After separation the glass plates were moved, resulting in MADI-MS-ready nanowells

containing separated analytes. Eleven Crizotinib chemical structure amine metabolites were putatively identified in CSF using this method [ 5•]. Li et al. integrated cell culturing and chiral chipCE–MS analysis in one LOC. Cell culturing was performed on a 0.22 μm filter on top of the sample inlet channel; downstream the separation channel, chiral selectors (moving opposite to the net flow) were introduced and periodically the extracellular matrix was sampled. ESI took place at corner of the chip, aided by a make-up flow. The enantioselective catabolism of racemic DOPA by neuronal cells was monitored [ 40], showing that chipCE is a feasible technique for analysis of in vitro cell models. Hyphenating in vitro cell models to MS is attractive as the information level provided by MS exceeds traditional optical detection techniques. Furthermore, on-line analysis allows following kinetics. Several LOC devices integrating biological experiments and sample preparation

have been developed by the Jin-Ming Lin group. In these devices, micro-solid phase extraction is integrated. The interfacing to MS is achieved via tubing connected Bosutinib manufacturer to an ESI needle. Applications include: measuring acetaminophen metabolism via cultured microsomes [ 41], quantitative analysis of tumor cell metabolism of genistein [ 42], testing of absorption of various concentrations of methotrexate and its cytotoxic effects [ 43] and the uptake of curcumin by CaCo2-cell lines [ 44]. One system was used for studying signalling molecules in cell-cell communications [ 45]. Emerging trends involving 3D cell culture and organ-on-a-chip will likely increase the attention for these types of systems. An overview incentives and

pre-requisites for adoption of LOC-MS systems is presented in Table 1. The incentives Anacetrapib to use LOC-MS are to enable small volume analysis, high throughput/parallelization and automation, time-continuous monitoring and on-line sample preparation. Several of these pre-requisites have already been fulfilled. Commercialized systems as well as cartridge-integrated set-ups are present especially in the chipLC–MS field. The added value and benefit of sample preparation on LOC are clear, especially in the proteomics field. The perfect match between the scaling efficiencies of enzymatic reactions with the decreasing volumes provided by droplet-sized microreactors, proteomics, and MS’ ability to deal with low-volume samples make it an ideal candidate for wide-spread usage within the proteomics community. However, robust datasets, are demonstrated sparsely, one example is continuous monitoring of enzyme kinetics on a micro-array plate. We foresee chipLC–MS becoming commonplace in upcoming years, especially since several commercial systems that offer increased throughput, sensitive analysis and allow easy operation are already available.