When a car's hazard lights are flashing, it’s a bad sign. Now, the same may be true when scientists see a culture of bacteria blinking.
By modifying the genetic material in Escherichia coli and tricking them into talking to each other across long distances, bioengineers have coaxed millions of bacteria to blink, or fluoresce, at the same time. Also, the researchers tweaked the E. coli to blink when arsenic entered their environment. Published in the Jan. 5 issue of Nature, the results could one day lead to the design of low-cost, hand-held sensors that use colonies of bacteria to detect toxic chemicals or disease-causing germs.
For several years, Prindle and other scientists in the lab of UCSD bioengineer Jeff Hasty lab have been working on ways to make bacteria fluoresce at the same time. First, they engineered a single bacteria to blink by inserting a fluorescing protein into the cell's plasma. Then the scientists exploited the bacteria’s natural quorum sensing—a process in which bacteria release molecules to alert neighboring cells of nearby food or danger—to coax thousands of the cells in a bacterial colony to blink in synch.
However, the team struggled to get more than one colony to fluoresce at the same time because the communication broke down over long distances, which in bacterial terms is about one millimeter. Now, Prindle and his colleagues have overcome that challenge by engineering E. coli to emit hydrogen peroxide vapor and arranging the colonies into columns and rows, or biopixels, on a microfluidic chip that resemble the pixels in LCD screens.
Each biopixel contains a colony of 5,000 cells that communicate through quorum sensing. Those biopixels then talk to each other through their reaction and emission of a hydrogen peroxide vapor, which can permeate throughout the microchip and synchs the bacteria's cell cycles so they blink at the same time.
In the first test of this technique, 20 colonies flashed on and off in unison, which Prindle said he never expected. "We were looking to synch two to three biopixels. We weren't prepared to look at 20," he said.
The success spurred the team to build their first large-scale biopixel array of 500 pixels, containing a total of 2.5 million E. coli cells that blinked at the same time. Then the team scaled up the array again to include 60 million bacterial cells. They too blinked in synch.
So Prindle and his colleagues re-wired the E. coli again so that they not only flashed on and off, but also reacted to arsenic. Adding the poison to the array, the scientists saw the bacteria's blinking frequency slow. With a bit more tinkering, the team engineered the array to flash only when it was hit with arsenic. Because bacteria are sensitive to other biological contaminants, the researchers think these biopixels could be used as sensors in low-cost, hand-held detectors that would indicate cadmium, mercury, heavy-metal, or disease-causing pathogenenic contamination in water and soil.
But before building the hand-held detectors, Prindle and colleagues must create biopixel arrays with even more colonies of E. coli in layers, or in a 3-D design, to improve the intensity of the signal and make the sensor more reliable. The team may also try to switch the sensing mechanism of the bacteria from fluorescence to an extra output of electrons, which would be better for integrating the biopixels into electronic devices.
- Prindle, A., P. Samayoa, I. Razinkov, T. Danino, L.S. Tsimring, and J. Hasty. 2012. A sensing array of radically coupled genetic ‘biopixels’. Nature 481:39–44.