Light-Addressing and Chemical Imaging Technologies for Electrochemical Sensing

Visualizing chemical components in a specimen is an essential technology in many branches of science and practical applications. This book deals with electrochemical imaging techniques based on semiconductor devices with capability of spatially resolved sensing. Two types of such sensing devices have been extensively studied and applied in various fields, i.e., arrayed sensors and light-addressed sensors. An ion-sensitive field-effect transistor (ISFET) array and a charge-coupled device (CCD) ion image sensor are examples of arrayed sensors. They take advantage of semiconductor microfabrication technology to integrate a large number of sensing elements on a single chip, each representing a pixel to form a chemical image. A light-addressable potentiometric sensor (LAPS), on the other hand, has no pixel structure. A chemical image is obtained by raster-scanning the sensor plate with a light beam, which can flexibly define the position and size of a pixel. This light-addressing approach is further applied in other LAPS-inspired methods. Scanning photo-induced impedance microscopy (SPIM) realized impedance mapping and light-addressable electrodes/light-activated electrochemistry (LAE) realized local activation of Faradaic processes. This book includes eight articles on state-of-the-art technologies of light-addressing/chemical imaging devices and their application to biology and materials science

Label-free detection of tuberculosis DNA with capacitive field-effect biosensors

The detection of pathogens from sample material from infected patients is the basis on which a considerable medical diagnosis can be made. Pathogens can be clearly identified based on their genomic material (DNA). A large number of different DNA detection methods with individual advantages and disadvantages have been established. If such methods should be used for certain applications, e.g. for point-of-care measurements, there are a number of requirements which should be considered: A measurement must be performed very fast, inexpensive, simple and reliable. It has been shown that label-free detection principles in particular the field-effect based detection-methods, meet the given requirements. In this thesis, the development of a new measuring method for the detection of DNA (with sequences from Mycobacterium tuberculosis) using a field-effect sensor, is described. The electrolyte-insulator-semiconductor (EIS) structure was selected as the basis for the sensor chip because it has the simplest structure of all field-effect sensors and is inexpensive to manufacture. EIS sensors are capacitive structures that can be read out using an impedance analyzer. The measured value is directly related to the surface potential of the sensor. If the DNA, which is negatively charged in solution, is brought close to the sensor surface, this causes a change in the surface potential via a change in the charge situation on the chip surface. This change in potential can be read out with the help of the EIS sensors: The detection method is based on the detection of a hybridization event on the sensor surface. The surface is modified with a probe single-strand DNA (ssDNA) which has a known sequence that is complementary to the ssDNA that is intended to be detected. As soon as the target ssDNA reaches the surface, a hybridization can occur, whereby a signal shift can be measured. The signal shift is caused by the additional negative charge of the hybridized target DNA molecules. In the case of non-complementary target DNA (ncDNA), there is no hybridization and the signal remains constant. The immobilization of the catcher ssDNA was carried out with by a surface modification using positively-charged polyelectrolyte (poly (allylamine hydrochloride), PAH). Compared to other immobilization strategies that are described in the literature, the capture ssDNA binds adsorptively to the sensor surface, which simplifies the preparation and can be carried out quickly and cheaply. The main topics of this thesis cover the selection of the sensor layout (EIS sensor with SiO2 as surface oxide), the selection and optimization of the surface modification (using PAH), the verification of the forming of double-stranded DNA and the evaluation of the measurement data acquisition by means of capacitive measurements. Due to the adsorptive binding, the DNA strands likely lie flat on the sensor surface. This means that the negative charge of the DNA is located closely to the surface, which means that a high measurement signal can be recorded. The developed protocol was also used with light-addressable potentiometric sensors (LAPS). LAPS are structurally very similar to EIS sensors and have the advantage that they can detect changes in the surface potential in a spatially resolved manner. This makes it possible, for example, to arrange an array so that several DNA experiments can be carried out simultaneously on one chip. However, the measurement setup is more complex because of the necessity of a light source. The measurement of the DNA hybridization on the sensor surface was realized by using the developed method: PAH/ssDNA-modified EIS chips were brought into contact with cDNA solutions. Measurable surface potential changes could show that the hybridization was successful. In direct comparison with experiments where ncDNA was applied to the modified sensor, signal differences of about 11 times higher were measured for cDNA than for ncDNA. The developed method also allows a very simple reuse of the chip by just a repeating of the modification steps on an already used chip. This reusability of the sensors was investigated by performing up to five repetitive surface modification and DNA attachment experiments sequentially with just one chip. A steady decrease in the sensor signal could be observed after each additional layer (PAH or DNA); however, this observation is related to the Debye screening effect. Finally, the developed biosensor was used to detect PCR-amplified cDNA. A detection of the target cDNA was successful and significant, although the additional (interfering) substances in the solution, that were necessary for the PCR process (enzymes, etc.), disturbed the measurement signal. Measurements in which a concentration series of cDNA were used to determine the lower detection limit (0.3 nM) and the sensitivity (7.2 mV / decade). Extracted and amplified target DNA from Mycobacterium tuberculosis-spiked human saliva-samples was also examined using the method. A clear differentiation between positive and negative material could be recognized with the help of the PAH / ssDNA-modified EIS sensor chips. All developed process steps were validated using fluorescence measurements as a reference method. With the PAH-modified capacitive field-effect biosensor, that was developed in this thesis, a quick, simple and inexpensive measurement platform for the DNA hybridization reaction is given. The detection of amplified genomic DNA from real Mycobacterium tuberculosis-spiked saliva samples underlines the potential of this procedure as a sensor approach for pathogen detection for medical applications

Real-Time Tracking of Individual Droplets in Multiphase Microfluidics

Multiphase microfluidics enables the high-throughput manipulation of droplets for multitude of applications, from the confined fabrication of nano- and micro-objects to the parallelization of chemical reactions of biomedical or biological interest. While the standard methods to follow droplets on a chip are represented by a visual observation through either optical or fluorescence microscopy, the conjunction of microfluidic platforms with miniaturized transduction mechanisms opens new ways towards the real-time and individual tracking of each independent reactor. Here we provide an overview of the most recent droplet sensing techniques, with a special focus on those based on electrical signals for an optics-less analysis

Selected Papers from the 1st International Electronic Conference on Biosensors (IECB 2020)

The scope of this Special Issue is to collect some of the contributions to the First International Electronic Conference on Biosensors, which was held to bring together well-known experts currently working in biosensor technologies from around the globe, and to provide an online forum for presenting and discussing new results. The world of biosensors is definitively a versatile and universally applicable one, as demonstrated by the wide range of topics which were addressed at the Conference, such as: bioengineered and biomimetic receptors; microfluidics for biosensing; biosensors for emergency situations; nanotechnologies and nanomaterials for biosensors; intra- and extracellular biosensing; and advanced applications in clinical, environmental, food safety, and cultural heritage fields

Electrical and Electro-Optical Biosensors

Electrical and electro-optical biosensing technologies are critical to the development of innovative POCT devices, which can be used by both professional and untrained personnel for the provision of necessary health information within a short time for medical decisions to be determined, being especially important in an era of global pandemics. This Special Issue includes a few pioneering works concerning biosensors utilizing electrochemical impedance, localized surface plasmon resonance, and the bioelectricity of sensing materials in which the amount of analyte is pertinent to the signal response. The presented results demonstrate the potential of these label-free biosensing approaches in the detection of disease-related small-molecule metabolites, proteins, and whole-cell entities

Analysis of relevant technical issues and deficiencies of the existing sensors and related initiatives currently set and working in marine environment. New generation technologies for cost-effective sensors

The last decade has seen significant growth in the field of sensor networks, which are currently collecting large amounts of environmental data. This data needs to be collected, processed, stored and made available for analysis and interpretation in a manner which is meaningful and accessible to end users and stakeholders with a range of requirements, including government agencies, environmental agencies, the research community, industry users and the public. The COMMONSENSE project aims to develop and provide cost-effective, multi-functional innovative sensors to perform reliable in-situ measurements in the marine environment. The sensors will be easily usable across several platforms, and will focus on key parameters including eutrophication, heavy metal contaminants, marine litter (microplastics) and underwater noise descriptors of the MSFD. The aims of Tasks 2.1 and 2.2 which comprise the work of this deliverable are: • To obtain a comprehensive understanding and an up-to-date state of the art of existing sensors. • To provide a working basis on “new generation” technologies in order to develop cost-effective sensors suitable for large-scale production. This deliverable will consist of an analysis of state-of-the-art solutions for the different sensors and data platforms related with COMMONSENSE project. An analysis of relevant technical issues and deficiencies of existing sensors and related initiatives currently set and working in marine environment will be performed. Existing solutions will be studied to determine the main limitations to be considered during novel sensor developments in further WP’s. Objectives & Rationale The objectives of deliverable 2.1 are: • To create a solid and robust basis for finding cheaper and innovative ways of gathering data. This is preparatory for the activities in other WPs: for WP4 (Transversal Sensor development and Sensor Integration), for WP(5-8) (Novel Sensors) to develop cost-effective sensors suitable for large-scale production, reducing costs of data collection (compared to commercially available sensors), increasing data access availability for WP9 (Field testing) when the deployment of new sensors will be drawn and then realized

Development of a PDMS Based Micro Total Analysis System for Rapid Biomolecule Detection

The emerging field of micro total analysis system powered by microfluidics is expected to revolutionize miniaturization and automation for point-of-care-testing systems which require quick, efficient and reproducible results. In the present study, a PDMS based micro total analysis system has been developed for rapid, multi-purpose, impedance based detection of biomolecules. The major components of the micro total analysis system include a micropump, micromixer, magnetic separator and interdigitated electrodes for impedance detection. Three designs of pneumatically actuated PDMS based micropumps were fabricated and tested. Based on the performance test results, one of the micropumps was selected for integration. The experimental results of the micropump performance were confirmed by a 2D COMSOL simulation combined with an equivalent circuit analysis of the micropump. Three designs of pneumatically actuated PDMS based active micromixers were fabricated and tested. The micromixer testing involved determination of mixing efficiency based on the streptavidin-biotin conjugation reaction between biotin comjugated fluorescent microbeads and streptavidin conjugated paramagnetic microbeads, followed by fluorescence measurements. Based on the performance test results, one of the micromixers was selected for integration. The selected micropump and micromixer were integrated into a single microfluidic system. The testing of the magnetic separation scheme involved comparison of three permanent magnets and three electromagnets of different sizes and magnetic strengths, for capturing magnetic microbeads at various flow rates. Based on the test results, one of the permanent magnets was selected. The interdigitated electrodes were fabricated on a glass substrate with gold as the electrode material. The selected micropumps, micromixer and interdigitated electrodes were integrated to achieve a fully integrated microfluidic system. The fully integrated microfluidic system was first applied towards biotin conjugated fluorescent microbeads detection based on streptavidin-biotin conjugation reaction which is followed by impedance spectrum measurements. The lower detection limit for biotin conjugated fluorescent microbeads was experimentally determined to be 1.9 x 106 microbeads. The fully integrated microfluidic system was then applied towards immuno microbead based insulin detection. The lower detection limit for insulin was determined to be 10-5M. The total detection time was 20 min. An equivalent circuit analysis was performed to explain the impedance spectrum results

Nanostructured biosensors with DNA-based receptors for real-time detection of small analytes

In zahlreichen lebenswichtigen Bereichen haben sich Biosensoren als unverzichtbare Messgeräte erwiesen. Der Nachweis von spezifischen Molekülen im Körper für eine frühzeitige Krankheitserkennung erfordert empfindliche und zugleich zuverlässige Messmethoden. Ein rasantes Fortschreiten im Bereich der Nanotechnologie führt dabei zur Entwicklung von Materialien mit neuen Eigenschaften, und damit verbunden, auch zu innovativen Anwendungsmöglichkeiten im Bereich der Biosensorik. Das Zusammenspiel von Nanotechnologie und Sensortechnik gewährleistet die Konstruktion von Sensoren mit empfindlicheren Nachweisgrenzen und kürzeren Reaktionszeiten. Die Option zur Integration und Miniaturisierung stellen daher einen erfolgreichen Einsatz in direkter Patientennähe in Aussicht, sodass Nanobiosensoren die Brücke zwischen Laborddiagnostik und Standardanwendungen schließen können. Die folgende Arbeit widmet sich der Anwendung von nanostrukturierten Biosensoren für einen empfindlichen und markierungsfreien Nachweis von Zielmolekülen. Ein Hauptaugenmerk liegt dabei auf der kontinuierlichen Messung von Biomarkern mit kompakten Auslesesystemen, die eine direkte Signalmeldung und somit eine Detektion in Echtzeit ermöglichen. Dies erfordert zunächst die sorgfältige Funktionalisierung von Sensoroberflächen mit geeigneten DNA-basierten Rezeptoren. Infolgedessen werden beispielhaft verschiedene Sensorsysteme, Analyten und Charakterisierungsmethoden vorgestellt sowie universelle Strategien für die erfolgreiche Konfiguration von Nanobiosensorplattformen präsentiert. Das erste Anwendungsbeispiel widmet sich einem plasmonischen Biosensor, bei dem vertikal ausgerichtete Gold-Nanoantennen Signale mittels sog. lokalisierter Oberflächenplasmonenresonanz (LSPR) erzeugen. Mit dem Sensor konnte erfolgreich die Immobilisierung, das nachträgliche Blocken sowie die anschließende Hybridisierung von DNA nachgewiesen werden. Mithilfe des LSPR-Sensors wurden gleichzeitig grundlegende Hybridisierungsmechanismen auf nanostrukturierten und planaren Oberflächen verglichen und damit verbunden die einzigartigen optischen Eigenschaften metallischer Nanostrukturen betont. In einem zweiten Anwendungsbeispiel misst ein elektrischer Biosensor kontinuierlich die Konzentration des Stressmarkers Cortisol im menschlichen Speichel. Der direkte, markierungsfreie Nachweis von Cortisol mit Silizium-Nanodraht basierten Feldeffekttransistoren (SiNW FET) wurde anhand zugrunde liegender Ladungsverteilungen innerhalb des entstandenen Rezeptor-Analyte-Komplexes bewertet, sodass ein Nachweis des Analyten innerhalb der sog. Debye-Länge ermöglicht wird. Die erfolgreiche Strategie zur Oberflächenfunktionalisierung im Zusammenspiel mit dem Einsatz von SiNW FETs auf einem tragbaren Messgerät wurde anhand des Cortisolnachweises im Speichel belegt. Ein übereinstimmender Vergleich der gemessenen Corisolkonzentrationen mit Werten, die mit einer kommerziellen Alternative ermittelt wurden, verdeutlichen das Potential der entwickelten Plattform. Zusammenfassend veranschaulichen beide vorgestellten Nanobiosensor-Plattformen die vielseitige und vorteilhafte Leistungsfähigkeit der Systeme für einen kontinuierlichen Nachweis von Biomarkern in Echtzeit und vorzugsweise in Patientennähe.:Kurzfassung I Abstract III Abbreviations and symbols V Content VII 1 Introduction 1 1.1 Scope of the thesis 4 1.2 References 6 2 Fundamentals 9 2.1 Biosensors 9 2.2 Influence of nanotechnology on sensor development 10 2.3 Biorecognition elements 12 2.3.1 Biorecognition element: DNA 13 2.3.2 Aptamers 14 2.3.3 Immobilization of receptors 15 2.4 Transducer systems 17 2.4.1 Optical biosensors - surface plasmon resonance 17 2.4.2 Electric Biosensors – Field-effect transistors (FETs) 21 2.5 Metal oxide semiconductor field-effect transistor - MOSFET 21 2.6 Summary 26 2.7 References 27 3 Materials and methods 33 3.1 Plasmonic biosensors based on vertically aligned gold nanoantennas 33 3.1.1 Materials 33 3.1.2 Manufacturing of nanoantenna arrays 34 3.1.3 Surface modification and characterization 35 3.1.4 Measurement setup for detection of analytes 38 3.2 SiNW FET-based real-time monitoring of cortisol 40 3.2.1 Materials 40 3.2.2 Manufacturing of silicon nanowire field effect transistors (SiNW FETs) 42 3.2.3 Integration of SiNW FETs into a portable platform 42 3.2.4 Biomodification and characterization of electronic biosensors SiNW FETs 42 3.2.5 Electric characterization of FETs 47 3.3 References 50 4 Plasmonic DNA biosensor based on vertical arrays of gold nanoantennas 51 4.1 Introduction - Optical biosensors operating by means of LSPR 53 4.2 Biosensing with vertically aligned gold nanoantennas 56 4.2.1 Sensor fabrication, characterization, and integration 56 4.2.2 Integration of microfluidics 58 4.2.3 Immobilization of probe DNA and backfilling 58 4.2.4 Hybridization of complementary DNA strands 62 4.2.5 Surface coverage and hybridization efficiency of DNA 69 4.2.6 Refractive index sensing 72 4.2.7 Backfilling and blocking 73 4.3 Summary 75 4.4 References 77 5 Label-free detection of salivary cortisol with SiNW FETs 83 5.1 Introduction 85 5.2 Design, integration, and performance of SiNW FETs into a portable platform 89 5.2.1 Structure and electrical characteristics of honeycomb SiNW FETs 89 5.2.2 Integration of SiNW FET into a portable measuring unit 91 5.2.3 Performance of SiNW FET arrays 93 5.3 Detection of biomolecules with SiNW FETs 102 5.3.1 General considerations for biodetection with FETs 102 5.3.2 Sensing aptamers with FETs 103 5.3.3 Biodetection of the analyte cortisol with SiNW FETs 104 5.3.4 Detection of cortisol with SiNW FETs 112 5.4 Summary 119 5.5 References 121 6 Summary and outlook 131 6.1 Summary 131 6.2 Perspectives – toward multiplexed biosensing applications 134 6.3 References 137 Appendix i A.1 Protocols i A.1.1 Functionalization of gold antennas with thiolated DNA i A.1.2 Functionalization of SiO2 with TESPSA and amino-modified receptors i A.1.3 Functionalization with APTES and carboxyl-modified receptors ii A.1.4 Preparation of microfluidic channels via soft lithography ii A.2 Predicted secondary structures iv A.2.1 Secondary structures of 100base pair target without probe-strands iv A.2.2 Secondary structures of 100base pair target with 25 base pair probe-strand x Versicherung xvii Acknowledgments xix List of publications xxi Peer-reviewed publications xxi Publications in preparation xxi Selected international conferences xxii Curriculum Vitae xxiiiBiosensors have proven to be indispensable in numerous vital areas. For example, detecting the presence and concentration of specific biomarkers requires sensitive and reliable measurement methods. Rapid developments in the field of nanotechnology lead to nanomaterials with new properties and associated innovative applications. Thus, nanotechnology has a far-reaching impact on biosensors' development, e.g., delivery of biosensing devices with greater sensitivity, shorter response times, and precise but cost-effective sensor platforms. In addition, nanobiosensors hold high potential for integration and miniaturization and can operate directly at the point of care - serving as a bridge between diagnostics and routine tests. This work focuses on applying nanostructured biosensors for the sensitive and label-free detection of analytes. A distinct aim is the continuous monitoring of biomarkers with compact read-out systems to provide direct, valuable feedback in real-time. The first step in achieving this goal is the adequate functionalization of nanostructured sensor surfaces with suitable receptors to detect analytes of interest. Due to their thermal and chemical stability with the possibility for customizable functionalization, DNA-based receptors are selected. Thereupon, universal strategies for confining nanobiosensor platforms are presented using different sensor systems, analytes, and characterization methods. As a first application, a plasmonic biosensor based on vertically aligned gold nanoantennas tracked the immobilization, blocking, and subsequent hybridization of DNA by means of localized surface plasmon resonance (LSPR). At the same time, the LSPR sensor was used to evaluate fundamental hybridization mechanisms on nanostructured and planar surfaces, emphasizing the unique optical properties of metallic nanostructures. In a second application, an electric sensor based on silicon nanowire field-effect transistors (SiNW FET) monitored the level of the stress marker cortisol in human saliva. Based on evaluating the underlying charge distributions within the resulting receptor-analyte complex of molecules, the detection of cortisol within the Debye length is facilitated. Thus, direct, label-free detection of cortisol in human saliva using SiNW FET was successfully applied to the developed platform and compared to cortisol levels obtained using a commercial alternative. In summary, both presented platforms indicate a highly versatile and beneficial performance of nanobiosensors for continuous detection of biomarkers in real-time and preferably point-of-care (POC).:Kurzfassung I Abstract III Abbreviations and symbols V Content VII 1 Introduction 1 1.1 Scope of the thesis 4 1.2 References 6 2 Fundamentals 9 2.1 Biosensors 9 2.2 Influence of nanotechnology on sensor development 10 2.3 Biorecognition elements 12 2.3.1 Biorecognition element: DNA 13 2.3.2 Aptamers 14 2.3.3 Immobilization of receptors 15 2.4 Transducer systems 17 2.4.1 Optical biosensors - surface plasmon resonance 17 2.4.2 Electric Biosensors – Field-effect transistors (FETs) 21 2.5 Metal oxide semiconductor field-effect transistor - MOSFET 21 2.6 Summary 26 2.7 References 27 3 Materials and methods 33 3.1 Plasmonic biosensors based on vertically aligned gold nanoantennas 33 3.1.1 Materials 33 3.1.2 Manufacturing of nanoantenna arrays 34 3.1.3 Surface modification and characterization 35 3.1.4 Measurement setup for detection of analytes 38 3.2 SiNW FET-based real-time monitoring of cortisol 40 3.2.1 Materials 40 3.2.2 Manufacturing of silicon nanowire field effect transistors (SiNW FETs) 42 3.2.3 Integration of SiNW FETs into a portable platform 42 3.2.4 Biomodification and characterization of electronic biosensors SiNW FETs 42 3.2.5 Electric characterization of FETs 47 3.3 References 50 4 Plasmonic DNA biosensor based on vertical arrays of gold nanoantennas 51 4.1 Introduction - Optical biosensors operating by means of LSPR 53 4.2 Biosensing with vertically aligned gold nanoantennas 56 4.2.1 Sensor fabrication, characterization, and integration 56 4.2.2 Integration of microfluidics 58 4.2.3 Immobilization of probe DNA and backfilling 58 4.2.4 Hybridization of complementary DNA strands 62 4.2.5 Surface coverage and hybridization efficiency of DNA 69 4.2.6 Refractive index sensing 72 4.2.7 Backfilling and blocking 73 4.3 Summary 75 4.4 References 77 5 Label-free detection of salivary cortisol with SiNW FETs 83 5.1 Introduction 85 5.2 Design, integration, and performance of SiNW FETs into a portable platform 89 5.2.1 Structure and electrical characteristics of honeycomb SiNW FETs 89 5.2.2 Integration of SiNW FET into a portable measuring unit 91 5.2.3 Performance of SiNW FET arrays 93 5.3 Detection of biomolecules with SiNW FETs 102 5.3.1 General considerations for biodetection with FETs 102 5.3.2 Sensing aptamers with FETs 103 5.3.3 Biodetection of the analyte cortisol with SiNW FETs 104 5.3.4 Detection of cortisol with SiNW FETs 112 5.4 Summary 119 5.5 References 121 6 Summary and outlook 131 6.1 Summary 131 6.2 Perspectives – toward multiplexed biosensing applications 134 6.3 References 137 Appendix i A.1 Protocols i A.1.1 Functionalization of gold antennas with thiolated DNA i A.1.2 Functionalization of SiO2 with TESPSA and amino-modified receptors i A.1.3 Functionalization with APTES and carboxyl-modified receptors ii A.1.4 Preparation of microfluidic channels via soft lithography ii A.2 Predicted secondary structures iv A.2.1 Secondary structures of 100base pair target without probe-strands iv A.2.2 Secondary structures of 100base pair target with 25 base pair probe-strand x Versicherung xvii Acknowledgments xix List of publications xxi Peer-reviewed publications xxi Publications in preparation xxi Selected international conferences xxii Curriculum Vitae xxii

Silicon nanowire field-effect transistors for the detection of proteins

In this dissertation I present results on our efforts to increase the sensitivity and selectivity of silicon nanowire ion-sensitive field-effect transistors for the detection of biomarkers, as well as a novel method for wireless power transfer based on metamaterial rectennas for their potential use as implantable sensors. The sensing scheme is based on changes in the conductance of the semiconducting nanowires upon binding of charged entities to the surface, which induces a field-effect. Monitoring the differential conductance thus provides information of the selective binding of biological molecules of interest to previously covalently linked counterparts on the nanowire surface. In order to improve on the performance of the nanowire sensing, we devised and fabricated a nanowire Wheatstone bridge, which allows canceling out of signal drift due to thermal fluctuations and dynamics of fluid flow. We showed that balancing the bridge significantly improves the signal-to-noise ratio. Further, we demonstrated the sensing of novel melanoma biomarker TROY at clinically relevant concentrations and distinguished it from nonspecific binding by comparing the reaction kinetics. For increased sensitivity, an amplification method was employed using an enzyme which catalyzes a signal-generating reaction by changing the redox potential of a redox pair. In addition, we investigated the electric double layer, which forms around charges in an electrolytic solution. It causes electrostatic screening of the proteins of interest, which puts a fundamental limitation on the biomarker detection in solutions with high salt concentrations, such as blood. We solved the coupled Nernst-Planck and Poisson equations for the electrolyte under influence of an oscillating electric field and discovered oscillations of the counterion concentration at a characteristic frequency. In addition to exploring different methods for improved sensing capabilities, we studied an innovative method to supply power to implantable biosensors wirelessly, eliminating the need for batteries. A metamaterial split ring resonator is integrated with a rectifying circuit for efficient conversion of microwave radiation to direct electrical power. We studied the near-field behavior of this rectenna with respect to distance, polarization, power, and frequency. Using a 100 mW microwave power source, we demonstrated operating a simple silicon nanowire pH sensor with light indicator