Practical Application of Space Research Science & Engineering to Health-care & Bioscience Event
12th March 2009
XMM-NEWTON
Case Study 4:High Count Rate Imaging Photo-multipliers for Biology
Jon Lapington
Chandra – HRCMicrochannel plate detectorUniversity of Leicester
Space Research Centre
Microelectronics GroupHigh speed ASICs
First solar x-rayspectrum-1946 XMM-Newton-1999
The rapid pace of technological change drives detector performance
Unexploited opportunities exist for fast imaging and event timing detectors in many fields
Space Science Atmospheric Science Biological Sciences Chemistry Environmental science Forensics Materials Science Medicine Physics Security
FRET imaging using fluorescence lifetime spectroscopy
IntensityG
FP-C
dc42
co
ntro
l G
FP-C
dc42
/ W
T PA
K-m
yc-C
y3
1.8 2.3τ (ns)
1.8 2.3τ (ns)
Lifetime
Figures courtesy Professors Ng, King's College London Vojnovic, Gray Cancer Institute
Fluorescence correlation spectroscopy measures multiple system parameters
Figures courtesy Schwille, “Fluorescence Correlation Spectroscopy” ebook
Event timing is used for a variety of other bioscience applications
• Other spectroscopies– Raman, polarization anisotropy, etc.
• Time resolved optical tomography• Time-of-flight PET• Molecular imaging• Luminescence/phosphorescence
"HiContent“ & “IRPICS”- a family of detectors designed specifically for life science applications
Detector attributes• Multi-channel / imaging• Photon counting• Time resolved• High throughput• Miniaturized electronics• Flexible, multi-purpose• Commercial product
Window
Photocathode
MCP stack
Electrode array
Readout electronics:PCB with ASIC electronics underside
Photon
Photoelectron
MCP electron gain
Current collected on readout electrode
ASIC preamp and discriminator timesphoton event
LVDS logic out TDC + FPGA processing
Detector Design
18 mm FOV
~20 mm
Multi-layer ceramic
8 x 8 array of independent 25 ps channels
Electronics on coupled PCBoutside vacuum
Vacuumenclosure
HiContent Detector Envelope
Prototype Tube Design
Multi-layer ceramic construction
The end goal is a 32 x 32 array, effectively 1024 independent PMTs
Electronics Design• Totally parallel, multi-channel design
– for high throughput operation
• Miniaturization and integration– Multichannel ASICs + compact 3D layout
• CERN NINO ASIC– 8 channel preamplifier/discriminator– Fast, 1 ns peaking time– Low noise (<5000 e- rms)– Low timing jitter (<20 ps above 100 fC)
• CERN HPTDC ASIC– 8/32 channel time-to-digital converter– 25/100 ps time resolution– 75 ns pulse pair resolution
NINO ASIC
Parameter Value
Peaking time 1ns
Signal range 100fC-2pC
Noise (with detector) < 5000 e- rms
Front edge time jitter < 25ps rms
Power consumption 30 mW/ch
Discriminator threshold 10fC to 100fC
Differential Input impedance 40Ω< Zin < 75Ω
Output interface LVDS
Input stageIn+
In-
Diff.Stage
× 6
Diff.Stage
× 6
Diff.Stage
× 6
Diff.Stage
× 6
Low Frequency Feedbackto control offset
and apply threshold
Pulsestretcher
LVDSOutput Driver
Out+
Out-
Hysteris
OR
OR
NINO channel
Input resistance adjustment ??Input resistance adjustment ??
Threshold adjustment(10 fC minimum)
Threshold adjustment(10 fC minimum)
Stretcher ON/OFF+ Stretch length adjustment
Stretcher ON/OFF+ Stretch length adjustment
Hysteresis ON / OFFHysteresis ON / OFFOther
channels
Other channels
64 Channel Prototype PCB
120 mm
NINO ASIC
Current Status• HiContent Prototype (8 x 8 Pixel2 )
– Detector and electronics design and manufacture complete– Measured time resolution (end-to-end electronics) – 37 ps rms– Initial phase of detector testing has begun– System tests will begin spring 2009– End-user field trials will take place in third quarter 2009
• HiContent (16 x 16 Pixel2 )– In-house HPTDC development board completed and under test– 64 channel HPTDC daughterboard design started– 256 channel system design under development
• IRPICS– Change to 40 mm detector format to maximize throughput– 1024 channel readout multi-layer ceramic design started– 32 channel low power NINO mk3 chip designed and manufactured– System design in progress
Project Goals• Economic goal – an affordable solution for FLIM and FCS
– Our goal ~1% of the cost per channel c.f. conventional systems– Single channel TCSPC system - £20k, max rate ≈ 1M Count/s
• Performance goal – challenge current TCSPC limitations– Overall event rate projected ≤ 100 M count/s
• Flexible operation for multi-purpose application– User selectable channel grouping for optimal performance trade-offs
• Several modes of FLIM operation – “Single pixel” detector with:
• up to 100 MHz rate capability • Simultaneous event capability (escape TCSPC single event per pulse limit)
– Multi-pixel simultaneous imaging• Detector pixellation used for simultaneous imaging of an illuminated area• Selectable “pixel” size by channel grouping• Provides image resolution versus count rate trade-off
We are exploring promising new detector materials:
Diamond Dynode Detectors
1) Basic Technology fundedProof of concept project
2) STFC PIPSS funded“High speed imaging with diamond dynode detectors ”
Smart materials such as diamond offer new opportunities
• Simple to produce– chemical vapour
deposition• Boron doped
– tuneable conductivity• Wide band-gap
– low noise / high temperature operation
• Robust– air-stable, easy to
reactivate
Images courtesy of Dr. Paul May, Diamond Group, University of Bristol
Dimaond is easily patterned and structured
SEM micrographs courtesy of Dr Paul May, University of Bristol
Sub-micron thick diamond membranes over apertures machined in silicon Dr. Bob Stevens - RAL
33 micron diameter dots of mono-crystalline diamond grit deposited by inkjet onto conductive glass.Dr. Neil Fox, University of Bristol
Advantages of diamond as a dynode material
• Negative electron affinity– high secondary electron yield = gain
• High gain– lower dynode count required
• High gain– lower gain variance per dynode
• Lower gain variance– improved signal to noise– event “energy” resolution possible– less demanding of electronics
• Lower dynode count– excellent time resolution
• Narrow energy and angular range– excellent time resolution
δθ
δE
Conventional materialN ≤ 15
δθ
δE
CVD DiamondN ≤ 80
Diamond yield characterization
Photograph (upper) and 2D “image” of secondary emission yield (lower) from 3 diamond samples using e-beam scanning
Secondary emission results –conventional versus CVD diamond
Conventional dynode materials
CVD Diamond
Our best result observed for H-terminated CVD-diamond
Measurements in black - J. E. Yater, A. Shih, and R. Abrams, Phys. Rev. B, V56, R4410.
Photonis PMT Handbook
Diamond detector configurations being investigated
-
Support Substrate
Diamond dynode
Primary electron -
Amplified signal
Transmission Reflection
Proof of principle exists already…in non-imaging mode
55 ps rise-time88 ps FWHM
The World’s fastest photomultiplier tube
Possible bioscience applications
• High resolution timing applications• Time-of-flight PET• Fluorescence life-time imaging• Fluorescence correlation spectroscopy• FRET imaging• Single molecule imaging• Time resolved optical tomography• Luminescence/phosphorescence• High content, high throughput analysis
Vision – opportunity for a revolution in detector design and performance
2D MicroPMT pixel arrays micro-machined in silicon large area devices monolithic, flat panel high speed imaging high time resolution
Analogous to the CRT to LCD revolution …
Diamond technology offers to revolutionize photon-counting detector design
AcknowledgementsHiContent and IRPICS Collaborators• CERN – Pierre Jarron & co-workers• Photek – Jon Howorth & co-workers• Gray Institute, Oxford University – Boris Vojnovic• Manchester University – David Clarke• Funding bodies – STFC, BBSRCDiamond dynode project collaborators• Bristol University – Paul May & Neil Fox• Photek – Jon Howorth & co-workers• Atomic Weapons Establishment – Colin Horsfield• Central Microstructure Facility, RAL – Bob Stevens• Funding bodies – RCUK, STFC & AWE