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 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 Images courtesy of - Even between expert pathologists. Gloucestershire Hospitals NHS Foundation Trust Project Overview Page 2 www.minerva-project.eu 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. Image of prostate tissue using mid-IR. [Courtesy of University of Exeter.] Multivariate Analysis Cancer Healthy Mid-IR spectroscopy Diagnosis Project Overview Page 3 www.minerva-project.eu 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 CaF 2 Mid-IR spectroscopy Collagen I 10 10 10 10 Collagen III 20 20 20 20 DNA 30 30 30 30 Correlation mapping Images courtesy of Oleic acid 40 40 40 40 Gloucestershire Hospitals NHS 20 20 40 40 60 60 80 80 100 100 20 20 40 40 60 60 80 80 100 100 Foundation Trust Albumin • MINERVA will combine novel mid-IR spectroscopy and correlation mapping • Could lead to a breakthrough diagnostic technology. Project Overview Page 4 www.minerva-project.eu Presentation
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 (InF 3 ) - 3-9 µm and 4-12 µm (chalcogenide) • Detectors - Using T2SL technology. Project Overview Page 5 www.minerva-project.eu Presentation
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. Project Overview Page 6 www.minerva-project.eu Presentation
Mid-IR optical fibre Making low optical loss preforms & fibre Chalcogenide glass low loss mid-IR optical fibre sources Preform extrusion MINERVA will produce new, robust, mid-IR fibres from ultra-high purity materials using innovative processing: • Rare-earth-ion Pr 3+ -doped Ge-As-Ga-Se Fibre drawing 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. Project Overview Page 7 www.minerva-project.eu Presentation
Passive components • 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 • 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. Project Overview Page 8 www.minerva-project.eu Presentation
Acousto-optic tunable filters (AOTFs) • AOTFs filter a broad supercontinuum spectrum into a few narrow spectral lines • Power and wavelength can be adjusted • Electronically selectable • 2-4 µm range • Established material (TeO 2 ) is suitable for this wavelength range • Exploit latest design techniques to optimise performance • 4-12 µm Range • TeO 2 not transparent beyond 4·5µm • MINERVA will develop calomel • World-beating crystal size • Develop new processing methodology. Project Overview Page 9 www.minerva-project.eu Presentation
Pump lasers • 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 Water absorption supercontinuum coefficient • 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. Project Overview Page 10 www.minerva-project.eu 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 Images courtesy the “fingerprint region”. of NKT Photonics Project Overview Page 11 www.minerva-project.eu 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! Project Overview Page 12 www.minerva-project.eu Presentation
Detectors: Type-II superlattice detectors (T2SL) • T2SL detector technology • High quality, high performance, cooled photon detector • Thin layers of InAs and GaSb - Broken band type-II alignment • Broadband - C ut off wavelengths from 2 to 30 µm Image using a 320 � 256 MWIR T2SL detector taken at 110 K [Courtesy of IRnova.] GaSb GaSb GaSb GaSb GaSb GaSb • A III/V-material • Good manufacturability at low Ec Ec cost Ev Ev • Higher operating temperature InAs InAs InAs InAs than InSb Band alignment of InAs / GaSb and the forming of minibands. • Lower cost than MCT. Project Overview Page 13 www.minerva-project.eu Presentation
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. Image of a module for 640x512 pixels using 15 µm pixel pitch. [Courtesy of IRnova.] *Noise Equivalent Temperature Difference Project Overview Page 14 www.minerva-project.eu Presentation
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