Study on Integrated Redox Image Sensor Employing Square Wave Voltammetry

豊橋技術科学大

Electrochemical Sensors and On-chip Optical Sensors

abstract: The microelectronics technology has seen a tremendous growth over the past sixty years. The advancements in microelectronics, which shows the capability of yielding highly reliable and reproducible structures, have made the mass production of integrated electronic components feasible. Miniaturized, low-cost, and accurate sensors became available due to the rise of the microelectronics industry. A variety of sensors are being used extensively in many portable applications. These sensors are promising not only in research area but also in daily routine applications. However, many sensing systems are relatively bulky, complicated, and expensive and main advantages of new sensors do not play an important role in practical applications. Many challenges arise due to intricacies for sensor packaging, especially operation in a solution environment. Additional problems emerge when interfacing sensors with external off-chip components. A large amount of research in the field of sensors has been focused on how to improve the system integration. This work presents new methods for the design, fabrication, and integration of sensor systems. This thesis addresses these challenges, for example, interfacing microelectronic system to a liquid environment and developing a new technique for impedimetric measurement. This work also shows a new design for on-chip optical sensor without any other extra components or post-processing.Dissertation/ThesisDoctoral Dissertation Electrical Engineering 201

Cheap and disposable gold and silver electrodes: Trends in the application of compact discs and digital versatile discs for electroanalytical chemistry

© 2017 Increasingly more reports have focused on the use of digital versatile discs (DVDs) and compact discs (CDs) for the fabrication of electrodes. The majority of discs use Al to reflect the laser. However, a notable percentage utilise Au or Ag. This layer can be mechanically or chemically exposed allowing for the economic fabrication of otherwise expensive Ag and Au electrodes. Cleaning steps are not required due to the layer's mirror like surface. Mass production of these discs means they are available, reproducible and disposable. Modifications can be made by laser, inkjet printing, etching or xurography. Self-assembled monolayers and the attachment of functional groups can also be made. This review (97 references and 6 figures) is divided into four sections. The first describes the development of these electrodes and their fabrication and modification. The next three sections focused on applications for the determination of metal ions, biomedical and environmental analysis

Towards Electrochemical PCR-Chips: Contributions to Couple Enzymatic Amplification and Electrochemical Detection of DNA

In this work the electrochemical DNA detection at heated electrodes as one alternative to the classical methods for the detection of DNA is presented. At elevated temperature an increase in sensitivity and selectivity as well as the minimization of electrode fouling could be observed. Surface modifications in the nano scale could further more improve the sensitivity. Procedures to detect genetically modified maize (MON 810) and PCR products were developed. The combination of DNA amplification and electrochemical detection was demonstrated.In dieser Arbeit wird die elektrochemische DNA-Detektion an geheizten Elektroden als Alternative zu den klassischen Detektionsmethoden vorgestellt. Messungen bei erhöhten Temperaturen zeigten eine Verbesserung der Empfindlichkeit und der Spezifität sowie eine Minimierung des Elektrodenfoulings. Oberflächenmodifikationen im Nanomaßstab konnten die Empfindlichkeit weiter verbessern. Methoden, um gentechnisch veränderten Mais (MON 810) und PCR Produkte nachzuweisen, wurden vorgestellt. Die Kombination aus DNA-Vervielfältigung und elektrochemischer Detektion wurde erfolgreich angewendet

The development of an electrochemical sensor for detecting and measuring circulating tumour DNA in human fluids

The high rates of mortality amongst cancer patients highlights the need for advances in rapid detection and enhanced point of care (PoC) testing. A simple approach tailored towards PoC cancer detection and monitoring using label-free electrochemical biosensors is presented. Screen-Printed Carbon electrodes (SPCEs) have been extensively employed as an economical transducer substrate for electrochemical biosensing applications due to their simplicity, affordability and versatility. In this work, a simple, low-cost DNA biosensor is presented which after initial work with Tp53 was developed specifically to detect mutations in a key oncogene (KRAS). Sensor arrays of SPCEs and carbon-nanotube (CNT) modified SPCEs were used to perform multiplexed measurements of DNA hybridisation. Various amplification techniques for enriching the pool of mutated DNA strands were explored and optimised. Amine-modified ssDNA probes were immobilized by modifying SPCEs and CNT-SPCEs with diazonium and EDC/NHS groups. The sensor performance was characterized using cyclic voltammetry, differential pulse voltammetry, square wave voltammetry and electrochemical impedance spectroscopy all to different extents. The detection principle was evaluated by showing effective on-chip DNA hybridization techniques, discrimination using negative controls, and performing multiple repetitions to ascertain reliability of the system. The developed sensor displayed some sensitivity and selectivity to Tp53, KRAS pG12D, and KRAS pG13D DNA, all of which are important mutations in cancer progression. For the amplified samples, 0.027 ng/µl amplicons were detectable while for the non-amplified samples, 0.85 ng/µl cfDNA concentration was detectable using the assay developed. The importance of these findings lies in the design of future electrochemical assays that are capable of discriminating between circulating tumour DNA in the blood prior to and post cancer therapy. The real-world application of this concept provides not only early diagnostic capability but an avenue for treatment decisions to be guided in such a way that health care providers can initiate, choose, avoid, alter or cease selected therapies when caring for patients that have shown symptoms for cancer or who are at risk of having recurrent cancers.The high rates of mortality amongst cancer patients highlights the need for advances in rapid detection and enhanced point of care (PoC) testing. A simple approach tailored towards PoC cancer detection and monitoring using label-free electrochemical biosensors is presented. Screen-Printed Carbon electrodes (SPCEs) have been extensively employed as an economical transducer substrate for electrochemical biosensing applications due to their simplicity, affordability and versatility. In this work, a simple, low-cost DNA biosensor is presented which after initial work with Tp53 was developed specifically to detect mutations in a key oncogene (KRAS). Sensor arrays of SPCEs and carbon-nanotube (CNT) modified SPCEs were used to perform multiplexed measurements of DNA hybridisation. Various amplification techniques for enriching the pool of mutated DNA strands were explored and optimised. Amine-modified ssDNA probes were immobilized by modifying SPCEs and CNT-SPCEs with diazonium and EDC/NHS groups. The sensor performance was characterized using cyclic voltammetry, differential pulse voltammetry, square wave voltammetry and electrochemical impedance spectroscopy all to different extents. The detection principle was evaluated by showing effective on-chip DNA hybridization techniques, discrimination using negative controls, and performing multiple repetitions to ascertain reliability of the system. The developed sensor displayed some sensitivity and selectivity to Tp53, KRAS pG12D, and KRAS pG13D DNA, all of which are important mutations in cancer progression. For the amplified samples, 0.027 ng/µl amplicons were detectable while for the non-amplified samples, 0.85 ng/µl cfDNA concentration was detectable using the assay developed. The importance of these findings lies in the design of future electrochemical assays that are capable of discriminating between circulating tumour DNA in the blood prior to and post cancer therapy. The real-world application of this concept provides not only early diagnostic capability but an avenue for treatment decisions to be guided in such a way that health care providers can initiate, choose, avoid, alter or cease selected therapies when caring for patients that have shown symptoms for cancer or who are at risk of having recurrent cancers

Portable Bio-Devices: Design of Electrochemical Instruments from Miniaturized to Implantable Devices

The integration of biosensors and electronic technologies allows the development of biomedical systems able to diagnose and monitoring pathologies by detecting specific biomarkers. The chapter presents the main modules involved in the development of such devices, generically represented in Fig. 1, and focuses its attention on the essential components of these systems to address questions such as: how is the device powered? How does it communicate the measured data? What kind of sensors could be used?, and What kinds of electronics are used

New analytical applications of gold nanoparticles

The work includes improvements of surface technology, new analytical applications of metallic nanoparticles and optimization of technological steps for production of different types of metallic nanoparticles in discrete and continuous modes. The technology of LbL deposition was optimized and applied for immobilization of metallic nanoparticles. SPR detection was used for the determination of optimal deposition conditions and on-line monitoring of the deposition process. Simple approach for automation of LbL deposition allowing one to deposit up to hundreds of layers was developed. The technology was proved by electrochemical analysis for deposition of electrochemically active polymers. A new diffusion based semi-quantitative assay for detection of sugars was suggested. Electrochemical oxidation of glucose and dopamine on electrodes modified with gold nanoparticles was studied. Conditions for electrochemical analysis of these substances in the presence of typical natural interferents were evaluated. A combination of voltammetry and impedance spectroscopy was used to demonstrate a formation of insulating layer on gold surface, this resulted in explanation of anomalous shape of voltammetric curves. A combination of electrochemical and SPR measurements demonstrated directly a formation of an insulating layer on the electrode surface and was used for optimization of the assay conditions. The results indicate a possibility to develop an enzyme free sensors for glucose and dopamine. It was discovered that gold nanoparticles are effective nucleating agents for protein crystallization. Nanoparticles induce protein crystallization at lower supersaturation and increase the number of protein crystals formed at higher supersaturation. The fact that this technology works with so different proteins as lysozyme and ferritin allows one to suggest that it may be also applied for many other proteins including the ones which are reluctant to crystallization by known technologies. Irreversible freezing indicators based on gold nanoparticles were developed. The filling suspension containing nanoparticles, nucleation and stabilization agents were optimized in sense of stability and irreversibility of color changes. A large scale production of this indicator will be started in spring 2008

Nanostructure-Based Electrochemical Immunosensors as Diagnostic Tools

Electrochemical immunosensors are affinity-based biosensors characterized by several useful features such as specificity, miniaturizability, low cost and simplicity, making them very interesting for many applications in several scientific fields. One of the significant issues in the design of electrochemical immunosensors is to increase the system’s sensitivity. Different strategies have been developed, one of the most common is the use of nanostructured materials as electrode materials, nanocarriers, electroactive or electrocatalytic nanotracers because of their abilities in signal amplification and biocompatibility. In this review, we will consider some of the most used nanostruc- tures employed in the development of electrochemical immunosensors (e.g., metallic nanoparticles, graphene, carbon nanotubes) and many other still uncommon nanomaterials. Furthermore, their diagnostic applications in the last decade will be discussed, referring to two relevant issues of present-day: the detection of tumor markers and viruses

Advanced solid state nano-electrochemical sensors and system for agri 4.0 applications

Global food production needs to increase in order to meet the demands of an ever growing global population. As resources are finite, the most feasible way to meet this demand is to minimize losses and improve efficiency. Regular monitoring of factors like animal health, soil and water quality for example, can ensure that the resources are being used to their maximum efficiency. Existing monitoring techniques however have limitations, such as portability, turnaround time and requirement for additional reagents. In this work, we explore the use of micro- and nano-scale electrode devices, for the development of an electrochemical sensing platform to digitalize a wide range of applications within the agri-food sector. With this platform, we demonstrate the direct electrochemical detection of pesticides, specifically clothianidin and imidacloprid, with detection limits of 0.22 ng/mL and 2.14 ng/mL respectively, and nitrates with a detection limit of 0.2 µM. In addition, interdigitated electrode structures also enable an in-situ pH control technique to mitigate pH as an interference and modify analyte response. This technique is applied to the analysis of monochloramine, a common water disinfectant. Concerning biosensing, the sensors are modified with bio-molecular probes for the detection of both bovine viral diarrhea virus species and antibodies, over a range of 1 ng/mL to 10 µg/mL. Finally, a portable analogue front end electronic reader is developed to allow portable sensing, with control and readout undertaken using a smart phone application. Finally, the sensor chip platform is integrated with these electronics to provide a fully functional end-to-end smart sensor system compatible with emerging Agri-Food digital decision support tools

Electrochemical studies toward proteomic analysis

This thesis provides the basis for a label-free bioanalytical platform using electrochemical analysis at liquid –liquid interfaces. The possibility to detect biomolecules such as proteins in a label-free manner via adsorption and ion-transfer was achieved. Several pre-treatment steps used in proteome analysis, such as protein pre-concentration and digestion, were studied. The results demonstrate the promise of this strategy for the detection and identification of proteins