Developing Multifunctional Surface Chemistry for Plasmonic Biosensing in Complex Media
During the past decades, plasmonic sensors have been explored extensively due to their ultra-sensitivity and emerged as a new generation of analytical tools. Two of the most widely used and studied plasmonic sensors are surface enhanced Raman scattering (SERS) sensors and surface plasmon resonance (SPR) sensors, which are focused in this dissertation. SERS is a phenomenon which can significantly magnify the Raman signals of the molecules adsorbed on a nanostructured metal surface for up to millions of folds and have led to the detections of single molecules. SERS can also provide chemical fingerprints representing vibrational or rotational transitions specific to the molecular structure to identify the analyte. The SPR optical sensor can enable the direct observation of molecular interaction in real-time and offer the benefits of rapid, sensitive and label-free detection of chemical and biological species. Based on these advantages such as ultra-sensitivity and molecular specificity, both of the sensors have already been used for a variety of applications ranging from chemical and biological sensing, environmental monitoring to diagnostics. However, reliable biosensing in complex biological media based on these two advanced plasmonic sensors is still very challenging due to several reasons. For example, SERS is a near-field effect; the enhancement effect decreases exponentially with increasing distance from the surface. A bare SERS-active surface lacks selectivity; anything adsorbed onto the surface can be detected. In the complex media, the background noise from interfering species could mask the signals from target analytes. In addition, nonspecific adsorption from the complex media could impede the adsorption of target analytes to SERS-active substrate surfaces. Thus, a method which can amplify the detection signals over unwanted background is highly desirable and it is also essential to introduce nonfouling modifications to protect the SERS-active surface from nonspecific adsorption. For an SPR sensor, the specificity of the SPR sensor is totally dependent on the biomolecular recognition species employed while the sensitivity depends on the amount of nonspecific binding. Thereby, the surface chemistry which can not only effectively resist nonspecific protein adsorption but also provides abundant sites for the ligand immobilization is desired. In this dissertation, we discuss the design and selection of probe molecules on the SERS surface for specific detection and signal amplification of target analytes with small Raman activity or no activity such as fructose or hydrogen ion. In addition, to overcome the protein fouling problem, we introduce a zwitterionic nonfouling surface modification to the SERS sensor. We design and synthesize a zwitterionic short thiol, which contains a carboxybetaine head group resisting the protein adsorption effectively. The CBT possesses a small Raman activity generating negligible background noise even with high packing density. To future improve the nonfouling property of the modification, we also introduce the zwitterionic poly(carboxybetaine acrylamide) (pCBAA) polymer brush on the SERS surface via surface-initiated atom transfer radical polymerization (SI-ATRP). This modification enables the SERS detection of several therapeutic drugs directly in the human undiluted plasma. For the SPR sensor, we develop a facile and stable nonfouling coating method based on the zwitterionic hydrogel. The hydrogel coating demonstrate ultra-low fouling property from the undiluted blood serum and high antibody loading capacity due to the three-dimensional structure. At last, we also propose a new method to detect the anti-PEG antibody in blood sample based on the PEG coated SPR sensor. The surface chemistry is studied and optimized to achieve an extremely low limit of detection showing better sensitivity compared with traditional ELISA detection methods. By tailoring and tuning the surface chemistry, we explore and expand the applications of the plasmonic sensor in complex media. On the one hand, we introduce the attracting and probing molecules to enhance the detection signals. And on the other hand, we modify the zwitterionic nonfouling materials on the surface of sensors to decrease the background noise and interference. With the improved signal/noise ratio, the sensitivity of sensors can be dramatically increased.
- Chemical engineering