Systems, methods, and devices are disclosed for monitoring or quantifying of various analyte levels in a biological fluid using one or more implantable sensors by providing in situ calibration and/or cleaning of such sensors when implanted in a patient. The systems and devices can continuously or serially measure analytes within a biological fluid in vivo (e.g., without extracting the biological fluid from the patient) and can be periodically calibrated and/or cleaned without using finger sticks or other calibration techniques. For example, the invention can facilitate continuous monitoring of glucose concentrations in subcutaneous interstitial fluid for several hours to a few days. In certain embodiments, the invention can employ two reservoirs, one containing and a known concentration of an analyte and the other containing a diluent, and a mixer for mixing analyte from the first reservoir diluent from the second reservoir to obtain a calibration fluid of a desired concentration.
