Electrical and Computer Engineering ETDs

Publication Date

Fall 12-10-2016

Abstract

Interfacing biological cells and solid-state devices is crucial in many applications, ranging from well-established fields, such as electrophisiology, to the newly developed areas of optogenetics and mechanobiology. Most biological cells are anchored to substrates with elastic modulus, E, in the range of ~1 to 100 kPa, the moduli of brain-tissue and osteoid, respectively. On the other hand, bulk semiconductor substrates have ~6 orders of magnitude higher elastic modulus. This large elastic mismatch between devices and cells natural microenvironments is an issue for bio-devices integration, as cells are highly sensitive to mechanical cues. Specifically, cells exert traction forces on their surroundings and adjust their adhesion mechanism, cytoskeleton, locomotion and overall state according to the stiffness of the substrate they are anchored to. This type of behavior makes it a significant challenge to integrate semiconductor devices with biological cells without altering the cell state. I demonstrate a new family of culture platforms to successfully integrate biological cells and electronic/photonic devices from a mechanical perspective. The proposed platforms are referred to as effectively compliant layered substrates (ECLS). ECLS are based on inorganic nanomembranes (NMs) partially suspended v or bonded to compliant substrates. The unique attribute of ECLS is that, the constitutive material of the NM provides the electrical and optical functionality necessary to a device operation, while the NM geometry and the nature of the supporting substrate can be tailored to match the mechanical response of biological tissues. Specifically, I present fabrication and bio-interfacing of ECLS comprising of device-grade, single-crystal Si NMs on a compliant PDMS substrate with tunable elastic modulus from ~kPa to ~MPa. NMs with thickness in the range of ~20-220 nm and ~ 1x1 cm2 lateral areas are used in this study. ECLS are obtained using a two-step process, including synthesis of the compliant supporting substrate and fabrication, release and transfer of the NM onto the compliant host. Characterization of the mechanical properties of the ECLS and of the bare compliant substrate is performed by nanoindentation. Finally, I access a 3T3 fibroblast cell culture on the fabricated ECLS, as well as on bulk silicon and bare soft substrates to investigate cell response to mechanical cues. Specifically, I investigate cytotoxicity of ECLS substrate and conduct a comparative analysis of cell proliferation, morphology, and adhesion mechanisms between bulk Si, and Si-based ECLS with different elastic moduli. Flow-cytometry, bright-field and confocal fluorescence microscopy are used for this study. The proposed ECLS approach has successfully allowed fabrication of device-graded platforms with varying elastic modulus over three orders of magnitude and matching the mechanical properties of a wide range of biological tissues. Fabricated ECLS allowed healthy bioactivity of 3T3 fibroblast with no toxic behavior. 3T3 fibroblast cultured on ECLS with different elastic modulus displayed a drastic change in cytoskeleton (size and shape) and adhesion mechanisms (stress fiber organization and focal adhesions) compared to that of bulk Si.

Document Type

Thesis

Language

English

Degree Name

Electrical Engineering

Level of Degree

Masters

Department Name

Electrical and Computer Engineering

First Committee Member (Chair)

Dr. Francesca Cavallo

Second Committee Member

Dr. Andrew P. Shreve

Third Committee Member

Dr. Mani Hossein-Zadeh

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