Sensors

Research

9 pages, 2108 KiB

Open AccessArticle

Label-Free Capacitive Biosensor for Detection of Cryptosporidium

by George Luka, Ehsan Samiei, Soroush Dehghani, Thomas Johnson, Homayoun Najjaran and Mina Hoorfar

Sensors 2019, 19(2), 258; https://doi.org/10.3390/s19020258 - 10 Jan 2019

Cited by 46 | Viewed by 6386

Abstract

Cryptosporidium, an intestinal protozoan pathogen, is one of the leading causes of diarrhea in healthy adults and death in children. Detection of Cryptosporidium oocysts has become a high priority to prevent potential outbreaks. In this paper, a label-free interdigitated-based capacitive biosensor has [...] Read more.

Cryptosporidium, an intestinal protozoan pathogen, is one of the leading causes of diarrhea in healthy adults and death in children. Detection of Cryptosporidium oocysts has become a high priority to prevent potential outbreaks. In this paper, a label-free interdigitated-based capacitive biosensor has been introduced for the detection of Cryptosporidium oocysts in water samples. Specific anti-Cryptosporidium monoclonal antibodies (IgG3) were covalently immobilized onto interdigitated gold electrodes as the capture probes, and bovine serum albumin was used to avoid non-specific adsorption. The immobilization of the antibodies was confirmed by measuring the change in the contact angle. The detection was achieved by measuring the relative change in the capacitive/dielectric properties due to the formation of Cryptosporidium-antibody complex. The biosensor has been tested for different concentrations of Cryptosporidium. The results show that the biosensor developed can accurately distinguish different numbers of captured cells and densities on the surface of the biosensor. The number of Cryptosporidium oocysts captured on the electrode surface was confirmed using a fluorescein isothiocyanate (FITC) immunofluorescence assay. The response from the developed biosensor has been mainly dependent on the concentration of Cryptosporidium under optimized conditions. The biosensor showed a linear detection range between 15 and 153 cells/mm² and a detection limit of 40 cells/mm². The label-free capacitive biosensor developed has a great potential for detecting Cryptosporidium in environmental water samples. Furthermore, under optimized conditions, this label-free biosensor can be extended for detection of other biomarkers for biomedical and environmental analyses. Full article

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

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11 pages, 2303 KiB

Open AccessArticle

Digital, Rapid, Accurate, and Label-Free Enumeration of Viable Microorganisms Enabled by Custom-Built On-Glass-Slide Culturing Device and Microscopic Scanning

by Donghui Song, Haomin Liu, Qiuchen Dong, Zichao Bian, Huixiang Wu and Yu Lei

Sensors 2018, 18(11), 3700; https://doi.org/10.3390/s18113700 - 31 Oct 2018

Cited by 11 | Viewed by 6248

Abstract

Accurately measuring the number of viable microorganisms plays an essential role in microbiological studies. Since the conventional agar method of enumerating visible colonies is time-consuming and not accurate, efforts have been made towards overcoming these limitations by counting the invisible micro-colonies. However, none [...] Read more.

Accurately measuring the number of viable microorganisms plays an essential role in microbiological studies. Since the conventional agar method of enumerating visible colonies is time-consuming and not accurate, efforts have been made towards overcoming these limitations by counting the invisible micro-colonies. However, none of studies on micro-colony counting was able to save significant time or provide accurate results. Herein, we developed an on-glass-slide cell culture device that enables rapid formation of micro-colonies on a 0.38 mm-thick gel film without suffering from nutrient and oxygen deprivation during bacteria culturing. Employing a phase contrast imaging setup, we achieved rapid microscopic scanning of micro-colonies within a large sample area on the thin film without the need of fluorescent staining. Using Escherichia coli (E. coli) as a demonstration, our technique was able to shorten the culturing time to within 5 h and automatically enumerate the micro-colonies from the phase contrast images. Moreover, this method delivered more accurate counts than the conventional visible colony counting methods. Due to these advantages, this imaging-based micro-colony enumeration technique provides a new platform for the quantification of viable microorganisms. Full article

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

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12 pages, 2359 KiB

Open AccessArticle

Bacteria Detection and Differentiation Using Impedance Flow Cytometry

by Casper Hyttel Clausen, Maria Dimaki, Christian Vinther Bertelsen, Gustav Erik Skands, Romen Rodriguez-Trujillo, Joachim Dahl Thomsen and Winnie E. Svendsen

Sensors 2018, 18(10), 3496; https://doi.org/10.3390/s18103496 - 17 Oct 2018

Cited by 71 | Viewed by 10835

Abstract

Monitoring of bacteria concentrations is of great importance in drinking water management. Continuous real-time monitoring enables better microbiological control of the water and helps prevent contaminated water from reaching the households. We have developed a microfluidic sensor with the potential to accurately assess [...] Read more.

Monitoring of bacteria concentrations is of great importance in drinking water management. Continuous real-time monitoring enables better microbiological control of the water and helps prevent contaminated water from reaching the households. We have developed a microfluidic sensor with the potential to accurately assess bacteria levels in drinking water in real-time. Multi frequency electrical impedance spectroscopy is used to monitor a liquid sample, while it is continuously passed through the sensor. We investigate three aspects of this sensor: First we show that the sensor is able to differentiate Escherichia coli (Gram-negative) bacteria from solid particles (polystyrene beads) based on an electrical response in the high frequency phase and individually enumerate the two samples. Next, we demonstrate the sensor’s ability to measure the bacteria concentration by comparing the results to those obtained by the traditional CFU counting method. Last, we show the sensor’s potential to distinguish between different bacteria types by detecting different signatures for S. aureus and E. coli mixed in the same sample. Our investigations show that the sensor has the potential to be extremely effective at detecting sudden bacterial contaminations found in drinking water, and eventually also identify them. Full article

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

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7 pages, 1151 KiB

Open AccessArticle

Simple and Label-Free Fluorescent Detection of Melamine Based on Melamine–Thymine Recognition

by Hualin Yang, Jiujun Wang, Qinghua Wu, Yun Wang, Li Li and Baomiao Ding

Sensors 2018, 18(9), 2968; https://doi.org/10.3390/s18092968 - 6 Sep 2018

Cited by 9 | Viewed by 4587

Abstract

In the past few years, melamine has been illegally added into dairy products to increase the apparent crude protein levels. If humans or animals drink the milk adulteration of melamine, it can form insoluble melamine–cyanurate crystals in their kidneys which causes kidney damage [...] Read more.

In the past few years, melamine has been illegally added into dairy products to increase the apparent crude protein levels. If humans or animals drink the milk adulteration of melamine, it can form insoluble melamine–cyanurate crystals in their kidneys which causes kidney damage or even death. In the present work, we constructed a simple and label-free fluorescent method for melamine detection based on melamine-thymine recognition. SYBR Green I was utilized as a reporter for this method as it did not require any modification or expensive equipment. In the absence of melamine, polythymine DNA was digested by Exo I, which caused a decrease in the fluorescence signal. In the presence of melamine, the polythymine DNA was able to fold into a double chain structure, however this was done with the help of T-melamine-T mismatches to prevent degradation. Then, the SYBR Green I combined with the double-stranded DNA to result in an intense fluorescence signal. The limit of detection in this method was 1.58 μM, which satisfied the FDA standards. This method also had a good linear relationship within the range of 10–200 μM. In addition, this new method has a good selectivity to distinguish melamine from the component of milk. As a result, we developed a simple and highly selectivity method for melamine detection. Full article

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

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10 pages, 2284 KiB

Open AccessArticle

Theoretical Analysis for Bending of Single-Stranded DNA Adsorption on Microcantilever Sensors

by Zou-Qing Tan, Yang-Chun Chen and Neng-Hui Zhang

Sensors 2018, 18(9), 2812; https://doi.org/10.3390/s18092812 - 26 Aug 2018

Cited by 2 | Viewed by 3048

Abstract

An energy-based model is presented to establish the bending deformation of microcantilever beams induced by single-stranded DNA (ssDNA) adsorption. The total free energy of the DNA-microcantilever sensor was obtained by considering the excluded-volume energy and the polymer stretching energy of DNA chains from [...] Read more.

An energy-based model is presented to establish the bending deformation of microcantilever beams induced by single-stranded DNA (ssDNA) adsorption. The total free energy of the DNA-microcantilever sensor was obtained by considering the excluded-volume energy and the polymer stretching energy of DNA chains from mean-field theory, and the mechanical energy of three non-biological layers. The radius of curvature and deflection of the cantilever were determined through the minimum principle of energy. The efficiency of the present model was confirmed through comparison with experimental data. The effects of length, grafting density, salt concentration, thickness, and elastic modulus of substrate on tip deflections are also discussed in this paper. These factors can significantly affect the deflections of the biosensor. This work demonstrates that it is useful to develop a theoretical model for the label-free nanomechanical detection technique. Full article

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

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12 pages, 2482 KiB

Open AccessArticle

A Proof-of-Concept of Label-Free Biosensing System for Food Allergy Diagnostics in Biophotonic Sensing Cells: Performance Comparison with ImmunoCAP

by Rocio L. Espinosa, María Fe Laguna, Fátima Fernández, Beatriz Santamaria, Francisco Javier Sanza, Maria Victoria Maigler, Juan J. Álvarez-Millán, Víctor Canalejas-Tejero and Miguel Holgado

Sensors 2018, 18(8), 2686; https://doi.org/10.3390/s18082686 - 15 Aug 2018

Cited by 8 | Viewed by 6224

Abstract

Food allergy is a common disease worldwide with over 6% of the population (200–250 million people) suffering from any food allergy nowadays. The most dramatic increase seems to be happening in children and young people. Therefore, improvements in the diagnosis efficiency of these [...] Read more.

Food allergy is a common disease worldwide with over 6% of the population (200–250 million people) suffering from any food allergy nowadays. The most dramatic increase seems to be happening in children and young people. Therefore, improvements in the diagnosis efficiency of these diseases are needed. Immunoglobulin type E (IgE) biomarker determination in human serum is a typical in vitro test for allergy identification. In this work, we used a novel biosensor based on label-free photonic transducers called BICELLs (Biophotonic Sensing Cells) for IgE detection. These BICELLs have a thin film of nitrocellulose over the sensing surface, they can be vertical optically interrogated, and are suitable for being integrated on a chip. The BICELLs sensing surface sizes used were 100 and 800 µm in diameter. We obtained calibration curves with IgE standards by immobilizating anti-IgE antibodies and identified with standard IgE calibrators in minute sample amounts (3 µL). The results, in similar assay format, were compared with commercially available ImmunoCAP^®. The versatility of the interferometric nitrocellulose-based sensing surface was demonstrated since the limit of detections for BICELLs and ImmunoCAP^® were 0.7 and 0.35 kU/L, respectively. Full article

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

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10 pages, 1416 KiB

Open AccessArticle

A Label-Free Fluorescent Assay for the Rapid and Sensitive Detection of Adenosine Deaminase Activity and Inhibition

by Xinxing Tang, Kefeng Wu, Han Zhao, Mingjian Chen and Changbei Ma

Sensors 2018, 18(8), 2441; https://doi.org/10.3390/s18082441 - 27 Jul 2018

Cited by 6 | Viewed by 4266

Abstract

Adenosine deaminase (ADA), able to catalyze the irreversible deamination of adenosine into inosine, can be found in almost all tissues and plays an important role in several diseases. In this work, we developed a label-free fluorescence method for the detection of adenosine deaminase [...] Read more.

Adenosine deaminase (ADA), able to catalyze the irreversible deamination of adenosine into inosine, can be found in almost all tissues and plays an important role in several diseases. In this work, we developed a label-free fluorescence method for the detection of adenosine deaminase activity and inhibition. In the presence of ADA, ATP has been shown to be hydrolyzed. The ATP aptamer was shown to form a G-quadruplex/thioflavin T (ThT) complex with ThT and exhibited an obvious fluorescence signal. However, the ATP aptamer could bind with ATP and exhibited a low fluorescence signal because of the absence of ADA. This assay showed high sensitivity to ADA with a detection limit of 1 U/L based on an SNR of 3 and got a good linear relationship within the range of 1–100 U/L with R² = 0.9909. The LOD is lower than ADA cutoff value (4 U/L) in the clinical requirement and more sensitive than most of the reported methods. This technique exhibited high selectivity for ADA against hoGG I, UDG, RNase H and λexo. Moreover, this strategy was successfully applied for assaying the inhibition of ADA using erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and, as such, demonstrated great potential for the future use in the diagnosis of ADA-relevant diseases, particularly in advanced drug development. Full article

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

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10 pages, 3319 KiB

Open AccessArticle

A Sensitive Potentiometric Sensor for Isothermal Amplification-Coupled Detection of Nucleic Acids

by Kang-Ho Lee, Dongkyu Lee, Jongsu Yoon, Ohwon Kwon and Jaejong Lee

Sensors 2018, 18(7), 2277; https://doi.org/10.3390/s18072277 - 14 Jul 2018

Cited by 6 | Viewed by 3917

Abstract

A disposable potentiometric sensor was newly developed for the amplification-coupled detection of nucleic acids. The hydrogen-ion is generally released during isothermal amplification of nucleic acids. The surface potential on the oxide-functionalized electrode of the extended gate was directly measured using full electrical circuits [...] Read more.

A disposable potentiometric sensor was newly developed for the amplification-coupled detection of nucleic acids. The hydrogen-ion is generally released during isothermal amplification of nucleic acids. The surface potential on the oxide-functionalized electrode of the extended gate was directly measured using full electrical circuits with the commercial metal-oxide semiconductor field-effect transistors (MOSFETs) and ring oscillator components, which resulted in cost-effective, portable and scalable real-time nucleic acid analysis. The current-starved ring oscillator changes surface potential to its frequency depending on the square of the variation in pH with a high signal-to-noise ratio during isothermal amplification. The device achieves a conversion rate of 20.5 kHz/mV and a detection resolution of 200 µV for the surface potential. It is demonstrated that the sensor successfully monitors in real-time isothermal amplification of the extracted nucleic acids from Salmonella pathogenic bacteria. The in situ variations in the frequency of the pH-sensitive sensor were compared with the results of both a conventional optical device and pH-meter during isothermal amplification. Full article

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

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13 pages, 3175 KiB

Open AccessArticle

A Non-Label and Enzyme-Free Sensitive Detection Method for Thrombin Based on Simulation-Assisted DNA Assembly

by Yingying Zhang, Luhui Wang, Yanan Wang and Yafei Dong

Sensors 2018, 18(7), 2179; https://doi.org/10.3390/s18072179 - 6 Jul 2018

Cited by 7 | Viewed by 3855

Abstract

Taking advantage of the high selectivity of aptamers and enzyme-free catalyzed hairpin assembly (CHA) amplification strategy, we herein describe a label-free and enzyme-free sensitive fluorescent and colorimetric strategy for thrombin detection in this paper. In the presence of target, the corresponding aptamer of [...] Read more.

Taking advantage of the high selectivity of aptamers and enzyme-free catalyzed hairpin assembly (CHA) amplification strategy, we herein describe a label-free and enzyme-free sensitive fluorescent and colorimetric strategy for thrombin detection in this paper. In the presence of target, the corresponding aptamer of the partial dsDNA probes will bind to the target and liberate the initiation strand, which is artfully designed as the “on” switch for hairpin assembly. Moreover, the displaced initiation strand partakes in a multi-cycle process and produces numerous G-quadruplexes, which have a remarkable enhancement in fluorescent/colorimetric signal from NMM (N-methyl-mesoporphyrin IX) and TMB (3,3′,5,5′-tetramethylbenzidine), respectively. The proposed amplification strategy for thrombin detection is of high sensitivity, down to 2.4 pM, and also achieves colorimetric signals that are able to be distinguished by naked eye. More importantly, the thermodynamics of interacting DNA strands used in our work, and the process of toehold strand displacement-driven assembly are simulated before biological testing, verifying the feasibility theoretically, and simplifying the subsequent actual experiments. Therefore, our approach and simulation have a certain potential application in biomarker detection and quantitatively monitor for disease diagnosis. Full article

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

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12 pages, 3059 KiB

Open AccessArticle

A Microelectrode Array with Reproducible Performance Shows Loss of Consistency Following Functionalization with a Self-Assembled 6-Mercapto-1-hexanol Layer

by Damion K. Corrigan, Vincent Vezza, Holger Schulze, Till T. Bachmann, Andrew R. Mount, Anthony J. Walton and Jonathan G. Terry

Sensors 2018, 18(6), 1891; https://doi.org/10.3390/s18061891 - 9 Jun 2018

Cited by 8 | Viewed by 5536

Abstract

For analytical applications involving label-free biosensors and multiple measurements, i.e., across an electrode array, it is essential to develop complete sensor systems capable of functionalization and of producing highly consistent responses. To achieve this, a multi-microelectrode device bearing twenty-four equivalent 50 µm diameter [...] Read more.

For analytical applications involving label-free biosensors and multiple measurements, i.e., across an electrode array, it is essential to develop complete sensor systems capable of functionalization and of producing highly consistent responses. To achieve this, a multi-microelectrode device bearing twenty-four equivalent 50 µm diameter Pt disc microelectrodes was designed in an integrated 3-electrode system configuration and then fabricated. Cyclic voltammetry and electrochemical impedance spectroscopy were used for initial electrochemical characterization of the individual working electrodes. These confirmed the expected consistency of performance with a high degree of measurement reproducibility for each microelectrode across the array. With the aim of assessing the potential for production of an enhanced multi-electrode sensor for biomedical use, the working electrodes were then functionalized with 6-mercapto-1-hexanol (MCH). This is a well-known and commonly employed surface modification process, which involves the same principles of thiol attachment chemistry and self-assembled monolayer (SAM) formation commonly employed in the functionalization of electrodes and the formation of biosensors. Following this SAM formation, the reproducibility of the observed electrochemical signal between electrodes was seen to decrease markedly, compromising the ability to achieve consistent analytical measurements from the sensor array following this relatively simple and well-established surface modification. To successfully and consistently functionalize the sensors, it was necessary to dilute the constituent molecules by a factor of ten thousand to support adequate SAM formation on microelectrodes. The use of this multi-electrode device therefore demonstrates in a high throughput manner irreproducibility in the SAM formation process at the higher concentration, even though these electrodes are apparently functionalized simultaneously in the same film formation environment, confirming that the often seen significant electrode-to-electrode variation in label-free SAM biosensing films formed under such conditions is not likely to be due to variation in film deposition conditions, but rather kinetically controlled variation in the SAM layer formation process at these microelectrodes. Full article

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

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13 pages, 2689 KiB

Open AccessArticle

Grating-Coupled Surface Plasmon Resonance (GC-SPR) Optimization for Phase-Interrogation Biosensing in a Microfluidic Chamber

by Stefano Rossi, Enrico Gazzola, Pietro Capaldo, Giulia Borile and Filippo Romanato

Sensors 2018, 18(5), 1621; https://doi.org/10.3390/s18051621 - 18 May 2018

Cited by 47 | Viewed by 5637

Abstract

Surface Plasmon Resonance (SPR)-based sensors have the advantage of being label-free, enzyme-free and real-time. However, their spreading in multidisciplinary research is still mostly limited to prism-coupled devices. Plasmonic gratings, combined with a simple and cost-effective instrumentation, have been poorly developed compared to prism-coupled [...] Read more.

Surface Plasmon Resonance (SPR)-based sensors have the advantage of being label-free, enzyme-free and real-time. However, their spreading in multidisciplinary research is still mostly limited to prism-coupled devices. Plasmonic gratings, combined with a simple and cost-effective instrumentation, have been poorly developed compared to prism-coupled system mainly due to their lower sensitivity. Here we describe the optimization and signal enhancement of a sensing platform based on phase-interrogation method, which entails the exploitation of a nanostructured sensor. This technique is particularly suitable for integration of the plasmonic sensor in a lab-on-a-chip platform and can be used in a microfluidic chamber to ease the sensing procedures and limit the injected volume. The careful optimization of most suitable experimental parameters by numerical simulations leads to a 30–50% enhancement of SPR response, opening new possibilities for applications in the biomedical research field while maintaining the ease and versatility of the configuration. Full article

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

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12 pages, 2134 KiB

Open AccessArticle

Determination of Tumor Marker Carcinoembryonic Antigen with Biosensor Based on Optical Quantum Weak Measurements

by Tian Guan, Xiangnan Wang, Dongmei Li, Yilong Zhang, Yonghong He, Lixuan Shi, Yiqing Liu, Yuxuan Yang, Yang Xu and Rui Cui

Sensors 2018, 18(5), 1550; https://doi.org/10.3390/s18051550 - 14 May 2018

Cited by 13 | Viewed by 3621

Abstract

A phase-sensitive weak measurement biosensor was proposed for the detection of carcinoembryonic antigen (CEA), one common category of tumor markers. The total internal reflection (TIR) at the interface of the prism without precious metal coating was exploited to introduce the phase delay between [...] Read more.

A phase-sensitive weak measurement biosensor was proposed for the detection of carcinoembryonic antigen (CEA), one common category of tumor markers. The total internal reflection (TIR) at the interface of the prism without precious metal coating was exploited to introduce the phase delay between horizontal and vertical polarizations, which can be determined through the central wavelength shift of output spectra for the sensing of the refractive index of the sample. In the weak measurement analysis, the specific binding reaction of tumor markers with a refractive index change on the surface of the prism can be monitored in real time through the central wavelength shift. With the specific absorption measurement, the feasibility of this weak measurement-based biosensor was experimentally demonstrated. We provide a low cost and convenient approach for tumor marker detection. Full article

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

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8 pages, 5663 KiB

Open AccessArticle

Electronic Detection of DNA Hybridization by Coupling Organic Field-Effect Transistor-Based Sensors and Hairpin-Shaped Probes

by Corrado Napoli, Stefano Lai, Ambra Giannetti, Sara Tombelli, Francesco Baldini, Massimo Barbaro and Annalisa Bonfiglio

Sensors 2018, 18(4), 990; https://doi.org/10.3390/s18040990 - 27 Mar 2018

Cited by 22 | Viewed by 6387

Abstract

In this paper, the electronic transduction of DNA hybridization is presented by coupling organic charge-modulated field-effect transistors (OCMFETs) and hairpin-shaped probes. These probes have shown interesting properties in terms of sensitivity and selectivity in other kinds of assays, in the form of molecular [...] Read more.

In this paper, the electronic transduction of DNA hybridization is presented by coupling organic charge-modulated field-effect transistors (OCMFETs) and hairpin-shaped probes. These probes have shown interesting properties in terms of sensitivity and selectivity in other kinds of assays, in the form of molecular beacons (MBs). Their integration with organic-transistor based sensors, never explored before, paves the way to a new class of low-cost, easy-to-use, and portable genetic sensors with enhanced performances. Thanks to the peculiar characteristics of the employed sensor, measurements can be performed at relatively high ionic strengths, thus optimizing the probes’ functionality without affecting the detection ability of the device. A complete electrical characterization of the sensor is reported, including calibration with different target concentrations in the measurement environment and selectivity evaluation. In particular, DNA hybridization detection for target concentration as low as 100 pM is demonstrated. Full article

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

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10 pages, 1825 KiB

Open AccessArticle

Real-Time Tau Protein Detection by Sandwich-Based Piezoelectric Biosensing: Exploring Tubulin as a Mass Enhancer

by Dujuan Li, Simona Scarano, Samuele Lisi, Pasquale Palladino and Maria Minunni

Sensors 2018, 18(4), 946; https://doi.org/10.3390/s18040946 - 22 Mar 2018

Cited by 18 | Viewed by 5896

Abstract

Human tau protein is one of the most advanced and accepted biomarkers for AD and tauopathies diagnosis in general. In this work, a quartz crystal balance (QCM) immunosensor was developed for the detection of human tau protein in buffer and artificial cerebrospinal fluid [...] Read more.

Human tau protein is one of the most advanced and accepted biomarkers for AD and tauopathies diagnosis in general. In this work, a quartz crystal balance (QCM) immunosensor was developed for the detection of human tau protein in buffer and artificial cerebrospinal fluid (aCSF), through both direct and sandwich assays. Starting from a conventional immuno-based sandwich strategy, two monoclonal antibodies recognizing different epitopes of tau protein were used, achieving a detection limit for the direct assay in nanomolar range both in HBES-EP and aCSF. Afterward, for exploring alternative specific receptors as secondary recognition elements for tau protein biosensing, we tested tubulin and compared its behavior to a conventional secondary antibody in the sandwich assay. Tau–tubulin binding has shown an extended working range coupled to a signal improvement in comparison with the conventional secondary antibody-based approach, showing a dose–response trend at lower tau concentration than is usually investigated and closer to the physiological levels in the reference matrix for protein tau biomarker. Our results open up new and encouraging perspectives for the use of tubulin as an alternative receptor for tau protein with interesting features due to the possibility of taking advantage of its polymerization and reversible binding to this key hallmark of Alzheimer’s disease. Full article

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

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16 pages, 2932 KiB

Open AccessArticle

Label-Free Quantification of Anti-TNF-α in Patients Treated with Adalimumab Using an Optical Biosensor

by Rosa Helena Bustos, Carlos Zapata, Efraín Esteban, Julio-César García, Edwin Jáuregui and Diego Jaimes

Sensors 2018, 18(3), 691; https://doi.org/10.3390/s18030691 - 26 Feb 2018

Cited by 11 | Viewed by 6172

Abstract

This study describes the development of an immunosensory label-free quantification methodology based on surface plasmon resonance (SPR) and its applicability in measuring/evaluating therapeutic drug monitoring (TDM) of anti-TNF-α monoclonal antibody (adalimumab) in rheumatoid arthritis (RA) patients. The experimental parameters evaluated in this study [...] Read more.

This study describes the development of an immunosensory label-free quantification methodology based on surface plasmon resonance (SPR) and its applicability in measuring/evaluating therapeutic drug monitoring (TDM) of anti-TNF-α monoclonal antibody (adalimumab) in rheumatoid arthritis (RA) patients. The experimental parameters evaluated in this study were immobilising ligands by pre-concentration assays, sensor surface regeneration, ascertaining the method’s sensitivity and correlating the results from quantifying plasma samples by ELISA immunoassay. The results showed that TNF-α quantification values (in RU) were significantly different when comparing patients (~50–250 RU) to controls (~10–20 RU). Likewise, there was 0.97 correlation for patients and 0.91 for healthy volunteers using SPR and ELISA comparison methodologies. SPR immunosensory detection provided a precise, sensitive strategy, along with real-time determination, for quantifying adalimumab, having great potential for clinical routine regarding TDM. Full article

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

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12 pages, 2947 KiB

Open AccessCommunication

Development of a Label-Free Immunosensor for Clusterin Detection as an Alzheimer’s Biomarker

by Kamrul Islam, Samar Damiati, Jagriti Sethi, Ahmed Suhail and Genhua Pan

Sensors 2018, 18(1), 308; https://doi.org/10.3390/s18010308 - 20 Jan 2018

Cited by 29 | Viewed by 8313

Abstract

Clusterin (CLU) has been associated with the clinical progression of Alzheimer’s disease (AD) and described as a potential AD biomarker in blood plasma. Due to the enormous attention given to cerebrospinal fluid (CSF) biomarkers for the past couple of decades, recently found blood-based [...] Read more.

Clusterin (CLU) has been associated with the clinical progression of Alzheimer’s disease (AD) and described as a potential AD biomarker in blood plasma. Due to the enormous attention given to cerebrospinal fluid (CSF) biomarkers for the past couple of decades, recently found blood-based AD biomarkers like CLU have not yet been reported for biosensors. Herein, we report the electrochemical detection of CLU for the first time using a screen-printed carbon electrode (SPCE) modified with 1-pyrenebutyric acid N-hydroxysuccinimide ester (Pyr-NHS) and decorated with specific anti-CLU antibody fragments. This bifunctional linker molecule contains succinylimide ester to bind protein at one end while its pyrene moiety attaches to the carbon surface by means of π-π stacking. Cyclic voltammetric and square wave voltammetric studies showed the limit of detection down to 1 pg/mL and a linear concentration range of 1–100 pg/mL with good sensitivity. Detection of CLU in spiked human plasma was demonstrated with satisfactory recovery percentages to that of the calibration data. The proposed method facilitates the cost-effective and viable production of label-free point-of-care devices for the clinical diagnosis of AD. Full article

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

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2449 KiB

Open AccessArticle

Label-Free Detection of Cancer Biomarkers Using an In-Line Taper Fiber-Optic Interferometer and a Fiber Bragg Grating

by Dandan Sun, Yang Ran and Guanjun Wang

Sensors 2017, 17(11), 2559; https://doi.org/10.3390/s17112559 - 6 Nov 2017

Cited by 69 | Viewed by 6722

Abstract

A compact and label-free optical fiber sensor based on a taper interferometer cascaded with a fiber Bragg grating (FBG) is proposed and experimentally demonstrated for detection of a breast cancer biomarker (HER2). The tapered fiber-optic interferometer is extremely sensitive to the ambient refractive [...] Read more.

A compact and label-free optical fiber sensor based on a taper interferometer cascaded with a fiber Bragg grating (FBG) is proposed and experimentally demonstrated for detection of a breast cancer biomarker (HER2). The tapered fiber-optic interferometer is extremely sensitive to the ambient refractive index (RI). In addition, being insensitive to the RI variation, the FBG can be applied as a temperature thermometer due to its independent response to the temperature. Surface functionalization to the sensor is carried out to achieve specific targeting of the unlabeled biomarkers. The result shows that the proposed sensor presents a low limit-of-detection (LOD) of 2 ng/mL, enabling its potentials of application in early diagnosis on the breast cancer. Full article

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

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Review

Jump to: Research, Other

18 pages, 2621 KiB

Open AccessReview

On the Determination of Uncertainty and Limit of Detection in Label-Free Biosensors

by Álvaro Lavín, Jesús De Vicente, Miguel Holgado, María F. Laguna, Rafael Casquel, Beatriz Santamaría, María Victoria Maigler, Ana L. Hernández and Yolanda Ramírez

Sensors 2018, 18(7), 2038; https://doi.org/10.3390/s18072038 - 26 Jun 2018

Cited by 92 | Viewed by 8634

Abstract

A significant amount of noteworthy articles reviewing different label-free biosensors are being published in the last years. Most of the times, the comparison among the different biosensors is limited by the procedure used of calculating the limit of detection and the measurement uncertainty. [...] Read more.

A significant amount of noteworthy articles reviewing different label-free biosensors are being published in the last years. Most of the times, the comparison among the different biosensors is limited by the procedure used of calculating the limit of detection and the measurement uncertainty. This article clarifies and establishes a simple procedure to determine the calibration function and the uncertainty of the concentration measured at any point of the measuring interval of a generic label-free biosensor. The value of the limit of detection arises naturally from this model as the limit at which uncertainty tends when the concentration tends to zero. The need to provide additional information, such as the measurement interval and its linearity, among others, on the analytical systems and biosensor in addition to the detection limit is pointed out. Finally, the model is applied to curves that are typically obtained in immunoassays and a discussion is made on the application validity of the model and its limitations. Full article

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

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11 pages, 4158 KiB

Open AccessReview

SPR Biosensors in Direct Molecular Fishing: Implications for Protein Interactomics

by Anna Florinskaya, Pavel Ershov, Yuri Mezentsev, Leonid Kaluzhskiy, Evgeniy Yablokov, Alexei Medvedev and Alexis Ivanov

Sensors 2018, 18(5), 1616; https://doi.org/10.3390/s18051616 - 18 May 2018

Cited by 21 | Viewed by 4713

Abstract

We have developed an original experimental approach based on the use of surface plasmon resonance (SPR) biosensors, applicable for investigation of potential partners involved in protein–protein interactions (PPI) as well as protein–peptide or protein–small molecule interactions. It is based on combining a SPR [...] Read more.

We have developed an original experimental approach based on the use of surface plasmon resonance (SPR) biosensors, applicable for investigation of potential partners involved in protein–protein interactions (PPI) as well as protein–peptide or protein–small molecule interactions. It is based on combining a SPR biosensor, size exclusion chromatography (SEC), mass spectrometric identification of proteins (LC-MS/MS) and direct molecular fishing employing principles of affinity chromatography for isolation of potential partner proteins from the total lysate of biological samples using immobilized target proteins (or small non-peptide compounds) as ligands. Applicability of this approach has been demonstrated within the frame of the Human Proteome Project (HPP) and PPI regulation by a small non-peptide biologically active compound, isatin. Full article

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

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17 pages, 891 KiB

Open AccessReview

Microwave Sensors for Breast Cancer Detection

by Lulu Wang

Sensors 2018, 18(2), 655; https://doi.org/10.3390/s18020655 - 23 Feb 2018

Cited by 125 | Viewed by 12800

Abstract

Breast cancer is the leading cause of death among females, early diagnostic methods with suitable treatments improve the 5-year survival rates significantly. Microwave breast imaging has been reported as the most potential to become the alternative or additional tool to the current gold [...] Read more.

Breast cancer is the leading cause of death among females, early diagnostic methods with suitable treatments improve the 5-year survival rates significantly. Microwave breast imaging has been reported as the most potential to become the alternative or additional tool to the current gold standard X-ray mammography for detecting breast cancer. The microwave breast image quality is affected by the microwave sensor, sensor array, the number of sensors in the array and the size of the sensor. In fact, microwave sensor array and sensor play an important role in the microwave breast imaging system. Numerous microwave biosensors have been developed for biomedical applications, with particular focus on breast tumor detection. Compared to the conventional medical imaging and biosensor techniques, these microwave sensors not only enable better cancer detection and improve the image resolution, but also provide attractive features such as label-free detection. This paper aims to provide an overview of recent important achievements in microwave sensors for biomedical imaging applications, with particular focus on breast cancer detection. The electric properties of biological tissues at microwave spectrum, microwave imaging approaches, microwave biosensors, current challenges and future works are also discussed in the manuscript. Full article

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

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