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Biosensors
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Biosensors for the Detection of Biomarkers
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Biosensors for the Detection of Biomarkers

A special issue of Biosensors (ISSN 2079-6374).

Deadline for manuscript submissions: closed (15 October 2017) | Viewed by 65056

Special Issue Editor

Prof. Dr. Chung-Chiun Liu

E-Mail Website
Guest Editor
Department of Chemical and Biomolecular Engineering and Electronics Design Center, Case Western Reserve University, Cleveland, OH 44106, USA
Interests: electrochemical-based chemical and bio-sensors; microfabrication technology; nano-catalysts and sensing meterials; CRISPR-related biosensing strategy; bio-conjugation technology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A biomarker is a measureable indicator reflecting the presence of a disease or physiological state of an organism. Specifically, a biomarker provides an indication of normal and disease processes in the body, the progression of a disease, assessment of therapeutic effectiveness and early-stage screening, diagnosis, and clinical end-point evaluation. A biomarker is also important in personalized medicine, tailored to a specific patient for highly efficient treatment of disease processes.

It is necessary to distinguish between Disease-related and drug-related biomarkers. In this Special Issue, we will focus on disease-related biomarkers, and biosensors are particularly effective for the detection of disease-related biomarkers. These biomarkers can be specific biomolecules, enzymes, antibodies, antigens, hormones, genes, and gene products. Complex organ functions can also serve as biomarkers.

The bio-recognition mechanism of a biosensor can be specifically tailored, providing selectivity and sensitivity in the detection of a biomarker. The test medium can be a physiological fluid, including cerebrospinal fluid (CSF), blood, urine, saliva, and even breath. The transduction mechanism of these biosensors for biomarker detection can be optical, electrochemical, surface plasmon resonance (SPR), etc. In this Special Issue, we seek unique research and development efforts, identifying biosensors for the detection of various biomarkers, and expending the scientific frontier of this very important and significant bio-medical endeavor.

Prof. Chung Chiun Liu
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.

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. Biosensors is an international peer-reviewed open access monthly 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 2700 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.

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Published Papers (6 papers)

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Research

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3227 KiB  
Article
Bloch Surface Waves Biosensors for High Sensitivity Detection of Soluble ERBB2 in a Complex Biological Environment
by Alberto Sinibaldi, Camilla Sampaoli, Norbert Danz, Peter Munzert, Frank Sonntag, Fabio Centola, Agostino Occhicone, Elisa Tremante, Patrizio Giacomini and Francesco Michelotti
Biosensors 2017, 7(3), 33; https://doi.org/10.3390/bios7030033 - 17 Aug 2017
Cited by 11 | Viewed by 7047
Abstract
We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of the cancer biomarker ERBB2 in cell lysates. Overexpression of the ERBB2 protein is associated with aggressive breast cancer subtypes. To detect soluble ERBB2, we developed an optical set-up [...] Read more.
We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of the cancer biomarker ERBB2 in cell lysates. Overexpression of the ERBB2 protein is associated with aggressive breast cancer subtypes. To detect soluble ERBB2, we developed an optical set-up which operates in both label-free and fluorescence modes. The detection approach makes use of a sandwich assay, in which the one-dimensional photonic crystals sustaining Bloch surface waves are modified with monoclonal antibodies, in order to guarantee high specificity during the biological recognition. We present the results of exemplary protein G based label-free assays in complex biological matrices, reaching an estimated limit of detection of 0.5 ng/mL. On-chip and chip-to-chip variability of the results is addressed too, providing repeatability rates. Moreover, results on fluorescence operation demonstrate the capability to perform high sensitive cancer biomarker assays reaching a resolution of 0.6 ng/mL, without protein G assistance. The resolution obtained in both modes meets international guidelines and recommendations (15 ng/mL) for ERBB2 quantification assays, providing an alternative tool to phenotype and diagnose molecular cancer subtypes. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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1766 KiB  
Article
In Vitro Quantified Determination of β-Amyloid 42 Peptides, a Biomarker of Neuro-Degenerative Disorders, in PBS and Human Serum Using a Simple, Cost-Effective Thin Gold Film Biosensor
by Yifan Dai, Alireza Molazemhosseini and Chung Chiun Liu
Biosensors 2017, 7(3), 29; https://doi.org/10.3390/bios7030029 - 20 Jul 2017
Cited by 19 | Viewed by 7726
Abstract
A simple in vitro biosensor for the detection of β-amyloid 42 in phosphate-buffered saline (PBS) and undiluted human serum was fabricated and tested based on our platform sensor technology. The bio-recognition mechanism of this biosensor was based on the effect of the interaction [...] Read more.
A simple in vitro biosensor for the detection of β-amyloid 42 in phosphate-buffered saline (PBS) and undiluted human serum was fabricated and tested based on our platform sensor technology. The bio-recognition mechanism of this biosensor was based on the effect of the interaction between antibody and antigen of β-amyloid 42 to the redox couple probe of K4Fe(CN)6 and K3Fe(CN)6. Differential pulse voltammetry (DPV) served as the transduction mechanism measuring the current output derived from the redox coupling reaction. The biosensor was a three-electrode electrochemical system, and the working and counter electrodes were 50 nm thin gold film deposited by a sputtering technique. The reference electrode was a thick-film printed Ag/AgCl electrode. Laser ablation technique was used to define the size and structure of the biosensor. Cost-effective roll-to-roll manufacturing process was employed in the fabrication of the biosensor, making it simple and relatively inexpensive. Self-assembled monolayers (SAM) of 3-Mercaptopropionic acid (MPA) was employed to covalently immobilize the thiol group on the gold working electrode. A carbodiimide conjugation approach using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and N–hydroxysuccinimide (NHS) was undertaken for cross-linking antibody of β-amyloid 42 to the carboxylic groups on one end of the MPA. The antibody concentration of β-amyloid 42 used was 18.75 µg/mL. The concentration range of β-amyloid 42 in this study was from 0.0675 µg/mL to 0.5 µg/mL for both PBS and undiluted human serum. DPV measurements showed excellent response in this antigen concentration range. Interference study of this biosensor was carried out in the presence of Tau protein antigen. Excellent specificity of this β-amyloid 42 biosensor was demonstrated without interference from other species, such as T-tau protein. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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3237 KiB  
Article
Development of an Immunosensor for PfHRP 2 as a Biomarker for Malaria Detection
by Aver Hemben, Jon Ashley and Ibtisam E. Tothill
Biosensors 2017, 7(3), 28; https://doi.org/10.3390/bios7030028 - 18 Jul 2017
Cited by 31 | Viewed by 10208
Abstract
Plasmodium falciparum histidine-rich protein 2 (PfHRP 2) was selected in this work as the biomarker for the detection and diagnosis of malaria. An enzyme-linked immunosorbent assay (ELISA) was first developed to evaluate the immunoreagent’s suitability for the sensor’s development. A gold-based [...] Read more.
Plasmodium falciparum histidine-rich protein 2 (PfHRP 2) was selected in this work as the biomarker for the detection and diagnosis of malaria. An enzyme-linked immunosorbent assay (ELISA) was first developed to evaluate the immunoreagent’s suitability for the sensor’s development. A gold-based sensor with an integrated counter and an Ag/AgCl reference electrode was first selected and characterised and then used to develop the immunosensor for PfHRP 2, which enables a low cost, easy to use, and sensitive biosensor for malaria diagnosis. The sensor was applied to immobilise the anti-PfHRP 2 monoclonal antibody as the capture receptor. A sandwich ELISA assay format was constructed using horseradish peroxidase (HRP) as the enzyme label, and the electrochemical signal was generated using a 3, 3′, 5, 5′tetramethyl-benzidine dihydrochloride (TMB)/H2O2 system. The performance of the assay and the sensor were optimised and characterised, achieving a PfHRP 2 limit of detection (LOD) of 2.14 ng·mL−1 in buffer samples and 2.95 ng∙mL−1 in 100% spiked serum samples. The assay signal was then amplified using gold nanoparticles conjugated detection antibody-enzyme and a detection limit of 36 pg∙mL−1 was achieved in buffer samples and 40 pg∙mL−1 in serum samples. This sensor format is ideal for malaria detection and on-site analysis as a point-of-care device (POC) in resource-limited settings where the implementation of malaria diagnostics is essential in control and elimination efforts. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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17236 KiB  
Article
A Label-Free and Ultrasensitive Immunosensor for Detection of Human Chorionic Gonadotrophin Based on Graphene FETs
by Kamrul Islam, Ahmed Suhail and Genhua Pan
Biosensors 2017, 7(3), 27; https://doi.org/10.3390/bios7030027 - 12 Jul 2017
Cited by 14 | Viewed by 9531
Abstract
We report on a label-free immunosensor based on graphene field effect transistors (G-FETs) for the ultrasensitive detection of Human Chorionic Gonadotrophin (hCG), as an indicator of pregnancy and related disorders, such as actopic pregnancy, choriocarcinoma and orchic teratoma. Pyrene based bioactive ester was [...] Read more.
We report on a label-free immunosensor based on graphene field effect transistors (G-FETs) for the ultrasensitive detection of Human Chorionic Gonadotrophin (hCG), as an indicator of pregnancy and related disorders, such as actopic pregnancy, choriocarcinoma and orchic teratoma. Pyrene based bioactive ester was non-covalently anchored onto the graphene channel in order to retain the sp2 lattice. The G-FET transfer characteristics showed repeatable and reliable responses in all surface modifying steps using a direct current (DC) readout system. The hCG concentration gradient showed a detection limit of ~1 pg·mL−1. The proposed method facilitates the cost-effective and viable production of graphene point-of-care devices for clinical diagnosis. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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2605 KiB  
Article
A Single-Use, In Vitro Biosensor for the Detection of T-Tau Protein, A Biomarker of Neuro-Degenerative Disorders, in PBS and Human Serum Using Differential Pulse Voltammetry (DPV)
by Yifan Dai, Alireza Molazemhosseini and Chung Chiun Liu
Biosensors 2017, 7(1), 10; https://doi.org/10.3390/bios7010010 - 19 Feb 2017
Cited by 51 | Viewed by 13580
Abstract
A single-use, in vitro biosensor for the detection of T-Tau protein in phosphate-buffer saline (PBS) and undiluted human serum was designed, manufactured, and tested. Differential pulse voltammetry (DPV) served as the transduction mechanism. This biosensor consisted of three electrodes: working, counter, and reference [...] Read more.
A single-use, in vitro biosensor for the detection of T-Tau protein in phosphate-buffer saline (PBS) and undiluted human serum was designed, manufactured, and tested. Differential pulse voltammetry (DPV) served as the transduction mechanism. This biosensor consisted of three electrodes: working, counter, and reference electrodes fabricated on a PET sheet. Both working and counter electrodes were thin gold film, 10 nm in thickness. Laser ablation technique was used to define the size and structure of the biosensor. The biosensor was produced using cost-effective roll-to-roll process. Self-assembled monolayers (SAM) of 3-mercaptopropionic acid (MPA) were employed to covalently immobilize the anti-T-Tau (T-Tau antibody) on the gold working electrode. A carbodiimide conjugation approach using N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) and N–hydroxysuccinimide (NHS) cross-linked anti-T-Tau to the carboxylic groups on one end of the MPA. A T-Tau protein ladder with six isoforms was used in this study. The anti-T-Tau concentration used was 500,000 pg/mL. The T-Tau protein concentration ranged from 1000 pg/mL to 100,000 pg/mL. DPV measurements showed excellent responses, with a good calibration curve. Thus, a practical tool for simple detection of T-Tau protein, a biomarker of neuro-degenerative disorders, has been successfully developed. This tool could also be extended to detect other biomarkers for neuro-degenerative disorders, such as P-Tau protein and β-amyloid 42. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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Review

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1359 KiB  
Review
Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics
by Jessica Z. Kubicek-Sutherland, Dung M. Vu, Heather M. Mendez, Shailja Jakhar and Harshini Mukundan
Biosensors 2017, 7(3), 25; https://doi.org/10.3390/bios7030025 - 4 Jul 2017
Cited by 32 | Viewed by 15470
Abstract
Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, [...] Read more.
Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential for their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. The biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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