The Lab-on-a-Chip concept aims at miniaturizing laboratory processes to enable automation and/or parallelization via microfluidic chips that are capable of handling minute sample volumes. Mass spectrometry is nowadays the detection method of choice, because of its selectivity, sensitivity and wide application range. We review the most interesting examples over the last two-and-a-half years where the two techniques were used for bioanalytical applications. Furthermore, we discuss the merits and limitations of such hyphenated systems. We inventorize the reported applications and approaches. We see an ongoing trend towards chip-based liquid chromatography-mass spectrometry usage and small volume analysis applications, particularly in the field of proteomics where bottom-up approaches profit from chip-based technologies and hyphenation with complex cell cultures.

Electroextraction (EE) and electromembrane extraction (EME) are sample preparation techniques that both require an electric field that is applied over a liquid‐liquid system, which enables the migration of charged analytes. Furthermore, both techniques are often used to pre‐concentrate analytes prior to analysis. In this review an overview is provided of the body of literature spanning April 2012–November 2015 concerning EE and EME, focused on hyphenation to analytical techniques. First, the theoretical aspects of concentration enhancement in EE and EME are discussed to explain extraction recovery and enrichment factor. Next, overviews are provided of the techniques based on their hyphenation to LC, GC, CE, and direct detection. These overviews cover the compounds and matrices, experimental aspects (i.e. donor volume, acceptor volume, extraction time, extraction voltage, and separation time) and the analytical aspects (i.e. limit of detection, enrichment factor, and extraction recovery). Techniques that were either hyphenated online to analytical techniques or show high potential with respect to online hyphenation are highlighted. Finally, the potential future directions of EE and EME are discussed.

We present a continuous-flow microelectroextraction flow cell that allows for electric field enhanced extraction of analytes from a large volume (1 mL) of continuously flowing donor phase into a micro volume of stagnant acceptor phase (13.4 μL). We demonstrate for the first time that the interface between the stagnant acceptor phase and fast-flowing donor phase can be stabilized by a phaseguide. Chip performance was assessed by visual experiments using crystal violet. Then, extraction of a mixture of acylcarnitines was assessed by off-line coupling to reversed phase liquid chromatography coupled to time-of-flight mass spectrometry, resulting in concentration factors of 80.0 ± 9.2 times for hexanoylcarnitine, 73.8 ± 9.1 for octanoylcarnitine, and 34.1 ± 4.7 times for lauroylcarnitine, corresponding to recoveries of 107.8 ± 12.3%, 98.9 ± 12.3%, and 45.7 ± 6.3%, respectively, in a sample of 500 μL delivered at a flow of 50 μL min(-1) under an extraction voltage of 300 V. Finally, the method was applied to the analysis of acylcarnitines spiked to urine, resulting in detection limits as low as 0.3-2 nM. Several putative endogenous acylcarnitines were found. The current flowing-to-stagnant phase microelectroextraction setup allows for the extraction of milliliter range volumes and is, as a consequence, very suited for analysis of low-abundant metabolites.