Schematic showing the use of magnetic hydrogel devices containing living sensors for studying the gut. Credit: Xinyue Liu et al
The last decade has seen a boom in research into the human microbiome and the microbes that are key to its function. This is because scientists now know that the entire system has a greater impact on our bodies than we thought. For example, imbalances in gut chemicals have been linked with diseases such as Parkinson's disease and Alzheimer's. Scientists are working on better treatments and diagnostics for gut diseases like colon cancer.
The gut is like a blackbox. This is the challenge. It's hard to study and access, so we don't know how to fully understand it," Maria Eugenia Inda is a Pew Postdoctoral Fellow in MIT's Department of Electrical Engineering and Computer Science.
Inda and her colleagues present a new solution to this problem in the journal Advanced Functional Materials. The researchers encapsulated living bacteria in a small, flexible hydrogel disc that can be ingested. These bacteria can then detect compounds that may indicate disease. The bacteria in the disc can then be analysed to determine what it has detected and at what concentrations.
The team created the magnetic disc to keep the living sensors in the stomach for as long as possible. This keeps the system internal for several days by using a small, wearable magnet. The magnet can be removed and the sensor and data are ready to be analysed.
Giovanni Traverso is the Karl Van Tassel (1925), Career Development Professor at MIT's Department of Engineering. "This technology offers a valuable tool to control and understand imbalances of chemicals in the gastrointestinal tract." Traverso did not participate in the research.
Timothy Lu, an MIT associate Professor of EECS, biological engineering, and Xuanhe Zhang, an MIT professor in mechanical engineering and civil and environmental engineering respectively, are the senior authors of Advanced Functional Materials paper. Lu is also affiliated to MIT's Materials Research Laboratory.
"We created new soft materials, such as magnetic hydrogels, and examined their extreme mechanics like deformation and adhesion within the gut. Zhao says that she collaborated with the Lu laboratory to explore soft materials' impact on biomedicine and living materials.
Maria Eugenia Inda and Xinyue Liu hold some equipment that they and MIT colleagues used for creating living sensors to study the gut. Liu is a MIT graduate student, Inda an MIT postdoctoral fellow. Credit: Maria Eugenia Inda and Xinyue Luu
Inda, Zhao, Lu and Shaoting Lin are also authors. Graduate student Xinyue Liu is a visiting student. Graduate student Shaoting Lin is a postdoctoral fellow. Graduate student Yoonho Kim is a postdoctoral associate. Dacheng Ma is a postdoctoral associate. Ma and Inda work in the Lu laboratory. The other authors are associated with the Zhao lab. Yang, Liu, Inda all contributed equally to this work.
Many challenges
In the Advanced Functional Materials paper, important developments were made towards making the hydrogel-bacteria system for the gut a reality. The researchers present the best "recipe for hydrogel disc" that not only allows the bacteria to reproduce but also survives the pressures and movements of the intestinal system.
The bacteria survived and thrived in the hydrogel disc for seven days, according to the team. The bacteria was able to sense bleeding in the stomach of mice. The scientists also demonstrated that the magnetic wearable magnet held the disc in place at multiple locations in the human gut, including the small intestine, ascending colon, and the stomach.
The Lu lab genetically engineered the bacteria to detect bleeding factors. The Lu lab is currently working to develop other genetically engineered bacteria that can not only detect multiple chemicals but also release therapeutics when there is a problem.
The team also included a tiny electronic temperature sensor into the hydrogel. This also worked and demonstrated the potential to integrate microelectronics with living sensors into the hydrogel system.
Inda stresses the collaborative nature of the work. Hydrogel experts like Xinyue LIu, for instance, aimed at making the gel matrix strong enough to survive in the gut. Inda and other biologists focused on maintaining the bacteria alive in the hydrogel disc. They developed a system that met both of these goals.
The Future is Possible
Inda says that although it will take some time for the system to work in humans, "it could still be used today in laboratory mice."
Rabia Yazicigil, assistant professor at Boston University's Department of Electrical and Computer Engineering, is a member of the Department of Electrical and Computer Engineering. Yazicigil, who did not participate in the research, said that "Biologic hypotheses can be easily tested in animal models by dietary changes, therapeutics, genetic alteration of hosts or microbes and this allows us to test our treatments."
These tests should yield new insights that can be applied to the human body.
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Additional information: Xinyue Liu et.al, Magnetic Living Hydrogels For Intestinal Retention and Diagnosis. Advanced Functional Materials (2021). Information from the Journal: Advanced Functional Materials Xinyue Liu et all, Magnetic Living Hydrogels For Intestinal Location, Retention and Diagnosis (2021). DOI: 10.1002/adfm.202010918
