Thesis (Ph. D.)--University of Washington, 2000Biosensors based on surface plasmon resonance (SPR) detect biological substances through changes in the refractive index (RI) at the sensor surface. We present two optical multisensors designed to improve the robustness of SPR sensing.Bulk RI interference is a serious drawback of SPR sensing. It has limited the application of SPR to laboratory experiments in which the bulk RI is kept constant. An SPR instrument can solve the problem of bulk RI effects by simultaneously measuring both the SPR response and the bulk RI of the analyte. In our SPR/internal reflection refractometry (IRR) sensor, the bulk RI is measured by critical angle refractometry. In experiments which investigated the ability of the instrument to compensate for bulk effects due to solution composition and temperature, the instrument was found to eliminate 85% to 99% of bulk RI interference.The SPR/IRR sensor must make high quality measurements of surface RI and bulk RI to realize the benefits of critical angle compensation. These measurements are performed under difficult conditions: the functionalized SPR sensor surface is prone to drift, and the sensor's cost must be minimized. We describe data analysis and calibration techniques which use linear algorithms combined with calibration measurements to produce high quality data under these circumstances.The SPR/IRR instrument demonstrates that a sensor which combines two sensing techniques can produce more robust measurements than an instrument which relies upon a single technique. We present a new SPR sensor which retains and enhances this multisensing capability in a streamlined configuration. The sensor is based on capillary tubes internally coated with gold. A focused laser beam strikes the capillary radially and is reflected from the interior surface at a range of angles. The reflected light is then intercepted by an array detector. The versatile optics of capillaries allow the implementation of several types of optical sensing, including critical angle measurement of bulk RI.Theory, modeling, fabrication, and characterization techniques for SPR capillary sensors are presented. Two techniques for depositing gold in capillaries were found to produce gold layers usable for SPR sensing
