Live cell tracking on an optical biochip platform
Njoh K., Smith PJ., Chappell SC., Summers HD., Matthews D., Morris D., Goater A., Burt J., Pope I., Vojnovic B., Ameer-Beg S., Errington RJ.
We have developed a range of optical biochip devices for conducting live and fixed cell-based assays. The devices encompass the ability to process an entire assay including fluorescently labelling cells, a microfluidic system to transport and maintain cells to deliver them to an optical area of the device for measurement, with the possibility of a incorporating a sorting step in between. On-chip excitation provided by red emitting LED and lasers define the excitation wavelength of the fluorophore to be incorporated into the assay readout. The challenge for such an integrated microfluidic optical biochip has been to identify and characterise a longterm fluorescent label suitable for tracking cell proliferation status in living cells. Traditional organic fluorophores have inherent disadvantages when considering their use for an on-chip device requiring longterm cellular tracking. This has led us to utilise inorganic quantum dots (QDots) as fluorophores for on- chip assays. QDs have unique properties such as photostability, broad absorption and narrow emission spectra and are available in a range of emission wavelengths including far red. They also have much higher quantum efficiencies than traditional organic fluorophores thus increasing the possible dynamic range for on-chip detection. Some of the QDots used have the added advantage of labelling intact cells and being retained and distributed among daughter cells at division, allowing their detection for up to 6 generations. The use of these QDs off-chip has suggested that they are ideal for live cell, non-perturbing labelling of division events, whereby over time the QD signal becomes diluted with each generation. Here we describe the use of quantum dots as live cell tracers for proliferating populations and the potential applications in drug screening and optical biochip environments.