An image acquisition semiconductor film for a high-resolution mass spectrometric imaging system, and a preparation method and an application. The image acquisition semiconductor film for the high-resolution mass spectrometric imaging system is prepared by using the following method: weighing semiconductor nanometer particles, putting the semiconductor nanometer particles into a muffle furnace for burning first, further grinding by using an agate mortar, and uniformly dispersing the semiconductor nanometer particles so as to obtain semiconductor nanometer powder; and finally, pressing the semiconductor nanometer powder in a compressor so as to obtain the semiconductor film. Based on laser activated electron tunnelling as well as photoelectron capture ionization and dissociation, sample molecules are ionized without background interference; the limitation of a conventional MALDI substrate is overcome; the semiconductor film is simple and easy to obtain, is stable in mass spectrometric signal, has a uniform and smooth surface, generates no background interference, and can be used for fingerprint analyzing and animal and plant tissue slice analysis; and the semiconductor film is particularly suitable for accurate mass spectrometric imaging of small molecular substances, so that quality control and industrialization can be performed conveniently.

A method of determining the structure of a macromolecular assembly (MMA) comprises the steps of (a) generating precursor ions of an MMA species to be investigated; (b) transporting the MMA precursor ions to a fragmentation zone; (c) carrying out pulsed fragmentation of the MMA precursor ions in the fragmentation zone; (d) for a first plurality of MMA precursor ions, detesting both a spatial distribution of the resultant MMA fragment ions, and an m/z distribution of the MMA fragment ions; (e) analyzing the spatial and m/z distributions of fragment ions formed from the said first plurality of precursor ions of the MMA species to be investigated, to determine the relative positions of those fragment ions within the structure of the precursor MMA; and (f) reconstructing the three dimensional (3D) structure of the MMA from the analysis of the spatial and m/z distributions of fragment ions.

A method for in-situ joint nanoscale three-dimensional imaging and chemical analysis of a sample. A single charged particle beam device is used for generating a sequence of two-dimensional nanoscale images of the sample, and for sputtering secondary ions from the sample. which are analysed using a secondary ion mass spectrometry device. The two-dimensional images are combined into a three-dimensional volume representation of the sample, the data of which is combined with the results of the chemical analysis.

A method is disclosed comprising providing a biological sample on a swab, directing a spray of charged droplets onto a surface of the swab in order to generate a plurality of analyte ions, and analysing the analyte ions.

A method is disclosed comprising providing a biological sample on a swab, directing a spray of charged droplets onto a surface of the swab in order to generate a plurality of analyte ions, and analysing the analyte ions.

The present invention relates to the high resolution imaging of samples using imaging mass spectrometry (IMS) and to the imaging of biological samples by imaging mass cytometry (IMCTM) in which labelling atoms are detected by IMS. LA-ICP-MS (a form of IMS in which the sample is ablated by a laser, the ablated material is then ionised in an inductively coupled plasma before the ions are detected by mass spectrometry) has been used for analysis of various substances, such as mineral analysis of geological samples, analysis of archaeological samples, and imaging of biological substances. However, traditional LA-ICP-MS systems and methods may not provide high resolution. Described herein are methods and systems for high resolution IMS and IMC.

A primary ion source subassembly for use with a secondary ion mass spectrometer may include a unitary graphite ionizer tube and reservoir base. A primary ion source may include a capillary insert defining an ionizer aperture. An ionizer aperture may be centrally arranged in an outwardly protruding conical or frustoconical surface, and may be overlaid with a refractory metal coating or sheath. Parameters including ionizer surface shape, ionizer materials, ionizer temperature, and beam stop plate orifice geometry may be manipulated to eliminate ghost images. A graphite tube gasket with a dual tapered surface may promote sealing of a source material cavity.

Disclosed herein is a method of generating a high resolution image of a cellular sample, the method including i) labeling a cellular sample with at least one mass tag, thereby producing a labeled sample in which a biological feature of interest is associated with the at least one mass tag, ii) scanning the sample with a continuous or near-continuous primary ion beam to generate sputtered secondary ions and sputtered neutral species, iii) photoionizing the sputtered neutrals to generate ionized neutral species, wherein the sputtered neutrals are photoionized at a site that is proximal to their source on the sample, iv) detecting the ionized neutral species by mass spectrometry, thereby obtaining spatially addressed measurements of the abundance of the at least one mass tag across an area of the sample, and v) producing an image of the sample using the measurements. A system for performing the method is also provided.

A extreme ultraviolet (EUV) imaging spectrometer includes: a radiation source to: produce EUV radiation; subject a sample to the EUV radiation; photoionize a plurality of atoms of the sample; and form photoions from the atoms subject to photoionization by the EUV radiation, the photoions being field evaporated from the sample in response to the sample being subjected to the EUV radiation; and an ion detector to detect the photoions: as a function of a time-of-arrival of the photoions at the ion detector after the sample is subjected to the EUV radiation; or as a function of a position of the photoions at the ion detector.

An imaging mass spectrometer includes: a storage configured to acquire and store data constituting a first imaging graphic indicating an ion intensity distribution in a specific one or plurality of m/z or m/z ranges based on data obtained by mass spectrometry for a sample; a Raman imaging data acquisition unit configured to acquire and store data constituting one or plurality of second imaging graphics obtained by Raman analysis that is a type different from mass spectrometry for the sample; a signal intensity normalization processor configured to perform data conversion processing of normalizing signal intensity in one or plurality of first and second imaging graphics; an adjustment processor configured to perform data processing of aligning spatial resolutions of the one or plurality of first and second imaging graphics; and a statistical analysis processor configured to execute statistical analysis processing on images and to classify the first and second imaging graphics.