Department of NanoEngineering

Optimal levodopa (L-Dopa) dosing for the personal management of Parkinson's disease represents a major clinical challenge due to L-Dopa's narrow therapeutic window and inter- and intra-patient absorption variability. Current methods for measuring L-Dopa, relying on repeated blood draws for centralized laboratory measurements, fall short of capturing dynamic L-Dopa fluctuations that are relevant for timely interventions. Here, we present a minimally invasive microneedle (MN)-based wearable biosensor for continuous monitoring of L-Dopa (CDM) in human subjects. The MN biosensor platform relies on a tyrosinase-functionalized working electrode for detecting L-Dopa in interstitial fluid (ISF) through enzymatic electrochemical detection. The device was evaluated in healthy volunteers and participants with Parkinson's disease in clinical settings, illustrating its ability to provide actionable temporal insights. Critical validation of the MN biosensor was carried out by comparing the ISF L-Dopa signals with plasma L-Dopa concentrations measured by high-performance liquid chromatography (HPLC). Using subject-specific calibration and lag-time correction, the ISF-derived drug profiles showed a close correlation with plasma L-Dopa pharmacokinetics, with a mean absolute relative difference (MARD) of 9.64%. An inverse correlation between the L-Dopa pharmacokinetics and the corresponding motor performance was observed. Such pioneering demonstration of the clinical feasibility of MN-based CDM in humans highlights its considerable potential for supporting the management of Parkinson's disease.

Precision management of Parkinson's disease (PD) requires frequent levodopa (L-dopa) dose adjustments, yet current monitoring relies on subjective symptom reporting and infrequent blood testing. Here, we present a soft, fingertip-mounted wearable platform for continuous, noninvasive L-dopa monitoring. By combining osmotically harvested passive sweat with soft hydrogels, a potentiometric sensing strategy, and individualized calibration, the platform estimates blood L-dopa information from sweat without external power or iontophoresis. Strong correlations between sweat and high-performance liquid chromatography (HPLC)-measured blood L-dopa concentrations were observed in healthy ([Formula: see text]) and PD subjects ([Formula: see text]) following a single immediate-release L-dopa/carbidopa dose. Low motor symptom scores aligned with peak L-dopa levels, confirming pharmacodynamic relevance. L-dopa cleared faster in PD patients despite similar bioavailability to healthy subjects, while recorded hemodynamic responses showed short hypotensive trends for both groups. Machine learning identified sweat and blood pressure as key contributors toward accurate estimation of blood L-dopa levels (mean absolute error = 2.02 µM vs. ground truth). Overall, our easy-to-use, energy-efficient wearable supports real-time, stimulation-free monitoring, potentially enabling at-home dosage adjustments and paving the way for future autonomous closed-loop L-dopa therapeutic system development.

Immunotherapy has emerged as a new pillar of cancer therapeutics that utilizes the patients own immune system to target tumor cells, a particular advantage in the context of hard-to-treat cancers. Virus-based immunotherapies have shown great potential as cancer treatments, including oncolytic viruses, viral vectors and virus-like particles. Here, we discuss the development, applications, challenges, and future opportunities of cowpea mosaic virus (CPMV) as a plant virus-based candidate for intratumoral immunotherapy, focusing on the treatment of aggressive, metastatic and refractory solid tumors. Evidence of antitumor efficacy has been gathered from mouse tumor models and veterinary clinical trials involving canine cancer patients. CPMV is promising as a monotherapy and as part of combination therapies, including chemotherapy, radiation, checkpoint inhibitors, and cytokine therapies. The putative mechanism of action is described, highlighting key features such as the capsid proteins and RNA acting as Toll-like receptor (TLR) agonists for TLR-2, TLR-4 and TLR-7, as well as the presentation of unique epitopes that prime a Th-1 balanced immune response. The nanoparticle structure of CPMV enhances efficacy by exerting multivalency and avidity effects. The biodistribution, toxicity, and agronomical safety profile of CPMV is also described, especially in relation to tumor retention, hematologic toxicity, allergenicity and adverse events, and viral shedding. This body of work provides a thorough exploration of a cancer immunotherapy candidate in development for more than 10 years, positioning CPMV as a promising intratumoral platform for hard-to-treat cancers.

A perovskite precursor solution that delivers power conversion efficiencies (PCEs) exceeding 26% in conventional n-i-p solar cells exhibits severe performance losses when directly applied to inverted p-i-n architectures, revealing that high-efficiency compositions are not inherently transferable. Here, we identify a buried-interface crystallization mismatch, arising from the distinct physicochemical natures of inorganic SnO2 electron-transporting layers and organic self-assembled hole-transporting monolayers (SA-HTLs), as the origin of this divergence. The methylammonium chloride (MACl)-associated intermediate phase, MA2Pb3I8·2DMSO, persists and decomposes with strong underlayer dependence, stabilizing beneficially on SnO2 but impeding crystallization on SA-HTLs. To overcome this limitation, we develop a chloride-origin engineering strategy that decouples chloride functionality from volatile organic ammonium species by incorporating low-solubility lead chloride (PbCl2) with strong Pb–Cl coordination. This enables controlled interfacial desolvation and nucleation on SA-HTLs, suppresses buried defects, and establishes buried-interface crystallization control as a design principle for architecture-convergent, high-efficiency perovskite solar cells.

This paper describes a method of micropatterning commercial silicone elastomers using a photodeactivated hydrosilylation inhibitor. The method uses small doses of 365 nm light and is compatible with common platinum-cured formulations of poly­(dimethylsiloxane) (PDMS). The hydrosilylation (cross-linking) inhibitor is a UV-sensitive emulsion composed of FeCl3 and a commercially available poly­(ethylene oxide)-co-PDMS copolymer. This mixture enables selective solidification of exposed regions while preventing solidification in unexposed areas. This approach facilitates the creation of complex geometries while preserving the mechanical tunability, biocompatibility, and optical transparency of the base silicone. The patterned structures have been successfully used to fabricate high-resolution microfluidic devices and substrates for measuring the contractility of cardiac cells with integrated strain gauges. The process achieves feature sizes as small as 20 μm and is compatible with standard photolithography tools.

Large-scale battery manufacturing requires understanding the fundamental principles of materials and interfaces and relies on advanced techniques for detailed interrogation. Despite advancements in the industrial scale production and their associated quality control tools, challenges such as electrode heterogeneity, internal defects, and large-scale material waste (e.g., scrap) can hamper manufacturing. Synchrotron X-ray characterization techniques offer spatial, temporal, and chemical resolution that can provide diagnostic insights for metrology across various manufacturing steps. This review examines the use of synchrotron tools to advance understanding of key steps in the battery manufacturing process. Recent examples demonstrate how synchrotron methods resolve manufacturing challenges and uncover degradation pathways that are otherwise inaccessible. Future directions for advancing battery manufacturing emphasize collaboration between academia and industry through the use of synchrotron X-ray techniques.

All-solid-state batteries using sulfur-based positive electrodes (cathodes) offer a cost-effective route to achieve high specific energy. However, low active material utilization and cycle life hinder performance. Here, we demonstrate a positive electrode design that employs sulfide solid-state electrolytes, where a high energy synthesis approach forms a metastable and ionically conductive interphase on the active material surface. This interphase facilitates high active material utilization and contributes capacity with cycling. We also show that tailoring active material particle sizes to the micron-scale improves rate performance and cycling stability. Structural analysis reveals that the substantial volume change of sulfur-based positive electrodes during operation can partially offset that of the negative electrodes, thereby mitigating internal mechanical stress. The combined design principles enable sulfur areal capacities up to 11 mAh cm-2 while maintaining stable cycling at 25 °C. We further demonstrate several specific-energy-focused cell architectures, particularly a Li2S anode-free pouch cell that operates under “low stack pressure” of 10 MPa. This work outlines practical design strategies for constructing high-specific-energy all-solid-state batteries for a broad range of emerging applications.

In this work, we developed a collagenase-responsive hydrogel system to covalently load cancer immunotherapy candidate cowpea mosaic virus (CPMV) using 3D Digital Light Processing (DLP) bioprinting technology. CPMV was functionalized with norbornene groups (CPMV-NB), which was then bioprinted into hydrogels with 8-arm polyethylene glycol (PEG) norbornene and a collagenase-cleavable peptide via photoinduced thiol-ene click chemistry. This strategy enabled stable retention of CPMV-NB within the hydrogels and achieved controlled release of CPMV-NB triggered by collagenase. Furthermore, released CPMV-NB retained its immunogenicity to stimulate immune cells.

The microscopic structure of water’s surface is crucial to many natural and industrial processes, but studying its hydrogen bond (H-bond) network directly remains challenging due to the required interfacial sensitivity of experimental techniques. By leveraging advances in flat liquid sheet microjets and terawatt-scale attosecond soft X-ray pulses from the LCLS X-ray free electron laser, we employed soft X-ray second harmonic generation (SXSHG) spectroscopy to examine the liquid water/vapor interface. SXSHG combines the elemental selectivity of X-ray spectroscopies with the surface selectivity of SHG and gives access to the electronic structure of interfacial species. Here, we show the SXSHG spectrum differs from bulk water’s X-ray absorption, with its peak shifted several eV, indicating a vastly different electronic environment at the interface as compared to the bulk. First-principles electronic structure calculations show the signal is highly sensitive to H-bond interactions, such as water molecules accepting a single H-bond, which are surface abundant.

BACKGROUND: Levodopa decreases blood pressure (BP) in persons with Parkinson's disease (PwP), but no pharmacodynamic studies integrating systemic levodopa concentration measurements have characterized its hypotensive effects. Understanding this relationship is clinically relevant for guiding therapeutic decisions, such as how aggressively to treat hypotension before initiating or increasing levodopa. In this pilot study, we aimed to determine the acute pharmacodynamic effects of oral immediate-release carbidopa/levodopa on BP in PwP. METHODS: PwP taking chronic oral carbidopa/levodopa with baseline BP ≥ 90/60 mmHg were recruited. Participants withheld antiparkinsonian medications overnight prior to the study visit and received carbidopa/levodopa immediate-release tablets at time 0. Capillary blood levodopa levels, seated BP measurements, and motor symptom assessments were performed at baseline and repeated every 10 min for 70-100 min. Non-compartmental pharmacokinetic parameters of levodopa were determined, including the area under the curve up to the last time point (AUC_{0 → last}), maximum concentration (C_max), and time to maximum concentration (T_max). RESULTS: Fourteen PwP were enrolled (mean age 69.5 ± 7.6 years, six females). Two participants had orthostatic hypotension at baseline (defined as a sustained drop in systolic BP ≥ 20 mmHg or diastolic BP ≥ 10 mmHg within 3 min of standing), and six were taking antihypertensive medications. Mean arterial pressure (MAP) declined during the study from an average of 105 ± 13.1 mmHg at baseline to a nadir of 84 ± 15.8 mmHg. The maximum MAP drop occurred at 100 min post-dose. Cumulative levodopa AUC negatively correlated with MAP (Pearson's r = -0.30; p = 0.00036). CONCLUSIONS: Oral levodopa is associated with acute hypotension in PwP, and levodopa exposure is inversely correlated with MAP. These effects should be considered when adjusting levodopa dosing, particularly in patients with hypotension, to improve safety outcomes.