This Small Business Innovation Research (SBIR) Phase I project will demonstrate the feasibility of a temperature-independent surface plasmon resonance (SPR) biosensor for sensitive detection of biological molecules. SPR bio-detection has been used for many years in biomedical research and drug development laboratories. Recent improvement in sensitivity and potentially lower cost enable the use of SPR-based biosensor in diagnostic application, including testing of pathogens, biomarkers, toxins and contaminants. However, current SPR instruments are susceptible to temperature-induced measurement errors that limit their use in the field. The thermal drift in SPR sensors is caused by the dependence of the refractive index of the sensor's optical medium and the sample material on ambient temperature. Currently, this thermal drift is mitigated in laboratory instruments by stabilizing the temperature in the instrument's test chamber and by incorporating temperature compensation channels into the sensor design. However, these active measures increase the instrument's complexity, cost, size and power consumption. The proposed temperature-independent SPR design addresses this fundamental deficiency and reduces by a factor of 100~1000 the thermal sensitivity of a waveguide-based SPR chip by matching the thermo-optic coefficients of the chip's optical substrate and the sample under test. If successful the proposed project will lead to expansion of the application range and market penetration of SPR biodetection technology. Based on the high-sensitivity and low cost of the proposed SPR sensor, a handheld instrument will be developed to support multiple field and point-of-care diagnostic applications in the areas of emergency medicine, veterinary medicine, food safety, aquaculture and biodefense