Electrically Guided Assembly of Nanostructures for Bio-Sensing and Tissue Engineering

The emerging areas of biosensing and tissue regeneration seek lab-on-a-chip device platforms for nanoscale control of guidance cues to signal receptors on the cell surfaces during cell culture, as well as means to sort cells, sense and locally deliver growth factors such as proteins and DNA. Electric fields are a highly effective methodology for fabrication, alignment, and assembly of nanostructures, due to their high magnitude at the edges of nanostructures, their scope for selectivity based on the frequency response of dielectric properties of the materials, and the presence of inherent charges within nanomaterials, which obviates the need to label them for electrical manipulation. In this work, we apply electrical methodologies on micro/nanofluidic device platforms for the assembly of nanostructures and biosystems of relevance to tissue regeneration and biosensing. Specifically, we establish the design principles for patterning of DC fields to enable alignment of sub-100 nm bio-compatible electrospun nanofibers and the application of characteristic dielectric frequency response for trapping and sorting of functional bio-particles within media of high conductivity. The regeneration of tissues, such as ligaments and nerves, requires highly-directional guidance cues to the cells during their culture to enable their elongation and parallel directionality for a typical longitudinal structure to the tissue. Aligned scaffolds of biocompatible polymer nanofibers are hence of interest for providing such directional cues. Towards this objective, we explore the application of patterned DC fields during electrospinning for the alignment of nanofibers due to balance of transverse fields versus residual charge fields due to un-discharged fibers within insulator gaps (Langmuir, 2010, iv 24,19022). Specifically, we aim to understand how nanofiber size, mode of alignment, and dielectric properties of the interfaces influence the degree of fiber alignment and their cell guidance characteristics. To enhance biosensing sensitivity, selectivity and speed, we explore the application of dielectrophoresis (DEP) within micro/nanofluidic device platforms for selective preconcentration of bio-markers. Dielectrophoresis (DEP) is the polarization of a neutral particle in a non-uniform electric field, to cause its translation to particular localized regions of high or low field gradients, under conditions of positive or negative DEP, respectively. Hence, through appropriate design of non-uniformities on a device, a range of bio-particles can be selectively manipulated and localized under AC fields of characteristic frequencies based on dielectric properties of the biomaterials, without the use of moving parts or pumps [Lab. Chip 2009, 9, 3212]. We examine device designs for enhancing the trapping forces on 10-100 nm sized bio-particles within high conductivity media to maintain their bio-functionality, over the dissipative electrothermal forces due to Joule heating that develops over time in conducting media. We envision that the availability of such microfluidic lab-on-a-chip device platforms for the electrically guided assembly of nanostructures can transformatively impact the fields of biosensing and regenerative medicine, by enabling a toolkit for nanoscale manipulation and sensing. v Approval Sheet The dissertation is submitted in partial fulfillment ofthe Requirements for the degree of Doctor of Philosophy in Electrical Engineering 1 Vasudha Chaurey (Author) This dissertation has been read and approved by the examining committee Dr. Nathan S. Swaini (Advisor) Dr. Edward . a Accepted for the School of Engineering and Applied Science M:!::. Q Ii l,Dean, School of .

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