Biosensors for cardiac biomarkers detection: a review

The cardiovascular disease (CVD) is considered as a major threat to global health. Therefore, there is a growing demand for a range of portable, rapid and low cost biosensing devices for the detection of CVD. Biosensors can play an important role in the early diagnosis of CVD without having to rely on hospital visits where expensive and time-consuming laboratory tests are recommended. Over the last decade, many biosensors have been developed to detect a wide range of cardiac marker to reduce the costs for healthcare. One of the major challenges is to find a way of predicting the risk that an individual can suffer from CVD. There has been considerable interest in finding diagnostic and prognostic biomarkers that can be detected in blood and predict CVD risk. Of these, C-reactive protein (CRP) is the best known biomarker followed by cardiac troponin I or T (cTnI/T), myoglobin, lipoprotein-associated phospholipase A(2), interlukin-6 (IL-6), interlukin-1 (IL-1), low-density lipoprotein (LDL), myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-α) has been used to predict cardiovascular events. This review provides an overview of the available biosensor platforms for the detection of various CVD markers and considerations of future prospects for the technology are addressed

Phase-sensitive plasmonic biosensor using a portable and large field-of-view interferometric microarray imager

Nanophotonics, and more specifically plasmonics, provides a rich toolbox for biomolecular sensing, since the engineered metasurfaces can enhance light–matter interactions to unprecedented levels. So far, biosensing associated with high-quality factor plasmonic resonances has almost exclusively relied on detection of spectral shifts and their associated intensity changes. However, the phase response of the plasmonic resonances have rarely been exploited, mainly because this requires a more sophisticated optical arrangement. Here we present a new phase-sensitive platform for high-throughput and label-free biosensing enhanced by plasmonics. It employs specifically designed Au nanohole arrays and a large field-of-view interferometric lens-free imaging reader operating in a collinear optical path configuration. This unique combination allows the detection of atomically thin (angstrom-level) topographical features over large areas, enabling simultaneous reading of thousands of microarray elements. As the plasmonic chips are fabricated using scalable techniques and the imaging reader is built with low-cost off-the-shelf consumer electronic and optical components, the proposed platform is ideal for point-of-care ultrasensitive biomarker detection from small sample volumes. Our research opens new horizons for on-site disease diagnostics and remote health monitoring.Peer ReviewedPostprint (published version

Biodetection Techniques for Quantification of Chemokines

Chemokines are a class of cytokine whose special properties, together with their involvement and relevant role in various diseases, make them a restricted group of biomarkers suitable for diagnosis and monitoring. Despite their importance, biodetection techniques dedicated to the selective determination of one or more chemokines are very scarce. For some years now, the critical diagnosis of inflammatory diseases by detecting both cytokine and chemokine biomarkers, has had a strong impact on the development of multiple detection platforms. However, it would be desirable to implement methodologies with a higher degree of selectivity for chemokines, in order to provide more precise information. In addition, better development of biosensor technology applied to this specific field would make it possible to address the main challenges of detection methods for several diseases with a high incidence in the population, avoiding high costs and low sensitivity. Taking this into account, this review aims to present the state of the art of chemokine biodetection techniques and emphasize the role of these systems in the prevention, monitoring and treatment of various diseases associated with chemokines as a starting point for future developments that are also analyzed throughout the article.Depto. de Química AnalíticaFac. de Ciencias QuímicasTRUEMinisterio de Ciencia, Innovación y UniversidadesComunidad de Madridpu

Application of flat panel OLED display technology for the point-of-care detection of circulating cancer biomarkers

abstract: Point-of-care molecular diagnostics can provide efficient and cost-effective medical care, and they have the potential to fundamentally change our approach to global health. However, most existing approaches are not scalable to include multiple biomarkers. As a solution, we have combined commercial flat panel OLED display technology with protein microarray technology to enable high-density fluorescent, programmable, multiplexed biorecognition in a compact and disposable configuration with clinical-level sensitivity. Our approach leverages advances in commercial display technology to reduce pre-functionalized biosensor substrate costs to pennies per cm[superscript 2]. Here, we demonstrate quantitative detection of IgG antibodies to multiple viral antigens in patient serum samples with detection limits for human IgG in the 10 pg/mL range. We also demonstrate multiplexed detection of antibodies to the HPV16 proteins E2, E6, and E7, which are circulating biomarkers for cervical as well as head and neck cancers.The final version of this article, as published in Scientific Reports, can be viewed online at: https://www.nature.com/articles/srep2905

Embedded disposable functionalized electrochemical biosensor with a 3D-printed flow cell for detection of hepatic oval cells (HOCs)

Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task for immunosensor technology. This work describes the development of a 3D-printed continuous flow system and exploits disposable screen-printed electrodes for the rapid detection of HOCs that over-express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT) electrodes have a chitosan film that serves as a scaffold for the immobilization of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of the biomarker and makes the designed sensor specific for oval cells. The developed sensor can be easily embedded into the 3D-printed flow cell to allow cells to be exposed continuously to the functionalized surface. The continuous flow is intended to increase capture of most of the target cells in the specimen. Contact angle measurements were performed to characterize the nature and quality of the modified sensor surface, and electrochemical measurements (cyclic voltammetry (CV) and square wave voltammetry (SWV)) were performed to confirm the efficiency and selectivity of the fabricated sensor to detect HOCs. The proposed method is valuable for capturing rare cells and could provide an effective tool for cancer diagnosis and detection

Desenvolvimento de um biossensor descartável para a deteção do antigene 15-3 do cancro da mama

This work describes the development of graphene electrochemical biosensors for the detection of CA15-3 protein, a recognized breast cancer tumor marker, using graphene-based field effect transistors (Gr-FET) functionalized with a specific antibody for this protein. The calibration model provided a correlation coefficient of 0.9959 and a detection limit of de 0.07 U mL-1. The recovery values obtained demonstrate its suitability for the quantification of CA15-3 protein in standard solutions. The ELISA method was also used as a comparison method for biosensor validation. Additionally, the feasibility of using the biosensor developed for detection and quantification of this marker in saliva samples was tested, aiming at the development of a low cost, disposable and fast technology that allows quantification using noninvasive methods, illustrating the potential of this method in the diagnosis of a highly prevalent disease.Este trabalho descreve o desenvolvimento de biossensores eletroquímicos com grafeno, para a deteção da proteína CA153, um reconhecido marcador tumoral do cancro da mama, utilizando transístores de efeito de campo com grafeno (GrFET), funcionalizados com um anticorpo específico para esta proteína. O modelo de calibração permitiu obter um coeficiente de correlação de 0.9959 e um limite de deteção de 0.07 U mL1. Os valores de recuperação obtidos demonstram a sua adequação para a quantificação da proteína CA15-3 em soluções padrão. O método de ELISA foi também utilizado como método de comparação para validação do biossensor. Adicionalmente, testou-se a exequibilidade de utilização do biossensor desenvolvido para a deteção e quantificação deste marcador em amostras de saliva, visando o desenvolvimento de uma tecnologia de baixo custo, descartável e rápida que permita uma quantificação recorrendo a métodos não invasivos, ilustrando o potencial deste método no diagnóstico de uma doença altamente prevalente.Mestrado em Materiais e Dispositivos Biomédico

Detecting and Screening of the Prostate Cancer by Using an Optical Nanoporous Thin-Film Sensor

Prostate cancer (PC) affects elderly men more than young men. The currently used cancer biomarker, prostate-specific antigen (PSA), highly overestimates PC population. Men with high PSA levels often have to go through unnecessary, but physically painful, and expensive prosesses, such as prostate biopsies. Finding a prostate cancer marker that is produced selectively by cancer, but not by normal prostate cells will increase the reliability of PC test. In 2006, our collaborator (Dr. Girish Shah) discovered a novel protein, referred as neuroendocrine marker (NEM), secreted only by malignant prostate cells and released in blood circulation. To examine whether the combined NEM-PSA test can improve the reliability for early PC detection, we have developed a nanoporous thin film sensor that can reliably detect PSA and NEM in patient samples. The thin film sensor is fabricated from nanoporous anodic aluminum oxide and uses an optical Fabry-Perot intereferometric technique. This optical sensor has been tested for several assay paradigms, including nonspecific binding, reliability, accuracy, precision, and sensitivity. The results demonstrate that the optical nanoporous thin film sensor is reliable and extremely sensitive when used with only 0.5 µl of patient serum (or even less) to measure levels of the PSA and NEM, even in a non-cancer individual. When compared with the traditional ELISA test for PSA, the nanosensor assay is several-fold more sensitive, and it elimnates the need for labeled antigen, sample processing, complex equipment, and highly experienced individuals. These benefits, along with the low cost, should make the technology suitable for Point-of-Care application to accurately screen elderly male populations for PC and to monitor the progress of patients undergoing PC treatment. Nanoporous thin-film sensor was able to detect prostate cancer markers concentrations as low as 1 pg/ml for NEM and 20 pg/ml for PSA

Fast screening for diagnostic of heart ischemic episodes

Dissertação para obtenção do Grau de Doutor em Química SustentávelCardiovascular diseases (CVD) are top-killer chronic diseases, accounting for al-most half of the European deaths in 2010 (Eurostat data). Most recent statistics in Portuguese territory confirm this scenario, with cardiovascular diseases killing about 11 persons per 100000 inhabitants. Reducing these numbers is urgent and requires early, quick and efficient diagnostic of the specific heart condition. Thus, the main goal of this proposal is to develop a low cost sensing-devices based on newly synthesized sensory biomaterials for screening cardiac bi-omarkers in point-of-care. These were applied to screen the conventional bi-omarkers of clinical interest, all peptides in nature. These include troponin T (TnT), creatine kinase isoenzyme (CK-MB) and myoglobin (Myo). This was achieved by means of novel and low cost biosensing materials that were designed to display good selectivity to each biomarker, assembled on nanostructured sens-ing units and tested on serum samples. The design of novel biosensing materials consisted on synthesizing plastic antibodies by means of novel molecular im-printing (MI) and enzymatic approaches. Nanostructured sensing units were as-sembled by modifying the surface of standard conductive materials with the pre-viously indicated biomaterials. Standard conductive supports selected for this purpose were carbon and gold. Overall, it is expected that the emerging biosensing materials and platforms out coming from this project may contribute for the development of new non-inva-sive or minimally invasive methods with clinical application in the early screen-ing of chronic diseases and fast-screening in point-of-care (POC) of acute events

Tiny Medicine: Nanomaterial-Based Biosensors

Tiny medicine refers to the development of small easy to use devices that can help in the early diagnosis and treatment of disease. Early diagnosis is the key to successfully treating many diseases. Nanomaterial-based biosensors utilize the unique properties of biological and physical nanomaterials to recognize a target molecule and effect transduction of an electronic signal. In general, the advantages of nanomaterial-based biosensors are fast response, small size, high sensitivity, and portability compared to existing large electrodes and sensors. Systems integration is the core technology that enables tiny medicine. Integration of nanomaterials, microfluidics, automatic samplers, and transduction devices on a single chip provides many advantages for point of care devices such as biosensors. Biosensors are also being used as new analytical tools to study medicine. Thus this paper reviews how nanomaterials can be used to build biosensors and how these biosensors can help now and in the future to detect disease and monitor therapies