A microfluidic platform enabling real-time control of dynamic biochemical stimuli to biological cells

In the present study, we report a microfluidic platform that enables real-time control of biochemical stimuli to biological cells. The microfluidic platform is designed by integrating a 'Christmas tree' inlet for pre-generating spatially linear concentration gradient, with a Y-shaped channel to modulate dynamic signals with an external programmable air pump. The proposed design is simple and straightforward, has negligible response time compared to the traditional Y-shaped channel, and for the first time, provides the capability of generating versatile waveforms of dynamic stimuli and implementing multiple dynamic stimulating signals with different amplitudes synchronously. The feasibility of the microfluidic platform is proved by both computational fluid dynamics simulation and fluorescein experiment. The applicability of the proposed platform is demonstrated by characterizing the intracellular calcium ion dynamics in human umbilical vein endothelial cells in response to multiple dynamic stimuli within a single run. The proposed platform provides a simple approach to rapidly control dynamic stimuli with versatile waveforms to biological cells and shows the potential for the quantitative study of biological cellular dynamic responses.