PImMS: Pixel Imaging Mass Spectrometry with Fast Pixel Detectors
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Transcript of PImMS: Pixel Imaging Mass Spectrometry with Fast Pixel Detectors
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PImMS: Pixel Imaging Mass Spectrometry with Fast Pixel Detectors
Mark Brouard, Edward Halford, Jason Lee, Craig Slater, Claire Vallance, Edward Wilman, Benjamin Winter, Weihao Yuen
Chemistry, University of Oxford
Jaya John John, Laura Hill, Andrei Nomerotski
Physics, University of Oxford
Andy Clark, Jamie Crooks, Renato Turchetta
Rutherford Appleton Laboratory
VERTEX 2011, June 2011
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Outline
PImMS: Pixel Imaging Mass Spectrometry
Proof of concept experiments
First results with PImMS1 Sensor
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Mass Spectrometry Very popular tool in chemistry, biology, pharmaceutical industry etc. TOF MS: Heavier fragments fly slower
Mass spectrum for human plasma
Total Time ~ 100 sec Measure detector current: limited to one dimension Mass resolution M/dM for TOF MS up to 50000
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Ion ImagingFix a mass peak
Measure full scattering distribution of fragment ions
Sensitive to fragmentation process
S atom ion images for OCS photodissociation at 248nm
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Visible Light vs Direct Detection
Visible light detection
MCP Phosphor
pixel sensor
Electron detection
MCPpixel sensor
E
Typically use visible light but direct detection of electrons after MCP is possible
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Pixel Imaging Mass Spec: PImMS
PImMS = Mass Spectroscopy Χ Ion Imaging
• Recent progress in silicon technologies: fast pixel detectors overcome the single mass peak limitation
• Since 2009 a 3-year project funded by STFC in UK to build a fast camera for mass spec applications
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Pixel Imaging Mass Spec: PImMS
Imaging of multiple masses in a single acquisition
Mass resolution determined by flight tube, phosphor decay time and camera speed
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Fast Framing CCD Camera
First proof of principle experiments:CCD camera by DALSA (ZE-40-04K07)
16 sequential images at 64x64 resolution
Pixel : 100 x 100 sq.micron
Max frame rate 100 MHz (!)
Principle: fast, local storage of charge in a CCD register at imaging pixel level
Limitation: number of frames
DALSA camera
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Velocity Mapped PImMS (1)
2007-2008: Proof of concept experiment successfully performed on dimethyldisulfide (DMDS)3
Ionization and fragmentation performed with a polarized laser, data recorded with DALSA camera.
CH3S2CH3
3: M. Brouard, E.K. Campbell, A.J. Johnsen, C. Vallance, W.H. Yuen, and A. Nomerotski, Rev. Sci. Instrum. 79, 123115, (2008)
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Possible applications (1)
Surface imaging for separate mass peaks
Replace scanning with wide-field imaging
R.Heeren et al
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Possible applications (2)
Parallel processing– high throughput sampling
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Possible applications (3) Fingerprinting of molecules
mass fingerprinting of human serum albumin(from Wikipedia)
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PImMS Sensor: Imager with time stamping
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Time stamping provides same information generating much less data
BUT needs low intensity (one pixel hit only once or less)
Fast Framing vs Time Stamping
Time stamping
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Spin-off of ILC Sensor R&D PImMS and International Linear Collider have similar data
structurePImMS : 0.2 ms duration @ 20 HzILC: 1.0 ms duration @ 5 Hz
337 ns
2820x
0.2 s
0.95 ms time
0.05 s
0.2 ms
PImMS
ILC
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Signal detected in thin epitaxial layer < 20 m
Limited functionality as only NMOS transistors are allowed PMOS transistors compete for charge
• INMAPS process developed at RAL
Shields n-wells with deep p+ implant
Full CMOS capability
Monolithic Active Pixel Sensors
PImMS1 sensor
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PImMS 1 Specs 72 by 72 pixel array 70 um by 70 um pixel 5 mm x 5 mm active area 50 ns timing resolution 12 bit time stamp storage 4 memories per pixel 1 ms maximum experimental period Programmable threshold and trim
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Ion Intensity Simulations
Important to be sensitive to heavy fragments
Simulated probability to have N hits/pixel
Four buffers allow higher intensity
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The PImMS Pixel
Charge Collection Diodes
Preamplifier
Shaper
Comparator
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PImMS Pixel
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PImMS1 Technology
615 transistors in every pixel Over 3 million transistors
Submitted in Aug 2010, received in Nov 2010
• 0.18 um CMOS fabrication
• INMAPS process (Rutherford Appleton Lab)
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PImMS1 Sensor
7.2 mm
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PImMS Camera System
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PImMS Testing
PImMS Camera
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PImMS Camera read out over a USB cable.
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First Analogue Image
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First Digital Readout Image
Two laser pulses separated by 300 ns
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PImMS1 Digital ReadoutFive laser pulses, each at a different time
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Digital Readout – 3D interpretation
Tim
ecod
e
Pixel position - x Pixel position - y
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Pixel Masking
Arbitrary masks are possible
Three laser pulses separated in time
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Sensor Characterization
Photon Transfer CurvePoisson distribution of signal Noise = sqrt(Signal) absolute calibration
Full well capacity 24ke
Quantum efficiency: 8-9% for visible light, max @ 470 nmFront illuminated sensor
Slope = 0.5
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Threshold Trim• Each pixel has a trim
register: 4 bits to adjust threshold
• Maximum trim ~50mV
• Calibration procedure equalizes thresholds for all pixels
• Dispersion (sigma) before and after calibration 12.8 3.6 mV (~70 e)
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TOF MS in Oxford Chemistry
PImMS sensor is mounted here
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Comparison of PImMS and PMT
Same mass peaks seen with PImMS as with a photomultiplier tube (PMT)
Two fragments of CHCA 1.5 kV MCP; 4.0 kV Phosphor screen
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One of the two PImMS peaks
PImMS : 50 ns per timecode FWHM ≈ 100ns in both
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Ions Detected vs MCP VoltageIons Detected vs MCP: 4kV Screen
0
50
100
150
200
250
300
350
400
1.32 1.34 1.36 1.38 1.4 1.42 1.44 1.46 1.48 1.5 1.52 1.54
MCP/kV
Ions
# of
ions
/cyc
le
MCP voltage (kV)
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FWHM vs MCP VoltageFWHM vs MCP: 4.0 kV Screen
0
0.05
0.1
0.15
0.2
0.25
1.32 1.34 1.36 1.38 1.4 1.42 1.44 1.46 1.48 1.5 1.52 1.54
MCP/kV
FWH
M/u
s
FWH
M (u
s)
MCP voltage (kV)
100 ns
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Spatial mappingVelocity mapping
Ion Imaging Modes
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Potential applications: forensics and tissue analysis
Ion image Microscope image (Trypan blue)
Spatial Mode Imaging
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Conventional CCD camera image oriented 45o to PImMS
First PImMS spatial imaging results
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Spatial map imagingFirst PImMS spatial imaging results
Spatial Imaging
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Spatial map imagingFirst PImMS spatial imaging results: four registers
Time of flight
Inte
nsi
ty
Multi-hit Capabilities
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Next Steps: PImMS 2 and beyond Larger Array 324 x 324 pixels 23 x 23 sq.mm active area 50 Frames/second with existing
PImMS camera Max 380 Frames/second Reduced interface pin count for
vacuum operation
Possible future directionsFaster: 101 ns
Larger: wafer scale sensors
More sensitive: backthinned
Intensity information: ToT
Build-in ADC
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Summary
Pixel Imaging Mass Spectroscopy is a powerful hybrid of usual TOF MS and Ion Imaging
Progress in sensor technologies allows simultaneous capture of images for multiple mass peaks
First PImMS sensor under tests since Feb 2011, second generation sensor in the end of 2011
Other applications, ex. atom probe tomography, fluorescent imaging etc