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Biosensors for the Detection of Biomarkers

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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 (28 October 2018) | Viewed by 82928

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Prof. Dr. Gabriele Favero

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Department of Environmental Biology, Sapienza University of Rome, 00185 Roma, Italy
Interests: chemistry of cultural heritage and the environment; soft matters for the cleaning of artistic surfaces and the monitoring of organic polluting species; sensors and biosensors with electrochemical transduction for applications in the environmental, food, and clinical fields; electrochemical techniques for diagnostics of cultural heritage
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Dear Colleagues,

The term “biomarker” or biological marker, generally refers to a measurable indicator of a normal biological state or condition, the insurgence of a pathogenesis, or a pharmacological response to therapeutic intervention; its quantified detection in biological fluids, allows the early detection of diseases or physiological mis-functions and eventually tracking disease progression in response to therapy. In this regard, biomarkers of interest span from simple molecules such as hydrogen peroxide, dopamine, uric acid, ascorbic acid to complex proteins, antigens and antibodies, hormones, enzymes and other markers for several types of cancer, cardiovascular diseases, organ function, Alzheimer’s and Parkinson’s diseases, allergies and infections.

The aim of this Special Issue is to focus on the most recent strategies and developments of biosensors in this field that, overcoming the need of expensive and time-consuming laboratory tests and making the analytical results readily available, can allow the early diagnosis and point-of-care diagnostics. Papers should address the employment of novel and more sensitive/selective biorecognition elements in place of classical bioreceptors, of reliable and miniaturizable or cellular-based transducers which combined to suitable microfluidics could lead to lab-on-chip devices, including the possibility of direct detection of biomarkers in biological fluids without sample preparations and multiple biomarker detection.

Both review articles and original research papers are welcome.

Prof. Gabriele Favero
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 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.

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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

biomarkers
biosensors
immunosensors
aptasensors
point-of-care analysis
lab-on-chip
microfluidics

Published Papers (14 papers)

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Research

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10 pages, 1855 KiB

Open AccessCommunication

Aptamer Conformation Switching-Induced Two-Stage Amplification for Fluorescent Detection of Proteins

by Qiao Yu, Fenfen Zhai, Hong Zhou and Zonghua Wang

Sensors 2019, 19(1), 77; https://doi.org/10.3390/s19010077 - 26 Dec 2018

Cited by 6 | Viewed by 3705

Abstract

Basing on the conformation change of aptamer caused by proteins, a simple and sensitive protein fluorescent assay strategy is proposed, which is assisted by the isothermal amplification reaction of polymerase and nicking endonuclease. In the presence of platelet-derived growth factor (PDGF-BB), the natural conformation of a DNA aptamer would change into a Y-shaped complex, which could hybridize with a molecular beacon (MB) and form a DNA duplex, leading to the open state of the MB and generating a fluorescence signal. Subsequently, with further assistance of isothermal recycling amplification strategies, the designed aptamer sensing platform showed an increment of fluorescence. As a benefit of this amplified strategy, the limit of detection (LOD) was lowered to 0.74 ng/mL, which is much lower than previous reports. This strategy not only offers a new simple, specific, and efficient platform to quantify the target protein in low concentrations, but also shows a powerful approach without multiple washing steps, as well as a precious implementation that has the potential to be integrated into portable, low-cost, and simplified devices for diagnostic applications. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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12 pages, 7250 KiB

Open AccessArticle

Bowel Sounds Identification and Migrating Motor Complex Detection with Low-Cost Piezoelectric Acoustic Sensing Device

by Xuhao Du, Gary Allwood, Katherine Mary Webberley, Adam Osseiran and Barry J. Marshall

Sensors 2018, 18(12), 4240; https://doi.org/10.3390/s18124240 - 03 Dec 2018

Cited by 24 | Viewed by 6320

Abstract

Interpretation of bowel sounds (BS) provides a convenient and non-invasive technique to aid in the diagnosis of gastrointestinal (GI) conditions. However, the approach’s potential is limited by variation between BS and their irregular occurrence. A short, manual auscultation is sufficient to aid in diagnosis of only a few conditions. A longer recording has the potential to unlock additional understanding of GI physiology and clinical utility. In this paper, a low-cost and straightforward piezoelectric acoustic sensing device was designed and used for long BS recordings. The migrating motor complex (MMC) cycle was detected using this device and the sound index as the biomarker for MMC phases. This cycle of recurring motility is typically measured using expensive and invasive equipment. We also used our recordings to develop an improved categorization system for BS. Five different types of BS were extracted: the single burst, multiple bursts, continuous random sound, harmonic sound, and their combination. Their acoustic characteristics and distribution are described. The quantities of different BS during two-hour recordings varied considerably from person to person, while the proportions of different types were consistent. The sensing devices provide a useful tool for MMC detection and study of GI physiology and function. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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9 pages, 4924 KiB

Open AccessArticle

Detection of Alpha-Fetoprotein in Hepatocellular Carcinoma Patient Plasma with Graphene Field-Effect Transistor

by Dae Hoon Kim, Hong Gi Oh, Woo Hwan Park, Dong Cheol Jeon, Ki Moo Lim, Hyung Jin Kim, Byoung Kuk Jang and Kwang Soup Song

Sensors 2018, 18(11), 4032; https://doi.org/10.3390/s18114032 - 19 Nov 2018

Cited by 33 | Viewed by 4843

Abstract

The detection of alpha-fetoprotein (AFP) in plasma is important in the diagnosis of hepatocellular carcinoma (HCC) in humans. We developed a biosensor to detect AFP in HCC patient plasma and in a phosphate buffer saline (PBS) solution using a graphene field-effect transistor (G-FET). The G-FET was functionalized with 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE) for immobilization of an anti-AFP antibody. AFP was detected by assessing the shift in the voltage of the Dirac point (ΔV_Dirac) after binding of AFP to the anti-AFP-immobilized G-FET channel surface. This anti-AFP-immobilized G-FET biosensor was able to detect AFP at a concentration of 0.1 ng mL⁻¹ in PBS, and the detection sensitivity was 16.91 mV. In HCC patient plasma, the biosensor was able to detect AFP at a concentration of 12.9 ng mL⁻¹, with a detection sensitivity of 5.68 mV. The sensitivity (ΔV_Dirac) depended on the concentration of AFP in either PBS or HCC patient plasma. These data suggest that G-FET biosensors could have practical applications in diagnostics. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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17 pages, 7645 KiB

Open AccessArticle

Indium Nitrite (InN)-Based Ultrasensitive and Selective Ammonia Sensor Using an External Silicone Oil Filter for Medical Application

by Sujeet Kumar Rai, Kun-Wei Kao, Shanjgr Gwo, Ashish Agarwal, Wei Da Lin and J. Andrew Yeh

Sensors 2018, 18(11), 3887; https://doi.org/10.3390/s18113887 - 11 Nov 2018

Cited by 7 | Viewed by 4833

Abstract

Ammonia is an essential biomarker for noninvasive diagnosis of liver malfunction. Therefore, selective detection of ammonia is essential for medical application. Here, we demonstrate a portable device to selectively detect sub-ppm ammonia gas. The presented gas sensor is composed of a Pt coating on top of an ultrathin Indium nitrite (InN) epilayer with a lower detection limit of 0.2 ppm, at operating temperature of 200 °C, and detection time of 1 min. The sensor connected with the external filter of nonpolar 500 CS silicone oil to diagnose liver malfunction. The absorption of 0.7 ppm acetone and 0.4 ppm ammonia gas in 10 cc silicone oil is 80% (0.56 ppm) and 21.11% (0.084 ppm), respectively, with a flow rate of 10 cc/min at 25 °C. The absorption of acetone gas is 6.66-fold higher as compared to ammonia gas. The percentage variation in response for 0.7 ppm ammonia and 0.7 ppm acetone with and without silicone oil on InN sensor is 17.5% and 4%, and 22.5%, and 14% respectively. Furthermore, the percentage variation in response for 0.7 ppm ammonia gas with silicone oil on InN sensor is 4.3-fold higher than that of 0.7 ppm acetone. The results show that the InN sensor is suitable for diagnosis of liver malfunction. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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10 pages, 1974 KiB

Open AccessArticle

Development of a Protein Microarray Chip with Enhanced Fluorescence for Identification of Semen and Vaginal Fluid

by Naseem Abbas, Xun Lu, Mohsin Ali Badshah, Jung Bin In, Won Il Heo, Kui Young Park, Mi-Kyung Lee, Cho Hee Kim, Pilwon Kang, Woo-Jin Chang, Seok-Min Kim and Seong Jun Seo

Sensors 2018, 18(11), 3874; https://doi.org/10.3390/s18113874 - 10 Nov 2018

Cited by 15 | Viewed by 4333

Abstract

The detection of body fluids has been used to identify a suspect and build a criminal case. As the amount of evidence collected at a crime site is limited, a multiplex identification system for body fluids using a small amount of sample is required. In this study, we proposed a multiplex detection platform using an Ag vertical nanorod metal enhanced fluorescence (MEF) substrate for semen and vaginal fluid (VF), which are important evidence in cases of sexual crime. The Ag nanorod MEF substrate with a length of 500 nm was fabricated by glancing angle deposition, and amino functionalization was conducted to improve binding ability. The effect of incubation time was analyzed, and an incubation time of 60 min was selected, at which the fluorescence signal was saturated. To assess the performance of the developed identification chip, the identification of semen and VF was carried out. The developed sensor could selectively identify semen and VF without any cross-reactivity. The limit of detection of the fabricated microarray chip was 10 times better than the commercially available rapid stain identification (RSID) Semen kit. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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10 pages, 4082 KiB

Open AccessArticle

Quantification of DNA by a Thermal-Durable Biosensor Modified with Conductive Poly(3,4-ethylenedioxythiophene)

by Yesong Gu, Po-Yuan Tseng, Xiang Bi and Jason H. C. Yang

Sensors 2018, 18(11), 3684; https://doi.org/10.3390/s18113684 - 30 Oct 2018

Cited by 8 | Viewed by 2848

Abstract

The general clinical procedure for viral DNA detection or gene mutation diagnosis following polymerase chain reaction (PCR) often involves gel electrophoresis and DNA sequencing, which is usually time-consuming. In this study, we have proposed a facile strategy to construct a DNA biosensor, in which the platinum electrode was modified with a dual-film of electrochemically synthesized poly(3,4-ethylenedioxythiophene) (PEDOT) resulting in immobilized gold nanoparticles, with the gold nanoparticles easily immobilized in a uniform distribution. The DNA probe labeled with a SH group was then assembled to the fabricated electrode and employed to capture the target DNA based on the complementary sequence. The hybridization efficiency was evaluated with differential pulse voltammetry (DPV) in the presence of daunorubicin hydrochloride. Our results demonstrated that the peak current in DPV exhibited a linear correlation the concentration of target DNA that was complementary to the probe DNA. Moreover, the electrode could be reused by heating denaturation and re-hybridization, which only brought slight signal decay. In addition, the addition of the oxidized form of nicotinamide adenine dinucleotide (NAD⁺) could dramatically enhance the sensitivity by more than 5.45-fold, and the limit-of-detection reached about 100 pM. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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12 pages, 3254 KiB

Open AccessArticle

Cadmium-Free Quantum Dots as Fluorescent Labels for Exosomes

by Garima Dobhal, Deanna Ayupova, Geoffry Laufersky, Zeineb Ayed, Thomas Nann and Renee V. Goreham

Sensors 2018, 18(10), 3308; https://doi.org/10.3390/s18103308 - 02 Oct 2018

Cited by 23 | Viewed by 7111

Abstract

Quantum dots are attractive alternatives to organic fluorophores for the purposes of fluorescent labeling and the detection of biomarkers. They can also be made to specifically target a protein of interest by conjugating biomolecules, such as antibodies. However, the majority of the fluorescent labeling using quantum dots is done using toxic materials such as cadmium or lead due to the well-established synthetic processes for these quantum dots. Here, we demonstrate the use of indium phosphide quantum dots with a zinc sulfide shell for the purposes of labeling and the detection of exosomes derived from the THP-1 cell line (monocyte cell line). Exosomes are nano-sized vesicles that have the potential to be used as biomarkers due to their involvement in complex cell processes. However, the lack of standardized methodology around the detection and analysis of exosomes has made it difficult to detect these membrane-containing vesicles. We targeted a protein that is known to exist on the surface of the exosomes (CD63) using a CD63 antibody. The antibody was conjugated to the quantum dots that were first made water-soluble using a ligand-exchange method. The conjugation was done using carbodiimide coupling, and was confirmed using a range of different methods such as dynamic light scattering, surface plasmon resonance, fluorescent microscopy, and Fourier transform infrared spectroscopy. The conjugation of the quantum dot antibody to the exosomes was further confirmed using similar methods. This demonstrates the potential for the use of a non-toxic conjugate to target nano-sized biomarkers that could be further used for the detection of different diseases. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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11 pages, 1688 KiB

Open AccessArticle

Membrane-Based Microwave-Mediated Electrochemical Immunoassay for the In Vitro, Highly Sensitive Detection of Osteoporosis-Related Biomarkers

by Hye Youn Kim, Shinobu Sato, Shigeori Takenaka and Min-Ho Lee

Sensors 2018, 18(9), 2933; https://doi.org/10.3390/s18092933 - 04 Sep 2018

Cited by 7 | Viewed by 4174

Abstract

Highly sensitive and multiplexed in vitro detection of osteoporosis-related biochemical markers were carried out based on the membrane-based microwave-mediated electrochemical immunoassay (MMeEIA), where we can dramatically reduce the sample preparation time by shortening the incubation time of conjugation to obtain sensitive detection based on three dimensional conjugation of antibodies with target antigens in nylon membrane disk. C-terminal cross-linked telopeptide of type I collagen (CTx), Osteocalcin (OC), parathyroid hormone (PTH), and N-terminal propeptide of type I collagen (P1NP), which can be utilized to monitor the progress of osteoporosis, were quantified using their corresponding antibody immobilized in membranes. Coefficient of variations in this intra- and inter-assays were within 8.0% for all markers. When compared with data obtained from clinically used standard equipment (Roche modular E170), their coefficients of determination, R² values, are mostly more than 0.9. They show that the results obtained from MMeEIA are in good agreement with that from the conventional clinical instruments. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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12 pages, 2020 KiB

Open AccessArticle

Label-Free Detection of Salivary Pepsin Using Gold Nanoparticle/Polypyrrole Nanocoral Modified Screen-Printed Electrode

by Doyeon Lee, Young Ju Lee, Young-Gyu Eun and Gi-Ja Lee

Sensors 2018, 18(6), 1685; https://doi.org/10.3390/s18061685 - 24 May 2018

Cited by 15 | Viewed by 5301

Abstract

Detection of salivary pepsin has been given attention as a new diagnostic tool for laryngopharyngeal reflux (LPR) disease, because saliva collection is non-invasive and relatively comfortable. In this study, we prepared polypyrrole nanocorals (PPNCs) on a screen-printed carbon electrode (SPCE) by a soft template synthesis method, using β-naphthalenesulfonic acid (NSA) (for short, PPNCs/SPCE). Gold nanoparticles (GNPs) were then decorated on PPNCs/SPCE by electrodeposition (for short, GNP/PPNCs/SPCE). To construct the immunosensor, pepsin antibody was immobilized on GNP/PPNCs/SPCE. Next, citric acid was applied to prevent non-specific binding and change the electrode surface charge before pepsin incubation. Electrochemical stepwise characterization was performed using cyclic voltammetry, and immunosensor response toward different pepsin concentrations was measured by differential pulsed voltammetry. As a result, our electrochemical immunosensor showed a sensitive detection performance toward pepsin with a linear range from 6.25 to 100 ng/mL and high specificity toward pepsin, as well as a low limit of detection of 2.2 ng/mL. Finally, we quantified the pepsin levels in saliva samples of LPR patients (n = 2), showing that the results were concordant with those of a conventional ELISA method. Therefore, we expect that this electrochemical immunosensor could be helpful for preliminarily diagnosing LPR through the detection of pepsin in saliva. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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Review

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34 pages, 6227 KiB

Open AccessReview

Advances in Molecularly Imprinting Technology for Bioanalytical Applications

by Runfa Li, Yonghai Feng, Guoqing Pan and Lei Liu

Sensors 2019, 19(1), 177; https://doi.org/10.3390/s19010177 - 06 Jan 2019

Cited by 53 | Viewed by 6516

Abstract

In recent years, along with the rapid development of relevant biological fields, there has been a tremendous motivation to combine molecular imprinting technology (MIT) with biosensing. In this situation, bioprobes and biosensors based on molecularly imprinted polymers (MIPs) have emerged as a reliable candidate for a comprehensive range of applications, from biomolecule detection to drug tracking. Unlike their precursors such as classic immunosensors based on antibody binding and natural receptor elements, MIPs create complementary cavities with stronger binding affinity, while their intrinsic artificial polymers facilitate their use in harsh environments. The major objective of this work is to review recent MIP bioprobes and biosensors, especially those used for biomolecules and drugs. In this review, MIP bioprobes and biosensors are categorized by sensing method, including optical sensing, electrochemical sensing, gravimetric sensing and magnetic sensing, respectively. The working mechanism(s) of each sensing method are thoroughly discussed. Moreover, this work aims to present the cutting-edge structures and modifiers offering higher properties and performances, and clearly point out recent efforts dedicated to introduce multi-sensing and multi-functional MIP bioprobes and biosensors applicable to interdisciplinary fields. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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17 pages, 2506 KiB

Open AccessReview

Disposable Voltammetric Immunosensors Integrated with Microfluidic Platforms for Biomedical, Agricultural and Food Analyses: A Review

by Fabiana S. Felix, Alexandre L. B. Baccaro and Lúcio Angnes

Sensors 2018, 18(12), 4124; https://doi.org/10.3390/s18124124 - 24 Nov 2018

Cited by 15 | Viewed by 3879

Abstract

Disposable immunosensors are analytical devices used for the quantification of a broad variety of analytes in different areas such as clinical, environmental, agricultural and food quality management. They detect the analytes by means of the strong interactions between antibodies and antigens, which provide concentration-dependent signals. For the herein highlighted voltammetric immunosensors, the analytical measurements are due to changes in the electrical signals on the surface of the transducers. The possibility of using disposable and miniaturized immunoassays is a very interesting alternative for voltammetric analyses, mainly, when associated with screen-printing technologies (screen-printed electrodes, SPEs), and microfluidic platforms. The aim of this paper is to discuss a carefully selected literature about different examples of SPEs-based immunosensors associated with microfluidic technologies for diseases, food, agricultural and environmental analysis. Technological aspects of the development of the voltammetric immunoassays such as the signal amplification, construction of paper-based microfluidic platforms and the utilization of microfluidic devices for point-of-care testing will be presented as well. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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26 pages, 7023 KiB

Open AccessReview

HCV Detection, Discrimination, and Genotyping Technologies

by Shrikant Dashrath Warkad, Satish Balasaheb Nimse, Keum-Soo Song and Taisun Kim

Sensors 2018, 18(10), 3423; https://doi.org/10.3390/s18103423 - 12 Oct 2018

Cited by 28 | Viewed by 7072

Abstract

According to the World Health Organization (WHO), 71 million people were living with Hepatitis C virus (HCV) infection worldwide in 2015. Each year, about 399,000 HCV-infected people succumb to cirrhosis, hepatocellular carcinoma, and liver failure. Therefore, screening of HCV infection with simple, rapid, but highly sensitive and specific methods can help to curb the global burden on HCV healthcare. Apart from the determination of viral load/viral clearance, the identification of specific HCV genotype is also critical for successful treatment of hepatitis C. This critical review focuses on the technologies used for the detection, discrimination, and genotyping of HCV in clinical samples. This article also focuses on advantages and disadvantages of the reported methods used for HCV detection, quantification, and genotyping. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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24 pages, 3257 KiB

Open AccessReview

Contact-Lens Biosensors

by Ryan Chang Tseng, Ching-Chuen Chen, Sheng-Min Hsu and Han-Sheng Chuang

Sensors 2018, 18(8), 2651; https://doi.org/10.3390/s18082651 - 13 Aug 2018

Cited by 95 | Viewed by 11594

Abstract

Rapid diagnosis and screening of diseases have become increasingly important in predictive and preventive medicine as they improve patient treatment strategies and reduce cost as well as burden on our healthcare system. In this regard, wearable devices are emerging as effective and reliable point-of-care diagnostics that can allow users to monitor their health at home. These wrist-worn, head-mounted, smart-textile, or smart-patches devices can offer valuable information on the conditions of patients as a non-invasive form of monitoring. However, they are significantly limited in monitoring physiological signals and biomechanics, and, mostly, rely on the physical attributes. Recently, developed wearable devices utilize body fluids, such as sweat, saliva, or skin interstitial fluid, and electrochemical interactions to allow continuous physiological condition and disease monitoring for users. Among them, tear fluid has been widely utilized in the investigation of ocular diseases, diabetes, and even cancers, because of its easy accessibility, lower complexity, and minimal invasiveness. By determining the concentration change of analytes within the tear fluid, it would be possible to identify disease progression and allow patient-oriented therapies. Considering the emerging trend of tear-based biosensing technology, this review article aims to focus on an overview of the tear fluid as a detection medium for certain diseases, such as ocular disorders, diabetes, and cancer. In addition, the rise and application of minimally invasive detection and monitoring via integrated contact lens biosensors will also be addressed, in regards to their practicality and current developmental progress. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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14 pages, 1999 KiB

Open AccessReview

Sensors for Enhanced Detection of Acetone as a Potential Tool for Noninvasive Diabetes Monitoring

by Artur Rydosz

Sensors 2018, 18(7), 2298; https://doi.org/10.3390/s18072298 - 16 Jul 2018

Cited by 115 | Viewed by 8122

Abstract

Measurement of blood-borne volatile organic compounds (VOCs) occurring in human exhaled breath as a result of metabolic changes or pathological disorders is a promising tool for noninvasive medical diagnosis, such as exhaled acetone measurements in terms of diabetes monitoring. The conventional methods for exhaled breath analysis are based on spectrometry techniques, however, the development of gas sensors has made them more and more attractive from a medical point of view. This review focuses on the latest achievements in gas sensors for exhaled acetone detection. Several different methods and techniques are presented and discussed as well. Full article

(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)

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