Label-free optical biosensors offer advantages for many applications due to their simplicity and low cost compared to fluorescence detection. Thus, it is desirable to develop label-free sensors that can be integrated with advanced microfluidic systems into dense, multi-purpose biosensor arrays. One candidate technology is ring resonators, which utilize the resonating whispering gallery modes to create a strongly enhanced optical field in the sensing volume. Because of the high Q-factor of ring resonators, the optical field can be enhanced by 2-3 orders of magnitude, which leads to much smaller required light-matter interaction length and sensing volume. These are critical characteristics for dense integration into lab-on-a-chip systems. We have developed a novel label-free ring resonator sensor based on a liquid core optical ring resonator (LCORR). This system uses a glass capillary as both the fluidics and the ring resonator. With the LCORR, we have demonstrated a measurable whispering gallery mode spectral shift of 30 pm/refractive-index-unit (RIU), which leads to a detection limit of approximately 10-6 RIU. Additionally, we have achieved an estimated detection limit for protein molecules of 10 pg/mm2. These experimental demonstrations of this novel sensing system will lead to the development of highly sensitive label-free sensors that are well-suited for dense integration with advanced microfluidics for lab-on-a-chip systems.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.