A practical tapered optical fiber (TOF) biosensing system was developed for label-free detection using antigen-antibody pairs with repeatable results and a very high degree of sensitivity. This was done by attaching molecular recognition agents to a tapered fiber surface for augmenting sensitivity and specificity of analyte. The entire system included three main parts: a tunable laser, a tapered fiber, and an optical detector. Light from an unpolarized tunable fiber laser was introduced into the tapered fiber from one end, and the transmitted intensity was detected by a photodetector. In the tapered fiber area, the evanescent electromagnetic field, which extends outside the fiber, was able to detect minute changes in the refractive index caused by antigen-antibody pairs. Recorded data was analyzed using an innovative Fourier analysis method to find phase changes, which are directly related to the biomolecular concentration coated on fiber, from which antibody-antigen concentrations are obtained. Two experiments were performed to confirm the concept using two very different agents. The first was the protein Interleukin-8 (IL-8). Repeatable results with a sensitivity of 10 pg/mL were achieved. The second was human coronavirus OC43 (HCoV-OC43), a surrogate viral particle for SARS-CoV-2, with a sensitivity of 50 viruses/mL. Critical sources of error were identified and addressed for the purpose of using the device for real clinical diagnosis in various real-life environments, where viruses can reside in water, phosphate-buffer solution, or saliva, the most popular three environments in real clinical diagnosis. Our device was designed according to the principle that only one specific kind of antibody and antigen can be combined together. The device demonstrated good accuracy to chosen analyte(s) tailored to specific applications and offered the potential to develop a point-of-care device used in clinics, as well as for detecting a variety of viruses and biocontaminants. The reproducibility of TOFs was confirmed through multiple fabrications and consistent results.