Rapid, Parallel Imaging in Surface Chemistry and Biochemistry

Lead Research Organisation: University of Oxford
Department Name: Oxford Physics

Abstract

Spatial imaging mass spectrometry is an analytical technique of growing importance, with a wide range of exciting applications ranging from forensics, tissue sampling, to parallel, high throughput chemical analysis, and is increasingly being applied to the characterization of biological samples. Spatial imaging MS is usually performed in one of two ways, microprobe or microscope mode. In the former, microprobe mode, an ionization source, such as a stream of ions or laser radiation, are focused to a small point on the sample and a mass spectrum is recorded at that precise location. If an ion beam is employed, the technique is usually referred to as secondary ion mass spectrometry, or SIMS. The sample or the ion source is then moved to a new position, and the process repeated until an entire spatially resolved mass spectrum is built up. By contrast, in microscope mode the entire surface is ionized, usually with an intense pulse of laser radiation, and the ions are typically recorded on a two-dimensional detector. Application of fast imaging sensors, with tens of nanosecond timing resolution, to microscope mode mass spectrometric imaging will allow the spatial imaging of all mass peaks in each experimental cycle. As all fragments can be detected simultaneously, far fewer laser shots and acquisition cycles are required for a full set of data to be acquired. A smaller amount of sample is required, samples suffer less degradation, and overall collection times are reduced.
Our proof-of-concept experiments in this area have yielded extremely promising results, and we are currently working to improve our spatial and mass resolution, and sample preparation techniques. SAI, a UK manufacturer of matrix-assisted laser desorption/ionization (MALDI) instruments, is very keen to collaborate on this aspect of the project, providing a specially modified commercial MALDI spectrometer, LaserToF LT2Plus, on which the fast imaging sensors can be tested. In the new instrument, the positions of release of the various molecular ions will be preserved and faithfully mapped onto a position sensitive detector. Their molecular weights can then be calculated from the time of flight of the various molecular ions. The spatial resolution of the instrument will be determined by a combination of the spherical aberration in the image forming electrostatic lens, the pore size of the ion detector, and the pixel size of the imaging sensor, and could in principle achieve 0.25 microns.
A number of established markets would benefit from this improvement in the measurement technology, in particular in the biochip testing industry. Biochips have been developed for high throughput analysis, and, in the case of reverse phase protein micro-arrays, some 500 samples are typically spotted in an area of less than five square millimetres. They are currently read sequentially, employing florescence or colorimetry techniques, which is costly and could be insufficiently sensitive. The proposed development will dramatically improve parallel measurements using biochip technology, yielding much faster analysis times and higher precision, whilst at the same time elimination the need for expensive photo-chemicals.

Publications

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Vallance C (2014) Fast sensors for time-of-flight imaging applications. in Physical chemistry chemical physics : PCCP

 
Title Post extraction inversion slice imaging for 3D velocity map imaging experiments 
Description An experimental configuration for velocity map ion imaging experiments is presented, in which a pulsed voltage defocusses the ion Newton sphere along the time-of-flight axis. This significantly spreads the times-of-flight for ions with the same mass-to-charge ratio, allowing for either sliced or three-dimensional velocity imaging with high slicing resolution along the time-of-flight axis. The technique is coupled to an event-triggered, position-sensitive sensor, enabling full three-dimensional Newton sphere imaging at high count rates, with significantly improved slicing resolution (~1-2%) compared to previous DC slicing approaches. Good slice imaging conditions can be brought about at relatively high extraction voltages, circumventing issues regarding image size, stray fields, and poor detection efficiency when operating at low extraction voltages. The method, termed Post Extraction Inversion Slice Imaging (PEISI) was optimised through ion trajectory simulations and experimentally verified on the well-studied photodissociation of OCS at around 230 nm. We demonstrate that this approach is suitable for recording full 3D angular distributions of systems lacking an axis of cylindrical symmetry in the detector plane, where conventional image inversion techniques are invalid. This method could be useful in a range of systems lacking cylindrical symmetry, including studies into angular momentum polarisation and bimolecular scattering. 
Type Of Art Film/Video/Animation 
Year Produced 2020 
URL https://tandf.figshare.com/articles/figure/Post_extraction_inversion_slice_imaging_for_3D_velocity_m...
 
Title Post extraction inversion slice imaging for 3D velocity map imaging experiments 
Description An experimental configuration for velocity map ion imaging experiments is presented, in which a pulsed voltage defocusses the ion Newton sphere along the time-of-flight axis. This significantly spreads the times-of-flight for ions with the same mass-to-charge ratio, allowing for either sliced or three-dimensional velocity imaging with high slicing resolution along the time-of-flight axis. The technique is coupled to an event-triggered, position-sensitive sensor, enabling full three-dimensional Newton sphere imaging at high count rates, with significantly improved slicing resolution (~1-2%) compared to previous DC slicing approaches. Good slice imaging conditions can be brought about at relatively high extraction voltages, circumventing issues regarding image size, stray fields, and poor detection efficiency when operating at low extraction voltages. The method, termed Post Extraction Inversion Slice Imaging (PEISI) was optimised through ion trajectory simulations and experimentally verified on the well-studied photodissociation of OCS at around 230 nm. We demonstrate that this approach is suitable for recording full 3D angular distributions of systems lacking an axis of cylindrical symmetry in the detector plane, where conventional image inversion techniques are invalid. This method could be useful in a range of systems lacking cylindrical symmetry, including studies into angular momentum polarisation and bimolecular scattering. 
Type Of Art Film/Video/Animation 
Year Produced 2020 
URL https://tandf.figshare.com/articles/figure/Post_extraction_inversion_slice_imaging_for_3D_velocity_m...
 
Description effectively a fast camera.
Exploitation Route in chemistry research
Sectors Other