Haeme-sensitive biosensors constructed from genetically engineered probiotic bacteria can diagnose gastric bleeding in real-time in a pig model, according to a new study.
The human gastrointestinal tract is a challenging environment to access. Endoscopy, the modality most frequently used for this purpose, is invasive, costly and requires an expert practitioner to achieve optimal results. Advances in miniaturizing electronic devices have opened the door to using ingestible capsules to deliver various sensors to the gastrointestinal tract. However, despite the relative clinical success of capsule endoscopes, a number of hurdles have prevented the development of sensors able to measure molecular biomarkers noninvasively.
“a number of hurdles have prevented the development of sensors able to measure molecular biomarkers noninvasively”
Biosensors, which use genetically engineered cells to detect levels of clinically relevant molecules, could offer a solution. “We realized that genetically engineered cells created by Tim Lu and his student Mark Mimee could be used as sensors in harsh and difficult-to-access environments,” explains author Phillip Nadeau. “I had been working on ultra-low power wireless circuits with my advisor Anantha Chandrakasan, and we thought we might be able to combine the cells together with low power wireless readout electronics that could fit into a small device.”
To create biosensors able to detect gastric bleeding, the researchers engineered a genetic construct consisting of bioluminescent reporter genes under the control of a promoter regulated by a haeme-responsive element. A gene encoding an outer-membrane haeme transporter was included in the construct to enable haeme internalization, and the entire gene circuit was introduced into a probiotic Escherichia coli strain.
Finally, these cells were incorporated into wells mounted in small ingestible capsules. “The resultant biosensors produce light in the presence of the target analyte and this luminescence can be detected by the electronic readout circuits in the capsule,” says Mimee. “Custom-designed electronics can process the luminescence data and transmit it wirelessly from inside the body to a cellular phone.” In a proof-of-concept study, the capsule was able to rapidly diagnose gastric bleeding in a porcine model — 100% sensitivity and specificity was achieved 2 h after device administration.
“We’re developing additional biosensors that can detect disease-related biomolecules other than blood,” concludes Mimee. “On the electronics front, we’re working on further miniaturizing the device by combining several components into a single integrated circuit.”
Mimee, M. et al. An ingestible bacterial-electronic system to monitor gastrointestinal health. Science 360, 915–918 (2018)
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Thomas, H. Ingestible biosensors for gastrointestinal diagnosis. Nat Rev Gastroenterol Hepatol 15, 455 (2018). https://doi.org/10.1038/s41575-018-0042-5
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