Novel microelectrode arrays for measuring bioelectrical activity in the gut

Abstract

The mechanical contractions responsible for the motility of the gastrointestinal (GI) tract are governed, in part, by an underlying electrophysiological phenomenon known as slow waves. The abnormal origin and propagation of slow waves are prevalent in a number of functional GI motility disorders. The ability to reliably detect and normalise GI dysrhythmias would be an important advance for the diagnosis and treatment of these disorders. In order to characterise the slow wave activity, rigid and flexible high-resolution (HR) electrode arrays have been developed in the GI field. The current HR electrode arrays have been optimised with 4-5 mm inter-electrode spacing as investigations of the GI myoelectrical activity have primarily applied to the serosal surface of the GI tract. However, the evaluation of intramural electrical activity within the GI wall has been a prolonged technical challenge due to the thin and complex laminar structure of the tissue. Alternative techniques and electrodes for recording the activity through the wall of the GI tract are required. Additionally, there has been a growing interest in the translation of GI mapping techniques for the investigation of smaller animals such as rodents. The ability of transgenic mice to replicate human disease conditions has been of special interest in the adaptation of smaller animals for GI investigations. Thus, this research aims to address these challenges by developing and validating a range of novel microelectrode arrays with spatial resolution suitable for mapping electrical activity through the GI wall or from the organs of small laboratory animals. A comprehensive evaluation of an extensive range of technologies was conducted through which a series of fabrication techniques suitable for the development of microelectrode arrays were identified. In total, 11 distinct and novel microelectrode arrays were designed and fabricated. In total, three Needle arrays (two linear microelectrode arrays (LMAs), one Cardiac-needle array), three printed circuit board (PCB) arrays (one Rigid PCB array, one Needle PCB array, one stiffened Needle PCB array), four Brush arrays (three Cable bundle arrays, one Microwire brush array (MBA)), and one Glass chip array were evaluated. The developed arrays were benchtop tested for functionality, followed by in-vivo application for serosal and transmural signal acquisition along the GI tract. The acquired data were qualitatively and quantitatively analysed, and compared against the standard flexible printed circuit array (FPC). In particular, the slow wave period, amplitude, velocity, and signal to noise ratio (SNR) parameters were evaluated. When applied to the serosal surface, all novel microarrays demonstrated conforming slow wave frequency values in comparison to the standard FPC array. The MBA and Glass chip array depicted higher amplitude signals than the FPC array (0.7-1.4 times higher). Based on the SNR computations, adequate signal quality was reported for all the developed microarrays. In particular, the MBA, Glass chip array, Rigid PCB array, and Needle PCB array reported SNR values greater than 9.0 dB, demonstrating higher quality of signals compared to the FPC array. Transmural myoelectrical activity was successfully acquired using the Rigid PCB array, LMA, and Cardiac-needle array. Consistent period values were reported against the standard FPC array with mean percentage differences below 8.2% for all the aforementioned arrays. Low amplitudes were reported in comparison to the serosal activity (reduction by a factor of 0.6-0.9). Both the Needle arrays had relatively higher amplitudes than the Rigid PCB array. In comparison to serosal measurements, lower SNRs were reported for the all transmural recordings. However, SNRs greater than 8.0 dB were achieved by all the arrays. The Needle arrays had higher SNR than the Rigid PCB array. With a comprehensive evaluation of translational fabrication technologies, 11 novel microelectrode arrays were introduced for the investigation GI myoelectrical activity. Particularly, the development of Glass chip array marks the first translation of photolithographic microfabrication technologies for electrical mapping in the field of GI with optimal miniaturisation. Upon implementation for the investigation of in-vivo GI myoelectrical activity, PCB and Glass chip arrays were concluded most applicable for serosal signal measurement based on the manufacturing feasibility and signal acquisition competencies. Moreover, based on similar attributes, the Needle arrays were considered best-suited for transmural signal acquisition. Thereby, the technical challenges of exploring the myoelectrical activity within the intramural layers of the GI wall have been successfully addressed; whilst also contributing to the translation of GI mapping techniques for the investigation of smaller animals.