Medical Imaging - Opportunities for Business Seminar
24/01/12
Session 2 Technology Showcase
Three technologies developed or enhances at the University of Leicester are presented
2. • A knowledge exchange project from the
Space Research Centre of the University of
Leicester
• Feed expertise developed from space
missions into commercial benefit for UK
industry.
• Delivering Innovative Design, Engineering,
Analysis and Support (IDEAS) to your
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• Part financed by the European Regional
Development Fund
• UK companies can access and benefit from
our technology and experience.
If your organisation would like to benefit from
our knowledge and expertise, please contact us
at enquiries@spaceideashub.com
About Space IDEAS Hub
3. 11:35 Detectors for high speed photon imaging
and timing
Dr Jon Lapington
11:55 Single Molecule Imaging Technology
Prof George Fraser
12:15 High Resolution SFOV Gamma Camera
Systems for Medical Imaging
Dr John Lees
Session 2 – Technology Showcase
4. Dr Jon Lapington, Reader in Space Physics, University of Leicester
Space Research Centre
5. Space Research Centre
Why photon counting?
How to image single photons
Microchannel plate detectors
HiContent
C-DIR
Applications
Conclusions
6. Space Research Centre
Provides the ultimate sensitivity
Extends dynamic range to lowest light levels
Capable of picosecond (or better) time
resolution
Can provide of high resolution imaging
Necessary for time coincidence or energy
discrimination techniques
Is intrinsically linear up to detector rate limit
7. Space Research Centre
Imaging technologies depend on photon energy
X-rays and γ-rays
produce measurable signal in silicon detectors e.g.
CCD
Optical photons
only produce 1 to a few electrons in silicon
Require some form of preamplification – gain
Silicon devices under development, but..
Only vacuum tube devices combine:
▪ High resolution imaging
▪ Low dark noise
▪ High time resolution
8. Space Research Centre
Farnsworth 1930 patent
Development of
resistive lead glass
Technology (1950s)
The Channeltron or
channel electron multiplier
Invention of the continuous
dynode technique
Miniaturization and
duplication (1960s)
The Microchannel plate
Conductive coating
Microchannel Plate Cross-section
Incident Radiation
-
+
Output Electrons
HV
9. Space Research CentreMCP
operation
Lead Glass MCP
Secondary emitter
Electrodes
High voltage
supply
Vacuum
Readout device
Particle detection
Electron, ion
Neutron
Photon (vacuum)
Photon (optical)
Optical window
Vacuum tube
Cross section through MCP detector
Readout Device
- +
n
OpticalWindow
10. Space Research Centre
Specification
High throughput multi-channel photon-counting
Photon timing with 25 picosecond accuracy
Up to 1024 parallel detection channels
Throughput up to 10M count/sec/channel
Compact integrated detector system
Retrofit-able to biological microscopes
Application-specific adaptability
Programmable digital processing capability
Techniques and Applications
Time resolved spectroscopies
Multi-channel TCSPC
FLIM, FRET, FCS, polarization anisotropy, Raman
High Content bio-assay
e.g. drug discovery, cell screening
confocal microscopy, optical tomography
Ratio of detected flux to input flux
0
0.2
0.4
0.6
0.8
1
1.2
1.00E+05 1.00E+06 1.00E+07 1.00E+08
Counts/cm^2/s
Outputrate/inputrate
UK/CERN Collaboration
Detector know-how from Astronomy
Electronics expertise from Particle Physics
Tube design from UK’s top manufacturer
Life science expertise
11. Space Research Centre
Event charge is localized on resistive layer
Transient signal induced through dielectric
Dielectric substrate part of vacuum housing
Induced signal sensed by C-DIR readout
C-DIR - a capacitively coupled electrode array
Capacitive division – breakthrough performance
A new concept in centroiding readouts
Purely capacitive – picosecond timing potential
No resistive noise – no partition noise
25 x 25 mm2 C-DIR – pattern capacitance of <8 pF!
Very low total noise (<200 e- rms at τ=250ns)
→ 1000 × 1000 pixel2 at 106 electrons.
Simple linear algorithm – minimal processing
Excellent linearity - utilize >80% of anode
Capacitances intrinsic in pattern geometry
Applications
Wide-field fluorescence lifetime imaging (FLIM)
Photon-timing/imaging e.g. LIDAR, TOFPET, 3D
pptv trace gas measurement using BBCEAS
Quantum Imaging, Quantum astronomy
TOF mass spectrometry
Molecular dynamics
Ring Imaging Cherenkov detectors for sLHC, FAIR
C-DIR – the “Capacitive Division Image Readout”
Proof-of-concept prototype
Prototype image data
C-DIR equivalent circuit
Optimised flex-PCB C-DIR readout
Linearity simulation
12. Space Research Centre
Time correlated single photon
counting
Pulsed, focussed laser
Laser spot scanned in x and y
Measure fluorescence decay time
(x,y) by accumulating histogram
PMT or gated intensifier (CCD)
Fluorescence limited to 0.01 events
per laser pulse with single channel
PMT
HiContent detector (641024 ch)
Multiple photons per pulse, or
Multiple imaged areas (Multiwell plate)
High content, high throughput bioassay
drug discovery
14. Space Research Centre
Pixellated photon counting
detector replaces CCD
camera
Event timing allows
Image reconstruction
Observation of dynamic signals
Advantages
Ultimate sensitivity
Reduced dark noise
No pixel aliasing effects
Much higher time resolution
Cucurbita; 6x6 Configuration vsWidefield; 20x Objective
Data and figure courtesy of Prof. Nick Hartell,UoL
BBSRC-funded project: DigitalConfocal Microscope For High Speed Microscopy
15. Space Research Centre
Revision: Cavity RingDown Spectroscopy
• Using a pulsed coherent light source
• Cavity output tails off exponentially
• No spectral information
• Requires pulsed laser
Laser Input
Pulse
Pulse in cavity
Cavity output
Intensity
16. Space Research Centre
fibre-optic
alignment mirrors
• Photon-counting provides phase shift of modulated
light source
• Uses broadband LED light source (no laser reqd.)
• Monitor LED source and cavity output simultaneously
• Simultaneous measurement at multiple wavelengths
• Discriminate multiple species simultaneously
• Technique is can be self calibrating
• Capable of parts per trillion sensitivity
C-DIR MCP
detector
Broadband Cavity Enhanced Absorption Spectroscopy
Broadband LED light source
cavity
17. Space Research Centre
We have developed complementary readout systems
to exploit microchannel plate performance envelope
for single photon counting
HiContent: Pixellated detector system with parallel
multichannel electronics (up to 1024 channels with
picosecond timing and very high throughput – 2.5
Mcount/ch/s)
C-DIR: Flexible, lost cost system with intrinsic high
time resolution and customisable imaging
performance - very high spatial resolution or
moderate resolution with high throughput
We’re now exploit opportunities in a range of
applications in the life science and other fields
18. 11:35 Detectors for high speed photon imaging
and timing
Dr Jon Lapington
11:55 Single Molecule Imaging Technology
Prof George Fraser
12:15 High Resolution SFOV Gamma Camera
Systems for Medical Imaging
Dr John Lees
Session 2 – Technology Showcase
19. Space IDEAS Hub Workshop , 24th January 2012.
Space Research Centre
Department of Physics and Astronomy,
Michael Atiyah Building,
University of Leicester
Single Molecule Imaging Technology
GW Fraser
e-mail gwf.le.ac.uk
Tel 0116 252 3542 (direct line) or 3491 (PA)
1. Superconducting Tunnel Junctions (STJs) to register the energy, position and arrival
time of single optical photons by measuring the charge deposited in a tantalum
superconductor at a temperature of 0.3K
2. Insights into the basic fluorescence process, coupled to in-depth knowledge of
detector physics, leading to novel algorithms for microarray analysis ?
20. Measurement of light fundamental to life sciences research
Current measuring devices (PMTs,CCDs) have major limitations
Monochrome
High noise
Low sensitivity
Life Sciences need detectors with:
The ability to scan entire colour spectrum, photon-by-photon
Greater sensitivity
Less noise and better linearity
Solution – the Superconducting Tunnel Junction (STJ)
Developed by the European Space Agency (ESA) for optical astronomy
Requires closed-cycle cooler capable of 0.3 K (or below!)
Only coarse (12 x 10) pixel arrays available
21. S-CAM
Developed by Tone Peacock, Mike
Perryman et al. at ESTEC, from
1992 onwards
Successfully employed for stellar
and planetary astronomy on the
William Herschel Telescope
STJ
22. 0
1
2
3
4
5
6
7
8
9
10
1 1.5 2 2.5 3
Photon energy (eV)
Alexa 594
Alexa 488
The detection of multiple fluorescent labels using
superconducting tunnel junction (STJ) detectors
G.W. Fraser*, J.S. Heslop-Harrison†, T. Schwarzacher†, A.D.Holland*, P. Verhoeve‡ and A. Peacock (*Space
Research Centre, Department of Physics and Astronomy and Department of Biology†, University of Leicester, Leicester LE1 7RH, UK. ‡ Science Payloads
Technology Division SCI-ST , Research and Scientific Support Department , Postbus 299, ESA/ESTEC, 2200 AG Noordwjik, The Netherlands.)
Review of Scientific Instruments, Volume 74, September 2003.
23. 0
0.1
0.2
400 500 600 700 800
Wavelength (nm)
Counts/10nm/second (a) Raw Spectra
Second ESTEC Campaign – single pixel Tantalum STJ
31. 2. Applications
in Life
Sciences
3. Requirement
for closed-cycle
cryogenic cooler
4.
Requirement
for Super
Resolution
Software
5. New
Applications
in Exoplanet
Detection?
1.Novel
Astronomical
Detector
Technology – the
optical STJ
37. MA plot after collapse of two-colour microarray data set on to
“line of parity” and imposition of noise threshold
38. Estimating the size
of the population of
expressed genes by
comparison with null
(Gaussian) cumulative
distribution
39. The Future of Biology is the Detection of Light
Acknowledgements
Trude Schwarzacher, Pat Heslop-Harrison, David Ray, David Gough, Alyson Reed
Rob Limpenny, Gauthier Torricelli, Sarah Botterill, Simon Lindsay, Daniel Brandt
Peter Verhoeve and Didier Martin
40. 11:35 Detectors for high speed photon imaging
and timing
Dr Jon Lapington
11:55 Single Molecule Imaging Technology
Prof George Fraser
12:15 High Resolution SFOV Gamma Camera
Systems for Medical Imaging
Dr John Lees
Session 2 – Technology Showcase
41. Dr John Lees
University of Leicester
High resolution SFOV
gamma camera systems for
medical imaging
Medical Imaging - Opportunities for Business
Due to confidentiality restrictions,
this presentation is not available online
42. If your organisation would like to benefit from
our knowledge and expertise, please contact us.
Space IDEAS Hub
W: www.spaceideashub.com
E: enquiries@spaceideashub.com
T: 0116 229 7700
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