Functional Photonics for Single Bioentities

An application for a Platform Grant in Biophotonics

from the University of Surrey

Present today:Jeremy Allam

Professor of Ultrafast OptoelectronicsOverview Questions related to Photonics

JohnJoe McFaddenProfessor of Molecular Genetics

Questions related to biomedical aspects

David CareyEPSRC Advanced Research Fellow

Interdisciplinarity and nanotechnology

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 groupQueen’s Award 2002 for 20 year contributionExtensive Collaborations (Bookham Technology, Thales, IQE, Qinetiq, Infineon...)

5* RAE rating Leading early work on DNA probes for infectious diseasesExtensive 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)

Relevant Activities at Surrey

Oncology

Molecular toxicology

PharmacologyMolecular 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

Relevant Activities at Surrey

Oncology

Molecular toxicology

PharmacologyMolecular Genetics

Functional Genomics

Quantum Dots

Photonic Devices

Ultrafast photonics

Optical Spectroscopy

Oncology

Molecular toxicology

PharmacologyMolecular Genetics

Functional Genomics

Quantum Dots

Photonic Devices

Ultrafast photonics

Optical Spectroscopy

BiosensorsComputational biophotonics

Relevant Activities at Surrey

Co-applicants

Physicists

Biologists

ClinicianHelen Coley Oncology

Fiona Green Functional Genomics George Kass Molecular ToxicologyNick Plant Molecular ToxicologyJohnJoe McFadden Molecular GeneticsNick Toms Pharmacology

Jeremy Allam Femtosecond photonicsAleksey Andreev Quantum DotsDavid Carey Spectroscopy/MicroscopyOrtwin Hess Computational BiophotonicsStephen Sweeney Integrated biophotonic sensors

Sub Reddy Biosensors

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 ...

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

• DNA-conjugated or antibody-conjugated quantum dots coupled to direct detection of signal for single molecule detection.

• Multiplex quantum dots for parallel probing.

Molecular probesBiophotonic Solutions

Molecular probesThe SBMS Experience

commercialisation

1990

1987

1987

1990

1992

2004 – recent work

PCR-ELISA for diagnosis of meningococcal disease in blood

substrate

colourproduct

This or similar test widely used in clinical laboratories around the worldBUT

• 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

Quantum Dot ELISA-PCR for diagnosis of meningococcal

disease in blood

substrate

colourproduct

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

Quantum Dot diagnosis of meningococcal disease in blood

single molecule QD Detection

Meningococcal DNA

Patient sample

DNA extraction

Quantum Dotsdirect

Without PCR, the test should be much quicker and more easily applied in clinical labs

Quantum Dot multiplex detection of meningitis pathogens in blood

single molecule QD Detection

DNA

Patient sample

DNA extraction

Quantum Dotsdirect

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

Genetic Disease: Quantum dots for multiplex SNP genotyping

single molecule QD Detection

DNA

Patient sample

DNA extraction

Quantum Dotsdirect

Genotyping, for diagnosis or for research, may employ tens or even hundreds of different DNA probes

Genetic Disease: Quantum Dots for Haplotyping

or

FRET

?

Are genetic markers on the same or different chromosomes?

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 neuronphotonic readout of rotary biomolecular motors, protein folding, etc

QD molecule

biomolecular motor

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

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