skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Magnetic Living Hydrogels for Intestinal Localization, Retention, and Diagnosis
Abstract Natural microbial sensing circuits can be rewired into new gene networks to build living sensors that detect and respond to disease‐associated biomolecules. However, synthetic living sensors, once ingested, are cleared from the gastrointestinal (GI) tract within 48 h; retaining devices in the intestinal lumen is prone to intestinal blockage or device migration. To localize synthetic microbes and safely extend their residence in the GI tract for health monitoring and sustained drug release, an ingestible magnetic hydrogel carrier is developed to transport diagnostic microbes to specific intestinal sites. The magnetic living hydrogel is localized and retained by attaching a magnet to the abdominal skin, resisting the peristaltic waves in the intestine. The device retention is validated in a human intestinal phantom and an in vivo rodent model, showing that the ingestible hydrogel maintains the integrated living bacteria for up to seven days, which allows the detection of heme for GI bleeding in the harsh environment of the gut. The retention of microelectronics is also demonstrated by incorporating a temperature sensor into the magnetic hydrogel carrier.  more » « less
Award ID(s):
1935291
PAR ID:
10641258
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Functional Materials
Volume:
31
Issue:
27
ISSN:
1616-301X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract 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. 
    more » « less
  2. 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. 
    more » « less
  3. The integration of an ingestible dosage form with sensing, actuation, and drug delivery capabilities can enable a broad range of surgical‐free diagnostic and treatment strategies. However, the gastrointestinal (GI) tract is a highly constrained and complex luminal construct that fundamentally limits the size of an ingestible system. Recent advancements in mesoscale magnetic crawlers have demonstrated the ability to effectively traverse complex and confined systems by leveraging magnetic fields to induce contraction and bending‐based locomotion. However, the integration of functional components (e.g., electronics) in the proposed ingestible system remains fundamentally challenging. Herein, the creation of a centralized compartment in a magnetic robot by imparting localized flexibility (MR‐LF) is demonstrated. The centralized compartment enables MR‐LF to be readily integrated with modular functional components and payloads, such as commercial off‐the‐shelf electronics and medication, while preserving its bidirectionality in an ingestible form factor. The ability of MR‐LF to incorporate electronics, perform drug delivery, guide continuum devices such as catheters, and navigate air–water environments in confined lumens is demonstrated. The MR‐LF enables functional integration to create a highly integrated ingestible system that can ultimately address a broad range of unmet clinical needs. An interactive preprint version of the article can be found athttps://doi.org/10.22541/au.166274072.23086985/v1. 
    more » « less
  4. Abstract The spatiotemporal structure of the human microbiome1,2, proteome3and metabolome4,5reflects and determines regional intestinal physiology and may have implications for disease6. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals7. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease. 
    more » « less
  5. Abstract Functioning ingestible capsules offer tremendous promise for a plethora of diagnostic and therapeutic applications. However, the absence of realistic and practical power solutions has greatly hindered the development of ingestible electronics. Microbial fuel cells (MFCs) hold great potential as power sources for such devices as the small intestinal environment maintains a steady internal temperature and a neutral pH. Those conditions and the constant supply of nutrient‐rich organics are a perfect environment to generate long‐lasting power. Although previous small‐scale MFCs have demonstrated many promising applications, little is known about the potential for generating power in the human gut environment. Here, this work reports the design and operation of a microbial biobattery capsule for ingestible applications. DormantBacillus subtilisendospores are a storable anodic biocatalyst that will provide on‐demand power when revived by nutrient‐rich intestinal fluids. A conductive, porous, poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate hydrogel anode enables superior electrical performance in what is the world's smallest MFC. Moreover, an oxygen‐rich cathode maintains its effective cathodic capability even in the oxygen‐deficit intestinal environment. As a proof‐of‐concept demonstration in stimulated intestinal fluid, the biobattery capsule produces a current density of 470 µA cm−2and a power density of 98 µW cm−2, ensuring its practical efficacy as a novel and sole power source for ingestible applications in the small intestine. 
    more » « less