ABSTRACT
In this scientific work, we demonstrate, for the first time, a new biosensing system and procedure to measure specifically the total Tau (T-Tau) protein in serum, one of the most relevant biomarkers of Alzheimer's disease (AD). AD is a progressive brain disorder that produces neuronal and cognitive dysfunction and affects a high percentage of people worldwide. For this reason, diagnosing AD at the earliest possible stage involves improving diagnostic systems. We report on the use of interferometric bio-transducers integrated with 65 microwells forming diagnostic KITs read-out by using the Interferometric Optical Detection Method (IODM). Moreover, biofunctionalized silicon dioxide (SiO2) nanoparticles (NPs) acting as interferometric enhancers of the bio-transducers signal allow for the improvement of both the optical read-out signal and its ability to work with less-invasive biological samples such as serum instead of cerebrospinal fluid (CSF). As a result, in this paper, we describe for the first time a relevant diagnostic alternative to detect Tau protein at demanding concentrations of 10 pg/mL or even better, opening the opportunity to be used for detecting other relevant AD-related biomarkers in serum, such as ß-amyloid and phosphorylated Tau (P-Tau), neurofilaments, among others that can be considered relevant for AD.
Subject(s)
Alzheimer Disease , Nanoparticles , Humans , Alzheimer Disease/diagnosis , Silicon Dioxide , tau Proteins , Amyloid beta-Peptides , Biomarkers , Peptide Fragments/cerebrospinal fluidABSTRACT
Despite the remarkable development related to Point-of-Care devices based on optical technology, their difficulties when used outside of research laboratories are notable. In this sense, it would be interesting to ask ourselves what the degree of transferability of the research work to the market is, for example, by analysing the relation between the scientific work developed and the registered one, through patent. In this work, we provide an overview of the state-of-the-art in the sector of optical Point-of-Care devices, not only in the research area but also regarding their transfer to market. To this end, we explored a methodology for searching articles and patents to obtain an indicator that relates to both. This figure of merit to estimate this transfer is based on classifying the relevant research articles in the area and the patents that have been generated from these ones. To delimit the scope of this study, we researched the results of a large enough number of publications in the period from 2015 to 2020, by using keywords "biosensor", "optic", and "device" to obtain the most representative articles from Web of Science and Scopus. Then, we classified them according to a particular classification of the optical PoC devices. Once we had this sampling frame, we defined a patent search strategy to cross-link the article with a registered patent (by surfing Google Patents) and classified them accordingly to the categories described. Finally, we proposed a relative figure called Index of Technology Transference (IoTT), which estimates to what extent our findings in science materialized in published articles are protected by patent.
Subject(s)
Point-of-Care Systems , Technology Transfer , BiotechnologyABSTRACT
In the present work, highly multiplexed diagnostic KITs based on an Interferometric Optical Detection Method (IODM) were developed to evaluate six Coronavirus Disease 2019 (COVID-19)-related biomarkers. These biomarkers of COVID-19 were evaluated in 74 serum samples from severe, moderate, and mild patients with positive polymerase chain reaction (PCR), collected at the end of March 2020 in the Hospital Clínico San Carlos, in Madrid (Spain). The developed multiplexed diagnostic KITs were biofunctionalized to simultaneously measure different types of specific biomarkers involved in COVID-19. Thus, the serum samples were investigated by measuring the total specific Immunoglobulins (sIgT), specific Immunoglobulins G (sIgG), specific Immunoglobulins M (sIgM), specific Immunoglobulins A (sIgA), all of them against SARS-CoV-2, together with two biomarkers involved in inflammatory disorders, Ferritin (FER) and C Reactive Protein (CRP). To assess the results, a Multiple Linear Regression Model (MLRM) was carried out to study the influence of IgGs, IgMs, IgAs, FER, and CRP against the total sIgTs in these serum samples with a goodness of fit of 73.01% (Adjusted R-Squared).
Subject(s)
COVID-19 Testing , COVID-19 , Biomarkers , C-Reactive Protein , COVID-19/diagnosis , COVID-19 Testing/instrumentation , Ferritins , Humans , Immunoglobulin A, Secretory , Reagent Kits, Diagnostic , SARS-CoV-2ABSTRACT
A design study of a nanostructured two-dimensional plasmonic crystal based on aluminum and polymeric material for label-free optical biosensing is presented. The structure is formed of Al nanohole and nanodisk array layers physically separated by a polymeric film. The photonic configuration was analyzed through finite-difference time-domain (FDTD) simulations. The calculated spectral reflectance of the device exhibits a surface plasmon polariton (SPP) resonance feature sensitive to the presence of a modeled biolayer adhered onto the metal surfaces. Simulations also reveal that the Al disks suppress an undesired SPP resonance, improving the device performance in terms of resolution as compared to that of a similar configuration without Al disks. On the basis of manufacturability issues, nanohole diameter and depth were considered as design parameters, and a multi-objective optimization process was employed to determine the optimum dimensional values from both performance and fabrication points of view. The effect of Al oxidation, which is expected to occur in an actual device, was also studied.