Characterization of drug permeability in Caco-2 monolayers by mass spectrometry on a membrane-based microfluidic device

Abstract

In this study, an integrated microfluidic device was developed for drug permeability assays with real-time online detection by a directly coupled mass spectrometer. The integrated microfluidic device contained two independent channels sandwiched by a semipermeable polycarbonate membrane for cell culture, and micro solid-phase extraction (SPE) columns for sample clean-up and concentration prior to mass spectrometry detection. Curcumin, a model drug, was delivered to an upper or bottom channel by a pressure-driven flow to mimic dynamic in vivo conditions, and it was forced to permeate into the other side channel. The concentration of curcumin permeated with time was directly detected by an electrospray ionization quadrupole time-of-flight mass spectrometer (ESI-Q-TOF MS) with high sensitivity after micro-SPE pretreatment. The total analysis time only needed about 30 min, and only 6 μL of the drug solution was required for each permeation experiment. The measured permeability of curcumin was consistent with the literature reported value. In addition, this technique offers the potential for parallelization and increasing throughput compared to conventional methods. Thus, the established platform provides a useful tool for drug permeability studies, which is crucial for drug discovery and development.

Development of a blood-brain barrier model in a membrane-based microchip for characterization of drug permeability and cytotoxicity for drug screening

“…1C and D, a µSPE column was connected to the bottom channel of the first microchip to purify samples before MS detection. The microfluidic design and fabrication have referred to our previous papers and the details were stated in the Supporting Information [28,29].…”

“…where C 0 is the sunitinib concentration in the upper channel (10 µM), C(t) is the concentration of the permeated sunitinib in the bottom channel, V is the fluid volume collected from the bottom channel (5 µL), A is the interface area of the upper layer and the bottom layer (2 mm 2 ), △t is permeation time [28].…”

Microfluidic approaches for epithelial cell layer culture and characterisation

“…collagen 66, 71 , fibronectin 72 , poly-L-lysine 73 …) in order to facilitate cell adhesion and cell differentiation. Coating is easily achieved by flowing an ECM-protein solution through the cell culture chamber.…”

Chemical and biochemical analysis on lab-on-a-chip devices fabricated using three-dimensional printing

“…For instance, by integrating various simple functional elements (e.g. valves, and pumps) and into a miniaturized multiple function analytical platform, it could manipulate small volumes of fluid [10][11][12][13]. Thus, lab-on-a-chip devices substantially reduced the consumption of reagents and samples, shortened length of analysis time, and simplified operation steps, without sacrificing the sensitivity or specificity.…”