Genetically engineered bacteria lets ingestible sensor monitor gut health
Science is only just coming to grips with the complex and symbiotic relationship we all have with bacteria. From making us sick to keeping us healthy, the effects of bacteria dominate our day-to-day experience, but more recently researchers have begun making these tiny microbes actively work for us. Engineering bacteria to undertake such varied tasks as identifying toxic substances in the environment to detecting inflammation in our colons is only the beginning of a burgeoning field of science learning how to recruit these tiny helpers.
Now a team of researchers at MIT has produced a novel "bacteria on a chip" system that combines genetically engineered bacteria that can detect intestinal bleeding with an ingestible electronic circuit that can wirelessly send a signal to a nearby computer.
"By combining engineered biological sensors together with low-power wireless electronics, we can detect biological signals in the body and in near real-time, enabling new diagnostic capabilities for human health applications," says Timothy Lu, one of the MIT researchers working on the project.
To begin, the team genetically engineered a probiotic strain of E. coli bacteria to respond to the presence of a chemical compound call heme, a compound found within red-blood cells and has been shown to be a reliable biomarker of internal bleeding. Upon encountering heme, the engineered bacteria emits a small amount of light.
The next step was developing a way to transport these bacterial sensors through a body and translate the signals into data that can be transmitted instantly. A capsule was created with four wells that hold the bacteria. Molecules from the body permeate through a membrane into the wells and, in the presence of heme, trigger the bacteria to emit light. That light is then measured by a phototransistor underneath each well which wirelessly relays the data to a nearby smartphone or computer.
"Our idea was to package bacterial cells inside a device," says Phillip Nadeau, one of the lead authors on the study. "The cells would be trapped and go along for the ride as the device passes through the stomach."
The entire device sits in a capsule-shaped cylinder about 1.5 inches (3.8 cm) long. The prototype device was equipped with a 2.7-volt battery that is estimated to offer 1.5 months use. However, future iterations could be entirely self-powered as a the same team previously developed a battery-free device that generates electricity from stomach acid.
Initial tests found the device accurately detected the presence of blood in the stomach of pigs, and the researchers have already developed two more bacterial sensors pointing to other potential future diagnostic uses. One proposed sensor detects thiosulfate, a compound linked to inflammatory conditions, while another sensor detects a molecule called AHL, a known biomarker for gastrointestinal infections.
"Most of the work we did in the paper was related to blood, but conceivably you could engineer bacteria to sense anything and produce light in response to that," says co-lead author on the project, Mark Mimee. "Anyone who is trying to engineer bacteria to sense a molecule related to disease could slot it into one of those wells, and it would be ready to go."
The next steps in the project will look to reduce the size of the capsule sensor and examine how long these engineered bacterial cells can survive. The goal is for these sensors to potentially be able to remain in a person's digestive tract for weeks, sending continuous signals that let a doctor instantly track a variety of conditions.
The research was published in the journal Science.