An ingestible bioimpedance sensing device for wireless monitoring of epithelial barriers

Abstract

Existing gastrointestinal (GI) diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus. In the GI tract, local inflammatory processes induce alterations in tight junction proteins, enhancing paracellular ion permeability. Although transepithelial electrical resistance (TEER) may be used in the laboratory to assess mucosal barrier integrity, there are no existing methodologies for characterizing tight junction dilation in vivo. Addressing this technology gap, intraluminal bioimpedance sensing may be employed as a localized, non-invasive surrogate to TEER electrodes used in cell cultures. Thus far, bioimpedance has only been implemented in esophagogastroduodenoscopy (EGD) due to the need for external electronics connections. In this work, we develop a novel, noise-resilient Bluetooth-enabled ingestible device for the continuous, non-invasive measurement of intestinal mucosal "leakiness." As a proof-of-concept, we validate wireless impedance readout on excised porcine tissues in motion. Through an animal study, we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure. Device measurements are validated using standard benchtop methods for assessing mucosal permeability.

Fig. 1. Overview schematic depicting the ingestible capsule monitoring bioimpedance in the small intestine.

a Diagram of an ingestible bioimpedance sensing device traversing through the GI tract, wirelessly transmitting impedance. Illustration of tight junction dilation during inflammatory processes in the small intestinal mucosa. b Electronics schematic of impedance sensing capsule and flex-rigid PCB

Fig. 2. Sensor illustration and PEDOT:PSS electrodeposition.

a Schematic diagram of cross-sectional view of sensor. b Exploded rendering of impedance sensor bending to conform to cylindrical package. c Illustration of PEDOT:PSS treatment on sensor, reducing interfacial impedances during impedance measurement on epithelial tissue. d (i) Chronopotentiogram of PEDOT:PSS electrodeposition onto Au electrodes at various current densities. (ii) Cyclic voltammogram of unmodified and PEDOT:PSS-coated Au electrodes (1 µA·mm⁻², 600 s) in PBS (Scan rate: 100 mV·s⁻¹). e EIS recording via EVAL-AD5941 portable potentiostat development kit of (i) unmodified and (ii) coated sensor (N = 3), exhibiting uniform frequency response and excellent sensitivity to ion content. f PEDOT:PSS-coated sensor performance after repeated EIS measurements in PBS: (i) impedance magnitude response to time at various frequencies, and (ii) relative increase in impedance magnitude from initial measurement after 150 min

Fig. 3. Comparison of untreated and PEDOT:PSS-coated electrodes on excised porcine intestinal tissue samples.

a EIS impedance magnitude recordings were obtained using the AD5941 devkit on five porcine small intestinal tissue samples with (i) PEDOT:PSS-coated and (ii) unmodified impedance sensors. The phase response was measured for (iii) PEDOT:PSS-coated and (iv) unmodified impedance sensor. b Photograph of assembled sensor-integrated capsule. c Illustration of capsule device obtaining initial measurements to wirelessly set bioimpedance LED threshold. d Average impedance magnitude reported for unmodified tissue and PBS-soaked tissue by Au and PEDOT:PSS-coated sensor following capsule-integration. e Linear translation of integrated capsule measuring impedance along porcine small intestinal tissue (pink) and dyed PBS-treated tissue (blue) depicting LED activation upon contact with treated tissue. f Impedance magnitude data transmitted to mobile device via Bluetooth during translation

Fig. 4. Mice experimentation overview in Ussing chamber and using fabricated sensor with and without integration with capsule electronics.

a Mice colonic tissue is extracted and treated with EDTA to disrupt tight junctions, reducing transepithelial resistance and hence mucosal bioimpedance. b Ussing chamber measurement confirms varying degrees of decreased tissue resistance following EDTA treatment over time for EDTA-treated samples A and B, and constant tissue resistance for the two control samples. When EDTA is replaced with KRB solution, tissue resistance slightly rises, denoting recovery. c Bioimpedance magnitude values sampled at 10.5 kHz among five mice using EVAL-AD5941. d Averaged magnitude values plotted relative to healthy, non-treated tissue impedance e Assembled capsule measurement at 10 kHz