Polymeric optical fiber biosensor with PAMAM dendrimer-based surface modification and PlGF detection for pre-eclampsia diagnosis.

Pre-eclampsia (PE) is a life-threatening complication that occurs during pregnancy, affecting a large number of pregnant women and newborns worldwide. Rapid, on-site and affordable screening of PE at an early stage is necessary to ensure timely treatment and minimize both maternal and neonatal morbidity and mortality rates. Placental growth factor (PlGF) is an angiogenic blood biomarker used for PE diagnosis. Herein, we report the plasmonic fiber optic absorbance biosensor (P-FAB) strategy for detecting PlGF at femtomolar concentration using polymethyl methacrylate (PMMA) based U-bent polymeric optical fiber (POF) sensor probes. A novel poly(amidoamine) (PAMAM) dendrimer based PMMA surface modification is established to obtain a greater immobilization of the bioreceptors compared to a linear molecule like hexamethylenediamine (HMDA). Plasmonic sandwich immunoassay was realized by immobilizing the mouse anti-PlGF (3H1) on the U-bent POF sensor probe surface and gold nanoparticles (AuNP) labels conjugated with mouse anti-PlGF (6H9). The POF sensor probes could measure PlGF within 30 min using the P-FAB strategy. The limit-of-detection (LoD) was found to be 0.19 pg/mL and 0.57 pg/mL in phosphate-buffered saline and 10× diluted serum, respectively. The clinical sample testing, with eleven positive and eleven negative preeclamptic pregnancy samples, successfully confirmed the accuracy, reliability, specificity, and sensitivity of the P-FAB based POF sensor platform, thereby paving the way for cost-effective technology for PlGF detection and its potential for pre-eclampsia diagnosis.

Metal-Organic Framework-Based Fiber Optic Sensor for Chromium(VI) Detection.

This study demonstrates a novel fiber optic sensing strategy for selective adsorption and rapid detection of Cr(VI) ions by exploiting a suitable metal-organic framework matrix and the characteristic spectral absorption of Cr(VI) at 395 nm wavelength, respectively. U-bent fiber optic sensor (U-FOS) probes that exhibit remarkably high evanescent wave-based absorbance sensitivity were employed to efficiently detect the Cr(VI) ions that are adsorbed to a stable zeolitic imidazolate framework (ZIF-67) matrix immobilized on the probe surface. A facile technique was developed for the fabrication of ZIF-67-coated U-FOS probes (FOS/ZIF-67) involving an in situ deposition process followed by heat treatment. Selectivity of the FOS/ZIF-67 probes to Cr(VI) was confirmed by optical absorption spectral investigations with 14 other heavy metals and interfering ions. The sensor performance was evaluated with a compact light-emitting diode-photodetector-based setup. FOS/ZIF-67 probes demonstrate an ability to detect Cr(VI) ions with a limit of detection of 1 ppb and a wide linear dynamic range from 0.005 to 100 ppm within a short response time of 5 to 10 min. These sensors show good recovery rates with real water samples and a shelf-life of at least 4 weeks under ambient conditions, thereby demonstrating their viability for real-world application.

Diffuse Reflectance Spectroscopy for The Assessment of Steatosis in Liver Phantom and Liver Donors - A Pilot Study.

This paper reports the application of a low-cost diagnostic modality for fat analysis in a liver phantom as well as human liver donors. The device works on the principle of diffuse reflectance spectroscopy, which absorbs and/or scatters depending upon the molecules that compose a tissue. Here, we describe the development of liver phantom of varying fat concentration using saturated fat mimicking liver steatosis. Followed by a pilot study in the human liver donor setting. Later, handheld device based on Infrared-LED and Photodetector for real-time time assessment of live donor liver and fat assessment. Clinical Relevance- This device can be used in the development of an accurate and non-invasive for quantification of liver fat in the deceased donor selection process. It has an error margin of 10% in the quantification of fat which is comparable to a standard biopsy technique.

Emerging trends in point-of-care sensors for illicit drugs analysis.

Consumption of illicit narcotic drugs and fatal or criminal activities under their influence has become an utmost concern worldwide. These drugs influence an individual's feelings, perceptions, and emotions by altering the state of consciousness and thus can result in serious safety breaches at critical workplaces. Point-of-care drug-testing devices have become the need-of-the-hour for many sections such as the law enforcement agencies, the workplaces, etc. for safety and security. This review focuses on the recent progress on various electrochemical and optical nanosensors developed for the analysis of the most common illicit drugs (or their metabolites) such as tetrahydrocannabinol (THC), cocaine (COC), opioids (OPs), amphetamines & methamphetamine, and benzodiazepine (BZDs). The paper also highlights the sensitivity and selectivity of various sensing modalities along with evolving parameters such as real-time monitoring and measurement via a smart user interface. An overall outlook of recent technological advances in point of care (POC) devices and guided insights and directions for future research is presented.

Attomolar analyte sensing techniques (AttoSens): a review on a decade of progress on chemical and biosensing nanoplatforms.

Detecting the ultra-low abundance of analytes in real-life samples, such as biological fluids, water, soil, and food, requires the design and development of high-performance biosensing modalities. The breakthrough efforts from the scientific community have led to the realization of sensing technologies that measure the analyte's ultra-trace level, with relevant sensitivity, selectivity, response time, and sampling efficiency, referred to as Attomolar Analyte Sensing Techniques (AttoSens) in this review. In an AttoSens platform, 1 aM detection corresponds to the quantification of 60 target analyte molecules in 100 µL of sample volume. Herein, we review the approaches listed for various sensor probe design, and their sensing strategies that paved the way for the detection of attomolar (aM: 10-18 M) concentration of analytes. A summary of the technological advances made by the diverse AttoSens trends from the past decade is presented.

Plasmonic Fiberoptic Absorbance Biosensor (P-FAB) for Rapid Detection of SARS-CoV-2 Nucleocapsid Protein.

SARS-CoV-2 nucleocapsid protein-based COVID-19 diagnosis is a promising alternative to the high-priced, time-consuming, and labor-intensive RT-PCR tests. Here, we developed a rapid, dip-type, wash-free plasmonic fiber optic absorbance biosensor (P-FAB) strategy for the point-of-care detection of SARS-CoV-2 N-protein, expressed abundantly during the infection. P-FAB involves a sandwich assay with plasmonic labels on the surface of a U-bent fiber optic sensor probe with a high evanescent wave absorbance (EWA) sensitivity. The SARS-CoV-2 N-protein is quantified in terms of the change in the intensity of the light propagating through the U-bent sensor probe coupled to a green LED and a photodetector. Firstly, the optical fiber material (silica vs. polymeric optical fiber), was evaluated to realize a sensitive sensor platform. The optimal size of AuNP labels (20, 40, and 60 nm) to achieve high sensitivity and a lower limit of detection (LoD) was investigated. Following the P-FAB strategy, fused silica/glass optical fiber (GOF) U-bent senor probe and citrate-capped AuNP labels (size ~40 nm) gave rise to an LoD down to ~2.5 ng/mL within 10 mins of read-out time. Further, studies on development and validation of a point of care (PoC) read-out device, and preclinical studies are in progress.

Development of a U-bent plastic optical fiber biosensor with plasmonic labels for the detection of chikungunya non-structural protein 3.

This study presents a novel plasmonic fiber optic sandwich immunobiosensor for the detection of chikungunya, an infectious mosquito-borne disease with chronic musculoskeletal pain and acute febrile illness, by exploiting non-structural protein 3 (CHIKV-nsP3) as a biomarker. A plasmonic sandwich immunoassay for CHIKV-nsP3 was realized on the surface of a compact U-bent plastic optical fiber (POF, 0.5 mm core diameter) with gold nanoparticles (AuNPs) as labels. The high evanescent wave absorbance (EWA) sensitivity of the U-bent probes allows the absorption of the light passing through the fiber by the AuNP labels, upon the formation of a sandwich immunocomplex of CHIKV-nsP3 on the core surface of the U-bent probe region. A simple optical set-up with a low-cost green LED and a photodetector on either end of the U-bent probe gave rise to a detection limit of 0.52 ng mL-1 (8.6 pM), and a linear range of 1-104 ng mL-1 with a sensitivity of 0.1043A530 nm/log(CnsP3). In addition, the plasmonic POF biosensor shows strong specificity towards the CHIKV-nsP3 analyte in comparison with Pf-HRP2, HIgG, and dengue whole virus. The results illustrate the potential of plasmonic POF biosensors for direct and sensitive point-of-care detection of the chikungunya viral disease.

A plasmonic fiberoptic absorbance biosensor for mannose-capped lipoarabinomannan based tuberculosis diagnosis.

Tuberculosis (TB) is a resurgent infectious disease affecting a large number of people in the developing countries. An on-site, affordable diagnostic screening at an early-stage for an immediate anti-TB treatment is known to tremendously minimize the high mortality rates. Lipoarabinomannan (LAM), a surface glycolipid, has been identified as a potential TB biomarker present in urine at ultra-low concentrations of a few fg/mL. Here, we report a plasmonic fiber optic absorbance biosensor (P-FAB) strategy for mannosylated LAM (Man-LAM or Mtb LAM) detection down to attomolar concentrations. It involves a plasmonic sandwich immunoassay on a U-bent fiber optic probe with gold plasmonic (AuNP) labels functionalized with anti-Mtb LAM immunoglobulin M (IgM) and anti-Mtb LAM IgG respectively. The Mtb LAM is quantified in terms of absorption of light passing through the fiber probe using a green LED and a photodetector. The choice of fiber optic probes (fused silica versus polymer), the optimum size (20, 40, 60 and 80 nm) and concentration (2 × , 10 × , and 20 × ) of AuNP labels were investigated to obtain high sensitivity and lower limits of analyte detection (LoD). P-FAB with a simple LED-photodetector pair, 200 µm fused silica U-bent fiber probe and 60 nm (20 × ) AuNP labels gave LoDs down to 1 fg/mL and 10 fg/mL in the buffer and synthetic urine respectively. Moreover, the anti-Mtb LAM IgM bound sensor probes and the AuNP reagent stored at 4 °C were stable up to 45 days. P-FAB based Mtb LAM sensor demonstrates its potential for an on-site TB diagnosis.

P-FAB: A Fiber-Optic Biosensor Device for Rapid Detection of COVID-19.

Rapid and low-cost diagnosis of COVID-19 is essential to identify the infected subjects, particularly the asymptomatic cases, primarily to arrest the spread of the disease through local transmission. Antibody-based chromatographic serological tests, as an alternative to RT-PCR, offer only limited help due to high false positives. We propose to exploit our field-deployable/portable plasmonic fiber-optic absorbance biosensor (P-FAB) platform for one-step, wash-free detection of SARS-CoV-2 virus particles directly in saliva sample with minimal sample pre-processing.

Nanomaterials based optical and electrochemical sensing of histamine: Progress and perspectives.

Histamine is known to be a principal causative agent associated with marine food poisoning outbreaks worldwide, which is typically formed in the contaminated food by decarboxylation of histidine by bacterial histidine decarboxylase. Upon quantification of histamine in different food products, one can comment on the quality of the food and use it as an indicator of the good manufacturing practices and the state of preservation. The United States Food and Drug Administration (FDA) has established 50 ppm (50 mg/kg) of histamine as the chemical index for fish spoilage. Consumption of foods containing histamine higher than the permissible limit can cause serious health issues. Several methods have been developed for the determination of histamine in a variety of food products. The conventional methods for histamine detection such as thin layer chromatography, capillary zone electrophoresis, gas chromatography, colorimetry, fluorimetry, ion mobility spectrometry, high-performance liquid chromatography, and enzyme-linked immunosorbent assay (ELISA), are being used for sensitive and selective detection of histamine. However, there are a number of disadvantages associated with the conventional techniques, such as multi-step sample processing and requirement of expensive sophisticated instruments, which restrict their applications at laboratory level only. In order to address the limitations associated with the traditional methods, new approaches have been developed by various research groups. Current advances in nanomaterial-based sensing of histamine in different food products have shown significant measurement accuracy due to their high sensitivity, specificity, field deployability, cost and ease of operation. In this review, we have discussed the development of nanomaterials-based histamine sensing assays/strategies where the detection is based on optical (fluorescence, surface enhanced Raman spectroscopy (SERS), localized surface plasmon resonance) and electrochemical (impedimetric, voltammetry, potentiometric, etc.). Further, the advantages, disadvantages and future scope of the nanomaterials-based histamine sensor research are highlighted.

Plasmonic biosensors for bacterial endotoxin detection on biomimetic C-18 supported fiber optic probes.

Bacterial endotoxins such as lipopolysaccharides (LPS) are major contaminants of most pharmaceutical and consumer products. We report an antibiotic-mediated plasmonic biosensor for LPS detection based on a facile U-bent fiber optic probe (UFOP) technology. Biomimetic self-assembled layer of octadecyltrichlorosilanes (OTS) were functionalized on the surface of optical fiber probes to hydrophobically entrap LPS from aqueous solutions. The binding of LPS molecules was monitored in real-time by measuring the change in refractive index (RI) in the evanescent layer. To add specificity and signal amplification, the bound LPS molecules were further tagged with antimicrobial polymyxin-B conjugated gold nanoparticles (PMB-AuNPs) in a sandwich format. The assay was extensively optimized by investigating the role of experimental parameters like OTS concentration, incubation time and addition of a silver reduction step at the end of the assay. The lower limit of detection (LOD) for LPS was found to be 0.4 ng/mL with a 36-fold improved sensitivity upon silver enhancement. The total assay time was 1 h. The assay was also found to be highly specific in the presence of common biopharmaceutical components and could thus serve as an efficient endotoxin detection platform for quality control testing during therapeutic development.

Self-assembled monolayers of thiols adsorbed on Au/ZnO-functionalized silica nanosprings: photoelectron spectroscopy-analysis and detection of vaporized explosives.

Self-assembled monolayers (SAMs) of thiols of L-cysteine, 6-mercaptohexanol, 4-mercaptobenzoic acid, DL-thioctic acid and 11-(1-pyrenyl)-1-undecathiol, which have been selected for their propensity to interact with vaporized explosives, have been attached from solution onto gold decorated ZnO-coated nanosprings. X-ray and ultraviolet photoelectron spectroscopies (XPS and UPS) have been used to investigate the surface electronic structure of the SAMs coated nanosprings. On the basis of XPS analysis, it has been determined that the packing densities of L-cysteine, 6-mercaptohexanol, 4-mercaptobenzoic acid, DL-thioctic acid and 11-(1-pyrenyl)-1-undecathiol on gold (zinc oxide) are 5.42 × 10(14) (2.83 × 10(14)), 3.26 × 10(14) (2.54 × 10(14)), 9.50 × 10(13), 2.55 × 10(14) (1.12 × 10(14)), and 5.23 × 10(13) molecules/cm(2), respectively. A single S 2p core level doublet is observed for 4-mercaptobenzoic acid and 11-(1-pyrenyl)-1-undecathiol, which is assigned to the S-Au bond. The S 2p core level for L-cysteine, 6-mercaptohexanol, and DL-thioctic acid consist of two doublets, where one is S-Au bond and the other is the S-Zn bond. Analysis of the C/S ratios agrees well with the stoichiometry of the respective thiols. UPS analysis shows that the hybridization of S 3p states and Au d-bands produces antibonding and bonding states, above and below the Au d-bands, which is characteristic of molecular chemisorption on Au nanoparticles. Gas sensors were constructed with thiolated nanosprings and their responsiveness to ammonium nitrate at 100-150 °C was tested. Nanosprings sensors functionalized with 4-mercaptobenzoic acid and 6-mercaptohexanol showed the strongest responses by a factor of 4 to 5 relative to the less responsive thiols. The response to ammonium nitrate can be correlated to the packing density and ordering of the SAMs.

Evanescent wave absorbance based fiber optic biosensor for label-free detection of E. coli at 280 nm wavelength.

A novel label-free technique for the detection of pathogens based on evanescent wave absorbance (EWA) changes at 280 nm from a U-bent optical fiber sensor is demonstrated. Bending a decladded fiber into a U-shaped structure enhances the penetration depth of evanescent waves and hence sensitivity of the probe. We show that the enhanced EWA response from such U-bent probes, caused by the inherent optical absorbance properties of bacterial cells or biomolecules specifically bound to the sensor surface, can be exploited for the detection of pathogens. A portable optical set-up with a UV light emitting diode, a spectrometer and U-bent fiber optic probe of 200 µm core diameter, 0.75 mm bend radius and effective probe length of 1cm demonstrated an ability to detect less than 1000 cfu/ml.

Novel U-bent fiber optic probe for localized surface plasmon resonance based biosensor.

The aim of this study is to develop an optical absorbance based biosensor suitable for wide scale use in resource-poor locales. A sensor for sensitive measurement of refractive index (RI) with the help of optical absorbance properties of gold nanoparticles (GNP) coupled to an efficient optical transducer in the form of a U-bent fiber optic probe is described. A U-bent probe was fabricated by a simple procedure. The absorbance due to the localized surface plasmon resonance (LSPR) of fiber-bound GNP was found to be linear to refractive index changes between 1.33 and 1.35. A U-bent probe of 200 microm diameter with a bend radius of 0.75 mm gave rise to a sensitivity of 35 DeltaA/RIU at 540 nm. The resolution of the sensor probe was 3.8x10(-5) RIU. Label-free biosensing was demonstrated using these probes with the help of IgG-anti IgG as bioreceptor-analyte pair.

Simple surface modification techniques for immobilization of biomolecules on SU-8.

SU-8, an epoxy based negative photoresist polymer has found wide range of applications in the field of microfabrication based biosensors. SU-8 surfaces need to be modified in order to immobilize bioreceptors. We studied the possibility of grafting desired functional groups by means of simple chemical treatments under normal laboratory conditions. These chemical treatments involve the use of crosslinkers that are expected to react with epoxy groups or hydroxyl groups generated by acid/alkali treatment. Here, a comparison of the results obtained on surface modification using glycine and 11-mercapto undecanoic acid as crosslinkers is presented. Human Immunoglobin G (HIgG) was covalently immobilized to carboxylic acid on SU-8 surface using carbodiimide/succinimide chemistry. The activity of immobilized HIgG was verified by using fluorescence imaging of FITC tagged goat anti HIgG bound to the surface. Fluorescence imaging was used to determine the chemistry best suited to functionalize SU-8 surface for biosensor applications.

Immobilization of antibodies on polyaniline films and its application in a piezoelectric immunosensor.

Conducting polymers, especially polyaniline (PAni), have been extensively used in biosensor applications. A protocol for covalent immobilization of human IgG on polyaniline using glutaraldehyde as the cross-linker is described in this report and utilized in development of a piezoelectric immunosensor. Here, PAni was used as the substrate for immobilization. The electropolymerization parameters were optimized to get suitable thickness and surface morphology of the PAni for obtaining high density and uniformity of immobilized antibodies on the surface of our films. Possible reaction between PAni thin films and glutaraldehyde was explored using FT-IR characterization in grazing angle mode and XPS. The protocol has been characterized with the help of quartz crystal microbalance analysis. An antibody surface density of 4.86 ng/mm2 was obtained. A piezoelectric biosensor developed for detection of IgG with the proposed protocol was capable of differentiating the target analyte concentrations between 500 ng/mL and 25 microg/mL with nonspecific binding of approximately 10%.