Quantum Control and Sensing by Spin Cooling
To reveal “invisible” NMR signal of surfaces, active sites, and functional species in catalysis, molecular recognition and quantum materials using out of the box tools.
Quantum Resonance Sensing of Molecular Activity in Water
SpinQubes
To transform the study of molecular and soft materials structure, dynamics and interactions using innovative magnetic resonance spectroscopy tools and through the design of coupled electron and nuclear spin systems as amplifiers and sensors.
Spins as Nature’s Quantum Reporters
The Han Lab pushes the frontiers of magnetic resonance and quantum information science with the goal of “seeing” chemical and biological building blocks and processes at the quantum limit. The two main themes of the Han Lab over the past 20 years have been spins and water. Electron and nuclear spins are the ultimate quantum reporters and contrast agents for biochemical processes and chemical building blocks. Advanced magnetic resonance sensing, control over the spatial organization of electron and nuclear spin clusters, and dual electron-nuclear magnetic resonance techniques have contributed to uncovering new design rules for molecular recognition, as well as the surface structuring, shaping, and ordering of biological water.
Recently, we have begun to ask the ultimate question: do quantum phenomena direct and control biological and chemical processes? The answer is yes, but high-quality experimental validations are key to qualifying the context and boundaries of these answers. Recent breakthrough developments by the Han Lab offer one-of-a-kind experimental tools that allow us to gain control over the initialization and manipulation of quantum spin states via spin cooling at high magnetic fields.
This development effort requires interdisciplinary research tools, including instrument development to combine electron and nuclear magnetic resonance with optical excitation and detection, the design of precisely tuned electron and nuclear spin qubits, spin dynamics simulations, and studies of the dynamics and thermodynamics of solvation to control biomolecular activity and assembly.
We are motivated by the power of “Seeing is Believing.” New tools for visualizing molecular interactions and materials interfaces—previously “invisible”—have fundamentally transformed our ability to discover solutions and ask new questions. The next frontier of visualization will be quantum microscopy that relies on spins as quantum reporters to deliver molecular insights that conventional microscopy cannot.
Areas Of Research
Research in the Han Lab develops novel tools to exploit spins as quantum reporters with unprecedented sensitivity and information content and as biological qubits with spin state control. Our core interest lies in advancing spin-based quantum information science, solvation science, and the molecular basis of signal transduction.
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Chromophore Receptors as Biological Qubits
To reveal long-standing questions on the structure and dynamics of water on proteins, membranes to catalyst support surfaces.
Water Directed Protein Fibrils and Tunable Hydrogels
To understand, control and engineer protein aggregation pathways, protein surface activity to protein liquid-liquid phase separation.
Publications
+ VIEW ALLSpectroscopically Dark Phosphate Features Revealed by Chemical Exchange Saturation Transfer
J. Lu, J. S. Straub, M. S. Nowotarski, S. Han, X. Xu, A. Jerschow NMR Biomed. 2024, 37:e5057
https://doi.org/10.1002/nbm.5057. PMID: 37853675.
Phosphate is an essential anion in the human body, comprising approximately 1% of the total body weight, and playing a vital role in metabolism, cell membranes, and bone formation. We have recently provided spectroscopic, microscopic, and computational evidence indicating that phosphates can aggregate much more readily in solution than previously thought. This prior work provided indirect evidence through the observation of unusual 31P NMR relaxation and line-broadening effects with increasing temperature. Here, we show that, under conditions of slow exchange and selective RF saturation, additional features become visible in chemical exchange saturation transfer (CEST) experiments, which appear to be related to the previously reported phosphate clustering. In particular, CEST shows pronounced dips several ppm upfield of the main phosphate resonance at low temperatures, while direct 31P spectroscopy does not produce any signals in that range. We study the pH dependence of these new spectroscopic features and present exchange and spectroscopic parameters based on fitting the CEST data. These findings could be of importance in the investigation of phosphate dynamics, especially in the biological milieu.
Control over Conformational Landscapes of Polypeptoids by Monomer Sequence Patterning
A. J. DeStefano, S. D. Mengel, M. W. Bates, S. Jiao, M. S. Shell, S. Han, R. A. Segalman Macromolecules 2024, 57, 4, 1469-1477
The ability to program chain conformation and structure through control over the monomer sequence of synthetic polymers has broad implications for next-generation material design. While related problems of protein folding and de novo design have generated accurate predictions of three-dimensional (3D) folded chain structures, generalization to synthetic polymers remains intractable due to the requirement of large structural databases and the intrinsically disordered nature of polymer building blocks. In this work, polypeptoids, a class of peptidomimetic synthetic polymers, are utilized to build a general workflow for the study of relationships between the monomer sequence and dynamic 3D chain structure in solution. This work demonstrates how control over the monomer sequence can alter the conformational landscape of synthetic polymers to deviate dramatically from classical chain statistics. Specifically, the distribution of end-to-end distances, as measured by double electron–electron resonance spectroscopy in dilute solvent, is systematically skewed toward shorter distances with an increasing number of hydrophobes and further refined by hydrophobe arrangement in amphiphilic polypeptoid chains.
Insights into Conformational Ensembles of Compositionally Identical Disordered Peptidomimetics
E. C. Day, K. C. Cunha, R. J. Zhao, A. J. DeStefano, J. N. Dodds, M. A. Yu, J. R. Bemis, S. Han, E. S. Baker, J.-E. Shea, R. B. Berlow, A. S. Knight Polym. Chem. 2026, 15, RP111093
https://doi.org/10.1039/d4py00341a. PMID: 39781370. PMCID: PMC11709448.
While the conformational ensembles of disordered peptides and peptidomimetics are complex and challenging to characterize, they are a critical component in the paradigm connecting macromolecule sequence, structure, and function. In molecules that do not adopt a single predominant conformation, the conformational ensemble contains rich structural information that, if accessible, can provide a fundamental understanding related to desirable functions such as cell penetration of a therapeutic or the generation of tunable enzyme-mimetic architecture. To address the fundamental challenge of describing broad conformational ensembles, we developed a model system of peptidomimetics comprised of polar glycine and hydrophobic N-butylglycine to characterize using a suite of analytical techniques. Using replica exchange molecular dynamics atomistic simulations and liquid chromatography coupled to ion mobility spectrometry, we were able to distinguish the conformations of compositionally identical model sequences. However, differences between these model sequences were more challenging to resolve with characterization tools developed for intrinsically disordered proteins and polymers, including double electron–electron resonance (DEER) spectroscopy and diffusion ordered spectroscopy (DOSY) NMR. Finally, we introduce a facile colorimetric assay using immobilized sequences that leverages a solvatochromic probe, Reichardt’s dye, to visually reveal conformational trends consistent with the experimental and computational analysis. This rapid colorimetric technique provides a complementary method to characterize the disorder of macromolecules and examine conformational ensembles as an isolated or multiplexed technique.
Recent News
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Wishing Everyone a Wonderful 25′ Holiday Season from Han Lab!
December 23, 2025
Three Defenses in the Festive Season: Congratulations to Our Newest PhDs
December 13, 2025
Interested in joining the Han research group? Reach us at han-ofc@northwestern.edu
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