Digital molecular kinetics enabled by large-scale nanopore arrays for multidimensional biophysical profiling
- 1Geneus Technologies (Chengdu) Co., Ltd.
Abstract
While widely used, traditional technologies like surface plasmon resonance (SPR) are limited by narrow temporal windows (transient capture and baseline drift), dynamic heterogeneity, and poor physiological temperature performance. Meanwhile, early nanopore approaches are often constrained by limited throughput and heavy reliance on customized modification schemes. Here, we present a digital molecular kinetics (DMK) platform based on large-scale nanopore arrays. By introducing a universal coupling and probe reporting system, DMK achieves broad versatility across diverse molecular pairs, including proteins, peptides, small molecules, DNA, and polymerase complexes. In addition to accurately recovering classical SPR association and dissociation rate constants, by harnessing massive single-molecule event analysis, DMK breaks traditional performance boundaries: it facilitates robust thermodynamic-kinetic profiling across a wide temperature range, resolves distinct conformations in heterogeneous samples, enables ultra-low dissociation rate quantification via maximum likelihood estimation, and reveals energy wells via voltage gradients for binding analysis against environmental perturbations. Furthermore, DMK enables the capture of rapid binding events missed by SPR, offering a new perspective on molecular interaction complexity. This platform offers an effective alternative and upgrade to SPR, opening a digital paradigm for complex molecular analysis and drug discovery.
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BibTeX
@misc{li2026digital,
title = {{Digital molecular kinetics enabled by large-scale nanopore arrays for multidimensional biophysical profiling}},
author = {K. Li and Y. Wang and Y. Cheng and T. Zheng and S. Long and L. Zhong and M. Wu and Y. Zou},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762428},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762428v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Digital molecular kinetics enabled by large-scale nanopore arrays for multidimensional biophysical profiling
AU - K. Li
AU - Y. Wang
AU - Y. Cheng
AU - T. Zheng
AU - S. Long
AU - L. Zhong
AU - M. Wu
AU - Y. Zou
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762428
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762428v1
AB - While widely used, traditional technologies like surface plasmon resonance (SPR) are limited by narrow temporal windows (transient capture and baseline drift), dynamic heterogeneity, and poor physiological temperature performance. Meanwhile, early nanopore approaches are often constrained by limited throughput and heavy reliance on customized modification schemes. Here, we present a digital molecular kinetics (DMK) platform based on large-scale nanopore arrays. By introducing a universal coupling and probe reporting system, DMK achieves broad versatility across diverse molecular pairs, including proteins, peptides, small molecules, DNA, and polymerase complexes. In addition to accurately recovering classical SPR association and dissociation rate constants, by harnessing massive single-molecule event analysis, DMK breaks traditional performance boundaries: it facilitates robust thermodynamic-kinetic profiling across a wide temperature range, resolves distinct conformations in heterogeneous samples, enables ultra-low dissociation rate quantification via maximum likelihood estimation, and reveals energy wells via voltage gradients for binding analysis against environmental perturbations. Furthermore, DMK enables the capture of rapid binding events missed by SPR, offering a new perspective on molecular interaction complexity. This platform offers an effective alternative and upgrade to SPR, opening a digital paradigm for complex molecular analysis and drug discovery.
ER -