In this study, we use NEGF quantum transport simulations to study the fundamental detection limit of ultra-scaled Si nanowire FET (NWT) biosensors. A N-doped NWT is found to be more sensitive for negatively charged analytes as explained by the nature of the detection mechanism. Our results predict threshold voltage shifts due to a single-charge analyte of tens to hundreds of mV in air or low-ionic solutions. However, with typical ionic solutions and SAM conditions, the sensitivity rapidly drops to the mV/q range. Our results are then extended to the detection of a single 20-base-long DNA molecule in solution. The impact of front- and/or back-gate biasing on the sensitivity and limit of detection is studied and a signal-to-noise ratio of 10 is predicted. Opportunities and challenges to reach down to single-analyte detection in such systems are also discussed, including the ionic and oxide-solution interface-charge screening and ways to recover unscreened sensitivities.