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.

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.

Provided is a time-of-flight mass spectrometer including: an ionization part receiving electron beams to thereby emit ions; a cold electron supply part injecting the electron beams to the ionization part; an ion detection part detecting the ions emitted from the ionization part; and an ion separation part connecting the ionization part and the ion detection part, wherein the cold electron supply part includes a microchannel plate receiving ultraviolet rays to thereby emit the electron beams, the ions emitted from the ionization part pass through the ion separation part to thereby reach the ion detection part, and the ion separation part has a straight tube shape.

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).

Before a sample is pierced with a probe of a PESI ion source, a total ion current is measured under a condition with no voltage applied from a high voltage generator to the probe as well as under a condition with the voltage applied. If the probe is properly attached to the holder, a considerable difference in total ion current occurs between the period with no voltage applied and the period with the voltage applied. By comparison, if the probe is improperly attached, no significant difference in the total ion current occurs between the period with no voltage applied and the period with the voltage applied. Referring to a threshold determined under the normal condition, a probe attachment checker detects an insufficient attachment of the probe by checking the difference in the total ion current, and displays an error message on a display unit if an improper attachment is detected.

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.

Provided is a substrate with a thin film for manufacturing a reflective mask that at least does not adversely affect performance of the reflective mask even when a thin film of a substrate with the thin film such as a reflective mask blank comprises impurities.

A substrate with a thin film comprises: a substrate; and at least one thin film formed on a main surface of the substrate. The thin film comprises a matrix material constituting the thin film and a small-amount material other than the matrix material. When secondary ion intensity emitted from the thin film is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS), a ratio (I.sub.2/I.sub.1) of secondary ion intensity (I.sub.2) of at least one of the small-amount material in the thin film to secondary ion intensity (I.sub.1) of the matrix material is more than 0 and 0.300 or less.

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.