A novel real-time optical phase sensing method based on the Mach-Zehnder interference principle has been proposed for the detection of calreticulin (CRT) levels in human serum samples. In this approach, anti-CRT antibodies are utilized to capture CRT molecules in serum, leading to a phase shift in both the measuring and reference arms of the system. By employing the concept of weak amplification within the framework of weak measurements, it becomes feasible to continuously monitor the response of CRT in real-time, allowing for the precise determination of serum CRT content at the picomolar level. Our achievement may pave the way in establishing CRT as a diagnostic biomarker for a wide range of medical applications, including rheumatoid arthritis.