UC Riverside

Advances in life sciences in recent decades have revolutionized our understandingof biochemical and biophysical interactions associated with diseases and disorders of the human body. This newly acquired knowledge has fueled intense interest in a range of biotechnological strategies that can improve health outcomes, spanning from biosensors to drug development to tissue engineering. There is thus an increasing need for even better understanding of biomolecular interactions at nanoscale to explore new medical frontiers, and for powerful analytical tools of increasing complexity and diversity in multiplexed bioanalysis. Surface plasmon resonance (SPR) is a core optical spectroscopic principle in the bioanalytical sphere, and its label-free methodology for bioassays has been broadly applied in drug discovery, medical diagnosis, and environmental monitoring. Advances in materials sciences, however, have provided new opportunities for re-invention of the technique and expansion of the range of analyses by SPR. The aim of this dissertation is to develop and improve the fundamental technological diversity of SPR based techniques for enhanced biosensing applications.

The main strategy for the development takes the form of integrating novelmethodologies and new materials to the SPR bioanalytical workflows. First, an orthogonal analytical platform was developed by combining SPR/SPR imaging with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). A multistep functionalized plasmonic microarray was developed into a new mode (SPR-MALDI) for the sensitive detection of bacterial toxin proteins in complex environmental matrices. The combination of the techniques allowed for both quantitative determination and unambiguous qualitative identification of biological identity of the target. Second, SPR techniques were integrated with three-dimensional (3D) printing for enhancing analytical performance. A novel hybrid 3D printing and PDMS molding process was developed that overcomes fundamental resolution limits of the 3D printed optical components for spectroscopy. Prisms of multiple geometries were fabricated that demonstrated surface roughness comparable to commercial, glass-based components, providing economical alternative while yielding high sensitivity towards SPR biosensing of protein targets. Finally, we have developed a high performing SPR platform based on a more fundamental shift, switching the plasmonic material from gold to aluminum. Al thin films under Kretschmann configuration demonstrated a 60 % higher optical sensitivity in imaging mode and reduced surface fouling by 75 %. They proved excellent substrates for array-based chemical surface modifications by ionic polymers that were further employed for successful analysis of urine-based chemokine biomarkers. The work presented here should pave the way for more complex modalities in developing the next generation of biotechnology.