Bridging chemistry, physics, and nanoengineering, our lab develops sophisticated experimental and computational techniques to visualize and manipulate single molecules and nanoparticles with nanometer precision.
PSF Theory
To image single molecules, we employ techniques like widefield microscopy, confocal scanning laser microscopy, and near-field scanning optical microscopy (NSOM). In NSOM, a tapered optical fiber acts as a nanoscale light source.
Underpinning all these imaging modalities is the point spread function (PSF), which characterizes the diffraction image arising from a small object. We are developing a comprehensive PSF theory for various illumination and detection modes and incorporate it into our free software PSFLab. Currently, PSFLab is utilized by research groups from over 50 countries across the world to model PSFs.
Corral Trapping
The physical and chemical properties of molecules originate from quasi-electrostatic interactions between atoms and molecules. It seems prudent, therefore, to leverage electrostatic forces to efficiently interact with molecules.
Based on this rationale, we conceived and developed a new approach for trapping and manipulating individual biomolecules and nanoparticles: corral trapping. Corral trapping utilizes electrostatic and dielectrophoretic forces to confine particles to substrate areas devoid of charge.
This technology unlocks new capabilities for the deliberate (rather than random) assembly of molecular-scale devices, detection of single-base DNA mutations at the single molecule level, and investigation of diffusion-limited biophysical phenomena over prolonged timescales.
Molecular Fields
Biological molecules like myoglobin and hemoglobin frequently utilize electric fields to perform their roles, implying these fields are vital to function. To further investigate, we employ fluorescent heme analogs that report on the active site’s electrostatic environment in these proteins.
Spectroscopic measurements involve applying external electric fields at cryogenic temperatures, which shift the electronic energy levels (Stark effect). Using quantum chemical approaches, we developed two new data analysis methods to derive the magnitude and orientation of the electric field created by the protein from such experiments.