Acceleration, simplification and potential parallelization of digital polymers sequencing by coupling tandem mass spectrometry with ion mobility
Year: 2025
Type: article
Abstract: Tailoring the structure of digital polymers is an efficient strategy for reliable reading of large amounts of data by tandem mass spectrometry. Notably, full sequence coverage of chains containing up to 33 bytes of information is achieved for block-truncated poly(phosphodiester)s designed to undergo controlled fragmentations. However, the previously established reading methodology based on multiple MS stages performed sequentially remains slow and not prone to automation. Here, we report a full gas-phase bottom-up workflow enabling production, separation and sequencing of all sub-sequences of block-truncated poly(phosphodiester)s in a single run. To do so, a multidimensional coupling involving two activation stages in tandem with ion mobility spectrometry has been optimized. Since blocks to be sequenced have their mobility varying in a predictable manner, proper selection of tags used for their identification permits to achieve mobility resolution prior to sequencing. Performing this coupling with MALDI further paves the way to automated imaging-based reading approaches.
Source: Nature Communications
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4416723887