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