Detection of low index liquid analytes in real-time, in-situ, and with high accuracy is of great importance in various scientific fields, particularly in medicine and biology. Accurate detection of plasma concentration in blood samples is one of the most significant usages of biosensors in medicine. In this paper, we report a highly sensitive biosensor using hollow core microstructure optical fibers (HC-MOFs) to detect low index liquid analytes with a particular focus on detection of plasma concentration in blood samples. We demonstrate how variations in plasma concentration in blood can change transmission spectra of the HC-MOF due to the photonic bandgap mechanism. We use the finite element approach to explore how the biosensor’s performance depends on the number of capillary rings encircling the hollow core of the fibre. An average spectral and amplitude sensitivity of 8928.57 nm/RIU and 1.21 dB/RIU is reported for the optimized design of HC-MOF for five capillary rings with a refractive index detection range of 1.333 to 1.3385 for different ratios of plasma in blood serum. The proposed biosensor can have potential application in liquid analyte detection in medicine, chemistry, and biology where real-time and accurate data about liquid analytes are necessary for human metabolism.