MINERVA Project overview presentation Project Overview - - PowerPoint PPT Presentation

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MId- to NEaR infrared spectroscopy for improVed medical diAgnostics MINERVA Project overview presentation Project Overview www.minerva-project.eu Presentation Motivation: to improve early cancer diagnosis One in four Europeans will die


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www.minerva-project.eu Project Overview Presentation

MId- to NEaR infrared spectroscopy for improVed medical diAgnostics

MINERVA

Project overview presentation

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www.minerva-project.eu Project Overview Presentation

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Motivation: to improve early cancer diagnosis

  • One in four Europeans will die from cancer
  • Early diagnosis reduces mortality
  • Single most important factor
  • Identification whilst cancer is surgically curative
  • Early identification is very difficult
  • Cancerous cells are very similar to healthy cells
  • Diagnosis becomes easier as the cancer develops
  • State-of-the-art diagnostic technique
  • Microscopic examination of tissue sample
  • Notoriously difficult
  • Subjective judgement
  • High inconsistency rate
  • Even between expert pathologists.

Images courtesy of Gloucestershire Hospitals NHS Foundation Trust

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www.minerva-project.eu Project Overview Presentation

Mid-IR spectroscopy: a new tool for pathologists

  • Mid-IR covers “fingerprint region” of the spectrum
  • Spectral region studied in MINERVA: 1.5 µm to 12 µm
  • Allows identification of biomolecules
  • Fats, proteins, carbohydrates etc.
  • Type and distribution
  • Provides important new information for disease diagnosis

BUT

  • Spotting “cancer markers” is NOT sufficient
  • Complex nature of biological samples
  • Inter-related distribution of species
  • Biochemical changes due to disease are difficult to detect
  • A more subtle technique is required
  • Multivariate analysis.

Mid-IR spectroscopy Diagnosis Cancer Healthy Multivariate Analysis

Page 3 Image of prostate tissue using mid-IR. [Courtesy of University of Exeter.]

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www.minerva-project.eu Project Overview Presentation

Multivariate analysis and correlation mapping

  • Multivariate analysis of mid-IR spectra
  • Computer-based mathematical technique
  • Automated process
  • Correlation mapping
  • A type of multivariate analysis
  • Identifies the location of different biochemicals in a sample
  • Enables visualisation of diseased regions or cells
  • MINERVA will combine novel mid-IR spectroscopy and

correlation mapping

  • Could lead to a breakthrough diagnostic technology.

Mid-IR spectroscopy Correlation mapping

CaF2 Collagen I Collagen III DNA Oleic acid Albumin

20 20 20 20 40 40 40 40 60 60 60 60 80 80 80 80 100 100 100 100 10 10 10 10 20 20 20 20 30 30 30 30 40 40 40 40

Images courtesy of Gloucestershire Hospitals NHS Foundation Trust Page 4

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Innovation & challenges: photonic hardware

  • MINERVA will develop new photonic hardware
  • Mid-IR glass fibres
  • Mid-IR components
  • Fused couplers
  • Acousto-optic modulators

– Calomel crystals

  • Novel pump lasers
  • 2.9 µm and 4.5 µm
  • Ultra-long wavelength supercontinuum sources
  • 1.5-4.5 µm (ZBLAN)
  • 1.5-5.5 µm (InF3)
  • 3-9 µm and 4-12 µm (chalcogenide)
  • Detectors
  • Using T2SL technology.
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Innovation & challenges: bio-medical

  • MINERVA will explore the mid-IR for medical applications
  • Analysis of mid-IR interaction with tissue
  • Prepared samples
  • In vitro modelling
  • Future extension to in vivo testing
  • Develop multivariate diagnostic algorithms
  • Demonstrate spectral discrimination
  • Cell types
  • Pathology types
  • Data handling methodologies
  • Real-time read-out
  • User interface
  • Dissemination activities.
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www.minerva-project.eu Project Overview Presentation

Mid-IR optical fibre

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Chalcogenide glass low loss mid-IR optical fibre sources MINERVA will produce new, robust, mid-IR fibres from ultra-high purity materials using innovative processing:

  • Rare-earth-ion Pr3+-doped Ge-As-Ga-Se
  • ptical fibre for 4.5 µm mid-IR pump

fibre laser

  • Step index As-Se / Ge-As-Se optical fibres

for a mid-IR supercontinuum broadband source from 4 to 12 µm wavelength

  • Microstructured As-Se/Ge-As-Se all-solid

& As-Se/air optical fibres for mid-IR supercontinuum broadband source from 3 to 9 µm wavelength. Making low optical loss preforms & fibre

Preform extrusion Fibre drawing

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www.minerva-project.eu Project Overview Presentation

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  • Developing fibre end protection

methods

  • End caps, tapers and heat

sinking

  • Splicing technique development
  • Silica-to-chalcogenide and

chalcogenide-to-chalcogenide, photonic crystal fibre (PCF)

  • Method of tapering mid-IR fibres.
  • New processes will be developed to enable the

production of mid-IR fused components

  • Develop a heating method suitable for fusing mid-

IR fibres

  • Produce packaging capabilities for safe

management of high-power mid-IR radiation

  • Develop a ‘family’ of mid-IR fused components

Passive components

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  • 2-4 µm range
  • Established material (TeO2) is suitable

for this wavelength range

  • Exploit latest design techniques to
  • ptimise performance
  • 4-12 µm Range
  • TeO2 not transparent beyond 4·5µm
  • MINERVA will develop calomel
  • World-beating crystal size
  • Develop new processing

methodology.

  • AOTFs filter a broad supercontinuum spectrum into a few narrow spectral lines
  • Power and wavelength can be adjusted
  • Electronically selectable

Acousto-optic tunable filters (AOTFs)

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www.minerva-project.eu Project Overview Presentation

Pump lasers

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  • 2.9 µm Q-switched fibre laser
  • MINERVA target: high power, high energy
  • Er:ZBLAN fibre laser
  • Applications
  • Primary MINERVA pump source for 3-9 µm

supercontinuum

  • High absorption by water makes it an

excellent laser for surgical cutting

  • 4.5 µm mode-locked fibre laser
  • MINERVA target: World first demonstration
  • Pr-doped chalcogenide ultrafast fibre laser
  • Pumped by 2 µm Tm-doped fibre laser
  • Applications
  • Primary MINERVA pump source for 4-12 µm supercontinuum
  • Biomedical spectroscopy
  • Precision surgery.

Water absorption coefficient

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www.minerva-project.eu Project Overview Presentation

Fluoride glass supercontinuum sources (1.5 to 5.5 µm)

  • ZBLAN fibres
  • Currently mid-IR supercontinuum

in fluoride fibres is limited to wavelengths below 4.5 µm

  • Limited by fibre attenuation
  • MINERVA will exploit
  • New fluoride glasses
  • Including indium fluoride fibres
  • Optimised fibre designs
  • Extend transmission spectrum
  • Seek to generate supercontinuum

beyond 5 µm in fluoride fibre

  • This provides an important part of

the “fingerprint region”.

Images courtesy

  • f NKT Photonics

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www.minerva-project.eu Project Overview Presentation

Ultra-long wavelength supercontinuum sources

  • MINERVA targets world-beating mid-IR supercontinuum sources
  • Based on new MINERVA pump sources, fibres and components
  • Modelling at DTU confirms theoretical design approach

– Advanced supercontinuum and dispersion simulations

  • Several ”stepping stones” defined with increasing technical risk
  • Sources based on MINERVA chalcogenide mid-IR fibres
  • Large core step-index fibres
  • Good power handling
  • All-solid Photonic Crystal Fibers (PCFs)
  • Air-glass PCFs
  • 3-9 µm sources with 2.9 µm pumping
  • World-beating wavelength range
  • 4-12 µm sources with 4.5 µm pumping
  • Covers whole fingerprint region
  • Requires all MINERVA target fibre, pumps and components!

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www.minerva-project.eu Project Overview Presentation

Detectors: Type-II superlattice detectors (T2SL)

Ec Ev GaSb InAs GaSb GaSb InAs Ec Ev GaSb InAs GaSb GaSb InAs

Band alignment of InAs / GaSb and the forming of minibands. Image using a 320256 MWIR T2SL detector taken at 110 K [Courtesy of IRnova.]

  • T2SL detector technology
  • High quality, high performance,

cooled photon detector

  • Thin layers of InAs and GaSb
  • Broken band type-II alignment
  • Broadband
  • Cut off wavelengths from 2 to 30 µm

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  • A III/V-material
  • Good manufacturability at low

cost

  • Higher operating temperature

than InSb

  • Lower cost than MCT.
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Detectors: MINERVA developments

  • MINERVA will push T2SL technology

to its limits

  • Development of detector in the mid-IR

wavelength band

  • 2-5.5 µm detector
  • NETD*<20 mK @120 K operating

temperature and f/4

  • 5.5-12 µm detector
  • NETD<20 mK @100 K operating

temperature and f/4

  • IRNova detectors hybridised with

Xenics designed readout circuits

  • Integrated in a state-of-the-art

module with a Stirling cooler.

*Noise Equivalent Temperature Difference

Image of a module for 640x512 pixels using 15 µm pixel pitch. [Courtesy of IRnova.] Page 14

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Demo: skin cancer identification

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  • Mid-IR spectroscopy for fast screening of human

body surfaces

  • Rigid probe for human skin surface examination
  • Identification of altered cells and tissue lesions
  • MINERVA work will use human skin equivalent

models (HSE)

  • Certified replacement of animal-based toxicology

testing in the EU

  • 3D test systems grown in petri dishes
  • Melanoma cell line HSEs are available
  • Evaluation of system for human skin analysis
  • Generation of reference spectra of HSEs
  • Acquisition of cell type & cell state specific spectra
  • Analysis of mid-IR spectral changes induced by

chemical cell fixation

  • Correlation of mid-IR spectra with confocal images
  • f fluorescence labelled cells.

HaCaT

Upper image: MINERVA kit at WWU Lower image shows HaCaT (cultured human keratinocyte)cells with the nuclei stained blue and a green actin cytoskeleton stain. [Courtesy of WWU]

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Demo: high volume screening

  • MINERVA will develop mid-IR micro-spectroscopy

for rapid screening

  • High intensity mid-IR microscope for rapid

analysis of disease-specific chemical signatures

  • Discrimination of
  • Abnormal cells from cytological specimens
  • Abnormal cells and tissues from unstained

tissue sections

  • Evaluation of system for ex vivo human samples
  • MINERVA will use human cells and tissues

collected during routine clinical testing

  • Acquisition of mid-IR spectra from cells and

tissues using globar mid-IR sources (hot SiC rod)

  • Comparison of performance with MINERVA

supercontinuum sources

  • Analysis of spectral changes and correlation with

gold standard histopathology / cytology.

Isabelle et al., JBO, 2010.

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Ly, Manfait et al, (2009)

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MINERVA impact

  • MINERVA target applications
  • Skin cancer detection
  • Rigid skin probe for use in hospitals and surgeries
  • MINERVA will only use skin models
  • Screening pathology
  • High throughput microscope-based screening
  • Hospital pathology labs
  • Cytological and histological
  • Impact: Fewer biopsies and improved survival rates
  • Potential spin-off applications
  • Spectroscopy
  • LIDAR
  • Laser surgery
  • Sensing.
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www.minerva-project.eu Project Overview Presentation

MINERVA Advisory Group

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  • MINERVA will establish a group of interested

parties to:

  • Guide MINERVA research
  • Develop new exploitation routes for mid-IR technology
  • Identify novel applications
  • Target organisations:
  • End users (hospitals, medical practitioners)
  • Research organisations (bio-medical and photonic)
  • Universities
  • Industrial companies.
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Project information

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  • MINERVA is funded under the European Commission’s Seventh

Framework Programme

  • Programme acronym FP7-ICT
  • http://cordis.europa.eu/fp7/ict/home_en.html
  • Funding scheme : Large-scale integrating project - CP-IP
  • Activity : ICT-8-3.5 - Core and disruptive photonic technologies
  • Project Reference 317803
  • Project cost 10.6 M€
  • Project funding 7.3 M€
  • Start date 01-Nov-2012
  • End date 31-Oct-2016
  • Duration 48 months.
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Consortium

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1 Gooch & Housego (UK) Ltd. UK (Coordinator) 2 NKT Photonics A/S DK 3 LISA Laser Products OHG D 4 BBT-Materials Processing SRO CZ 5 Xenics NV B 6 IR Nova AB S 7 University of Nottingham UK 8 Technical University of Denmark DK 9 Vivid Components Ltd. D 10 Westfaelische Wilhelms-Universitaet Muenster D 11 The University of Exeter UK 12 Gloucestershire Hospitals NHS Foundation Trust UK 13 Universidad Politecnica de Valencia E

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www.minerva-project.eu Project Overview Presentation

Contact

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Thanks for your attention!

www.minerva-project.eu Project website

For further information, please contact:

jward@goochandhousego.com Technical bruce@vividcomponents.co.uk Admin & Advisory Group