Microfluidic cell culture and metabolism detection with electrospray ionization quadrupole time-of-flight mass spectrometer.

ABSTRACT

A novel method for the characterization of drug metabolites was developed by integrating chip-based solid-phase extraction (SPE) with an online electrospray ionization quadrupole time-of-fight mass spectrometer (ESI-Q-TOF-MS). The integrated microfluidic device was composed of circular chambers for cell culture and straight microchannels with shrink ends to pack the solid-phase material for sample cleanup and concentration prior to mass analysis. By connecting the two separated microchannels with polyethylene tubes, drug metabolism studies related to functional units, including cell culture, metabolism generation, sample pretreatment, and detection, were all integrated into the microfluidic device. To verify the feasibility of a drug metabolism study on the microfluidic device, the metabolism of vitamin E in human lung epithelial A549 cells was studied. The metabolites were successfully detected by online ESI-Q-TOF-MS with high sensitivity and short analysis time (8 min). By integrating several parallel channels, the desalting and concentration process could be simultaneously achieved. The total sample pretreatment time only needed about 15 min, and solvent consumption could be reduced to less than 100 microL. All this demonstrated that the developed microfluidic device could be a potential useful tool for cellular drug metabolism research.