State Key Laboratory of Applied Optics, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, PR China.
University of Chinese Academy of Sciences, Beijing 100039, PR China.
ACS Sens. 2021 Dec 24;6(12):4304-4314. doi: 10.1021/acssensors.1c01031. Epub 2021 Nov 20.
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.
无标记光纤免疫传感器由于其高灵敏度，在近几十年受到了广泛关注。然而，在现有的无标记光纤生物传感器中，血清中的非特异性吸附仍然是一个关键的瓶颈，这阻碍了它们在诊断中的广泛应用。此外，临床人血清（HS）中的个体差异对生物传感结果有负面影响。在这项工作中，采用了改良的血清预吸附策略，通过在光纤微环耦合器（OMC）上形成饱和的抗污界面来减少非特异性吸附。此外，为了减少个体 HS 样本之间差异的影响，我们提出了一种新方法，由于 Sigma HS 与临床血清相比更接近其他血清，因此将其用作波长偏移参考来减少差异。首先使用 Sigma HS 来减少免疫传感器之间的差异，然后再对临床样本进行测试，通过多个传感器的独立校准，在宽动态范围内实现定量检测，该传感器通过解离过程实现。通过 Sigma HS 对 25% HS 的个体差异进行校正。作为概念验证，无标记 OMC 免疫传感器在不同浓度的 25% Sigma HS 中对癌胚抗原（CEA）的检测表现出良好的灵敏度和特异性。CEA 的检测限低至 34.6 fg/mL（0.475 fM）。此外，根据校准曲线，使用这种 OMC 免疫传感器对 CEA 进行了无标记定量检测的实验验证，结果与临床检查检测结果吻合良好。据我们所知，这是首次将 OMC 免疫传感器应用于临床 HS 的无标记定量检测。
