Development of real-time cellular impedance analysis system

The cell impedance analysis technique is a label-free, non-invasive method, which simplifies sample preparation and allows applications requiring unmodified cell retrieval. However, traditional impedance measurement methods suffer from various problems (speed, bandwidth, accuracy) for extracting the cellular impedance information. This thesis proposes an improved system for extracting precise cellular impedance in real-time, with a wide bandwidth and satisfactory accuracy. The system hardware consists of five main parts: a microelectrode array (MEA), a stimulation circuit, a sensing circuit, a multi-function card and a computer. The development of system hardware is explored. Accordingly, a novel bioimpedance measurement method coined digital auto balancing bridge method, which is improved from the traditional analogue auto balancing bridge circuitry, is realized for real-time cellular impedance measurement. Two different digital bridge balancing algorithms are proposed and realized, which are based on least mean squares (LMS) algorithm and fast block LMS (FBLMS) algorithm for single- and multi-frequency measurements respectively. Details on their implementation in FPGA are discussed. The test results prove that the LMS-based algorithm is suitable for accelerating the measurement speed in single-frequency situation, whilst the FBLMS-based algorithm has advantages in stable convergence in multi-frequency applications. A novel algorithm, called the All Phase Fast Fourier Transform (APFFT), is applied for post-processing of bioimpedance measurement results. Compared with the classical FFT algorithm, the APFFT significantly reduces spectral leakage caused by truncation error. Compared to the traditional FFT and Digital Quadrature Demodulation (DQD) methods, the APFFT shows excellent performance for extracting accurate phase and amplitude in the frequency spectrum. Additionally, testing and evaluation of the realized system has been performed. The results show that our system achieved a satisfactory accuracy within a wide bandwidth, a fast measurement speed and a good repeatability. Furthermore, our system is compared with a commercial impedance analyzer (Agilent 4294A) in biological experiments. The results reveal that our system achieved a comparable accuracy to the commercial instrument in the biological experiments. Finally, conclusions are given and the future work is proposed

PTB-INRIM comparison of novel digital impedance bridges with graphene impedance quantum standards

This paper describes an onsite comparison of two different digital impedance bridges when performing measurements on a quantum Hall resistance standard with the purpose of realizing the SI unit of capacitance, the farad. In the EMPIR Joint Research Project 18SIB07 GIQS, graphene impedance quantum standards, the Physikalisch-Technische Bundesanstalt (PTB), Germany, developed a Josephson impedance bridge, and the Istituto Nazionale di Ricerca Metrologica (INRIM) and the Politecnico di Torino (POLITO), Italy, developed an electronic digital impedance bridge. The former is based on Josephson waveform generators and the latter on an electronic waveform synthesizer. The INRIM–POLITO impedance bridge was moved to PTB and the two bridges were compared by measuring both temperature-controlled standards and a graphene AC quantized Hall resistance (QHR) standard. The uncertainties for the calibration of 10 nF capacitance standards at 1233 Hz are within 1 × 10−8 for the PTB's bridge and around 1 × 10−7 for the INRIM–POLITO's bridge. The comparison mutually validates the two bridges within the combined uncertainty. The result confirms that digital impedance bridges allow the realization of the SI farad from the QHR with uncertainties comparable with the best calibration capabilities of the BIPM and the major National Metrology Institutes

Integrated dielectric spectrometer for wideband and highspeed measurements using pseudo-noise codes

The paper gives a short introduction into some system-theoretic aspects and features of dielectric measurements by periodic wideband signals. Based on these considerations, a related measurement concept will be presented which is well suited for both compact device implementation and monolithic integration. Some implementation examples are shown and first measurement results are presented

Une plate-forme sans fil pour electrochimique spectroscopie d'impédance

Avec l’émergence soutenue de capteurs et de dispositifs électrochimiques innovants, la spectroscopie d'impédance électrochimique est devenue l'un des outils les plus importants pour la caractérisation et la modélisation de la matière ionique et de l'interfaçage des capteurs. La capacité de détecter automatiquement, à l’aide de dispositifs électrochimiques peu couteux, les caractéristiques physiques et chimiques de la matière ionique ouvre une gamme d’application très variée pour la compréhension et l’optimisation des procédés ou interviennent les processus électrochimiques. Cette thèse décrit le développement d’une plate-forme microélectronique miniaturisée, connectée, multiplexée, et à faible coût pour la spectroscopie d'impédance diélectrique (SID) conçue pour les mesures électrochimiques in-situ et adaptée aux architectures de réseau sans fil. La plate-forme développée durant ce travail de maitrise a été testée et validée au sein d’une maille ZigBee et a été en mesure d'interfacer jusqu'à trois capteurs SID en même temps et de relayer l'information à travers le net Zigbee pour l'analyse de données et le stockage. Le système a été construit à partir de composants microélectroniques disponibles commercialement et bénéficie des avantages d'une calibration système on-the-fly qui effectue la calibration du capteur de manière aisée. Dans ce mémoire de maitrise, nous rapportons la modélisation et la caractérisation de senseurs électrochimiques de nitrate; notamment nous décrivons la conception microélectronique, la réponse d'impédance de Nyquist, la sensibilité et la précision de la mesure électrochimique, et les résultats de tests de la plate-forme pour les applications de spectroscopie d'impédance relatives à la détection du nitrate, de la détection de la qualité de l'eau, et des senseurs tactiles.The emergence of the various applications of electrochemical sensors and devices, electrochemical impedance spectroscopy became one of the most important tools for characterizing and modeling of the material and interfacing the sensors. The ability to sense in an automatic manner enables a wide variety of processes to be better understood and optimized cost-effectively. This thesis describes the development of a low-cost, miniaturized, multiplexed, and connected platform for dielectric impedance spectroscopy (DIS) designed for in-situ measurements and adapted to wireless network architectures. The platform has been tested and used as a DIS sensor node on a ZigBee mesh and was able to interface up to three DIS sensors at the same time and relay the information through the Zigbee net for data analysis and storage. The system was built from commercial microelectronics components and benefits from an on-the-fly calibration system that makes sensor calibration easy. The thesis reports characterizing and modeling of two electro-chemical devices (i.e. nitrate sensor and optically-transparent electrically-conductive glasses) and also describes the microelectronics design, the Nyquist impedance response, the measurement sensitivity and accuracy, and the testing of the platform for in-situ dielectric impedance spectroscopy applications pertaining to fertilizer sensing, water quality sensing, and touch sensing

Smartphone acoustic impedance sensing based on additive sum mixing technique

We have developed a method to perform impedance measurement using general purpose smartphones that will not require the presence of external power source. The need for battery-less impedance sensing methods is greatly demanded given recent years’ advancements in impedance based sensing technologies, such as impedance tomography, which will enable patients to perform medical tests such as breast cancer self-detection using only a smartphone. The work discussed in this thesis is an early prototype of the impedance sensing method done using MATLAB simulation of both hardware and algorithm for impedance sensing. The battery-less acoustic impedance sensing technique is a combination of both hardware circuit design as well as control software algorithm. The circuit hardware technology is based on the additive summing mixer technology that is widely used in professional audio production mixing consoles. The results presented in this thesis can be accurate to within 0.1% of target device characteristics in simulation as far as tested. Although not discussed in this work, in our early physical hardware prototypes, the measurement based on the method discussed in this thesis has achieved accuracy within 10% of the target value with all the noise and parameter approximations

A multi-chanel electrical impedance meter based on digital lock-in technology

Abstract The presented multichannel measuring system working on various frequencies is suitable either for electrical impedance spectroscopy or tomography. The authors of this paper have developed the complete measurement system and a graphical user interface platform. The accuracy of impedance amplitude and phase are 1 ppm and 0.01°, respectively. The basic instrument works with 8 channels and can be expanded to 64 channels with the application of multiplexing or multiple parallel connected instruments in the same system

Integrated Electronics for Molecular Biosensing

This thesis, Integrated electronics for molecular biosensing, focuses on different approaches to sense the presence and activity of a specific analyte by using integrated electronic platforms. The aim of the first platform is to detect the enzyme telomerase. Telomerase causes the elongation of telomeres, which are part of the chromosomes, and determines the lifespan of cells. Telomerase expression is a marker of malignity in tumoral cells and its evaluation can be exploited for early diagnosis of many types of cancer cells. To detect the telomerase enzyme, a CMOS (complementary metal-oxide semiconductor) biosensor based on CMFET (Charge-Modulated Field Effect Transistor) able to measure kinetics of DNA replication and telomerase reaction was developed. The sensor can be functionalized by immobilizing single strands of DNA that contain the telomeric sequence, used as probes. If telomerase is present, the probes will be elongated by the enzyme and the charge on the sensing area will change, which reflects in a variation of the output current or voltage. The chip includes three different readout schemes (voltage, current- and time-based), each of which has different measuring ranges and operating conditions. The measured data is then digitized, stored, and can be sent off-chip through SPI (Serial Peripheral Interface) protocol. A total of 1024 biosensors have been integrated in a single chip with a size of 10x10 mm2. Each sensor can be independently addressed and functionalized by an electrochemical procedure using an integrated potentiostat, thus requiring no external equipment. Although the sensors have been tailored and optimized to perform telomerase detection, the sensing areas can be functionalized to be used with different analytes. This feature turns the chip into a complete bioassay platform. The second part of this work rises from the idea that bacteria, like Escherichia coli, can detect analytes in solution even at extremely low concentrations and change their movement through a process called chemotaxis, to move towards chemical gradients in the solution. E. coli moves by rotating its flagella either clockwise (for random tumbles) or counterclockwise (for straight runs, when it senses a chemical it is attracted to). Therefore, observing bacteria flagellar rotation can give enough information on the presence of a specific analyte in the solution. To electronically detect bacteria movement, an active surface covered in electrodes has been designed. By measuring the impedance between each pair of electrodes through an integrated LIA (lock-in amplifier), it is possible to know how a single bacterium is moving. By that, the presence or absence of the analyte can be deduced, thus effectively turning bacteria into chemical sensors