Miniaturized Capsule System Toward Real-Time Electrochemical Detection of H2 S in the Gastrointestinal Tract.

Hydrogen sulfide (H2 S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H2 S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H2 S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas-sensing ingestible capsule is developed to enable real-time, wireless amperometric measurement of H2 S in GI conditions. A gold (Au) three-electrode sensor is modified with a Nafion solid-polymer electrolyte (Nafion-Au) to enhance selectivity toward H2 S in humid environments. The Nafion-Au sensor-integrated capsule shows a linear current response in H2 S concentration ranging from 0.21 to 4.5 ppm (R2 = 0.954) with a normalized sensitivity of 12.4% ppm-1 when evaluated in a benchtop setting. The sensor proves highly selective toward H2 S in the presence of known interferent gases, such as hydrogen (H2 ), with a selectivity ratio of H2 S:H2 = 1340, as well as toward methane (CH4 ) and carbon dioxide (CO2 ). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold-based notification is investigated, showing potential for in vivo application. Thus, the developed H2 S capsule platform provides an analytical tool to uncover the complex biology-modulating effects of intraluminal H2 S.

Freestanding region-responsive bilayer for functional packaging of ingestible devices.

Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal (GI) disease. As device complexity increases, so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations. While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions, their application is limited due to the geometric restrictions imposed by standard coating methods. Dip, pan, and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment. However, some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery. To this end, we present the freestanding region-responsive bilayer (FRRB), a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components. The bilayer is composed of rigid polyethylene glycol (PEG) under a flexible pH-responsive Eudragit® FL 30 D 55, which protects the contents of the capsule until it arrives in the targeted intestinal environment. The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms, some of which are demonstrated here. In this paper, we characterize and validate the use of this technology in a simulated intestinal environment, confirming that the FRRB can be tuned for small intestinal release. We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.