The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryo-electron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.

Packed-tip electrospray ionization (ESI) emitters for mass spectrometry are described. In one aspect an ESI emitter stores a first type of particle. A liquid chromatography (LC) column is coupled with the emitter via a junction. The LC column stores a different type of particle than the ESI emitter to facilitate better chromatographic and ESI performance.

A method of ionising a sample is disclosed comprising nebulising a sample which includes first biomolecules such as bovine insulin comprising one or more disulphide (S—S) bonds. A stream of droplet or charged droplets comprising one or more disulphide (S—S) bonds is directed so as to impact upon a target (106) or electrode so as to cause the breaking of a portion of the disulphide bonds. Alternatively, charged droplets may pass through an electric field region determined by an electrode (106) arranged downstream of a nebuliser or electrospray probe and an ion inlet (104) of a mass spectrometer so as to cause the breaking of a portion of the disulphide bonds.

The invention generally relates to apparatuses for focusing ions at or above ambient pressure and methods of use thereof. In certain embodiments, the invention provides an apparatus for focusing ions that includes an electrode having a cavity, at least one inlet within the electrode configured to operatively couple with an ionization source, such that discharge generated by the ionization source is injected into the cavity of the electrode, and an outlet. The cavity in the electrode is shaped such that upon application of voltage to the electrode, ions within the cavity are focused and directed to the outlet, which is positioned such that a proximal end of the outlet receives the focused ions and a distal end of the outlet is open to ambient pressure.

The present invention comprises novel methods of continuously monitoring the performance of an atmospheric pressure ionization (API) system. The methods of the invention allow for improved quality monitoring of the processes that leads to the formation of ions at atmospheric pressure. The methods of the invention further allow for continuously monitoring for the quality of the ion formation process in API without the addition of extraneous material (such as labelled compounds or control known compounds) to the system being monitored.

A device that produces charged droplets whose composition is optimized for the creation of ions by electro spray composed of: a transport device that is operative to transfer sample components from a liquid sample to a processing chamber, a flowing stream of liquid through the processing chamber into which the samples are deposited, a controller mechanism operative to control the amount of sample transferred, a transport tube through which the flowing liquid containing the sample is directed to an electro spray emitter with a high electric field at the exit, a flow of expanding gas surrounding the electro spray emitter creating a pressure drop at the exit, and, a mass spectrometer for measuring the number of ions produced from the charged droplets emanating from the emitter; wherein the dilution of the sample in the processing chamber and transport fluid is from 100 to 10,000-fold.

Methods and apparatuses for the identification and/or characterization of properties of a sample using mass spectrometry. The method involves using a measured spectrum of data from a sample taken with a mass spectrometer, deconvoluting the measured spectrum of data by applying parsimony weighting to minimize the number of charge states based on one or more of: the number of intense peaks in the mass spectrum; the number of harmonic relationships (e.g., masses in small integer ratios); and the number of off-by-one relationships (e.g., m/z bins with high probability for two adjacent charges). Thus, the underlying m/z spectrum may be inferred from the family of plausible deconvoluted spectra determined by applying parsimony and the inferred m/z spectrum may be used to identify and/or characterize the sample.

The probe drive unit (21) collects a sample (8) at the tip of the probe (6) by lowering and raising the probe (6) under the control of the control unit (25). After that, the high voltage generating unit (20) applies a high voltage whose voltage value increases in a slope shape to the probe (6), and meanwhile, the mass spectrometry unit behind the capillary tube (10) performs product ion scan measurements on the two-step probe voltage, and the mass spectrum data obtained in each measurement is stored in the first and the second probe voltage corresponding data storage units (301 and 302). When the ionization efficiencies of the plurality of types of components contained in the sample (8) have a probe voltage dependence, ion peaks derived from different types of components appear in the two mass spectra. Thus, a plurality of types of components contained in the sample can be roughly separated, and the identification performance based on the mass spectrum and the quantitative performance based on the chromatogram can be improved.

A mass spectrometry device and process may include the use of helium as a nebulizing gas to provide increased signal strength in mass spectrum results. This may be implemented in, for example, ESI-based and/or DESI-based systems and/or processes. The process may be implemented utilizing a unique ionization source and, optionally, other unique components. One or more process parameters may be adjusted to provide increased signal intensity in mass spectrum results.

Disclosed is an analysis method for ionizing a sample arranged in an ionizing unit of an analysis device in a state where the sample is in contact with a solvent to perform analyzation. The method includes a first mass analysis step of obtaining first measurement data by causing the solvent not in contact with the sample to adhere to a probe, and then performing mass analysis to the solvent adhering to the probe, a second mass analysis step, performed subsequently to the first mass analysis step, of obtaining second measurement data by causing the sample in the solvent to adhere to the probe or causing the sample adhering to the probe to be brought into contact with the solvent, and then performing mass analysis to the solvent and the sample adhering to the probe, and a measurement data generation step of generating measurement data, associated with the sample, based on the first measurement data and the second measurement data.