Waters Technologies Corporation

Waters Investments Limited

Waters Technologies Ireland Limited

Steven J Ciavarini

Scott Geromanos

Joshua A Shreve

Marc Victor Gorenstein

Robert J Dumas

Curt Devlin

Daniel Golick

Stanley P Pensak, Jr

Keith Fadgen

Paul B Keenan

John Lamoureux

Miguel Soares

John Heden

Joseph A Luongo

Michael R Jackson

James Ian Langridge

John Angelosanto

Christopher Seith

Weibin Chen

Hongji Liu

Jeffrey W Finch

Frank Rubino

John Leason

Kara O'Donnell

Robert Tacconi

Patrick Brophy

Stephane Houel

Brad J Williams

Michael J Nold

Marisa Gioioso

Ovidiu Pop

Joshura A Shreve

Frank A Rubino

Robert Q Tacconi

Scott J Geromanos

Exemplary embodiments provide methods, mediums, and systems for analyzing spectrometry and/or chromatography data, and in particular to techniques to improve the reproducibility of results of spectrographic and/or chromatographic experiments. For example, some embodiments provide techniques for normalizing mass spectrometry (MS) and/or liquid chromatography (LC) data across different experimental devices, allowing data from different cohorts to be directly compared. To this end, exemplary embodiments provide a reliable, reproducible target library usable across different platforms, laboratories, and users. One embodiment leverages statistical techniques to select experimental parameters configured to reduce or minimize the chance of misidentifying a target molecule. Another embodiment leverages the law of large numbers to produce a composite product ion spectrum usable across different experiments. The composite product ion spectrum allows regression curves to be generated, where the regression curves can be used to normalize an experimental mass spectrum.

Methods, mediums, and systems to compare data within and between cohorts

Techniques and apparatus for generating encoded representations of compounds are described. In one embodiment, for example, an apparatus may include at least one memory, and logic coupled to the at least one memory. The logic may be configured receive analytical information associated with at least one compound, generate at least one encoded representation of the at least one compound, the encoded representation comprising at least one segment representing at least one property of the at least one compound using a plurality of symbols. Other embodiments are described.

Techniques for generating encoded representations of compounds

A method of mass spectrometry is disclosed comprising mass analysing an eluent from a chromatography device and obtaining parent ion data sets and corresponding product ion data sets, and determining whether, in a first product ion data set, one or more product ions are present that are related to one or more parent ions in a corresponding first parent ion data set, based on the mass or mass to charge ratio and/or intensity of the one or more product ions and the one or more parent ions. If it is determined that the one or more product ions are present, the method further comprises removing the one or more product ions from one or more second product ion data sets to produce one or more second modified product ion data sets and/or removing ions other than the one or more product ions from the first product ion data set to produce a first modified product ion data set.

Method to remove ion interferences

A method of analyzing a complex sample includes performing a sequential chromatographic-IMS-MS analysis of a sample to obtain a plurality of experimental mass spectra having isotopic clusters, wherein each spectrum of the plurality of spectra is associated with a chromatographic retention time and an ion-mobility drift time. The method also includes calculating a model isotopic cluster of a precursor or product ion associated with a candidate compound in the sample, in correspondence to the natural isotopic-abundance ratios of elements composing the compound. The method further includes comparing peaks of the model isotopic cluster to corresponding peaks of an isotopic cluster of one of the experimental mass spectra to extract one or more saturated or interfered peaks of the experimental isotopic cluster, wherein at least one of the peaks of the experimental isotopic cluster is un-saturated and un-interfered.

Method and an apparatus for analyzing a complex sample

Techniques for performing data acquisition and analysis are described. A multi-mode acquisition strategy may be performed which iteratively selects mass isolation windows of different sizes in different scan cycles to acquire experimental data. The mass isolation windows selected may provide for acquiring elevated energy scan data for a defined set of m/z values. Single scan data analysis may be performed. Data analysis may include forming precursor charge clusters, chaining precursor charge clusters having the same mass to charge ratio to form peaks profiles, and using criteria to align precursor and product ions of the experimental data. Unsupervised and supervised clustering may be performed using a database and composite ion spectra formed from experimental data. Also described are a small molecule acquisition enhancement and additional techniques applicable for biopharmaceutical and other applications.

Techniques for processing of mass spectral data

Exemplary embodiments of the present disclosure are directed to manipulating pressure-related hysteresis in a pressurized flow system by setting the pressure of the system to a predetermined location in the hysteresis band to advantageously minimize an effect of the pressure related hysteresis on the pressure of the system or to advantageously benefit from the effects of the hysteresis on the pressure of the system.

Pressure related hysteresis manipulation in a pressurized flow system

Techniques and apparatus for analyzing mass spectrometry data are described. In one embodiment, for example, an apparatus may include logic to access a product ion data set generated via mass analyzing a sample comprising a target precursor, access precursor composition information for elements of the target precursor that includes nominal mass and mass defect information, determine nominal mass (NM)-mass defect (MD) relationship information for ion fragments associated with the target precursor based on the precursor composition information, determine one or more fragment upper boundaries and one or more fragment lower boundaries, extract candidate ion fragments from the ion fragments via applying the one or more fragment upper boundaries and the one or more fragment lower boundaries to the NM-MD relationship information, and determine target ion fragments from the plurality of candidate ion fragments based on fragmentation efficiency information associated with the candidate ion fragments. Other embodiments are described and claimed.

Techniques for mass analyzing a complex sample based on nominal mass and mass defect information

A method of mass spectrometry comprises ionising a sample eluting from a separation device in order to generate a plurality of parent ions. Multiple cycles of operation are performed as the sample elutes from the separation device. Each cycle of operation comprises mass analysing the parent ions to obtain parent ion mass spectral data, and mass analysing fragment or product ions derived from the parent ion to obtain fragment or product ion mass spectral data. Each cycle of operation also comprises mass analysing fragment or product ions derived from parent ions having mass to charge ratios within a first range to obtain first fragment or product ion mass spectral data, and mass analysing fragment or product ions derived from parent ions having mass to charge ratios within a second different range to obtain second fragment or product ion mass spectral data. The method can provide a hybrid data independent acquisition (DIA) and data dependent acquisition (DDA) approach.

Analysis of complex biological matrices through targeting and advanced precursor and product ion alignment

A method of mass spectrometry comprises ionizing a sample eluting from a separation device in order to generate a plurality of parent ions. The method further comprises generating a target list of ions, which includes a predicted mass to charge ratio, a predicted chromatographic retention or elution time, and a predicted ion mobility drift time, derived from a model. Multiple cycles of operation are then performed as the sample elutes from the separation device. Each cycle of operation includes mass filtering the parent ions so that selected ions having mass to charge ratios within a first mass to charge ratio range are onwardly transmitted to a fragmentation or reaction device. The target list is then checked and the model is updated accordingly. The first mass to charge ratio range can then be adjusted in response to the updated model.

Intelligent target-based acquisition

Described is a method for vacuum degassing of a liquid such as a solvent for a liquid chromatography system. The method includes modulating application of a vacuum to a fluid channel of a degasser so that each volume of a liquid drawn from the degasser experiences a residence time that is equal to the residence times of the other volumes. The residence time is determined as a time that the volume resides in the fluid channel under application of the vacuum and to a magnitude of the applied vacuum. The method is advantageous for use with liquid chromatography systems where differences in the diffusion rates of solvents into the degasser vacuum can otherwise introduce error into the composition gradient of a mobile phase.

Synchronized vacuum degassing for liquid chromatography

A method of mass spectrometry comprises ionizing a sample and obtaining mass spectral data relating to a plurality of ion detection events. The method then comprises applying match tolerances for mass to charge ratio (m/z), chromatographic retention time (t), and ion mobility drift time (t), to the ion detection events in order to determine possible charge state connections. The method also comprises constructing a tentative isotope chain and querying ion detection events for a match to the tentative isotope chain. Once a tentative isotope chain has been constructed, the method further comprises determining a corresponding theoretical molecular mass and a corresponding theoretical isotopic distribution, querying one or more lookup tables and returning one or more parameters (New X, New X', &#x394; New X&#x2032;) related to the fractional mass to charge ratio (f) and at least one of: ion mobility drift time (t); and nominal mass to charge ratio (N), of the ion detection events, and using the one or more parameters (New X, New X&#x2032;, &#x394; New X&#x2032;) to determine a unique charge state of the ions.

System and method for enhancing charge-state determination in electrospray mass spectrometry

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Natick, MA, United States of America

Steven J Ciavarini