Department of NanoEngineering

The structural and chemical properties of metal nanoparticles are often dictated by their interactions with molecular ligand shells. These interactions are highly material-specific and can vary significantly even among elements within the same group or materials with similar crystal structure. In this study, we surveyed the heterogeneous interactions between an m-terphenyl isocyanide ligand and Au and Ag nanoparticles (NPs) at the single-molecule limit. Specifically, we found that the ligation behavior with this molecule differs significantly between that of Au and AgNPs. Surface-enhanced Raman spectroscopy measurements revealed unique enhancement factors for two molecular vibrational modes between two metal surfaces, indicating different ligand binding geometries. Molecular-level characterization using scanning tunneling microscopy allowed us to directly visualize these variations between Ag and Au surfaces, which we assign as two distinct binding mechanisms. This molecular-scale visualization provides clear insights into the different ligand-metal interactions as well as the chemical behavior and spectroscopic characteristics of isocyanide-functionalized NPs.

Controlling molecular actions on demand is a critical step toward developing single-molecule functional devices. Such control can be achieved by manipulating the interactions between individual molecules and their nanoscale environment. In this study, we demonstrate the conformational transition of a single pyrrolidine molecule adsorbed on a Cu(100) surface, driven by vibrational excitation through tunneling electrons using scanning tunneling microscopy. We identify multiple transition pathways between two structural states, each governed by distinct vibrational modes. The nuclear motions corresponding to these modes are elucidated through density functional theory calculations. By leveraging fundamental forces, including van der Waals interactions, dipole-dipole interactions, and steric hindrance, we precisely tune the molecule-environment coupling. This tuning enables the modulation of vibrational energies, adjustment of transition probabilities, and selection of the lowest-energy transition pathway. Our findings highlight how tunable force fields in a nanoscale cavity can govern molecular conformational transitions, providing a pathway to engineer molecule-environment interactions for targeted molecular functionalities.

Poisoning by organophosphate (OP) nerve agents remains a pressing global threat due to their extensive use in chemical warfare agents and pesticides, potentially causing high morbidity and mortality worldwide. This urgent need for effective countermeasures has driven considerable interest in innovative detoxification approaches. Among these, nanoparticle technology stands out for its multifunctional potential and wide-ranging applications. This review highlights recent advancements in nanoparticle platforms developed for OP detoxification, focusing on five main types: inorganic nanoparticles, lipid-based nanoparticles, polymer-based nanoparticles, metal-organic framework nanoparticles, and cellular nanoparticles. For each platform, we discuss representative examples that illustrate how structural and functional properties enhance their effectiveness as nanocarriers, nanocatalysts, or nanoscavengers, ultimately enabling safe and efficient OP detoxification. This review aims to stimulate further technological innovation in OP-detoxifying nanoparticles and encourage broader development of detoxification strategies.

Rechargeable Li-SO₂ batteries offer low-cost, high-energy density benefits and can leverage manufacturing processes for the existing primary version at a commercial scale. However, they have so far only been demonstrated in an "open-system" with continuous gas supply, preventing practical application. Here, the utilization and reversibility of SO₂ along with the lithium stability are addressed, all essential for long-life, high-energy batteries. The study discovers that high SO₂ utilization is achievable only from SO₂ dissolved in electrolytes between the lithium anode and carbon cathode. This results from a unique osmosis phenomenon where SO₂ consumption increases salt concentration, driving the influx of organic solvents rather than SO₂ from outside the current path. This insight leads to configure a bobbin-cell with all electrolytes between the electrodes, realizing nearly 70% of SO₂ utilization, > 12x greater than in conventional coin cells. To improve reaction rate and SO₂ reversibility, triphenylamine is employed to the electrolyte, creating an electron-rich environment that alleviates the disproportionation of discharge products. Incorporating this additive into a bobbin-cell with a lithium protective layer yields a cell with a projected energy density exceeding 183.2 Wh kg^-1. The work highlights the potential of Li-SO₂ batteries as affordable, sustainable energy storage options.

The structural and chemical properties of metal nanoparticles are often dictated by their interactions with molecular ligand shells. These interactions are highly material-specific and can vary significantly even among elements within the same group or materials with similar crystal structure. In this study, we surveyed the heterogeneous interactions between an m-terphenyl isocyanide ligand and Au and Ag nanoparticles (NPs) at the single-molecule limit. Specifically, we found that the ligation behavior with this molecule differs significantly between that of Au and AgNPs. Surface-enhanced Raman spectroscopy measurements revealed unique enhancement factors for two molecular vibrational modes between two metal surfaces, indicating different ligand binding geometries. Molecular-level characterization using scanning tunneling microscopy allowed us to directly visualize these variations between Ag and Au surfaces, which we assign as two distinct binding mechanisms. This molecular-scale visualization provides clear insights into the different ligand-metal interactions as well as the chemical behavior and spectroscopic characteristics of isocyanide-functionalized NPs.

Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating the interferon-inducible ubiquitin-like modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) that incorporate unnatural amino acids into the C-terminal tail of ISG15, enabling the selective detection of USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) such as USP5 and USP14. Combined with a ubiquitin-based DUB ABP, the USP18 ABP is employed in a chemoproteomics screening platform to identify and assess inhibitors of DUBs including USP18. We further demonstrate that USP18 ABPs can be utilized to profile differential activities of USP18 in lung cancer cell lines, providing a strategy that will help define the activity-related landscape of USP18 in different disease states and unravel important (de)ISGylation-dependent biological processes.

Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes. However, the invasive nature of intratracheal administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method of delivering microrobots to the lungs. A nebulizer is employed to encapsulate picoeukaryote algae microrobots within small aerosol particles, enabling them to reach the lower respiratory tract. Post nebulization, the microrobots retain their motility (~55 μm s-1) to help achieve a homogeneous lung distribution and long-term retention exceeding five days in the lungs. Therapeutic efficacy is demonstrated in a mouse model of acute methicillin-resistant Staphylococcus aureus pneumonia using this pulmonary inhalation approach to deliver microrobots functionalized with platelet membrane-coated polymeric nanoparticles loaded with vancomycin. These promising findings underscore the benefits of inhalable biohybrid microrobots in a setting that does not require anesthesia, highlighting the substantial translational potential of this delivery system for routine clinical applications.

Sulfide solid-state electrolytes (SSEs) are promising candidates to realize all solid-state batteries (ASSBs) due to their superior ionic conductivity and excellent ductility. However, their hypersensitivity to moisture requires processing environments that are not compatible with today's lithium-ion battery manufacturing infrastructure. Herein, we present a reversible surface modification strategy that enables the processability of sulfide SSEs (e. g., Li₆PS₅Cl) under humid ambient air. We demonstrate that a long chain alkyl thiol, 1-undecanethiol, is chemically compatible with the electrolyte with negligible impact on its ion conductivity. Importantly, the thiol modification extends the amount of time that the sulfide SSE can be exposed to air with 33% relative humidity (33% RH) with limited degradation of its structure while retaining a conductivity of above 1 mS cm^-1 for up to 2 days, a more than 100-fold improvement in protection time over competing approaches. Experimental and computational results reveal that the thiol group anchors to the SSE surface, while the hydrophobic hydrocarbon tail provides protection by repelling water. The modified Li₆PS₅Cl SSE maintains its function after exposure to ambient humidity when implemented in a Li_0.5In | |LiNi_0.8Co_0.1Mn_0.1O₂ ASSB. The proposed protection strategy based on surface molecular interactions represents a major step forward towards cost-competitive and energy-efficient sulfide SSE manufacturing for ASSB applications.

Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells' electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput. However, accessing intracellular potentials with NEAs remains challenging. This study presents an AI-supported technique that leverages thousands of synchronous eAP and iAP pairs from stem-cell-derived cardiomyocytes on NEAs. Our analysis revealed strong correlations between specific eAP and iAP features, such as amplitude and spiking velocity, indicating that extracellular signals could be reliable indicators of intracellular activity. We developed a physics-informed deep learning model to reconstruct iAP waveforms from extracellular recordings recorded from NEAs and Microelectrode arrays (MEAs), demonstrating its potential for non-invasive, long-term, high-throughput drug cardiotoxicity assessments. This AI-based model paves the way for future electrophysiology research across various cell types and drug interactions.