Signals from engineered bacteria found from a distance

Bacteria can be designed to sense various molecules, such as pollutants or soil nutrients. However, in most cases, these signals can only be detected by viewing cells under a microscope or similarly sensitive laboratory equipment, making them impractical for large-scale use.

MIT engineers use a new method to trigger a cell to produce a unique combination of molecules, suggesting that they can read these bacterial signals from 90 meters away. Their work could lead to the development of bacterial sensors for agriculture and other applications, which can be monitored by drones or satellites.

“This is a new way to get information from a cell,” said Christopher Voigt, head of the bioengineering department of MIT and senior author of the new study.

In the papers that appear today Natural Biotechnologythe researchers showed that they could design two different types of bacteria to produce molecules that emit unique light lengths on visible and infrared spectra that can be imaged with hyperspectral cameras. The researchers say these reporter molecules are related to genetic circuits that detect nearby bacteria, but this approach can also be used in conjunction with any existing sensors, such as sensors for arsenic or other contaminants.

“The benefit of this technology is that you can plug in any sensor you need,” said Yonatan Chemla of MIT PostDoc, one of the leading authors of this article. “There is no reason no sensor will be compatible with the technology.”

Itai Levin PhD ’24 is also the lead author of the paper. Other authors include former undergraduates Yueyang Fan ’23 and Anna Johnson ’22, and Connor Coley, associate professor of chemical engineering at MIT.

Hyperspectral imaging

There are many ways to design bacterial cells so that they can sense specific chemicals. Most work by connecting the detection of molecules to outputs such as green fluorescent protein (GFP). These are very effective for laboratory studies, but these sensors cannot be measured from long distances.

For long-distance sensing, the MIT team proposed an idea to design molecules that cells generate hyperspectral reports that can be detected using hyperspectral cameras. These cameras were originally invented in the 1970s and can determine the number of each color wavelength in each given pixel. Instead of simply displaying in red or green, each pixel contains information about hundreds of different wavelengths of light.

Currently, hyperspectral cameras are used for applications such as detecting the presence of radiation. In the area around Chernobyl, these cameras have been used to measure the slight color changes produced by radioactive metals in chlorophyll in plant cells. Hyperspectral cameras are also used to look for signs of malnutrition or pathogen attack in plants.

This work inspired the MIT team to explore whether they could design bacterial cells to produce hyperspectral reports when detecting target molecules.

To make hyperspectral reporters most useful, it should have a spectral signature and have multiple wavelengths of light peaks, making it easier to detect. The researchers performed quantum computing to predict the hyperspectral characteristics of about 20,000 naturally occurring cellular molecules, allowing them to identify the most unique light emission patterns of people. Another key feature is the number of enzymes that need to be designed in the cell to make it produce a reporter – this feature will vary by different types of cells.

“The ideal molecule is really different from all other objects, it can be detected and requires minimal enzymes to produce it in the cell,” Voigt said.

In this study, the researchers identified two different molecules that are most suitable for both types of bacteria. For bacteria called soil Pseudomonas PutidaThey used a reporter called Biliverdin, a pigment caused by a heme collapse. Used for aquatic bacteria rubrivivax gelatinThey used a bacterial green leaf. For each bacteria, the researchers designed the enzymes needed to generate host cells by reporters and then link them to genetically engineered sensor circuits.

“You can add one of these reporters to a bacteria or any cell in the genome that has a genetic code for sensors. So it may react to metals, radiation or metals in the soil, radiation or toxins, nutrients in the soil, or anything you wish it could respond. Then, the production of this molecule could be the production of that molecule that is said from afar.

Long-distance sensing

In this study, the researchers linked hyperspectral reporters to circuits designed for legal sensing, which allows cells to detect other nearby bacteria. In the work that follows this article, they also show that these reporter molecules can be associated with sensors of chemicals including arsenic.

When testing sensors, researchers deployed them in a box so that they could be kept in the box. Place the box on the roof of a field, desert, or building, and the signals generated by the cells can be detected using a hyperspectral camera mounted on the drone. The camera takes about 20 to 30 seconds to scan the field of view, and then the computer algorithm analyzes the signal to reveal whether there is a hyperspectral reporter.

In this article, the researchers reported imaging at a maximum distance of 90 meters, but they are now working to extend those distances.

They envisioned that these sensors could be used for agricultural purposes, such as sensing nitrogen or nutrient levels in soil. For these applications, sensors can also be designed to function in plant cells. Detection of landmines is another potential application of such sensing.

Prior to deployment, the sensor will need to be regulated by the Environmental Protection Agency and the USDA if used in agriculture. Voigt and Chemla have been working with two agencies, the scientific community and other stakeholders to determine what questions need to be answered before approving these technologies.

“We have been busy over the past three years to understand what regulatory landscapes are, what security issues are, what risks are, what benefits are of this technology?” Chemla said.

The study was funded by the U.S. Department of Defense, U.S. Military Research Bureau and Israeli Department of Defense.