This paper presents an analytical model of a bio-molecule-induced threshold voltage shift (ΔVth) in a normally-off AlGaN/GaN metal-oxide-semiconductor high-electron-mobility transistors (MOSHEMTs) used as bio-particle sensors. In the analytical model, the presence of biomolecules is represented by using the dielectric modulation (DM) technique for label-free electrical detection. The dielectric/semiconductor interface density-of-State (DOS)-dependent model for the density of two dimensional electron gas (2DEG) is obtained by solving a 2-D Poisson equation demonstrating required energy band diagrams. The effective capacitance in the cavity region and the threshold voltage are obtained by using dielectric modulation and the Poisson equation. Subsequently, the changes in the threshold voltage and the drain current of the device are used as the sensing metric for the detection of bio-molecules in the cavity region. Interestingly, the charge of the biomolecules can also used as a sensing parameter. The predicted sensing metric characteristics of the developed analytical model are in good agreement with the result of technology computer-aided design (TCAD) simulations, thus confirming the validity of the proposed model.