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Tunnel field-effect transistors (TFETs) have emerged as promising candidates for next-generation low-power and high-sensitivity biosensing applications, offering a significant advantage over conventional metal-oxide-semiconductor field-effect transistor (MOSFET)-based technologies. Leveraging the principle of band-to-band tunneling, TFETs can achieve the subthreshold swing values below the thermionic limit of 60 mV/decade, resulting in ultra-low-power operation and minimal leakage currents—critical requirements for wearable, implantable, and battery-operated biomedical devices. This work comprises a thorough comparative analysis of multiple TFET architectures tailored for biosensing, including SG-ESTFET, DG-ESTFET, DS-DC-TG-VTFET, ES-VTFET, Ge source pocket TFET, DM-SGox HTFET, V-JL-TFET, inverted T-shaped negative capacitance TFET (NC-TFET), and ME-DG-TFET. The study evaluates their performance based on metrics such as shift in threshold voltage, drain current sensitivity, I ON /I OFF ratio, and transconductance, under the influence of various biomolecular charges and dielectric environments. Among the devices analyzed, DS-DC-TG-VTFET and Ge source TFETs exhibit outstanding performance in terms of linearity, current sensitivity, and noise immunity, whereas structures such as DM-SGox HTFET and ME-DG-TFET show enhanced sensitivity due to heterostructure and dielectric modulation techniques. The insights provided through this study aim to guide future research and development of practical, low-power TFET-based biosensors, paving the way for their deployment in medical diagnostics, environmental monitoring, and health management systems.