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Special Issue "Label-free Optical Nanobiosensors"

A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Biosensors".

Deadline for manuscript submissions: closed (15 August 2018).

Special Issue Editor

Guest Editor
Prof. Carlos Angulo Barrios

Instituto de Sistemas Optoelectrónicos y Microtecnología (ISOM), ETSI Telecomunicación, Universidad Politécnica de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
Website | E-Mail
Interests: photonics; materials science; sensors; nanotechnology

Special Issue Information

Dear Colleagues,

Label-free optical biosensing benefits from the well-known advantages of the label-free paradigm, and those associated to optical transduction mechanisms. Typical label-free optical biosensors are based on optical interferometry, Raman spectroscopy and plasmon resonance. The incorporation of nanomaterials and nanostructures, with their enhanced properties, into optical biosensor architectures have opened new and promising paths for performance improvement, miniaturization and parallel and multiplexed detection. Potential application areas include healthcare (medical diagnostics), environmental monitoring, food and agriculture control, defense and security.

This Special Issue welcomes both reviews and original research articles on the field of label-free optical nanobiosensors. Topics include, but are not restricted to, plasmonic configurations, metamaterials and metasurfaces for optical biosensing, surface enhanced Raman spectroscopy (SERS) substrates, nanophotonic biosensors (e.g., ring and disk resonators and photonic crystals), and label-free optical platforms, such as lab-on-a-chip and optical fiber sensing, based on nanostructures. Bioreceptor immobilization procedures and integration of synthetic receptors, like molecularly imprinted polymers, into nanostructured optical transducers, as well as novel concepts and applications of this type of biosensors are also of interest. We invite and encourage your participation in this Special Issue.

Prof. Carlos Angulo Barrios
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Sensors is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Label-free
  • Optical biosensing
  • Nanotechnology
  • Nanophotonics
  • Surface Plasmon resonance
  • SERS
  • Optical resonators
  • Optical interferometry
  • Metamaterials
  • Metasurfaces
  • Lab on a chip
  • Multiplexed detection
  • Bioreceptor immobilization
  • Synthetic receptors

Published Papers (10 papers)

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Research

Jump to: Review

Open AccessArticle
Automated Chemical Sensing Unit Integration for Parallel Optical Interrogation
Sensors 2019, 19(4), 878; https://doi.org/10.3390/s19040878
Received: 28 December 2018 / Revised: 13 February 2019 / Accepted: 15 February 2019 / Published: 20 February 2019
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Abstract
We report the integration of an automated chemical optical sensing unit for the parallel interrogation of 12 BICELLs in a sensing chip. The work was accomplished under the European Project Enviguard (FP7-OCEAN-2013-614057) with the aim of demonstrating an optical nano-biosensing unit for the [...] Read more.
We report the integration of an automated chemical optical sensing unit for the parallel interrogation of 12 BICELLs in a sensing chip. The work was accomplished under the European Project Enviguard (FP7-OCEAN-2013-614057) with the aim of demonstrating an optical nano-biosensing unit for the in-situ detection of various chemical pollutants simultaneously in oceanic waters. In this context, we designed an optical sensing chip based on resonant nanopillars (R-NPs) transducers organized in a layout of twelve biophotonic sensing cells (BICELLs). The sensing chip is interrogated in reflection with a 12-channels optical spectrometer equipped with an embedded computer-on-chip performing image processing for the simultaneous acquisition and analysis (resonant mode fitting) of the 12 spectra. A microfluidic chip and an automated flow control system composed of four pumps and a multi-path micro-valve makes it possible to drive different complex protocols. A rack was designed ad-hoc for the integration of all the modules. As a proof of concept, fluids of different refractive index (RI) were flowed in the system in order to measure the time response (sensogram) of the R-NPs under optical reflectance, and assess the sensors’ bulk sensitivity (285.9 ± 16.4 nm/RIU) and Limit of Detection (LoD) (2.95 × 10−6 RIUS). The real-time response under continuous flow of a sensor chip based on R-NP is showed for the first time, obtaining 12 sensograms simultaneously, featuring the unit as a potential excellent multiplexed detection system. These results indicate the high potential of the developed chemical sensing unit to be used for in-situ, multiplex and automatic optical biosensing. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessArticle
Selective Uropathogenic E. coli Detection Using Crossed Surface-Relief Gratings
Sensors 2018, 18(11), 3634; https://doi.org/10.3390/s18113634
Received: 31 August 2018 / Revised: 23 October 2018 / Accepted: 24 October 2018 / Published: 26 October 2018
Cited by 1 | PDF Full-text (1320 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Urinary tract infections (UTIs) are one of the major burdens on public healthcare worldwide. One of the primary causes of UTIs is the invasion of the urinary tract by uropathogenic Escherichia coli (UPEC). Improper treatment of bacterial infections like UTIs with broad-spectrum antibiotics [...] Read more.
Urinary tract infections (UTIs) are one of the major burdens on public healthcare worldwide. One of the primary causes of UTIs is the invasion of the urinary tract by uropathogenic Escherichia coli (UPEC). Improper treatment of bacterial infections like UTIs with broad-spectrum antibiotics has contributed to the rise of antimicrobial resistance, necessitating the development of an inexpensive, rapid and accurate detection of UPEC. Here, we present real-time, selective and label-free detection of UPEC using crossed surface-relief gratings (CSRGs) as nanometallic sensors incorporated into an optical sensing platform. CSRGs enable real-time sensing due to their unique surface plasmon resonance (SPR)-based light energy exchange, resulting in detection of a very-narrow-bandwidth SPR signal after the elimination of residual incident light. The platform’s sensing ability is experimentally demonstrated by the detection of bulk refractive index (RI) changes, with a bulk sensitivity of 382.2 nm/RIU and a resolution in the order of 10−6 RIU. We also demonstrate, for the first time, CSRG-based real-time selective capture and detection of UPEC in phosphate-buffered saline (PBS) solution, in clinically relevant concentrations, as opposed to other UTI-causing Gram-negative bacteria. The platform’s detection limit is calculated to be 105 CFU/mL (concentration on par with the clinical threshold for UTI diagnosis), with a dynamic range spanning four orders of magnitude. This work paves the way for the development of inexpensive point-of-care diagnosis devices focusing on effective treatment of UTIs, which are a burden on public healthcare due to the rise in the number of cases and their recurrences in the recent past. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessFeature PaperArticle
Design of an Aluminum/Polymer Plasmonic 2D Crystal for Label-Free Optical Biosensing
Sensors 2018, 18(10), 3335; https://doi.org/10.3390/s18103335
Received: 14 September 2018 / Revised: 2 October 2018 / Accepted: 3 October 2018 / Published: 5 October 2018
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Abstract
A design study of a nanostructured two-dimensional plasmonic crystal based on aluminum and polymeric material for label-free optical biosensing is presented. The structure is formed of Al nanohole and nanodisk array layers physically separated by a polymeric film. The photonic configuration was analyzed [...] Read more.
A design study of a nanostructured two-dimensional plasmonic crystal based on aluminum and polymeric material for label-free optical biosensing is presented. The structure is formed of Al nanohole and nanodisk array layers physically separated by a polymeric film. The photonic configuration was analyzed through finite-difference time-domain (FDTD) simulations. The calculated spectral reflectance of the device exhibits a surface plasmon polariton (SPP) resonance feature sensitive to the presence of a modeled biolayer adhered onto the metal surfaces. Simulations also reveal that the Al disks suppress an undesired SPP resonance, improving the device performance in terms of resolution as compared to that of a similar configuration without Al disks. On the basis of manufacturability issues, nanohole diameter and depth were considered as design parameters, and a multi-objective optimization process was employed to determine the optimum dimensional values from both performance and fabrication points of view. The effect of Al oxidation, which is expected to occur in an actual device, was also studied. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessFeature PaperArticle
Indirect Microcontact Printing to Create Functional Patterns of Physisorbed Antibodies
Sensors 2018, 18(9), 3163; https://doi.org/10.3390/s18093163
Received: 31 July 2018 / Revised: 14 September 2018 / Accepted: 17 September 2018 / Published: 19 September 2018
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Abstract
Microcontact printing (µCP) is a practical and versatile approach to create nanostructured patterns of biomolecular probes, but it involves conformational changes on the patterned bioreceptors that often lead to a loss on the biological activity of the resulting structures. Herein we introduce indirect [...] Read more.
Microcontact printing (µCP) is a practical and versatile approach to create nanostructured patterns of biomolecular probes, but it involves conformational changes on the patterned bioreceptors that often lead to a loss on the biological activity of the resulting structures. Herein we introduce indirect µCP to create functional patterns of bioreceptors on solid substrates. This is a simple strategy that relies on physisorbing biomolecular probes of interest in the nanostructured gaps that result after patterning backfilling agents by standard µCP. This study presents the approach, assesses bovine serum albumin as backfilling agent for indirect µCP on different materials, reports the limitations of standard µCP on the functionality of patterned antibodies, and demonstrates the capabilities of indirect µCP to solve this issue. Bioreceptors were herein structured as diffractive gratings and used to measure biorecognition events in label-free conditions. Besides, as a preliminary approach towards sensing biomarkers, this work also reports the implementation of indirect µCP in an immunoassay to detect human immunoglobulin E. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessArticle
Label-Free Colorimetric Detection of Mercury (II) Ions Based on Gold Nanocatalysis
Sensors 2018, 18(9), 2807; https://doi.org/10.3390/s18092807
Received: 21 July 2018 / Revised: 17 August 2018 / Accepted: 22 August 2018 / Published: 25 August 2018
Cited by 2 | PDF Full-text (3305 KB) | HTML Full-text | XML Full-text
Abstract
Herein, a label-free colorimetric nanosensor for Hg(II) is developed utilizing the hindering effect of Hg(II) on the kinetic aspect of gold nanoparticle (AuNPs) growth on the surface of gold nanostars (AuNSs). H-AuNS probes are synthesized and modified by 2-[4-(2-hydroxyethel) piperazine-1-yl] ethanesulfonic acid (HEPES). [...] Read more.
Herein, a label-free colorimetric nanosensor for Hg(II) is developed utilizing the hindering effect of Hg(II) on the kinetic aspect of gold nanoparticle (AuNPs) growth on the surface of gold nanostars (AuNSs). H-AuNS probes are synthesized and modified by 2-[4-(2-hydroxyethel) piperazine-1-yl] ethanesulfonic acid (HEPES). After the formulation of the reagents and testing conditions are optimized, HEPES-capped AuNSs (H-AuNSs) demonstrates good selectivity and sensitivity towards Hg(II) determination. A H-AuNS probe, in the presence of HCl/Au(III)/H2O2, is capable of detecting a Hg(II) concentration range of 1.0 nM–100 µM, with a detection limit of 0.7 nM, at a signal-to-noise ratio of 3.0, and a visual detection limit of 10 nM with naked eyes. For practicality, the H-AuNS probe is evaluated by measuring Hg(II) in the environmental water matrices (lake water and seawater) by a standard addition and recovery study. The detection limits for environmental samples are found to be higher than the lab samples, but they are still within the maximum allowable Hg concentration in drinking water (10 nM) set by the US Environmental Protection Agency (EPA). To create a unique nanosensor, the competitive interaction between Hg(II) and Pt(IV) toward the H-AuNSs probe is developed into a logic gate, improving the specificity in the detection of Hg(II) ions in water samples. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessArticle
Comparative Computational and Experimental Detection of Adenosine Using Ultrasensitive Surface-Enhanced Raman Spectroscopy
Sensors 2018, 18(8), 2696; https://doi.org/10.3390/s18082696
Received: 26 July 2018 / Revised: 11 August 2018 / Accepted: 14 August 2018 / Published: 16 August 2018
Cited by 1 | PDF Full-text (3313 KB) | HTML Full-text | XML Full-text
Abstract
To better understand detection and monitoring of the important neurotransmitter adenosine at physiological levels, this study combines quantum chemical density functional modeling and ultrasensitive surface-enhanced Raman spectroscopic (SERS) measurements. Combined simulation results and experimental data for an analyte concentration of about 10−11 [...] Read more.
To better understand detection and monitoring of the important neurotransmitter adenosine at physiological levels, this study combines quantum chemical density functional modeling and ultrasensitive surface-enhanced Raman spectroscopic (SERS) measurements. Combined simulation results and experimental data for an analyte concentration of about 10−11 molar indicate the presence of all known molecular forms resulting from adenosine’s complex redox-reaction. Detailed analysis presented here, besides assessing potential Raman signatures of these adenosinic forms, also sheds light on the analytic redox process and voltammetric detection. Examples of adenosine Raman fingerprints for different molecular orientations with respect to the SERS substrate are the vibrational line around 920 ± 10 cm−1 for analyte physisorption through the carbinol moiety and around 1600 ± 20 cm−1 for its fully oxidized form. However, both hydroxyl/oxygen sites and NH2/nitrogen sites contribute to molecule’s interaction with the SERS environment. Our results also reveal that contributions of partially oxidized adenosine forms and of the standard form are more likely to be detected with the first recorded voltammetric oxidation peak. The fully oxidized adenosine form contributes mostly to the second peak. Thus, this comparative theoretical–experimental investigation of adenosine’s vibrational signatures provides significant insights for advancing its detection, and for future development of opto-voltammetric biosensors. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessArticle
Spectral Imaging Analysis for Ultrasensitive Biomolecular Detection Using Gold-Capped Nanowire Arrays
Sensors 2018, 18(7), 2181; https://doi.org/10.3390/s18072181
Received: 31 May 2018 / Revised: 4 July 2018 / Accepted: 5 July 2018 / Published: 6 July 2018
Cited by 2 | PDF Full-text (1711 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A spectral integration combined with a threshold method for the analysis of spectral scanning surface plasmon resonance (SPR) images can significantly increase signal recognition at low concentration of antibody solution. The 12-well SPR sensing plates consisted of gold-capped nanowire arrays with 500-nm period, [...] Read more.
A spectral integration combined with a threshold method for the analysis of spectral scanning surface plasmon resonance (SPR) images can significantly increase signal recognition at low concentration of antibody solution. The 12-well SPR sensing plates consisted of gold-capped nanowire arrays with 500-nm period, 80-nm linewidth and 50-nm gold thickness which were used for generating multiple SPR images. A threshold method is introduced to eliminate background noises in spectral scanning images. Combining spectral integration and the threshold method, the detection limit of antibody concentration was 1.23 ng/mL. Using multiple-well SPR sensing plates and the proposed analytical method, multiple kinetic responses with spectral and spatial information on different sensing areas can be sensitively measured. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessArticle
A Molecularly Imprinted Polymer on a Plasmonic Plastic Optical Fiber to Detect Perfluorinated Compounds in Water
Sensors 2018, 18(6), 1836; https://doi.org/10.3390/s18061836
Received: 8 May 2018 / Revised: 4 June 2018 / Accepted: 4 June 2018 / Published: 5 June 2018
Cited by 4 | PDF Full-text (1837 KB) | HTML Full-text | XML Full-text
Abstract
A novel Molecularly Imprinted Polymer (MIP) able to bind perfluorinated compounds, combined with a surface plasmon resonance (SPR) optical fiber platform, is presented. The new MIP receptor has been deposited on a D-shaped plastic optical fiber (POF) covered with a photoresist buffer layer [...] Read more.
A novel Molecularly Imprinted Polymer (MIP) able to bind perfluorinated compounds, combined with a surface plasmon resonance (SPR) optical fiber platform, is presented. The new MIP receptor has been deposited on a D-shaped plastic optical fiber (POF) covered with a photoresist buffer layer and a thin gold film. The experimental results have shown that the developed SPR-POF-MIP sensor makes it possible to selectively detect the above compounds. In this work, we present the results obtained with perfluorooctanoate (PFOA) compound, and they hold true when obtained with a perfluorinated alkylated substances (PFAs) mixture sample. The sensor’s response is the same for PFOA, perfluorooctanesulfonate (PFOS) or PFA contaminants in the C4–C11 range. We have also tested a sensor based on a non-imprinted polymer (NIP) on the same SPR in a D-shaped POF platform. The limit of detection (LOD) of the developed chemical sensor was 0.13 ppb. It is similar to the one obtained by the configuration based on a specific antibody for PFOA/PFOS exploiting the same SPR-POF platform, already reported in literature. The advantage of an MIP receptor is that it presents a better stability out of the native environment, very good reproducibility, low cost and, furthermore, it can be directly deposited on the gold layer, without modifying the metal surface by functionalizing procedures. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Open AccessArticle
Electron-Beam-Lithographed Nanostructures as Reference Materials for Label-Free Scattered-Light Biosensing of Single Filoviruses
Sensors 2018, 18(6), 1670; https://doi.org/10.3390/s18061670
Received: 22 March 2018 / Revised: 14 May 2018 / Accepted: 20 May 2018 / Published: 23 May 2018
Cited by 1 | PDF Full-text (3425 KB) | HTML Full-text | XML Full-text
Abstract
Optical biosensors based on scattered-light measurements are being developed for rapid and label-free detection of single virions captured from body fluids. Highly controlled, stable, and non-biohazardous reference materials producing virus-like signals are valuable tools to calibrate, evaluate, and refine the performance of these [...] Read more.
Optical biosensors based on scattered-light measurements are being developed for rapid and label-free detection of single virions captured from body fluids. Highly controlled, stable, and non-biohazardous reference materials producing virus-like signals are valuable tools to calibrate, evaluate, and refine the performance of these new optical biosensing methods. To date, spherical polymer nanoparticles have been the only non-biological reference materials employed with scattered-light biosensing techniques. However, pathogens like filoviruses, including the Ebola virus, are far from spherical and their shape strongly affects scattered-light signals. Using electron beam lithography, we fabricated nanostructures resembling individual filamentous virions attached to a biosensing substrate (silicon wafer overlaid with silicon oxide film) and characterized their dimensions with scanning electron and atomic force microscopes. To assess the relevance of these nanostructures, we compared their signals across the visible spectrum to signals recorded from Ebola virus-like particles which exhibit characteristic filamentous morphology. We demonstrate the highly stable nature of our nanostructures and use them to obtain new insights into the relationship between virion dimensions and scattered-light signal. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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Review

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Open AccessReview
Optical Biosensors for Label-Free Detection of Small Molecules
Sensors 2018, 18(12), 4126; https://doi.org/10.3390/s18124126
Received: 17 October 2018 / Revised: 20 November 2018 / Accepted: 21 November 2018 / Published: 24 November 2018
Cited by 2 | PDF Full-text (6264 KB) | HTML Full-text | XML Full-text
Abstract
Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addition to multiplexing capabilities. However, development of label-free optical biosensors for small molecules can be challenging [...] Read more.
Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addition to multiplexing capabilities. However, development of label-free optical biosensors for small molecules can be challenging as most of them are not naturally chromogenic or fluorescent, and in some cases, the sensor response is related to the size of the analyte. To overcome some of the limitations associated with the analysis of biologically, pharmacologically, or environmentally relevant compounds of low molecular weight, recent advances in the field have improved the detection of these analytes using outstanding methodology, instrumentation, recognition elements, or immobilization strategies. In this review, we aim to introduce some of the latest developments in the field of label-free optical biosensors with the focus on applications with novel innovations to overcome the challenges related to small molecule detection. Optical label-free methods with different transduction schemes, including evanescent wave and optical fiber sensors, surface plasmon resonance, surface-enhanced Raman spectroscopy, and interferometry, using various biorecognition elements, such as antibodies, aptamers, enzymes, and bioinspired molecularly imprinted polymers, are reviewed. Full article
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
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