Mds Inc.

Fluidigm Canada Inc.

Perkinelmer Health Sciences, Inc.

Fluidigm Corporation

Dvs Sciences Inc.

Other

Mds Sciex

Dh Technologies Development Pte. Ltd.

Mds Inc., Doing Business As Mds Sciex

Dmitry Roman Bandura

Vladimir I Baranov

Scott D Tanner

Alexei Antonov

Alexander V Loboda

Zoe Quinn

Hamid Badiei

Olga Ornatsky

Kaveh Kahen

Steven A Beres

The inventors have improved mass cytometer to facilitate its use for the analysis of particles.

Mass cytometry apparatus and methods

An analytical instrument has a sample introduction system for generating a stream of particles from a sample. An ionization system atomizes and ionizes particles in the stream as they are received. The instrument has an ion pretreatment system and a mass analyzer. The ion pretreatment system is adapted to transport ions generated by the ionization system to the mass analyzer. The mass analyzer is adapted measure the amount of at least one element in individual particles from the stream by performing mass analysis on the ions from the atomized particles. The instrument can be adapted to measure the amount of many different tags, for example at least five different tags, at the same time to facilitate multi-parametric analysis of cells and other particles.

Mass spectrometry based multi-parametric particle analyzer

A method for cellular analysis of cellular particles tagged with elemental tags, such as lanthanide-based elemental tags. Particles or element tags associated with particles can be vaporized, atomized, and ionized, such as with an inductively coupled plasma device or a glow discharge device. The vaporized, atomized, and ionized particles or element tags can be analyzed using mass spectrometry, such as using a time of flight mass spectrometer or a magnetic sector mass spectrometer. The amount of at least one element in individual particles can be measured through mass analysis. The amount of many different tags, for example at least five different tags, can be measured at the same time to facilitate multi-parametric analysis of cells and other particles. The vaporized, atomized, and ionized particles or element tags can be pretreated in an ion pretreatment system to filter out low mass ions, such as using a high-pass mass filter or a bandpass mass filter, to allow the elemental tags to pass therethrough.

An analytical instrument for cellular analysis of cellular particles tagged with elemental tags, such as lanthanide-based elemental tags. The analytical instrument has a sample introduction system for generating a stream of particles from the sample. An inductively coupled plasma ionization system atomizes and ionizes particles in the stream as they are received. The instrument has an ion pretreatment system and a mass analyzer. The ion pretreatment system is adapted to transport ions generated by the ionization system to the mass analyzer. The ion pretreatment system can filter out low mass ions, such as using a high-pass mass filter or a bandpass mass filter, to allow the elemental tags to pass therethrough. The mass analyzer is adapted to measure the amount of at least one element in individual particles from the stream by performing mass analysis on the ions from the atomized particles. The instrument can be adapted to measure the amount of many different tags, for example at least five different tags, at the same time to facilitate multi-parametric analysis of cells and other particles.

The invention relates to methods and devices for molecular cytometry. The molecular cytometer is for use in the analysis of molecular tag labeled particles. In the molecular cytometer, volatile molecular tags attached to the particles, such as cells, are released as groups of molecular tags and ionized by the method of soft ionization to produce corresponding groups of molecular ions. The molecular cytometer has two detectors, one to detect the presence of the groups of molecular ions and the other to detect mobility separated molecular ions. The mobility separated molecular ions are synchronized to correspond with the groups of molecular ions.

Molecular cytometry

A mass spectrometer has a particle introduction system and a vaporizer, atomizer, and ionizer configured to produce ions from elements associated with the particle. An ion mass-to-charge ratio analyzer is configured to separate ions according to their mass-to-charge ratio. A detector is positioned to detect at least some of the separated ions. A digital processor is configured to: (a) acquire data from the detector including at least first data in a primary detection group defined to comprise one or more mass-to-charge ratio channels of the mass spectrometer; (b) determine whether or not ions detected during at least one sampling cycle meet at least one selection criterion indicating a presence of a particle in the mass spectrometer; and (c) determine whether or not to use data in a secondary detection group based on whether or not the at least one selection criterion is met.

Apparatus for elemental analysis of particles by mass spectrometry

A mass analysis system including a sample inlet arranged to introduce a sample and an ion source coupled to the sample inlet and arranged to ionize a portion of the sample into ions. The system also includes a sampler element having a sample orifice arranged to receive the sample ions into a first vacuum chamber. The system includes a skimmer element having a skimmer orifice arranged to receive the sample ions from the first vacuum chamber into a second vacuum chamber where the skimmer orifice is of a first size. The system further includes a third cone element having a third cone orifice of a second size arranged to receive the sample ions from the second vacuum chamber into a third vacuum chamber where the third cone is configured to allow a continuum flow of ions through the third cone orifice. The third chamber includes an ion optics assembly and mass analyzer.

Cone-shaped orifice arrangement for inductively coupled plasma sample introduction system

An apparatus for elemental analysis of particles such as single cells or single beads by mass spectrometry is described. The apparatus includes means for particle introduction; means to vaporize, atomize and ionize elements associated with a particle; means to separate the ions according to their mass-to-charge ratio; means to detect the separated ions, means to digitize the output of the means to detect the ions; means to transfer and/or to process and/or record the data output of the means to digitize, having means to detect the presence of a particle in a mass spectrometer; and means to synchronize one of the means for ion detection, data digitization, transfer, processing and recording with the means to detect the presence of a particle. Methods and computer readable code implementing aspects of the apparatus, and for reducing the rates of data generation, digitization, transfer, processing and recording are also described.

Apparatus and method for elemental analysis of particles by mass spectrometry

An analytical instrument has a sample introduction system for generating a stream of particles from a sample and an ionization system for receiving the particles. The ionization system is operable to atomize the particles received from the sample introduction system and ionize atoms from the atomized particles. The instrument has an ion pretreatment system and a magnetic sector mass analyzer comprising an array detector. The ion pretreatment system is adapted to transport ions generated by the ionization system to the mass analyzer. The mass analyzer is adapted to detect a transient signal of at least one element from individual particles from said stream by performing mass analysis on the ions from the atomized particles. The magnetic sector mass analyzer is adapted determine an amount of said at least one element from an individual particle using the transient signal detected during mass analysis of the ions from said individual particle.

Magnetic sector mass spectrometry based multi-parametric particle analyzer

Methods for the detection and measurement of tagged (labeled) biologically active materials in a sample are described. The tagged biologically active materials are detected using an atomic mass or optical spectrometer having a source of atoms or atomic ions. Element-labeled biologically active materials, comprising antibodies, antibody Fab' fragments, antigens, aptamers, protein complexes, growth factors, hormones, receptors and other biologically active materials attached to a stable elemental tag, can be used in specific binding assays and measured by elemental spectroscopic detection. Also described are methods for the determination of metals in samples of interest using specific antibodies to isolate the target metals and elemental spectroscopy for detection and quantitation. Kits are provided comprising reagents to detect and measure labeled biologically active materials or labeled competition analytes.

Elemental analysis of tagged biologically active materials

An apparatus () for sequentially analyzing particles such as single cells or single beads, by spectrometry. The apparatus, an elemental flow cytometer, includes means () for sequential particle introduction, means () to vaporize, atomize and excite or ionize the particles, or an elemental tag associated with an analyte on the particles, and means () to analyze the elemental composition of the vaporized, atomized and excited or ionized particles, or an elemental tag associated with the particles. Methods for sequentially analyzing particles such as singe cells or single beads by spectrometry are also described.

Growing community of inventors

Aurora, Canada

Dmitry Roman Bandura