(2o) Nano Biomanufacturing for Medicine and the Environment | AIChE

(2o) Nano Biomanufacturing for Medicine and the Environment

Authors 

Bizmark, N. - Presenter, Princeton University
Research Interests

Nanobiotechnology has revolutionized the manufacturing of nanoscale materials for drug delivery, disease diagnosis, and environmental clean-up. For example, nanoparticles have been at the core of developing vaccines for coronavirus disease 2019 (COVID-19). By controlling the physicochemical properties of nanoparticles, my research team will integrate our fundamental understandings of colloids, soft matter, surface/interface science, transport phenomena, and polymer physics with engineering concepts to establish solutions to problems in vaccine manufacturing, drug delivery, and environmental cleanup.

My team will specifically target the following research directions:

  1. Lipid nanoparticles (LNPs) for vaccine and therapeutic delivery,
  2. Stimuli-responsive structured nano/micro gels for oral therapeutic delivery,
  3. Janus nanoparticles for biphasic reactions.

In the absence of natural immunity, protection against diseases can be developed actively or passively. Liposomes and LNPs have shown to be promising in encapsulating, transporting, and delivering therapeutics in vaccine and drug formulations. LNP-based mRNA vaccines for COVID-19 are among the most recent and critically important examples of such advanced formulations. While the efficacy of these novel formulations requires rigorous in vivo and clinical studies, a solid understanding of how LNPs are formed and how their internal structures can be manipulated during the in vitro production to support the best in vivo results is missing. In my research, we will fill this gap. Additionally, instead of the traditional route of co-loading LNPs with the desired therapeutic RNAs, we will assess an alternative route to produce LNP-based vaccines: post-loading empty LNPs (eLNPs) with therapeutic RNAs at the time of registration. In this alternative route, we will eliminate the need to freeze LNP-based vaccines at extreme conditions (e.g., -40 °C or -70 °C for Moderna and Pfizer COVID vaccines, respectively), making LNP-based vaccines more accessible globally. There are a number of questions regarding the proposed route: i. how does the internal structure of eLNPs change after post-loading? ii. how does the viability of post-loaded LNPs compare to that for co-loaded LNPs? and iii. how can the post-loading process be controlled?

Under the platform of using renewable biomass resources in my research lab, I propose the use of biomass-derived microgels to manufacture structured nano/micro gels that are responsive to changes in pH and temperature. To accomplish this critical task, we will produce gels from cellulose ethers, including methyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose as well as chitosan and alginate. As I explored in my postdoctoral work, different morphologies including spherical globules and long fibrils are formed during their thermally-induced phase transition at elevated temperatures. These transitions highly depend on the molecular architecture of these macromolecules. Therefore, by controlling the temperature and crosslinking density, we will engineer the size, elasticity, and mesh size of microgels via continuous processes including aerosolizing and microfluidics.

Biphasic reactions are important in chemical transformations including the synthesis of fine chemicals, biocatalysis and biomass refining. Micro reactors created by Pickering emulsions show the highest reaction rate compared to any other alternative setting. While this is promising, the limited functionalities of stabilizers restrict pathways towards flexible operation and expansion to various biphasic reactions for biological and environmental applications. To generate Pickering emulsions with tunable functionalities, I propose a novel engineering application of surface-active Janus nanoparticles derived from renewable resources (e.g., cellulosic-derived biopolymers). We will follow a multiscale approach from a single colloidal scale to multiple interfaces scale to address this goal. Depending on the desired application, the Pickering emulsion reactor will be tested for enzymatic reactions, (bio)hazardous substance reduction in water and wastewater streams, resource recovery, or biological compartmentalization.

Teaching Interest:

I have taught undergraduate and graduate courses as a course instructor, guest lecturer, teaching assistant, lab mentor, and private tutor during my graduate and postdoctoral trainings. I acquired advanced teaching skills by completing the Fundamentals of University Teaching (FUT) program at UW. Through mock teaching mini sessions in the FUT program, I practiced strategies and ideas to keep the class engaged, plan to receive feedback effectively from the class, and build a constructive relationship with students. I have taught undergraduate and graduate courses as a course instructor, guest lecturer, teaching assistant, and lab mentor during my graduate and postdoctoral studies. I have mentored 17 undergrad/grad students; hosted and facilitated conference sessions as well as journal clubs. I acquired advanced teaching skills by completing the Fundamentals of University Teaching during my PhD studies at the University of Waterloo, Canada. I have been the instructor for two undergraduate courses: Chemistry for Engineers (a 1st year course) and Equilibrium Stage Operations (a 2nd year course) at the University of Waterloo.

I am equipped with multiple skills to design and deliver courses effectively, reflected in my previous course evaluations. Following the Student-Centered Learning teaching philosophy, I design my classes to be collaborative and interactive. As an educator, I will be excited to teach undergraduate- and graduate-level courses in chemical engineering, including Chemical Engineering Fundamentals, Separation Processes, Transport Phenomena, and Thermodynamics, as well as elective courses in Colloids and Interfacial Phenomena, Pharmaceutical Engineering, Soft Materials, Green Engineering, and Transport in Porous Media.

Background:

I hold a Ph.D. degree in chemical engineering from the University of Waterloo (UW) where I focused on improving the fundamental understanding and engineering applications of colloidal ethyl cellulose (EC) nanoparticles. For the first time, I revealed the dynamics of irreversible adsorption of nanoparticles at fluid interfaces and rationalized the preparation of emulsions stabilized by EC nanoparticles to produce green membranes for water clean-up applications. I am currently an associate research scholar at Princeton University. Here, I have explored physicochemical behaviors in soft materials in a wide range of settings. I have elaborated our understanding of the mechanism behind the phase transition of thermo-responsive natural biopolymers to produce the next generation of hydrogels. Moreover, using Flash NanoPrecipitation and microfluidic frameworks, I have designed and produced a wide range of lipid nanoparticles as well as structured polymer colloids (Janus, patchy, and core-shell) sourced from biomass. Finally, with a unique experimental approach, I have visualized the transport of microplastics in model porous media to reveal the extent to which microplastics spread in aquifers and soils. I envision to continue my research in nanobiotechnology as an independent principal investigator.

Publications: 19 journals [12 (co-)first author, 4 second author], 2 book chapters, 1 book, 3 technology disclosures, 1 artwork, 51 conferences

Selected Awards:

  • Postdoc to Faculty Workshop, American Chemistry Society (2023)
  • I-Corps Northeast Hub Regional Grant, The National Science Foundation (2022)
  • Polymeric Materials Science & Engineering Future Faculty Scholar, American Chemistry Society (2021)
  • ACS-ENVR Certificate of Merit Award, American Chemistry Society (2021)
  • Materials Science Postdoctoral Fellowship, Princeton Materials Institute, Princeton University (2018-2021)
  • Doctoral Thesis Completion Award (oneD. student in chemical engineering), University of Waterloo (2017)
  • RBC Water Scholars Graduate Scholarship, Water Institute and Royal Bank of Canada (2016-2017)
  • Waterloo Institute of Nanotechnology Fellowship, University of Waterloo (2015-2016)
  • Annual Best Performance Graduate Scholarship, University of Waterloo (2012, 2013, 2015)
  • Chemical Engineering Best Publication Prize, University of Waterloo (2014)
  • Ontario Graduate Scholarship (five international students university-wide), Government of Ontario (2014-2015)
  • President’s Graduate Scholarship, University of Waterloo (2014-2015)
  • Outstanding Achievements in Grad Studies (five MASc students university-wide), University of Waterloo (2013)

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