The work is a potential breakthrough for these scientists who think the device will help them figure out more precisely how genes and proteins interact with one another and how the relationship drives cellular functions.

Although researchers have had the technology to track single cells and measure the protein levels within them, the new device allows cell activity to be tracked for a longer period of time whilst also controlling gene activity.

The microfluidic device uses electrovalves to control media flow, which travels through a tube eventually diffusing across a permeable membrane to reach the budding yeast cells.

The cells are clamped between this membrane and a soft material, which forces them to bud horizontally without damage.

"That was the major design hurdle," Gilles Charvin, a postdoc who works with both Eric Siggia, head of the Laboratory of Theoretical Condensed Matter Physics, and Frederick Cross, head of the Laboratory of Yeast Molecular Genetics at Rockefeller University. "To create a device in which cells don't move, so that you can track hundreds of single cells for a long time, about eight rounds of cell division, which typically lasts 12 hours."

The use of time-lapse microscopy to study time dependent processes such as the cell cycle and signal transduction has been the preferred method of choice since the 1970s.

Its success was based on easy availability of numerous fluorescently tagged proteins along with the ease of integrating digital imaging with software to control the experiments.

Most applications to yeast grow the cells under a gel pad, a quick and easy method which provides fair confinement and a source of nutrients. However, it has two major limitations: first, continuous tracking of single cells becomes impossible after five divisions since cells pile up, so that large-scale and long-term collection of data (for the study of the cell cycle, epigenetic inheritance, adaptation and signal transduction pathways) are compromised.

Second, it is impossible to vary the growth media, yet the need to investigate the single cell response to time-dependent stimuli is of major importance in cell cycle research and more generally for yeast cell biology.

In order to induce the activity of a gene and then control it, the researchers used inducer molecules that diffuse through the cell membrane and control DNA segments called promoters.

The molecule's presence silences the promoter, which silences the expression of the gene; the molecule's absence, on the other hand, activates the promoter, which activates the gene to crank up the molecule's production.

By exploiting this principle, the scientists showed that they could successfully turn specific genes on and off by controlling the flow of an inducer molecule called methionine. They observed that pulses as short as 10 minutes led to changes in protein levels that could be measured.

"Like slaves, the cells relied on the external pulse we gave them to figure out what to do next," said Charvin.

"We thought this was a pretty striking illustration of the capabilities of this device."

By putting a gene that must be expressed for cells to divide under the control of the methionine promoter, the researchers demonstrated that budding yeast cells would stop and start dividing in perfect synchrony with alternating pulses of media that did and didn't contain methionine.

Control of gene reproduction opens up a wealth of possibilities not previously thought possible. "Genetic screens and genome wide expression data sets provide hints of the complex networks that underlie cellular function. Flow cell technology and time lapse imaging of single cells are essential for performing well-controlled dynamic measurements," said the report.

"This is a practical way to follow multiple fluorescent markers, and construct complete cell pedigrees over many cycles of division and growth comparable to conditions in liquid culture, combined with the ability to pulse with inducers."

The study: 'A Microfluidic Device for Temporally Controlled Gene Expression and Long-Term Fluorescent Imaging in Unperturbed Dividing Yeast Cells,' can be found here .