Detecting infectious organisms: A concerted approach using genomics, molecular engineering and nano-enabled bio-MEMS technologies (AptaMEMS-ID)

The functional integration of man-made devices and biological systems represents one of the grand challenges of science and technology and it is now widely accepted that a combination of nanotechnology and engineering that harnesses the full potential of genomic information through real-time predictive, preventive, point-of-care healthcare provision will lead to the next technological revolution. However, major progress in the field is unlikely without guidance from the user community combined with interdisciplinary input from molecular genetics and bioinformatics.This project, which lies at the heart of the confluence of nano-, bio-, micro- and genomic technologies, proposes to use nano-enabled biological sensor technology for the development of a point-of-care system for the rapid detection of infectious organisms. The proposal is based around the clinical and societal need for rapid detection of specific nosocomal infections for screening, diagnostic and epidemiological uses and involves a combination of technologies encompassing; comparative genomics, novel bioinformatics, confirmatory proteomics, molecular engineered peptide aptamer ligands and microelectromechanical (MEMS) sensor technologies which exploit effectively at the nano-scale: design, manufacture, functionalization and molecular patterning.The ability of Newcastle University researchers to use e-Science Grid-based workflows to exploit data from microbial genome sequences is at the heart of this proposal. This technology will be used for the characterisation of proteins displayed at bacterial cell surfaces (SAPs). Once putative SAPs are identified and characterised, the composition of the surface proteome will be analysed to identify proteins that are common to target groups of organisms. If performed manually this would normally take many weeks whereas our approach takes less than a day to establish the workflows and to process the data. Once target proteins have been identified, a combination of proteomics and transcriptomics will be used to determine the expression of the target genes in clinical samples.These developments will then be combined with molecular engineering to produce a range of bespoke engineered biomolecules, peptide aptamers, which will recognize specifically the SAP proteins. Peptide aptamers, which are small, robust peptide sequences designed to act as protein recognition modules, will be prepared by the commercial collaborator Aptuscan. The selected aptamers will then be integrated with nanometre resolution, using our patented photolithographic 3-dimensional patterning technique, into solid-state MEMS microsystems which will be designed and developed to incorporate multi-analyte capabilities on a single sensor surface, using a combination of our patented sensor and molecular patterning technologies, to simultaneously detect multiple diverse harmful microorganisms. Finally, the technology will be assessed in healthcare demand-driven application areas by collaboration with Dr John Magee, Director of the Health Protection Agency regional laboratory in Newcastle and Professor Kate Gould, Director of Infection Prevention and Control at the Newcastle upon Tyne Hospitals NHS Foundation Trust.The innovations encompassed in this programme of research will allow the development of a suite of rapid, quantitative sensor systems engineered at the molecular, nano- and micro-scale levels for the specific detection and identification of pathogenic microorganisms on the basis of the fingerprint of SAPs which will provide organism-specific unique identifier motifs. These devices will constitute valuable aids to front line monitoring of infection diagnosis, progress and epidemiology. This has the potential to provide profound economic and human advantages for the NHS through improved patient care and management.