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Portable point-of-care (POC) medical diagnostic devices demand low power consumption, efficient use of low sample and reagent volumes, and small size. A “digital” electrowetting-on-dielectric (EWD) microfluidics system with integrated optical sensors is a promising platform for portable POC diagnostic devices that integrate sample preparation with sensing. Herein is reported the highest sensitivity and figure of merit (FOM) microresonator sensor integrated with an EWD system to date [FOM is the product of the quality (Q) factor and the sensitivity (S)]. The EWD system embedded microresonator sensor had a measured FOM of 0.60 × 106 nm/RIU (Q = 8,400, S = 72 nm/RIU) in 2-cSt silicone oil and water, which is nearly double the best FOM previously reported for an microresonator placed on top of an EWD system. Additionally, a nominal FOM of 1.2 × 106 nm/RIU (Q = 15 000, S = 82 nm/RIU) was measured for the vertically coupled sensor fabricated on a standard SiO2/Si substrate. This FOM is the highest reported to date for SU-8 microresonators probed at wavelengths around 1550 nm. These results indicate that high-performance polymer sensors can be integrated with low-power-consumption EWD microfluidics sample preparation systems toward the development of portable POC diagnostic devices.