Current nanotechnology advances in diagnostic biosensors

Current diagnostics present challenges that are imposed by increased life expectancy in the worldwide population. These challenges are related, not only to satisfy the need for higher performance of diagnostic tests, but also to the capacity of creating pointâ ofâ care, wearable, multiplexing and implantable diagnostic platforms that will allow early detection, continuous monitoring and treatment of health conditions in a personalized manner. These health challenges are translated into technological issues that need to be solved with multidisciplinary knowledge. Nanoscience and technology play a fundamental role in the development of miniaturized sensors that are cheap, accurate, sensitive and consume less power. At nanometre scale, these materials possess higher volumeâ toâ surface ratio and display novel properties (composition, charge, reactive sites, physical structure and potential) that are exploited for sensing purposes. These nanomaterials can therefore be integrated into diagnostic sensing platforms allowing the creation of novel technologies that tackle current health challenges. These nanomaterialâ enhanced sensors are extremely diverse, since they use numerous types of materials, nanostructures and detection modes for a multitude of biomarkers. The purpose of this review is to summarize the current stateâ ofâ theâ art of nanomaterialâ enhanced sensors, emphasizing and discussing the diagnostic challenges that are addressed by the different engineering and nanotechnology approaches. This review also aims to identify the drawbacks of nanomaterialâ enhanced sensors, as well as point out future developmental directions.This research was funded by FCT- FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA, grant numbers: PTDC/EMD-EMD/31590/2017 and PTDC/BTM-ORG/28168/2017

3D biosensors in advanced medical diagnostics of high mortality diseases

Cardiovascular diseases, cancer, and diabetes are high mortality diseases, which account for almost two thirds of all deaths worldwide. Their early detection and continuous evaluation is fundamental for an improved patient prognosis and reduced socioeconomic impact. Current biosensor technologies are typically based on the analysis of whole blood samples from patients for the detection of disease-specific biomarkers. However, these technologies display serious shortcomings, such as reduced sensitivity and dynamic range, limited in vivo applicability, and lack of continuous monitoring. There is the urgent need for new diagnostic and treatment follow-up tools, which allow for the early detection of the pathology as well as for the continuous monitoring of the physiological response to specific therapies. During the last years, a new generation of biosensor technologies with improved performance has emerged in the biomedical sector. The combination of advanced biomaterial methods, biochemical tools, and micro/nanotechnology approaches has resulted in the development of innovative three-dimensional (3D) biosensor platforms for advanced medical diagnosis. In this review, we report the most recent advances in the field of 3D biosensors for clinical applications, focusing on the diagnosis and monitoring of cardiovascular diseases, cancer, and diabetes. We discuss about their clinical performance compared to standard biosensor technologies, their implantable capability, and their integration into microfluidic devices to develop clinically-relevant models. Overall, we anticipate that 3D biosensors will drive us toward a new paradigm in medical diagnosis, resulting in real-time in vivo biosensors capable to significantly improve patient prognosis.V.M.C., S.C.K, and D.C. acknowledge thefinancial support from theEuropean Union Framework Programme for Research and InnovationHorizon 2020 on Forefront Research in 3D Disease Cancer Models asinvitroScreening Technologies (FoReCaST) under Grant agreement no.668983. V.M.C also thanks the Portuguese Foundation for Science andTechnology (FCT) for his distinction attributed under the FCTInvestigator program (IF/01214/2014). D.C. and S.C.K also acknowl-edge the support from the FCT under the scope of the project ModellingCancer Metastasis into the Human Microcirculation System using aMulti-organ-on-a-Chip Approach (2MATCH) (PTDC/BTM-ORG/28070/2017) funded by the Programa Operacional Regional do Norte sup-ported by Fundo Europeu de Desenvolvimento Regional (FEDER). A.I.B.acknowledges thefinancial support of project FROnTHERA (NORTE-01-0145-FEDER-000023

Chitosan micro-membranes with integrated gold nanoparticles as an LSPR-based sensing platform

Currently, there is an increasing need to develop highly sensitive plasmonic sensors able to provide good biocompatibility, flexibility, and optical stability to detect low levels of analytes in biological media. In this study, gold nanoparticles (Au NPs) were dispersed into chitosan membranes by spin coating. It has been demonstrated that these membranes are particularly stable and can be successfully employed as versatile plasmonic platforms for molecular sensing. The optical response of the chitosan/Au NPs interfaces and their capability to sense the medium’s refractive index (RI) changes, either in a liquid or gas media, were investigated by high-resolution localized surface plasmon resonance (HR-LSPR) spectroscopy, as a proof of concept for biosensing applications. The results revealed that the lowest polymer concentration (chitosan (0.5%)/Au-NPs membrane) presented the most suitable plasmonic response. An LSPR band redshift was observed as the RI of the surrounding media was incremented, resulting in a sensitivity value of 28 ± 1 nm/RIU. Furthermore, the plasmonic membrane showed an outstanding performance when tested in gaseous atmospheres, being capable of distinguishing inert gases with only a 10−5 RI unit difference. The potential of chitosan/Au-NPs membranes was confirmed for application in LSPR-based sensing applications, despite the fact that further materials optimization should be performed to enhance sensitivity.This research was sponsored by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UIDB/04650/2020, by the project CO2Plasmon with reference EXPL/CTM-REF/0750/2021 and by the project with reference PTDC/CTM-CTM/2846/2020. Diana I. Meira acknowledges her Ph.D. Scholarship from FCT, with reference SFRH/BD/143262/2019. Manuela Proença acknowledges her Ph.D. Scholarship from FCT, with reference SFRH/BD/137076/2018

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazili an centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome83289298CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SUL - FAPERGSSem informaçãoSem informação2006/60402-1; 2010/51547-1; 2013/01476-9; 2014/06570-6; 2009/50575-4; 2010/51546-5; 2012/21942-116/2551-0000482-

Spatial Evaluation and Modeling of Dengue Seroprevalence and Vector Density in Rio de Janeiro, Brazil

Dengue is a major public health problem in many tropical regions of the world, including Brazil, where Aedes aegypti is the main vector. We present a household study that combines data on dengue fever seroprevalence, recent dengue infection, and vector density, in three neighborhoods of Rio de Janeiro, Brazil, during its most devastating dengue epidemic to date. This integrated entomological–serological survey showed evidence of silent transmission even during a severe epidemic. Also, past exposure to dengue virus was highly associated with age and living in areas of high movement of individuals and social/commercial activity. No association was observed between household infestation index and risk of dengue infection in these areas. Our findings are discussed in the light of current theories regarding transmission thresholds and relative role of mosquitoes and humans as vectors of dengue viruses

Production of electrospun fast-dissolving drug delivery systems with therapeutic eutectic systems encapsulated in gelatin

Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/ v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.The research leading to these results has received funding from Fundação para a Ciência e a Tecnologia (FCT) through the projects ENIGMA - PTDC/EQU-EPR/ 121491/2010 and UID/CTM/50025/2013, LAQVREQUIMTE: UID/QUI/50006/2013, UCIBIO-REQUIMTE: UID/Multi/04378/2013 (co-financed by the ERDF under the PT2020 Partnership Agreement [POCI-01-0145-FEDER- 007728]) and by FEDER through the COMPETE 2020 Programme. Marta Martins is grateful for financial support from FCT through the grant BIM/PTDC/EQUEPR/121491/ 2010/ENIGMA. This research has also received funding from the European Union Seventh Framework Programme (FP7/ 2007-2013) under grant agreement number REGPOTCT2012-316331-POLARIS and from the project BNovel smart and biomimetic materials for innovative regenerative medicine approaches^ RL1 - ABMR - NORTE-01-0124- FEDER-000016) co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine

Background: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.info:eu-repo/semantics/publishedVersio