An analyte monitoring sensor configured for in vivo measurement of at least one analyte is provided, the sensor comprising a substrate having a substrate surface, an aptamer protective layer encapsulating at least a portion of the substrate surface, the aptamer protective layer permeable to the at least one analyte, one or more aptamer conjugates associated with at least a portion of the substrate surface and positioned between the aptamer protective layer and the substrate for obtaining measurements related to the at least one analyte in vivo. Methods of extending in vivo performance of the analyte monitoring sensor are also described.