In this research, we have developed a rapid diagnostic assay using a high-electron-mobility transistor (HEMT)-based biosensor to screen for fibrinogen in clinical plasma samples. High sensitivity over a wide detection range (0-5 g/L), good selectivity, low-cost fabrication, portability, and simplicity of use are key features of our biosensor. Early diagnosis of heart disease in low-, medium-, and high-risk patients is possible with an assay turnaround time of 5 min and a plasma sample volume of 5-10 µL. High sensitivity and low detection limits (0.5 g/L) are made possible in environments with high salt concentrations because the HEMT sensor design overcomes the charge screening effect associated with a very small Debye length. This biosensor technology demonstrates the potential for development as a point-of-care or homecare diagnostic device for quick and easy assessment of cardiovascular disease (CVD) risk.