Label-enhanced surface plasmon resonance: a new concept for improved performance in optical biosensor analysis.

Surface plasmon resonance (SPR) is a well-established optical biosensor technology with many proven applications in the study of molecular interactions as well as in surface and material science. SPR is usually applied in the label-free mode which may be advantageous in cases where the presence of a label may potentially interfere with the studied interactions per se. However, the fundamental challenges of label-free SPR in terms of limited sensitivity and specificity are well known. Here we present a new concept called label-enhanced SPR, which is based on utilizing strongly absorbing dye molecules in combination with the evaluation of the full shape of the SPR curve, whereby the sensitivity as well as the specificity of SPR is significantly improved. The performance of the new label-enhanced SPR method was demonstrated by two simple model assays: a small molecule assay and a DNA hybridization assay. The small molecule assay was used to demonstrate the sensitivity enhancement of the method, and how competitive assays can be used for relative affinity determination. The DNA assay was used to demonstrate the selectivity of the assay, and the capabilities in eliminating noise from bulk liquid composition variations.

Non-labeled monitoring of targeted liposome interactions with a model receptor surface: effect of flow rate and water content.

In this study, we present a novel in vitro approach that utilizes two surface-sensitive and label-free techniques, i.e. surface plasmon resonance (SPR) and quartz crystal microbalance (QCM), to study the interfacial events during liposome-target surface interactions. The flow channels of SPR and QCM devices were first synchronized via hydrodynamic modeling. Biotin-streptavidin was used as a model pair and self-assembled monolayers (SAMs) were utilized as model surfaces for targeted liposome-surface interaction studies. The interactions between biotin-liposomes and the streptavidin-biotin-SAM surfaces were investigated under controlled shear flows using the synchronized SPR and QCM devices. The response of the liposome interaction was monitored as a function of the flow rate. The affinity and the amount of bound liposome indicated that the increased flow rate improved the binding of the targeted liposomes to the model membrane surfaces. The combined use of the synchronized SPR and QCM devices for nanoparticle interaction studies clearly demonstrates the effect of the flow rate (or the shear stress) on the liposome binding. Our results suggest that the binding of liposomes to the model membranes is flow rate and shear stress regulated. Thus, the flow rate (or the shear stress), which is usually neglected, should be taken into account during the development and optimization of targeted liposome formulations. In addition, the water content within the liposome layer (including the water inside the liposomes and the water between the liposomes) had a significant influence on the visco-elasticity and the binding kinetics to the SAM surfaces.