Biological and Applied Nanotechnology Research
Accordions
We are leaders in the development of nanoparticle (NP)-particle composite materials and the science and engineering of their interactions. Our research in this area was motivated by the desire to obtain stable semiconductor quantum dots (QDs) for biological imaging, and currently focuses on two NP types: fluorescent QDs and superparamagnetic iron oxide NPs (SPIONs). Unfortunately, many inorganic NPs, including QDs, are manufactured in the organic phase, necessitating surface modification for compatibility in biological environments. We developed methods to encapsulate multiple NPs in polymer micelles or nanoparticles. These composite nanostructures are comprised of amphiphilic block copolymers encapsulating QDs (I.e., MultiDots), SPIONs (i.e., SuperMags), or their combination (i.e., MagDots). These nanocomposites average ~ 20-100 nm in size, can increase QD brightness up to 13X, reduce QD susceptibility to photo-oxidation damage by 7.5X, and can achieve NP volume fractions of up to 30%. This makes these materials some of the brightest and most magnetic materials on a volume basis compared to other same class materials. We have used the materials for applications in biosensing, cell separations, and detection, and formed a start-up company for their commercialization. These materials form an important component of our toolbox and we continue to refine and improve their structure. Our current work in this area includes development of magnetic reagents for RNA capture and cell separations with built-in fluorescence quantification.
Image: Transmission electron microscopy image of SPIONs encapsulated in a polymer micelle. Stripes indicate SPIONs, white sections are polymer. NPs align in polymer blocks generating internal ordering.
We are at the forefront of nanomanufacturing commercialization strategies to manufacture nanoparticles and nanoparticle composites. Our research focuses on two design strategies based on electrospray and jet mixing reactors for semi-batch to continuous production. Electrospray systems can operate in liquid-air-liquid or liquid-in-liquid modes. In the first, charged organic solution is atomized via an induced voltage generating a fine emulsion collected in aqueous solution. At this point, nanoparticles can undergo self-assembly via the interfacial instability effect. In the second version, organic stream injected into aqueous media is rapidly mixed via electrohydrodynamic flow induced by an applied voltage in solution. Organic can be immiscible with aqueous media, leading to assembly via interfacial instability, or miscible leading to assembly via nanoprecipitation mechanisms. In jet mixing, streams are rapidly mixed through impingement in a confined volume. If solutions are miscible, particles form via nanoprecipitation mechanisms, if immiscible, then interfacial instability results. We have used these methods to encapsulate inorganic quantum dots and superparamagnetic iron oxide nanoparticles, drugs, and fluorophores and chromophores in polymer carriers formed from amphiphilic block copolymers. Our current work in this area is focuses on optimizing drug encapsulation in vehicles manufactured using liquid-in-liquid electrospray and in manufacturing inorganic nanoparticles in high temperature jet mixing reactors. In addition, we are developing fundamental knowledge toward commercialization, including scaling laws and theoretical models of heat transfer and fluid dynamics in these systems.
Video: In this video, we demonstrate a new nanomanufacturing method for polymer nanoparticles in which electric voltage applied to the needle tip and a grounding electrode is used to generate electrohydrodynamic mixing of organic and aqueous phases. Nanoparticles then self-assemble in the solution. Collaboration with Dr. Barbara Wyslouzil.
A primary goal in our work is creating technologies that impact the real world, and one of our main foci is applying bionanotechnology in pathology. Our initial work focused on applying our fluorescent MultiDots to leukemia and lymphoma detection via flow cytometry, and a start-up company was initiated from our patented work. However, our primary area of expertise is in microscopy. We have collaborated with others to develop labels for Stochastic Optical Reconstruction Microscopy (STORM) and to develop protocols for imaging cells cultured in 3D tissue engineered in vitro models via traditional pathological techniques. Our current work, in collaboration with Dr. Jose Otero, focuses on solid tissue pathology (e.g., biopsy specimens). We are developing technologies for erasable pathological imaging using chromophores, consistent with current practice. This work combines DNA nanotechnology with our micelle carrier vehicles and scalable nanomanufacturing processes to develop pathological labels and methods for brain cancer detection and patient triage.
Image: Erasable labeling of actin staining in U87 glioma cell using fluorescent polymer-DNA nanotechnology composites.
A second real world application of our technologies is in molecular delivery. We collaborate with researchers at the OSU Wexner Medical Center to develop and manufacture drug carriers for treatment of cancers and other diseases. In this work, we focus on the manufacturing aspects, using materials that are already well established and accepted by the FDA. We help clinicians scale up technologies to enable animal studies of compounds that have already been validated in vitro. Our current work has focused on new therapeutics for the treatment of glioblastoma brain cancers and vehicles that can cross the blood brain barrier and anti-cancer nutraceuticals for oral cancer prevention. In addition, our work has recently been adapted for applications in sustainable agriculture. With our collaborator, Dr. Alison Bennett, we are developing ‘smart’ release systems that respond to compounds produced by the agricultural microbiome to deliver nutrients on demand. This approach supports synergistic plant-symbiote partnerships reducing nutrient and water demands toward sustainable agriculture.
Image: Trafficking of drug delivery vehicles containing fluorophore dyes (A) to cells and (B) across the blood brain barrier in mouse. Image A was published in Int. J. Nanomed. 2018:13, 351—366.
A new direction of study for us is the combination of DNA with inorganic nanoparticles. DNA is an interesting material because of its biological function, but also because it can be used to template and control nanoparticle assemblies. DNA is nature’s computer and RNA is nature’s robot. DNA holds information that is processed by ribonucleic acid comprised ribosomes. Ribosomes have complex 3D structures and perform repetitive processes using information provided by DNA strands. This process even includes process control elements through miRNA and siRNA regulation. We are using DNA to template nanoparticles into specific geometries to explore emergent applications, such as sensing or self-healing materials. We are also using DNA to pattern ligand presentation on nanoparticle surfaces, and we are combining DNA with nanoparticles to create small machines, toward nanorobots.
Image: In collaboration with Dr. Carlos Castro, we developed small machines with angular rotation. These "hinges" are closed by nanoparticle binding. Changing the size of the nanoparticle can change the available degrees of freedom for angular rotation. Such machines form the building blocks toward nanorobots.
We have established several in vitro models to study cancer cell migration, primarily for analysis of glioblastoma multiforme (GB). GB is a form of brain cancer that is particularly lethal, with an average patient survival of ~ 15 months. Unfortunately, GB grows differently from other cancers in brain and brain metastases in that it is highly invasive. Whereas most cancer therapies focus on proliferation, in GB, migration may be a better drug target. We have created in vitro models to control and manipulate the GB tumor microenvironment, studying the effects of topography, mechanics, pressure, cell-cell interactions, and chemical signaling on GB cell migration. These models are comprised of electrospun nanofibers, polymer hydrogels, and engineering fluid mechanics constructs. Our current work is focused on the mesenchymal to amoeboid transition in GB cell migration and interactions between normal and cancerous astrocytes in brain. We are also interested in studying differences between GB and other cancers, and are investigating differential responses of breast metastases and brain cancers in our 3D models.
Video: Glioblastoma tumor cells are shown migrating on electrospun nanofibers, an in vitro migration model. Electrospun nanofibers mimic the topography of white matter, one of the primary migration highways for GB cells.
Emerging from our development of in vitro cancer models, we are also highly interested on nanomaterial effects on cell adhesion and migration. We have developed methods to generate nanostructured materials, including electrospinning and hot embossing, and explored their effects on cell adhesion and migration. Within this area, we have particularly explored the role of mechanics on cell response, highlighting the importance of edge effects, viscoelasticity, and tension in cell responses. Much current research focuses on characterization via Young’s modulus alone, which is highly flawed as it misses these important effects. In addition, we are interested in cell adhesion and migration molecular mechanisms through the integrin-actin-focal adhesion kinase signaling cascade and interactions between nanomaterials and actin and microtubule cytoskeletal proteins. With our collaborator, Dr. George Bachand, we have used MagDot particles to steer and detach microtubules from kinesin coated surfaces to study their binding interactions. Our current work is investigating the impact of mechanics on brain tumor cell survival and migration. We are also integrating DNA machines with our microtubule-kinesin models.
Video: A microtubule moving on a kinesin coated surface is steered using magnetic quantum dots and magnetic nanowires. The microtubule begins on the far right of the screen and is induced to change direction by interacting with the zigzag shaped nanowires.
Press Articles and Media
Tiles
YouTube Video
“From Chemical Engineer to Cancer Warrior,” March 26, 2016, Museum of Science, Boston.
Additional Podcasts
“NanoDays 2016: Cancer Research from Bench to Bedside,” March 26, 2016, Museum of Science, Boston Podcast Series.
“Scale-Up for Nanobiotech,” July 29, 2014, Museum of Science Podcast.
“New Nanoparticles for Biomedical Testing,” April 7, 2011, Genengnews.
Tiles
Animation
"Jessica's Dream" a QSTORM animation in collaboration with the New England Institute of Art.
Articles and Links
“Do I Have to Leave to Launch,” May 10, 2016, Science Magazine
“20 People to Know in Technology,” January 17, 2014, Columbus Business First
“OSU prof could be ‘Henry Ford of nanotechnology’ by streamlining production”, October 7, 2013, Columbus Business First.
“Ohio State prof hopes Quantum leap with spinoff pays off,” October 19, 2012, Columbus Business First .
“A New Twist to Quantum Dot Tracking,” Wiley Analytical Science, September 25, 2011.
“Quantum Dots Light up Nanoparticles,” Chemical Engineer Progress, May 2011.
“Novel quantum dot nanocomposites reconcile blinking/tracking issues”, Nanowerk, Feb 24, 2011.
“Tiny particles may help surgeons by marking brain tumors,” PhysOrg.com, April 29, 2010.
“Coatings to help medical implants connect with neurons,” PhysOrg, August 21, 2008.
"Plastic coatings helps medical implants to connect with neurons" Nanowerk, August 21, 2008.
"Coatings Encourage Neurons in the Body to Grow" Nano A to Z, August 21, 2008.
"Coatings to help medical implants connect with neurons," E Science News, August 21, 2008.
Archived Articles
“Engineering Our Future,” 08/25/2017, The Columbus Dispatch
“Twinkle, Twinkle, Quantum Dot – New Particles Can Change Colors and Tag Molecules, OSU Research News, March 30, 2011.
“New particles can change colors and tag molecules,” R&D Magazine, March 29, 2011
“Drawing a bead on the brain,” OSU On Campus Magazine, May 5, 2010.
“Tiny particles may help surgeons by marking brain tumors,” OSU Research News, May 5, 2010; Nanotechnology Now, April 30, 2010; Science Daily, April 30, 2010; Innovations Report, April 29, 2010; e! Science News, April 29, 2010; Science Stage, April 29, 2010; Check Orphan, April 30, 2010.
“Coatings to help medical implants connect with neurons,” OSU Research News, August 21, 2008; Nanotechnology Today, September 27, 2008; My Vision Test, August 22, 2008.