PImMS – An event-triggered time-stamping CMOS Image Sensor for Mass Spectrometry Andy Clark, Jamie Crooks, Renato Turchetta STFC Rutherford Appleton Laboratory Mark Brouard, Ewen Campbell, Jason Lee, Craig Slater, Claire Vallance, Ed Wilman, Ben Winter, Weihao Yuen Chemistry, University of Oxford Jaya John John, Laura Hill, Andrei Nomerotski Physics, University of Oxford IWoRID 2011 – Zurich

Outline Pixel Imaging Mass Spectrometry = PImMS! PImMS Sensor Overview Results Conclusions

S atom ion images for OCS photodissociation at 248nm Imaging Mass Spec Mass spectrum for human plasma ~ 100 µs Combines Mass Spectroscopy and Ion Imaging S atom ion images for OCS photodissociation at 248nm

Mass Spectrometry Sample Laser Ionization and Fragmentation Ion Optics MCP Phosphor Screen Lens Sensor

Proof of Concept Using fast framing CCD imager (64 x 64, 16 frames, @ 10 MHz) 2007-2008: Proof of concept experiment successfully performed on dimethyldisulfide (DMDS) * CH3S2CH3 Limitations: System must be pre programmed with target mass flight time Only 8 masses per measurement Requires multiple measurement to analyse complex molecules *: M. Brouard, E.K. Campbell, A.J. Johnsen, C. Vallance, W.H. Yuen, and A. Nomerotski, Rev. Sci. Instrum. 79, 123115, (2008)

PImMS Pixel Preamplifier Charge Collection Diodes Shaper Comparator Mention analogue output and triming Comparator

Ion Intensity Simulations Important to be sensitive to heavy fragments Simulated probability to have N hits/pixel Four buffers allow higher intensity

PImMS Pixel 70 µm

PImMS 1 Made on the INMAPS process, 180 nm 72 by 72 pixel array < 50 ns timing resolution 12 bit time stamp storage 4 Memories per pixel > 1 ms maximum experimental period Programmable threshold and trim 7.2 mm 5 mm

Camera Cooling system Option for dry air/nitrogen flushing of sensor chamber F-mount SLR lens USB output

Optical Testing Quantum Efficiency 8-9% for visible light Max @ 470 nm Fill factor 20% for front illuminated Full well capacity 24,000 e-

Calibration Each pixel has a 4 bit trim register Maximum trim ~50 mV Calibration equalizes thresholds for all pixels Dispersion (sigma) before and after calibration 12.8 -> 3.6 mV

Masking Masking allows for sub array selection during calibration Register in pixel disables comparator Arbitrary masks are possible

Multi Hit Detection

Multi Hit Detection Timecode Pixel position - y Pixel position - x

PImMS vs PMT

Conventional CCD Image Spatial Imaging Conventional CCD Image PImMS Image

PImMS 2 Larger Array 324 by 324 pixels 23 mm by 23 mm active area 380 Experiments/sec Potential 400,000 measurements per experimental cycle Designed to also work directly after MCP

PImMS 2 Larger array Improved power supply and reference routing Increased on-chip control On-chip bias and reference generation Serial output Extended output bandwidth Reduced pin count for vacuum applications Schedule: Submission this September Testing at the end of the year

Summary Spatial resolution can be used to map a surface (increasing throughput) or to perform velocity mapping providing structural information CMOS and INMAPS enable effective imaging at more than 20 million frames per second! Multiple memories allow simultaneous capture of different mass peaks The PImMS sensor has been proven to operate within the TOF MS system with timing resolution of < 50 ns Second generation sensor will be ready at the beginning of 2012 Other applications, ex. atom probe tomography, fluorescent imaging etc

Questions?

Applications Parallel processing – High throughput sampling

Applications Surface imaging for separate mass peaks Replace scanning with wide-field imaging R.Heeren et al

Fingerprinting of molecules Applications Fingerprinting of molecules mass fingerprinting of human serum albumin (from Wikipedia)