The system, being called bacteria-on-a-chip, uses sensors with living cells and ultra-low power electronics that can convert a bacterial response into wireless signals that can be read by a smartphone.
“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,” Timothy Lu, a MIT associate professor of electrical engineering and computer science, said in a press release.
A study of the bacteria-on-a-chip showed that the sensor responded to heme and worked in a pig. The sensors could also respond to a molecule that is a marker of inflammation.
While synthetic biologists have been engineering bacteria to respond to different stimuli like markers of disease, specialized lab equipment is still needed to measure the response from bacteria. The MIT researchers wanted to create something that makes the engineered bacteria more useful in the real-world. So, they combined the bacteria with an electronic chip that translates the bacterial response into a wireless signal.
“Our idea was to package bacterial cells inside a device,” Phillip Nadeau, one of the researchers, said. “The cells would be trapped and go along for the ride as the device passes through the stomach.”
Their initial testing of the chip focused on bleeding in the GI tract. To do this, the researchers engineered a probiotic strain of E. col to express a genetic circuit that makes bacteria emit light when they come into contact with heme.
The bacteria was placed into four wells on the custom-designed sensor and was covered by a semipermeable membrane that lets small molecules from the surrounding environment to diffuse through. Each well has a phototransistor beneath the surface that measures the amount of light produced by bacterial cells that can then relay the information to a microprocessor that sends the wireless signal to a nearby computer or smartphone. The researchers also developed an Android app to go with the chip to analyze the data.
The sensor is cylindrical and is about 1.5 in. long and requires approximately 13 microwatts of power. It has a 2.7 V battery that can power the device for about 1.5 months of continuous use, according to the researchers. The sensor can also be powered by a voltaic cell that is sustained by acidic fluids in the stomach.
“The focus of this work is on system design and integration to combine the power of bacterial sensing with ultra-low-power circuits to realize important health sensing applications,” said Anantha Chandrakasan, dean of MIT’s school of Engineering and a senior author on the study.
So far, the researchers have tested the chip on pigs and have shown that they could see whether there was blood in the stomach or not. The researchers hope that this type of sensor could either be used for a one-time use or for staying in the digestive tract for several days or weeks while sending continuous wireless signals.
Patients who have suspected bleeding from a gastric ulcer traditionally have to undergo an endoscopy to diagnose the problem, which also requires sedation.
“The goal with this sensor is that you would be able to circumvent an unnecessary procedure by just ingesting the capsule, and within a relatively short period of time, you would know whether or not there was a bleeding event,” Mark Mimee, one of the study’s lead authors, said.
The researchers plan to make the sensors smaller so that the technology can be used in humans. They also want to study how long the bacteria cells can survive in the digestive tract and hope to develop the sensor to detect gastrointestinal conditions other than bleeding. The researchers suggest that the sensors could also be modified to carry multiple strains of bacteria that could allow them to diagnose a variety of conditions.
“Right now, we have four detection sites, but if you could extend it to 16 or 256, then you could have multiple different types of cells and be able to read them all out in parallel, enabling more high-throughput screening,” Nadeau said.
The research was funded by Texas Instruments, the Hong Kong Innovation and Technology Fund, the Office of Naval Research, the National Science Foundation, the Center for Microbiome Informatics and Therapeutics, Brigham and Women’s Hospital, a Qualcomm Innovation Fellowship, and the Natural Sciences and Engineering Council of Canada. The study was published in the Science journal.