Experimental physical chemistry

Chemical Dynamics, One Molecule or Particle at a Time

Our aim is a first-principles, predictive understanding of the chemical dynamics of single stochastic entities: how determinate function emerges from random motion.

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From the Laboratory

Camera view of a single nanoparticle held at the center — A 3D μs-tracking module holds a single nanoparticle at the center of a microscope objective’s focus, while others rapidly random walk past.

Trajectory of a micro-swimmer — A single micro-swimmer steered to a target by photon nudging.

Trajectory of a nanoparticle beside a two-photon image of its surroundings — Multiresolution spectral imaging in action: a single nanoparticle tracked in 3D with μs⁠–⁠nm resolution (left), and the concurrently recorded two-photon laser-scanning image of its surroundings (right).

Trajectory of a nanoparticle at a cell surface — A virus-sized, peptide-coated nanoparticle approaches and lands on a live cell.

Trajectory of a single pseudovirus at a cell — The 3D trajectory of a single HIV-1 pseudovirus moving toward a live CD4 cell.

Theories Verified, Mechanisms Resolved, Discoveries Unexpected

Single-molecule fluorescence intensity trajectories from the study

J. Chem. Phys. · 2026

An apparent power law, resolved into first-order steps

Randomness can mimic law: the apparent power-law kinetics of a blinking dark quencher can be understood as the statistical temporal overlap of independent first-order processes, DNA binding and photoblinking, on top of photobleaching.

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Diffusivity near a liquid–solid interface and a contextual image of nanoparticles

J. Phys. Chem. B · 2025

Continuum fluidic physics near a wall holds down to ~65 nm

The first direct test of the complete Faxén–Brenner solutions on the same nanoparticle: its diffusivity divaricates with distance and direction as predicted, with no adjustable parameters.

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A nanoparticle moving and rotating with a surrounding temperature field

J. Phys. Chem. C · 2025

Hot Brownian motion theory: translation and rotation diverge

Temperature-jump tracking of freely diffusing gold nanoparticles gave the first parameter-free experimental verification of the theory’s prime prediction.

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Artwork depicting conformational dynamics in a nonribosomal peptide synthetase

Nat. Chem. · 2024

Enzyme subdomain dynamics enable chemical chain reactions

The first single-molecule FRET study of a nonribosomal peptide synthetase revealed an ensemble of extended conformations that the enzyme must traverse between its two catalytic conformations.

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Technology & method development

The Technologies behind Our Science

Photon by Photon let data speak for themselves Model-Free Statistical Inference New experimental tools need new ways of analyzing the data to deliver their full potential; after all, it is the unknown chemical dynamics that we hope to uncover. 10 μs & sub-10 nm a single nanoparticle as a dynamics pen and its surroundings, all at once with full 3D fidelity 3D Multiresolution Imaging Records at more than one spatiotemporal resolution concurrently and registers the data in the same 3D frame. RT-3DSPT keeping a fast-moving nanoprobe at the focus at all times Real-Time 3D Single-Particle Tracking Active μs-feedback keeps a freely moving nanoparticle in focus while spectroscopic measurements are made on it. sub-ms & 5 Å 2–4 Å distance accuracy Single-Molecule FRET Every point of a distance–time trajectory carries error bars in both distance and time. SP-DLS time-dependent spectroscopy of individual nanoparticles in solution Single-Particle Dynamic Light Scattering A new type of spectroscopy: it uncovers the signatures and distributions that conventional dynamic light scattering averages away. Maxwell’s Demon control of individual self-propelled swimmers amid thermal fluctuations Photon Nudging The swimmer’s own rotational random walk reorients it; a laser pushes it along its body axis only when it points toward the target. Sort by Valency the number of DNA strands and their digital codes set a nanoparticle artificial atom’s valency DNA-Valency Sorting A new principle of separation in preparative quantities, agnostic to DNA sequence and to particle size, material and shape.

Join the lab

We Are Recruiting

We are looking for experimentalists. Holders of physics and engineering degrees are particularly encouraged to apply.

Two Ph.D. programs at Princeton lead to the lab:

Both admit through Princeton’s Graduate School, with applications due December 1 annually. Graduate School application

Prospective postdocs and students are welcome to write to Haw directly about the ideas they would like to pursue with us: hawyang (at) princeton.edu

Research areas

Chemical Dynamics In Situ and In Operando

Illustration of an enzyme’s conformations along a free-energy ribbon, filmed by single-molecule FRET

Single-Molecule Protein Dynamics

How do the molecular machines of life function under thermal fluctuation?

Single-molecule studies uncover transient conformations and how their spontaneous dynamics enable enzyme-catalyzed chemical transformations.

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Illustration of the trajectory of a nanoparticle as it approaches and lands on a live cell

3D Multiresolution Spectral Imaging

What is the pathway mechanism by which a virus or a therapeutic nanocarrier approaches and enters a specimen?

We pioneered real-time 3D multiresolution microscopy, which tracks a single nanoprobe while concurrently imaging its surroundings; with it we directly monitor chemical dynamics near and at interfaces.

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Illustration of a factory that sorts nanoparticles by the number of DNA strands they carry

Nanoparticle Artificial Molecules

What are the rules governing nanoparticle artificial molecules and what properties could be emergent?

We introduced DNA-valency sorting technology which enables purification of nanoparticles with a well-defined number of DNA strands at reagent scale and, in turn, allows us to explore new chemistry not governed by quantum mechanics.

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