Highly sensitive detection of urinary protein variations using tilted fiber grating sensors with plasmonic nanocoatings

Surface plasmon resonance (SPR) optical fiber biosensors can be used as a cost-effective and relatively simple-to-implement alternative to well established bulky prism configurations for high sensitivity biological sample measurements. The miniaturized size and remote operation ability offer them a multitude of opportunities for single-point sensing in hard-to-reach spaces, even possibly in vivo. The biosensor configuration reported in this work uses a tilted fiber Bragg grating (TFBG) in a commercial single mode fiber coated with a nanometer scale silver film. The key point is that by reducing the silver film thickness to around 20-30 nm (rather than 50 nm for optimal SPR excitation), different modes of the TFBG spectrum present very high but opposite sensitivities to refractive index (RI) changes around the TFBG. Experimental results obtained with the coated TFBG embedded inside a microfluidic channel show an amplitude sensitivity greater than 8000 dB/RIU (Refractive Index Unit) and a limit of detection of 10−5 RIU. Using this device, the effect of different concentrations of protein in rat urine was clearly differentiated between healthy samples, nephropatic samples and samples from individuals under treatment, with a protein concentration sensitivity of 5.5 dB/(mg/ml) and a limit of detection of 1.5×10−3 mg/ml. Those results show a clear relationship between protein outflow and variations in the RI of the urine samples between 1.3400 and 1.3408, pointing the way to the evaluation and development of new drugs for nephropathy treatments. The integration of TFBGs with microfluidic channels enables precise measurement control over samples with sub-microliter volumes and does not require accurate temperature control because of the elimination of the temperature cross-sensitivity inherent in TFBG devices. Integration of the TFBG with a hypodermic needle on the other hand would allow similar measurements in vivo. The proposed optical fiber/microfluidic plasmonic biosensor represents an appealing solution for rapid, low consumption and highly sensitive detection of analytes at low concentrations in medicine as well as in chemical and environmental monitoring.