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Increased level of CD44 protein in serum is observed in several cancers and is associated with tumor burden and metastasis. Current clinically used detection methods of this protein are time-consuming and use labeled reagents for analysis. Therefore exploring new label-free and fast methods for its quantification including its detection in situ is of importance. This study reports the first optical fiber biosensor for CD44 protein detection, based on a spherical fiber optic tip device. The sensor is easily fabricated from an inexpensive material (single-mode fiber widely used in telecommunication) in a fast and robust manner through a CO2 laser splicer. The fabricated sensor responded to refractive index change with a sensitivity of 95.76 dB/RIU. The spherical tip was further functionalized with anti-CD44 antibodies to develop a biosensor and each step of functionalization was verified by an atomic force microscope. The biosensor detected a target of interest with an achieved limit of detection of 17 pM with only minor signal change to two control proteins. Most importantly, concentrations tested in this work are very broad and are within the clinically relevant concentration range. Moreover, the configuration of the proposed biosensor allows its potential incorporation into an in situ system for quantitative detection of this biomarker in a clinical setting.

Optical fiber ball resonators based on single-mode fibers in the infrared range are an emerging technology for refractive index sensing and biosensing. These devices are easy and rapid to fabricate using a CO2 laser splicer and yield a very low finesse reflection spectrum with a quasi-random pattern. In addition, they can be functionalized for biosensing by using a thin-film sputtering method. A common problem of this type of device is that the spectral response is substantially unknown, and poorly correlated with the size and shape of the spherical device. In this work, we propose a detection method based on Karhunen−Loeve transform (KLT), applied to the undersampled spectrum measured by an optical backscatter reflectometer. We show that this method correctly detects the response of the ball resonator in any working condition, without prior knowledge of the sensor under interrogation. First, this method for refractive index sensing of a gold-coated resonator is applied, showing 1594 RIU−1 sensitivity; then, this concept is extended to a biofunctionalized ball resonator, detecting CD44 cancer biomarker concentration with a picomolar-level limit of detection (19.7 pM) and high specificity (30–41%).

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