Passive impedance sensing using a SAW resonator-coupled biosensor for zero-power wearable applications

A bio-sensing scheme, which acquires impedance information of a capacitive biosensor by using the reflected RF signal from a surface acoustic wave (SAW) resonator connected to the biosensor, is proposed. This technique requires no power to be supplied to the biosensor node and hence is highly applicable to wearable applications. Theoretical analysis has demonstrated that the sensitivity of the SAW resonator-coupled biosensor is higher than that of traditional impedance loaded SAW sensors and therefore it is more suitable for measuring the very small impedance changes in biosensors. The passive detection of the change in the impedance of a capacitive biosensor, as a result of biological binding events associated with the capture of a target analyte, has been demonstrated by preliminary experimentation. Dry tests of the SAW coupled capacitive biosensor using a cable connected network analyzer showed the aF level capacitance measurement resolution, which was only achieved in transistor level circuits previously, could be attained. When liquid samples with concentrations of C-Reactive Protein (CRP) in the range of 0.1 to 2 μg/ml were applied to the biosensor, a corresponding change in the resonant frequency of the SAW resonator-coupled biosensor (in the order of sub-hundred kHz) was observed. This has demonstrated the potential for applying this technique in applications where a zero-power requirement at the biosensor node could be a distinct advantage, when the cable link between the network analyzer and the biosensor node is replaced by the RF transmission

Sub-Femto-Farad Resolution Electronic Interfaces for Integrated Capacitive Sensors: A Review

Capacitance detection is a universal transduction mechanism used in a wide variety of sensors and applications. It requires an electronic front-end converting the capacitance variation into another more convenient physical variable, ultimately determining the performance of the whole sensor. In this paper we present a comprehensive review of the different signal conditioning front-end topologies targeted in particular at sub-femtofarad resolution. Main design equations and analysis of the limits due to noise are reported in order to provide the designer with guidelines for choosing the most suitable topology according to the main design specifications, namely energy consumption, area occupation, measuring time and resolution. A data-driven comparison of the different solutions in literature is also carried out revealing that resolution, measuring time, area occupation and energy/conversion lower than 100 aF, 1 ms 0.1 mm2, and 100 pJ/conv. can be obtained by capacitance to digital topologies, which therefore allow to get the best compromise among all design specifications

A Label Free CMOS-Based Smart Petri Dish for Cellular Analysis

RÉSUMÉ Le dépistage de culture cellulaire à haut débit est le principal défi pour une variété d’applications des sciences de la vie, y compris la découverte de nouveaux médicaments et le suivi de la cytotoxicité. L’analyse classique de culture cellulaire est généralement réalisée à l’aide de techniques microscopiques non-intégrées avec le système de culture cellulaire. Celles-ci sont laborieuses spécialement dans le cas des données recueillies en temps réel ou à des fins de surveillance continue. Récemment, les micro-réseaux cellulaires in-vitro ont prouvé de nombreux avantages dans le domaine de surveillance des cellules en réduisant les coûts, le temps et la nécessité d’études sur des modèles animaux. Les microtechniques, y compris la microélectronique et la microfluidique,ont été récemment utilisé dans la biotechnologie pour la miniaturisation des systèmes biologiques et analytiques. Malgré les nombreux efforts consacrés au développement de dispositifs microfluidiques basés sur les techniques de microscopie optique, le développement de capteurs intégrés couplés à des micropuits pour le suivi des paramètres cellulaires tel que la viabilité, le taux de croissance et cytotoxicité a été limité. Parmi les différentes méthodes de détection disponibles, les techniques capacitives offrent une plateforme de faible complexité. Celles-ci ont été considérablement utilisées afin d’étudier l’interaction cellule-surface. Ce type d’interaction est le plus considéré dans la majorité des études biologiques. L’objectif de cette thèse est de trouver des nouvelles approches pour le suivi de la croissance cellulaire et la surveillance de la cytotoxicité à l’aide d’un réseau de capteurs capacitifs entièrement intégré. Une plateforme hybride combinant un circuit microélectronique et une structure microfluidique est proposée pour des applications de détection de cellules et de découverte de nouveaux médicaments. Les techniques biologiques et chimiques nécessaires au fonctionnement de cette plateforme sont aussi proposées. La technologie submicroniques Standard complementary metal-oxide-Semiconductor (CMOS) (TSMC 0.35 μm) est utilisée pour la conception du circuit microélectronique de cette plateforme. En outre, les électrodes sont fabriquées selon le processus CMOS standard sans la nécessité d’étapes de post-traitement supplémentaires. Ceci rend la plateforme proposée unique par rapport aux plateformes de dépistage de culture cellulaire à haut débit existantes. Plusieurs défis ont été identifiés durant le développement de cette plateforme comme la sensibilité, la bio-compatibilité et la stabilité et les solutions correspondantes sont fournies.----------ABSTRACT High throughput cell culture screening is a key challenge for a variety of life science applications, including drug discovery and cytotoxicity monitoring. Conventional cell culture analysis is widely performed using microscopic techniques that are not integrated into the target cell culture system. Additionally, these techniques are too laborious in particular to be used for real-time and continuous monitoring purposes. Recently, it has been proved that invitro cell microarrays offer great advantages for cell monitoring applications by reducing cost, time, and the need for animal model studies. Microtechnologies, including microelectronics and microfluidics, have been recently used in biotechnology for miniaturization of biological and analytical systems. Despite many efforts in developing microfluidic devices using optical microscopy techniques, less attention have been paid on developing fully integrated sensors for monitoring cell parameters such as viability, growth rate, and cytotoxicity. Among various available sensing methods, capacitive techniques offer low complexity platforms. This technique has significantly attracted attentions for the study of cell-surface interaction which is widely considered in biological studies. This thesis focuses on new approaches for cell growth and cytotoxicity monitoring using a fully integrated capacitive sensor array. A hybrid platform combining microelectronic circuitry and microfluidic structure is proposed along with other required biological and chemical techniques for single cell detection and drug discovery applications. Standard submicron complementary metal–oxide–semiconductor (CMOS) technology (TSMC 0.35 μm) is used to develop the microelectronic part of this platform. Also, the sensing electrodes are fabricated in standard CMOS process without the need for any additional post processing step, which makes the proposed platform unique compared to other state of the art high throughput cell assays. Several challenges in implementing this platform such as sensitivity, bio-compatibility, and stability are discussed and corresponding solutions are provided. Specifically, a new surface functionalization method based on polyelectrolyte multilayers deposition is proposed to enhance cell-electrode adherence and to increase sensing electrodes’ life time. In addition, a novel technique for microwell fabrication and its integration with the CMOS chip is proposed to allow parallel screening of cells. With the potential to perform inexpensive, fast, and real-time cell analyses, the proposed platform opens up the possibility to transform from passive traditional cell assays to a smart on-line monitoring system

A Capacitance-to-Frequency Converter with On-Chip Passivated Microelectrodes for Bacteria Detection in Saline Buffers up to 575 MHz

To enable impedimetric sensing of whole-cell bacteria in saline buffer with passivated microelectrodes, we designed a very high frequency (up to 575 MHz) CMOS oscillator connected to on-chip Al/Al2O3 interdigitated microelectrodes. The output frequency was theoretically and experimentally shown to be inversely proportional to the permittivity of the solution with maximal error of 2 %, up to an electrical conductivity of 1 S/m. As a biosensing proof-of-concept, successful experimental detection of whole-cell Staphylococcus epidermidis was performed in physiological buffers, showing a detection limit of 10^7 CFU/ml after 20 min of bacterial incubation. The 0.25 μm CMOS circuit, combining sensing/readout parts, has a 0.05 mm2 area, consumes 29 mW at 250 kS/s and can be connected to microcontrollers, making the system suitable for point-of-care diagnostics

EUROSENSORS XVII : book of abstracts

Fundação Calouste Gulbenkien (FCG).Fundação para a Ciência e a Tecnologia (FCT)

Microfluidics and Nanofluidics Handbook

The Microfluidics and Nanofluidics Handbook: Two-Volume Set comprehensively captures the cross-disciplinary breadth of the fields of micro- and nanofluidics, which encompass the biological sciences, chemistry, physics and engineering applications. To fill the knowledge gap between engineering and the basic sciences, the editors pulled together key individuals, well known in their respective areas, to author chapters that help graduate students, scientists, and practicing engineers understand the overall area of microfluidics and nanofluidics. Topics covered include Finite Volume Method for Numerical Simulation Lattice Boltzmann Method and Its Applications in Microfluidics Microparticle and Nanoparticle Manipulation Methane Solubility Enhancement in Water Confined to Nanoscale Pores Volume Two: Fabrication, Implementation, and Applications focuses on topics related to experimental and numerical methods. It also covers fabrication and applications in a variety of areas, from aerospace to biological systems. Reflecting the inherent nature of microfluidics and nanofluidics, the book includes as much interdisciplinary knowledge as possible. It provides the fundamental science background for newcomers and advanced techniques and concepts for experienced researchers and professionals

Applications and Experiences of Quality Control

The rich palette of topics set out in this book provides a sufficiently broad overview of the developments in the field of quality control. By providing detailed information on various aspects of quality control, this book can serve as a basis for starting interdisciplinary cooperation, which has increasingly become an integral part of scientific and applied research