Andrei Nomerotski

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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