High Sensitivity Label-Free Quantitative Method for Detecting Tumor Biomarkers in Human Serum by Optical Microfiber Couplers.

Abstract

Label-free optical fiber immunosensors have attracted widespread attention in recent decades due to their high sensitivity. However, nonspecific adsorption in serum has remained a critical bottleneck in existing label-free fiber optic biosensors, which hinders their widespread use in diagnostics. In addition, individual differences in clinical human serum (HS) negatively impact biosensing results. In this work, the modified serum preadsorption strategy was applied to reduce nonspecific adsorption by forming a saturated antifouling interface on an optical microfiber coupler (OMC). Furthermore, to reduce the effect of the differences between individual HS samples, we proposed a new method where Sigma HS was used as a wavelength shift reference due to being close to clinical serum compared to other serums. Sigma HS was used first to reduce the differences in immune sensors before performing a clinical sample test in which quantitative detection was achieved based on the independent calibration of several sensors with wide dynamic ranges via dissociation processes. The individual differences in 25% HS were corrected by 30% Sigma HS. As a proof of concept, the label-free OMC immune sensor demonstrates good sensitivity and specificity for the detection of carcinoembryonic antigen (CEA) in 25% Sigma HS at different concentrations. The detection limit of CEA reached as low as 34.6 fg/mL (0.475 fM). Additionally, label-free quantitative detection of CEA using this OMC immune sensor was verified experimentally according to the calibration line, and the results agree well with clinical examination detection. To our knowledge, it is the first study to employ an OMC immune sensor in point-of-care label-free quantitative detection for clinical HS.