Bioimpedance monitoring system for pervasive biomedical applications

Abstract

Nowadays, Point-of-Care (PoC) are making a shifting of the classical medical procedures and treatment protocols, enhancing the performance of medical surveillance in all the world. It is a reliable and very cost-effective solution, specially in mid to low income countries and areas where access to specialized clinical laboratories is very restricted. However, there are several operational challenges and technical issues that must be addressed when aiming for a clinical system based on PoC devices health surveillance, decentralized patient self-testing and centralized data management for devices, pathologies treatment and patient monitoring improvement. The aim of this research is to design, fabricate and test a novel device / technology for PoC instantaneous screening and monitoring of cellular species, to address these issues and add new functionalities to existing devices to create Lab-on-a-Chip devices. The technique used to cellular monitoring is based on direct measurement from samples by means of its inherent electrical impedance, in order to overcome the operational challenges present on the actual PoC devices on the market.

The state of the art of PoC devices have been analysed to study their strengths and weakness, and determine the necessary improvements. This is, the development of instrumentation electronics, sensing systems as well as design protocols for truly PoC devices, relying on straight forward standards for economic, low power consumption, versatile, safe and reliable devices. The development of such technologies and devices is entailed to the evolution of these systems as implantable LOC devices for in vivo continuous monitoring of the patients. In this case, the development of simplified low-power electronics and sensing systems, leads to its miniaturization and integration in a single microchip with multiple functionalities. A discrete bench-top system for IA have been designed, fabricated and tested. The design and validation of different instrumentation electronics and sensing systems is presented, as well as design protocols for truly PoC devices. The device has been designed to perform an Impedance Spectrometry (IS) experiment in order to validate the whole device electronics as well as to characterize the sensing system and its interface accurately.

A first approach to a portable and compact device for PoC early instantaneous detection of anaemia, relying on hematocrit (HCT) screening, is described. This device has been designed to work directly with fresh whole blood samples. An experimental set-up and protocol of operation have been defined for instant impedance detection to determine the system detection accuracy, sensitivity and coefficient of variation. As you will notice, the device has been developed using prototyping tools from National Instruments for fast development and validation, as well as application functionalities.

Moreover, the possibilities of the integration of this technology within other devices, for increased functionalities, have been validated. The experiments were carried out with different instrumentations front-end as well as different sensing systems typologies, and the same back-end electronics for signal processing and system control. The analysed samples and its environment were dramatically different: laboratory sample formed by E. coli 5K strains working as a monitoring functionality of a DEP-enhanced concentrator for automated detection and concentration of bacteriological species.

Finally, it has been developed a specific PoC device for HCT detection and validated through a clinical assessment with whole blood samples. The design is based in the previously presented device’s electronic instrumentation and sensing system with the addition of an economic and low power back-end solution. A clinical study has been performed and the results obtained during the experimental procedures are shown, analysed and discussed. We summarize the conclusions obtained after this research and recommend future developments that could be done to develop truly last generation PoC devices and integrated LOC single-chip devices.

L’objectiu de la tesi és la realització d’equipaments electrònics per aplicacions biomèdiques de caràcter Poin-of-Care en entorns d’investigació, control i tractament clínic. Aquest projecte es troba en el marc de les activitats de recerca del grup, on el desenvolupament d’electròniques d’interface amb el mon biomèdic i la recerca de noves tecnologies i aplicacions d’instrumentació són unes de les principals tasques que porten a terme. Donades aquestes consideracions, a l’últim any s’ha definit un camí dintre dels sistemes d’instrumentació PoC orientats al control d’agents biològics cel·lulars amb tècniques d’anàlisi d’impedància. Aquests dispositius estan basats en dos conceptes claus: el disseny d’instrumentació electrònica senzilla, econòmica i de baix consum, així com sistemes de sensat versàtils i d’un sol us. D’aquesta manera, és possible desenvolupar equipaments versàtils, portables i de baix cost que poden aportar gran rendiment en diferents camps de la biomedicina. Amb aquestes premisses, s’ha desenvolupat un equipament d’anàlisi d’impedància independent del sistema de sensat, el que comporta la possibilitat d’utilitzar multitud de tipus de sistemes de sensat. Aquest equipament, consta d’una senzilla instrumentació electrònica basada en un sistema de sensat preparat per diferents tipus de sensors, tot controlat per un microprocessador encarregat del control automatitzat del hardware, post-processat de dades i comunicació amb un ordinador remot. El sistema és capaç de treballar en un rang de freqüències molt ampli, amb diferent tipus de potència de senyal i diferent tipus d’anàlisi i representació, com ara Electrochemical Impedance Spectroscopy (EIS) amb representació amb diagrames de Bode i Nyquist, o la selecció de punts de freqüencials concrets per un tipus d’anàlisi més específic per a un experiment biomèdic més concret, senzill i ràpid. Es tracta d’un equipament econòmic, fiable i senzill per l’anàlisi d’hematòcrit, que aporta avenços com la gran capacitat d’integració en ambients clínics, la possibilitat de fer un control medico sanitari instantani i reportar telemàticament els resultats o la possibilitat d’implementar un sistema de control mèdic integrat i automatitzat.