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Digital Microfluidic Lab-on-a-Chip Platform for Tissue Engineering

  • Author(s): Bender, Brian Francis
  • Advisor(s): Garrell, Robin L
  • et al.
Abstract

Stem cell technology and tissue engineering offer exciting opportunities for improving medical therapies. Success in these endeavors will depend on advances in our basic understanding of tissue culture and the development of supporting technologies. Digital microfluidics (DµF) is one technology that could offer important and unique advantages for automating stem cell culture and cell-based assays to support tissue culture, drug discovery and basic biomedical research.

Digital microfluidics refers to a miniaturized lab-on-a-chip platform that enables the automation of a wide array of laboratory procedures by handling liquids as droplets rather than streams. It has been applied to many chemical and biochemical protocols and assays. Advantages include reduced reaction times and reduced reagent volumes, and the ability to process multiple samples in an automated way: in series or in parallel, identically or uniquely.

This dissertation describes technological advances and applications of DµF for tissue engineering. Vertical dimensionality was developed by stacking multiple layers and incorporating a protocol for transferring droplets between layers. This added functionality enables new applications, exemplified by the demonstration of three previously un-achievable applications: creating a calcium alginate hydrogel with a radial crosslink density; creating a hydrogel based particle sieve; and the ability to retrieve 3D embryoid bodies on-chip. Protocols for growing three-dimensional tissue structures were established by encapsulating cells within hydrogel matrices. This protocol was used to demonstrate invasion assays for modeling tumor growth. Stem cell microenvironments were investigated by developing a protocol for the long-term growth and differentiation of embryoid bodies for cardiac tissue engineering. Non-invasive impedance assays were demonstrated for observing phenotypic behavior, maturation, and responses to chronotropic and inotropic agents. Finally, preliminary experiments were carried out to explore the feasibility of integrating piezoelectric PZT-based materials into DµF devices for added functionality. The voltage change generated via the pyroelectric effect was measured for exothermic chemical reactions, and strain induced in the substrate produced from contracting cardiomyocytes was monitored via piezoelectric effect.

The innovations presented here will provide the DµF and tissue engineering communities with design parameters and processing protocols necessary for manipulating collagen, producing 3D cell-ECM constructs, and creating a stem cell microenvironment for cardiomyogenesis.

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