www.minerva-project.eu Project Overview Presentation MId- to NEaR infrared spectroscopy for improVed medical diAgnostics MINERVA Project overview presentation
www.minerva-project.eu Project Overview
Presentation
MId- to NEaR infrared spectroscopy for improVed medical diAgnostics
MINERVA
Project overview presentation
www.minerva-project.eu Project Overview
PresentationPage 2
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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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 diagnosisBUT
• 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
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Image of prostate tissue using mid-IR.[Courtesy of University of Exeter.]
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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
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Images courtesy of Gloucestershire Hospitals NHS
Foundation Trust
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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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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
optical 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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• 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 optimise 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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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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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 of NKT Photonics
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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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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 320×256 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.]
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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 of fluorescence labelled cells.
HaCaT
Upper image: MINERVA kit at WWULower image shows HaCaT (cultured humankeratinocyte)cells with the nuclei stained blue and agreen 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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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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Contact
Page 21
Thanks for your attention!
www.minerva-project.eu Project website
For further information, please contact:
[email protected] Technical
[email protected] Admin &
Advisory Group