Frühjahrsforum 2015 Frankfurt, 7. Mai 2015 Hochempfindliche Lichtdetektoren für den Einsatz in der diagnostischen Bildgebung und In-vitro Diagnostik: Digital Photon Counters (DPC, dSiPM) LDTEC Consulting Dr. York Haemisch, Sauerlach (Munich), Germany Detector Technology Clinical Imaging Pre-clinical Imaging Business Development Market Research Short CV [email protected] • 1990-1993: Ph.D. on quantum structures in III-V semiconductors • 1993-1996: General Electric, Medical Systems (med. imaging) • 1997-1999: ADAC Laboratories Europe B.V. (med. imaging) • 1999-2002: ADAC Laboratories Inc., San Jose, USA (med. imaging) (acquired by Philips in 2000) • 2002-2006: Philips Healthcare Europe (med. imaging) • 2006-2010: Bioscan Inc., Washington D.C. (pre-clinical imaging) • 2010-2014: Philips Corporate Technologies, Aachen (dSiPM) • recently: freelancing technology and business consultant, Munich YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 2 Outline • Light detection in industry • Photomultiplier tubes vs. solid state detectors • Silicon Photomultipliers (SiPM) • Digital vs. analog concept • Impact on applications (PET and IVDX) • Scalability of technology • Summary YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 3 Application of light detectors (> 1 B US$/year) High Energy Physics (HEP) Medical Imaging (MI) Clinical & preclinical nuclear imaging (e.g. PET/CT or Pet/MR), organ specific devices, operative probes Radiation and particle detectors for accelerator and astrophysics experiments using conversion via light detection Safety & Security (SS) In-vitro diagnostics (IVDX) (Time-resolved) fluorescence imaging as in microscopy, cytometry, spectroscopy, DNA sequencing, polymerase chain reaction… YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Industrial Automation (IA) LIDAR & distance measurements, 3D viewing in robotics, process & surface control…. 4 Radiation detection, baggage/cargo screening, nuclear power plant safeguarding, nuclear decommissioning….. Conventional Medical Imaging Modalities Diagnostic Imaging Magnetic Resonance Ultrasound X-Ray, CT Scintigraphy SPECT PET Transmission, Echo, Reflection Emission X-ray absorption as f(density) Biological distribution of radioisotopes (γ-emission & detection) Radiowaves (Nuclear Spin relaxation) YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 5 US wave reflection as f(density) Ionizing Radiation in medical imaging Transmission Roentgen (X)-rays CT planar (radiography) ~ 100 MHz/cm² (integrating) < 100 keV YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Emission β+ -annihilation (2γ) γ – single photon Sczintigraphy & SPECT ~ kHz/cm² 80-360 keV 6 PET (counting) ~ 1 MHz/cm² 511 keV 128 years of light detection (and PMTs still dominating) From Photomultiplier Tubes (PMTs) to Photodiodes (PDs), Avalanche PD’s (APDs) to Arrays of Geiger-Mode APDs (Silicon Photomultipliers (SiPMs)) 1960‘ Late 1980‘s - today 1934 1887 1905 Lenard Hertz Einstein PD, APD PMT • Vacuum tube • High voltage • 1-10 channels/cm² YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 • Multi-Anode PMT • Micro-PMT • MEMS 7 G-APD SPAD-arrays • Si- or III-V based • CMOS, low voltage • 10’s-1000’s channels/cm² Radiation conversion detectors (γ to light) in MI PMT based Si based Indirect conversion (via scintillation light) Light Detectors! YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 8 • Light sharing (non-linearity) • Few channels • Susceptive to magnetic fields • 1:1 coupling (linearity) • Many channels • Compatible with magnetic fields ToF as fundamental trigger for SiPM development No TOF TOF YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 9 Fast scintillators require fast photodetectors e.g. LSO, LYSO, LSF, LaBr e.g. PMT, APD, SiPM Graph courtesy of Spanoudaki & Levin, Stanford, in: Sensors, 10, 2010 YORK HAEMISCH – IVAM/COMPAMED 10 Frühjahrsforum 2015 Analog SiPM is in fact a solid state PMT (Analog) PMT • Linear mode • Large Anodes, multi-anode PMT’s with max 256 channels, expensive • Very low noise • Timing resolution limited by e-multiplication • HV needed YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Analog SiPM (aSiPM) 100’s-1000’s SPADs = SiPM (SPADs = “cells”) 11 • Geiger mode • µm cells • Single Photon • 102 pstiming resolution • Linear mode • mm cells • No Single Photon • No Timing resolution • HV needed aSiPM delivers summed pulses only Analog SiPM • Optimal signal in simulation/on single channel/ with discrete electronics • For higher integrated systems ASICS are needed • ASICS need to be adapted to SiPMs very carefully (impedance, capacitance,… YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 12 Problematic signal readout from aSiPMs Individual threshold (requires calibration) Introduces pedestal! (requires calibration) Desired information is number of photons, not amplitude 3 2 5 1 4 amplitude amplitude This is a low-pass filter! (smears out impulse response) • Temperature time YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 • Sum current gives analog signal • Caution with connections! • peak-shape analysis needed for • Area (energy) • Slope (time) • Pulse shape analysis influenced by external parameters: • Magnetic field • Noise time 13 • … G-APD or SPAD intrinsically is a digital device Digital Photon Counter (DPC) G-APD SPAD APD PD “Therefore, while the APD is a linear amplifier for the input optical signal with limited gain, the SPAD is a trigger device so the gain concept is meaningless.” (source: http://en.wikipedia.org/w/index.php?title=Single-photon-avalanche-diode&oldid=603577212) YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 14 Digital Photon Counter (DPC) operation principle • First photon hits sensor cell (there are several 100’/cm²) • Integrated photon counter switches from 0 to 1 • Trigger pulse is sent to TDC (arrival time of first photon) • Third photon hits another sensor cell • Integrated photon counter switches from 0 to 1 • Second photon hits another sensor cell • Integrated photon counter switches from 0 to 1 • • • • Internal clock reaches Integration time limit Device readout is started Jtag register sums all the “1”s Digital word with photon number and time stamp sent out Degenhardt et al. Nuclear Science Symposium Conference Record (NSS/MIC), 2009 IEEE. IEEE, 2009 Frach et al. Nuclear Science Symposium Conference Record (NSS/MIC), 2009 IEEE. IEEE, 2009. YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 15 SiPM topography and terminology (example DPC) Die = 4 pixel Array = 4x4 dies = 8x8 pixel 2 line TDC‘s 180° offset Pixel = 3200 SPADs • • • • • 8x8 pixels per array Configurable event validation (on sub-pixel and pixel level) Data correction on array level Calibration data stored in flash memory Upgradeable firmware/firmware library YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 16 DPC: electronics are laterally integrated Reverse Excess Voltage Quench Resistor Comparator SPAD 1 bit Ram Cell electronics • Area: 120 μm2 • 25 transistors including 6T SRAM • 6% of total cell area • Modified 0.18μm 5 metal layer CMOS YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 17 Die electronics: • • • 4 pixels per sensor, 6396/3200 cells per pixel Two delay line TDCs (180 degree offset) and pixel controller LVDS and LV CMOS clock and sync inputs, JTAG interface GAPD/SPAD readout: digital vs. analog Trigger Network Reverse Excess Voltage Quench Transistor Comparator SPAD TDCs + QDCs Shaper 1 bit Ram • Photon detection signal is digital by nature (photon or no photon) • Further processing fully digital by counting number of triggered cells with on-chip digital electronics • Chip output is (digital) number of photons with timestamp ↪ Fully digital processing chain ensures minimal impact of external parameter changes YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 18 DPC: configurable sensor with 4-layer interface FPGA • • • • • Power & Bias Clock distribution Data collection/ concentration TDC linearization Saturation correction Skew correction FPGA 200 MHz ref. clock Serial configuration interface Serial Data output (x2) Flash Memory YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Detector array Flash 8 x 8 dSiPMs • • • • Temp. sensor 19 FPGA firmware TDC calibration data Configuration Inhibit memory maps DPC: intrinsic timing f(jitter & avalanche formation) Contribution of: YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 TDC network 20 TDC network + diodes (avalanche formation time) DPC: better intrinsic timing proven in experiments „Time resolution below 100 ps for the SciTil detector of PANDA employing SiPM“ S. E. Brunner, L. Gruber , J. Marton , H. Orth and K. Suzuki, Preprint from JINST, Jan. 2014 analog SPTR: digital 45 ps σ 85 ps σ “… several types of SiPM have been investigated using a proton test beam. In the experiment, a time resolution of about 85 ps has been achieved using SiPM from **** and **** with a sensitive area of 3 x 3 mm². Employing the Digital Photon Counter from Philips, a time resolution of about 45 ps could be measured.” YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 21 Detector timing depends on crystal aspect ratio 3x3x5 mm³ LYSO (AR: 0.55) 4x4x22 mm³ LYSO (AR: 1.375) 250 ps FWHM YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 22 DPC enables use of monolithic crystals (3D detector) 20 mm LSO YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 23 Digitization: control of detector parameters (DCR) YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 24 Advantages of digital vs. analog SiPM • Significantly reduced temperature sensitivity (~10-1) • Active quenching reduces afterpulsing & crosstalk • Individually addressable cells enable DC control • Better linearity (&correction) • Better intrinsic timing resolution due to integrated TDCs (~ factor 2) • No analog electronics, no ADCs, no ASICs YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 25 Solid state: dramatic increase in sampling density PMT (analog) 4 channels No. (LOR) = n²/2 x n x N n ~ 600 (no. of crystals/ring) (~76 cm diameter) N ~ 60 (no. of rings) (24 cm AFOV) ~ 6.5 Billion LOR! @ ~ 100 kHz/LOR YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 26 Solid State 256 channels Sampling and timing are 2 key factors in PET Increased sampling density Factors 50 -200 PMT sampling (analog) non-TOF YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Solid State sampling (digital) 500 ps 250 ps Improved timing (currently factor 2) 27 100 ps ToF @ 250 ps and 1:1 improve S/N and spatial res. With TOF 4.8 mm rods 200 mm 70 mm DPC based 4.7 mm 3.2 mm Deluxe Jaszczak Phantom Without TOF PMT based YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 4.7 mm 28 3.2 mm Impact on Applications (here: PET imaging) DPC based PET PMT based PET 1:1 coupling, 2 mm voxels (light sharing, 4 mm voxels) Images courtesy of University Hospitals, Cleveland, USA YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 29 Impact on Applications (here: PET imaging) PMT based PET DPC based PET Images courtesy of University Hospitals Cleveland YORK HAEMISCH – 25 years TEP, Würzburg 2015 30 Impact on Applications (here: PET imaging) PMT based PET DPC based PET Images courtesy of University Hospitals Cleveland YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 31 Apps in IVDX: FCM, MPR, Microscopy, Sequencers… Microplate readers (MPR) Flow Cytometers (FCM) YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 32 VCI 2013 32 IVDX: FCM principle (up to 18 channels) Flow cytometers use separate fluorescence (FL-) channels to detect light emitted. The number of detectors will vary according to the machine and its manufacturer. Detectors are either silicon photodiodes, CCD arrays or photomultiplier tubes (PMTs). Silicon photodiodes are usually used to measure forward scatter when the signal is strong. PMTs are more sensitive instruments and are ideal for YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 33 scatter and fluorescence readings. IVDX technology trend: multichannel solid state Spectral imaging In general, CCD camera speed is a major limitation for spectral imaging with the collection of a single lambda stack requiring several minutes or more. Digital cameras also require repetitive scans to capture a lambda stack, which can lead to increased photobleaching and phototoxicity. The speed situation is far more critical in live-cell imaging where labeled structures can change spatial location during the acquisition of a lambda stack that consumes several minutes. 34 YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Single channel Multichannel Dual channel FARICH prototype detector @ CERN Die neue LSM 8 Familie: Schnelle Konfokalmikroskope mit GaAsP Detektoren (III-V) und Airyscan Das Airyscan-Prinzip Ein klassisches Konfokalmikroskop beleuchtet eine Stelle Ihrer Probe, um das emittierte Fluoroszenzsignal zu detektieren. Außerhalb des Fokus auftreffendes Emissionslicht wird bei einem Pinhole, dessen Größe bestimmt, welcher Teil der Airy Disk den Detektor erreicht, zurückgewiesen. Sie können die Auflösung erhöhen, indem Sie das Pinhole verkleinern. Das führt jedoch dazu, dass das Signal-Rausch-Verhältnis stark absinkt, da weniger wertvolles Emissionslicht durchgelassen wird. Mit Airyscan führt ZEISS ein neues Konzept ein. Anstatt das an einem Pinhole auftreffende Licht auszusondern, sammelt ein 32-Kanal-Flächendetektor das gesamte Licht einer Airy Disk gleichzeitig. Dabei funktioniert jedes Detektorelement als einzelnes, winziges Pinhole. Die Kenntnis des Strahlenganges und der räumlichen Verteilung jeder Airy- Disk ermöglicht eine äußerst lichteffiziente Bildgebung: Sie können nun alle von Ihrem Objektiv gesammelten Photonen verwenden. http://www.zeiss.de/microscopy/de_de/produkte/confocal-microscopes/lsm-880.html#airysca 35 YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Scalability means maintaining Intrinsic Performance *Using 4x4x22 mm³ LYSO crystals CRT ~ 250 ps* Increasing no. of channels CRT ~ 250 ps* CRT ~ 250 ps* CRT ~ 250 ps* 20 x 20 cm² Cherenkov detector with 48 ps σ ! CRT ~ 250 ps* YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 36 Digitization, Miniaturization, Integration… Photography Television Transistor Telephony + SOFTWARE ! Next?: Light Detection X-Ray imaging DPC is in sync with current technology trends YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 37 Summary • The digital implementation of SiPM overcomes the drawbacks of the analog version and makes it a truly scalable technology. • The scalability of technology is essentially enabled by early digitization and has been demonstrated by e.g.: - PET test ring, Philips PET product - FARICH detector prototype (not shown here) • In medical application (PET) DPC demonstrated impact in terms of sampling (spatial resolution) and timing (ToF) leading to significantly improved image quality. • By opening the road to software and firmware programmable detectors DPC is likely to be implemented in IVDX too, supporting the trend to multichannel/parallelization. • The digital technology (like any other CMOS) needs volume to succeed. 38 YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Thank you for your attention! Thanks also to: Special thanks to: Philips DPC: Thomas Frach Mezbah Shaber Carsten Degenhardt Louis Meesen Ben Zwaans Oliver Muelhens Ralf Schulze Sebastian Reinartz Ralf Dorscheid Rik de Gruyter Shu Xu Anja Schmitz Kathrin Budde YORK HAEMISCH – IVAM/COMPAMED Frühjahrsforum 2015 Philips Research: Andreia Trinidade Pedro Rodrigues Andreas Thon Volkmar Schulz Torsten Solf Andre Salomon 39 FZ Juelich: Siegfried Jahnke Gerhard Roeb Simone Beer Matthias Streun Günther Kemmerling Holger Nöldgen Marco Dautzenberg
© Copyright 2024 ExpyDoc
