Cambridge Analytical Biotechnology

Cambridge Analytical Biotechnology (CAB) has a special interest in in-vitro diagnostics: the understanding of how biology can be interfaced with electronic, mechanical and optical systems and the development of new instrumentation and techniques to answer fundamental and applied questions concerning new biological measurement regimes and conquering challenges concerned with analysis and diagnosis with bioelectronics.

The unique CAB approach is characterised by end-to-end analytical systems from dynamics of molecular signalling to transduction technologies and application; this requires interdisciplinarity, adopting methods from biotechnology, engineering and chemistry. The group has a world-class reputation for its lead in applied innovative research, bridging theoretical methods and modelling with lab-based experimental science.

The research project base is designed to achieve a necessary balance between fundamental investigation (blue skies research) and precompetitive application-orientated collaboration with industry. Industrially sponsored research is organised to achieve a truly collaborative format, with active input from all partners and 2-way exchange of expertise, intellectual and commercial invention and development.

CAB also has a special interest in improving access to diagnostics in low and middle income countries (LMICs) without global purchasing price parity across borders. Partnering with colleagues in LMICs the group  is using synthetic biology techniques to develop local integrated diagnostic manufacturing and designing affordable local production and testing without a cold chain.

CAB also has a special interest in improving access to diagnostics in low and middle income countries (LMICs) without global purchasing price parity across borders.

Protein engineering for sensors and bioelectronics

Even though protein based biosensors have been successfully developed, they have typically used naturally occurring enzymes that have not evolved for the purpose of being used in a biosensor. Similarly, the hunt for naturally occurring bioelectronic components does not reveal structures optimised for assembly and deployment in circuitry. A powerful tool currently being used to expand the family of biomaterials and integrate them with transduction elements is protein engineering.

Starting from the basic concept that a biosensor for in vivo diagnostics requires an analyte biorecognition element, for example an enzyme, antibody or other binding protein, biosensor design begins with that element. The vision converges towards modular molecular-engineering in which integrated signal transduction function and binding site characteristics are engineered in tandem with self-assembling nanostructures or modular self-immobilising peptide sequences. These design principles have allowed protein isolation without many of the normal downstream steps and avoiding chemical modification, while achieving stabilisation of the proteins without such stringent cold chain needs.

Protein engineering allows both structure and function to be embedded into a fusion protein and optimised to become a novel bioanalytical component. For example, a construct of an enzyme or antibody with honeybee silk protein appended with fluorescent protein can be expressed in E. coli and spun to fibres which can be fashioned into swabs and included in a design for a self-indicating in vitro diagnostic.

Our ‘gene to diagnostic’ programme takes an approach to materials that can be expressed in vivo in E. coli with one step purification and silica biosensor integration and can be produced with minimal resources at low cost. A fusion protein construct combines A) the central functional assay protein (e.g. enzyme); B) a visualizing protein (e.g. fluorescent protein) to provide a reference measurement in the final diagnostic and facilitating visual monitoring of the production and isolation without a laboratory infrastructure; C) an in-built immobilization peptide which is fundamental to stabilization and effective interfacing with (i) the sample (ii) the diagnostic platform and importantly (iii) plays a key role in simplifying isolation and purification. Depending on the choice of peptide, different platform substrate materials can be chosen (e.g. paper, silica, metals, carbon etc.).

Using synthetic biology we have also used properties of energy transfer to design a self referencing firefly luciferase enzyme which measures ATP and taking into account the distance between the redox site and the electrode have engineered redox proteins to allow direct electron transfer between protein and electrode. Hybrid protein-redox polymer structures have been achieved whose oxidation state and charge storage can be controlled by electrode polarisation voltage.