Dh Technologies Development Pte. Ltd.

Purdue Research Foundation

University of Toronto

Yves LeBlanc

Thomas R Covey

Don Wesley Arnold

Takashi Baba

John Lawrence Campbell

Chang Liu

Bradley B Schneider

Aaron Ray Wheeler

Scott A McLuckey

Kihwan Choi

Kerry M Hassell

Bradley A Schneider

Methods and apparatus for processing fluids are described. In various aspects, a fluid processing system may include a magnetic assembly that includes a plurality of magnetic structures configured to generate a magnetic field gradient within a fluid container. The magnetic structures may be formed as a plurality of electromagnets configured to be individually actuated by a controller. Each of the electromagnets may generate a magnetic field within the fluid container. The electromagnets may be differentially actuated to create a magnetic field gradient within the fluid container to agitate, mix, or otherwise influence magnetic particles disposed within the fluid container. Activation of the electromagnets of an electromagnetic structure may generate a magnetic field gradient that influences magnetic particles in an x-y direction. In addition, activation of the electromagnets of a plurality of electromagnetic structures may generate magnetic field gradients that influences magnetic particles in an x-y direction and z-direction.

Electromagnetic assemblies for processing fluids

Methods and systems for separating and/or quantifying compounds, using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicants' teachings, the methods and systems can provide for the quantification of one or more compounds, for example, using isomeric labels that can be less costly to produce relative to conventional tags that incorporate stable-isotope labels. The present teachings can quantify the relative amount of a compound based on the effect of using an easily charged functional group as well as a functional group positioned at a resonant or non-resonant position through a DMS. In some aspects, methods and systems in accordance with various aspects of the present teachings provide for the detection and/or quantification of the analytes labeled with isomeric tags that can be differentiated via a DMS upstream of a first stage mass analyzer and/or prior to fragmentation of the labeled analyte, for example.

Isomeric reagent tags for differential mobility spectrometry

Because most ion optics of mass spectrometry systems are subject to ion deposition and may exhibit significantly different behavior following substantial contamination (e.g., loss of sensitivity), fouled surfaces must be regularly cleaned to maintain sensitivity. While the surfaces of front-end components (e.g., curtain plates, orifice plates, Qjet, Q, IQ) may be relatively easy to clean, the fouling of components contained within the downstream high-vacuum chambers (e.g., Q, IQ) can incur substantial delays and expense as the high-vacuum chambers must be vented and substantially disassembled prior to cleaning. Methods and systems for controlling contamination of components of mass spectrometer systems are provided herein. By reducing the transmission of contaminating ions during non-data acquisition periods, the present teachings can increase throughput, improve robustness, and/or decrease the downtime typically required to vent/disassemble/clean the fouled components.

Methods and systems for controlling ion contamination

Methods and systems for processing fluids utilizing a digital microfluidic device and transferring droplets from the digital microfluidic device to a downstream analyzer are described herein. Methods and systems in accordance with the present teachings can allow for the withdrawal of fluid from a digital microfluidic device, and can in some aspects enable the integration of a digital microfluidic device as a direct, in-line sample processing platform from which a droplet can be transferred to a downstream analyzer.

Fluid transfer from digital microfluidic device

Methods and systems for separating and/or quantifying peptides using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicant's teachings, the methods and systems can provide for the separation of one or more peptides, for example, peptides that may be difficult to separate with conventional techniques, such as mass spectrometry (MS), by complexing the peptides with a metal cation (e.g., Ca2+) prior to DMS. In some aspects, the present teachings can prevent proton stripping from ionized peptides that can occur in DMS to prevent unintended and/or undesirable alterations to the peptide's charge state distribution.

Methods for detection in differential mobility spectrometer using a peptide metal complex

A method for analyzing a sample that contains a plurality of lipid isomers is described that involves forming one or more lipid metal ion adducts and transporting the one or more lipid metal ion adducts through a differential mobility spectrometer to cause separation of the one or more lipid metal ion adducts from each other. The lipid isomers can be chosen, for example, from fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipids, and prenol lipids. Particular examples include phosphatidylcholine regioisomers such as 1-palmatoyl-2-oleoyl-sn-phosphatidylcholine (POPC) and 1-oleoyl-2-palmatoyl-sn-phosphatidylcholine and triacylglycerols containing palmetic and oleic acid groups. The metal chosen can include a cationization reagent that contains sodium, potassium, silver or lithium.

Methods for analysis of isomeric lipids

An apparatus, system and method of providing that allow for the generation of reagent ions within an inner region of a mass spectrometer for use in ion-ion reactions such as PTRs and ETD using a reagent ion generator. The location where these reagent ions are generated can be as close as possible to the point of action, or the reaction zone where the reagent ion and analyte ions will interact via ion-ion reactions to cause, e.g., PTRs and/or ETD.

Generation of reagent ions for ion-ion reactions

An electrospray ion source method and system is provided for detecting emitter failure comprising a liquid chromatography column suitable for chromatographic separation of a sample. The column can have an inlet for receiving the sample; and an outlet for ejecting the sample. A make-up flow channel is provided for introducing make-up flow of liquid to the sample post-column, wherein the make-up flow normalizes the spray current. An electrospray ionization source is provided having one or more electrospray ionization emitter nozzles for receiving the make-up flow containing sample. A power supply can provide a voltage to the one or more emitter nozzles, and a measurement device can measure and monitor the spray current.

Method and system for introducing make-up flow in an electrospray ion source system

Methods and systems for performing mass spectrometry of analytes labeled with isobaric tags are provided herein. In accordance with various aspects of the applicants' teachings, the methods and systems can enable enhanced discrimination between an analyte of interest and one or more interfering species when using isobaric tagging techniques.

Reducing interferences in isobaric tag-based quantification

Methods and systems for performing ion mobility spectrometry are provided herein. In accordance with various aspects of the applicant's teachings, the methods and systems can provide for the separation of biologically relevant acids that may be difficult to separate with conventional MS techniques. In various aspects, methods and systems in accordance with applicant's teachings can enable a differential mobility spectrometer to resolve biologically relevant acids through the use of COas the drift gas in combination with Acetone.

Methods for selective detection of biologically relevant acids

An apparatus and method for a sample using a mass spectrometer is described, including, generating ions of a first polarity from an analyte using electrospray ionization; generating ions of a second polarity from a reagent; injecting the ions of the first polarity and ions of the second polarity in sequence into a chamber of the mass spectrometer such that the ions of the first polarity and the ions of the second polarity interact in the chamber to form analyte ions having the second polarity; and, analyzing the mass spectrum of the analyte ions of the second polarity. A reagent such as a polyamidomine is selected to preferentially yield analyte ions of the second polarity having a desired mass-to-charge ratio.

Method and apparatus for conversion of multiple analyte cation types to a single analyte anion type via ion/ion charge inversion

An apparatus and method are provided for analyzing samples of molecules. The apparatus comprises a mass analysis system including a differential mobility spectrometer, which includes at least three filter electrodes defining two ion flow paths where the filter electrodes generate electric fields for passing through selected portions of the sample ions based on the mobility characteristics of the sample ions. The differential mobility spectrometer also includes a voltage source that provides DC and RF voltages to at least one of the filter electrodes to generate the electric field, a first and a second ion inlet that receive sample ions, and an ion outlet that outputs the selected portion of the sample ions. A mass spectrometer receives some or all of the selected portion of the sample ions.

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Newmarket, Canada

Yves LeBlanc