If I told you that in your job as a scientist you would need to dissect two thousand yeast cells every day, would you want the job? I suspect that almost nobody would want to do it. But as a scientist studying aging in yeast, this is the tedious challenge that I face. Because every hour and a half, yeast mother cells (the cells that I want to track) start to bud. We call the newly budded cells “daughter cells.”
Continuous budding of daughters results in exponential growth so that the mother cells are rapidly outnumbered by daughter cells. At the end of an experiment, it is impossible to find the aging mother cells. In a yeast-aging research lab, traditionally, researchers must look through a microscope and carefully remove each daughter cell using a small needle, over and over and over again. The mother cell can produce, on average, about 25 daughters before it dies. Moreover, just as with other animal models, there is significant variation in lifespan between individual yeast cells, even when they are genetically identical. This means that a minimum of 40 mother cells have to be used to generate a reliable lifespan data set, which needs the researcher to manually remove approximately 1,000 daughter cells.
A new microfluidic device is now available to save this yeast aging researcher’s life. The technique was developed by Yi Zhang et al. and Sung Sik Lee et al in 2012. It uses liquid media and tiny chambers (micro-jails) on a special chip to retain the mother cells, but allows daughter cells to be flushed away due to their smaller size.)
This device is coupled to a powerful long-term high-resolution imaging apparatus to image the entire lifespan.
Such a set-up allows scientists to monitor the aging process of single cells from “young” to “dead.” In the video below, you can see the mother cells trapped in the micro-jails, while the daughter cells disappear from the video as they get flushed away. This device is a major labor saver!
As the mother cells age, we are able to observe changes in the shape and function of intracellular organelles such as vacuoles, which became fragmented with age, and mitochondria, which show increased dysfunction with age. Microfluidic devices provide an easy and efficient way to help scientists not only identify molecular markers of aging, but also to usher in large-scale screening to identify small molecules that could modulate aging. However, it is worth mentioning that microfluidic systems have a limitation: poor yield of old cells, which are required, if the scientists want to do further biochemical tests on them.
Now that we have this microfluidic system – much of the pain is gone. Come along for the ride in your easier job as a yeast aging biologist!