We show that a custom ResNet-inspired CNN architecture trained on simulated biomolecule trajectories surpasses the performance of standard algorithms in terms of tracking and determining the molecular weight and hydrodynamic radius of biomolecules in the low-kDa regime in optical microscopy. We show that high accuracy and precision is retained even below the 10-kDa regime, constituting approximately an order of magnitude improvement in limit of detection compared to current state-of-the-art, enabling analysis of hitherto elusive species of biomolecules such as cytokines (~5-25 kDa) important for cancer research and the protein hormone insulin (~5.6 kDa), potentially opening up entirely new avenues of biological research.
We show that a custom ResNet-inspired CNN architecture trained on simulated biomolecule trajectories surpasses the performance of standard algorithms in terms of tracking and determining the molecular weight and hydrodynamic radius of biomolecules in the low-kDa regime in NSM optical microscopy. We show that high accuracy and precision is retained even below the 10-kDa regime, constituting approximately an order of magnitude improvement in limit of detection compared to current state-of-the-art, enabling analysis of hitherto elusive species of biomolecules such as cytokines (~5-25 kDa) important for cancer research and the protein hormone insulin (~5.6 kDa), potentially opening up entirely new avenues of biological research.
We present a nanofluidic optical device based on light-scattering microscopy, which enables label-free detection and quantitative analysis of individual biomolecules freely moving in solution. The key component is a nanochannel with subwavelength dimensions, which is imaged by dark-field microscopy. Due to interference between light scattered by the nanochannel and a biomolecule inside it, a single biomolecule can be directly detected. In addition, the molecular weight can be measured, both by tracking the Brownian motion and from the optical contrast. This is demonstrated for both single DNAs and proteins with molecular weights ranging down to tens of kDa.
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