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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.

 

Serotonin (5-HT) is one of the key neurotransmitters in the human body, regulating numerous physiological functions. A disruption in 5-HT homeostasis could result in serious health problems, including neurodegenerative disorders, depression, and 5-HT syndrome. Detection of 5-HT concentrations in biological fluids, such as urine, is a potential solution for early diagnosis of these diseases. In this study, we developed a novel, simple, and low-cost electrochemical sensing platform consisting of a portable workstation with customized electrodes for 5-HT detection in artificial biological fluids. Nafion/carbon nanotubes (CNTs) and electrochemically modified carbon fiber microelectrodes (Nafion–CNT/EC CFMEs) displayed improved 5-HT sensitivity and selectivity. Together with a customized Ag/AgCl reference electrode and Pt counter electrode, the portable 5-HT sensing platform had a sensitivity of 0.074 μA μM −1 and a limit of detection (LOD) of 140 nM. This system was also assessed to measure 5-HT spiked in artificial urine samples, showing nearly full recovery rates. These satisfactory results demonstrated that the portable system exhibits outstanding performance and confirmed the feasibility of 5-HT detection, which can be used to provide point-of-care analysis in actual biological samples. 

Hydrogen sulfide (H₂S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H₂S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H₂S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas‐sensing ingestible capsule is developed to enable real‐time, wireless amperometric measurement of H₂S in GI conditions. A gold (Au) three‐electrode sensor is modified with a Nafion solid‐polymer electrolyte (Nafion‐Au) to enhance selectivity toward H₂S in humid environments. The Nafion‐Au sensor‐integrated capsule shows a linear current response in H₂S concentration ranging from 0.21 to 4.5 ppm (R²= 0.954) with a normalized sensitivity of 12.4% ppm⁻¹when evaluated in a benchtop setting. The sensor proves highly selective toward H₂S in the presence of known interferent gases, such as hydrogen (H₂), with a selectivity ratio of H₂S: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 H₂S capsule platform provides an analytical tool to uncover the complex biology‐modulating effects of intraluminal H₂S.

 

Ingestible capsule systems continue to evolve to overcome drawbacks associated with traditional gastrointestinal (GI) diagnostic and therapeutic processes, such as limitations on which sections of the GI tract can be accessed or the inability to measure local biomarker concentrations. We report an integrated capsule sensing system, utilizing a hybrid packaging scheme coupled with triglyceride film-coated capacitive sensors, for measuring biochemical species present in the duodenum, such as pancreatic lipase and bile acids. The system uses microfabricated capacitive sensors interfaced with a Bluetooth low-energy (BLE)-microcontroller, allowing wireless connectivity to a mobile app. The triglyceride films insulate the sensor surface and react either with 0.01–1 mM lipase via hydrolysis or 0.07–7% w/v bile acids via emulsification in simulated fluids, leading to measurable changes in capacitance. Cross reactivity of the triglyceride films is evaluated in both phosphate buffered saline (PBS) as well as pancreatic trypsin solutions. The film morphology is observed after exposure to each stimulus to better understand how these changes alter the sensor capacitance. The capsule utilizes a 3D-printed package coated with polymers that remain intact in acid solution (mimicking gastric conditions), then dissolve at a duodenum-mimicking neutral pH for triggered opening of the sensing chamber from which we can subsequently detect the presence of pancreatic lipase. This device strategy represents a significant step towards using embedded packaging and triglyceride-based materials to target specific regions of the GI tract and sensing biochemical contents for evaluating gastrointestinal health. 

Current systemic therapies for inflammatory gastrointestinal (GI) disorders are unable to locally target lesions and have substantial systemic side effects. Here, a compact mesoscale spring actuator capable of delivering an anchoring drug deposit to point locations in the GI tract is demonstrated. The mechanism demonstrated here is intended to complement existing ingestible capsule‐based sensing and communication technologies, enabling treatment based on criteria such as detected GI biomarkers or external commands. The 3D‐printed actuator has shown on command deployment in 14.1 ± 3.0 s, and a spring constant of 25.4 ± 1.4 mN mm⁻¹, sufficient to insert a spiny microneedle anchoring drug deposit (SMAD) into GI tissue. The complementary SMAD showed a 22‐fold increase in anchoring force over traditional molded microneedles, enabling reliable removal from the actuator and robust prolonged tissue attachment. The SMAD also showed comparable drug release characteristics (R² = 0.9773) to penetrating molded microneedles in agarose phantom tissue with a drug spread radius of 25 mm in 168 h. The demonstrated system has the potential to enable on command delivery and anchoring of drug‐loaded deposits to the GI mucosa for sustained treatment of GI inflammation while mitigating side effects and enabling new options for treatment.