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As the population ages, the worldwide prevalence of Alzheimer's disease (AD) as the most common dementia in the elderly is increasing dramatically. However, a long-term challenge is to achieve rapid and accurate early diagnosis of AD by detecting hallmarks such as amyloid beta (Aβ 42 ). Here, a multi-channel microfluidic-based plasmonic fiber-optic biosensing platform is established for simultaneous detection and differentiation of multiple AD biomarkers. The platform is based on a gold-coated, highly-tilted fiber Bragg grating (TFBG) and a custom-developed microfluidics. TFBG excites a high-density, narrow-cladding-mode spectral comb that overlaps with the broad absorption of surface plasmons for high-precision interrogation, enabling ultrasensitive monitoring of analytes. In situ detection and in-parallel discrimination of different forms of Aβ 42 in cerebrospinal fluid (CSF) are successfully demonstrated with a detection of limit in the range of ≈30-170 pg mL -1 , which is one order of magnitude below the clinical cut-off level in AD onset, providing high detection sensitivity for early diagnosis of AD. The integration of the TFBG sensor with multi-channel microfluidics enables simultaneous detection of multiple biomarkers using sub-µL sample volumes, as well as combining initial binding rate and real-time response time to differentiate between multiple biomarkers in terms of binding kinetics. With the advantages of multi-parameter, low consumption, and highly sensitive detection, the sensor represents an urgently needed potentials for large-scale diagnosis of diseases at early stage., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

A methodology to enhance the sensitivity of long-period fiber gratings (LPFGs) based on the combination of three different enhancement approaches is presented; the methods here adopted are the working near mode transition (MT) of a cladding mode (CM), working near the turn-around point of a CM and the enhancement of the evanescent field of CMs by reducing the cladding diameter or by increasing the order number of CMs. In order to combine these enhancement methodologies, an electrostatic self-assembly (ESA) process was used to deposit a polymeric overlay, with a chosen thickness, onto the etched fiber. The add-layer sensitivity of the sensor was theoretically calculated, and the demonstration of the real applicability of the developed LPFG as a biosensor was performed by means of an IgG/anti-IgG immunoassay in human serum in a thermostated microfluidic system. The limits of detection (LODs) calculated by following different procedures (three times the standard deviation of the blank and the mean value of the residuals) were 6.9 × 10 -8 µg/mL and 4.5 × 10 -6 µg/mL, respectively. The calculated LODs demonstrate the effectiveness of the applied methodology for sensitivity enhancement.

In this work, the development and testing of a novel fiber-optic based label-free biosensor is presented, whose performance were verified through the detection of C-reactive protein (CRP) in serum. The device is based on a long period grating fabricated in a double cladding fiber with a W-shaped refractive index (RI) profile. As a result, the working point of the device was tuned to the mode transition region by chemical etching of the outer fiber cladding, obtaining a significant enhancement of the RI sensitivity and an excellent visibility of the grating resonances due to the mode transition in an all-silica structure. The fiber transducer was coated with a nanometric thin layer of graphene oxide in order to provide functional groups for the covalent immobilization of the biological recognition element. A very low limit of detection of about 0.15 ng/mL was obtained during the detection of CRP in serum, and a large working range (1 ng/mL - 100 μg/mL) of clinical relevance has been also achieved., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Therapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA)., Methods: We analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed., Results: Using LC-MS/MS, the free concentrations of CsA ( f CsA) and MPA ( f MPA) were detectable and the time courses of total and free CsA comparable. f CsA and f MPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, f CsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82)., Conclusions: The new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

The advent of optical fiber-based biosensors combined with that of nanotechnologies has provided an opportunity for developing in situ, portable, lightweight, versatile, and high-performance optical sensing platforms. We report on the generation of lossy mode resonances by the deposition of nanometer-thick metal oxide films on optical fibers, which makes it possible to measure precisely and accurately the changes in optical properties of the fiber-surrounding medium with very high sensitivity compared to other technology platforms, such as long period gratings or surface plasmon resonances, the gold standard in label-free and real-time biomolecular interaction analysis. This property, combined with the application of specialty structures such as D-shaped fibers, permits enhancing the light-matter interaction. SEM and TEM imaging together with X-EDS tool have been utilized to characterize the two films used, i.e., indium tin oxide and tin dioxide. Moreover, the experimental transmission spectra obtained after the deposition of the nanocoatings have been numerically corroborated by means of wave propagation methods. With the use of a conventional wavelength interrogation system and ad hoc developed microfluidics, the shift of the lossy mode resonance can be reliably recorded in response to very low analyte concentrations. Repeated experiments confirm a big leap in performance thanks to the capability to detect femtomolar concentrations in human serum, improving the detection limit by 3 orders of magnitude when compared with other fiber-based configurations. The biosensor has been regenerated several times by injecting sodium dodecyl sulfate, which proves the capability of sensor to be reused.

The design of Whispering Gallery Mode Resonators (WGMRs) used as an optical transducer for biosensing represents the first and crucial step towards the optimization of the final device performance in terms of sensitivity and Limit of Detection (LoD). Here, we propose an analytical method for the design of an optical microbubble resonator (OMBR)-based biosensor. In order to enhance the OMBR sensing performance, we consider a polymeric layer of high refractive index as an inner coating for the OMBR. The effect of this layer and other optical/geometrical parameters on the mode field distribution, sensitivity and LoD of the OMBR is assessed and discussed, both for transverse electric (TE) and transverse magnetic (TM) polarization. The obtained results do provide physical insights for the development of OMBR-based biosensor., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

A plastic optical fibre biosensor based on surface plasmon resonance for the detection of C-reactive protein (CRP) in serum is proposed. The biosensor was integrated into a home-made thermo-stabilized microfluidic system that allows avoiding any thermal and/or mechanical fluctuation and maintaining the best stable conditions during the measurements. A working range of 0.006-70 mg L -1 and a limit of detection of 0.009 mg L -1 were achieved. These results are among the best compared to other SPR-based biosensors for CRP detection, especially considering that they were achieved in a real and complex medium, i.e. serum. In addition, since the sensor performances satisfy those requested in physiologically-relevant clinical applications, the whole biosensing platform could well address high sensitive, easy to realize, real-time, label-free, portable and low cost diagnosis of CRP for future lab-on-a-chip applications. 3D sketch (left) of the thermo-stabilized home-made flow cell developed to house the SPR-based plastic optical fibre biosensor. Exemplary response curve (shift of the SPR wavelength versus time) of the proposed biosensor (right) for the detection of C-reactive protein in serum., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An evanescent wave optical fiber biosensor based on titania-silica-coated long period grating (LPG) is presented. The chemical overlay, which increases the refractive index (RI) sensitivity of the sensor, consists of a sol-gel-based titania-silica thin film, deposited along the sensing portion of the fiber by means of the dip-coating technique. Changing both the sol viscosity and the withdrawal speed during the dip-coating made it possible to adjust the thickness of the film overlay, which is a crucial parameter for the sensor performance. After the functionalization of the fiber surface using a methacrylic acid/methacrylate copolymer, an antibody/antigen (IgG/anti-IgG) assay was carried out to assess the performance of sol-gel based titania-silica-coated LPGs as biosensors. The analyte concentration was determined from the wavelength shift at the end of the binding process and from the initial binding rate. This is the first time that a sol-gel based titania-silica-coated LPG is proposed as an effective and feasible label-free biosensor. The specificity of the sensor was validated by performing the same model assay after spiking anti-IgG into human serum. With this structured LPG, detection limits of the order of tens of micrograms per liter (10(-11) M) are attained.

Optical fiber sensors, thanks to their compactness, fast response and real-time measurements, have a large impact in the fields of life science research, drug discovery and medical diagnostics. In recent years, advances in nanotechnology have resulted in the development of nanotools, capable of entering the single cell, resulting in new nanobiosensors useful for the detection of biomolecules inside living cells. In this paper, we provide an application of a nanotip coupled with molecular beacons (MBs) for the detection of DNA. The MBs were characterized by hybridization studies with a complementary target to prove their functionality both free in solution and immobilized onto a solid support. The solid support chosen as substrate for the immobilization of the MBs was a 30 nm tapered tip of an optical fiber, fabricated by chemical etching. With this set-up promising results were obtained and a limit of detection (LOD) of 0.57 nM was reached, opening up the possibility of using the proposed nanotip to detect mRNAs inside the cytoplasm of living cells.

Optical fibre gratings, especially long period gratings, have been recently proposed as optical devices for biochemical sensing. A biochemical interaction along the grating portion induces a refractive index change and hence a change in the fiber transmission spectrum. This provides an alternative methodology with respect to other label-free optical approaches, such as surface plasmon resonance, interferometric configurations and optical resonators. The fibre biofunctionalization has been carried out by means of a novel chemistry using Eudragit L100 copolymer as opposed to the commonly used silanization procedure. Antigen-antibody interaction has been analysed by means of an IgG/anti-IgG bioassay. The biosensor was fully characterised, monitoring the kinetics during the antibody immobilization and the antigen interaction and achieving the calibration curve of the assay. A comparison of the biosensor performance was made by using two different long period gratings with distinct periods., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Whispering gallery mode resonators (WGMR) are an efficient tool for the realization of optical biosensors. A high Q factor preservation is a crucial requirement for good biosensor performances. In this work we present an Eudragit®L100 coated microspherical WGMR as an efficient immunosensor. The developed resonator was morphologically characterized using fluorescence microscopy. The functionalization process was tuned to preserve the high Q factor of the resonator. The protein binding assay was optically characterized in terms of specificity in buffer solution.

An optical fiber sensor for measuring the pH in interstitial fluid is described. Microdialysis is the approach followed for extracting the sample from the subcutaneous adipose tissue. The interstitial fluid drawn flows through a microfluidic circuit formed by a microdialysis catheter in series with a pH glass capillary. The pH indicator (phenol red) is covalently immobilized on the internal wall of the glass capillary. An optoelectronic unit that makes use of LEDs and photodetectors is connected to the sensing capillary by means of optical fibers. Optical fibers are used to connect the interrogating unit to the sensing capillary. A resolution of 0.03 pH units and an accuracy of 0.07 pH units are obtained. Preliminary in vivo tests are carried out in pigs with altered respiratory function.