Bioelectronics for Amperometric Biosensors

The Discrete-to-Integrated Electronics group (D2In), at the University of Barcelona, in partnership with the Bioelectronics and Nanobioengineering Group (SICBIO), is researching Smart Self-Powered Bio-Electronic Systems. Our interest is focused on the development of custom built electronic solutions for bio-electronics applications, from discrete devices to Application-specific integrated circuit (ASIC) solutions. The integration of medical and electronic technologies allows the development of biomedical devices able to diagnose and/or treat pathologies by detecting and/or monitoring pathogens, multiple ions, PH changes, and so on. Currently this integration enables advances in various areas such as microelectronics, microfluidics, microsensors and bio-compatible materials which open the door to developing human body Lab-on-a-Chip implantable devices, Pointof- Care in vitro devices, etc. In this chapter the main attention is focused on the design of instrumentation related to amperometrics biosensor: biopotentiostat amplifiers and lock-in amplifiers. A potentiostat is a useful tool in many fields of investigation and industry performing electrochemical trials [1], so the quantity and variety of them is very extensive. Since they can be used in studies and targets as different as the study of chemical metal conversions [2] or carcinogenic cells detection, neuronal activity detection or Deoxyribonucleic acid (DNA) recognition, their characteristics are very varied..

Bioimpedance Technique for Point-of-Care Devices Relying on Disposable Label-Free Sensors – An Anemia Detection Case

In this chapter, the development of a point-of-care device for bio-medical applications has been discussed. Our main objective is to research new electronic solutions for the detection, quantification, and monitoring of important biological agents in medical environments. The proposed systems and technologies rely on label-free disposable sensors, with portable electronics for user-friendly, low-cost solutions for medical disease diagnosis, monitoring, and treatment. In this chapter, we will focus on a specific point-of-care device for cellular analysis, applied to the case of anemia detection and monitoring. The methodology used for anemia monitoring is based on hematocrit measurement directly from whole blood samples by means of impedance analysis. The designed device is based on straightforward electronic standards for low power consumption and low-cost disposable sensor for low volume samples, resulting in a robust and low power consumption device for portable monitoring purposes of anemia. The device has been validated through different whole blood samples to prove the response, effectiveness, and robustness to detect anemia

Combined dielectrophoresis and impedance systems for bacteria analysis in microfluidic on-chip platforms

Bacteria concentration and detection is time-consuming in regular microbiology procedures aimed to facilitate the detection and analysis of these cells at very low concentrations. Traditional methods are effective but often require several days to complete. This scenario results in low bioanalytical and diagnostic methodologies with associated increased costs and complexity. In recent years, the exploitation of the intrinsic electrical properties of cells has emerged as an appealing alternative approach for concentrating and detecting bacteria. The combination of dielectrophoresis (DEP) and impedance analysis (IA) in microfluidic on-chip platforms could be key to develop rapid, accurate, portable, simple-to-use and cost-effective microfluidic devices with a promising impact in medicine, public health, agricultural, food control and environmental areas. The present document reviews recent DEP and IA combined approaches and the latest relevant improvements focusing on bacteria concentration and detection, including selectivity, sensitivity, detection time, and conductivity variation enhancements. Furthermore, this review analyses future trends and challenges which need to be addressed in order to successfully commercialize these platforms resulting in an adequate social return of public-funded investments

An Instantaneous low-cost point-of-care anemia detection device

We present a small, compact and portable device for point-of-care instantaneous early detection of anemia. The method used is based on direct hematocrit measurement from whole blood samples by means of impedance analysis. This device consists of a custom electronic instrumentation and a plug-and-play disposable sensor. The designed electronics rely on straightforward standards for low power consumption, resulting in a robust and low consumption device making it completely mobile with a long battery life. Another approach could be powering the system based on other solutions like indoor solar cells, or applying energy-harvesting solutions in order to remove the batteries. The sensing system is based on a disposable low-cost label-free three gold electrode commercial sensor for 50 μL blood samples. The device capability for anemia detection has been validated through 24 blood samples, obtained from four hospitalized patients at Hospital Clínic. As a result, the response, effectiveness and robustness of the portable point-of-care device to detect anemia has been proved with an accuracy error of 2.83% and a mean coefficient of variation of 2.57% without any particular case above 5%

Non-invasive multiparametric approach to determine sweat-blood lactate bioequivalence

Many sweat-based wearable monitoring systems have been recently proposed, but the data provided by those systems often lack a reliable and meaningful relation to standardized blood values. One clear example is lactate, a relevant biomarker for both sports and health sectors, with a complex sweat–blood bioequivalence. This limitation decreases its individual significance as a sweat-based biomarker. Taking into account the insights of previous studies, a multiparametric methodology has been proposed to predict blood lactate from non-invasive independent sensors: sweat lactate, sweat rate, and heart rate. The bioequivalence study was performed with a large set of volunteers (>30 subjects) in collaboration with sports institutions (Institut Nacional d’Educació Física de Catalunya, INEFC, and Centre d’Alt Rendiment, CAR, located in Spain). A neural network algorithm was used to predict blood lactate values from the sensor data and subject metadata. The developed methodology reliably and accurately predicted blood lactate absolute values, only adding 0.3 mM of accumulated error when compared to portable blood lactate meters, the current gold standard for sports clinicians. The approach proposed in this work, along with an integrated platform for sweat monitoring, will have a strong impact on the sports and health fields as an autonomous, real-time, and continuous monitoring toolThe authors kindly acknowledge the support from the Spanish Ministerio de Indústria, Energía y Turismo (AEI Clusters Program, AEI2009L1CA011), Ministerio de Ciencia y Innovació n (PID2020-114070RB-I00), Agencia Estatal de Investigación (RED2018-102829-T and CPP2021-009021), and AGAUR (2019 DI 18 and 2021PROD00064)Postprint (published version

Bioimpedance monitoring system for pervasive biomedical applications

[eng] Nowadays, Point-of-Care (PoC) are making a shifting of the classical medical procedures and treatment protocols, enhancing the performance of medical surveillance in all the world. It is a reliable and very cost-effective solution, specially in mid to low income countries and areas where access to specialized clinical laboratories is very restricted. However, there are several operational challenges and technical issues that must be addressed when aiming for a clinical system based on PoC devices health surveillance, decentralized patient self-testing and centralized data management for devices, pathologies treatment and patient monitoring improvement. The aim of this research is to design, fabricate and test a novel device / technology for PoC instantaneous screening and monitoring of cellular species, to address these issues and add new functionalities to existing devices to create Lab-on-a-Chip devices. The technique used to cellular monitoring is based on direct measurement from samples by means of its inherent electrical impedance, in order to overcome the operational challenges present on the actual PoC devices on the market. The state of the art of PoC devices have been analysed to study their strengths and weakness, and determine the necessary improvements. This is, the development of instrumentation electronics, sensing systems as well as design protocols for truly PoC devices, relying on straight forward standards for economic, low power consumption, versatile, safe and reliable devices. The development of such technologies and devices is entailed to the evolution of these systems as implantable LOC devices for in vivo continuous monitoring of the patients. In this case, the development of simplified low-power electronics and sensing systems, leads to its miniaturization and integration in a single microchip with multiple functionalities. A discrete bench-top system for IA have been designed, fabricated and tested. The design and validation of different instrumentation electronics and sensing systems is presented, as well as design protocols for truly PoC devices. The device has been designed to perform an Impedance Spectrometry (IS) experiment in order to validate the whole device electronics as well as to characterize the sensing system and its interface accurately. A first approach to a portable and compact device for PoC early instantaneous detection of anaemia, relying on hematocrit (HCT) screening, is described. This device has been designed to work directly with fresh whole blood samples. An experimental set-up and protocol of operation have been defined for instant impedance detection to determine the system detection accuracy, sensitivity and coefficient of variation. As you will notice, the device has been developed using prototyping tools from National Instruments for fast development and validation, as well as application functionalities. Moreover, the possibilities of the integration of this technology within other devices, for increased functionalities, have been validated. The experiments were carried out with different instrumentations front-end as well as different sensing systems typologies, and the same back-end electronics for signal processing and system control. The analysed samples and its environment were dramatically different: laboratory sample formed by E. coli 5K strains working as a monitoring functionality of a DEP-enhanced concentrator for automated detection and concentration of bacteriological species. Finally, it has been developed a specific PoC device for HCT detection and validated through a clinical assessment with whole blood samples. The design is based in the previously presented device’s electronic instrumentation and sensing system with the addition of an economic and low power back-end solution. A clinical study has been performed and the results obtained during the experimental procedures are shown, analysed and discussed. We summarize the conclusions obtained after this research and recommend future developments that could be done to develop truly last generation PoC devices and integrated LOC single-chip devices.[cat] L’objectiu de la tesi és la realització d’equipaments electrònics per aplicacions biomèdiques de caràcter Poin-of-Care en entorns d’investigació, control i tractament clínic. Aquest projecte es troba en el marc de les activitats de recerca del grup, on el desenvolupament d’electròniques d’interface amb el mon biomèdic i la recerca de noves tecnologies i aplicacions d’instrumentació són unes de les principals tasques que porten a terme. Donades aquestes consideracions, a l’últim any s’ha definit un camí dintre dels sistemes d’instrumentació PoC orientats al control d’agents biològics cel·lulars amb tècniques d’anàlisi d’impedància. Aquests dispositius estan basats en dos conceptes claus: el disseny d’instrumentació electrònica senzilla, econòmica i de baix consum, així com sistemes de sensat versàtils i d’un sol us. D’aquesta manera, és possible desenvolupar equipaments versàtils, portables i de baix cost que poden aportar gran rendiment en diferents camps de la biomedicina. Amb aquestes premisses, s’ha desenvolupat un equipament d’anàlisi d’impedància independent del sistema de sensat, el que comporta la possibilitat d’utilitzar multitud de tipus de sistemes de sensat. Aquest equipament, consta d’una senzilla instrumentació electrònica basada en un sistema de sensat preparat per diferents tipus de sensors, tot controlat per un microprocessador encarregat del control automatitzat del hardware, post-processat de dades i comunicació amb un ordinador remot. El sistema és capaç de treballar en un rang de freqüències molt ampli, amb diferent tipus de potència de senyal i diferent tipus d’anàlisi i representació, com ara Electrochemical Impedance Spectroscopy (EIS) amb representació amb diagrames de Bode i Nyquist, o la selecció de punts de freqüencials concrets per un tipus d’anàlisi més específic per a un experiment biomèdic més concret, senzill i ràpid. Es tracta d’un equipament econòmic, fiable i senzill per l’anàlisi d’hematòcrit, que aporta avenços com la gran capacitat d’integració en ambients clínics, la possibilitat de fer un control medico sanitari instantani i reportar telemàticament els resultats o la possibilitat d’implementar un sistema de control mèdic integrat i automatitzat

Amperometric and impedance monitoring systems for biomedical applications

The book presents the conception and realization of a pervasive electronic architecture for electrochemical applications, focusing on electronic instrumentation design and device development, particularly in electrochemical Point-of-Care and Lab-on-a-Chip devices, covering examples based on amperometric (DC) and impedance detection (AC) techniques. The presented electronics combine tailored front-end instrumentation and back-end data post-processing, enabling applications in different areas, and across a variety of techniques, analytes, transducers and environments. It addresses how the electronics are designed and implemented with special interest in the flow process: starting from electronic circuits and electrochemical biosensor design to a final validation and implementation for specific applications. Similarly, other important aspects are discussed throughout the book, such as electrochemical techniques, different analytes, targets, electronics reliability and robustness. The book also describes the use of the presented electronics in different electrochemical applications through some examples: instantaneous and non-destructive cellular monitoring and portable glucose monitoring device. Moreover, the book aims to introduce a comprehensive approach to electronic circuits, techniques and electrochemical sensors in POC devices to a general audience of students in biomedical and electronics engineering, scientists, and engineers

Dossier de Pràctiques: Estudi i disseny d'un potenciostat per mesurar una cel·la electroquímica

Recull de tots els guions de les pràctiques per l'assignatura d'electrònica aplicada del Grau d'enginyera Biomèdica de la Universitat de Barcelona. El conjunt de les pràctiques es basen en la metodologia PBL guiada mitjançant el desenvolupament d'un instrument de mesura de sensors electroquímics anomenat potenciostat.GIDC IDEES-TIC (RIMDA

Dossier de Pràctiques: Estudi i disseny d'un potenciostat per mesurar una cel·la electroquímica

Recull de tots els guions de les pràctiques per l'assignatura d'electrònica aplicada del Grau d'enginyera Biomèdica de la Universitat de Barcelona. El conjunt de les pràctiques es basen en la metodologia PBL guiada mitjançant el desenvolupament d'un instrument de mesura de sensors electroquímics anomenat potenciostat.GIDC IDEES-TIC (RIMDA