Special Issue "Biomarkers and Nanosensors: New Approaches for Biology and Medicine"
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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 (29 February 2012)
Special Issue Editors
Guest Editor
Prof. Dr. Matt Trau
Centre for Biomarker Research and Development, Australian Institute of Bioengineering & Nanotechnology , Level 5, Bldg 75, The University of Queensland, Brisbane QLD 4072, Australia
Website: http://www.aibn.uq.edu.au/researchers#Trau
E-Mail: m.trau@uq.edu.au
Phone: +61 7 3346 4173
Fax: +61 7 3346 3973
Interests: the nanostructured assembly and manipulation of matter to produce materials and devices for application in medicine and biotechnology
Guest Editor
Dr. Muhammad J. A. Shiddiky
Centre for Biomarker Research and Development, Australian Institute of Bioengineering & Nanotechnology, Level 5, Bldg 75, The University of Queensland, Brisbane QLD 4072, Australia
Website: http://www.uq.edu.au/uqresearchers/researcher/shiddikymja.html
E-Mail: m.shiddiky@uq.edu.au
Phone: +61 7 33464169
Fax: +61 7 33463973
Interests: microfluidic and nanofluidic devices for circulating tumor cells (CTCs) and protein biomarker analysis
Special Issue Information
Dear Colleagues,
In the past decade, biomarker research has experienced phenomenal growth powered by novel molecular readout (nano) technology in genomics, proteomics and metabolomics. The biological markers of disease are now enabling many new and innovative applications in the field of medicine, molecular biology and biotechnology. This special issue will focus on convergence of biomarkers and nanotechnology based molecular readout systems and clinical applications.
Prof. Dr. Matt Trau
Dr. Muhammad J. A. Shiddiky
Guest Editors
Submission
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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 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 1600 CHF (Swiss Francs).
Keywords
- diagnostic micro and nanodevices
- personalized medicine
- single-molecule readout systems
- early disease detection
- arrayed microbiosensors
- molecular devices
- DNA nanomachines
- DNA methylation
- epigenetic
- circulating tumor cells (CTCs) analysis
- biomarkers
- biosensors
- immunosensors
Published Papers (13 papers)
Zhi Heng Chen, Shou Qing Huang, Yande Wang, Ai Zhen Yang, Jian Wen, Xiao Hong Xu, Yan Chen, Qu Bo Chen, Ying Hong Wang, Ellen He, Ji Zhou and Sven Skog
Received: 30 September 2011; in revised form: 30 October 2011 / Accepted: 22 November 2011 / Published: 28 November 2011
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Abstract: Serological thymidine kinase 1 (STK1) is a reliable proliferation marker for prognosis, monitoring tumour therapy, and relapse. Here we investigated the use of STK1 in health screening for early detection of pre-malignant and malignant diseases. The investigation was based on 35,365 participants in four independent health screening studies in China between 2005–2011. All participants were clinically examined. The concentration of STK1 was determined by a sensitive chemiluminescent dot blot ECL assay. The ROCvalue of the STK1 assay was 0.96. At a cut-off STK1 value of 2.0 pM, the likelihood (+) value was 236.5, and the sensitivity and the specificity were 0.78 and 0.99, respectively. The relative number of city-dwelling people with elevated STK1 values (≥2.0 pM) was 0.8% (198/26,484), while the corresponding value for the group of oil-field workers was 5.8% (514/8,355). The latter group expressed significantly higher frequency of refractory anaemia, fatty liver, and obesity, compared to the city dwellers, but no cases of breast hyperplasia or prostate hyperplasia. Furthermore, people working in oil drilling/oil transportation showed higher STK1 values and higher frequency of pre-malignancies and benign diseases than people working in the oil-field administration. In the STK1 elevated group of the city-dwelling people, a statistically significantly higher number of people were found to have malignancies, pre-malignancies of all types, moderate/severe type of hyperplasia of breast or prostate, or refractory anaemia, or to be at high risk for hepatitis B, compared to people with normal STK1 values (< 2.0 pM). No malignancies were found in the normal STK1 group. In the elevated STK1 group 85.4% showed diseases linked to a higher risk for pre-/early cancerous progression, compared to 52.4% of those with normal STK1 values. Among participants with elevated STK1 values, 8.8% developed new malignancies or progress in their pre-malignancies within 5 to 72 months, compared to 0.2% among people with normal STK1 values. People who showed elevated STK1 values were at about three to five times higher risk to develop malignancies compared to a calculated risk based on a cancer incidence rate of 0.2–0.3%. We conclude that serological TK1 protein concentration is a reliable marker for risk assessment of pre/early cancerous progression.
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Received: 29 November 2011; in revised form: 31 December 2011 / Accepted: 4 January 2012 / Published: 9 January 2012
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Abstract: Recently, aptamers have attracted the attention of many scientists, because they not only have all of the advantages of antibodies, but also have unique merits, such as thermal stability, low cost, and unlimited applications. In this review, we present the reasons why aptamers are known as alternatives to antibodies. Furthermore, several types of in vitro selection processes, including nitrocellulose membrane filtration, affinity chromatography, magnetic bead, and capillary electrophoresis-based selection methods, are explained in detail. We also introduce various applications of aptamers for the diagnosis of diseases and detection of small molecules. Numerous analytical techniques, such as electrochemical, colorimetric, optical, and mass-sensitive methods, can be utilized to detect targets, due to convenient modifications and the stability of aptamers. Finally, several medical and analytical applications of aptamers are presented. In summary, aptamers are promising materials for diverse areas, not just as alternatives to antibodies, but as the core components of medical and analytical equipment.
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Received: 1 December 2011; in revised form: 20 January 2012 / Accepted: 14 February 2012 / Published: 16 February 2012
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Abstract: During the last years, proteomics has facilitated biomarker discovery by coupling high-throughput techniques with novel nanosensors. In the present review, we focus on the study of label-based and label-free detection systems, as well as nanotechnology approaches, indicating their advantages and applications in biomarker discovery. In addition, several disease biomarkers are shown in order to display the clinical importance of the improvement of sensitivity and selectivity by using nanoproteomics approaches as novel sensors.
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Received: 16 February 2012; in revised form: 27 February 2012 / Accepted: 6 March 2012 / Published: 8 March 2012
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Abstract: Small noncoding microRNAs (miRNAs) are important regulators of post-transcriptional gene regulation and have altered the prevailing view of a linear relationship between gene and protein expression. Aberrant miRNA expression is an emerging theme for a wide variety of diseases, highlighting the fundamental role played by miRNAs in both physiological and pathological states. The identification of stable miRNAs in bodily fluids paved the way for their use as novel biomarkers amenable to clinical diagnosis in translational medicine. Identification of miRNAs in exosomes that are functional upon delivery to the recipient cells has highlighted a novel method of intercellular communication. Delivery of miRNAs to recipient cells via blood, with functional gene regulatory consequences, opens up novel avenues for target intervention. Exosomes thus offer a novel strategy for delivering drugs or RNA therapeutic agents. Though much work lies ahead, circulating miRNAs are unequivocally ushering in a new era of novel biomarker discovery, intercellular communication mechanisms, and therapeutic intervention strategies.
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Received: 21 February 2012; in revised form: 16 March 2012 / Accepted: 20 March 2012 / Published: 26 March 2012
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Abstract: Preterm birth is the leading cause of perinatal morbidity and mortality. Fetal fibronectin (fFN), a glycoprotein in the extracellular matrix of the amniotic membranes, is the most powerful biomarker for predicting the risk of preterm birth. Biosensors using the surface plasmon resonance (SPR) response are potentially useful in quantitatively measuring molecules. We established a standard calibration curve of SPR intensity against fFN concentration and used the SPR-based biosensor to detect fFN concentrations in the cervicovaginal secretions of pregnant women between 22 and 34 weeks of gestation. The calibration curve extends from 0.5 ng/mL to 100 ng/mL with an excellent correlation (R2 = 0.985) based on standard fFN samples. A cutoff value of 50 ng/mL fFN concentration in commercial ELISA kits corresponds to a relative intensity of 17 arbitrary units (a.u.) in SPR. Thirty-two pregnant women were analyzed in our study. In 11 women, the SPR relative intensity was greater than or equal to 17 a.u., and in 21 women, the SPR relative intensity was less than 17 a.u. There were significant differences between the two groups in regular uterine contractions (p = 0.040), hospitalization for tocolysis (p = 0.049), and delivery weeks (p = 0.043). Our prospective study concluded that SPR-based biosensors can quantitatively measure fFN concentrations. These results reveal the potential utility of SPR-based biosensors in predicting the risk of preterm birth.
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Received: 8 February 2012; in revised form: 22 March 2012 / Accepted: 16 April 2012 / Published: 18 April 2012
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Abstract: Cardiovascular disease is the leading cause of death worldwide, with high medical costs and rates of disability. It is therefore important to evaluate the use of cardiovascular biomarkers in the early diagnosis of coronary artery disease (CAD). We have screened a variety of recently identified bioactive peptides candidates in anticipation that they would allow detection of atherosclerotic CAD. Especially, we have focused on novel anti-atherogenic peptides as indicators and negative risk factors for CAD. In vitro, in vivo and clinical studies indicated that human adiponectin, heregulin-β1, glucagon-like peptide-1 (GLP-1), and salusin-α, peptides of 244, 71, 30, and 28 amino acids, respectively, attenuate the development and progression of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-coenzyme A: cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are significantly decreased in patients with CAD compared to patients without CAD. Receiver operating characteristic analyses showed that salusin-α is a more useful biomarker, with better sensitivity and specificity, compared with the others for detecting CAD. Therefore, salusin-α, heregulin-β1, adiponectin, and/or GLP-1, alone or in various combinations, may be useful as biomarkers for atherosclerotic CAD.
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Received: 1 March 2012; in revised form: 27 March 2012 / Accepted: 18 April 2012 / Published: 20 April 2012
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Abstract: Over the last 10 years, it has become clear that patients with head and neck cancer can be stratified into two distinct subgroups on the basis of the etiology of their disease. Patients with human papillomavirus-related cancers have significantly better survival rates and may necessitate different therapeutic approaches than those with tobacco and/or alcohol related cancers. This review discusses the various biomarkers currently in use for identification of patients with HPV-positive cancers with a focus on the advantages and limitations of molecular and nano-scale markers.
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Received: 3 February 2012; in revised form: 30 March 2012 / Accepted: 23 April 2012 / Published: 2 May 2012
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Abstract: Non-invasive detection and monitoring of lethal diseases, such as cancer, are considered as effective factors in treatment and survival. We describe a new disease diagnostic approach, denoted “reactomics”, based upon reactions between blood sera and an array of vesicles comprising different lipids and polydiacetylene (PDA), a chromatic polymer. We show that reactions between sera and such a lipid/PDA vesicle array produce chromatic patterns which depend both upon the sera composition as well as the specific lipid constituents within the vesicles. The chromatic patterns were processed through machine-learning algorithms, and the bioinformatics analysis could distinguish both between cancer-bearing and healthy patients, respectively, as well between two types of cancers. Size-separation and enzymatic digestion experiments indicate that lipoproteins are the primary components in sera which react with the chromatic biomimetic vesicles. This colorimetric reactomics concept is highly generic, robust, and does not require a priori knowledge upon specific disease markers in sera. Therefore, it could be employed as complementary or alternative approach for disease diagnostics.
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Received: 20 March 2012; in revised form: 18 April 2012 / Accepted: 27 April 2012 / Published: 2 May 2012
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Abstract: It has been shown that a suppressive protein, acting as an immune suppressor, is generated in animals and humans under particular stresses. However, studies related to immunosuppressive factors in response to the stress resulting from acute exercise are limited. This study compares the effects of pre- and post-exercise human serum on concanavalin A stimulated lymphocyte proliferation of mice. In the present study, blood samples in eight male undergraduates (age 21 ± 0.7 years) were taken before and immediately after ten sets of exercise consisting of 15 free and 30 10-kg loaded squat jumps in each set. The suppression of lymphocyte proliferation was analysed with high pressure liquid chromatography. It was noted from the result of gel chromatography columns that the post-exercise values of the suppression of lymphocyte proliferation, in comparison to corresponding pre-exercise values, were generally greater with significant differences observed in 7.5th–9th min post-exercise eluates (P < 0.05). Such findings suggest that intense eccentric type exercise may lead to generation of immunosuppressive factor(s) in young males.
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Received: 1 March 2012; in revised form: 13 April 2012 / Accepted: 27 April 2012 / Published: 2 May 2012
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Abstract: In multiple sclerosis (MS) the gold standard for the diagnosis and prognosis is, up to now, the use of magnetic resonance imaging markers. No alternative simpler assays proven of use, except for cerebrospinal fluid analysis, have been provided in MS diagnosis. Therefore, there is a need to develop non-invasive, sensitive, simple new techniques for the clinical routine. Herein we present the evaluation of the feasibility of a glycopeptide-based biosensor to detect MS specific antibodies in sera using the surface plasmon resonance technology. The previously described glycopeptide antigen CSF114(Glc) has been immobilized on a gold sensor chip and the method has been optimized for real-time specific autoantibody detection directly in sera. A population of 60 healthy blood donors and 61 multiple sclerosis patients has been screened. The receiver operating characteristic (ROC)-based analysis has established the optimal diagnostic cut-off value for the method obtaining a sensitivity of 36% and a specificity of 95%. Sample sera have been also screened with a previously validated ELISA.

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Received: 29 February 2012; in revised form: 12 April 2012 / Accepted: 2 May 2012 / Published: 4 May 2012
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Abstract: Various nanowire or nanotube-based devices have been demonstrated to fulfill the anticipated future demands on sensors. To fabricate such devices, electric field-based methods have demonstrated a great potential to integrate one-dimensional nanostructures into various forms. This review paper discusses theoretical and experimental aspects of the working principles, the assembled structures, and the unique functions associated with electric field-based assembly. The challenges and opportunities of the assembly methods are addressed in conjunction with future directions toward high performance sensors.
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Received: 8 March 2012; in revised form: 27 March 2012 / Accepted: 5 April 2012 / Published: 10 May 2012
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Abstract: Cancer is a leading cause of death worldwide. New early tumor markers are needed to treat the disease at curable stages. In addition, new therapeutic targets are required to treat patients not responding to available treatments. Ion channels play major roles in health and disease, including cancer. Actually, several ion channels have been suggested as potential tumor markers and therapeutic targets for different types of malignancies. One of most studied ion channels in cancer is the voltage-gated potassium channel Eag1 (ether à go-go 1), which has a high potential to be used as a cancer biomarker. Eag1 is expressed in most human tumors, in contrast to its restricted distribution in healthy tissues. Several findings suggest Eag1 as a potential early marker for cervical, colon, and breast cancer. In addition, because Eag1 amplification/expression is associated with poor survival in leukemia, colon and ovarian cancer patients, it has also been proposed as a prognosis marker. Moreover, inhibition of either expression or activity of Eag1 leads to reduced proliferation of cancer cells, making Eag1 a potential anticancer target. Using Eag1 in cancer detection programs could help to reduce mortality from this disease.

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Received: 15 March 2012; in revised form: 1 May 2012 / Accepted: 14 May 2012 / Published: 25 May 2012
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Abstract: Pioneered by Clark’s microelectrode more than half a century ago, there has been substantial interest in developing new, miniaturized optical methods to detect molecular oxygen inside cells. While extensively used for animal tissue measurements, applications of intracellular optical oxygen biosensors are still scarce in plant science. A critical aspect is the strong autofluorescence of the green plant tissue that interferes with optical signals of commonly used oxygen probes. A recently developed dual-frequency phase modulation technique can overcome this limitation, offering new perspectives for plant research. This review gives an overview on the latest optical sensing techniques and methods based on phosphorescence quenching in diverse tissues and discusses the potential pitfalls for applications in plants. The most promising oxygen sensitive probes are reviewed plus different oxygen sensing structures ranging from micro-optodes to soluble nanoparticles. Moreover, the applicability of using heterologously expressed oxygen binding proteins and fluorescent proteins to determine changes in the cellular oxygen concentration are discussed as potential non-invasive cellular oxygen reporters.
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Last update: 23 March 2012