Self-Powered Portable Electronic Reader for Point-of-Care Amperometric Measurements

In this work, we present a self-powered electronic reader (e-reader) for point-of-care diagnostics based on the use of a fuel cell (FC) which works as a power source and as a sensor. The self-powered e-reader extracts the energy from the FC to supply the electronic components concomitantly, while performing the detection of the fuel concentration. The designed electronics rely on straightforward standards for low power consumption, resulting in a robust and low power device without needing an external power source. Besides, the custom electronic instrumentation platform can process and display fuel concentration without requiring any type of laboratory equipment. In this study, we present the electronics system in detail and describe all modules that make up the system. Furthermore, we validate the device's operation with different emulated FCs and sensors presented in the literature. The e-reader can be adjusted to numerous current ranges up to 3 mA, with a 13 nA resolution and an uncertainty of 1.8%. Besides, it only consumes 900 µW in the low power mode of operation, and it can operate with a minimum voltage of 330 mV. This concept can be extended to a wide range of fields, from biomedical to environmental applications

Electrochemical Plug-and-Power e-readers for Point-of-Care Applications

Point-of-Care diagnostic tests enable monitor health conditions and obtain fast results close to the patient, reducing medical costs, and allowing the control of infectious outbreaks. The interest in developing Point-of-Care devices is increasing due to they are suitable for a wide variety of applications. This doctoral thesis focuses on the development of Plug-and-Power electronic readers (e- readers) for electrochemical detections and the demonstration of their possibilities as Point-of-Care diagnostic testing. The solutions proposed in this study make it possible to improve Point-of-Care tests whose premises are laboratory decentralization, personalized medicine, rapid diagnosis, and improvement of patient care. Developed electronic readers can be powered from a conventional system, such as a USB port or a lithium battery, or can be defined as self-powered systems, capable of extracting energy from alternative energy sources, such as fuel cells, defining Plug-and-Power systems. The designed electrochemical detection devices in this thesis are based on low-power consumption electronic instrumentation circuits. These circuits are capable of controlling the sensing element, measuring its response, and representing the result quantitatively. The implemented devices can work with both electrochemical sensors and fuel cells. Furthermore, it is possible to adapt its measurement range, enabling its use in a wide variety of applications. Thanks to their reduced energy consumption, some of these developments can be defined as self-powered platforms able to operate only with the energy extracted from the biological sample, which in turn is monitored. These devices are easy-to-use and plug-and-play, enabling those unskilled individuals to carry out tests after prior training. Moreover, thanks to their user-friendly interface, results are clear and easy to understand. This doctoral dissertation is presented as an article compendium and composed of three publications detailed in chronological order of publication. The first contribution describes an innovative portable Point-of-Care device able to provide a quantitative result of the glucose concentration of a sample. The proposed system combines an e-reader and a disposable device based on two elements: a glucose paper-based power source, and a glucose fuel cell-based sensor. The battery-less e-reader extracts the energy from the disposable unit, acquires the signal, processes it, and shows the glucose concentration on a numerical display. Due to low-power consumption of the e-reader, the whole electronic system can operate only with the energy extracted from the disposable element. Furthermore, the proposed system minimizes the user interaction, which only must deposit the sample on the strip and wait a few seconds to see the test result. The second publication validates the e-reader in other scenarios following two approaches: using fuel cells as a power element, and as a dual powering and sensing element. The device was tested with glucose, urine, methanol, and ethanol fuel cells and electrochemical sensors in order to show the adaptability of this versatile concept to a wide variety of fields beyond clinical diagnostics, such as veterinary or environmental fields. The third study presents a low-cost, miniaturized, and customizable electronic reader for amperometric detections. The USB-powered portable device is composed of a full- custom electronic board for signal acquisition, and software, which controls the systems, represents and saves the results. In this study, the performance of the device was compared against three commercial potentiostats, showing comparable results to those obtained using three commercial systems, which were significantly more expensive. As proof of concept, the system was validated by detecting horseradish peroxidase samples. However, it could be easily extended its scope and measure other types of analytes or biological matrices since it can be easily adapted to detect currents a wide range of currents.Las pruebas de diagnostico Point-of-Care permiten monitorizar las condiciones de salud y obtener resultados rápidos cerca del paciente, reduciendo los costes médicos y permitiendo controlar brotes infecciosos. El interés por desarrollar dispositivos de Point- of-Care está aumentando debido a que son aplicables a una amplia variedad de aplicaciones. Esta tesis doctoral se centra en el desarrollo de lectores electrónicos (e-readers) Plug-and- Power para detecciones electroquímicas y la demostración de sus posibilidades como pruebas de diagnóstico de punto de atención (Point-of-Care). Las soluciones propuestas en este trabajo permiten mejorar las pruebas Point-of-Care, cuyas premisas son la descentralización de laboratorio, la medicina personalizada, el diagnóstico rápido y la mejora de la atención al paciente. Los lectores electrónicos desarrollados pueden ser alimentados desde un sistema convencional, como puede ser un puerto USB o una batería de litio, o definirse como sistemas autoalimentados, capaces de extraen energía de fuentes alternativas de energía, como celdas de combustible (fuel cells), definiendo así sistemas Plug-and-Power. Los dispositivos de detección electroquímica diseñados se basan en circuitos de instrumentación electrónica de bajo consumo. Estos circuitos son capaces controlar el elemento de sensado, medir su respuesta y representar el resultado de forma cuantitativa. Los dispositivos implementados pueden trabajar tanto con sensores electroquímicos como con fuel cells. Además, es posible adaptar su rango de medida, permitiendo su utilización en una amplia variedad de aplicaciones. Gracias a su reducido consumo de energía, algunos de estos desarrollos pueden definirse como plataformas autoalimentadas capaces de operar solo con la energía extraída de la muestra biológica, que a su vez es monitorizada. Estas plataformas electrónicas son fáciles de usar y Plug-and-Play, permitiendo que personas no cualificadas puedan utilizarlas después de un previo entrenamiento. Además, gracias a su interfaz fácil de usar, los resultados son claros y fáciles de interpretar

Penitsilliinide jääkide määramine piimas läbivoolulise biosensorsüsteemi abil

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Penitsilliinid on beetalaktaamide hulka kuuluvad antibiootikumid, mida kasutatakse peamiselt Gram-positiivsete bakterite poolt tekitatud haiguste raviks. Penitsilliini ja teiste antibiootikumide jäägid piimas tekitavad inimestel allergilisi reaktsioone ning soodustavad resistentsete mikroobitüvede teket, mistõttu on antibiootikumide jääkide lubatud sisaldus toidus rangelt reguleeritud. Tavaliselt kasutatakse antibiootikumide jääkide määramiseks piimas mitmesuguseid kromatograafial põhinevaid meetodeid ning erinevaid mikroobse inhibeerimise ja immuunoretseptor teste. Kuid tihtipeale on need meetodid kallid ning aeganõudvad. Üheks võimalikuks alternatiiviks traditsioonilistele analüüsimeetoditele on biosensorite kasutamine. Biosensorite eeliseks on nende lihtsus, suhteline odavus ning kiirus, mis võimaldab nende kasutamist kiireteks analüüsideks reaalajas. Käesoleva doktoritöö eesmärgiks oli välja töötada ning testida biosensorsüsteem penitsilliinide jääkide kiireks määramiseks toorpiimas. Selleks, et kiirendada eksperimentaalsete andmete analüüsi, me pakkusime välja matemaatiline mudel biosensori kalibratsiooniparameetrite arvutamiseks ning uurisime võimalusi biosensorites toimuvate äratundmisreaktsioonide kiirendamiseks. Töö praktilises osas testisime biosensori kasutamist penitsilliinide jääkide kiireks määramiseks toorpiimas. Töö tulemusena leidsime, et glükoosi tase piimas on heaks indikaatoriks penitsilliini jääkide määramiseks toorpiimas. Seega, kasutatud biosensorsüsteem on rakendatav kiireks penitsillinide jääkide määramiseks toorpiimas piimafarmides. Kiire lüpstava piima analüüs võimaldaks mittekvaliteetse piima õigeaegset eraldamist kvaliteetsest toodangust ning kogu toodetava piima kvaliteedi tõstmist. Kasutatud biosensorsüsteemi on erinevate antibiotikumide jääkide määramiseks toorpiimas võimalik tulevikus modifitseerida täiendavate biosensorite lisamisega.The use of antibiotics for the treatment of food-producing animals generates the risk to human health due to the transmission of the residues and metabolites of these compounds into food chain. In addition, scientists and health experts also fear that wide application of antimicrobial agents, including the first discovered penicillin antibiotics, is contributing to the rise and spread of antibiotic-resistant bacteria. At present, strict regulations have been established for the levels of antibiotic residues and metabolites in food of animal origin. Antibiotic residues in food are commonly determined with the help of chromatography and special tests. The application of biosensors for the detection of antibiotic residues in milk is a good alternative to traditional methods. The benefits of biosensors are their low cost, simplicity and possibility for rapid real-time analysis. The main goal of the present work was to propose a rapid method for real-time detection of penicillins’ residues in milk, to propose a simple but sufficiently accurate model to describe the quick response of biosensor and to test this biosensorsystem. The application of the model allowed to predict optimal biosensor parameters for obtaining maximal sensitivity and high stability on one hand, and to obtain fast results from the initial phase of the reaction on the other hand. The biosensor was applied to detect the penicillins in the milk of cows with mastitis. Glucose concentration in their milk decreased significantly compared to glucose levels in high quality milk, enabling to use glucose concentration as an indicator of the presence of penicillin residues in milk. The studied biosensor set-up has high potential to serve as a system for real-time automatic control of the quality of raw milk in the milk production farms. The application of this system allows the separation of substandard milk from the milk flow prior to milk collection tank. The system can be further modified by attaching additional biosensors to build up a more robust biosensor array, where the signals of individual biosensors form a typical pattern of milk sample, which changes in the presence of different antibiotics

Integrated impedance spectroscopy biosensors

textAffinity-based biosensors, or in short biosensors, are extremely powerful and versatile analytical tools which are used for the detection of a wide variety of bio-molecules. In recent times, there has been a need for developing low-cost and portable affinity-based biosensor platforms. Such systems need to have a high density of detection sites (i.e biosensing elements) in order to simultaneously detect multiple analytes in a single sample. This has led to the creation of integrated biosensors, which make use of integrated circuits (ICs) for bio-molecular detection. In such systems, it has been demonstrated that by taking advantage of the capabilities of semiconductor and very large scale integrated (VLSI) circuit fabrication processes, it is possible to build compact miniaturized biosensors, which can be used in wide variety of applications such as in molecular diagnostics and for environmental monitoring. Among the various detection modalities for biosensors, Electrochemical Impedance Spectroscopy (EIS) permits real-time detection and has label-free detection capabilities. EIS is fully electronic in nature. Hence, it can be implemented using standard IC technologies. The versatility and ease of integration of EIS makes it a promising candidate for developing integrated biosensor platforms. In this thesis, we first examine the underlying principles of EIS method of biosensing. By analyzing an immunosensor assay as an example, we show that EIS based biosensing is a highly sensitive detection method, which can be used for the detection of a wide variety of analytes. Since EIS relies on small impedance changes in order to perform detection, it requires highly accurate models for the electrode-electrolyte systems. Hence, we also introduce a compact modeling technique for the distributed electrode-electrolyte systems with non-uniform electric fields, which is capable of modelling noise and other non-idealities in EIS. In the second part of this thesis, we describe the design and implementation of an integrated EIS biosensor array, built using a standard complementary metal-oxide-semiconductor (CMOS) process. The chip is capable of measuring admittance values as small as 10nS and has a wide dynamic range (90dB) over a wide range of frequencies (10Hz-50MHz). We also report the results obtained from the DNA and protein detection experiments performed using this chip.Electrical and Computer Engineerin