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Label-Free Optical Biosensors

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

Deadline for manuscript submissions: closed (30 September 2016) | Viewed by 100625

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Special Issue Editors

Dr. Alexandre François

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Guest Editor

School of Electrical and Information Engineering, University of South Australia, Adelaide, Australia
Interests: optics spectroscopy; label free optical biosensors; plasmonics; whispering gallery modes; surface functionalization; immunoassays; point of care diagnostics
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Al Meldrum

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Guest Editor

Department of Physics, University of Alberta, Edmonton, AB T6G2E1, Canada
Interests: quantum dots; microcavities; microlasers; optical sensors and devices; polymer light emitting materials; OLEDs

Dr. Nicolas Riesen

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Guest Editor

Institute for Photonics and Advanced Sensing, School of Physical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia
Interests: optical microcavities; label-free optical biosensors; whispering gallery modes; nonlinear optics; optical waveguide theory; integrated optics

Special Issue Information

Dear Colleagues,

The field of label-free optical biosensing comprises various techniques, ranging from, but not limited to, plasmonics, Raman spectroscopy, optical interferometry and the measurement of cavity resonances. The field has gained considerable interest over the last decade and promises a wide range of applications in biological research, medical diagnostics, and environmental monitoring, as well as applications in defence, security and agriculture.

We invite manuscripts for this forthcoming Special Issue in all aspects pertinent to label-free optical biosensing. Both reviews and original research articles are welcome. Reviews should provide an up-to-date and critical overview of state-of-the-art technologies such as surface or localized plasmon resonance, whispering gallery modes, Bragg gratings, Raman spectroscopy or any other label-free optical sensing mechanism relevant to biosensing. Original research papers that describe the utilization of label-free optical platforms in biosensing, such as lab-on-a-chip, optical fiber sensing or new concepts and fundamental studies with potential relevance to biosensing, as well as surface functionalization strategies for the detection of specific biomolecules in complex clinical samples are also of interest. If you have suggestions that you would like to discuss beforehand, please feel free to contact us. We look forward to and welcome your participation in this Special Issue

Dr. Alexandre François
Prof. Dr. Al Meldrum
Dr. Nicolas Riesen
Guest Editors

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 submissions that pass pre-check are 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 2600 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

optical biosensing

label free

surface plasmon resonance

Bragg grating

whispering gallery modes

Raman spectroscopy

optical fiber sensors

lab-on-a-chip

surface functionalization

point of care diagnostic

Published Papers (14 papers)

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Research

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2019 KiB

Open AccessArticle

Investigating Effects of Proteasome Inhibitor on Multiple Myeloma Cells Using Confocal Raman Microscopy

by Jeon Woong Kang, Surya P. Singh, Freddy T. Nguyen, Niyom Lue, Yongjin Sung, Peter T. C. So and Ramachandra R. Dasari

Sensors 2016, 16(12), 2133; https://doi.org/10.3390/s16122133 - 14 Dec 2016

Cited by 17 | Viewed by 5979

Abstract

Due to its label-free and non-destructive nature, applications of Raman spectroscopic imaging in monitoring therapeutic responses at the cellular level are growing. We have recently developed a high-speed confocal Raman microscopy system to image living biological specimens with high spatial resolution and sensitivity. In the present study, we have applied this system to monitor the effects of Bortezomib, a proteasome inhibitor drug, on multiple myeloma cells. Cluster imaging followed by spectral profiling suggest major differences in the nuclear and cytoplasmic contents of cells due to drug treatment that can be monitored with Raman spectroscopy. Spectra were also acquired from group of cells and feasibility of discrimination among treated and untreated cells using principal component analysis (PCA) was accessed. Findings support the feasibility of Raman technologies as an alternate, novel method for monitoring live cell dynamics with minimal external perturbation. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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38442 KiB

Open AccessArticle

Optical Microbubble Resonators with High Refractive Index Inner Coating for Bio-Sensing Applications: An Analytical Approach

by Andrea Barucci, Simone Berneschi, Ambra Giannetti, Francesco Baldini, Alessandro Cosci, Stefano Pelli, Daniele Farnesi, Giancarlo C. Righini, Silvia Soria and Gualtiero Nunzi Conti

Sensors 2016, 16(12), 1992; https://doi.org/10.3390/s16121992 - 25 Nov 2016

Cited by 14 | Viewed by 4876

Abstract

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. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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2404 KiB

Open AccessArticle

Low-Coherence Reflectometry for Refractive Index Measurements of Cells in Micro-Capillaries

by Francesca Carpignano, Giulia Rigamonti, Giuliano Mazzini and Sabina Merlo

Sensors 2016, 16(10), 1670; https://doi.org/10.3390/s16101670 - 11 Oct 2016

Cited by 12 | Viewed by 5345

Abstract

The refractive index of cells provides insights into their composition, organization and function. Moreover, a good knowledge of the cell refractive index would allow an improvement of optical cytometric and diagnostic systems. Although interferometric techniques undoubtedly represent a good solution for quantifying optical path variation, obtaining the refractive index of a population of cells non-invasively remains challenging because of the variability in the geometrical thickness of the sample. In this paper, we demonstrate the use of infrared low-coherence reflectometry for non-invasively quantifying the average refractive index of cell populations gently confined in rectangular glass micro-capillaries. A suspension of human red blood cells in plasma is tested as a reference. As a use example, we apply this technique to estimate the average refractive index of cell populations belonging to epithelial and hematological families. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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4036 KiB

Open AccessArticle

An Infrared Absorbance Sensor for the Detection of Melanoma in Skin Biopsies

by Valeria Fioravanti, Lukas Brandhoff, Sander Van den Driesche, Heimo Breiteneder, Melitta Kitzwögerer, Christine Hafner and Michael J. Vellekoop

Sensors 2016, 16(10), 1659; https://doi.org/10.3390/s16101659 - 10 Oct 2016

Cited by 15 | Viewed by 6300

Abstract

An infrared (IR) absorbance sensor has been designed, realized and tested with the aim of detecting malignant melanomas in human skin biopsies. The sensor has been designed to obtain fast measurements (80 s) of a biopsy using a small light spot (0.5 mm in diameter, typically five to 10 times smaller than the biopsy size) to investigate different biopsy areas. The sensor has been equipped with a monochromator to record the whole IR spectrum in the 3330–3570 nm wavelength range (where methylene and methyl stretching vibrations occur) for a qualitative spectral investigation. From the collected spectra, the CH₂ stretch ratio values (ratio of the absorption intensities of the symmetric to asymmetric CH₂ stretching peaks) are determined and studied as a cancer indicator. Melanoma areas exhibit different spectral shapes and significantly higher CH₂ stretch ratios when compared to healthy skin. The results of the infrared investigation are compared with standard histology. This study shows that the IR sensor is a promising supportive tool to improve the diagnosis of melanoma during histopathological analysis, decreasing the risk of misdiagnosis. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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3773 KiB

Open AccessArticle

Patterned Array of Poly(ethylene glycol) Silane Monolayer for Label-Free Detection of Dengue

by Nor Zida Rosly, Shahrul Ainliah Alang Ahmad, Jaafar Abdullah and Nor Azah Yusof

Sensors 2016, 16(9), 1365; https://doi.org/10.3390/s16091365 - 25 Aug 2016

Cited by 2 | Viewed by 6990

Abstract

In the present study, the construction of arrays on silicon for naked-eye detection of DNA dengue was demonstrated. The array was created by exposing a polyethylene glycol (PEG) silane monolayer to 254 nm ultraviolet (UV) light through a photomask. Formation of the PEG silane monolayer and photomodifed surface properties was thoroughly characterized by using atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and contact angle measurements. The results of XPS confirmed that irradiation of ultraviolet (UV) light generates an aldehyde functional group that offers conjugation sites of amino DNA probe for detection of a specific dengue virus target DNA. Employing a gold enhancement process after inducing the electrostatic interaction between positively charged gold nanoparticles and the negatively charged target DNA hybridized to the DNA capture probe allowed to visualize the array with naked eye. The developed arrays demonstrated excellent performance in diagnosis of dengue with a detection limit as low as 10 pM. The selectivity of DNA arrays was also examined using a single base mismatch and noncomplementary target DNA. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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1838 KiB

Open AccessArticle

Integrating a DNA Strand Displacement Reaction with a Whispering Gallery Mode Sensor for Label-Free Mercury (II) Ion Detection

by Fengchi Wu, Yuqiang Wu, Zhongwei Niu and Frank Vollmer

Sensors 2016, 16(8), 1197; https://doi.org/10.3390/s16081197 - 29 Jul 2016

Cited by 20 | Viewed by 8039

Abstract

Mercury is an extremely toxic chemical pollutant of our environment. It has attracted the world’s attention due to its high mobility and the ease with which it accumulates in organisms. Sensitive devices and methods specific for detecting mercury ions are, hence, in great need. Here, we have integrated a DNA strand displacement reaction with a whispering gallery mode (WGM) sensor for demonstrating the detection of Hg²⁺ ions. Our approach relies on the displacement of a DNA hairpin structure, which forms after the binding of mercury ions to an aptamer DNA sequence. The strand displacement reaction of the DNA aptamer provides highly specific and quantitative means for determining the mercury ion concentration on a label-free WGM sensor platform. Our approach also shows the possibility for manipulating the kinetics of a strand displacement reaction with specific ionic species. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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4093 KiB

Open AccessArticle

Multiplexed Simultaneous High Sensitivity Sensors with High-Order Mode Based on the Integration of Photonic Crystal 1 × 3 Beam Splitter and Three Different Single-Slot PCNCs

by Jian Zhou, Lijun Huang, Zhongyuan Fu, Fujun Sun and Huiping Tian

Sensors 2016, 16(7), 1050; https://doi.org/10.3390/s16071050 - 07 Jul 2016

Cited by 26 | Viewed by 6799

Abstract

We simulated an efficient method for the sensor array of high-sensitivity single-slot photonic crystal nanobeam cavities (PCNCs) on a silicon platform. With the combination of a well-designed photonic crystal waveguide (PhCW) filter and an elaborate single-slot PCNC, a specific high-order resonant mode was filtered for sensing. A 1 × 3 beam splitter carefully established was implemented to split channels and integrate three sensors to realize microarrays. By applying the three-dimensional finite-difference-time-domain (3D-FDTD) method, the sensitivities calculated were S₁ = 492 nm/RIU, S₂ = 244 nm/RIU, and S₃ = 552 nm/RIU, respectively. To the best of our knowledge, this is the first multiplexing design in which each sensor cite features such a high sensitivity simultaneously. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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3788 KiB

Open AccessArticle

Characterization of a Functional Hydrogel Layer on a Silicon-Based Grating Waveguide for a Biochemical Sensor

by Yoo-Seung Hong, Jongseong Kim and Hyuk-Kee Sung

Sensors 2016, 16(6), 914; https://doi.org/10.3390/s16060914 - 18 Jun 2016

Cited by 8 | Viewed by 4829

Abstract

We numerically demonstrated the characteristics of a functional hydrogel layer on a silicon-based grating waveguide for a simple, cost-effective refractive index (RI) biochemical sensor. The RI of the functional hydrogel layer changes when a specific biochemical interaction occurs between the hydrogel-linked receptors and injected ligand molecules. The transmission spectral profile of the grating waveguide shifts depends on the amount of RI change caused by the functional layer. Our characterization includes the effective RI change caused by the thickness, functional volume ratio, and functional strength of the hydrogel layer. The results confirm the feasibility of, and set design rules for, hydrogel-assisted silicon-based grating waveguides. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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2029 KiB

Open AccessArticle

Label-Free Fluorescence Assay of S1 Nuclease and Hydroxyl Radicals Based on Water-Soluble Conjugated Polymers and WS₂ Nanosheets

by Junting Li, Qi Zhao and Yanli Tang

Sensors 2016, 16(6), 865; https://doi.org/10.3390/s16060865 - 13 Jun 2016

Cited by 17 | Viewed by 6136

Abstract

We developed a new method for detecting S1 nuclease and hydroxyl radicals based on the use of water-soluble conjugated poly[9,9-bis(6,6-(N,N,N-trimethylammonium)-fluorene)-2,7-ylenevinylene-co-alt-2,5-dicyano-1,4-phenylene)] (PFVCN) and tungsten disulfide (WS₂) nanosheets_. Cationic PFVCN is used as a signal reporter, and single-layer WS₂ is used as a quencher with a negatively charged surface. The ssDNA forms complexes with PFVCN due to much stronger electrostatic interactions between cationic PFVCN and anionic ssDNA, whereas PFVCN emits yellow fluorescence. When ssDNA is hydrolyzed by S1 nuclease or hydroxyl radicals into small fragments, the interactions between the fragmented DNA and PFVCN become weaker, resulting in PFVCN being adsorbed on the surface of WS₂ and the fluorescence being quenched through fluorescence resonance energy transfer. The new method based on PFVCN and WS₂ can sense S1 nuclease with a low detection limit of 5 × 10⁻⁶ U/mL. Additionally, this method is cost-effective by using affordable WS₂ as an energy acceptor without the need for dye-labeled ssDNA. Furthermore, the method provides a new platform for the nuclease assay and reactive oxygen species, and provides promising applications for drug screening. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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2303 KiB

Open AccessArticle

Effects of Nanocylinders on the Whispering Gallery Modes in a Microcylinder

by Jinwoo Han

Sensors 2016, 16(4), 512; https://doi.org/10.3390/s16040512 - 09 Apr 2016

Cited by 6 | Viewed by 5837

Abstract

Optical biosensors have been studied extensively for the detection and characterization of biological entities, such as viruses, bacteria, and biomolecules. A two-dimensional (2D) microcylinder resonator (

Q \sim 2 \times 10^{5}

) was designed, and the effects of a nanocylinder on the [...] Read more.

Q \sim 2 \times 10^{5}

) was designed, and the effects of a nanocylinder on the whispering gallery modes (WGMs) were examined numerically. For this purpose, the finite element method with COMSOL multiphysics software was employed. The perturbation of the WGM resonances can be characterized by the shift and splitting of the resonance peaks, which varies according to the position, size, and refractive index of an embedded nanocylinder. The positional dependence shows a large splitting in the region of strong electric fields, and the size dependence shows a broad peak of the splitting at

R_{c} = 110 nm

. These results are attributed to the changing degree of overlap of the WGMs with the nanocylinder. The refractive index dependences of splitting show linear behavior for a nanocylinder less than 50 nm in size, and the nonlinear behavior increases with increasing size of the nanocylinder. The optical resonator system is shown to be suitable for detecting impurity particles, which are smaller than the sizes of the node and antinode regions. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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14353 KiB

Open AccessArticle

Developing an Efficient and General Strategy for Immobilization of Small Molecules onto Microarrays Using Isocyanate Chemistry

by Chenggang Zhu, Xiangdong Zhu, James P. Landry, Zhaomeng Cui, Quanfu Li, Yongjun Dang, Lan Mi, Fengyun Zheng and Yiyan Fei

Sensors 2016, 16(3), 378; https://doi.org/10.3390/s16030378 - 16 Mar 2016

Cited by 19 | Viewed by 7193

Abstract

Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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Review

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3052 KiB

Open AccessReview

Label-Free Biological and Chemical Sensing Using Whispering Gallery Mode Optical Resonators: Past, Present, and Future

by Judith Su

Sensors 2017, 17(3), 540; https://doi.org/10.3390/s17030540 - 08 Mar 2017

Cited by 59 | Viewed by 8804

Abstract

Sensitive and rapid label-free biological and chemical sensors are needed for a wide variety of applications including early disease diagnosis and prognosis, the monitoring of food and water quality, as well as the detection of bacteria and viruses for public health concerns and chemical threat sensing. Whispering gallery mode optical resonator based sensing is a rapidly developing field due to the high sensitivity and speed of these devices as well as their label-free nature. Here, we describe the history of whispering gallery mode optical resonator sensors, the principles behind detection, the latest developments in the fields of biological and chemical sensing, current challenges toward widespread adoption of these devices, and an outlook for the future. In addition, we evaluate the performance capabilities of these sensors across three key parameters: sensitivity, selectivity, and speed. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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3175 KiB

Open AccessReview

Plasmonic Fiber Optic Refractometric Sensors: From Conventional Architectures to Recent Design Trends

by Elizaveta Klantsataya, Peipei Jia, Heike Ebendorff-Heidepriem, Tanya M. Monro and Alexandre François

Sensors 2017, 17(1), 12; https://doi.org/10.3390/s17010012 - 23 Dec 2016

Cited by 171 | Viewed by 14841

Abstract

Surface Plasmon Resonance (SPR) fiber sensor research has grown since the first demonstration over 20 year ago into a rich and diverse field with a wide range of optical fiber architectures, plasmonic coatings, and excitation and interrogation methods. Yet, the large diversity of SPR fiber sensor designs has made it difficult to understand the advantages of each approach. Here, we review SPR fiber sensor architectures, covering the latest developments from optical fiber geometries to plasmonic coatings. By developing a systematic approach to fiber-based SPR designs, we identify and discuss future research opportunities based on a performance comparison of the different approaches for sensing applications. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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5820 KiB

Open AccessReview

Optical Microbottle Resonators for Sensing

by Pablo Bianucci

Sensors 2016, 16(11), 1841; https://doi.org/10.3390/s16111841 - 02 Nov 2016

Cited by 47 | Viewed by 7648

Abstract

Whispering gallery mode (WGM) optical microresonators have been shown to be the basis for sensors able to detect minute changes in their environment. This has made them a well-established platform for highly sensitive physical, chemical, and biological sensors. Microbottle resonators (MBR) are a type of WGM optical microresonator. They share characteristics with other, more established, resonator geometries such as cylinders and spheres, while presenting their unique spectral signature and other distinguishing features. In this review, we discuss recent advances in the theory and fabrication of different kinds of MBRs, including hollow ones, and their application to optofluidic sensing. Full article

(This article belongs to the Special Issue Label-Free Optical Biosensors)

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