timShift: lon Mobility Tags for High-Throughput Proteomic Enrichment

Background & Unmet Need

• Mass Spectrometry (MS) enables precise identification and quantification of molecules, making it essential for proteomics & drug target discovery
• Proteomics relies on labeling and enrichment methods to simplify the proteome and amplify proteins of interest 
• Current enrichment methods are primarily liquid chromatography (LC)-based, which requires labor-intensive workflows that increase process complexity, variability, and analyte loss
• Gas-phase separation enables streamlined MS integration and reduces sample loss, but suffers from poor ionization efficiency, resolution, and selectivity due to short ion residence times and limited separation dimensions
• Unmet Need: A method to improve the efficiency and selectivity of gas-phase separation while maintaining high throughput and sensitivity

Technology Overview

• The Technology: timShift, a gas phase, in-spectrometer approach for enhanced reactive amino acid profiling using peptide modification tags affecting ion mobility
• The timShift tags enrich target molecules by introducing a fixed +1 or +2 positive charge that enable physical separation of tagged and untagged molecules with minimal impact on mass 
• The technique reduces the amount of input material required without compromising depth for high-throughput proteomics discovery for both flexible and targeted data acquisition methods
• PoC Data: The timShift tags outperformed desthiobiotin/streptavidin enrichment in a study of reactive cysteine quantitation
• The timShift tags were further applied to profile an array of cysteine reactive covalent fragments using a rapid 96-well plate workflow

Technology Applications

• Screening of covalent interactions for drug discovery
• Proteomics profiling on covalent modifications across conditions and diseases
• Integration with other tagging techniques for improved proteomic analysis

Technology Advantages

• “In spectrometer” enrichment reduces workflow complexity and minimizes material loss
• Does not suffer from endogenous biotin background
• Compatible with as few as 20K cells
• Can measure both reactive cysteine sites and whole protein abundances in a single analysis