MId- to NEaR infrared spectroscopy for improVed medical ... · Project Overview Presentation MId- to NEaR infrared spectroscopy for improVed medical diAgnostics MINERVA Project overview

www.minerva-project.eu Project Overview

Presentation

MId- to NEaR infrared spectroscopy for improVed medical diAgnostics

MINERVA

Project overview presentation


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.]


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

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40404040

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.


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

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


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 of NKT Photonics

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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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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 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.


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.

*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]


Presentation

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.


Presentation

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.


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.


Presentation

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


Presentation

Contact

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Thanks for your attention!

www.minerva-project.eu Project website

For further information, please contact:

[email protected] Technical

[email protected] Admin &

Advisory Group

Documents

MId- to NEaR infrared spectroscopy for improVed medical ... · Project Overview Presentation MId- to NEaR infrared spectroscopy for improVed medical diAgnostics MINERVA Project overview