The performance of many biosensors is limited by the rate at which a soluble analyte solution is transported to a complementary receptor immobilized on the sensor transducer. In these cases, transport limitations due to the lack of sample mixing in the sensor can impede analyte transport to the immobilized receptors and thereby reduce the sensor performance. In this study, we apply methods that have been successfully used to mix bulk fluid streams in a microfluidic device, to stir the analyte solution as it passes over receptors bound to the surface of an optical biosensor. A three-dimensional serpentine microchannel, which has been shown to provide chaotic mixing in the sample flow, was interfaced with a surface plasmon resonance biosensor. The binding kinetics of soluble rabbit IgG to protein A, immobilized on one of the microchannel walls, was measured both in the serpentine device and in a straight channel. A comparison of the initial rates of analyte detection in these two devices shows that the mixing characteristics in the serpentine microchannel can double the initial rate of analyte detection. The serpentine mixer is thus a promising method for improving the performance of surface-based microfluidic biosensors.