Multi-robot-based nanoassembly planning with automated path generation

In this paper, a novel approach of automated multirobot nanoassembly planning is presented. This approach uses an improved self-organizing map to coordinate assembly tasks of nanorobots while generating optimized motion paths at run time with a modified shunting neural network. It is capable of synchronizing multiple nanorobots working simultaneously and efficiently on the assembly of swarms of objects in the presence of obstacles and environmental uncertainty. Operation of the presented approach is demonstrated with experiments at the end of the paper

PROTEIN-NANOPARTICLE CO-ENGINEERING: SELF-ASSEMBLY, INTRACELLULAR PROTEIN DELIVERY, AND CRISPR/CAS9-BASED GENE EDITING

Direct cytoplasmic delivery of gene editing nucleases such CRISPR/Cas9 systems and therapeutic proteins provides enormous opportunities in curing human genetic diseases, and assist research in basic cell biology. One approach to attain such a goal is through engineering nanotechnological tools to mimic naturally existing intra- and extracellular protein delivery/transport systems. Nature builds transport systems for proteins and other biomolecules through evolution-derived sophisticated molecular engineering. Inspired by such natural assemblies, I employed molecular engineering approaches to fabricate self-assembled nanostructures to use as intracellular protein delivery tools. Briefly, proteins and gold nanoparticles were co-engineered to carry complementary electrostatic recognition elements. When these materials were mixed together, they formed highly sophisticated, multi-layered, and hierarchical self-assembled nanostructures of few hundred-nanometer size. These structures carried a large number of engineered proteins, got fused to cell membrane upon incubation, and delivered the encapsulated protein content directly into cell cytoplasm. Using this technology, we delivered a wide range of proteins, and CRISPR/Cas9-ribonucleoprotein that resulted high efficient gene editing

Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs for Intracellular Delivery of Biologics

Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also help strengthen the fundamental chemical understanding to meet the future need of this rapidly evolving field. Designing a supramolecular container that is capable of stably holding sensitive active and releasing them at target site upon environmental changes is a promising solution to tackle many complex challenges associated with functional delivery of therapeutics. Addressing this requires a basic understanding of the structural and functional factors to be engineered into the delivery vehicle. To this end, we have explored the interactions between synthetic polymers with various biologics to form well-defined self-assembled structures, wherein the function of the encapsulated active is only revealed upon specific structural modulation of the polymer surrounding it. In this dissertation, we have discussed the development of three distinct self-assembly strategies to reversibly capture sensitive biologics, viz. protein, nucleic acid and antibody. A covalent self-assembly strategy is employed for proteins irrespective of their isoelectric points (chapter 2). Our second strategy utilizes non-covalent interactions (electrostatic and hydrophobic) for complexation with negatively charged nucleic acids (chapter 3). Finally, we studied a combination of covalent and non-covalent interactions for encapsulating large proteins and antibodies (chapter 4 and 5). This dissertation will focus on the inherent challenges associated with functional delivery of proteins and nucleic acids. It will highlight the advantages of rational designs to control the complex interplay between the structural features of the polymers and their biological outcomes

Development of Quantum Dots as Biosensing Probes

Appendix E Movie 1: Nanoassembly transport around a microdisc. Control is demonstrated by magnetic trapping of the nanoassembly. A reverse motion around the disk is shown from 11-16 seconds, and then the particle continues its clockwise trajectory. After 33 seconds the nanoassembly is released from the microdisc.Appendix E Movie 2: Nanoassembly transport on nanowires via vertex-to-vertex hopping.Appendix E Movie 3: Simultaneous magnetic transport of red protein (avidin) and green DNA (p53 ssDNA) nanoassemblies via vertex to vertex hopping on magnetic nanowire arrays.Appendix E Movie 4: Red, magnetic protein nanoassemblies (i.e., avidin as the molecular target, containing SPIONs) are trapped and transported from vertex-to-vertex, whereas green, non-magnetic DNA nanoassemblies (p53 ssDNA as the molecular target, containing no SPIONs) are not trapped and display motion resulting from Brownian motion or liquid flow.Appendix E Movie 5: Following addition of DNA-targeting SPION micelles, green, magnetic DNA nanoassemblies (p53 ssDNA as the molecular target, containing QDs and SPIONs) are transported, showing rapid conjugation of SPIONs to green micelle structures.Appendix E Movies 1 - 5 reproduced from: K. D. Mahajan, G. Ruan, G. Vieira, T. Porter, J. J. Chalmers, R. Sooryakumar and J. O. Winter, J. Mater. Chem. B, 2020, Advance Article, https://doi.org/10.1039/C9TB02481F - Reproduced by permission of The Royal Society of Chemistry.Quantum dots (QDs) are semiconductor nanoparticles that exhibit size-dependent optical properties. Compared to other common fluorophores such as dyes and fluorescent proteins, QDs possess higher photon emission rates. Additionally, they have broad absorption spectra and narrow, size-tunable emission spectra that enable color multiplexing. Their resistance to photobleaching also makes them suitable for tracking over long periods of time. Thus, QDs possess numerous properties that make them attractive for biosensing applications. However, several concerns must be addressed for their widespread implementation in sensing applications. For instance, the most common QDs contain cadmium, raising concerns of toxicity. Additionally, several groups anecdotally report decreases in fluorescence intensity during QD processing. The research described in this document explores several aspects of these difficulties, including a toxicity characterization of QDs made of alternative nontoxic materials with various surface chemistries. Further, a systematic analysis of QD colloidal stability and fluorescence loss during common processing steps such as dilution, centrifugal filtration, and buffer exchange is discussed. After addressing these difficulties, the utility of QDs are demonstrated in a novel magneto-fluorescent detection and separation platform used on protein and DNA analytes. Finally, the development of novel QD-DNA conjugates and the wide-reaching potential applications of these QD-DNA conjugates are discussed.NSF DBI-1555470NSF CMMI-0900377DMR-1206745EEC-0914790DMR-0820414U. S. Army Research Office under Contract W911NF-10-1-053Ohio State University Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical DevicesMaterials Science and Engineering Research Center for Emergent MaterialsInstitute for Materials Research; a "Thousand Young Global Talents" award from the Chinese Central Government"Tian-Di" Foundation, College of Modern Engineering and Applied Sciences, Nanjing University, ChinaCollege of Engineering Undergraduate Research ScholarshipNo embargoAcademic Major: Chemical Engineerin

Tin-graphene tubes as anodes for lithium-ion batteries with high volumetric and gravimetric energy densities.

Limited by the size of microelectronics, as well as the space of electrical vehicles, there are tremendous demands for lithium-ion batteries with high volumetric energy densities. Current lithium-ion batteries, however, adopt graphite-based anodes with low tap density and gravimetric capacity, resulting in poor volumetric performance metric. Here, by encapsulating nanoparticles of metallic tin in mechanically robust graphene tubes, we show tin anodes with high volumetric and gravimetric capacities, high rate performance, and long cycling life. Pairing with a commercial cathode material LiNi0.6Mn0.2Co0.2O2, full cells exhibit a gravimetric and volumetric energy density of 590 W h Kg-1 and 1,252 W h L-1, respectively, the latter of which doubles that of the cell based on graphite anodes. This work provides an effective route towards lithium-ion batteries with high energy density for a broad range of applications

Development and applications of inkjet printed conducting polymer micro-rings

A drying sessile drop moves the solute particles to the periphery where they get deposited in the form of a ring. This phenomenon is prevalent even with micro drops falling at high velocity from a piezo-actuator based inkjet printer. In polymer microelectronic field, this phenomenon is a major challenge for fabricating devices using inkjet printing. We exploited this problem and applied it for various novel applications in the field of polymer microelectronics. Various dispensing techniques and temperature variations for micro-drop printing were used for modifying the micro-drops in such a way that the periphery of the micro-ring holds most of the solute as compared to inner base layer. Reactive ion etching (RIE) was used for removing the inner base layer in order to make the micro-rings completely hollow from the center. These micro-rings were applied in the fabrication of polymer light emitting diode, humidity sensor and vertical channel field effect transistor. High resolution polymer light emitting diode array (\u3e200 pixels/inch) was fabricated by inkjet printing of micro-ring and each micro-ring acts as a single pixel. These micro-rings were applied as a platform for layer-by-layer (LbL) nano-assembly of poly-3,4-ethylenedioxythiophene:poly-styrenesulfonate (PEDOT:PSS) for the fabrication of humidity sensor. Enhanced sensitivity of the humidity sensor was obtained when the inkjet printed micro-rings are combined with LbL assembled PEDOT:PSS films. During the fabrication of vertical channel field effect transistors, inkjet printed PEDOT:PSS micro-rings were used as source and the inner spacers between the adjacent micro-rings were used to make channel. These micro-rings can also find other applications in the field of biological sciences. These micro-rings can be used as cell culture plates and as scaffolds for cell and/or tissue growth

Engineering Stem Cell Responses with Two-Dimensional Nanomaterials

Two-dimensional (2D) nanomaterials are an emerging class of biomaterials that have garnered unprecedented attention due to their unique atomically thin, layered, and well-defined structure. These nanomaterials, however, have limited investigations into their cytocompatibility and potential use in regenerative medicine particularly from the perspective of 3D scaffolds. Here we report two chemically unique 2D nanomaterials and their biophysical and biochemical interactions with stem cells. The first is a naturally occurring nanosilicate which is made up of a unique combination of minerals (Na^+, L^i+, Mg^2+, Si(OH)v4) within an octahedral sheet sandwiched between two tetrahedral lattices (Laponite XLG®). The second is a transition metal dichalcogenide (TMD) of molybdenum disulfide (MoSv2) which forms 2D sheets nanometers in thickness. Using molecular biology techniques that capture a holistic snapshot of cell signaling, like RNA-sequencing (RNA-seq), we can begin to examine mechanisms behind changes in behavior. With this information, we can then interrogate specific pathways of interest to generate a desired cell response. Furthermore, we can incorporate these nanomaterials into polymeric scaffolds to localize both cells and bioactive materials for delivery in vivo. Specifically, we utilized formulations of the polysaccharide kappa-Carrageenan with the nanosilicates and a thiol-modified 4-arm polyethylene glycol (PEG) with 2D MoSv2. Using these studies as a framework, researchers can begin to tailor new polymeric scaffolds around emergent 2D nanomaterials for a variety of regenerative applications including bioprinting

Studying DNA-Directed Nanoassembly, Hybridization and Mismatch-Discrimination via Plasmon Scattering of Gold Nanoparticles

Ph.DDOCTOR OF PHILOSOPH

Plasma Nanoscience: from Nano-Solids in Plasmas to Nano-Plasmas in Solids

The unique plasma-specific features and physical phenomena in the organization of nanoscale solid-state systems in a broad range of elemental composition, structure, and dimensionality are critically reviewed. These effects lead to the possibility to localize and control energy and matter at nanoscales and to produce self-organized nano-solids with highly unusual and superior properties. A unifying conceptual framework based on the control of production, transport, and self-organization of precursor species is introduced and a variety of plasma-specific non-equilibrium and kinetics-driven phenomena across the many temporal and spatial scales is explained. When the plasma is localized to micrometer and nanometer dimensions, new emergent phenomena arise. The examples range from semiconducting quantum dots and nanowires, chirality control of single-walled carbon nanotubes, ultra-fine manipulation of graphenes, nano-diamond, and organic matter, to nano-plasma effects and nano-plasmas of different states of matter.Comment: This is an essential interdisciplinary reference which can be used by both advanced and early career researchers as well as in undergraduate teaching and postgraduate research trainin