Genetic networks mimic electronic circuits to perform a range of logic functions — ScienceDaily

Synthetic Biologists at Northwestern University has developed an inexpensive, easy-to-use, hand-held device that can notify users – in minutes – if their water is safe to drink.

The new device works using powerful and programmable genetic networks that mimic electronic circuits to perform a number of logical functions.

Among DNA-based chains, for example, researchers have created cell-free molecules in an analog-to-digital converter (ADC), a ubiquitous type of circuit found in almost all electronic devices. In a water quality device, the ADC circuit processes the analog input (contamination) and generates a digital output (a visual signal to inform the user).

The study will be published Feb. 17 in the journal Nature Chemical Biology.

Equipped with a series of eight small test tubes, the device glows green when it detects contamination. The number of tubes that glow depends on the amount of contamination. If only one tube glows, then there are traces of contamination in the water sample. But if all eight tubes glow, then the water is heavily polluted. In other words, a higher concentration of contaminant leads to a higher signal.

“We programmed each tube to a different contamination threshold,” said Julius B. Lax of Northwestern, who led the study. “The tube with the lowest threshold will burn all the time. If all the tubes catch fire, then there is a big problem. Chain construction and programmable DNA calculations open up a lot of possibilities for other types of intelligent diagnostics.”

Lax is a professor of chemical and biological engineering at McCormick School of Engineering in the Northwest State and a member of the Center for Synthetic Biology. The co-authors of the article are Jeon Jung, Chloe Archuleta and Khalid Alam – all from the Northwest.

Meet RALINDA

The new system is based on the work in which Lax and his team published The Nature of Biotechnology in July 2020. In this work, the team introduced ROSALIND (named after renowned chemist Rosalind Franklin and abbreviated from “ligand-induced RNA output sensors”), which could detect 17 different contaminants in a single drop of water. If the test found a contaminant that exceeded the standards of the U.S. Environmental Protection Agency, it either glowed green or did not give a simple, easy-to-read positive or negative result.

To develop ROSALIND Lax and his team used cell-free synthetic biology. Using synthetic biology, researchers select molecular mechanisms – including DNA, RNA and proteins – from cells and then reprogram this mechanism to perform new tasks. At the time, Lax compared Rosalind’s inner work to “molecular taste buds.”

“We found out how bacteria naturally taste things in water,” he said. “They do this through small“ taste buds ”at the molecular level. Cell-free synthetic biology allows us to extract these little molecular taste buds and put them in a test tube. We can then “connect” them to produce a visual signal. It glows so that the user can quickly and easily see if there is a contaminant in the water.

Molecular brain

Now, in a new version called ROSALIND 2.0, Lax and his team have added a “molecular brain”.

“The initial platform was a biosensor that acted as a flavoring recipe,” Lax said. “Now we’ve added a genetic network that works like a brain. The biosensor detects pollution, but then the output of the biosensor goes into the genetic network, or a circuit that works like a brain to execute logic.”

The researchers froze the reprogrammed “molecular brains” to make them stable during storage, and put them in test tubes. Adding a drop of water to each test tube triggers a network of reactions and interactions, ultimately causing sublimation-dried granules to glow in the presence of contamination.

To test the new system, Lax and his team demonstrated that it could successfully determine levels of zinc, an antibiotic and an industrial metabolite. Indicating the level of pollution – rather than a simple positive or negative outcome – is important for informing mitigation strategies, Lax said.

“After we introduced ROSALIND, people said they wanted a platform that could also provide concentration,” he said. “Different pollutants at different levels require different strategies. If your water, for example, is low in lead, then you can transfer it by flushing the plumbing before using them. But if you have high levels, then you need to stop drinking water immediately and replace water supply “.

Empowering individuals

After all, Lax and his team hope to enable people to check their own water regularly. With inexpensive portable devices such as ROSALIND, this could quickly become a reality.

“It is clear that we need to enable people who have information to make important, sometimes saving decisions,” Lax said. “We see this with home tests on COVID-19. People need tests at home because they need this information quickly and regularly. It’s like water. There are many cases where water quality needs to be measured regularly. It’s not a one-time thing, so that the level of pollution may change over time ”.

The study “Programming Cellular Biosensors Using DNA Chain Movements” was supported by the U.S. Department of Defense, the National Science Foundation, the Crown Family and Israeli Center for Jewish and Israeli Studies, and the Searle Foundation at the Chicago Public Foundation.

Video: https://youtu.be/OAQCnDHzqaE

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