The present disclosure generally relates in certain embodiments to the creation of ionized molecules, e.g., for detection in a mass spectrometer, or for other uses such as lithography, sputtering machines, propulsion etc. Some embodiments include an ion source comprising a capillary tip that may allow for direct ion evaporation of samples with an applied electric field. In some cases, the tip may have an opening with a cross-section less than 100 nm. In addition, certain aspects are directed to using a capillary tip that allow for detection of samples (e.g. amino acids), and in some cases allows for sequencing. For instance, some embodiments are directed to allowing single ions and ionic clusters to be evaporated at a high rate directly from aqueous samples in a mass spectrometer. Other aspects are directed to methods for making or using such ionized molecules, methods for making or using devices to create such ionized molecules, or the like.

An apparatus for detecting a substance comprising a direct analysis in real time apparatus; a neutral excluder; a mass spectrometer; and a vessel in. The apparatus may also comprise a separator, a gas, an alcohol, a filter, and a pump. The apparatus may also comprise electrodes in communication with the direct analysis in real time apparatus and the neutral excluder. A method for detecting a substance comprising contacting the substance with a direct analysis in real time apparatus ion stream; forming an ion and a neutral particle; flowing the ion and the neutral particle into a neutral excluder; contacting the ion and the neutral particle with a gas; and flowing the ion into a mass spectrometer.

A method of analyzing and/or sorting selected cells or other biological components, for example for cell-based therapy, includes sampling a sample with an open end of a probe to obtain a fluid stream with the sample in it. The probe with the open end also has a fluid supply to convey fluid to the open end, and a fluid exhaust to convey the fluid stream away from the open end. The method then includes conveying the fluid stream to a flow cytometer and analyzing the fluid stream by flow cytometry; and/or separating it into at least two components. An apparatus with the probe connected to the flow cytometer may support this method. The method can provide for sampling of multiple samples efficiently, in particular to select cells for cell-based therapies.

Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which the flow of desorption solvent within a sampling probe fluidly coupled to an ion source can be selectively controlled such that one or more analyte species can be desorbed from a sample substrate inserted within the sampling probe within a decreased volume of desorption solvent for subsequently delivery to the ion source. In various aspects, sensitivity can be increased due to higher desorption efficiency (e.g., due to increased desorption time) and/or decreased dilution of the desorbed analytes. The methods and systems described herein can additionally or alternatively provide for the selective control of the flow rate of the desorption solvent within the sampling interface so as to enable additional processing steps to occur within the sampling probe (e.g., multiple samplings, reactions).

A system for sampling a sample material includes a probe which can have an outer probe housing with an open end. A liquid supply conduit within the housing has an outlet positioned to deliver liquid to the open end of the housing. The liquid supply conduit can be connectable to a liquid supply for delivering liquid at a first volumetric flow rate to the open end of the housing. A liquid exhaust conduit within the housing is provided for removing liquid from the open end of the housing. A liquid exhaust system can be provided for removing liquid from the liquid exhaust conduit at a second volumetric flow rate. A droplet dispenser can dispense drops of a sample or a sample-containing solvent into the open end of the housing. A sensor and a processor can be provided to monitor and maintain a liquid dome present at the open end.

The invention generally relates to ion generation using modified wetted porous materials. In certain aspects, the invention generally relates to systems and methods for ion generation using a wetted porous substrate that substantially prevents diffusion of sample into the substrate. In other aspects, the invention generally relate to ion generation using a wetted porous material and a drying agent. In other aspects, the invention generally relates to ion generation using a modified wetted porous substrate in which at least a portion of the porous substrate includes a material that modifies an interaction between a sample and the substrate.

Method and devices are provided for assessing tissue samples from a plurality of tissue sites in a subject using molecular analysis. In certain aspects, devices of the embodiments allow for minimally invasive collection of liquid tissue samples and delivery of the samples for mass spectrometry analysis.

Sampling probes and interfaces for mass spectrometry systems and methods are described to analyze a composition of a substance. The system includes a liquid reservoir containing solvent; a gas reservoir containing nebulizer gas; a conduit that is in fluid communication with the liquid reservoir, the conduit comprising a first and second portion and a junction portion, the first and second portion being joined at the junction portion, and defining an angle therebetween at the junction and the junction portion contains an aperture that is open to the atmosphere. A nebulizer conduit that is co-axial and partially surrounds the second portion and completely surrounds an end of the second portion can also be present, the nebulizer conduit being fluidly connected to the gas reservoir and that allows a gas to flow from the gas reservoir over an external surface of the second portion and the end of the second portion.

A system and method for sampling a sample material includes a device for directing sample into a capture probe. The device for supplying sample material to the probe can be a device for radiating energy to the surface to eject sample from the sample material. A probe includes an outer probe housing having an open end. A liquid supply conduit has an outlet positioned to deliver liquid to the open end. An exhaust conduit removes liquid from the open end of the housing. The liquid supply conduit can be connectable to a liquid supply for delivering liquid at a first volumetric flow rate to the open end of the housing. A liquid exhaust system can be in fluid connection with the liquid exhaust conduit for removing liquid from the liquid exhaust conduit at a second volumetric flow rate such that gas with sample is withdrawn with the liquid.

An optimization control system may receive mass spectra of ions emitted from an ionization emitter toward an inlet of a mass spectrometer and control, based on the mass spectra, an automated motion system to adjust a position of the emitter relative to the inlet.