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A silicon-based miniaturized sensor chip combined with an advanced microfluidic module for the simultaneous, label-free immunochemical determination of four allergens, bovine milk protein, peanut protein, soy protein, and gliadin, is presented. The sensor chip consists of an array of 10 broad-band Mach-Zehnder interferometers (BB-MZIs) monolithically integrated on silicon, along with their respective broad-band light sources. The BB-MZIs were biofunctionalized with the targeted allergens and their responses during immunoreaction were monitored by multiplexing their transmission spectra through an external miniaturized spectrometer. The assay is performed by running mixtures of calibrators or samples with the antibodies against the four allergens followed by an antispecies specific antibodies solution. Employing a fluidic module of nearly one-dimensional geometry, that provided for uniform delivery of the reagents, CV values <6% were achieved for the responses of the 10 BB-MZIs, allowing for reliable multianalyte determinations. The analysis is completed in 6.5 min, and the detection limits were 0.04 μg/mL for bovine k-casein, 1.0 μg/mL for peanut protein, 0.80 μg/mL for soy protein, and 0.10 μg/mL for gliadin. The assays were accurate (recoveries 88-118%) and repeatable (intra- and interassay CVs <7% for all four allergens). Finally, the sensor was evaluated by analyzing samples from a cleaning in place system (CIP) of a dairy industry and the results obtained were in good agreement with those received by the respective ELISAs. The analytical characteristics of the sensor combined with the short analysis time and the small chip size make the proposed system an ideal tool for on-site multianalyte determinations.

An immunosensor for fast and accurate determination of C-reactive protein (CRP) in human serum samples based on an array of all-silicon broad-band Mach-Zehnder interferometers (BB-MZIs) is demonstrated. The detection was based on monitoring the spectral shifts during the binding of CRP on the antibody molecules that have been immobilized on the sensing arms of the BB-MZIs. By employing the reaction rate as the analytical signal the assay time was compressed to few minutes. The detection limit was 2.1ng/mL, the quantification limit was 4.2ng/mL and the linear dynamic range extended up to 100ng/mL. The measurements performed in human serum samples with the developed immunosensor were characterized by high repeatability and accuracy as it was demonstrated by dilution linearity and recovery experiments. In addition, the concentration values determined were in excellent agreement with those determined for the same samples by a standard clinical laboratory method. The compact size of the chip makes the proposed immunosensor attractive for incorporation into miniaturized devices for the determination of clinical analytes at the point-of-need., (Copyright © 2017 Elsevier B.V. All rights reserved.)

An optical biosensor for label-free detection of ochratoxin A (OTA) in beer samples is presented. The biosensor consists of an array of ten Mach-Zehnder interferometers (MZIs) monolithically integrated along with their respective broad-band silicon light sources on the same Si chip (37mm 2 ). The chip was transformed to biosensor by functionalizing the MZIs sensing arms with an OTA-ovalbumin conjugate. OTA determination was performed by pumping over the chip mixtures of calibrators or samples with anti-OTA antibody following a competitive immunoassay format. An external miniaturized spectrometer was employed to continuously record the transmission spectra of each interferometer. Spectral shifts obtained due to immunoreaction were transformed to phase shifts through Discrete Fourier Transform. The assay had a detection limit of 2.0ng/ml and a dynamic range 4.0-100ng/ml in beer samples, recoveries ranging from 90.6 to 116%, and intra- and inter-assay coefficients of variation of 9% and 14%, respectively. The results obtained with the sensor using OTA-spiked beer samples spiked were in good agreement with those obtained by an ELISA developed using the same antibody. The good analytical performance of the biosensor and the small size of the proposed chip provide for the development of a portable instrument for point-of-need determinations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The application of fully monolithically-integrated Mach-Zehnder interferometer arrays fabricated by standard silicon technology to the label-free detection of analytes is introduced. Detection with the presented biosensor is based on a novel concept, the Frequency-Resolved Mach-Zehnder Interferometry (FR-MZI). In addition, a smart encapsulation based on an appropriately designed microfluidic system and performed at the wafer scale scheme for the easy delivery of the samples to be analyzed is demonstrated. Testing of the FR-MZI biosensors with model binding assays demonstrated the detection of streptavidin binding to immobilized biotin at concentrations in the sub nM range. This is the first experimental demonstration of the FR-MZI concept as well as the first demonstration of a monolithically fully-integrated MZI biosensor.