Integrated fluid handling system for biomolecular interaction analysis.

Abstract

An integrated fluid handling system used for multichannel biomolecular interaction analysis is described. Reactions between biological molecules are monitored in real time by measuring changes in the angular position where surface plasmon resonance occurs at a biospecific active surface. The adsorption efficiency of the analyte onto the biospecific active surface is up to approximately 3%, due to the low channel height, 50 microns, in the flow cell. When a large part of the total biospecific active surface for surface plasmon resonance probing (approximately 0.15 mm2) is used, the sensitivity is high. Sample sizes in the order of 1-50 microL can be injected. The sample zone dispersion is minimized by the low dead volume in the system (approximately 0.4 microL) accomplished by using integrated sample loops and thin conduits. An asset of this integration is the low reagent consumption. The sensor chip with the biospecific active surface is reusable and easily exchanged. Experimental results obtained with a theophylline monoclonal antibody as the analyte are compared with a theoretical model. The standard deviation for the repeatability is approximately 5% typically with 50 microL of 250 pM analyte, and the assay time is 10 min. The detection limit is approximately 10 pg of the analyte on the probed spot of the surface. Possible improvements of the sensitivity and detection limit are discussed.