SERS assisted sandwich immunoassay platforms for ultrasensitive and selective detection of human Thyroglobulin.

We developed an immunoassay platform for the detection of human Thyroglobulin (Tg) to be integrated with fine-needle aspiration biopsy for early detection of lymph node metastases in thyroid cancer patients. The sensing platform detects Tg by a sandwich immunoassay involving a self-assembled surface-enhanced Raman scattering (SERS) substrate assisted by functionalized gold nanoparticles that provide additional Raman signal amplification and improved molecular specificity. Specifically, the SERS-active substrates were functionalized with Tg Capture antibodies and fabricated either on-chip or on optical fiber tips by nanosphere lithography. Gold nanoparticles were functionalized with Detection antibodies and conjugated with 4-mercaptobenzoic acid, which serves as a Raman reporter. The sandwich assay platform was validated in the planar configuration and a detection limit as low as 7 pg/mL was successfully achieved. Careful morphological examination of the SERS substrates before and after Tg measurements further assessed the effective capture of nanoparticles and correlated the average nanoparticle coverage with the Tg concentration obtained by SERS measurements. The sandwich assay was successfully demonstrated on washout fluids of fine needle aspiration biopsies from cancer patients and confirmed the high specificity of the proposed methodology when complex biological matrices are considered. Finally, SERS optrodes were fabricated and successfully used to detect Tg concentration by applying the same bio-recognition strategy and Raman interrogation through an optical fiber. This opens the possibility of transferring the Tg detection approach to the optical fiber tip to develop point-of-care platforms that can be directly integrated into fine needle aspiration biopsies.

Self-assembly on optical fibers: a powerful nanofabrication tool for next generation "lab-on-fiber" optrodes.

Self-assembly offers a unique resource for the preparation of discrete structures at the nano- and microscale, which are either not accessible by other fabrication techniques or require highly expensive and technologically demanding processes. The possibility of obtaining spontaneous organization of separated components, whether they are molecules, polymers, nano- or micro-objects, into a larger functional unit, enables the development of ready-to-use plug and play devices and components at lower costs. Expanding the applicability of self-assembly approaches at the nanoscale to non-conventional substrates would open up new avenues towards multifunctional platforms customized for specific applications. Recently, the combination of the amazing morphological and optical features of self-assembled patterns with the intrinsic properties of optical fibers to conduct light to a remote location has demonstrated the potentiality to open up new intriguing scenarios featuring unprecedented functionalities and performances. The integration of advanced materials and structures at the nanoscale with optical fiber substrates is the idea behind the so-called lab-on-fiber technology, which is an emerging technology at the forefront of nanophotonics and nanotechnology research. Self-assembly processes can have a key role in implementing cost-effective solutions suitable for the mass production of technologically advanced platforms based on optical fibers towards their real market exploitation. Novel lab-on-fiber optrodes would arise from the sustainable integration of functional materials at the nano- and microscale onto optical fiber substrates. Such devices are able to be easily integrated in hypodermic needles and catheters for in vivo theranostics and point-of-care diagnostics, opening up new frontiers in multidisciplinary technological development to be exploited in life science applications. This work is conceived to provide an overview of the latest strategies, based on self-assembly processes, which have been implemented for the realization of lab-on-fiber optrodes with particular emphasis on the perspectives and challenges that lie ahead. We discuss the main fabrication techniques and strategies aimed at developing new multifunctional optical fiber nanoprobes and their application in real scenarios. Finally, we highlight some of the other self-assembly processes that have not yet been applied to optical fiber sensors, but have the potentiality to be exploited in the fabrication of future lab-on-fiber devices.

Optical fiber tip templating using direct focused ion beam milling.

We report on a method for integrating sub-wavelength resonant structures on top of optical fiber tip. Our fabrication technique is based on direct milling of the glass on the fiber facet by means of focused ion beam. The patterned fiber tip acts as a structured template for successive depositions of any responsive or functional overlay. The proposed method is validated by depositing on the patterned fiber a high refractive index material layer, to obtain a 'double-layer' photonic crystal slab supporting guided resonances, appearing as peaks in the reflection spectrum. Morphological and optical characterizations are performed to investigate the effects of the fabrication process. Our results show how undesired effects, intrinsic to the fabrication procedure should be taken into account in order to guarantee a successful development of the device. Moreover, to demonstrate the flexibility of our approach and the possibility to engineering the resonances, a thin layer of gold is also deposited on the fiber tip, giving rise to a hybrid photonic-plasmonic structure with a complementary spectral response and different optical field distribution at the resonant wavelengths. Overall, this work represents a significant step forward the consolidation of Lab-on-Fiber Technology.

Near field behavior of SnO(2) particle-layer deposited on standard optical fiber by electrostatic spray pyrolysis method.

We report the emergent optical near field profiles from standard single mode optical fibers on the cleaved end of which were deposited particle layers of SnO(2). The layers, composed of micron and sub-micron sized particles, were deposited by means of Electrostatic Spray Pyrolysis (ESP) technique. Powerful analytical tools such as Atomic Force Microscopy (AFM) and Scanning Near-field Optical Microscopy (SNOM) were used to obtain simultaneously the SnO(2) layers topography and the related optical near field intensity distribution, when the fiber-substrate is illuminated by a light radiation in NIR range. We show that isolated microstructures, positioned in correspondence of the fiber core, reveal highly unusual capability of locally enhancing the collected optical near field. The observed phenomenon leads to new concepts of fiber optic chemical sensors and in fiber microsystems as well.