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Alpha-fetoprotein (AFP) is a typical tumor marker in early diagnosis. Highly specific detection of the AFP was demonstrated using AlGaAs/GaAs high electron mobility transistors (HEMTs). Anti-AFP antibody was immobilized to the Au-coated gate area of the HEMT by a covalent modification method. To avoid any nonspecific binding, the gate was blocked by bovine serum albumin after the reduction of the carbonyl group. A detection limit for the AFP as low as a few picograms/milliliter was achieved, and cross reactivity of the sensor was found negligible, demonstrating its high selectivity. Successful detection with minute quantity of the sample indicates that the sensor has great potential in practical screening for a wide population.