UC Santa Cruz

We are living in an exciting era of a fast-paced confluence of wide-ranging research fields and technological breakthroughs that are profoundly altering our biomedical practices. In particular, the marriage of micro-nanotechnology and biotechnology is propelling our technical capabilities to new horizons. Despite tremendous progress made over the past 20 years, many challenges still exist for a broad range of biomedical applications spanning from few nanometers to tens of microns.

In this thesis, I aim to address three important biomedical problems at three different length scales. I first present an innovative and low-cost acousto-microfluidic approach that overcomes the diffusion limitations imposed by laminar flow profile in microfluidic channels at a challenging flow regime corresponding to extremely low Reynolds (Re~10-4) and high Péclet (Pe~106) numbers. Using this novel approach, we achieve immunoaffinity based isolation of cells using a simple rectangular channel without resorting to chaotic mixing processes or magnetic forces. Our acousto-microfluidic method uses a combination of pure and quasi-standing surface acoustic waves that are generated at a safe power (~ 1-10 W/cm2) and frequency (~10 MHz) regime comparable to those used in ultrasound imaging (e.g. fetal imaging). By exploiting the local shear forces in the vicinity of the bottom channel boundary (defined capture surface), we achieve selective separation of desired particles/cells using pre-functionalized cell specific biomolecules. We demonstrate selective enrichment of low-abundance T lymphocyte cells with a separation efficiency of about 80% at a high flow rate of 1.2 mL/hr, a separation efficiency that is comparable to most advanced rare cell isolation technologies. In the second part of my thesis (Chapter 2), I introduce a novel nanophotonic approach for enhanced inactivation of multidrug-resistant bacterial pathogens using visible light at 405 nm. To achieve this, I introduce precisely engineered aluminum nanoantenna arrays using a space mapping algorithm enabling inverse design of nanostructures from the desired spectral response. The nanoantenna arrays are optimized using radiative decay engineering principles to maximize the near-field enhancements and photothermal heating at 405 nm, a wavelength which bacteria is extremely sensitive to light and used as an emerging light-based disinfection technology alternative to ultraviolent (UV) light. In our experiments with low illumination intensities (2.5 mW/mm2), we demonstrate that our aluminum nanoantenna array (ANA) enables rapid eradication (~20 min) of multidrug-resistant Vibrio Cholerae biofilms with more than 500-fold inactivation efficiency (~99.995%) with respect to the 405 nm light alone. In the final part of my thesis (Chapter 3), I introduce a subwavelength thick (<200 nm) Optofluidic PlasmonIC (OPtIC) microlens that effortlessly achieves objective-free focusing and self-alignment of opposing optical scattering and fluidic drag forces for selective separation of exosome size bioparticles at low flow rates (< 5 m/s). Our optofluidic microlens provides a self-collimating mechanism for particle trajectories with a spatial dispersion that is inherently minimized by the optical gradient and radial fluidic drag forces working together to align the particles along the optical axis. I demonstrate that this facile platform facilitates complete separation of small size bioparticles (i.e., exosomes) from a heterogenous mixture through negative depletion and provides a robust selective separation capability for same size nanoparticles based on their differences in chemical composition. Unlike existing optical chromatography techniques that require complicated instrumentation (lasers, objectives and precise alignment stages), our OPtIC microlenses with a foot-print of 4 μm × 4 μm open up the possibility of multiplexed sorting of nanoparticles on a chip using low-cost broadband light sources (LEDs).