A separation device separates an unknown intact mAb or reduced mAb subunits of a known mAb class from a sample. An ion source device ionizes the mAb. A mass spectrometer fragments the ionized mAb using an ECD device and mass analyzes resulting product ions using a mass analyzer, producing one or more product ion spectra. Theoretical product ion peaks are calculated for one or more constant portions of the mAb class. The theoretical product ion peaks are removed from the one or more product ion spectra, producing one or more difference product ion spectra. De novo sequencing is applied to the one or more difference product ion spectra, producing one or more candidate sequences for one or more variable portions of the mAb. A genome database is searched for matches to the one or more candidate sequences, producing one or more matched sequences for the one or more variable portions.

A method of ionising a sample is disclosed comprising nebulising a sample which includes first biomolecules such as bovine insulin comprising one or more disulphide (S—S) bonds. A stream of droplet or charged droplets comprising one or more disulphide (S—S) bonds is directed so as to impact upon a target (106) or electrode so as to cause the breaking of a portion of the disulphide bonds. Alternatively, charged droplets may pass through an electric field region determined by an electrode (106) arranged downstream of a nebuliser or electrospray probe and an ion inlet (104) of a mass spectrometer so as to cause the breaking of a portion of the disulphide bonds.

The present disclosure is directed at an antibody conjugate having an antibody and a tag, wherein one or more element(s) present in the antibody exhibit an isotope ratio which differs from the naturally occurring isotope ratio of the one or more element(s), wherein the amount of the isotope which is less-common in nature, is increased to at least 4% of the atoms of the respective element in the antibody, as well as uses thereof.

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Provided is a tag for labeling a biomolecule, comprising a polymer backbone, one or more pendant moieties, and an end group capable of binding to the biomolecule, wherein each of the pendant moieties is attached to the polymer backbone and capable of chelating with an element. Also provided is a conjugate, comprising a biomolecule covalently coupled with the tag.

Systems and methods are provided for the analysis of single particles with inductively coupled plasma time of flight mass spectrometry. Single particles may be isolated from whole cells, microorganisms, viruses, etc. The systems may include curved ion guides including such elements as multipoles, angled or rounded surfaces, and an ion manipulation device including elements such as an ion tunnel, ion funnel, quadrupole, and variations of each element.

The present invention centers upon a novel “molecular amplification spike,” which is an admixture of two components, namely, an aliquot of a quantity of a molecule, composition, compound or element of interest (an “analyte”) in its natural isotopic state and an aliquot of an isotopically enriched form of the same molecule, composition, compound or element. The molecular amplification spike contains 20% natural-abundance isotope, balance enriched isotope. The molecular amplification spike may optionally contain more than 20% natural-abundance isotope, with concomitantly reduced balance of enriched isotope. Such an admixed spike, when added to a sample prior to mass spectrometric analysis of that sample, creates new and significantly improved percentage of errors and quantification or confirmation of the absence of the molecule, composition, compound or element of interest in the sample.

A compound and a method of detecting CLN3 are provided. The compound includes a heavy isotope labeled CLN3 proteotypic peptide. The method includes i) selecting a CLN3 proteotypic peptide that exhibits linear behavior in the mass spectrometer; ii) generating a stable isotope labeled standard; iii) spiking known amounts of the stable isotope labeled standard into a sample to form a spiked sample; iv) determining retention times and establishing calibration curves using the spiked sample; and v) detecting unlabeled selected CLN3 proteins in the sample.

The present invention relates to a method for preparing a plasma sample comprising amyloid beta peptides for analysis by mass spectrometry, comprising the steps of: a) contacting said plasma sample with a denaturing agent, b) performing a first solid phase extraction step on the solution obtained in step a) to recover a first eluate, c) performing a second solid phase extraction step on said first eluate obtained in step b) to recover a second eluate, and d) drying said second eluate obtained in step c) and processing it for analysis by mass spectrometry, wherein the solution obtained in step d) comprises intact amyloid beta peptides Aβ40 and Aβ42.

Methods for performing bead-based analytical assays for detecting changes in abundance of target analytes in biological samples are disclosed. In an embodiment, a method involves eluting bead-captured analytes from a bead array under conditions that preserve spatial localization of the eluted analytes.