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In this work, nanowire field-effect transistors (NW-FETs) constructed from a top-down approach has been utilized for the detection of biomolecules. Here, we demonstrate that the sensitivity of NW-FET sensors can be greatly enhanced when the same dopant type is used for both channel region and source and drain. This type of FET, known as accumulation mode field-effect transistors (AM-FETs), functions under different operating principle compared with conventional inversion mode FETs. The improved sensitivity is attributed to the different conduction mechanism and current components of AM devices. The results have been verified through a direct comparison with a conventional FET.