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.

The present invention relates to improving the ability of a hyphenated instrument to analyze a sample benefiting from having the first instrument's analysis of the same sample. A fast switching mechanism can be used as the interface between an ion mobility spectrometer (IMS) and a mass spectrometer (MS) such that the obtained IMS spectrum is converted into a timing diagram that controls the vacuum inlet's size dynamically during analysis of a neutral and/or charged chemical and/or biological species such that a smaller pumping system can be used. In various operational modes of the IMS-MS device, mobility-separated ions are allowed to pass through an ion gate and the vacuum inlet for mass analysis.

Imaging by cryo-electron microscopy (cryo-EM) requires that a sample be encased in an amorphous solid, such as amorphous ice. In current cryo-EM preparation systems, once the sample has been deposited on an EM grid and coated in the amorphous solid, the EM grid must be removed from vacuum and then transferred into the vacuum of the cryo-EM system. As a result, samples deposited on the grid are exposed to damage and contamination. The present invention provides improved EM grid handling systems and devices compatible with advanced cryo-EM sample preparation techniques and which reduce or eliminate exposure of the sample on the grid to atmosphere and elevated temperatures. These methods and devices will also significantly reduce handling time and complexities associated with cryo-EM sample preparation.

Slide analysis a gripper with three sensors for controlling a slide grip sequence and at least one rotatable carousel with a slide receiving channel. The systems also include a robot with a robot arm that holds a slide gripper residing inside the housing in communication with the rotatable carousel. The systems also include a load lock chamber and a door sealably coupled to the second end portion and an acquisition vacuum chamber with an X-Y stage and a slide holder with a vacuum seal.

Exemplary embodiments may deploy a valve that introduces a sample of a calibrant coaxially with flow exiting a source of a mobile phase flow, such as a liquid chromatography (LC) column, on a path to an ion source for the mass spectrometer (MS). The valve may be positioned remotely on a branch that has a junction with the path leading form the source of the mobile phase flow to the ion source. Alternatively, the valve may be positioned in line on the flow path from the source of the mobile phase flow to the ion source of the MS. A novel five port valve design may be employed. With this valve design, a first position of the valve allows a sample loop for the calibrant to be filled. In a second position, the calibrant is added coaxially to the flow from the source of the mobile phase to the MS. In a third position of the valve, diversion of or infusion to a post-source flow is enabled.

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).

Valve assemblies are described that provide segmented shuttle of liquid into sample vessels and automatic mixing via bubbles in the segmented liquid. A valve assembly includes a first valve member having ports configured to receive a pressurized gas, a first fluid, and a second fluid. The valve assembly also includes a second valve member coupled adjacent to the first valve member. The second valve member comprises a plurality of channels configured to interface with the first valve member. In a first configuration, the first fluid is loaded into an external loop. In the second configuration, the second fluid is eluted from the column into a vial in a segmented stream via bubbles of pressurized gas. Bubbles of gas automatically mix the eluted sample fluid.

Disclosed herein is an apparatus for supplying reagent ions, for example ETD or PTR reagent ions, to a mass spectrometer. The apparatus includes a reagent material reservoir, coupled to a carrier gas supply, which delivers an entrained reagent vapor flow to an inlet of a mixing junction through a first flow restrictor. A control gas flow of carrier gas is delivered to another inlet of the mixing junction via a variable pressure regulator and a second flow restrictor. The outlet of the mixing junction is coupled via a third flow restrictor and a reagent transfer junction to an inlet of an ionizer, such as a glow-discharge ionizer. By dynamic adjustment of the output pressure of the variable pressure regulator, the flow rate of reagent vapor may be controlled over a broad range, even for reagent materials of relatively high volatility.

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.

Certain embodiments of ion interfaces are described that can provide higher sensitivities improved ion transmission and multiple operating modes. In some configurations, the ion interface may comprise a first element and a second element each of which can receive a non-zero voltage. In one configuration, the first element can be a hyperskimmer cone and the second element can be a cylindrical lens. Systems and methods using the interface are also described.