1. Andrei Nomerotski 1 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

2. Andrei Nomerotski 2 Outline  PImMS: Pixel Imaging Mass Spectrometry  Proof of concept experiments  First results with PImMS1 Sensor

3. Andrei Nomerotski 3 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

4. Andrei Nomerotski 4 Ion Imaging Fix a mass peak Measure full scattering distribution of fragment ions Sensitive to fragmentation process S atom ion images for OCS photodissociation at 248nm

5. Andrei Nomerotski 5 Visible Light vs Direct Detection Visible light detection MCP Phosphor pixel sensor Electron detection MCP pixel sensor E Typically use visible light but direct detection of electrons after MCP is possible

6. Andrei Nomerotski 6 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

7. Andrei Nomerotski 7 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

8. Andrei Nomerotski 8 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

9. Andrei Nomerotski 9 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. CH 3 S 2 CH 3 3: M. Brouard, E.K. Campbell, A.J. Johnsen, C. Vallance, W.H. Yuen, and A. Nomerotski, Rev. Sci. Instrum. 79, 123115, (2008)

10. Andrei Nomerotski 10 Possible applications (1)  Surface imaging for separate mass peaks  Replace scanning with wide-field imaging R.Heeren et al

11. Andrei Nomerotski 11 Possible applications (2)  Parallel processing– high throughput sampling

12. Andrei Nomerotski 12 Possible applications (3)  Fingerprinting of molecules mass fingerprinting of human serum albumin (from Wikipedia)

13. Andrei Nomerotski 13 PImMS Sensor: Imager with time stamping

14. Andrei Nomerotski 14  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

15. Andrei Nomerotski 15 Spin-off of ILC Sensor R&D  PImMS and International Linear Collider have similar data structure PImMS : 0.2 ms duration @ 20 Hz ILC: 1.0 ms duration @ 5 Hz 337 ns 2820x 0.2 s 0.95 ms time 0.05 s 0.2 ms PImMS ILC

16. Andrei Nomerotski 16  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

17. Andrei Nomerotski 17 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

18. Andrei Nomerotski 18 Ion Intensity Simulations  Important to be sensitive to heavy fragments  Simulated probability to have N hits/pixel  Four buffers allow higher intensity

19. Andrei Nomerotski 19 The PImMS Pixel Charge Collection Diodes Preamplifier Shaper Comparator

20. Andrei Nomerotski 20 PImMS Pixel

21. Andrei Nomerotski 21 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)

22. Andrei Nomerotski 22 PImMS1 Sensor 7.2 mm

23. Andrei Nomerotski 23 PImMS Camera System

24. Andrei Nomerotski 24 PImMS Testing PImMS Camera

25. Andrei Nomerotski 25 PImMS Camera  read out over a USB cable.

26. Andrei Nomerotski 26 First Analogue Image

27. Andrei Nomerotski 27 First Digital Readout Image Two laser pulses separated by 300 ns

28. Andrei Nomerotski 28 PImMS1 Digital Readout Five laser pulses, each at a different time

29. Andrei Nomerotski 29 Digital Readout – 3D interpretation Timecode Pixel position - x Pixel position - y

30. Andrei Nomerotski 30 Pixel Masking  Arbitrary masks are possible  Three laser pulses separated in time

31. Andrei Nomerotski 31 Sensor Characterization  Photon Transfer Curve Poisson distribution of signal  Noise = sqrt(Signal)  absolute calibration Full well capacity 24ke  Quantum efficiency: 8-9% for visible light, max @ 470 nm Front illuminated sensor Slope = 0.5

32. Andrei Nomerotski 32 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)

33. Andrei Nomerotski 33 TOF MS in Oxford Chemistry PImMS sensor is mounted here

34. Andrei Nomerotski 34 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

35. Andrei Nomerotski 35 One of the two PImMS peaks  PImMS : 50 ns per timecode  FWHM ≈ 100ns in both

36. Andrei Nomerotski 36 Ions Detected vs MCP Voltage # of ions/cycle MCP voltage (kV)

37. Andrei Nomerotski 37 FWHM vs MCP Voltage FWHM (us) MCP voltage (kV) 100 ns

38. Andrei Nomerotski 38 Spatial mappingVelocity mapping Ion Imaging Modes

39. Andrei Nomerotski 39 Potential applications: forensics and tissue analysis Ion image Microscope image (Trypan blue) Spatial Mode Imaging

40. Andrei Nomerotski 40 Conventional CCD camera image oriented 45 o to PImMS First PImMS spatial imaging results

41. Andrei Nomerotski 41 Spatial map imaging First PImMS spatial imaging results Conventional cameraPImMS sensor Spatial Imaging

42. Andrei Nomerotski 42 Spatial map imaging First PImMS spatial imaging results: four registers   Time of flight Intensity  Multi-hit Capabilities

43. Andrei Nomerotski 43 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 directions Faster: 10  1 ns Larger: wafer scale sensors More sensitive: backthinned Intensity information: ToT Build-in ADC

44. Andrei Nomerotski 44 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