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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.

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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.

SEE ALL RESEARCH

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.

Chromophore Receptors

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.

On the left is a box with two graphs side by side on the bottom, the left one showing a shorter "hill" than the one on the right. Both graphs on the left show EPR signal as a function of field. Above each one are two alpha-helix strands represented by ovals, the left red and the right orange, each ending in a Gd spin label represented by a purple circle. The distance between the two strands is longer for the one on the right than for the one on the left. To the right of this box with figures is a figure up top showing a similar "hill" except in blue for laser on and black for laser off, and below it is a buildup curve. There is an arrow pointing from the blue hill figure down to the buildup curve figure (Linewidth in Gauss vs time) that reads "Extract Change in Linewidth that scales with Gd(III) spin distance". The box on the left points to the laser on/off chart on the right with an arrow labeled "Rapid Scan TiGGER"
Field-domain rapid-scan EPR at 240 GHz for studies of protein functional dynamics at room temperature
B. D. Price, A. Sojka, S. Maity, I. M. Chavez, M. Starck, M. Z. Wilson, and M. S. Sherwin J. Magn. Reson., 366 (2024), 107744.
https://doi.org/10.1016/j.jmr.2024.107744. PMID: 39096714. PMCID: PMC12459749.

We present field-domain rapid-scan (RS) electron paramagnetic resonance (EPR) at 8.6 T and 240 GHz. To enable this technique, we upgraded a homebuilt EPR spectrometer with an FPGA-enabled digitizer and real-time processing software. The software leverages the Hilbert transform to recover the in-phase (𝐼) and quadrature (𝑄) channels, and therefore the raw absorptive and dispersive signals, 𝜒′ and 𝜒′′, from their combined magnitude (√𝐼2+𝑄2). Averaging a magnitude is simpler than real-time coherent averaging and has the added benefit of permitting long-timescale signal averaging (up to at least 2.5 × 106 scans) because it eliminates the effects of sourcereceiver phase drift. Our rapid-scan (RS) EPR provides a signal-to-noise ratio that is approximately twice that of continuous wave (CW) EPR under the same experimental conditions, after scaling by the square root of acquisition time. We apply our RS EPR as an extension of the recently reported time-resolved Gd-Gd EPR (TiGGER) [Maity et al., 2023], which is able to monitor inter-residue distance changes during the photocycle of a photoresponsive protein through changes in the Gd-Gd dipolar couplings. RS, opposed to CW, returns field-swept spectra as a function of time with 10 ms time resolution, and thus, adds a second dimension to the static field transients recorded by TiGGER. We were able to use RS TiGGER to track time-dependent and temperature-dependent kinetics of AsLOV2, a light-activated phototropin domain found in oats. The results presented here combine the benefits of RS EPR with the improved spectral resolution and sensitivity of Gd chelates at high magnetic fields. In the future, field-domain RS EPR at high magnetic fields may enable studies of other real-time kinetic processes with time resolutions that are otherwise difficult to access in the solution state.

On the left is a chromophore radical chemical structure labeled "PDI" in a blue oval highlight, with green lighting hitting two electron spins on it. On the right is a BDPA molecular structure in a red circular highlight with one electron spin. An arrow going from the left to the right structure labeled "ESP" is shown. A cycle arrow with NOVEL and REVERSE NOVEL is also shown on the right, with the Reverse NOVEL side including two blacked out spins. There is a wave pattern labeled "uW" for "microwave" coming out of the BDPA side.
Coherent Control over Nuclear Hyperpolarization Using an Optically Initializable Chromophore-Radical System
H. M. Le, J. S. Straub, Q. Stern, A. Equbal, Y. Qiu, M. D. Krzyaniak, M. R. Wasielewski, and S. Han J. Am. Chem. Soc., 147 (39) (2025), 35313–35322.

Chromophore radicals (CR) are emerging as important components for molecular quantum information science (QIS), especially in the context of quantum sensing. Here, we demonstrate that the optically hyperpolarized electrons in a 1,6,7,12-tetrakis(4-tert-butylphenoxy)-perylene-3,4,9,10-bis(dicarboximide) (tpPDI) covalently linked to a partially deuterated 1,3-bis(diphenylene)-d16-2-phenylallyl radical (BDPA-d16) can be coherently manipulated via pulsed dynamic nuclear polarization (DNP) methods to transfer polarization to nuclear spins and back. Under light illumination at 85 K, electron hyperpolarization in BDPA is enhanced 2.1- to 2.4-fold over thermal polarization and lasts for more than 100 ms. By applying nuclear orientation via electron spin-locking (NOVEL) DNP, this optically amplified electron hyperpolarization was successfully transferred to a 1H nuclear spin within the CR system and efficiently returned to the electron spin for readout via reverse-NOVEL. The NOVEL transfer efficiency of 65% amounts to a 688-fold nuclear spin hyperpolarization of the target nuclear spin, considering the 2.1-fold electron spin hyperpolarization. This reversible coherent manipulation of hyperpolarization transfer highlights the utility of CR systems to initialize and read out nuclear spin states in a disordered matrix at moderate cryogenic temperatures. Coupled with CRs’ environmental compatibility, tunability, and precise state initialization, these results highlight the promising role of nuclear spins in CRs for QIS applications, including quantum sensing and memory.

Structure-specific Mini-Prion Model for Alzheimer’s Disease Tau Fibrils
V. Vijayan, G. E. Merz, K. Tsay, A. P. Longhini, S. Lobo, A. Quddus, K. L. S. Nakagawa, M. P. Vigers, A. A. Melo, E. Tse, J.-E. Shea, M. S. Shell, K. S. Kosik, D. R. Southworth, S. Han bioRxiv, (2025).

A critical discovery of the past decade is that tau protein fibrils adopt disease-specific hallmark structures in each tauopathy. The faithful generation of synthetic fibrils adopting hallmark structures that can serve as targets for developing diagnostic and/or therapeutic strategies remains a grand challenge. We report on a rational design of synthetic fibrils built of a short peptide that adopts a critical structural motif in tauopathy fibrils found in Alzheimer’s Disease (AD) and Chronic Traumatic Encephalopathy (CTE). They serve as minimal prions with exquisite seeding competency, in vitro and in tau biosensor cells, for recruiting tau constructs ten times larger its size en route to AD or CTE fibril structures. We demonstrate that the generation of AD and CTE-like fibril structures is dramatically catalyzed in the presence of mini-AD prions and further influenced by salt composition in solution. Double Electron-Electron Resonance studies confirmed the preservation of AD-like folds across multi-generational seeding. Fibrils formed with the full AD/CTE-like core show strong seeding competency, with their templating effect dominating over the choice of salt composition that tunes the initial selection of AD- and CTE-like fibril populations. The mini-AD prions serve as a potent catalyst with templating capabilities that offer a novel strategy to design pathological tau fibril models.

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Interested in joining the Han research group? Reach us at han-ofc@northwestern.edu

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