The Platinum device from Quantum-Si company is the first system enabling next-generation protein sequencing (NGPS). Unlike traditional protein sequencing methods, such as Edman degradation or mass spectrometry, the NGPS method allows sequencing of amino acids, the basic building blocks of proteins, in millions of protein molecules simultaneously, delivering single-molecule and single amino acid resolution. This approach makes the NGPS high-throughput method, thus increasing the overall amount of information that can be obtained within a single experiment.

The sample preparation workflow involves degradation of the protein into shorter peptides, from which a peptide library containing millions of fragments of the original protein is created through a series of enzymatic reactions. Peptide libraries are then immobilized on sequencing chip. The sequencing process is facilitated via the use of amino acid recognizers, which repeatedly bind to the protruding ends of peptide molecules, and depending on their binding partner and stability of their interaction, a specific optical signal is emitted, which allows the identification of the first amino acid in the sequence. The amino acids from individual peptides are gradually cleaved using aminopeptidases, enabling the identification process to repeat itself on the next amino acid in the sequence. The higly-specific optical signal captured from the surface on the chip is automatically processed by the integrated analytical software, and the resulting order of amino acids in the sequenced protein is then compared to a chosen reference, allowing the identification of potentially pathological protein variants or a new functional type of protein in the sample from which the peptide library was prepared. Due to the binding properties of the recognizers, it is also possible to detect some specific variations of amino acids, which arise during protein formation in cells in processes known as post-translational modifications, significantly affecting the resulting function, localization, or lifespan of the final protein. Unlike mass spectrometry, NGPS is not dependent on the charge of amino acid residues, making it possible to study proteins that would otherwise represent a substantial challenge for mass spectrometry (e.g., membrane proteins, etc.).

A visual depiction of the described sequencing process can be viewed on the manufacturer’s website here: https://www.quantum-si.com/technology/