High Throughput Synthesis of Micellar Nanocomposites via Liquid-Liquid Electrospray

Engineering: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)Purpose of the study: The primary objective of this study is to develop a novel synthesis route for micellar nanocomposites, or micelles, via Liquid-Liquid Electrospray (LLE) in a surfactant free environment. The proposed work will establish a semi-continuous platform to generate high quality nanocomposites for a number of biological applications, including bio-imaging and drug delivery. Multimodal nanocomposites that integrate two or more types of nanoparticles have gained significant attention in the biomedical science and engineering.1-6 More specifically, micelles are polymeric colloids comprises with amphiphilic block copolymers; the presence of both hydrophobic and hydrophilic regions promotes the self-assembly of polymer chains to form a hydrophobic core surrounded by a hydrophilic corona in an aqueous environment. Most applications utilize this unique structural characteristic by loading hydrophobic molecules and/or nanoparticles at the core.7 Standard synthesis techniques (i.e. dialysis, sonication, film hydration) include emulsion based methods8,9, encapsulation during nucleation10,11, and self-assembly12-14. Among these techniques, self-assembly produces the most monodisperse products because the process is thermodynamically driven, minimizing the effect of having a wide range of emulsion droplet size. Interfacial instability (IS) developed by Hayward utilizes the self-assembly of block copolymers to generate micelles. In IS, an organic solvent comprises with block copolymer chains and hydrophobic nanoparticles and/or drug molecules are emulsified in an aqueous solvent.15 As the emulsion droplets undergo the sudden reduction in surface tension due to the hydrophilic block moving toward the organic/aqueous interface, smaller droplets get ejected.15,16 This process repeats itself until the critical concentration of materials is reached to promote self-assembly of nanocomposites. However, these methods are limited to a small scale production due to both energy and material transfer limitations in emulsion formation. As a result, it is desired to establish a scalable synthesis route with an ability to consistently make emulsion droplets. In order to accomplish this goal, electrospray techniques can be employed to atomize organic droplets; by incorporating electrospray, the organic solvent can be dispersed into fine droplets semi-continuously. Furthermore, unlike the conventional electrospray (i.e. aerosol), the spray can be done inside of an aqueous environment (Liquid-in-Liquid), enabling the emulsification without the surfactant that eliminates the downstream purification steps for biological applications. Research method: Liquid-Liquid Electrospray, or LLE, utilizes a stainless steel nozzle that processes organic solvent with micelle constituents. The nozzle is surrounded by a ceramic insulator and placed inside of an aqueous environment (i.e. ultrapure water). In addition to the insulated nozzle, a grounded electrode is placed inside of the aqueous medium. High voltage is applied at the top of the nozzle using a high-voltage power supply, which generates an electric field between the nozzle tip and the grounded electrode inside of the aqueous medium18-20. As the organic solvent is processes through the nozzle, the presence of electric field results in electrohydrodynamic atomization (EHDA)17-20, dispersing the organic solvent into emulsion droplets. These droplets then undergo IS, generating micelles via self-assembly. Overall, this method incorporates both top-down (electrospray) and bottom-up (self-assembly) techniques to produce high quality micelles. Findings: LLE has successfully synthesized nanocomposites encapsulating quantum dots (QDs), superparamagnetic iron oxide nanoparticles (SPIONs), and drug molecules. Size and morphology of nanocomposite were analyzed. Molar ratio of nanoparticles to polymer present in organic phase was found to be the important parameter in tuning the morphology of nanocomposites; by tuning this ratio, fairly monodispersed nanocomposites were obtained. In addition, this study provided valuable insights on the role of surfactants; the absence of surfactant seems to have significant effect on the stability of nanocomposites even after the completion of thermodynamically stable micelle structure. Implication: This study has successfully demonstrated the surfactant free nanocomposite synthesis method at significantly higher throughput in comparison to standard methods. Nanocomposites produced via LLE have been characterized and their functionalities for biological applications (i.e. bio-imaging) have been studied by labeling breast cancer cells with fluorescent QDs. References 1. R. Bakalova, Z. Zhelev, I. Aoki, H. Ohba, Y. Imai, and I. Kanno, Silica-shelled single quantum dot micelles as imaging probes with dual or multimodality. Analytical Chemistry, 2006. 78(16): p. 5925-32. 2. M.F. Kircher, U. Mahmood, R.S. King, R. Weissleder, and L. 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Urashima, Dielectric liquid-in-liquid dispersion by applying pulsed voltage. Dielectrics and Electrical Insulation, IEEE Transactions, 2009. 16(2): p. 391-395.A five-year embargo was granted for this item