Localized surface plasmon resonance biosensors for real-time biomolecular binding study

Surface Plasmon Resonance (SPR) and localized surface plasmon resonance (LSPR) biosensors have brought a revolutionary change to in vitro study of biological and biochemical processes due to its ability to measure extremely small changes in surface refractive index (RI), binding equilibrium and kinetics. Strategies based on LSPR have been employed to enhance the sensitivity for a variety of applications, such as diagnosis of diseases, environmental analysis, food safety, and chemical threat detection. In LSPR spectroscopy, absorption and scattering of light are greatly enhanced at frequencies that excite the LSPR, resulting in a characteristic extinction spectrum that depends on the RI of the surrounding medium. Compositional and conformational change within the surrounding medium near the sensing surface could therefore be detected as shifts in the extinction spectrum. This dissertation specifically focuses on the development and evaluation of highly sensitive LSPR biosensors for in situ study of biomolecular binding process by incorporating nanotechnology. Compared to traditional methods for biomolecular binding studies, LSPR-based biosensors offer real-time, label free detection. First, we modified the gold sensing surface of LSPR-based biosensors using nanomaterials such as gold nanoparticles (AuNPs) and polymer to enhance surface absorption and sensitivity. The performance of this type of biosensors was evaluated on the application of small heavy metal molecule binding affinity study. This biosensor exhibited ∼7 fold sensitivity enhancement and binding kinetics measurement capability comparing to traditional biosensors. Second, a miniaturized cell culture system was integrated into the LSPR-based biosensor system for the purpose of real-time biomarker signaling pathway studies and drug efficacy studies with living cells. To the best of our knowledge, this is the first LSPR-based sensing platform with the capability of living cell studies. We demonstrated the living cell measurement ability by studying the VEGF signaling pathway in living SKOV-3 cells. Results have shown that the VEGF secretion level from SKOV-3 cells is 0.0137 ± 0.0012 pg per cell. Moreover, we have demonstrated bevacizumab drug regulation to the VEGF signaling pathway using this biosensor. This sensing platform could potentially help studying biomolecular binding kinetics which elucidates the underlying mechanisms of biotransportation and drug delivery.

Development of hardware in the loop real-time control techniques for hybrid power systems involving distributed demands and sustainable energy sources

The future power grid will effectively utilize renewable energy resources and distributed generation to respond to energy demand while incorporating information technology and communication infrastructure for their optimum operation. This dissertation contributes to the development of real-time techniques, for wide-area monitoring and secure real-time control and operation of hybrid power systems. ^ To handle the increased level of real-time data exchange, this dissertation develops a supervisory control and data acquisition (SCADA) system that is equipped with a state estimation scheme from the real-time data. This system is verified on a specially developed laboratory-based test bed facility, as a hardware and software platform, to emulate the actual scenarios of a real hybrid power system with the highest level of similarities and capabilities to practical utility systems. It includes phasor measurements at hundreds of measurement points on the system. These measurements were obtained from especially developed laboratory based Phasor Measurement Unit (PMU) that is utilized in addition to existing commercially based PMU’s. The developed PMU was used in conjunction with the interconnected system along with the commercial PMU’s. The tested studies included a new technique for detecting the partially islanded micro grids in addition to several real-time techniques for synchronization and parameter identifications of hybrid systems. ^ Moreover, due to numerous integration of renewable energy resources through DC microgrids, this dissertation performs several practical cases for improvement of interoperability of such systems. Moreover, increased number of small and dispersed generating stations and their need to connect fast and properly into the AC grids, urged this work to explore the challenges that arise in synchronization of generators to the grid and through introduction of a Dynamic Brake system to improve the process of connecting distributed generators to the power grid.^ Real time operation and control requires data communication security. A research effort in this dissertation was developed based on Trusted Sensing Base (TSB) process for data communication security. The innovative TSB approach improves the security aspect of the power grid as a cyber-physical system. It is based on available GPS synchronization technology and provides protection against confidentiality attacks in critical power system infrastructures. ^

Localized Surface Plasmon Resonance Biosensors for Real-Time Biomolecular Binding Study

Surface Plasmon Resonance (SPR) and localized surface plasmon resonance (LSPR) biosensors have brought a revolutionary change to in vitro study of biological and biochemical processes due to its ability to measure extremely small changes in surface refractive index (RI), binding equilibrium and kinetics. Strategies based on LSPR have been employed to enhance the sensitivity for a variety of applications, such as diagnosis of diseases, environmental analysis, food safety, and chemical threat detection. In LSPR spectroscopy, absorption and scattering of light are greatly enhanced at frequencies that excite the LSPR, resulting in a characteristic extinction spectrum that depends on the RI of the surrounding medium. Compositional and conformational change within the surrounding medium near the sensing surface could therefore be detected as shifts in the extinction spectrum. This dissertation specifically focuses on the development and evaluation of highly sensitive LSPR biosensors for in situ study of biomolecular binding process by incorporating nanotechnology. Compared to traditional methods for biomolecular binding studies, LSPR-based biosensors offer real-time, label free detection. First, we modified the gold sensing surface of LSPR-based biosensors using nanomaterials such as gold nanoparticles (AuNPs) and polymer to enhance surface absorption and sensitivity. The performance of this type of biosensors was evaluated on the application of small heavy metal molecule binding affinity study. This biosensor exhibited ~7 fold sensitivity enhancement and binding kinetics measurement capability comparing to traditional biosensors. Second, a miniaturized cell culture system was integrated into the LSPR-based biosensor system for the purpose of real-time biomarker signaling pathway studies and drug efficacy studies with living cells. To the best of our knowledge, this is the first LSPR-based sensing platform with the capability of living cell studies. We demonstrated the living cell measurement ability by studying the VEGF signaling pathway in living SKOV-3 cells. Results have shown that the VEGF secretion level from SKOV-3 cells is 0.0137 ± 0.0012 pg per cell. Moreover, we have demonstrated bevacizumab drug regulation to the VEGF signaling pathway using this biosensor. This sensing platform could potentially help studying biomolecular binding kinetics which elucidates the underlying mechanisms of biotransportation and drug delivery.