Surface Plasmon Resonance Biosensing with Colloidal Au Amplification

For more than a decade, biosensors based on surface plasmon resonance (SPR) have been commercially available (1–4), making real-time, tagless biomolecular interaction analysis accessible to those in biochemistry-related fields. In parallel with (and largely driven by) these commercial successes, there have been large increases in the number of academic pursuits involving biosensing and bioassays with SPR (5–9). The motivations for these studies are quite diverse. Most attempts have been aimed at lowering the accessible range of the sensor platform with respect to both molecular weight and concentration. However, methods by which SPR can be interfaced with other instruments to form hyphenated techniques have been developed (10–13). Reports of multichannel and imaging sensors for highthroughput applications are now available (5,14–17). Finally, despite the traditional tagless format practiced in SPR, a number of systems using paniculate and molecular tags for sensitivity enhancement have been reported (7,16,18–21). This chapter will detail the fundamentals and early application of one of these tag-amplified SPR methods: colloidal Au-enhanced biosensing (7,20,21). We first describe the basics of SPR sensing as it is traditionally practiced. A general discussion of how particulate materials modulate the SPR of smooth metal surface follows. Experimental results from nonbiological SPR studies of colloidal