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

Design and analysis of dual-mode numerically controlled oscillators based controlled oscillator frequency modulation

In this paper, the design and analysis of dual-mode numerically controlled oscillators (NCO) based controlled oscillator frequency Modulation is implemented. Initially, input is given to the analog to digital (ADC) converter. This will change the input from analog to digital converter. After that, the pulse skipping mode (PSM) logic and proportional integral (PI) are applied to the converted data. After applying PSM logic, data is directly transferred to the connection block. The proportional and integral block will transfer the data will be decoded using the decoder. After decoding the values, it is saved using a modulo accumulator. After that, it is converted from one hot residue (OHR) to binary converter. The converted data is saved in the register. Now both data will pass through the gate driver circuit and output will be obtained finally. From simulation results, it can observe that the usage of metal oxide semiconductor field effect transistors (MOSFETs) and total nodes are very less in dual-mode NCO-based controlled oscillator frequency modulation

A 36 µW 1.1 mm2 reconfigurable analog front-end for cardiovascular and respiratory signals recording

© 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other worksThis paper presents a 1.2 V 36 µW reconfigurable analog front-end (R-AFE) as a general-purpose low-cost IC for multiple-mode biomedical signals acquisition. The R-AFE efficiently reuses a reconfigurable preamplifier, a current generator (CG), and a mixed signal processing unit, having an area of 1.1 mm2 per R-AFE while supporting five acquisition modes to record different forms of cardiovascular and respiratory signals. The R-AFE can interface with voltage-, current-, impedance-, and light-sensors and hence can measure electrocardiography (ECG), bio-impedance (BioZ), photoplethysmogram (PPG), galvanic skin response (GSR), and general-purpose analog signals. Thanks to the chopper preamplifier and the low-noise CG utilizing dynamic element matching, the R-AFE mitigates 1/f noise from both the preamplifier and the CG for improved measurement sensitivity. The IC achieves competitive performance compared to the state-of-the-art dedicated readout ICs of ECG, BioZ, GSR, and PPG, but with approximately 1.4×-5.3× smaller chip area per channel.Peer ReviewedPostprint (author's final draft

Multi-frequency segmental bio-impedance device:design, development and applications

Bio-impedance analysis (BIA) provides a rapid, non-invasive technique for body composition estimation. BIA offers a convenient alternative to standard techniques such as MRI, CT scan or DEXA scan for selected types of body composition analysis. The accuracy of BIA is limited because it is an indirect method of composition analysis. It relies on linear relationships between measured impedance and morphological parameters such as height and weight to derive estimates. To overcome these underlying limitations of BIA, a multi-frequency segmental bio-impedance device was constructed through a series of iterative enhancements and improvements of existing BIA instrumentation. Key features of the design included an easy to construct current-source and compact PCB design. The final device was trialled with 22 human volunteers and measured impedance was compared against body composition estimates obtained by DEXA scan. This enabled the development of newer techniques to make BIA predictions. To add a ‘visual aspect’ to BIA, volunteers were scanned in 3D using an inexpensive scattered light gadget (Xbox Kinect controller) and 3D volumes of their limbs were compared with BIA measurements to further improve BIA predictions. A three-stage digital filtering scheme was also implemented to enable extraction of heart-rate data from recorded bio-electrical signals. Additionally modifications have been introduced to measure change in bio-impedance with motion, this could be adapted to further improve accuracy and veracity for limb composition analysis. The findings in this thesis aim to give new direction to the prediction of body composition using BIA. The design development and refinement applied to BIA in this research programme suggest new opportunities to enhance the accuracy and clinical utility of BIA for the prediction of body composition analysis. In particular, the use of bio-impedance to predict limb volumes which would provide an additional metric for body composition measurement and help distinguish between fat and muscle content

Firmware design of a portable medical device to measure the quadriceps muscle group after a total knee arthroplasty by EMG, LBIA and clinical score methods

El objetivo de este proyecto es el diseño del firmware de un dispositivo médico portátil para mediciones de EMG y LBIA, que se utilizará para la evaluación de pacientes de artroplastia total de rodilla, para estudiar la progresión de diferentes prótesis de rodilla (Medial-Pivot y Ultra-Congruente). En la tesis, se expone el conocimiento actual de los estudios y aplicaciones de EMG y LBIA, junto con los dispositivos comerciales utilizados actualmente. Además, se han estudiado e implementado las diferentes técnicas de filtrado y procesamiento digital para señales de EMG y LBIAs. Adicionalmente, se ha realizado un estudio estadístico preliminar con datos LBIA de 12 pacientes de artroplastia total de rodilla. El diseño del firmware de esta tesis incluye: los procesos de adquisición de datos con el uso de diferentes ADCs (Conversor Analógico a Digital) (de la propia placa y externos, utilizando la interfaz SPI) y un DAC (Conversor Digital a Analógico), el correspondiente procesamiento de la señal y la extracción de sus características, la comunicación con un dispositivo externo utilizando un módulo BLE externo con interfaz UART, el proceso de encriptación de los datos médicos, la funcionalidad de manejo de errores y la aproximación del nivel de batería. En esta tesis, todos los flujos de trabajo de los procesos se exponen y explican mediante diagramas de flujo, mientras que se justifica cada cálculo y configuración. Además, todo el código correspondiente se ha programado en lenguaje C y se expone en los anexos. También se ha revisado la normativa aplicable y se ha analizado tanto el impacto ambiental como el coste económico del producto. Por último, se proponen mejoras para futuros trabajos.The aim of this project is the firmware design for a portable medical device for EMG and LBIA measurements which will be used for the assessment of total knee arthroplasty patients to study the progression of different knee prostheses (Medial-Pivot and Ultra-Congruent). For its realization, the state of the art of the EMG and LBIA studies and applications are exposed, along with the currently used medical devices. In addition, the different digital filtering and processing techniques for these studies have been studied and implemented. Furthermore, a preliminary statistical study has been performed with LBIA data from 12 patients with total knee arthroplasty. The firmware design of this thesis includes: the acquiring data processes with the use of different ADCs (from the actual board and external, using the SPI interface) and a DAC, the corresponding signal processing and feature abstraction, the communication with an external device using an external BLE module with UART interface, the medical data encrypting process, the error handling functionality, and the battery level approximation. In this work, all the process workflows are exposed and explained using flowcharts, while every calculation and configuration is justified. In addition, all the corresponding code has been programmed using C language and exposed in the Annexes. Moreover, the applicable regulation has been reviewed, and both the environmental impact and economic cost of the product have been analyzed. Finally, improvements are proposed for future work.L'objectiu d'aquest projecte és el disseny del microprogramari d'un dispositiu mèdic portàtil per a mesures d'EMG i LBIA. L’aparell mèdic s'utilitzarà per a l'avaluació de pacients d'artroplàstia total de genoll per estudiar la progressió de dues pròtesis de genoll (Medial-Pivot i Ultra- Congruent). En el treball, s'exposa el coneixement actual dels estudis i aplicacions d'EMG i LBIA, juntament amb els dispositius comercials utilitzats actualment. A més, s'han estudiat i implementat les diferents tècniques de filtrat i processament digital dels senyals de EMG i LBIA. Addicionalment, s'ha fet un estudi estadístic preliminar amb dades de LBIA de 12 pacients amb artroplàstia total de genoll. El disseny del microprogramari d'aquesta tesi inclou: els processos d'adquisició de dades fent ús de diferents ADCs (de la pròpia placa i externs, utilitzant la interfície SPI) i un DAC, el processament dels senyals i l'abstracció de les seves característiques, la comunicació amb un dispositiu extern utilitzant un mòdul BLE extern amb interfície UART, el procés d'encriptació de les dades mèdiques, la funcionalitat de l’avaluació d'errors i l'aproximació del nivell de bateria. En aquest treball, totes les funcionalitats del dispositiu s'exposen i s'expliquen mitjançant diagrames de flux i es justifiquen els càlculs i configuracions corresponents. Tot el codi desenvolupat s'ha programat en llenguatge C i s'exposa als annexos. A més, s'ha revisat la normativa aplicable i s'ha analitzat tant l'impacte ambiental com el cost econòmic de l’aparell. Finalment, es proposen millores per a futurs desenvolupaments

Novel Methods for Weak Physiological Parameters Monitoring.

M.S. Thesis. University of Hawaiʻi at Mānoa 2017

HIGH FIDELITY MEASUREMENT OF BIOELECTRICAL SIGNALS

Previous research regarding the acquisition and electrical characterization of bio- electrical signals of both noninvasive “oriundis in vivo”, generally associated with elec- tromyography (EMG), electrocardiography (EKG), or electroencephalography (EEG), and active “oriundis ex vivo et vitro” material characterization, generally associated with bioimpedance spectroscopy (BIS); while successfully providing beneficial results, was ul- timately plagued with a variety of intrinsic electrical distortions [1] [2]. Conversely, the frequent manifestation of such distortions resulted in an investigation into the nature of their occurrence, which subsequently resulted in my research into the nature of such dis- tortions, the conditions in which they occur, useful techniques to model and minimize their impact, and the underlying methodology needed to obtain the highest fidelity possi- ble when acquiring such measurements. Furthermore, the techniques developed are then applied to both noninvasively obtained “oriundis in vivo” and active “oriundis ex vivo et vitro” applied bioelectrical signals, and the compensated measurements are compared with the uncompensated measurements obtained within the previously mentioned research

Bioimpedance sensors: a tutorial

Electrical bioimpedance entails the measurement of the electrical properties of tissues as a function of frequency. It is thus a spectroscopic technique. It has been applied in a plethora of biomedical applications for diagnostic and monitoring purposes. In this tutorial, the basics of electrical bioimpedance sensor design will be discussed. The electrode/electrolyte interface is thoroughly described, as well as methods for its modelling with equivalent circuits and computational tools. The design optimization and modelling of bipolar and tetrapolar bioimpedance sensors is presented in detail, based on the sensitivity theorem. Analytical and numerical modelling approaches for electric field simulations based on conformal mapping, point electrode approximations and the finite element method (FEM) are also elaborated. Finally, current trends on bioimpedance sensors are discussed followed by an overview of instrumentation methods for bioimpedance measurements, covering aspects of voltage signal excitations, current sources, voltage measurement front-end topologies and methods for computing the electrical impedance

Electronics for Sensors

The aim of this Special Issue is to explore new advanced solutions in electronic systems and interfaces to be employed in sensors, describing best practices, implementations, and applications. The selected papers in particular concern photomultiplier tubes (PMTs) and silicon photomultipliers (SiPMs) interfaces and applications, techniques for monitoring radiation levels, electronics for biomedical applications, design and applications of time-to-digital converters, interfaces for image sensors, and general-purpose theory and topologies for electronic interfaces