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.

Systems and approaches for semiconductor metrology and surface analysis using Secondary Ion Mass Spectrometry (SIMS) are disclosed. In an example, a secondary ion mass spectrometry (SIMS) system includes a sample stage. A primary ion beam is directed to the sample stage. An extraction lens is directed at the sample stage. The extraction lens is configured to provide a low extraction field for secondary ions emitted from a sample on the sample stage. A magnetic sector spectrograph is coupled to the extraction lens along an optical path of the SIMS system. The magnetic sector spectrograph includes an electrostatic analyzer (ESA) coupled to a magnetic sector analyzer (MSA).

Systems and approaches for semiconductor metrology and surface analysis using Secondary Ion Mass Spectrometry (SIMS) are disclosed. In an example, a secondary ion mass spectrometry (SIMS) system includes a sample stage. A primary ion beam is directed to the sample stage. An extraction lens is directed at the sample stage. The extraction lens is configured to provide a low extraction field for secondary ions emitted from a sample on the sample stage. A magnetic sector spectrograph is coupled to the extraction lens along an optical path of the SIMS system. The magnetic sector spectrograph includes an electrostatic analyzer (ESA) coupled to a magnetic sector analyzer (MSA).

Methods and devices for mass spectrometry are described, specifically the use of nanoparticulate implantation as a matrix for secondary ion and more generally secondary particles. A photon beam source or a nanoparticulate beam source can be used a desorption source or a primary ion/primary particle source.

A method for characterizing a sample combining an X-ray tomography characterization technique and a secondary ionization mass spectrometry characterization technique, includes: a step of providing a tip that includes first and second end surfaces, a first cylindrical region bearing the first end surface and a second region in contact with the first cylindrical region and becoming slimmer towards the second end surface; a step of machining the second region to obtain a sample holder including a flat surface, the flat surface forming an end surface of the sample holder, the area of the flat surface being less than the area of the first end surface; a step of placing the sample on the flat surface of the sample holder; a first step of characterization of the sample using an X-ray characterization technique; a second step of characterization of the sample using a secondary ionization mass spectrometry characterization technique.

A method of analyzing a population of cells is disclosed. In certain embodiments, the method includes i) obtaining an array of cells on a substrate, wherein the cells are labeled with one or more mass tags and are separated from one another, ii) measuring, using secondary ion mass spectrometry (SIMS), the abundance of the one or more mass tags at a plurality of locations occupied by the cells, thereby generating, for each individual cell measured, a set of data, and iii) outputting the set of data for each of the cells analyzed. Also provided herein are systems that find use in performing the subject method. In some embodiments, the system is an automated system for analyzing a population of cells using SIMS.

The disclosure features systems and methods that include: exposing a biological sample to an ion beam that is incident on the sample at a first angle to a plane of the sample by translating a position of the ion beam on the sample in a first direction relative to a projection of a direction of incidence of the ion beam on the sample; after each translation of the ion beam in the first direction, adjusting a focal length of an ion source that generates the ion beam; and measuring and analyzing secondary ions generated from the sample by the ion beam after adjustment of the focal length to determine mass spectral information for the sample, where the sample is labeled with one or more mass tags and the mass spectral information includes populations of the mass tags at locations of the sample.

A method of evaluating a region of a sample that includes a first sub-region and a second sub-region, adjacent to the first sub-region, the region comprising a plurality of sets of vertically-stacked double-layers extending through both the first and second sub-regions with a geometry or orientation of the vertically-stacked double layers in the first sub-region being different than a geometry or orientation of the vertically-stacked double layers in the second region resulting in the first sub-region having a first milling rate and the second sub-region having a second milling rate different than the first milling rate, the method including: milling the region of a sample by scanning a focused ion beam over the region a plurality of iterations in which, for each iteration, the focused ion beam is scanned over the first sub-region and the second sub-region generating secondary electrons and secondary ions from each of the first and second sub-regions; detecting, during the milling, at least one of the generated secondary electrons or the secondary ions; generating, in real-time, an endpoint detection signal from the at least one of detected secondary electrons or secondary ions, the endpoint detection signal including a fast oscillating signal having a first frequency and a slow oscillating signal having a second frequency, slower than the first frequency; analyzing the fast and slow oscillating signals to determine original first and second frequencies of the fast and slow oscillating signals; and estimating, in real-time, a depth of each of the first and second sub-regions based on the determined first and second frequencies.

Machine learning approach can combine mass spectral imaging (MSI) techniques, one with low spatial resolution but intact molecular spectra and the other with nanometer spatial resolution but fragmented molecular signatures, to predict molecular MSI spectra with submicron spatial resolution. The machine learning approach can perform transformations on the spectral image data of the two MSI techniques to reduce dimensionality, and using a correlation technique, find relationships between the transformed spectral image data. The determined relationships can be used to generate MSI spectra of desired resolution.