Plasmonic Optical Fiber-Grating Immunosensing: A Review <s> Detection of Cancer Biomarkers <s> This study reports on the development of a surface plasmon resonance (SPR) optical fiber biosensor based on tilted fiber Bragg grating technology for direct detection of small biomarkers of interest for lung cancer diagnosis. Since SPR principle relies on the refractive index modifications to sensitively detect mass changes at the gold coated surface, we have proposed here a comparative study in relation to the target size. Two cytokeratin 7 (CK7) samples with a molecular weight ranging from 78 kDa to 2.6 kDa, respectively CK7 full protein and CK7 peptide, have been used for label-free monitoring. This work has first consisted in the elaboration and the characterization of a robust and reproducible bioreceptor, based on antibody/antigen cross-linking. Immobilized antibodies were then utilized as binding agents to investigate the sensitivity of the biosensor towards the two CK7 antigens. Results have highlighted a very good sensitivity of the biosensor response for both samples diluted in phosphate buffer with a higher limit of detection for the larger CK7 full protein. The most groundbreaking nature of this study relies on the detection of small biomolecule CK7 peptides in buffer and in the presence of complex media such as serum, achieving a limit of detection of 0.4 nM. <s> BIB001 </s> Plasmonic Optical Fiber-Grating Immunosensing: A Review <s> Detection of Cancer Biomarkers <s> This work presents the development of an innovative plasmonic optical fiber (OF) immunosensor for the detection of cytokeratin 17 (CK17), a biomarker of interest for lung cancer diagnosis. The development of this sensing platform is such that it can be assessed in non-liquid environments, demonstrating that a surface plasmon resonance (SPR) can be excited in this case. For this purpose, detections have been first carried out on CK17 encapsulated in gel matrix in the aim of mimicking tissue samples. Gold-coated OF immunosensors were embedded in a specifically designed packaging providing enough stiffness to penetrate into soft matters. Resulting reflected spectra have revealed, for the first time, the presence of a stable SPR signal recorded in soft matters. Experiments conducted to detect CK17 trapped in a porous polyacrylamide gel matrix have highlighted the specific and selective biosensor response towards the target protein. Finally, the packaged OF immunosensor has been validated by a preliminary test on human lung biopsy, which has confirmed the ex-vivo CK17 detection. Consequently, this work represents an important milestone towards the detection of biomarkers in tissues, which is still a clinical challenge for minimally-invasive in vivo medical diagnosis. <s> BIB002
This subsection summarizes the standard roadmap usually pursued to build plasmonic fiber-grating immunosensors. It shows the generic process, on the one hand, and focuses on a practical example linked to a relevant clinical issue, on the other hand: the minimally invasive detection of cancer biomarkers. In BIB001 BIB002 , the focus was made on cytokeratins (both CK7 and CK17) that are usually used for diagnosis in oncology, especially in the differential diagnosis of lung carcinomas, since primary tumors express CK7 while secondary tumors are deficient. Moreover, it has been demonstrated that cytokeratin fragments can be released from malignant cells and can reach the blood circulation. They are, therefore, easily accessible with an optical fiber that has been properly modified. Sensors prototyped for minimally invasive diagnosis, as those reported in BIB001 BIB002 , can be prepared following the main steps listed in Table 2 below. Table 2 . Main steps required to modify an optical-fiber section into a plasmonic fiber-grating immunosensor.