Fast, high resolution mass spectrometry imaging using a medipix pixelated detector

Abstract

In mass spectrometry imaging, spatial resolution is pushed to its limits with the use of ion microscope mass spectrometric imaging systems. An ion microscope magnifies and then projects the original spatial distribution of ions from a sample surface onto a position-sensitive detector, while retaining time-of-flight mass separation capabilities. Here, a new type of position-sensitive detector based on a chevron microchannel plate stack in combination with a 512 ϫ 512 complementary metal-oxide-semiconductor based pixel detector is coupled to an ion microscope. Spatial resolving power better than 6 m is demonstrated by secondary ion mass spectrometry and 8 -10 m spatial resolving power is achieved with laser desorption ionization. A detailed evaluation of key performance criteria such as spatial resolution, acquisition speed, and data handling is presented. (J Am Soc Mass Spectrom 2010, 21, 2023-2030 © 2010 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry M ass spectrometry imaging (MSI) [1-3] measurements allow the visualization of the spatial structure and identification of the molecular masses from complex surfaces. High spatial resolution is accomplished with ion-microscope mass spectrometers, where ions are extracted from the sample surface and projected onto a position-sensitive detector. A spatial resolution better than 4 m has been reported using UV/IR laser surface probes in matrix assisted laser desorption ionization (MALDI) [4 -8]. A pulsed primary ion beam as a surface probe can achieve higher spatial resolving powers (1 m) [9,10]. The spatial resolution can be further improved by using a more focused primary ion/laser desorption ionization surface probe. However, fragmentation of the surface molecules and long measurement times are undesired side effects of decreasing the surface probe area. For instance, at a 2 ϫ 2 m pixel size (4 m lateral resolution) and a sample size of 1 ϫ 1 mm, a typical measurement comprises 250,000 measurement points and can last several hours. An alternate approach to increase the spatial resolution is the use of microscope mode MSI. In the microscope mode, surface molecules are desorbed and ionized over a large sample area, typically 200 -300 m in diameter. An ion microscope employs ion optics to project the ionized surface compounds onto a position-sensitive detector while magnifying the image and retaining the spatial information defined by the sample surface. With a field of view of 200 ϫ 200 m and a sample size of 1 ϫ 1 mm, a microscope mode imaging experiment involves 25 measurement points and retains the 4 m lateral resolution given the corresponding ion optical magnification factor. The ion optical magnification allows high-resolution images to be obtained independent of the ionization source. Microscope mode MSI enables fast, highresolution large area imaging provided that an adequate, i.e., fast and position-sensitive, detector is used to record high quality molecular images [4].Position-sensitive detectors most commonly used for microsc...

Microscope mode secondary ion mass spectrometry imaging with a Timepix detector

“…The Timepix spectral mass resolution is slightly less, due to the relatively long clock cycles of the detector (10 ns, detailed evaluation in Ref. 26). Since the ion mass is determined from its time-of-flight in TOF-SIMS measurements, the minimum clock cycle length determines the obtainable mass resolution.…”

“…The main advantage of these detector systems is the capability to obtain position- 26 and timeresolved 27-29 ion images. The small pixel size of such a detector (here, 55 μm), combined with a high quality ion microscope mass spectrometer with a good magnification factor (typically up to 100×), make these detectors very well-suited for high spatial resolution microscope mode imaging, i.e., a detector pixel (with a physical dimension of 55 μm × 55 μm) probes 550 nm on the sample surface at a magnification factor of 100×.…”

“…The advantages of a pixelated detector have been previously demonstrated using a MALDI ion microscope. 26,28,29 However, this technology and its benefits have not yet been applied for SIMS imaging.…”

Photon counting phosphorescence lifetime imaging with TimepixCam

“…This readout chip, after the addition of a bump-bonded silicon sensor, has been previously used for the detection of charged particles and X-rays and applied, for example, to ion imaging. 24,25 For the ion detection, some measurements used bare Timepix chips placed in the vacuum behind an MCP to collect the electrons from the MCP directly. The chip was also used for the detection of visible light in a specialized vacuum device with a photocathode and MCP, [26][27][28] where metal pads of the Timepix pixels were directly sensing electrons after the MCP.…”

IonCCD Detector for Miniature Sector-Field Mass Spectrometer: Investigation of Peak Shape and Detector Surface Artifacts Induced by keV Ion Detection

“…A detector family that is rapidly gaining importance employs the emerging technology of pixilated array detectors such as Medipix/Timepix (developed by CERN and the Nikhef Institute in Amsterdam) for X-ray detection [27], velocity mapping imaging [28], and for mass spectrometric applications [29].…”