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
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Water-Mediated Phosphoryl Wires Stabilize Pathological Tau Fibrils
L. R. Potnuru, A. DuBose, F. Mon, M. S. Nowotarski, M. Vigers, B. Zhang, C.-T. Han, and S. Han Angew. Chem. Int. Ed. 2026; 0:e21499
https://doi.org/10.1002/anie.202521499. PMID: 39185239. PMCID: PMC11343107.
Hyperphosphorylation of tau is a hallmark of tauopathies, with specific phosphorylation sites elevated in pathological fibrils. Yet, the molecular role of this post-translational modification (PTM) in driving tau aggregation remains unclear. Tau proteins assemble in register, placing high-phosphoryl groups ~4.8 Å apart for high abundance PTMs, requiring an energetically favorable arrangement. This study tests the hypothesis that phosphoryl groups within the fibril core-forming segment readily associate into an extended “wire” that stabilizes the amyloid fibril, counter to the common assumption that closely packed phosphoryl groups is energetically unfavorable due to electrostatic repulsion. We examined two phosphorylation sites linked to neurodegeneration, serine 305 (S305p) and tyrosine 310 (Y310p), using seeding-competent fibrils of the tau peptide jR2R3-P301L. Multiple-quantum spin counting (MQ-SC) by 31P solid-state NMR with dynamic nuclear polarization revealed at least six phosphorus spins arranged in 1D within a protofibril, consistent with the observed MQ coherence order of four. Molecular dynamics simulations and 2D 1H-31P heteronuclear correlation NMR and revealed water-mediated phosphoryl wires enhancing the stability and seeding competency of fibrils made of S305p-phosphorylated jR2R3-P301L compared to the unmodified one. This work introduces the concept that phosphorylation within tau’s core can promote fibril registry and stability through water-mediated hydrogen-bonded phosphoryl wires.
Detection of Mutation-Induced Conformational Changes in an Intrinsically Disordered Protein by Double Quantum Coherence Electron Spin Resonance Methodology
A. S. Roy, K. Tsay, P. P. Borbat, A. Destefano, S. Han, M. Srivastava, J. H. Freed. J. Am. Chem. Soc., 2026, 148, 2378-2387. https://doi.org/10.1021/jacs.5c16298
Corrections J. Am. Chem. Soc. 2026, 148, 8, 9140,. https://doi.org/10.1021/jacs.6c02082
Intrinsically disordered proteins (IDPs) underlie essential cellular functions and drive neurodegenerative diseases through mutation-induced structural changes, yet their conformational heterogeneity often evades crystallography and cryo-EM. Electron spin resonance (ESR) pulsed dipolar spectroscopy (PDS), which determines distance distributions between a pair of spin-labeled residues in a protein, can provide complementary and meaningful information related to conformational heterogeneity in IDPs. Double quantum coherence (DQC) is an important ESRPDS technique, capable of measuring a wide range of distances(∼10toat least80Å), and is a single-frequency technique with a small back ground that can be easily removed. This makes DQC an ideal candidate to probe IDPs. We present a complete theoretical framework for DQC data analysis, incorporating pseudo-secular dipolar coupling and finite pulse effects, enabling rapid and accurate reconstruction of complex distance distributions in doubly nitroxide-labeled IDPs. We validate the method on rigid biradicals with known inter-spin distances. The application to a tau protein fragment(jR2R3) reveals distinct end-to-end distance distributions for the wild-type vs the disease-associated P301Lmutant. The results expose differences in their conformational distributions, which likely govern their divergent aggregation propensities. This advance also establishes DQCESR as a powerful, accessible tool for probing disorders in biomolecular systems.
Exchange coupling-assisted 13C dynamic nuclear polarization in microdiamond at 14 T
Q. Stern, J. Cui, R. Chaklashiya, C. Tobar, M. Judd, O. Nir-Arad, D. Shimon, I. Kaminker, H. Takahashi, J. R. Sirigiri, and S. Han Phys. Chem. Chem. Phys., 2026. https://doi.org/10.1039/D5CP04594K
We investigate nitrogen substitution defects, also known as P1 centers, in Type 1b diamonds generated under high pressure and high temperature (HPHT) as a source of electron spin polarization. The open question was how readily electron spin polarization in this diamond transfers to 13C nuclear spins within the diamond matrix at 14 T by dynamic nuclear polarization (DNP). The goal was to refine the model for clustered P1 centers in HPHT diamonds and evaluate their potential as a source for DNP hyperpolarization or contrast. The study relied on frequency-stepped measurements of DNP profiles under magic angle spinning (MAS) using the mm-wave output of a frequency-tunable gyrotron and a regular superconducting NMR magnet at a single field. We observe up to 700-fold 13C on/off signal enhancements in both MAS and static mode at room temperature, and 130-fold between 35 and 100 K. Modelling the experimental results revealed the dominant role of P1 clusters harboring inter-P1 dipolar and exchange couplings exceeding 100 MHz in achieving 13C DNP at 14.1 T. Our results exemplify the importance of exchange coupling for high-field DNP and provides a refined model for DNP via P1 centers of HPHT diamonds.
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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