Plasma-based ambient ionization mass spectrometry techniques are gaining growing interest due to their specific features, such as the need for little or no sample preparation, its high analysis speed, and the ambient experimental conditions. Samples can be analyzed in gas, liquid, or solid forms. These techniques allow for a wide range of applications, like warfare agent detection, chemical reaction control, mass spectrometry imaging, polymer identification, and food safety monitoring, as well as applications in biomedical science, e.g., drug and pharmaceutical analysis, medical diagnostics, biochemical analysis, etc. Until now, the main drawback of plasma-based techniques is their quantitative aspect, but a lot of efforts have been done to improve this obstacle.

Adolescence is a critical developmental period during which most adult smokers initiate their habit. Adolescents are more vulnerable than adults to nicotine's long-term effects on addictive and cognitive behavior. We investigated whether adolescent nicotine exposure in rats modifies expression of nicotinic acetylcholine receptors (nAChRs) in medial prefrontal cortex (mPFC) in the short and/or long term, and whether this has functional consequences. Using receptor binding studies followed by immunoprecipitation of nAChR subunits, we showed that adolescent nicotine exposure, as compared with saline, caused an increase in mPFC nAChRs containing α4 or β2 subunits (24 and 18%, respectively) 24 h after the last injection. Nicotine exposure in adulthood had no such effect. This increase was transient and was not observed 5 wk following either adolescent or adult nicotine exposure. In line with increased nAChRs expression 1 d after adolescent nicotine exposure, we observed a 34% increase in amplitude of nicotine-induced spontaneous inhibitory postsynaptic currents in layer II/III mPFC pyramidal neurons. These effects were transient and specific, and observed only acutely after adolescent nicotine exposure, but not after 5 wk, and no changes were observed in adult-exposed animals. The acute nicotine-induced increase in α4β2-containing receptors in adolescents interferes with the normal developmental decrease (37%) of these receptors from early adolescence (postnatal day 34) to adulthood (postnatal day 104) in the mPFC. Together, this suggests that these receptors play a role in mediating the acute rewarding effects of nicotine and may underlie the increased sensitivity of adolescents to nicotine.

Tandem mass spectrometry coupled to HPLC is the state of the art technique in proteomic research. Here we describe a highly sensitive nano liquid chromatography system (nano HPLC) for analysis of protein digests. Using preconcentration in a column-switching set-up, we were able to inject large sample volumes (< or =250 microL) without significant loss of sensitivity. The major problem with this type of preconcentration is usually the occurrence of void volumes. In order to diagnose void volumes a simple and easy test was developed by which the UV trace and the pressure profile in the separation column were monitored. Part by part replacement of connection tubing restored a void volume-free system. A major pre-requisite for handling samples in the femtomol range was found to be the use of protein/peptide-saturated columns tryptic digests of cytochrome C were injected directly onto the reversed-phase nano separation column (75 microm inner diameter) and the separation results were compared with chromatograms obtained from separations using column switching. By using column switching we were able to inject large sample volumes in a short time period without losing resolution.

Evaluation of cellular processes and their changes at the level of protein expression and post-translational modifications may allow identification of novel proteins and the mechanisms involved in pathogenic processes. However, the number of proteins and, after tryptic digestion, of peptides from a single cell can be tremendously high. Separation and analysis of such complex peptide mixtures can be performed using multidimensional separation techniques such as two-dimensional gel electrophoresis or two-dimensional-high-performance liquid chromatography (2-D-HPLC). The aim of this work was to establish a fully automated on-line 2-D-HPLC separation method with column switching for the separation of complex tryptic digests. A model mixture of five proteins as well as a nuclear matrix protein sample were digested with trypsin and separated using a strong cation exchange (SCX) column in the first dimension and nano reversed phase in the second dimension. Separated peptides were detected using an ion trap mass spectrometer. The advantages of this new fully automated method are rapid sample loading, the possibility of injecting large volumes and no introduction of salt into the mass spectrometer. Furthermore, column switching allows the independent control and optimization of the two dimensions independently.

Expectations for continuous miniaturization in mass spectrometry are not declining for years. Portable instruments are highly welcome by the industry, science, space agencies, forensic laboratories, and many other units. All are striving for the small, cheap, and as good as possible instruments. This review describes the recent developments of miniature mass spectrometers and also provides selected applications where these devices are used. Upcoming perspectives of further development are also discussed. @ 2019 John Wiley & Sons Ltd. Mass Spec Rev