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A literature review of biosensors for multiple sclerosis: Towards personalized medicine and point-of-care testing

December 2020
Multiple Sclerosis and Related Disorders 48(10076):102675

DOI:10.1016/j.msard.2020.102675

Authors:

TOBB University of Economics and Technology

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system that leads to severe motor and sensory deficits in patients. Although some biomolecules in serum or cerebrospinal fluid have been suggested as biomarkers for MS diagnosis, following disease activity and monitoring treatment response, most of these potential biomarkers are not currently in clinical use and available for all patients. The reasons behind this are generally related to insufficient robustness of biomarker or technical difficulties, high prices, and requirements for technical personnel for their detection. Point-of-care testing (POCT) is an emerging field of healthcare that can be applied at the hospital as well as at home without the need for a centralized laboratory. Biosensor devices offer a convenient means for POCT. A biosensor is a compact analytical device that uses a bioreceptor, such as an antibody, enzyme, or oligonucleotide, to capture the analyte of interest. The interaction between the analyte and the bioreceptor is sensed and transduced into a suitable signal by the signal transducer. The advantages of using a biosensor for detecting the biomolecule of interest include speed, simplicity, accuracy, relatively lower cost, and lack of requirements for highly qualified personnel to perform the testing. Owing to these advantages and with the help of innovations in biosensor development technologies, there has been a great interest in developing biosensor devices for MS in recent years. Hence, the purpose of this review was to provide researchers with an up-to-date summary of the literature as well as to highlight the challenges and opportunities in this translational research field. In addition, because this is a highly interdisciplinary field of study, potentially concerning MS specialists, neurologists, biomedical researchers, and engineers, another aim of this review was to bridge the gap between these disciplines.

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Corresponding author: Birsen CAN DEMĠRDÖĞEN

Address: Department of Biomedical Engineering, TOBB University of Economics and Technology, Söğütözü

06560, Ankara, Turkey

Tel: +90 312 292 42 79

Email: bcandemirdogen@etu.edu.tr, birsencan.demirdogen@gmail.com

A literature review of biosensors for multiple sclerosis: towards personalized medicine and point-of-care

testing

Birsen CAN DEMİRDÖĞEN, PhD

Department of Biomedical Engineering, TOBB University of Economics and Technology, Ankara, Turkey

Abstract

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system that leads to

severe motor and sensory deficits in patients. Although some biomolecules in serum or cerebrospinal fluid have

been suggested as biomarkers for MS diagnosis, following disease activity and monitoring treatment response,

most of these potential biomarkers are not currently in clinical use and available for all patients. The reasons

behind this are generally related to insufficient robustness of biomarker or technical difficulties, high prices, and

requirements for technical personnel for their detection.

Point-of-care testing (POCT) is an emerging field of healthcare that can be applied at the hospital as well as at

home without the need for a centralized laboratory. Biosensor devices offer a convenient means for POCT. A

biosensor is a compact analytical device that uses a bioreceptor, such as an antibody, enzyme, or

oligonucleotide, to capture the analyte of interest. The interaction between the analyte and the bioreceptor is

sensed and transduced into a suitable signal by the signal transducer. The advantages of using a biosensor for

detecting the biomolecule of interest include speed, simplicity, accuracy, relatively lower cost, and lack of

requirements for highly qualified personnel to perform the testing. Owing to these advantages and with the help

of innovations in biosensor development technologies, there has been a great interest in developing biosensor

devices for MS in recent years.

Hence, the purpose of this review was to provide researchers with an up-to-date summary of the literature as

well as to highlight the challenges and opportunities in this translational research field. In addition, because this

is a highly interdisciplinary field of study, potentially concerning MS specialists, neurologists, biomedical

researchers, and engineers, another aim of this review was to bridge the gap between these disciplines.

Keywords: Biomarker; immunosensor; lab-on-a-chip; microfluidic; nanomaterial; nanoparticle; point-of-care

testing; patient-centered healthcare; personalized medicine

Electroanalysis and Sensors for Biomedical and Clinical Applications

Chapter

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Biosensor is a biorecognition element device that measures biological reactions via physical and chemical sensing. Enzymes, antibodies, nucleic acids, proteins, receptor molecules, or any other intercellular agent that acts as an input, recognizes, and transfers signals and outputs them as digitalization, color, absorbance, or odor could be the biorecognition element. Biosensors play an unquestionable role in clinical and biomedical settings because they reduce diagnostic time, produce rapid results, are portable to any location where there is an emergence or natural disaster, are small in size, economically affordable, and have high sensitivity, specificity with a low detection limit. According to forecasts, clinical biosensors will be worth more than $36.7 billion by 2036, even though the biosensor function is prominent and enormous during covid-19. This chapter will focus on biosensors and their clinical applications.

Immunosensors for Autoimmune-Disease-Related Biomarkers: A Literature Review

Article

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Jul 2023
SENSORS-BASEL

Immunosensors are a special class of biosensors that employ specific antibodies for biorecognition of the target analyte. Immunosensors that target disease biomarkers may be exploited as tools for disease diagnosis and/or follow-up, offering several advantages over conventional analytical techniques, such as rapid and easy analysis of patients’ samples at the point-of-care. Autoimmune diseases have been increasingly prevalent worldwide in recent years, while the COVID-19 pandemic has also been associated with autoimmunity. Consequently, demand for tools enabling the early and reliable diagnosis of autoimmune diseases is expected to increase in the near future. To this end, interest in immunosensors targeting autoimmune disease biomarkers, mainly, various autoantibodies and specific pro-inflammatory proteins (e.g., specific cytokines), has been rekindled. This review article presents most of the immunosensors proposed to date as potential tools for the diagnosis of various autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. The signal transduction and the immunoassay principles of each immunosensor have been suitably classified and are briefly presented along with certain sensor elements, e.g., special nano-sized materials used in the construction of the immunosensing surface. The main concluding remarks are presented and future perspectives of the field are also briefly discussed.

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

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Apr 2023

Lokesh Pathak

Applications of Gelatin in Biosensors: Recent Trends and Progress

Article

Full-text available

Aug 2022

Gelatin is a natural protein from animal tissue with excellent biocompatibility, biodegradability, biosafety, low cost, and sol–gel property. By taking advantage of these properties, gelatin is considered to be an ideal component for the fabrication of biosensors. In recent years, biosensors with gelatin have been widely used for detecting various analytes, such as glucose, hydrogen peroxide, urea, amino acids, and pesticides, in the fields of medical diagnosis, food testing, and environmental monitoring. This perspective is an overview of the most recent trends and progress in the development of gelatin-based biosensors, which are classified by the function of gelatin as a matrix for immobilized biorecognition materials or as a biorecognition material for detecting target analytes.

A novel sandwich ELISA method for quantifying CHI3L1 in blood serum and cerebrospinal fluid multiple sclerosis patients using sustainable photo-irradiated zero-valence gold nanoparticles

Article

Oct 2024

A B S T R A C T The widespread occurrence of chronic demyelinating MS presents a significant challenge for ongoing research aimed at comprehending its progression, diagnosis, and treatment. In our research, we have devised a novel approach to quantify CHI3L1 (Chitinase-3-like protein 1), which has emerged as a valuable biomarker in MS because of its involvement in inflammation, tissue remodeling, and immune response—crucial factors in regulating damaged nerve cells and preventing their accumulation in the brain, utilizing sandwich ELISA technology. This innovative method primarily depends on gold nanoparticles synthesized through a novel process of photo- irradiation with ultraviolet light. The crystal structure and particle size of sustainable zero-valent gold nanoparticles were measured using X-ray diffraction (XRD), which proved the cubic shape, with a cubic unit cell edge length of 4.0095 Å. The transmission electron microscopy (TEM) and field emission scanning electron microscope (FE-SEM) demonstrated that the distribution of Au NPs is uniform, with an average diameter of 22 nm. The UV–Vis spectrum, displaying a pronounced absorbance peak at a wavelength of 548 nm, suggests the presence of Au NPs. The optimal conditions for the formation of the Au-biotinylated antibody-HRP complex were studied. The optimum pH was 7, the dilution ratio of AuNPs with biotinylated antibody-HRP was 1:3, and the concentration of nanogold was (1 ×10− 3 mg/ml) to avoid increasing it. Then a standard curve was drawn for this method and compared to the traditional method, and it was found to be twice as sensitive as the traditional method, with a high accuracy of CV% (3–6 %) as well as a rapid color generation for measurement. This method, based on gold nanoparticles that are considered a carrier for biotinylated antibody-HRP, was applied for the first time to measure CHI3L1 in the sera and cerebrospinal fluid of patients with multiple sclerosis, and the results demonstrated the accuracy and sensitivity of the method. The method has the potential to be an excellent tool for evaluating CHI3L1 and may have applications in other diseases for rapid diagnosis and timely treatment.

Biological and technical factors affecting the point-of-care diagnostics in not-oncological chronic diseases

Article

Aug 2024
BIOSENS BIOELECTRON

Inexpensive point-of-care (POC) analytical solutions have the potential to allow the implementation of large-scale screening campaigns aimed at identifying the initial stages of pathologies in the population, reducing morbidity, mortality and, indirectly, also the costs for the healthcare system. At global level, the most common preventive screening schemes address some cancer pathologies or are used to monitor the spread of some infective diseases. However, systematic testing might become decisive to improve the care response even in the case of chronic pathologies and, in this review, we analyzed the state-of-the-art of the POC diagnostics for Chronic Kidney Disease, Chronic Obstructive Pulmonary Disease and Multiple Sclerosis. The different technological options used to manufacture the biosensors and evaluate the produced data have been described and this information has been integrated with the present knowledge relatively to the biomarkers that have been proposed to monitor such diseases, namely their availability and reliability. Finally, the nature of the macromolecules used to capture the biomarkers has been discussed in relation to the biomarker nature.

A simplified method for relapsing-remitting multiple sclerosis detection: Insights from resting EEG signals

Article

Jun 2024
COMPUT BIOL MED

Highlights • Introduction of the first healthy-MS classification method achieving 100% accuracy using only two channels of EEG signals obtained during rest. •Utilization of band powers, band power ratios, and relative powers of subbands obtained through the Fast Fourier Transform (FFT) during the resting state for classification purposes. •Implementation of subject-independent classification through Leave-One Subject Out Cross Validation, ensuring robustness and generalizability of the classification model. •Comprehensive classification of all possible channel pairs in EEG using various algorithms such as LDA, SVM, CART, and kNN, followed by comparison of their performances to determine the most effective approach. Abstract Background and Objective: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease affecting the central nervous system, leading to various neurological symptoms. Early detection is paramount to prevent enduring damage during MS episodes. Although magnetic resonance imaging (MRI) is a common diagnostic tool, this study aims to explore the feasibility of using electroencephalography (EEG) signals for MS detection, considering their accessibility and ease of application compared to MRI. Methods: The study involved the analysis of EEG signals during rest from 17 MS patients and 27 healthy volunteers to investigate MS-healthy patterns. Power spectral density features (PSD) were extracted from the 32-channel EEG signals. The study employed Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), Classification and Regression Trees (CART), and k-Nearest Neighbor (kNN) classifiers to identify channels with the highest accuracy. Notably, the study achieved 100% accuracy in MS detection using the “Fp1” and “Pz” channels with the LDA classifier. A statistical analysis, utilizing the independent sample t-test, was conducted to explore whether PSD features of these channels differed significantly between healthy individuals and those with MS. Results: The results of the study demonstrate that effective detection of MS can be achieved using PSD features from only two channels of the EEG signal. Specifically, the “Fp1” and “Pz” channels exhibited 100% accuracy in MS detection with the LDA classifier. The statistical analysis further explored and confirmed the significant differences in PSD features between healthy individuals and MS patients. Conclusion: The study concludes that the proposed method, utilizing PSD features from specific EEG channels, offers a straightforward and efficient diagnostic approach for the effective detection of MS. The findings suggest the potential utility of EEG signals as a non-invasive and accessible alternative for MS detection, highlighting the importance of further research in this direction.

Magnetic materials-based medical devices for diagnosis, surgery, and therapy

Chapter

Jan 2023

Enzyme-immobilized microfluidic devices for biomolecule detection

Article

Dec 2022
TRAC-TREND ANAL CHEM

Biomolecules, such as nutrients in the bloodstream and lymph, are important indicators of overall health and body function. Biomolecule detection using low-cost and disposable sensor devices could help improve health monitoring and treatment outcomes. Point-of-care testing is expected to be a rapid and economical diagnostic tool compared with conventional laboratory-based testing. Recently, the integration of microfluidics and enzyme immobilization technology has enabled the development of low-cost, time-efficient, and high-accuracy analytical biosensors for detecting biomolecules. Herein, we reviewed recent advancements in enzyme-immobilized microfluidic devices for biomolecule measurement, and summarized techniques for the preparation of immobilized enzymes for use as biosensors and in biomolecule detection techniques. Additionally, the advantages, limitations, and future perspectives of enzyme-immobilized microfluidic devices are discussed.

Advances in nanotechnology versus stem cell therapy for the theranostics of multiple sclerosis disease

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Multiple sclerosis (MS) is an autoimmune disease afflicting over 2.8 million people worldwide. Symptoms of this disorder include discrepancies in speech, hearing impairment, fatigue, muscle weakness, walking problems, balance issues, and spasticity, which could eventually lead to paralysis. There have been reports of several treatment approaches that have had some side effects. Also, there is no certain test or indicator for the diagnosis of MS, so far. The recent therapeutic are trying to find out an actual dealing to stop or reduce progression of MS diseases and conserve nervous injury such as mesenchymal stem cells (MSCs). Using stem cell and nanotechnology as new therapeutic strategies may increase the efficacy of therapies. Although nanotechnology approaches and cell-based therapies seem to be separate area in the treatment of MS, they share similarities and could be used in combination for much more significant results. Nanoparticles harvested from stem cells, such as MSCs harvested exosomes, have shown significant anti-inflammatory effects similar to stem cells. Moreover, nanoparticles are also used for labeling and tracking the stem cells and as agents to facilitate their delivery. More interestingly, nanotechnology could be used as a tool to apply changes to stem cells by delivering genes and small RNA into stem cells to make them potent. Together, evidence is promising and positive regarding both stem cell and nanotechnology therapies for MS. These approaches harbor the great potential to introduce effective and innovative therapies. Although, there is no research that has compared and combined new strategies to manage MS management and some diseases have been treated with a combination of one or more modern therapy techniques, no previous research has compared and combined new strategies to manage MS. Therefore, this review has been performed to explore the feasibility and efficiency of integrating stem cells and nanotechnology in the treatment of MS for the first time

Molecular biomarkers in multiple sclerosis

Article

Full-text available

Dec 2019
J NEUROINFLAMM

Multiple sclerosis (MS) is an inflammatory-neurodegenerative disease of the central nervous system presenting with significant inter- and intraindividual heterogeneity. However, the application of clinical and imaging biomarkers is currently not able to allow individual characterization and prediction. Complementary, molecular biomarkers which are easily quantifiable come from the areas of immunology and neurobiology due to the causal pathomechanisms and can excellently complement other disease characteristics. Only a few molecular biomarkers have so far been routinely used in clinical practice as their validation and transfer take a long time. This review describes the characteristics that an ideal MS biomarker should have and the challenges of establishing new biomarkers. In addition, clinically relevant and promising biomarkers from the blood and cerebrospinal fluid are presented which are useful for MS diagnosis and prognosis as well as for the assessment of therapy response and side effects.

High-performance modified cellulose paper-based biosensors for medical diagnostics and early cancer screening: A concise review

Article

Full-text available

Oct 2019
CARBOHYD POLYM

A remarkable progress in the development of portable paper-based biosensors (PBBs) and microfluidic paper-based analytical devices (μPADs) has recently been achieved. In these devices, a paper formed of microfibers of cellulose, a carbohydrate biopolymer, offers both an ample space in its micropores for analytical reagents storage and a capillary force to drive liquid samples to a dedicated reaction zone for instantaneous detection of the desired analytes. Owing to the low cost and ultra-high sensitivity, these novel devices have become a promising alternative to traditional advanced analytical instruments and offer great potential for applications in medical emergencies, health diagnostics at points-of-care, and broad early-cancer screening. In this review, we focus particularly on recent important achievements in utilization of cellulose and its modifications in portable sensing devices for biomedical applications. The progress in functionalization of cellulose papers with antibodies, nucleic acids and nanomaterials in PBBs and μPADs, is discussed and critically evaluated.

Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Article

Full-text available

Mar 2019
LANCET NEUROL

Background: Multiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level. Methods: We assessed the epidemiology of multiple sclerosis from 1990 to 2016. Epidemiological outcomes for multiple sclerosis were modelled with DisMod-MR version 2.1, a Bayesian meta-regression framework widely used in GBD epidemiological modelling. Assessment of multiple sclerosis as the cause of death was based on 13 110 site-years of vital registration data analysed in the GBD's cause of death ensemble modelling module, which is designed to choose the optimum combination of mathematical models and predictive covariates based on out-of-sample predictive validity testing. Data on prevalence and deaths are summarised in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. We used the Socio-demographic Index, a composite indicator of income per person, years of education, and fertility, to assess relations with development level. Findings: In 2016, there were 2 221 188 prevalent cases of multiple sclerosis (95% uncertainty interval [UI] 2 033 866-2 436 858) globally, which corresponded to a 10·4% (9·1 to 11·8) increase in the age-standardised prevalence since 1990. The highest age-standardised multiple sclerosis prevalence estimates per 100 000 population were in high-income North America (164·6, 95% UI, 153·2 to 177·1), western Europe (127·0, 115·4 to 139·6), and Australasia (91·1, 81·5 to 101·7), and the lowest were in eastern sub-Saharan Africa (3·3, 2·9-3·8), central sub-Saharan African (2·8, 2·4 to 3·1), and Oceania (2·0, 1·71 to 2·29). There were 18 932 deaths due to multiple sclerosis (95% UI 16 577 to 21 033) and 1 151 478 DALYs (968 605 to 1 345 776) due to multiple sclerosis in 2016. Globally, age-standardised death rates decreased significantly (change -11·5%, 95% UI -35·4 to -4·7), whereas the change in age-standardised DALYs was not significant (-4·2%, -16·4 to 0·8). YLLs due to premature death were greatest in the sixth decade of life (22·05, 95% UI 19·08 to 25·34). Changes in age-standardised DALYs assessed with the Socio-demographic Index between 1990 and 2016 were variable. Interpretation: Multiple sclerosis is not common but is a potentially severe cause of neurological disability throughout adult life. Prevalence has increased substantially in many regions since 1990. These findings will be useful for resource allocation and planning in health services. Many regions worldwide have few or no epidemiological data on multiple sclerosis, and more studies are needed to make more accurate estimates. Funding: Bill & Melinda Gates Foundation.

The MRZ reaction and a quantitative intrathecal IgG synthesis may be helpful to differentiate between primary central nervous system lymphoma and multiple sclerosis

Article

Full-text available

May 2018
J NEUROL

Some patients with primary central nervous system lymphoma (PCNSL) may initially present with similar clinical, magnetic resonance imaging, and routine cerebrospinal fluid (CSF) findings as those observed in multiple sclerosis (MS). The MRZ reaction (MRZR), composed of the three respective antibody indices (AIs) against measles, rubella, and varicella zoster virus, appears to be the most specific CSF marker for MS. This study aimed to determine whether a positive MRZR and other routine CSF markers help differentiate between MS and PCNSL. Data regarding brain biopsy, CSF routine tests, cytopathological examination and immunophenotyping of CSF cells were assessed in 68 PCNSL patients. MRZR was determined, as possible, in PCNSL patients (n = 37) and in those with MS (n = 74; age and sex matched to PSCNL patients) and psychiatric disorders (PD; n = 78). Two stringency levels for a positive antibody index (AI) evaluation (AI ≥ 1.5 and 2.0) were applied, and MRZR was considered positive in cases with ≥ 2 positive AIs (MRZR-2). Using the common AI threshold of ≥ 1.5, MS patients exhibited positive MRZR-2 (58.1%) more frequently than PCNSL (8.1%) and PD patients (2.6%; p < 0.0001 for each comparison with the MS group) corresponding to a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 78.0%. On applying the stricter AI threshold of ≥ 2.0, 37.8% of MS patients were MRZR-2 positive; however, all patients with PCNSL and PD were MRZR-2 negative (p < 0.0001 for each comparison with the MS cohort) resulting in a PPV of 100% and an NPV of 71.4%. Consequently, a positive MRZR-2 result may contribute toward the distinction between MS and PCNSL owing to its high specificity and PPV for MS in the context of the present study. Among the other CSF parameters only a quantitative intrathecal IgG synthesis (present in 49.3% of MS patients but in none of the PCNSL or PD patients; p < 0.0001 for each comparison with the MS group) reliably indicated MS rather than PCNSL.

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

Article

Full-text available

Dec 2017
LANCET NEUROL

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

A miRNA biosensor based on localized surface plasmon resonance enhanced by surface-bound hybridization chain reaction

Article

Aug 2020
BIOSENS BIOELECTRON

The dysregulation of the concentration of individual circulating microRNAs or small sets of them has been recognized as a marker of disease. For example, an increase of the concentration of circulating miR-17 has been linked to lung cancer and metastatic breast cancer, while its decrease has been found in multiple sclerosis and gastric cancer. Consequently, techniques for the fast, specific and simple quantitation of microRNAs are becoming crucial enablers of early diagnosis and therapeutic follow-up. DNA based biosensors can serve this purpose, overcoming some of the drawbacks of conventional lab-based techniques. Herein, we report a cost-effective, simple and robust biosensor based on localized surface plasmon resonance and hybridization chain reaction. Immobilized gold nanoparticles are used for the detection of miR-17. Specificity of the detection was achieved by the use of hairpin surface-tethered probes and the hybridization chain reaction was used to amplify the detection signal and thus extend the dynamic range of the quantitation. Less than 1 h is needed for the entire procedure that achieved a limit of detection of about 1 pM or 50 amol/measurement, well within the reported useful range for diagnostic applications. We suggest that this technology could be a promising substitute of traditional lab-based techniques for the detection and quantification of miRNAs after these are extracted from diagnostic specimens and their analysis is thus made possible.

Potential role of calcifying nanoparticles in the etiology of multiple sclerosis

Article

May 2019
MED HYPOTHESES

Birsen Can Demirdöğen

A simple and universal enzyme-free approach for the detection of multiple microRNAs using a single nanostructured enhancer of surface plasmon resonance imaging

Article

Aug 2018

Here we describe a simple approach for the simultaneous detection of multiple microRNAs (miRNAs) using a single nanostructured reagent as surface plasmon resonance imaging (SPRi) enhancer and without using enzymatic reactions, sequence specific enhancers or multiple enhancing steps as normally reported in similar studies. The strategy involves the preparation and optimisation of neutravidin-coated gold nanospheres (nGNSs) functionalised with a previously biotinylated antibody (Ab) against DNA/RNA hybrids. The Ab guarantees the recognition of any miRNA sequence adsorbed on a surface properly functionalised with different DNA probes; at the same time, gold nanoparticles permit to detect this interaction, thus producing enough SPRi signal even at a low ligand concentration. After a careful optimisation of the nanoenhancer and after its characterisation, the final assay allowed the simultaneous detection of four miRNAs with a limit of detection (LOD) of up to 0.5 pM (equal to 275 attomoles in 500 μL) by performing a single enhancing injection. The proposed strategy shows good signal specificity and permits to discriminate wild-type, single- and triple-mutated sequences much better than non-enhanced SPRi. Finally, the method works properly in complex samples (total RNA extracted from blood) as demonstrated by the detection of four miRNAs potentially related to multiple sclerosis used as case study. This proof-of-concept study confirms that the approach provides the possibility to detect a theoretically unlimited number of miRNAs using a simple protocol and an easily prepared enhancing reagent, and may further facilitate the development of affordable multiplexing miRNA screening for clinical purposes.

Recent advances in microfluidic chip integrated electronic biosensors for multiplexed detection

Article

Aug 2018
BIOSENS BIOELECTRON

Utilizing biosensors for multiplexed detection can greatly increase analysis throughput and thus, the amount of information obtained in a single assay. The microfluidic chip, a type of micro-total analysis system (µTAS), has provided a necessary platform for portable and high-throughput biosensors. Biosensors and microfluidic chips are powerful individually, and their super combination is very meaningful for analytical especially for biological applications. In this paper, every kind of microfluidic-chip-integrated electronic biosensors including some emerging technologies for simultaneous detection of multiple analytes are reviewed. Different ways to reduce or avoid cross-talking and more efforts to achieve lab on chip multisensors were also introduced to help readers form a general idea of current developments in different angles.

Multiple sclerosis genetics: Results from meta-analyses of candidate-gene association studies

Article

Nov 2017

Kalthoum Tizaoui

As a complex disease, multiple sclerosis (MS) susceptibility implicates many genetic and environmental factors. Usually, individual genetic association studies have several limitations, and results are specific to the population of study. The Meta-analysis approach has been proposed to resolve these limitations and to increase the power of statistical analyses. In this review, we summarize results from meta-analyses of candidate genes of MS. Using the keywords: multiple sclerosis, genetic polymorphism and meta-analysis, we searched electronic databases (PubMed, Embase and Web of Sciences) for published meta-analyses until May 2017. Meta-analyses confirmed the association of polymorphisms in fifteen candidate genes with MS disease. However, polymorphisms in fourteen genes showed none significant association. Results outlined the importance of confirmed genes to understand signaling pathways in MS disease and shed light on their utility to develop new drugs targets.

A literature review of biosensors for multiple sclerosis: Towards personalized medicine and point-of-care testing

Abstract

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