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Nickel cantilevers with integrated diffraction gratings are used as resonant mass sensors with a resolution of 500 femtograms. Their applicability to biosensing is demonstrated with human opioid receptors. The device is fabricated through a single-mask lithographic process. The microoptical readout provides a simple measurement platform with one external photodiode. Thanks to its AC operation principle, the device is immune to environmental noise and entails a high tolerance to fabrication defects. Obtained signal-to-noise ratio is comparable to that of a high-end Doppler vibrometer. The device with these aspects for systems integration and microarray technology is a candidate for low-cost portable sensors.