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Single-molecule microscopy has become an indispensable tool for biochemical analysis. The capability of characterizing distinct properties of individual molecules without averaging has provided us with a different perspective for the…

Applied Physics · Physics 2020-05-21 Miao-Hsuan Chien , Silvan Schmid

The clinical need for ultra-sensitive molecular analysis has motivated the development of several endpoint assay technologies capable of single molecule readout. These endpoint assays are now primarily limited by the affinity and…

Biological Physics · Physics 2019-05-22 Derin Sevenler , Jacob Trueb , M. Selim Ünlü

A protein undergoes conformational dynamics with multiple time scales, which results in fluctuating enzyme activities. Recent studies in single molecule enzymology have observe this "age-old" dynamic disorder phenomenon directly. However,…

Biomolecules · Quantitative Biology 2009-11-10 Zhanghan Wu , Vlad Elgart , Hong Qian , Jianhua Xing

The photo-kinetics of fluorescent molecules have enabled the circumvention of far-field optical diffraction-limit. Despite its enormous potential, the necessity to label the sample may adversely influence the delicate biology under…

Label-free biosensors enable the monitoring of biomolecular interactions in real-time, which is key to the analysis of the binding characteristics of biomolecules. While refractometric optical biosensors are sensitive and well-established,…

Recent experimental results have shown that active enzymes can diffuse faster when they are in the presence of their substrates. Fluorescence correlation spectroscopy (FCS), which relies on analyzing the fluctuations in fluorescence…

Subcellular Processes · Quantitative Biology 2019-09-25 Mengqi Xu , Lyanne Valdez , Aysuman Sen , Jennifer L. Ross

Single-molecule fluorescence techniques have revolutionized our ability to study proteins. However, the presence of a fluorescent label can alter the protein structure and/or modify its reaction with other species. To avoid the need for a…

Biological Physics · Physics 2022-04-07 Aleksandr Barulin , Prithu Roy , Jean-Benoît Claude , Jérôme Wenger

Engineered electromagnetic fields in plasmonic nanopores enable enhanced optical detection and their use in single molecule sequencing. Here, a plasmonic nanopore prepared in a thick nanoporous film is used to investigate the interaction…

Electromagnetic hot-spots at ultra-narrow plasmonic nanogaps carry immense potential to drive detection limits down to few molecules in sensors based on surface enhanced Raman or Fluorescence spectroscopies. However, leveraging the EM…

Time-resolved spectral techniques play an important analysis tool in many contexts, from physical chemistry to biomedicine. Customarily, the label-free detection of analytes is manually performed by experts through the aid of classic…

Machine Learning · Computer Science 2020-11-17 Stefano Rini , Hirotsugu Hiramatsu

Cyclic Voltammetry (CV) is the most commonly used method in electrochemistry to characterize electrochemical reactions, usually involving macroscopic electrodes. Here we demonstrate an optical CV technique called Opto-iontronic Microscopy,…

Soft Condensed Matter · Physics 2026-01-15 Zhu Zhang , Haolan Tao , Cheng Lian , René van Roij , Sanli Faez

The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an…

Protein phosphorylation provides a dynamic readout of cellular signaling yet remains difficult to detect at low abundance and stoichiometry. Single-molecule surface-enhanced Raman spectroscopy (SM-SERS) using particle-in-pore plasmonic…

Mesoscale and Nanoscale Physics · Physics 2026-04-09 Mulusew W. Yaltaye , Yingqi Zhao , Kuo Zhan , Vahid Farrahi , Jian-An Huang

Surface-enhanced Raman spectroscopy (SERS) is a sensitive label-free optical method that can provide fingerprint Raman spectra of biomolecules such as DNA, amino acids and proteins. While SERS of single DNA molecule has been recently…

High-Q optical resonators allow label-free detection of individual nanoparticles through perturbation of optical signatures but have practical limitations due to reliance on random diffusion to deliver particles to the sensing region. We…

Optics · Physics 2016-10-03 Jeewon Suh , Kewen Han , Christopher W Peterson , Gaurav Bahl

Current advances in ultrafast electron microscopy make it possible to combine optical pumping of a nanostructure and electron beam probing with sub{\aa}ngstrom and femtosecond spatiotemporal resolution. We present a theory predicting that…

Investigating the dynamics of single biomolecules is essential for unlocking new frontiers in biophysics and medicine. Here, we present a transformative approach using metamaterial optical tweezers to trap and study individual urease…

Plasmon-enhanced chemical transformations at the solid-liquid interface can be imaged with high sensitivity, chemical selectivity, and nanoscale precision through tip-enhanced Raman scattering (TERS). We demonstrate the latter for the first…

Chemical Physics · Physics 2019-03-29 Ashish Bhattarai , Patrick Z. El-Khoury

Single molecule detection provides detailed information about molecular structures and functions, but it generally requires the presence of a fluorescent marker which can interfere with the activity of the target molecule or complicate the…

Enzymes are essential to maintain organisms alive. Some of the reactions they catalyze are associated with a change in reagents chirality, hence their activity can be tracked by using optical means. However, illumination affects enzyme…