Precision manipulation of organic and inorganic nanoentities for enhanced optical biodetection at deterministic positions

Liu, Chao, Ph. D. in materials science and engineering
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In the last decade, considerable research interests are focused on applying semiconductor quantum dots (QDs) for bioimaging, sensing, and therapeutic delivery. Compared to traditional organic dyes, semiconductor QDs exhibit higher fluorescent brightness, better resistance to photo-bleaching, tunable sizes/colors, wider absorption peak and larger stokes shifts. However, the applications of QDs as biosensors are still largely conducted in bulk colloidal suspensions, which present considerable difficulties in sensing a minute amount of bioanalyte. It is highly desirable if the QDs can be registered at designated locations for position-predicable optical analysis and sensing. Raman scattering spectroscopy has been utilized to unambiguously identify molecules based on their intrinsic vibrational "fingerprint" states. However, due to the relatively small Raman scattering cross-section, the intensity of Raman signal is usually 1/10⁶ of that of Rayleigh scattering. The recent discovery of Surface enhanced Raman scattering (SERS) dramatically improves the Raman signal and rejuvenates this field. An enhancement factor (EF) as high as 10¹² have been reported, which can readily detect various single molecules, essential for early-stage disease detection, warfare agent detection, environmental pollutant detection, and biomolecule detection. However, SERS substrates with such high EF usually suffer from reproducibility and uniformity issues. Moreover, SERS detection is still largely conducted in a seek-and-find manner which substantially limits the detection efficiency. Most SERS detections are carried out by drying analyte solutions on SERS substrates to force molecules to attach to hotspots before the detection. The employed drying methods can be different among individual research groups. Quantitative comparison of these results should be conducted carefully. It is highly desirable to directly detect molecules in suspension to accurately evaluate the performances of different SERS substrates. However, when directly measuring SERS signals of molecules in suspension, due to the inefficient diffusion based binding process, much less molecules can closely interact with hot spots compared to those on dried SERS samples. As a result, direct SERS detection from suspension can often be less sensitive by a few orders of magnitudes compares to those in dried condition. It is of great interest to investigate new mechanisms to detect analyte molecules directly from analyte solutions with high sensitivity. In this research, I rationally designed and synthesized various types of nanostructures, including ZnO, Si, and Au nanowires, ZnO nanosuperstructures, and hybrid nanocapsules. Such materials have unique optical/plasmonic properties and could be used in various applications, particularly in biochemical sensing. Two types of optical nanobiosensors have been designed, fabricated, characterized, and investigated. They are fluorescence-based QD-on-nanowire assemblies and SERS-photonic-crystal hybrid nanosensors. The QD-on-nanowire florescent nanosensors operated uniquely by focusing analyte molecules to the assembled QDs on tips of nanowires before detection via specific biochemical conjugation. Molecules, such as biotin, can be revealed unambiguously in a location deterministic manner with substantially enhanced sensitivity. In the development of SERS-photonic-crystal hybrid nanosensors, two enhancement mechanisms, including guided-mode resonance (GMR) and electrokinetic effect, were studied and applied in improving the sensitivity and efficiency of molecule detection, respectively. Such a hybrid device has been proposed and studied for the first time, which can readily improve the detection sensitivity by a robust 4-5 times in addition to the 10⁹-10¹⁰ SERS enhancement. This dissertation work, exploring innovative materials design, synthesis, and manipulation, has made an important forward step in the next-generation biochemical detection platform.