Development of new biomolecule patterning techniques for integrated biosystems

Amani Salim, Purdue University

Abstract

In this dissertation, we discuss the development of several new biomolecule patterning techniques suitable for integrated biosystems. Adjustable force contact lithography provides an improvement over conventional PDMS stampers, by allowing users to control contact force. The technique was used to pattern IgG on fragile microresonator structures. We fabricated a micromachined hydrogel stamper to replace PDMS for controlled biomolecule delivery and subsequent biomolecule patterning. The hydrogel stamper exhibits several advantages over conventional PDMS stampers by providing: (1) soft contact force without denaturing biomolecules, (2) a biologically compatible built-in reservoir, (3) a suitable medium for patterning polar molecules such as proteins, and (4) minimized surface contamination from stamper fragments. X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy and contact angle measurements were used to characterize deposited bovine serum albumin protein on hydrophilic silicon surfaces. Results from the characterization of this model system provide a better understanding of the biomolecule thickness, biomolecule adhesion to hydrophobic and hydrophilic surfaces, and chemical elemental composition on -OH modified surfaces. Due to the lower Young's modulus of the hydrogel, we could print arrays of biomolecule with dimension ratios of 20:1 using a single stamper when used with a suitable spacer thickness and external applied force. The ability of the hydrogel stamper to deliver active biomolecules and produce multiple stampings was confirmed via immunoblotting technique of E-coli antibodies. As a proof of concept for sensing applications, the hydrogel stamper was used to deposit a small volume of BSA-FITC on silicon microcantilevers. We utilized photolithography to pattern hydrophobic polymers such as Teflon and Parylene and investigated the adsorption of BSA-FITC on these surfaces. We immobilized streptavidin coated silica beads specifically on the silicon microresonators’ sensing platforms using hydrophobic Teflon thin film with adsorbed BSA as blocking agent. This method successfully reduced non-specific binding on the surface. We also developed a new method to pattern non-woven polyethylene oxide nanofibers to lithographic scale spots. FEMLAB electrostatic simulation was performed to investigate the electrodynamic focusing effect that guides the deposition direction of the nanofibers. We mixed BSA model proteins with the polymer to be electrospun, creating micropatterns of nonwoven PEO nanofibers, with embedded BSA-FITC. The results of these studies demonstrate the effectiveness of the new patterning techniques for creating novel platforms for biosensing and tissue/cell engineering.

Degree

Ph.D.

Advisors

Ziaie, Purdue University.

Subject Area

Biomedical engineering

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