June 12, 2024
The UW Institute for Nano-engineered Systems (NanoES) has awarded three seed grants to UW researchers to use nanotechnology tools to develop new, innovative technologies and devices. Shijie Cao, professor of pharmaceutics, Ali Sadeghi, postdoctoral scholar in neurological surgery, and Shijing Sun, professor of mechanical engineering will receive up to $10,000 to carry out work in the UW’s Washington Nanofabrication Facility (WNF) and Molecular Analysis Facility (MAF). WNF and MAF are key nanotechnology facilities in the Northwest Nanotechnology Infrastructure, which is one of 16 sites in the NSF’s National Nanotechnology Coordinated Infrastructure (NNCI) program.
“NanoES and the teams at WNF and MAF are excited to help Shijie, Ali and Shijing’s research,” said NanoES Director Karl Böhringer, who is also a professor in the Departments of Electrical & Computer Engineering and Bioengineering. “The grants will aid Shijie’s team to showcase the importance of defining the relationship between nanoparticle structure and function, Ali pioneer the development of novel electrodes tailored for use in a preclinical setting, and Shijing catalyze interdisciplinary collaboration between chemistry and mechanical engineering through research in lab automation.”
Nanotechnology Seed Grants enable first-time facility users both inside and outside the UW to build and characterize prototypes, obtain preliminary results and conduct proof of concept studies. Applications for 2025-26 support will open early in 2025. More information can be found here.
“Advanced imaging and structural characterization of a novel, hybrid nano-prodrug delivery system for microbiome-derived metabolites,” by Shijie Cao.
Abstract: In recent years, the gut microbiome has emerged as a valuable source of novel therapeutics. Short-chain fatty acids (SCFAs) are bacterially produced metabolites that serve as crucial mediators of host-microbe communication. These metabolites activate immune tolerance programs, which restrict inappropriate immune responses to microbiome-, food-, and self-derived antigens. Reduced SCFA production upon gut dysbiosis has been linked to a myriad of immune-mediated diseases, such as inflammatory bowel diseases, allergies, and autoimmune diseases. Thus, administering SCFAs therapeutically represents an approach toward promoting immune tolerance without suppressing natural immune functions, offering an attractive alternative to current immunomodulatory drugs. While abundant evidence supports the therapeutic potential of SCFAs, their extensive absorption/metabolism after oral administration and their foul odor/taste necessitate the use of drug delivery systems to effectively translate this potential into the clinic.
The Cao Lab is developing a novel, microfluidic-enabled nano-prodrug platform designed to target the delivery of SCFAs to their intended site of action in the distal gut. We have successfully formulated SCFA-conjugated polymers into nanoparticles using lipids as the encapsulating materials, and have obtained high-level information regarding their size, polydispersity index, and surface charge using dynamic light scattering. With this proposal, we aim to utilize the state-of-the-art instrumentation housed in the Molecular Analysis Facility to thoroughly characterize the molecular anatomy of our nanoparticles. Specifically, we aim to employ scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) to precisely resolve the nanostructures of lipid-coated particles as well as those encapsulated within other shell materials, such as bacterial outer membrane vesicles and pH dependent polymer (Eudragit®) coatings. These techniques will enable us to determine the composition and distribution of materials within our particles with improved sensitivity and granularity, thus facilitating the development of our platform into a viable therapeutic with the potential to be employed in numerous disease contexts.
“Fabrication of novel epidural spinal electrode for chronic electrical stimulation in the animal model of spinal cord injury,” by Ali Sadeghi.
Abstract: Traumatic spinal cord injury (TSCI) is a devastating condition, often resulting in severe and permanent functional disabilities. More than 450,000 persons living in the United States are permanently disabled due to TSCI with approximately 11,000 new cases each year. TSCI substantially reduces quality of life and poses a significant functional and economic burden on both the individual and societal levels. Recently, along with other groups, we have demonstrated that spinal cord stimulation (SCS) may offer promising results in promoting recovery of sensorimotor abilities after TSCI in preclinical and clinical studies.
Electrical stimulation may enhance neural plasticity and increase the excitability of neuronal networks below the lesion which eventually will facilitate sensory and motor functional recovery. However, traditional bulky SCS electrodes may cause additional spinal damage during implantation and increase the impedance of the electrode-tissue interface over time due to foreign body reactions that encapsulate the electrode. Higher impedance can compromise the effectiveness of the stimulation and result in failure of the therapeutic outcomes of SCS.
In addition, there is scientific evidence from in-vitro studies that electrical simulation can guide axonal elongation along the electrical field. Through this preclinical project, we propose a novel flexible ultra-thin electrode that could be implanted in the epidural space of the animal model of TSCI with minimized tissue trauma during implantation. The electrode could deliver a specific stimulation regime with a unique contact configuration to facilitate directional axonal regeneration to bridge the rostral and caudal sites of the spinal lesion. The surface of the electrode will be also coated with a conductive biocompatible polymer to tissue reactivity and maintain low impedance over time. This implant will deliver therapeutic SCS that we have recently developed to recover function following TSCI. The result of this animal study could be later translated to the clinic for patients with TSCI.
“Precise morphology control of metal-organic framework crystals for clean energy innovation,” by Shijing Sun.
Abstract: Metal-Organic Frameworks (MOFs) are porous materials with a significant surface area and self-assembly capabilities, arising from metal ions and organic ligands. They show great promise for clean energy applications, such as gas adsorption, separation, storage, and catalysis. However, the transition of MOFs from laboratory research to the marketplace faces challenges such as scalability and processability. This is exemplified by the lack of precise control over crystal morphology, which is essential for industrial applications like pelletized materials and mixed-matrix membranes. The lack of a systematic approach to manipulating the shape of MOF crystals stems from the vast synthetic parameter space, the complexity of the crystallization process, and the lack of understanding of anisotropic crystal growth.
This project introduces a novel approach to achieve precise control of MOF crystal morphology by combining robotic synthesis and multiscale characterization. Leveraging the MARA robotic synthesis platform at the UW Sun Lab, we aim to develop novel synthetic pathways for precise MOF crystal growth manipulation at nano and micro scales. Recent studies have shown that Co-based MOFs can transition from rod-like to platelet-like shapes favorable for membrane applications for gas separation through buffered coordination modulation. Our preliminary findings have confirmed the crystallization of the reference rod-like Co2 (dobdc). Through high throughput experimental screening, we will quantify synthetic parameters such as temperature, solvent systems, and additives that contribute to anisotropic MOF crystal growth. Optical microscopy will allow us to determine the distributions of crystal yields, shapes, and sizes. Additionally, SEM will enable high-resolution imaging of the crystal morphology, including facets and orientation. X-ray diffraction will serve as the routine method for assessing phase purity and identifying side-phases, while Raman spectroscopy will aid in identifying phase transitions.
The project’s successful execution is poised to profoundly impact materials science and clean energy technology. By creating a scalable and adaptable synthesis framework, we aim to narrow the gap between laboratory research and industrial application significantly. This effort facilitates the broader adoption of porous hybrid materials in clean energy applications. The innovative blend of robotic synthesis and characterization across scales for crystal morphology control is set to redefine materials engineering standards, accelerating materials discovery and rational design, and address climate change and sustainable energy needs.