Abstract: Aspects of the subject application include applying a spatial barcode to a cellular sample and then performing suspension mass cytometry on the cellular sample. For example, a sample barcode comprising a known distribution of sample barcode isotopes may be applied to the sample such that cells in different locations receive a unique combination or ratio of barcode isotopes, after which cells are suspended (e.g., dissociated from tissue) and processed by suspension mass cytometry. While barcode isotopes are described in a number of embodiments herein, non-enriched elements may be used instead of, or in addition to, enriched isotopes. Mass cytometry methods and reagents are discussed below, followed by a further description of spatial barcoding and kits thereof.

Abstract: The present invention relates to the high resolution imaging of samples using imaging mass spectrometry (IMS) and to the imaging of biological samples by imaging mass cytometry (IMC™) in which labelling atoms are detected by IMS. LA-ICP-MS (a form of IMS in which the sample is ablated by a laser, the ablated material is then ionised in an inductively coupled plasma before the ions are detected by mass spectrometry) has been used for analysis of various substances, such as mineral analysis of geological samples, analysis of archaeological samples, and imaging of biological substances. However, traditional LA-ICP-MS systems and methods may not provide high resolution. Described herein are methods and systems for high resolution IMS and IMC.

Abstract: A coupling tube made of a stretchable elastomeric material. The “stretchy” coupling tubing allows for improved reliability/repeatability of coupling performance. For example, the stretch provided can take up tolerances between positions of imager and reader instruments. In one example, the stretch can take up tolerances between positions of the junction between the rigid portion of tubing inside the IMC unit and the injector to an ionization source. The coupling tube may also be provided with a reduced inner diameter (ID) as compared to standard coupling components. A taper in the inner diameter (ID) can occur before the flow enters the stretchable coupling tube. Barbed ends may also be provided for securing the coupling tube into place.

Abstract: We describe in this application systems and methods for autofocusing in imaging mass spectrometry. The present application describes improvements over current IMS and IMC apparatus and methods through an autofocus component including a plurality of apertures in the autofocus system, such as a plurality of apertures arranged in 2 dimensions. As a plurality of apertures is used, the autofocus system provides redundancy in the event that measurement of focus on the sample from the illuminating radiation passed through one or more of the apertures fails so as to reduce the number of unsuccessful autofocus attempts.

Abstract: Embodiments of the present invention relate to reagents and their use for elemental imaging mass spectrometry of biological samples. Embodiments include a method for quantifying one or more analytes within a sample. The method may include providing the sample. One or more analytes may be immobilised to a mass cytometry sample carrier. The sample may have been labelled with one or more mass-tagged SBPs including one or more labelling atoms. The method may include performing mass cytometry on the sample to determine a level of the one or more labelling atoms, where the level of the one or more labelling atoms corresponds to the copy number of the one or more analytes to quantify the analytes.

Abstract: Inductively coupled plasma (ICP) analyzers use an ICP torch to generate a plasma in which a sample is atomized an ionized. Analysis of the atomic ions can be performed by atomic analysis, such as mass spectrometry (MS) or atomic emission spectrometry (AES). Particle based ICP analysis includes analysis of particles such as cells, beads, or laser ablation plumes, by atomizing and ionizing particles in an ICP torch followed by atomic analysis. In mass cytometry, mass tags of particles are analyzed by mass spectrometry, such as by ICP-MS. Systems and methods of the subject application include one or more of: a demountable ICP torch holder assembly, an external ignition device; an ICP load coil comprising an annular fin, particle suspension sample introduction fluidics, and ICP analyzers thereof.

Abstract: The present invention relates to the high resolution imaging of samples using imaging mass spectrometry (IMS) and to the imaging of biological samples by imaging mass cytometry (IMC®) in which labelling atoms are detected by IMS. LA-ICP-MS (a form of IMS in which the sample is ablated by a laser, the ablated material is then ionised in an inductively coupled plasma before the ions are detected by mass spectrometry) has been used for analysis of various substances, such as mineral analysis of geological samples, analysis of archaeological samples, and imaging of biological substances. However, traditional LA-ICP-MS systems and methods may not provide high resolution. Described herein are methods and systems for high resolution IMS and IMC.

Abstract: Analyzing samples injected into an inductively coupled plasma source can be improved by one or more of a stabilizing solution mixable with a sample prior to injection and a heated injector. The stabilizing solution can minimize the difference in osmotic pressure between the solution and the cells with a relatively low amount of dissolved solids (e.g., at or below about 0.2%). The stabilizing solution can contain a salt (e.g., ammonium nitrate) present in concentrations of at least 5 mM. The injector can be heated before and/or during injection. In some cases, heat from adjacent parts can be channeled into the injector to improve heating of the injector. An injector heated to sufficient temperatures can minimize solute buildup and can extend the usable time between cleanings. These improvements can be especially useful in elemental analysis, such as inductively coupled plasma mass spectrometry or inductively coupled plasma optical emission spectrometry.

Abstract: We describe in this application systems and methods for autofocusing in imaging mass spectrometry. The present application describes improvements over current IMS and IMC apparatus and methods through an autofocus component including a plurality of apertures in the autofocus system, such as a plurality of apertures arranged in 2 dimensions. As a plurality of apertures is used, the autofocus system provides redundancy in the event that measurement of focus on the sample from the illuminating radiation passed through one or more of the apertures fails so as to reduce the number of unsuccessful autofocus attempts.

Abstract: The present disclosure relates to reagents and their use for elemental imaging mass spectrometry of biological samples.

Abstract: Element tags based on novel metal-polymer conjugates are provided for elemental analysis of analytes, including ICP-MS. A polymer backbone is functionalized to irreversibly bind metals that are selected prior to use by the user. The polymer is further functionalized to attach a linker which allows for attachment to antibodies or other affinity reagents. The polymer format allows attachment of many copies of a given isotope, which linearly improves sensitivity. The metal-polymer conjugate tags enable multiplexed assay in two formats: bulk assay, where the average biomarker distribution in the sample is diagnostic, and single cell format to distinguish a rare (for example a diseased) cell in a complex sample (for example, blood).

Abstract: Inductively coupled plasma (ICP) analyzers use an ICP torch to generate a plasma in which a sample is atomized an ionized. Analysis of the atomic ions can be performed by atomic analysis, such as mass spectrometry (MS) or atomic emission spectrometry (AES). Particle based ICP analysis includes analysis of particles such as cells, beads, or laser ablation plumes, by atomizing and ionizing particles in an ICP torch followed by atomic analysis. In mass cytometry, mass tags of particles are analyzed by mass spectrometry, such as by ICP-MS. Systems and methods of the subject application include one or more of: a demountable ICP torch holder assembly, an external ignition device; an ICP load coil comprising an annular fin, particle suspension sample introduction fluidics, and ICP analyzers thereof.

Abstract: Analyzing samples injected into an inductively coupled plasma source can be improved by one or more of a stabilizing solution mixable with a sample prior to injection and a heated injector. The stabilizing solution can minimize the difference in osmotic pressure between the solution and the cells with a relatively low amount of dissolved solids (e.g., at or below about 0.2%). The stabilizing solution can contain a salt (e.g., ammonium nitrate) present in concentrations of at least 5 mM. The injector can be heated before and/or during injection. In some cases, heat from adjacent parts can be channeled into the injector to improve heating of the injector. An injector heated to sufficient temperatures can minimize solute buildup and can extend the usable time between cleanings. These improvements can be especially useful in elemental analysis, such as inductively coupled plasma mass spectrometry or inductively coupled plasma optical emission spectrometry.

Abstract: Embodiments of the present invention relate to reagents and their use for elemental imaging mass spectrometry of biological samples. The embodiments comprising methods for quantifying one or more analytes within a sample, comprising the steps of: (a) providing the sample, wherein the one or more analytes are immobilized to a sample carrier, wherein the sample has been labelled with one or more mass tags comprising one or more labelling atoms, (b) performing mass cytometry on the sample to determine the level of the one or more labelling atoms, wherein the level of the one or more labelling atoms corresponds to the copy number of the one or more analytes.

Abstract: Inductively coupled plasma (ICP) analyzers use an ICP torch to generate a plasma in which a sample is atomized an ionized. Analysis of the atomic ions can be performed by atomic analysis, such as mass spectrometry (MS) or atomic emission spectrometry (AES). Particle based ICP analysis includes analysis of particles such as cells, beads, or laser ablation plumes, by atomizing and ionizing particles in an ICP torch followed by atomic analysis. In mass cytometry, mass tags of particles are analyzed by mass spectrometry, such as by ICP-MS. Systems and methods of the subject application include one or more of: a demountable ICP torch holder assembly, an external ignition device; an ICP load coil comprising an annular fin, particle suspension sample introduction fluidics, and ICP analyzers thereof.

Abstract: Inductively coupled plasma (ICP) analyzers use an ICP torch to generate a plasma in which a sample is atomized an ionized. Analysis of the atomic ions can be performed by atomic analysis, such as mass spectrometry (MS) or atomic emission spectrometry (AES). Particle based ICP analysis includes analysis of particles such as cells, beads, or laser ablation plumes, by atomizing and ionizing particles in an ICP torch followed by atomic analysis. In mass cytometry, mass tags of particles are analyzed by mass spectrometry, such as by ICP-MS. Systems and methods of the subject application include one or more of: a demountable ICP torch holder assembly, an external ignition device; an ICP load coil comprising an annular fin, particle suspension sample introduction fluidics, and ICP analyzers thereof.

Abstract: Described herein are reagents and methods for improving signal in imaging mass cytometry. Aspects include mass tags with a large number of labeling atoms, chemical modifications to mass tags and additional reagents to reduce background and/or maintain target binding of mass tagged specific binding partners (SBPs), and schemes for associating a plurality of mass tags with a single SBP. As such, embodiments include any combination of one or more reagents and their use. The reagents, kits and methods herein may be used for mass cytometry, including imaging mass cytometry. In some aspects, reagents, kits or methods may be used for delivery of a large number of radioisotopes to a target analyte, for example for therapeutic use or radiometric detection. In certain aspects, only non-radioactive isotopes may be used for mass cytometry.

Abstract: Described herein are systems and methods for imaging mass spectrometry, including imaging mass cytometry. Aspects of the subject application include apparatus and methods for imaging mass spectrometry (IMS) that improve speed of sample acquisition, signal sensitivity, and/or signal stability. Systems and methods described herein may minimize the transfer time and/or may minimize the spread of plumes of sample material ablated from a sample to be transferred to the components of the imaging mass spectrometer or mass cytometer that ionize and analyze the sample material.

Abstract: The invention relates to methods and devices for analysis of samples using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The invention provides methods and devices in which individual ablation plumes are distinctively captured and transferred to the ICP, followed by analysis by mass cytometry.