The development of sensitive methods for in situ detection of biomarkers is a real challenge to bring medical diagnosis a step forward. The proof-of-concept of a remote multiplexed biomolecular interaction detection through a plasmonic optical fiber bundle is demonstrated here. The strategy relies on a fiber optic biosensor designed from a 300 µm diameter bundle composed of 6000 individual optical fibers. When appropriately etched and metallized, each optical fiber exhibits specific plasmonic properties. The surface plasmon resonance phenomenon occurring at the surface of each fiber enables to measure biomolecular interactions, through the changes of the retro-reflected light intensity due to light/plasmon coupling variations. The functionalization of the microstructured bundle by multiple protein probes was performed using new polymeric 3D-printed microcantilevers. Such soft cantilevers allow for immobilizing the probes in micro spots, without damaging the optical microstructures nor the gold layer. We show here the potential of this device to perform the multiplexed detection of two different antibodies with limits of detection down to a few tenths of nanomoles per liter. This tool, adapted for multiparametric, real-time, and label free monitoring is minimally invasive and could then provide a useful platform for in vivo targeted molecular analysis.
23 February 2019 in Analytical and Bioanalytical Chemistry
Improving the sensitivity of plasmonic optical fiber sensors constitutes a major challenge as it could significantly enhance their sensing capabilities for the label-free detection of biomolecular interactions or chemical compounds. While many efforts focus on developing more sensitive structures, we present here how the sensitivity of a sensor can be significantly enhanced by improving the light analysis. Contrary to the common approach where the global intensity of the light coming from the core is averaged, our approach is based on the full analysis of the retro-reflected intensity distribution that evolves with the refractive index of the medium being analyzed. Thanks to this original and simple approach, the refractive index sensitivity of a plasmonic optical fiber sensor used in reflection mode was enhanced by a factor of 25 compared to the standard method. The reported approach opens exciting perspectives for improving the remote detection as well as for developing new sensing strategies.
Multiplexed remote bio‐detection is demonstrated through an optical waveguide assembly coated with interferometric layers. Image conduits (IC)s, composed of 3012 individual cores, are coated with interferometric layers of tantalum pentoxide (Ta2O5) and silica (SiO2) to transform each core into a sensitive sensor. The spectral response of the IC as a function of refractive index (RI) changes is obtained and compared with the simulated one. The experimental sensitivities and resolutions of individual cores of the waveguide are assessed in remote detection mode by imaging through the optical assembly. For 75% of the cores, a sensitivity better than 510%. RIU−1 (RI Unit) is obtained, corresponding to a resolution better than 7 × 10−4 RIU. Furthermore, the coated face of IC is functionalized with two localized arrays of hundred‐micrometer droplets containing two different oligonucleotide (ODN) probes using a polymeric 3D‐printed microcantilever. Hybridization of complementary ODN strands is detected for one of the probes, the second being a negative control. Interaction kinetics are monitored in functionalized areas by grouping several cores or on individual cores. Thus, multiplexed bio‐detection on the surface of an interferometric waveguide is demonstrated for the first time paving the way for applications in multiplex in situ biosensing, and, ultimately, in vivo endoscopic diagnosis.