Hybrid Hydrogel-Magnetic Driven Capsule for Automatic Intestinal Microbiome Sampling

Academic Background

The gut microbiome is composed of a large and diverse community of microorganisms that significantly impact human health, including conditions such as cancer, diabetes, and inflammatory bowel disease (IBD). Current methods for studying the gut microbiota mainly include fecal sampling, ileostomy, or colonoscopy. However, these methods have various issues: fecal sampling cannot provide information specific to certain intestinal segments, while ileostomy and colonoscopy are highly invasive. Therefore, there is a need for a non-invasive tool capable of targeted sampling in the small intestine.

In recent years, swallowable capsules have emerged as a solution. While performing targeted sampling, these capsules also have functions such as drug delivery, tissue biopsy, and active locomotion. However, existing liquid sampling capsules still face size limitations and high complexity. An effective design for an automatic sampling capsule with active locomotion is still scarce.

Research Source

This paper, co-authored by Yung P. Lai, Taeyoung Lee, Daniel Sieben, Lyle Gauthier, Jaekwang Nam, and Eric Diller (IEEE Senior Member), was published in the “IEEE Transactions on Biomedical Engineering” and accepted on May 7, 2024. The research was partially funded by the Natural Sciences and Engineering Research Council of Canada (grant number: RGPIN-2020-04551). The authors are from the Department of Mechanical and Industrial Engineering, Institute of Robotics, Institute of Biomedical Engineering at the University of Toronto, and Kwangwoon University in South Korea.

Research Details

Research Process

The study designed two different capsule designs (Design A: sampling volume 31 µl, size 8 mm × 19 mm; Design B: sampling volume 41 µl, size 8 mm × 21 mm). The capsule uses two different mechanisms:

1. pH-responsive hydrogel-triggered sampling: The hydrogel automatically triggers liquid sampling when the ambient pH exceeds 6.
2. Active locomotion mechanism: Active movement of the capsule is achieved through an external rotating magnetic field.

Specific process steps are as follows:

Design and Manufacturing: - The capsule consists of an upper part containing a magnetic lock, pH-responsive hydrogel, sliding components, and two small cubic spring magnets, and a lower part containing a molding star-shaped O-ring seal, a piston magnet, a sampling chamber cover, a sampling chamber, and an activation magnet.

Experimental Validation: - The capsule’s automatic sampling function was tested in simulated gastric juice (pH = 1.2) and simulated intestinal fluid (pH = 6.8). - The capability for active locomotion was tested using an external rotating magnetic field. - Sealing tests were conducted to demonstrate sample contamination control effectiveness.

Main Experimental Results

1. Automatic Sampling and pH Response Verification:

   • In simulated intestinal fluid, the hydrogel triggered fast sampling, achieving automatic sample collection. Design A completed sampling within 6-15 hours, while Design B completed sampling in 15.2 hours.
   • The sampling mechanism was realized through the sliding of the sample chamber piston, driven by the swelling of the hydrogel. The capsule performed the entire open-sampling-close process using magnetic sliding.

2. Active Locomotion Function:

   • Under the drive of an external rotating magnetic field (magnetic field strength <10 mT), the capsule successfully achieved rotational, rolling, and tumbling movements. Rotational movement was carried out in ducts, rolling movement in an open environment, and tumbling movement was realized under the constraints of tube walls.

3. Sealing Performance:

   • Comparisons between water seals and oil seals under static conditions showed that oil seals provided better protection against sample contamination.
   • Test results indicated that the initial and final sealing pressures of the capsule were both higher than the intra-abdominal pressure of a normal adult, demonstrating excellent sealing performance.

Research Conclusion

This study proposes an innovative hybrid hydrogel-magnet driven capsule design featuring: - Automatic sampling capability: Utilizing pH-responsive hydrogel to automatically trigger sampling without external activation. - Active locomotion function: Achieving multiple movement modes through an external rotating magnetic field, enhancing the capsule’s mobility within the intestine. - Excellent sealing performance: Using an oil seal to effectively prevent sample contamination, ensuring the integrity of the collected samples.

Research Significance and Value

This study has important scientific and application value in multiple aspects. First, it provides a more accurate, non-invasive method for gut microbiome sampling, promising significant improvements in current gut microbiota research techniques. Secondly, the multifunctionality and compact design of this capsule make it widely applicable in clinical settings, especially in nutrition absorption and chronic disease monitoring. Moreover, this design reduces the need for complex external controls and guidance, improving operational simplicity. This research not only brings innovative breakthroughs in capsule design and operation mechanisms but also provides valuable references for future medical device development, promising to advance the field of gut microbiome research.