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Micro and Nanofabrication Technologies for 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 (31 May 2017) | Viewed by 98206

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Special Issue Editors

Prof. Dr. Nathan Lindquist

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Guest Editor

Physics Department, Bethel University, St. Paul, MN 55112, USA
Interests: nano-photonics and plasmonics; super-resolution imaging and microscopy; digital holographic microscopy; optical biosensing; spectroscopy; nanofabrication

Dr. Nathan Wittenberg

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Guest Editor

Lehigh University, 27 Memorial Dr W, Bethlehem, PA 18015, USA
Interests: biological surface chemistry; membrane biochemistry and biophysics; optical, electrochemical, and accoustic sensing; microscopy; neuroscience

Prof. Dr. Sang-Hyun Oh

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Guest Editor

Department of Electrical and Computer Engineering, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA
Interests: microfluidic biotechnology; optical biosensors; plasmonics; optics at the nanoscale; nanofabrication

Special Issue Information

Dear Colleagues,

Advances in micro- and nanofabrication technologies in recent years have given researchers unprecedented capabilities to engineer metallic, semiconducting, or dielectric structures for biochemical sensing with high throughput, high precision, and ever increasing functionalities. Furthermore, a wide range of microfluidic platforms and surface modification techniques have been developed to interface these engineered micro/nanostructures with various cells, biomolecules and soft matter, manipulating and sensing target analytes with high specificity.

We invite manuscripts for this forthcoming Special Issue covering new and exciting technologies to engineer micro/nanostructures toward manipulating, trapping (via optical, electrical, or magnetic mechanisms), and sensing biomolecules and biological particles. Original research papers that describe novel fabrication technologies, sensing platforms (mechanical, optical, electrochemical, acoustic, electromechanical, magnetic etc.,) surface modification strategies, scaling phenomena in micro/nanoscale sensors, biological interfacing and novel microfluidic integration methods are of great interest. We look forward to receiving your manuscripts in this Special Issue.

Dr. Nathan Lindquist
Dr. Nathan Wittenberg
Dr. Sang-Hyun Oh
Guest Editors

Manuscript Submission Information

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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

microfabrication
nanofabrication
plasmonics
biosensor
optical sensors
acoustic sensors
electrochemical sensors
magnetic sensors
MEMS
spectroscopy
lithography
microfluidics

Published Papers (10 papers)

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Research

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2655 KiB

Open AccessFeature PaperArticle

Low-Cost and Rapid Fabrication of Metallic Nanostructures for Sensitive Biosensors Using Hot-Embossing and Dielectric-Heating Nanoimprint Methods

by Kuang-Li Lee, Tsung-Yeh Wu, Hsuan-Yeh Hsu, Sen-Yeu Yang and Pei-Kuen Wei

Sensors 2017, 17(7), 1548; https://doi.org/10.3390/s17071548 - 02 Jul 2017

Cited by 25 | Viewed by 6128

Abstract

We propose two approaches—hot-embossing and dielectric-heating nanoimprinting methods—for low-cost and rapid fabrication of periodic nanostructures. Each nanofabrication process for the imprinted plastic nanostructures is completed within several seconds without the use of release agents and epoxy. Low-cost, large-area, and highly sensitive aluminum nanostructures on A4 size plastic films are fabricated by evaporating aluminum film on hot-embossing nanostructures. The narrowest bandwidth of the Fano resonance is only 2.7 nm in the visible light region. The periodic aluminum nanostructure achieves a figure of merit of 150, and an intensity sensitivity of 29,345%/RIU (refractive index unit). The rapid fabrication is also achieved by using radio-frequency (RF) sensitive plastic films and a commercial RF welding machine. The dielectric-heating, using RF power, takes advantage of the rapid heating/cooling process and lower electric power consumption. The fabricated capped aluminum nanoslit array has a 5 nm Fano linewidth and 490.46 nm/RIU wavelength sensitivity. The biosensing capabilities of the metallic nanostructures are further verified by measuring antigen–antibody interactions using bovine serum albumin (BSA) and anti-BSA. These rapid and high-throughput fabrication methods can benefit low-cost, highly sensitive biosensors and other sensing applications. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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5704 KiB

Open AccessFeature PaperArticle

Nanoporous Gold Nanocomposites as a Versatile Platform for Plasmonic Engineering and Sensing

by Fusheng Zhao, Jianbo Zeng and Wei-Chuan Shih

Sensors 2017, 17(7), 1519; https://doi.org/10.3390/s17071519 - 28 Jun 2017

Cited by 21 | Viewed by 5738

Abstract

Plasmonic metal nanostructures have shown great potential in sensing applications. Among various materials and structures, monolithic nanoporous gold disks (NPGD) have several unique features such as three-dimensional (3D) porous network, large surface area, tunable plasmonic resonance, high-density hot-spots, and excellent architectural integrity and environmental stability. They exhibit a great potential in surface-enhanced spectroscopy, photothermal conversion, and plasmonic sensing. In this work, interactions between smaller colloidal gold nanoparticles (AuNP) and individual NPGDs are studied. Specifically, colloidal gold nanoparticles with different sizes are loaded onto NPGD substrates to form NPG hybrid nanocomposites with tunable plasmonic resonance peaks in the near-infrared spectral range. Newly formed plasmonic hot-spots due to the coupling between individual nanoparticles and NPG disk have been identified in the nanocomposites, which have been experimentally studied using extinction and surface-enhanced Raman scattering. Numerical modeling and simulations have been employed to further unravel various coupling scenarios between AuNP and NPGDs. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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2082 KiB

Open AccessFeature PaperArticle

Probing the Interaction of Dielectric Nanoparticles with Supported Lipid Membrane Coatings on Nanoplasmonic Arrays

by Abdul Rahim Ferhan, Gamaliel Junren Ma, Joshua A. Jackman, Tun Naw Sut, Jae Hyeon Park and Nam-Joon Cho

Sensors 2017, 17(7), 1484; https://doi.org/10.3390/s17071484 - 23 Jun 2017

Cited by 16 | Viewed by 5814

Abstract

The integration of supported lipid membranes with surface-based nanoplasmonic arrays provides a powerful sensing approach to investigate biointerfacial phenomena at membrane interfaces. While a growing number of lipid vesicles, protein, and nucleic acid systems have been explored with nanoplasmonic sensors, there has been only very limited investigation of the interactions between solution-phase nanomaterials and supported lipid membranes. Herein, we established a surface-based localized surface plasmon resonance (LSPR) sensing platform for probing the interaction of dielectric nanoparticles with supported lipid bilayer (SLB)-coated, plasmonic nanodisk arrays. A key emphasis was placed on controlling membrane functionality by tuning the membrane surface charge vis-à-vis lipid composition. The optical sensing properties of the bare and SLB-coated sensor surfaces were quantitatively compared, and provided an experimental approach to evaluate nanoparticle–membrane interactions across different SLB platforms. While the interaction of negatively-charged silica nanoparticles (SiNPs) with a zwitterionic SLB resulted in monotonic adsorption, a stronger interaction with a positively-charged SLB resulted in adsorption and lipid transfer from the SLB to the SiNP surface, in turn influencing the LSPR measurement responses based on the changing spatial proximity of transferred lipids relative to the sensor surface. Precoating SiNPs with bovine serum albumin (BSA) suppressed lipid transfer, resulting in monotonic adsorption onto both zwitterionic and positively-charged SLBs. Collectively, our findings contribute a quantitative understanding of how supported lipid membrane coatings influence the sensing performance of nanoplasmonic arrays, and demonstrate how the high surface sensitivity of nanoplasmonic sensors is well-suited for detecting the complex interactions between nanoparticles and lipid membranes. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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2187 KiB

Open AccessFeature PaperArticle

Fabrication and Characterization of Plasmonic Nanopores with Cavities in the Solid Support

by Bita Malekian, Kunli Xiong, Gustav Emilsson, Jenny Andersson, Cecilia Fager, Eva Olsson, Elin M. Larsson-Langhammer and Andreas B. Dahlin

Sensors 2017, 17(6), 1444; https://doi.org/10.3390/s17061444 - 20 Jun 2017

Cited by 15 | Viewed by 6225

Abstract

Plasmonic nanostructures are widely used for various sensing applications by monitoring changes in refractive index through optical spectroscopy or as substrates for surface enhanced Raman spectroscopy. However, in most practical situations conventional surface plasmon resonance is preferred for biomolecular interaction analysis because of its high resolution in surface coverage and the simple single-material planar interface. Still, plasmonic nanostructures may find unique sensing applications, for instance when the nanoscale geometry itself is of interest. This calls for new methods to prepare nanoscale particles and cavities with controllable dimensions and curvature. In this work, we present two types of plasmonic nanopores where the solid support underneath a nanohole array has been etched, thereby creating cavities denoted as ‘nanowells’ or ‘nanocaves’ depending on the degree of anisotropy (dry or wet etch). The refractometric sensitivity is shown to be enhanced upon removing the solid support because of an increased probing volume and a shift of the asymmetric plasmonic field towards the liquid side of the finite gold film. Furthermore, the structures exhibit different spectral changes upon binding inside the cavities compared to the gold surface, which means that the structures can be used for location-specific detection. Other sensing applications are also suggested. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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2909 KiB

Open AccessArticle

Ultrasensitive Magnetic Nanoparticle Detector for Biosensor Applications

by Yu-Chi Liang, Long Chang, Wenlan Qiu, Arati G. Kolhatkar, Binh Vu, Katerina Kourentzi, T. Randall Lee, Youli Zu, Richard Willson and Dmitri Litvinov

Sensors 2017, 17(6), 1296; https://doi.org/10.3390/s17061296 - 06 Jun 2017

Cited by 23 | Viewed by 6251

Abstract

Ta/Ru/Co/Ru/Co/Cu/Co/Ni₈₀Fe₂₀/Ta spin-valve giant magnetoresistive (GMR) multilayers were deposited using UHV magnetron sputtering and optimized to achieve a 13% GMR ratio before patterning. The GMR multilayer was patterned into 12 sensor arrays using a combination of e-beam and optical lithographies. Arrays were constructed with 400 nm × 400 nm and 400 nm × 200 nm sensors for the detection of reporter nanoparticles. Nanoparticle detection was based on measuring the shift in high-to-low resistance switching field of the GMR sensors in the presence of magnetic particle(s). Due to shape anisotropy and the corresponding demag field, the resistance state switching fields were significantly larger and the switching field distribution significantly broader in the 400 nm × 200 nm sensors as compared to the 400 nm × 400 nm sensors. Thus, sensor arrays with 400 nm × 400 nm dimensions were used for the demonstration of particle detection. Detection of a single 225 nm Fe₃O₄ magnetic nanoparticle and a small number (~10) of 100 nm nanoparticles was demonstrated. With appropriate functionalization for biomolecular recognition, submicron GMR sensor arrays can serve as the basis of ultrasensitive chemical and biological sensors. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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2677 KiB

Open AccessArticle

Characterizing Esophageal Cancerous Cells at Different Stages Using the Dielectrophoretic Impedance Measurement Method in a Microchip

by Hsiang-Chen Wang, Ngoc-Viet Nguyen, Rui-Yi Lin and Chun-Ping Jen

Sensors 2017, 17(5), 1053; https://doi.org/10.3390/s17051053 - 06 May 2017

Cited by 23 | Viewed by 4842

Abstract

Analysis of cancerous cells allows us to provide useful information for the early diagnosis of cancer and to monitor treatment progress. An approach based on electrical principles has recently become an attractive technique. This study presents a microdevice that utilizes a dielectrophoretic impedance measurement method for the identification of cancerous cells. The proposed biochip consists of circle-on-line microelectrodes that are patterned using a standard microfabrication processes. A sample of various cell concentrations was introduced in an open-top microchamber. The target cells were collectively concentrated between the microelectrodes using dielectrophoresis manipulation, and their electrical impedance properties were also measured. Different stages of human esophageal squamous cell carcinoma lines could be distinguished. This result is consistent with findings using hyperspectral imaging technology. Moreover, it was observed that the distinguishing characteristics change in response to the progression of cancer cell invasiveness by Raman spectroscopy. The device enables highly efficient cell collection and provides rapid, sensitive, and label-free electrical measurements of cancerous cells. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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2380 KiB

Open AccessArticle

Electrochemical Detection of Dopamine Using 3D Porous Graphene Oxide/Gold Nanoparticle Composites

by Sung-Sik Choo, Ee-Seul Kang, Inbeom Song, Donghyun Lee, Jeong-Woo Choi and Tae-Hyung Kim

Sensors 2017, 17(4), 861; https://doi.org/10.3390/s17040861 - 14 Apr 2017

Cited by 75 | Viewed by 9980

Abstract

The detection of dopamine in a highly sensitive and selective manner is crucial for the early diagnosis of a number of neurological diseases/disorders. Here, a report on a new platform for the electrochemical detection of dopamine with a considerable accuracy that comprises a 3D porous graphene oxide (pGO)/gold nanoparticle (GNP)/pGO composite-modified indium tin oxide (ITO) is presented. The pGO was first synthesized and purified by ultrasonication and centrifugation, and it was then further functionalized on the surface of a GNP-immobilized ITO electrode. Remarkably, owing to the synergistic effects of the pGO and GNPs, the 3D pGO-GNP-pGO-modified ITO electrode showed a superior dopamine-detection performance compared with the other pGO- or GNP-modified ITO electrodes. The linear range of the newly developed sensing platform is from 0.1 μM to 30 μM with a limit of detection (LOD) of 1.28 μM, which is more precise than the other previously reported GO-functionalized electrodes. Moreover, the 3D pGO-GNP-pGO-modified ITO electrodes maintained their detection capability even in the presence of several interfering molecules (e.g., ascorbic acid, glucose). The proposed platform of the 3D pGO-GNP-pGO-modified ITO electrode could therefore serve as a competent candidate for the development of a dopamine-sensing platform that is potentially applicable for the early diagnosis of various neurological diseases/disorders. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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2470 KiB

Open AccessArticle

Development of Fluorescent FRET Probes for “Off-On” Detection of L-Cysteine Based on Gold Nanoparticles and Porous Silicon Nanoparticles in Ethanol Solution

by Hongyan Zhang and Zhenhong Jia

Sensors 2017, 17(3), 520; https://doi.org/10.3390/s17030520 - 05 Mar 2017

Cited by 9 | Viewed by 5736

Abstract

A new type of fluorescence “off-on” probe was designed for L-Cysteine (L-Cys) based on the fluorescence resonance energy transfer (FRET) between negatively charged amino-capped porous silicon nanoparticles (SiNPs) and positively charged citrate-stabilized Au nanoparticles (AuNPs). In this proposed FRET immunosensor, novel water-soluble amino-conjugated porous SiNPs in ethanol with excellent photoluminescence properties act as the energy donor. Excellent quenching efficiency between SiNPs-ethanol and citrate-stabilized AuNPs by electrostatic interaction via FRET provides an ideal “off-state” (turn-off). The addition of L-Cys leads to releasing the adsorbed AuNPs from the surface of SiNPs and hence the fluorescence emission of SiNPs-ethanol is restored (turn-on), which means the coordination ability of the thiols with AuNPs is stronger than that of the electrostatic interaction. The fluorescence intensity of SiNPs-AuNPs in ethanol is sensitive to L-Cys, and such a restored fluorescence is proportional to the concentration of L-Cys. The method will broadly benefit the development of a new thiol biosensor based on nanostructured porous materials, and the proposed procedure is also expected to develop a variety of functional nanoparticles to form other novel kinds of nanosensors. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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Review

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8653 KiB

Open AccessFeature PaperReview

Metamaterials and Metasurfaces for Sensor Applications

by Yohan Lee, Sun-Je Kim, Hyeonsoo Park and Byoungho Lee

Sensors 2017, 17(8), 1726; https://doi.org/10.3390/s17081726 - 27 Jul 2017

Cited by 189 | Viewed by 16251

Abstract

Electromagnetic metamaterials (MMs) and metasurfaces (MSs) are artificial media and surfaces with subwavelength separations of meta-atoms designed for anomalous manipulations of light properties. Owing to large scattering cross-sections of metallic/dielectric meta-atoms, it is possible to not only localize strong electromagnetic fields in deep subwavelength volume but also decompose and analyze incident light signal with ultracompact setup using MMs and MSs. Hence, by probing resonant spectral responses from extremely boosted interactions between analyte layer and optical MMs or MSs, sensing the variation of refractive index has been a popular and practical application in the field of photonics. Moreover, decomposing and analyzing incident light signal can be easily achieved with anisotropic MSs, which can scatter light to different directions according to its polarization or wavelength. In this paper, we present recent advances and potential applications of optical MMs and MSs for refractive index sensing and sensing light properties, which can be easily integrated with various electronic devices. The characteristics and performances of devices are summarized and compared qualitatively with suggestions of design guidelines. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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9072 KiB

Open AccessReview

The Boom in 3D-Printed Sensor Technology

by Yuanyuan Xu, Xiaoyue Wu, Xiao Guo, Bin Kong, Min Zhang, Xiang Qian, Shengli Mi and Wei Sun

Sensors 2017, 17(5), 1166; https://doi.org/10.3390/s17051166 - 19 May 2017

Cited by 217 | Viewed by 29658

Abstract

Future sensing applications will include high-performance features, such as toxin detection, real-time monitoring of physiological events, advanced diagnostics, and connected feedback. However, such multi-functional sensors require advancements in sensitivity, specificity, and throughput with the simultaneous delivery of multiple detection in a short time. Recent advances in 3D printing and electronics have brought us closer to sensors with multiplex advantages, and additive manufacturing approaches offer a new scope for sensor fabrication. To this end, we review the recent advances in 3D-printed cutting-edge sensors. These achievements demonstrate the successful application of 3D-printing technology in sensor fabrication, and the selected studies deeply explore the potential for creating sensors with higher performance. Further development of multi-process 3D printing is expected to expand future sensor utility and availability. Full article

(This article belongs to the Special Issue Micro and Nanofabrication Technologies for Biosensors)

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