Capabilities of Double-Resonance LPG and SPR Methods for Hypersensitive Detection of SARS-CoV-2 Structural Proteins: A Comparative Study.

The danger of the emergence of new viral diseases and their rapid spread demands apparatuses for continuous rapid monitoring in real time. This requires the creation of new bioanalytical methods that overcome the shortcomings of existing ones and are applicable for point-of-care diagnostics. For this purpose, a variety of biosensors have been developed and tested in proof-of-concept studies, but none of them have been introduced for commercial use so far. Given the importance of the problem, in this study, long-period grating (LPG) and surface plasmon resonance (SPR) biosensors, based on antibody detection, were examined, and their capabilities for SARS-CoV-2 structural proteins detection were established. Supersensitive detections of structural proteins in the order of several femtomoles were achieved by the LPG method, while the SPR method demonstrated a sensitivity of about one hundred femtomoles. The studied biosensors are compatible in sensitivity with ELISA and rapid antigen tests but, in contrast, they are quantitative, which makes them applicable for acute SARS-CoV-2 infection detection, especially during the early stages of viral replication.

Real-time isothermal DNA amplification monitoring in picoliter volumes using an optical fiber sensor.

Rolling circle amplification (RCA) of DNA can be considered as a great alternative to the gold standard polymerase chain reaction (PCR), especially during this pandemic period, where rapid, sensitive, and reliable test results for hundreds of thousands of samples are required daily. This work presents the first research to date on direct, real-time and label-free isothermal DNA amplification monitoring using a microcavity in-line Mach-Zehnder interferometer (µIMZI) fabricated in an optical fiber. The solution based on µIMZI offers a great advantage over many other sensing concepts - making possible optical analysis in just picoliter sample volumes. The selectivity of the biosensor is determined by DNA primers immobilized on the microcavity's surface that act as selective biorecognition elements and trigger initiation of the DNA amplification process. In this study, we verified the sensing concept using circular DNA designed to target the H5N1 influenza virus. The developed biosensor exhibits an ultrahigh refractive index sensitivity reaching 14 000 nm per refractive index unit and a linear detection range between 9.4 aM and 94 pM of the target DNA sequence. Within a 30 min period, the amplification of as little as 9.4 aM DNA can be effectively detected, with a calculated limit of detection of as low as 0.2 aM DNA, suggesting that this methodology holds great promise in practical disease diagnosis applications in the future.

Long-Period Gratings and Microcavity In-Line Mach Zehnder Interferometers as Highly Sensitive Optical Fiber Platforms for Bacteria Sensing.

Selected optical fiber sensors offer extraordinary sensitivity to changes in external refractive (RI), which make them promising for label-free biosensing. In this work the most sensitive ones, namely long-period gratings working at (DTP-LPG) and micro-cavity in-line Mach-Zehnder interferometers (µIMZI) are discussed for application in bacteria sensing. We describe their working principles and RI sensitivity when operating in water environments, which is as high as 20,000 nm/RIU (Refractive index unit) for DTP-LPGs and 27,000 nm/RIU for µIMZIs. Special attention is paid to the methods to enhance the sensitivity by etching and nano-coatings. While the DTP-LPGs offer a greater interaction length and sensitivity to changes taking place at their surface, the µIMZIs are best suited for investigations of sub-nanoliter and picoliter volumes. The capabilities of both the platforms for bacteria sensing are presented and compared for strains of Escherichia coli, lipopolysaccharide E. coli, outer membrane proteins of E. coli, and Staphylococcus aureus. While DTP-LPGs have been more explored for bacteria detection in 102-106 Colony Forming Unit (CFU)/mL for S. aureus and 103-109 CFU/mL for E. coli, the µIMZIs reached 102-108 CFU/mL for E. coli and have a potential for becoming picoliter bacteria sensors.

Dataset of MAPLE Parameters for Hemoglobin Deposition upon long period gratings.

Matrix-assisted pulsed laser evaporation (MAPLE) is an alternative and complimentary method to pulsed laser deposition. MAPLE has been demonstrated to be a less harmful approach for transporting and depositing delicate, highly sensitive molecules. Metalloproteins are considered sensitive molecules since their bioactivity is determined not only by their chemical structure but also by conformational changes that can be altered by deposition methods. Here we report a dataset of MAPLE deposition parameters of haemoglobin (Hb) that ensures the retention of its bioactivity. Methods for parameters optimization are also described. The data and analysis should be valuable for researchers interested in application of MAPLE techniques for metalloprotein immobilization since it provides a unique opportunity for direct immobilization. The data presents the results of previously conducted experiments on the basis of which is based the research article entitled "A Highly Efficient Biosensor based on MAPLE Deposited Hemoglobin on LPGs Around Phase Matching Turning Point" [1].

Combined Long-Period Fiber Grating and Microcavity In-Line Mach-Zehnder Interferometer for Refractive Index Measurements with Limited Cross-Sensitivity.

This work discusses sensing properties of a long-period grating (LPG) and microcavity in-line Mach-Zehnder interferometer (µIMZI) when both are induced in the same single-mode optical fiber. LPGs were either etched or nanocoated with aluminum oxide (Al2O3) to increase its refractive index (RI) sensitivity up to ≈2000 and 9000 nm/RIU, respectively. The µIMZI was machined using a femtosecond laser as a cylindrical cavity (d = 60 µm) in the center of the LPG. In transmission measurements for various RI in the cavity and around the LPG we observed two effects coming from the two independently working sensors. This dual operation had no significant impact on either of the devices in terms of their functional properties, especially in a lower RI range. Moreover, due to the properties of combined sensors two major effects can be distinguished-sensitivity to the RI of the volume and sensitivity to the RI at the surface. Considering also the negligible temperature sensitivity of the µIMZI, it makes the combination of LPG and µIMZI sensors a promising approach to limit cross-sensitivity or tackle simultaneous measurements of multiple effects with high efficiency and reliability.

Immunosensor Based on Long-Period Fiber Gratings for Detection of Viruses Causing Gastroenteritis.

Since the norovirus is the main cause of acute gastroenteritis all over the world, its fast detection is crucial in medical diagnostics. In this work, a rapid, sensitive, and selective optical fiber biosensor for the detection of norovirus virus-like particles (VLPs) is reported. The sensor is based on highly sensitive long-period fiber gratings (LPFGs) coated with antibodies against the main coat protein of the norovirus. Several modification methods were verified to obtain reliable immobilization of protein receptors on the LPFG surface. We were able to detect 1 ng/mL norovirus VLPs in a 40-min assay in a label-free manner. Thanks to the application of an optical fiber as the sensor, there is a possibility to increase the user's safety by separating the measurement point from the signal processing setup. Moreover, our sensor is small and light, and the proposed assay is straightforward. The designed LPFG-based biosensor could be applied in both fast norovirus detection and in vaccine testing.

Label-free cocaine aptasensor based on a long-period fiber grating.

In this Letter, we combined a promising bioreceptor, a cocaine aptamer MN6, with an ultrasensitive optical platform long-period fiber grating (LPFG) to create a new cocaine biosensor. The cocaine induces a conformational rearrangement of the aptamer which changes the refractive index around the LPFG producing a measurable shift of the transmission spectrum. We were able to track subtle interaction between the receptor and cocaine molecules over a concentration range of 25 to 100 µM. The presented biosensor does not require labeling or signal enhancement, resulting in a simple user-friendly device.

Ultrasensitive tantalum oxide nano-coated long-period gratings for detection of various biological targets.

In this work we discussed a label-free biosensing application of long-period gratings (LPGs) optimized in refractive index (RI) sensitivity by deposition of thin tantalum oxide (TaOx) overlays. Comparing to other thin film and materials already applied for maximizing the RI sensitivity, TaOx offers good chemical and mechanical stability during its surface functionalization and other biosensing experiments. It was shown theoretically and experimentally that when RI of the overlay is as high as 2 in IR spectral range, for obtaining LPGs ultrasensitive to RI, the overlay's thickness must be determined with subnanometer precision. In this experiment the TaOx overlays were deposited using Atomic Layer Deposition method that allowed for achieving overlays with exceptionally well-defined thickness and optical properties. The TaOx nano-coated LPGs show RI sensitivity determined for a single resonance exceeding 11,500 nm/RIU in RI range nD= 1.335-1.345 RIU, as expected for label-free biosensing applications. Capability for detection of various in size biological targets, i.e., proteins (avidin) and bacteria (Escherichia coli), with TaOx-coated LPGs was verified using biotin and bacteriophage adhesin as recognition elements, respectively. It has been shown that functionalization process, as well as type of recognition elements and target analyte must be taken into consideration when the LPG sensitivity is optimized. In this work optimized approach made possible detection of small in size biological targets such as proteins with sensitivity reaching 10.21 nm/log(ng/ml).

Live E. coli bacteria label-free sensing using a microcavity in-line Mach-Zehnder interferometer.

The paper presents the first study to date on selective label-free biosensing with a microcavity in-line Mach-Zehnder interferometer induced in an optical fiber. The sensing structures were fabricated in a single-mode fiber by femtosecond laser micromachining. In contrast to other studies of this sensing scheme, where only the sensitivity to refractive index changes in the cavity was investigated, this research used chemical surface treatment of the sensor to ensure detection specificity. Immobilized MS2 bacteriophages were applied as recognition elements specifically targeting live E. coli C3000 bacteria. It is shown that the sensor allows for real-time monitoring of biological phenomena taking place on the surface of the microcavity. The developed biosensor exhibits ultrahigh refractive index sensitivity of 15,000 nm/RIU and is capable of detecting live E. coli bacteria concentrations as low as 100 colony forming units (CFU)/mL in liquid volume as low as picoliters.

Ambient Refractive-Index Measurement with Simultaneous Temperature Monitoring Based on a Dual-Resonance Long-Period Grating Inside a Fiber Loop Mirror Structure.

In this work, we report the experimental results on optimizing the optical structure for ambient refractive index measuring with temperature changes monitoring. The presented optical structure is based on a dual-resonance long-period grating embedded inside a fiber loop mirror, where the long-period grating acts as the head of the refractive-index sensor, whereas the section of polarization maintaining fiber in the loop mirror ensures suitable temperature sensing. The optimization process was comprised of tuning the resonance and interferometric peaks by changing the state of polarization of propagating beams. Experimental results establish that the response of the proposed sensor structure is linear and goes in opposite directions: an increase in the ambient refractive index reduces the signal response, whereas a temperature increase produces an increased response. This enables us to distinguish between the signals from changes in the refractive index and temperature. Due to the filtering properties of the interferometric structure, it is possible to monitor variation in these physical parameters by observing optical power changes instead of wavelength shifts. Hence, the refractive index sensitivity has been established up to 2375.8 dB/RIU in the narrow RI range (1.333⁻1.341 RIU) and temperature sensitivities up to 1.1 dBm/°C in the range of 23⁻41 °C. The proposed sensor is dedicated to advanced chemical and biological sensor applications.

Transition between bulk and surface refractive index sensitivity of micro-cavity in-line Mach-Zehnder interferometer induced by thin film deposition.

In this work we discuss the refractive index (RI) sensitivity of a micro-cavity in-line Mach-Zehnder interferometer in the form of a cylindrical hole (40-50 µm in diameter) fabricated in a standard single-mode optical fiber using a femtosecond laser. The surface of the micro-cavity was coated with up to 400 nm aluminum oxide thin film using the atomic layer deposition method. Next, the film was progressively chemically etched and the influence on changes in the RI of liquid in the micro-cavity was determined at different stages of the experiment, i.e., at different thicknesses of the film. An effect of transition between sensitivity to the film thickness (surface) and the RI of liquid in the cavity (bulk) is demonstrated for the first time. We have found that depending on the interferometer working conditions determined by thin film properties, the device can be used for investigation of phenomena taking place at the surface, such as in case of specific label-free biosensing applications, or for small-volume RI analysis as required in analytical chemistry.

Compact and cost-effective temperature-insensitive bio-sensor based on long-period fiber gratings for accurate detection of E. coli bacteria in water.

We propose and demonstrate a novel temperature-insensitive bio-sensor for accurate and quantitative detection of Escherichia coli (E. coli) bacteria in water. Surface sensitivity is maximized by operating the long-period fiber grating (LPFG) closest to its turnaround wavelength, and the temperature insensitivity is achieved by selectively exciting a pair of cladding modes with opposite dispersion characteristics. Our sensor shows a nominal temperature sensitivity of ∼1.25 pm/°C, which can be further reduced by properly adjusting the LPFG lengths, while maintaining a high refractive index sensitivity of 1929 nm/RIU. The overall length of the sensor is ∼3.6 cm, making it ideally suitable for bio-sensing applications. As an example, we also show the sensor's capability for reliable, quantitative detection of E. coli bacteria in water over a temperature fluctuation of room temperature to 40°C.

Towards refractive index sensitivity of long-period gratings at level of tens of µm per refractive index unit: fiber cladding etching and nano-coating deposition.

In this work we report experimental results on optimizing the refractive index (RI) sensitivity of long-period gratings (LPGs) by fiber cladding etching and thin aluminum oxide (Al2O3) overlay deposition. The presented LPG takes advantage of work in the dispersion turning point (DTP) regime as well as the mode transition (MT) effect for higher-order cladding modes (LP09 and LP010). The MT was obtained by depositing Al2O3 overlays with single-nanometer precision using the Atomic Layer Deposition method (ALD). Etching of both the overlay and the fiber cladding was performed using hydrofluoric acid (HF). For shallow etching of the cladding, i.e., DTP observed at next = 1.429 and 1.439 RIU for an LPG with no overlay, followed by deposition of an overlay of up to 167 nm in thickness, HF etching allowed for post-deposition fine-tuning of the overlay thickness resulting in a significant increase in RI sensitivity mainly at the DTP of the LP09 cladding mode. However, at an external RI (next) above 1.39 RIU, the DTP of LP010 was noticed, and its RI sensitivity exceeded 9,000 nm/RIU. Deeper etching of the cladding, i.e., DTP observed for next above 1.45 RIU, followed by the deposition of thicker overlays (up to 201 nm in thickness) allowed the sensitivity to reach values of over 40,000 nm/RIU in a narrow RI range. Sensitivity exceeding 20,000 nm/RIU was obtained in an RI range suitable for label-free biosensing applications.

Label-free Gram-negative bacteria detection using bacteriophage-adhesin-coated long-period gratings.

This paper presents a novel application of a highly sensitive sensor based on long-period gratings (LPGs) coated with T4 bacteriophage adhesin for Gram-negative bacteria detection. We show here, that the sensor evidently recognizes Escherichia coli K-12 (PCM2560), whereas in the reference tests - ELISA and BIAcore - the results are questionable. For LPGs sensor the resonant wavelength shift observed for E. coli K-12 was approximately half of that measured for E.coli B (positive control). The BIAcore readings (RU) for E. coli K-12 were at 10% level of the signal obtained for E .coli B. These results confirm the improved sensitivity of the LPGs sensor. Moreover, we also show that application of adhesin may allow for efficient detection of E. coli O111 (PCM418), Klebsiella pneumoniae O1 (PCM1) and Yersinia enterocolitica O1 (PCM1879). The specificity of binding bacteria by the adhesin is discussed and it is determined by a distinct region of lipopolysaccharide receptors and/or by the presence of outer-membrane protein C in an outer membrane of Gram-negative bacteria.

Improving the electric field sensing capabilities of the long-period fiber grating coated with a liquid crystal layer.

The hybrid liquid crystal long-period fiber grating structure presented here uses the 1702 liquid crystal as a thin layer on the bare long-period fiber grating. To achieve the highest long-period fiber grating sensitivity to the liquid crystal layer presence, a UV-induced host grating, with a relatively short period of 226.8 µm, was chosen. This design makes it possible to couple light from the propagating core mode to a cladding mode at a wavelength near the phase-matching turning point. This phenomenon is exploited here for the first time to measure the thermal and electric field responses of the liquid crystal long-period fiber grating structure. All experimental results achieved in this work are supported by theoretical analysis.

Label-free sensitivity of long-period gratings enhanced by atomic layer deposited TiO(2) nano-overlays.

In this paper, we discuss an impact of thin titanium dioxide (TiO(2)) coatings on refractive index (RI) sensitivity and biofunctionalization of long-period gratings (LPGs). The TiO(2) overlays on the LPG surfaces have been obtained using atomic layer deposition (ALD) method. This method allows for a deposition of conformal, thickness-controlled, with well-defined optical properties, and high-RI thin films which are highly desired for optical fiber sensors. It has been found that for LPGs working at a dispersion turning point of higher order cladding modes only tens of nanometers of TiO(2) overlay thickness allow to obtain cladding mode transition effect, and thus significant improvement of RI sensitivity. When the TiO(2) overlay thickness reaches 70 nm, it is possible to obtain RI sensitivity exceeding 6200 nm/RIU in RI range where label-free sensors operate. Moreover, LPGs with TiO(2)-enhanced RI sensitivity have shown improved sensitivity to bacteria endotoxin (E. coli B lipopolysaccharide) detection, when TiO(2) surface is functionalized with endotoxin binding protein (adhesin) of T4 bacteriophage.

Recognition of bacterial lipopolysaccharide using bacteriophage-adhesin-coated long-period gratings.

In this paper we present a new type of highly sensitive label-free sensor based on long-period gratings (LPG) coated with T4 bacteriophage (phage) adhesin. The adhesin (gp37) binds Escherichia coli B (E. coli B) by recognizing its bacterial lipopolysaccharide (LPS). The LPG biofunctionalization methodology is based on coating LPG surface with nickel ions capable of gp37 histidine tag reversible binding. For the first time recombinant adhesive phage protein has been used as a receptor molecule in biosensing scheme. The specificity of LPS binding by adhesin has been tested with LPG-based device and confirmed using Western blot, Enzyme-Linked Immunosorbent Assay (ELISA) and BIACORE methods. The LPG-based sensor can measure bacterial contamination in real time and with a high accuracy. We show that T4 phage adhesin binds E. coli B LPS in its native or denatured form. The binding is highly specific and irreversible. The applied procedure allows for obtaining reusable biosensors.

Temperature insensitive single-mode-multimode-single-mode fiber optic structures with two multimode fibers in series.

We propose and demonstrate a temperature insensitive single-mode-multimode-single-mode fiber optic structure consisting of two in-series multimode fibers of appropriate lengths and of opposite temperature sensitivities. A simple approximate expression to estimate the required length ratio of the multimode fiber sections has also been derived whose prediction is found in good agreement with the experiment. The study should be useful in realizing various fiber optic devices based on multimode interference with zero temperature cross sensitivity.

Measurements of reactive ion etching process effect using long-period fiber gratings.

The paper presents for the first time a study of long-period fiber gratings (LPFGs) applied for the measurements of reactive ion etching (RIE) process effect in various places of a plasma reactor. For the purposes of the experiment a number of highly sensitive LPFGs working at the dispersion turning point was fabricated using electric arc discharges. We show that the LPFGs allow for monitoring of the phenomena taking place in the reactor, especially those resulting in reduction of the LPFG diameter. Results of the measurements supported by simulations have shown that etching rate significantly decreases with elevation of the sample up to 3.6 mm over the electrode in the reactor, and stays constant above this height.