec R&D, nano electronics and digital technologies (imec-int.com) (Belgium) with opportunity for scientific visits and training.

A first degree (typically BSc or Masters) in Engineering, Chemistry, Material Sciences, Physics or Biology is required. Applications including CV and detailed education with grades should be addressed to Professor Paula Mendes ([email protected])

Subject Areas:

Surface Chemistry, Switchable Biological Surfaces, Bionanotechnology, Electrochemistry and Biosensing, CMOS.

References:

1. Daniel P. Carroll, Paula M. Mendes, “Recent Advances in Surface Modification and Antifouling Strategies for Electrochemical Sensing in Complex Biofluids” Current Opinion in Electrochemistry, 2023, 101319.

2. Bárbara Simões, Wanda J. Guedens, Charlie Keene, Karina Kubiak-Ossowska, Paul Mulheran, Anna M. Kotowska, David J. Scurr, Morgan Alexander, Alexis Broisat, Steven Johnson, Serge Muyldermans, Nick Devoogdt, Peter Adriaensens, Paula M. Mendes, “Direct immobilization of engineered nanobodies on gold sensors”, ACS Appl. Mater. Interfaces, 2021, 13, 15, 17353–17360.

3. B. Santos Gomes, E. Cantini, S. Tommasone, J. S. Gibson, X. Wang, Q. Zhu, J. Ma, J. D. McGettrick, T. M. Watson, J. A. Preece, J. C. Kirkman-Brown, S. J. Publicover, P. M. Mendes, “On-Demand Electrical Switching of Antibody-Antigen Binding on Surfaces”, ACS Appl. Bio Mater., 2018, 1, 738-747.

4. B. Santos Gomes, B. Simões,P. M. Mendes, “The increasing dynamic, functional complexity of bio-interface materials”, Nat. Rev. Chemistry, 2018, 2, 0120.