Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

Electrocatalysis by heme enzymes—applications in biosensing

Funding Information: The APC was funded by TIMB3 project, European Union's Horizon 2020 Research and Innovation Program grant agreement No 810856. Funding Information: Acknowledgments: We acknowledge the support from Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE 2020-Programa Operacional Competitividade e Internacionalização (POCI); from FCT—Fundação para a Ciência e a Tecnologia (PTDC/BIA-BFS/31026/2017 and 2020.05017.BD) and from the European Union's Horizon 2020 Research and Innovation Program, through TIMB3 and B-LigZymes projects (grant agreements No 810856 and 824017, respectively). We thank Edilson Galdino for critical reading of the manuscript and helpful discussions. Funding Information: Funding: The APC was funded by TIMB3 project, European Union's Horizon 2020 Research and Innovation Program grant agreement No 810856. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Heme proteins take part in a number of fundamental biological processes, including oxygen transport and storage, electron transfer, catalysis and signal transduction. The redox chemistry of the heme iron and the biochemical diversity of heme proteins have led to the development of a plethora of biotechnological applications. This work focuses on biosensing devices based on heme proteins, in which they are electronically coupled to an electrode and their activity is determined through the measurement of catalytic currents in the presence of substrate, i.e., the target analyte of the biosensor. After an overview of the main concepts of amperometric biosensors, we address transduction schemes, protein immobilization strategies, and the performance of devices that explore reactions of heme biocatalysts, including peroxidase, cytochrome P450, catalase, nitrite reductase, cytochrome c oxidase, cytochrome c and derived microperoxidases, hemoglobin, and myoglobin. We further discuss how structural information about immobilized heme proteins can lead to rational design of biosensing devices, ensuring insights into their efficiency and long-term stability.publishersversionpublishe

Electrochemical devices for cholesterol detection

Cholesterol can be considered as a biomarker of illnesses such as heart and coronary artery diseases or arteriosclerosis. Therefore, the fast determination of its concentration in blood is interesting as a means of achieving an early diagnosis of these unhealthy conditions. Electrochemical sensors and biosensors have become a potential tool for selective and sensitive detection of this biomolecule, combining the analytical advantages of electrochemical techniques with the selective recognition features of modified electrodes. This review covers the different approaches carried out in the development of electrochemical sensors for cholesterol, differentiating between enzymatic biosensors and non-enzymatic systems, highlighting lab-on-a-chip devices. A description of the different modification procedures of the working electrode has been included and the role of the different functional materials used has been discussed

Biosensors & enzymatic fuel cells based on direct electron transfer of dehydrogenases: characterization and applications

Il lavoro svolto durante i tre anni di dottorato è stato indirizzato verso lo sviluppo di nuovi metodi di sintesi ed elettrosintesi di nanomateriali metallici o carboniosi per il miglioramento del trasferimento elettronico diretto tra l’enzima e l’elettrodo. Questo miglioramento si traduce in un notevole incremento della sensibilità, stabilità e selettività dei biosensori sviluppati nonché della potenza generata da una pila enzimatica a biocombustibile, (Biofuel Cell). La prima parte della tesi riguarda lo studio e l’ottimizzazione del trasferimento elettronico diretto della cellobiosio deidrogenasi (CDH), un enzima appartenente alle flavoemeossidoreduttasi, costituito da due subunità dotate rispettivamente di cofattore FAD (subunità I) e heme b (subunità II). In questa parte abbiamo sintetizzato nanoparticelle di oro e di argento con un nuovo metodo “green”, che impiega come agente riducente la quercetina, un noto flavonoide presente in numerosi alimenti e bevande (es. tè, capperi, mirtilli, etc.). La reazione è stata condotta a temperatura ambiente e a pressione atmosferica senza ulteriore purificazione in quanto la quercetina è nota avere un comportamento stabilizzante delle sospensioni colloidali. Le suddette nanoparticelle sono state impiegate nella costruzione di biosensori per la determinazione del lattosio e di una pila a biocombustibile glucosio/ossigeno. Successivamente, abbiamo sviluppato un nuovo metodo per l’elettrodeposizione di nanoparticelle di oro in modo da ottenere una superficie nanostrutturata ordinata che ha portato allo sviluppo di un biosensore per la determinazione del glucosio nella saliva. La seconda parte della tesi riguarda lo studio del meccanismo del trasferimento elettronico diretto della fruttosio deidrogenasi (FDH), con particolare attenzione rivolta all’influenza dei cationi monovalenti e bivalenti, all’influenza della forma delle nanoparticelle sulla catalisi enzimatica, all’individuazione dei siti “heme” coinvolti nel trasferimento elettronico diretto attraverso l’accesso ad una porzione idrofobica dell’enzima, ed infine allo sviluppo di un biosensore per la determinazione del fruttosio realizzato immobilizzando la FDH su elettrodi di oro altamente poroso.The aim of this thesis is the study and the enhancement of the direct electron transfer of two different dehydrogenases, by means of a proper nanostructuration of the electrodes, for biosensors and enzymatic fuel cells (EFCs) development. Cellobiose dehydrogenase (CDH) is an extracellular enzyme belonging to the oxidoreductase group. CDH contains two subunits: (a) subunit I is the dehydrogenase domain (DHCDH), similar to the domain of other oxidoreductases, which belongs to the glucose-methanol-choline (GMC) oxidoreductase superfamily with a flavin adenine dinucleotide (FAD) co-factor covalently bound to the enzyme structure; (b) subunit II is the cytochrome domain (CYTCDH), which contains a heme b and acts as a built-in mediator by shuttling the electrons to a modified electrode. Both subunits are connected through a flexible linker responsible of the modulation of the internal electron transfer (IET) rate by varying the experimental conditions, such as changes of pH and divalent cations the concentration. Fructose dehydrogenase (FDH) is a membrane-bound flavocytochrome oxidoreductase which also belongs to the hemoflavoproteins family. FDH is a heterotrimeric membrane-bound enzyme complex with a molecular mass of 146.4 kDa, consisting of three subunits: (a) subunit I (DHFDH) is the catalytic domain with a covalently bound flavin adenine dinucleotide (FAD) cofactor, where D-(-)-fructose is involved in a 2H+/2e- oxidation to 5-dehydro-D-(-)-fructose; (b) subunit II (CYTFDH) acts as a built-in electron acceptor with three heme c moieties covalently bound to the enzyme scaffold and two of them involved in the electron transfer pathway; (c) subunit III is not involved in the electron transfer but plays a key role for the enzyme complex stability. The central target of the present thesis is the possibility to improve the electron transfer through the electrode nanostructuration, which can be realized by exploiting new nanomaterials as well as new nanostructuration methods (e.g. “green” synthesized metal nanoparticles, electrodeposition etc.). In the thesis much attention has been paid also to the understanding of the electron transfer pathway of FDH, which would be of fundamental interest in the near future for the development of highly sensitive biosensors and efficient EFCs. The biosensors realized and optimized in this thesis are prototypes of devices that, hopefully, will be commercially available on the market in the next future

Electrochemical chemically based sensors and emerging enzymatic biosensors for antidepressant drug detection: a review

Major depressive disorder is a widespread condition with antidepressants as the main pharmacological treatment. However, some patients experience concerning adverse reactions or have an inadequate response to treatment. Analytical chromatographic techniques, among other techniques, are valuable tools for investigating medication complications, including those associated with antidepressants. Nevertheless, there is a growing need to address the limitations associated with these techniques. In recent years, electrochemical (bio)sensors have garnered significant attention due to their lower cost, portability, and precision. Electrochemical (bio)sensors can be used for various applications related to depression, such as monitoring the levels of antidepressants in biological and in environmental samples. They can provide accurate and rapid results, which could facilitate personalized treatment and improve patient outcomes. This state-of-the-art literature review aims to explore the latest advancements in the electrochemical detection of antidepressants. The review focuses on two types of electrochemical sensors: Chemically modified sensors and enzyme-based biosensors. The referred papers are carefully categorized according to their respective sensor type. The review examines the differences between the two sensing methods, highlights their unique features and limitations, and provides an in-depth analysis of each sensor.info:eu-repo/semantics/publishedVersio

Recent advances in the development of electrochemical hydrogen peroxide carbon nanotube–based (bio)sensors

The relevance of H2O2 as biomarker for different neurodegenerative diseases and cancer has been one of the most significant incentives for the development of new (bio)sensors that allow a more sensitive, selective, fast, and stable quantification of H2O2. In this regard, the association of carbon nanotubes with hemoproteins, nanoparticles, and other nanostructures and different electrochemical transducers has offered new avenues for the construction of innovative H2O2 bioanalytical platforms. This short review highlights the most relevant contributions in the field of electrochemical (bio)sensors for H2O2 based on carbon nanotubes published in the period 2016–2018.Fil: Eguílaz Rubio, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Dalmasso, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Rubianes, María Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Gutierrez, Fabiana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Rodriguez, Marcela Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Gallay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: López Mujica, Michael Earvin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Ramírez, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Tettamanti, Cecilia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Montemerlo, Antonella Evelin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Rivas, Gustavo Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Nanostructures in hydrogen peroxide sensing

In recent years, several devices have been developed for the direct measurement of hydrogen peroxide (H2O2 ), a key compound in biological processes and an important chemical reagent in industrial applications. Classical enzymatic biosensors for H2O2 have been recently outclassed by electrochemical sensors that take advantage of material properties in the nano range. Electrodes with metal nanoparticles (NPs) such as Pt, Au, Pd and Ag have been widely used, often in combination with organic and inorganic molecules to improve the sensing capabilities. In this review, we present an overview of nanomaterials, molecules, polymers, and transduction methods used in the optimization of electrochemical sensors for H2O2 sensing. The different devices are compared on the basis of the sensitivity values, the limit of detection (LOD) and the linear range of application reported in the literature. The review aims to provide an overview of the advantages associated with different nanostructures to assess which one best suits a target application.Fil: Trujillo, Ricardo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Barraza, Daniela Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Zamora, Martín Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Cattani Scholz, Anna. Universitat Technical Zu Munich; AlemaniaFil: Madrid, Rossana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; Argentin

Applications of Graphene Quantum Dots in Biomedical Sensors

Due to the proliferative cancer rates, cardiovascular diseases, neurodegenerative disorders, autoimmune diseases and a plethora of infections across the globe, it is essential to introduce strategies that can rapidly and specifically detect the ultralow concentrations of relevant biomarkers, pathogens, toxins and pharmaceuticals in biological matrices. Considering these pathophysiologies, various research works have become necessary to fabricate biosensors for their early diagnosis and treatment, using nanomaterials like quantum dots (QDs). These nanomaterials effectively ameliorate the sensor performance with respect to their reproducibility, selectivity as well as sensitivity. In particular, graphene quantum dots (GQDs), which are ideally graphene fragments of nanometer size, constitute discrete features such as acting as attractive fluorophores and excellent electro-catalysts owing to their photo-stability, water-solubility, biocompatibility, non-toxicity and lucrativeness that make them favorable candidates for a wide range of novel biomedical applications. Herein, we reviewed about 300 biomedical studies reported over the last five years which entail the state of art as well as some pioneering ideas with respect to the prominent role of GQDs, especially in the development of optical, electrochemical and photoelectrochemical biosensors. Additionally, we outline the ideal properties of GQDs, their eclectic methods of synthesis, and the general principle behind several biosensing techniques.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

The influence of the shape of Au nanoparticles on the catalytic current of fructose dehydrogenase

Graphite electrodes were modified with triangular (AuNTrs) or spherical (AuNPs) nanoparticles and further modified with fructose dehydrogenase (FDH). The present study reports the effect of the shape of these nanoparticles (NPs) on the catalytic current of immobilized FDH pointing out the different contributions on the mass transfer–limited and kinetically limited currents. The influence of the shape of the NPs on the mass transfer–limited and the kinetically limited current has been proved by using two different methods: a rotating disk electrode (RDE) and an electrode mounted in a wall jet flow-through electrochemical cell attached to a flow system. The advantages of using the wall jet flow system compared with the RDE system for kinetic investigations are as follows: no need to account for substrate consumption, especially in the case of desorption of enzyme, and studies of product-inhibited enzymes. The comparison reveals that virtually identical results can be obtained using either of the two techniques. The heterogeneous electron transfer (ET) rate constants (kS) were found to be 3.8 ± 0.3 s−1 and 0.9 ± 0.1 s−1, for triangular and spherical NPs, respectively. The improvement observed for the electrode modified with AuNTrs suggests a more effective enzyme-NP interaction, which can allocate a higher number of enzyme molecules on the electrode surface