ABSTRACT

In view of basic science, understanding biological systems increasingly depends on our ability to dynamically and quantitatively measure the molecular processes with high spatial and temporal resolution, within the context of a living cell. A living cell responds to its changing environment both inside and outside itself in such a dynamic way that signaling proteins, enzymes, mRNA, and transcription and translation factors are continuously modi-‡ed or synthesized, transferred from one organelle to another, and ‡nally transported to the locations where they perform appropriate cell function. These intracellular biomolecular complexes are not only heterogeneously distributed in space, but perpetually changed over time with the change of surrounding microenvironments.1 To quantitatively follow the intracellular biochemical distribution locally and temporarily is vital for understanding

CONTENTS

5.1 Introduction ........................................................................................................................ 103 5.2 Theoretical Background .................................................................................................... 104 5.3 Controlled Synthesis and Nanofabrication of Plasmonic Nanostructures ............... 108

5.3.1 Bottom-up Chemical Synthesis ............................................................................ 108 5.3.2 Top-Down Nanofabrication .................................................................................. 109

5.3.2.1 Electron Beam Lithography ................................................................... 110 5.3.2.2 Nanoimprint Lithography ..................................................................... 110 5.3.2.3 Template-Based Methods ....................................................................... 110 5.3.2.4 Nanosphere Lithography ....................................................................... 111 5.3.2.5 Oblique Angle Deposition and Glancing Angle Deposition ............ 111

5.4 Surface Biofunctionalization of Plasmonic Nanomaterials ......................................... 113 5.5 Application .......................................................................................................................... 114

5.5.1 Case 1: Molecular Plasmonic Rulers ................................................................... 114 5.5.2 Case 2: Multiplexed LSPR Detection ................................................................... 115 5.5.3 Case 3: Coupling LSPR with SERS ...................................................................... 117

5.6 Summary ............................................................................................................................. 119 Acknowledgment ........................................................................................................................ 120 References ..................................................................................................................................... 120

intracellular organization and function in cell signaling, growth, differentiation, apoptosis, cell developmental processes, and relevant diseases. Moreover, in biotechnology industry, combinatorial methods are increasingly applied to synthesize new biocatalysts or drugs, demanding simultaneous analysis of thousands of pathogens, mutants, or therapeutic drugs. Furthermore, in personalized medicine, as dictated by economic reasons, mass application of screening and diagnostic tools has to be fast, convenient, and low cost, requiring miniaturization, parallelization, integration, as well as automation of biosensing devices.