Cancerous versus healthy omental tissue voltage measurements: Methods and circuits
Creators: name: Wu, Wen
Publisher: name: Imperial College London
Year: 2016

description: This thesis presents a novel method of measuring tissue biopotentials to diagnose cancerous tissue and a study of corresponding readout circuits. The new voltage measurement is carried out using a pair of electrodes (an Ag/AgCl reference electrode and a tungsten electrode), a conventional instrumentation amplifier (IA) and a conventional data acquisition instrument. The proposed measurement setup paves the way for implementing real-time diagnostics during surgery through a portable medical device and in vivo monitoring through a miniaturised low-power implanted medical device (IMD). First, the biological aspects of the measurement are discussed. The thesis describes the novel measurement method, and uses a double-layer equivalent circuit to explain the underlying mechanism of the existence of different potentials between cancerous and non-cancerous tissues. The equivalent circuit is then verified by media-only experiments and cancerous-omentum-tissue measurements, respectively. The experimental results concur with the corresponding theoretical analysis of the double-layer equivalent. Second, the thesis elaborates upon a circuit topology of a miniaturized low power microelectronic chip to substitute the conventional IA and data acquisition instrument to read out electrochemical signals and transmit the signals out. The circuit topology is composed of a multiplexer, a wide-linear-range (WLR) operational transconductance amplifier (OTA) and a current-controlled oscillator (CCO). The multiplexer enables multi-channel measurements in parallel, the WLR OTA converts the electrochemical signal into current mode in a wide input range, and the CCO converts the current signal into frequency mode for wireless transmission via coil-based transcutaneous coupling. Notably, a novel method called non-linear term cancellation is proposed. The method uses popularity of cross-coupled pairs to implement an OTA linear range stretch rather than using conventional transconductance attenuation. Its merits include better linearisation and theoretically infinite expansion. Finally, the chip design was fabricated by using AMS 0.35um technology and tested in Hammersmith hospital's primary lab. For the first time, it shows the possibility of reading out the electrochemical signal by a miniaturised low-power microelectronic chip rather than conventional electronic equipment. The thesis elaborates upon a study of a potential IMD prototype in the appendix. Selections of radio frequency (RF) bands and low power RF chips are investigated, together with analogue-to-digital (A to D) interfacing chip designs, antenna technologies, battery technologies, etc. Notably, in the interfacing chip design, the thesis demonstrates an ultra-low power topology by combining the novel WLR OTA with a time-based A to D circuit. Based on all of the practical parameters collected in the investigation, a proof-of-concept prototype is proposed at simulation level for the implementation of an IMD using the novel method of tissue voltage measurement. Biocompatibility and radiative safety concerns are also discussed. Prospectively, future work may be done on implementing the prototype using widely available technologies.