Reference channel-based microfluidic resistance sensing for single yeast cell volume growth measurement

A reference channel-based microfluidic sensing scheme for real-time measurements of volume growth rates of single cells has been demonstrated with single budding yeast. The microfluidic platform consists of two side-by-side microchannels of the same geometry serving as the sensing channel and the reference channel, respectively, which allows for cancelation of the effects of baseline ionic current drift that commonly exists in microfluidic circuits. For a single cell growing inside the sensing channel, its volume growth rate is proportional to the resistance change in the sensing channel, which can be precisely measured in a continuous manner with the aid of the reference channel to effectively eliminate the fluctuations and drifts of the ionic current inside microfluidic channels. Compared with the commonly used resistive-pulse sensing technique, the reported label-free sensing scheme can detect long-term volume growth rates of single cells attached to a substrate in real time, which is required for most mammalian cells to survive, without the involvement of expensive imaging instruments.