Quantum-Si Incorporated announced on June 10, 2025, a new preprint from researchers at Quantum-Si and ESPCI Paris. The study introduces a powerful method for measuring single-molecule binding kinetics at scale using the benchtop Quantum-Si Platinum Next-Gen Protein Sequencing instrument.
This approach directly links nanobody function to identity without the need for genotype-phenotype coupling, allowing scientists to study protein interactions at single-molecule resolution across tens of variants in parallel. The method involves tagging protein variants with sequence-specific peptide barcodes, immobilizing them, and then measuring ligand-binding kinetics using single-molecule fluorescence before sequencing the barcodes.
The team validated results across 20 nanobody variants with over a 1,000-fold range in affinity, showing strong correlation with surface plasmon resonance (SPR). This method offers high-throughput measurement, genotype-phenotype linking, extended kinetic range, and strong reproducibility, and even revealed previously hidden biological behaviors like conformational isomerism.
This work makes single-molecule analysis more practical and routine, accelerating drug discovery, protein engineering, and the understanding of disease biology. With upcoming chemistry and hardware updates, the system has the potential to scale to over 1,000-member barcode sets, making it suitable for applications in synthetic biology and AI-driven protein engineering.
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