1. Functional Photonics for Single Bioentities An application for a Platform Grant in Biophotonics from the University of Surrey

2. Present today: Jeremy Allam Professor of Ultrafast Optoelectronics Overview Questions related to Photonics JohnJoe McFadden Professor of Molecular Genetics Questions related to biomedical aspects David Carey EPSRC Advanced Research Fellow Interdisciplinarity and nanotechnology

3. The Surrey Scene School of Electronics & Physical Sciences (SEPS) School of Biomedical and Molecular Sciences (SBMS) Postgraduate Medical School (PGMS) 5* RAE rating Leading optoelectronics / photonics group Queen’s Award 2002 for 20 year contribution Extensive Collaborations (Bookham Technology, Thales, IQE, Qinetiq, Infineon...) 5* RAE rating Leading early work on DNA probes for infectious diseases Extensive collaborations with pharmaceutical companies (GlaxoSmithKline, Pharmacia/Pfizer, Xenova, AstraZenecca, Oxagen, Cyclacel …) Formed 2000 to support health-related research Link to NHS and clinicians (St George’s Hospital Medical School, Royal Surrey County Hospital)

4. Relevant Activities at Surrey Oncology Molecular toxicology Pharmacology Molecular Genetics Functional Genomics Quantum Dots Photonic Devices Ultrafast photonics Optical Spectroscopy School of Electronics & Physical Sciences School of Biomedical and Molecular Sciences Postgraduate Medical School

5. Relevant Activities at Surrey Oncology Molecular toxicology Pharmacology Molecular Genetics Functional Genomics Quantum Dots Photonic Devices Ultrafast photonics Optical Spectroscopy

6. Oncology Molecular toxicology Pharmacology Molecular Genetics Functional Genomics Quantum Dots Photonic Devices Ultrafast photonics Optical Spectroscopy BiosensorsComputational biophotonics Relevant Activities at Surrey

7. Co-applicants Physicists Biologists Clinician Helen ColeyOncology Fiona Green Functional Genomics George KassMolecular Toxicology Nick Plant Molecular Toxicology JohnJoe McFaddenMolecular Genetics Nick TomsPharmacology Jeremy AllamFemtosecond photonics Aleksey AndreevQuantum Dots David CareySpectroscopy/Microscopy Ortwin HessComputational Biophotonics Stephen SweeneyIntegrated biophotonic sensors Sub ReddyBiosensors

8. University Support for Relevant Interdisciplinary Research Interdisciplinary Research Institutes: Advanced Technology Institute £5M from JIF + £5M from UniS incorporating photonics and electronics research extensive new device fabrication facilities centre of excellence in Medical Research opening March 2005 to promote health related research and build University-NHS links Infrastructure funding: Functional Genomics Laboratory £2.3M from SRIF1 genomics and proteomics facilities Nano-bioelectronics facility £3.8M from SRIF2 nanofabrication, e.g. focussed ion beam, surface plasmon resonance apparatus + staff recruitment...

9. Biomedical Objectives Our proposal is strongly focussed on important biomedical applications: Infectious disease diagnosis: detection and identification of pathogens Pharmacology: drug-receptor dynamics in health and disease Human genetics: genotyping and haplotyping

10. DNA-conjugated or antibody-conjugated quantum dots coupled to direct detection of signal for single molecule detection. Multiplex quantum dots for parallel probing. Molecular probes Biophotonic Solutions

11. Molecular probes The SBMS Experience commercialisation 1990 1987 1990 1992 2004 – recent work

12. PCR-ELISA for diagnosis of meningococcal disease in blood substrate colour product This or similar test widely used in clinical laboratories around the world BUT takes 24-36 hours (too slow! - patients may die of meningitis within hours of first symptoms) can only be performed in specialist labs Meningococcal DNA Patient sample PCR amplification DNA extraction enzyme ELISA Plate hospitals like these!! ELISA Plate Scanner Newcombe, … McFadden 1996 J.Clin.Microbiol. 34, 1637-1640

13. Quantum Dot ELISA-PCR for diagnosis of meningococcal disease in blood substrate colour product Compare with existing ELISA-PCR to benchmark quantum dot probes Meningococcal DNA Patient sample PCR amplification DNA extraction ELISA Plate hospitals like these!! ELISA Plate Scanner Quantum Dots

14. Quantum Dot diagnosis of meningococcal disease in blood single molecule QD Detection Meningococcal DNA Patient sample DNA extraction Quantum Dots direct Without PCR, the test should be much quicker and more easily applied in clinical labs

15. Quantum Dot multiplex detection of meningitis pathogens in blood single molecule QD Detection DNA Patient sample DNA extraction Quantum Dots direct Rapid identification of specific agent involved (there are many that cause meningitis), or detection of drug-resistance gene, may be vital for implementing appropriate treatment regime

16. Genetic Disease: Quantum dots for multiplex SNP genotyping single molecule QD Detection DNA Patient sample DNA extraction Quantum Dots direct Genotyping, for diagnosis or for research, may employ tens or even hundreds of different DNA probes

17. Genetic Disease: Quantum Dots for Haplotyping or FRET ? Are genetic markers on the same or different chromosomes?

18. Functional QD Probes optical properties of QDs depend on electric field, molecular vibrations, orientation, proximity, etc, hence QDs as functional probes real-time spatio-temporal dynamics of biomolecular function We will calculate QD properties and hence design functional probes. Information will be supplied to collaborators for fabrication of the QDs spatio-temporal imaging of neuron photonic readout of rotary biomolecular motors, protein folding, etc QD molecule biomolecular motor

19. PBG optical waveguide Nano-VCSEL Laser Integrated Biophotonic Sensors Alternative approaches to high-sensitivity, multiplexed biophotonic sensors: resonance condition for high sensitivity (e.g. dual-stripe mode-locked laser) spatial readout exploit bio-nano size match ‘new’ operational modes e.g. photonic bandgaps (PBG) Photonic Bandgap Biosensor

20. What it will mean for us exploit our existing research strengths in new directions fully exploit large investment in infrastructure and capital equipment help retain significant research staff support training of students in new interdisciplinary areas make an impact in an important emerging research field