Simple paper 'litmus' test detects disease, infection

A bandage that changes colour if a wound turns septic, environmental sensors or even cheap, portable tests for infectious diseases such as ebola could be a reality in the near future, thanks to a technique that allows simple DNA tests to be printed onto paper.

A result of a collaboration between two teams at the Wyss Institute lead by core faculty members James Collins, PhD, and Peng Yin, PhD, the test goes beyond the simple chemistry used in such applications as pregnancy tests -- instead, it embeds synthetic gene networks into the paper. These paper strips can then be freeze-dried and stored at room temperature for up to a year, to be dampened when required for use.

"In the last fifteen years, there have been exciting advances in synthetic biology," said Collins, who is also Professor of Biomedical Engineering and Medicine at Boston University, and Co-Director and Co-Founder of the Center of Synthetic Biology. "But until now, researchers have been limited in their progress due to the complexity of biological systems and the challenges faced when trying to re-purpose them. Synthetic biology has been confined to the laboratory, operating within living cells or in liquid-solution test tubes."

The tests are made using standard equipment and commercially available cell-free systems, which are embedded on to the paper along with fluorescent and colour-changing proteins. A new, special gene switch, called a "toehold switch" is also included, which is activated when it detects the presence of specific RNA -- such as, for example, the specific RNA code for the ebola virus. This then triggers the protein to change colour, effectively diagnosing the presence of the virus.

"We've harnessed the genetic machinery of cells and embedded them in the fiber matrix of paper, which can then be freeze dried for storage and transport -- we can now take synthetic biology out of the lab and use it anywhere to better understand our health and the environment," said lead author Keith Pardee, PhD.

"Where it would normally take two or three days to validate a tool inside of a living cell, this can be done using a synthetic biology paper-based platform in as little as 90 minutes."

The reason the test works so effectively is down to that toehold switch, co-invented by Alex Green, PhD, and Yin. It can be programmed to only interact with very specific, intended targets -- to precisely detect almost any kind of RNA target, then turn on protein production. And many different toehold switches can operate simultaneously in the same cell, which could then be programmed to carry out multi-step functions.

Although some medical knowledge would be required to effectively use the tests, their accessibility could make a huge difference -- they could cost as little as four cents each to develop.

You can watch some videos about the development of the test below, and read the full paper, "Toehold Switches: De-Novo-Designed Regulators of Gene Expression", online in the journal Cell.