(6gf) Engineering Nanomaterials for Biomedical Applications

Engineering Nanomaterials for Biomedical Applications

Nanoscale materials often possess functionalities that go beyond conventional molecular systems. Unlike bulk materials, their properties not only depend on their composition, but may vary with the size, shape, and relative arrangements of constituents. As a chemist with extensive training in nanotechnology, I have expertise in the synthesis, characterization, and assembly of nanomaterials, as well as their interfacing with biological systems. In addition, I have had the opportunity of working in multiple different areas spanning many different length scales of “small structures”, including cluster physics (molecular scale), nanomaterial design for drug delivery and cellular imaging (nanoscale), and microdroplet chemistry (micron scale). I have worked in collaboration with physicists, chemists, engineers, and medical doctors, and published 19 articles in total (11 as first or a co-first author). In my independent career, I aim to develop a research program that will explore the fundamental properties of novel nanoscale materials and then exploit them for various biomedical applications. In particular, I am interested in learning how nanomaterials interact with biological systems and utilizing this knowledge for developing improved nanomaterial-based diagnostic and therapeutic platforms.

Postdoctoral research with Prof. Chad A. Mirkin at Northwestern University

Nanomaterial-based tools for bioimaging. My research focuses on engineering nucleic acid-based probes for imaging intracellular analytes in live cells. By using aptamers, oligonucleotide sequences that bind to target analytes with high selectivity and sensitivity, it is possible to detect almost any analyte, provided the binding event can be transduced into a signaling event. I have developed a new class of signaling aptamers called “FIT-aptamers”. These aptamers contain a visco-sensitive dye that is forced to intercalate or FIT between base pairs upon target binding, turning the fluorescence on due to the restricted rotation of the dye. The FIT strategy reduces false-positive signals common to all fluorophore-quencher systems, provides up to 20-fold fluorescence enhancement upon target binding, and allows target detection down to nanomolar concentrations in complex milieu such as human serum. I am now interfacing these FIT-aptamers with nanoparticles to enable transfection-reagent free cellular uptake for live cell imaging applications.

Graduate research with Prof. Richard N. Zare at Stanford University

Electroresponsive nanoparticles for drug delivery on demand. Programmable and controllable delivery of drugs is one of the main challenges in drug administration today. My thesis work was focused on developing an electroresponsive drug delivery system (DDS) as a solution to this problem. The DDS consists of drug-loaded polypyrrole nanoparticles (PPy NPs) that undergo changes in redox state upon electric stimulation, releasing their drug cargo with spatiotemporal precision. I demonstrated that various drugs ranging from small molecules to polypeptides can be released in a pulsed manner by applying <1 V. Moreover, by incorporating metallic elements into the PPy scaffold, we developed an improved DDS that can release drugs at unprecedented low voltages (50-75 mV). The widened window of operating voltage allows the release of methotrexate, an anti-cancer drug susceptible to redox degradation at higher voltages, with retained bioactivity. We next proceeded to couple PPy NPs to wireless electronics to develop a next-generation implantable DDS. In collaboration with the Arbabian Lab (Stanford Engineering), we demonstrated that drug release can be triggered wirelessly through acoustic excitation using a millimeter-sized piezoelectric transducer. Taken together, these results represent a cornerstone towards developing minimally invasive implants which can treat various chronic diseases (e.g. chronic pain/diabetes/cancer).

Reactions in aqueous microdroplets. Bulk water serves as an inert solvent for many chemical/biological reactions. We demonstrated that in micron-sized water droplets, various molecules undergo spontaneous redox reactions without any added electron donors/acceptors or applied voltage. While none of these reactions proceeds spontaneously in bulk water, redox efficiencies can reach >90% in microdroplets. Moreover, we observed that gold nanoparticles form spontaneously from metal precursors in aqueous microdroplets and self-assemble to form nanowires, representing the first example of self-assembly without using added ligands, templates, or electric fields. The size/shape can be controlled/temporally resolved by modulating the microdroplet lifetime. Compared to bulk synthesis, the size and growth rate of AuNPs are enhanced by 2- and 100,000-fold, respectively, in microdroplets. These results demonstrate that microdroplets have a unique environment and could be potentially used as powerful microreactors for synthesizing various compounds and nanomaterials.

Teaching Interests:

I believe teaching is an integral part of learning. As a graduate student, I have taught over 450 students in both lab and lecture-based settings. Specifically, I have been a teaching assistant for various courses such as General Chemistry (Beginner and Advanced), Organic Chemistry, Analytical Chemistry, and Physical Chemistry. I have also had the opportunity to design and teach my own courses through the Stanford Splash! program to ~130 high school students. My most enjoyable teaching endeavor has been as a research mentor to 12 students including high school, undergraduate, and graduate students. Notably, all my mentees are currently pursuing science-related degrees or careers. My ideal teaching program would be focused on teaching upper-level undergraduate classes or specialized topic courses for graduate students, including Separation Science, Thermodynamics, Soft Matter and Interfacial Phenomena, Chemical Kinetics, Molecular Engineering, and Design of Drug Delivery and Diagnostic Systems.

Funding

I have assisted Prof. Zare at Stanford University and Prof. Mirkin at Northwestern University in writing multi-PI proposals resulting in >$15 million in funding from the NIH and DOE. As a graduate student, I secured self-funding (~$150,000) for two years from the Center for Molecular Analysis and Design at Stanford. I was supported for another two years by a Stanford Graduate Fellowship. As a postdoctoral fellow, I have received $10,000 in research support as an HHMI Hanna Gray Fellow finalist.