Dh Technologies Development Pte. Ltd.

University of Toronto

John Lawrence Campbell

Yves LeBlanc

Chang Liu

Yves Le Blanc

Thomas R Covey

Stephen Alexander Tate

David Michael Cox

Eva Duchoslav

Takashi Baba

Scott Hopkins

Don Wesley Arnold

Alexandre V Loboda

James Walter Hager

Subhasish Purkayastha

Bradley B Schneider

Nic G Bloomfield

Aaron Ray Wheeler

Lyle Lorrence Burton

Igor V Chernushevich

Paul Baker

Brendon Seale

Kihwan Choi

Stephen Blanksby

Todd Mitchell

Adam San-Ho Lau

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

A DMS device receives a curtain gas that includes a chemical modifier into its curtain plate. Before or while receiving ions of an analyte, the DMS device steps the CoV through a series of values in order to apply different CoV values to at least one precursor ion derived from the chemical modifier. For each CoV value of the series of values, a mass spectrometer selects and mass analyzes the at least one precursor ion. An intensity is produced for each CoV value of the series of values. An intensity versus CoV value peak is calculated from the intensities measured. A representative CoV value is calculated for the peak. The difference between the representative CoV value and known CoV values that represent an uncontaminated curtain plate is calculated. If the difference is greater than or equal to a predetermined threshold value, the curtain plate is determined to be contaminated.

Determining curtain plate integrity in differential mobility spectrometry

Each of one or more unknown compounds are separated from a sample over a separation time period. Separated compounds are ionized, producing one or more compound precursor ions for each of the unknown compounds and a plurality of background precursor ions. A precursor ion mass spectrum is measured for the combined compound and background precursor ions at each time step of a plurality of time steps spread across the separation time period, producing a plurality of precursor ion mass spectra. One or more background precursor ions are selected from the plurality of precursor ion mass spectra that have a resolving power in a range below a threshold expected resolving power. A separation time is detected for an unknown compound when a decrease in an intensity measurement of the selected background precursor ions over a time period exceeds a threshold decrease in intensity with respect to time.

Agnostic compound elution determination

A plurality of known compounds with known CCS values is analyzed using a DMS device. The DMS device determines how the intensities of their transmitted ions vary with different separation voltages (SVs) and compensation voltages (CVs). A machine learning algorithm builds a data model from the known m/z value, known CCS value, and measured pairs of CV and SV values that provide optimal transmission through the DMS device for each of the known compounds. An unknown compound with an unknown CCS value is then analyzed. The DMS device determines how the intensity of its ions varies with the same different SVs and CVs. Finally, the machine learning algorithm predicts the CCS value of the unknown compound from the data model, the known m/z of the unknown compound, and the measured pairs of CV and SV values that provide optimal transmission through the DMS device for the unknown compound.

Predicting molecular collision cross-section using differential mobility spectrometry

Systems and methods are disclosed for utilizing an ion mobility cell to improve desolvation prior to interaction with a hydrogen-deuterium exchange reagent, thereby improving the accuracy of the HDX data generated by MS and reducing the effects of conformational changes that can occur with increased temperatures.

Methods and systems for mass spectrometry analysis utilizing hydrogen-deuterium exchange

Methods and systems for separating, detecting, and/or quantifying sample enantiomers 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 racemic or non-racemic mixtures of sample enantiomers that may be difficult to separate with conventional techniques, such as mass spectrometry (MS), by reacting the sample enantiomers with an enantiomerically-pure compound to form diastereomers separable by DMS.

Methods for detection of sample enantiomers using differential mobility spectrometry

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

A method and apparatus for analyzing samples using mass spectrometry are disclosed. The apparatus includes a reaction device configured to dissociate sample ions into fragments by reacting the sample ions with a charged species (e.g., electrons) such as through ECD, EID, or EIEIO. The kinetic energy of the charged species is such that the fragments may be detected and produce spectra that allow for the determination of isomeric species in the sample and the location of double bonds and/or the orientation of those double bonds within the sample molecules. The fragments may include radical fragments and non-radical fragments. Spectra resulting from analysis of the fragments may allow for the determination of the oxygen-radical fragments resulting from the dissociation of the sample molecules as confirmation of the presence of those radical fragments.

Method and apparatus for analyzing samples using mass spectrometry

Methods and apparatus for processing fluids on a macro- or micro-scale are described. In various aspects, a fluid may have a plurality of elongated (i.e., substantially rod-shaped) magnetic elements disposed therein within a fluid container. An illustrative fluid container is an actuator electrode or a processing vial of a microfluidic device, such as a digital microfluidic device. A magnet component may be configured to generate a magnetic force sufficient to influence the movement of the plurality of elongated magnetic elements within the fluid to be processed. For example, the magnetic force (or magnetic force gradient) may influence the plurality of elongated magnetic elements to rotate, spin, and/or move laterally side-to-side. The shape and movements of the plurality of elongated magnetic elements facilitate the rapid and efficient processing of the fluid, such as fluid mixing and/or fluid separation.

Magnetic elements for processing fluids

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 are provided herein for varying the CoV about a nominal CoV-apex while monitoring the ion of interest corresponding to the nominal CoV-apex as it is transmitted by a DMS. In various aspects, the CoV can be swept or stepped across a series of values during the injection of ions into the DMS such that a composite spectra of the ion of interest transmitted by the DMS (or its product ions following one or more stages of fragmentation) can be generated so as to include the transmission of the particular ion at a CoV with optimum sensitivity (i.e., if distinct from the CoV-apex), thereby improving the robustness, accuracy, and/or selectivity during experimental conditions relative to known DMS techniques, which typically used a fixed CoV value for each ion of interest.

Differential mobility spectrometry method

Systems and methods are provided for providing a DMS precursor ion survey scan. An ion source configured to receive a sample is instructed to ionize the sample using a processor. A DMS device configured to receive ions from the ion source is instructed to separate precursor ions received from the ion source and transmit precursor ions using two or more CoVs using the processor. A mass analyzer configured to receive transmitted precursor ions from the DMS device is instructed to measure the m/z intensities of the transmitted precursor ions across an m/z range at each CoV of the two or more CoVs using the processor. The measured m/z intensities of the transmitted precursor ions received from the mass analyzer are stored as a function of m/z value and CoV using the processor. This produces a stored two-dimensional mapping of m/z intensities of the precursor ions of the sample.

Dynamic orthogonal analysis method

Systems and methods prevent potentially convolved precursor ion peaks from being excluded in subsequent cycles of an IDA experiment so that additional product ion data is collected. A sample is ionized producing an ion beam. A plurality of cycles of an IDA experiment are performed on the ion beam. During each cycle of the IDA experiment and for each precursor ion peak on a filtered peak list produced in the filtering step of each cycle, several steps are performed. The precursor ion peak is identified in the precursor ion spectrum produced in the MS survey scan step of the cycle. It is determined if the precursor ion peak in the precursor ion spectrum includes a feature of convolution. If the precursor ion peak includes a feature of convolution, the precursor ion peak is prevented from being excluded in a filtering step of one or more subsequent cycles.

Method for deconvolution

A method and apparatus for analyzing samples using mass spectrometry are disclosed. The apparatus includes a reaction device configured to dissociate sample ions into fragments by reacting the sample ions with a charged species (e.g., electrons) such as through ECD, EID, or EIEIO. The kinetic energy of the charged species is such that the fragments may be detected and produce spectra that allow for the determination of isomeric species in the sample and the location of double bonds of sample molecules. The fragments may include radical fragments and non-radical fragments. The apparatus may also include an oxygen gas source configured to react with the radical fragments to produce oxygen-radical fragments. Spectra resulting from analysis of the fragments may allow for the determination of the oxygen-radical fragments resulting from the dissociation of the sample molecules.

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Milton, Canada

John Lawrence Campbell