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Original website designed in 2009 by Freckles Studio/HY; revised in 2026 by HY.
Multiresolution Spectral Imaging
The interior of a cell is highly heterogeneous; there, molecular and nanoscale dynamics span multiple time and length scales, all in three dimensions (3D). For example: How does a viral particle or a vaccine-delivery vehicle approach a living cell and become internalized? What are the dynamic molecule-level interactions that lead to a (un)successful entry? How does the intracellular cargo get delivered to its destination? To understand the molecule-nanoscale dynamics in the live-cell context, time must be explicitly considered. My lab recognized this problem very early on and has developed a real-time 3D single-particle tracking (RT-3DSPT) technology which enables us to follow a tagged nanoscale probe with 10 μs time resolution and sub-10 nm spatial localization precision. We are also developing new ways to integrate this RT-3DSPT technology with a variety of imaging microscopy modalities as well as single-particle spectroscopy of a freely moving nanoparticle such as the measurement of single-particle 3D reorientation dynamics.
Technical Advances Made
3D Real-Time Multiresolution Microscopy
We pioneered 3D real-time multiresolution microscopy. It integrates, at the hardware level, high-resolution RT-3DSPT (see below) with a concurrent, lower-resolution imaging modality that captures the larger surrounding environment. With it, we directly monitored chemical dynamics at interfaces, for example.
Links:
Appl. Phys. Lett., 88, 223901 (2006): conceptualization;
J. Phys. Chem. C, 111, 32–35 (2007): initial realization, with 2D-only contextual imaging;
Opt. Lett., 32, 2729–2731 (2007): confocal microscope guided by the tracked nanoparticle;
Nat. Nanotechnol., 9, 198–203 (2014): concurrent 3D contextual imaging realization;
Faraday Discuss., 184, 359–379 (2015): technical review;
J. Microbiol. Immunol. Infect., 56, 257–266 (2023): tracking individual viruses.
3D Multi-focal Volumetric Imaging at Video Rates
We have implemented a spatial light modulator (SLM)-based multi-color, multi-focal microscope (MFM) to acquire 3D volume images at video rates (> 20 frames/second). We are currently using this to understand diffusion in confined environments.
Links:
PLoS ONE, 15, e0230217 (2020): new approach to achieve uniform intensity;
Proc. SPIE, 11649, 116490P (2021): SLM-MFM optimization algorithm;
J. Opt. Soc. Am. B, 38, 2792–2798 (2021): MFM localization precision;
Sci. Rep., 12, 16343 (2022): multi-color MFM.
Real-Time 3D Single-Particle Tracking & Spectroscopy
We pioneered real-time 3D single-particle tracking and have since been continually furthering the concept both technically and theoretically. In 2021, we implemented hardware-based lifetime gating to achieve much improved signal-to-background ratio. Most recently, we incorporated a temperature-jump module into the tracking instrument for temperature-jump tracking spectroscopy.
Links:
J. Chem. Phys., 155, 164201 (2021): lifetime-gated RT-3DSPT;
J. Phys. Chem. C, 129, 2083–2089 (2025): temperature-jump tracking spectroscopy.
Contributions to Scientific Problems
Colloidal physics:
Direct experimental observation of direction- and distance-dependent diffusivity divarication
A classical problem in colloidal physics is the behavior of a spherical particle when it randomly walks close to the interface between a fluid and a rigid wall. Solutions to the two complementary aspects of this problem have been provided by Faxén and Brenner, respectively, based on continuum mechanics. Their results predict that the closer the particle is to the interface the slower it moves, but the pace of the slow-down depends on whether the particle steps parallel with or perpendicular to the interface; that is, the particle’s diffusivity divaricates in a distance- and direction-dependent manner. While the theoretical predictions enjoy unequivocal experimental support for μm-sized particles, their applicability on the smaller length scales remains unclear, however. Our work provides the first direct experimental test for the complete Faxén–Brenner solutions and shows that the underlying fluid-dynamics physical picture is valid down to ∼65 nm. Our results thus point to next experimental challenges being in the sub-100-nm regime where finite-temperature fluctuations and the molecularity of the fluid are expected to become increasingly noticeable for smaller nanoparticles.
Updated: 2026.11.07.