This report demonstrates a method for high-resolution refractometric measurements using, what we have termed as, a Diffractive Interference Optical Analyzer (DiOpter). The setup consists of a laser, polarizer, a transparent diffraction grating and Si-photodetectors. The sensor is based on the differential response of diffracted orders to bulk refractive index changes. In these setups, the differential read-out of the diffracted orders suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6x10-7 RIU was achieved in glass. This work focuses on devices with integrated sample well, made on low-cost PDMS. As the detection methodology is experimentally straightforward, it can be used across a wide array of applications, ranging from detecting changes in surface adsorbates via binding reactions to estimating refractive index (and hence concentration) variations in bulk samples. An exciting prospect of this technique is the potential integration of this device to smartphones using a simple interface based on transmission mode configuration. In a transmission configuration, we were able to achieve an LoD of 4x10-4 RIU which is sufficient to explore several applications in food quality testing and related fields. We are envisioning the future of this platform as a personal handheld optical analyzer for applications ranging from environmental sensing to healthcare and quality testing of food products.