Atomically layered transition metal dichalcogenides (TMDCs) exhibit a significant potential to enable low-cost transistor biosensors that permit single-molecule-level quantification of biomolecules. Two different principles for operating such biosensors are presented. In one arrangement, antibody receptors are functionalized on an insulating layer deposited onto the channel of the transistor. The charge introduced through antigen-antibody binding is capacitively coupled with the channel and shifts the threshold voltage without significantly changing the transconductance. In another arrangement, antibodies are functionalized directly on the channel of the transistor. Antigen-antibody binding events mainly modulate the ON-state transconductance, which is attributed to the disordered potential formed in channel material.