Mass Spectrometry “Sensor” forin VivoAcetylcholine Monitoring

Abstract

Developing sensors for in vivo chemical monitoring is a daunting challenge. An alternative approach is to couple sampling methods with online analytical techniques; however, such approaches are generally hampered by lower temporal resolution and slow analysis. In this work, microdialysis sampling was coupled with segmented flow electrospray ionization mass spectrometry (ESI-MS) to perform in vivo chemical monitoring. Use of segmented flow to prevent Taylor dispersion of collected zones and rapid analysis with direct ESI-MS allowed 5 s temporal resolution to be achieved. The MS “sensor” was applied to monitoring acetylcholine in the brain of live rats. The detection limit of 5 nM was sufficient to monitor basal acetylcholine as well as dynamic changes elicited by microinjection of neostigmine, an inhibitor of acetycholinesterase that evoked rapid increases in acetycholine, and tetrodotoxin, a blocker of Na+ channels, that lowered the acetylcholine concentration. The versatility of the sensor was demonstrated by simultaneously monitoring metabolites and infused drugs.

Towards Practical Endoscopic Mass Spectrometry

“…18) Nowadays, it is relatively convenient to couple the microdialysis probe to an ESI source. [19][20][21] For a solid or biological surface, extraction of analytes can be performed by the following methods.…”

Small-Volume Analysis of Cell–Cell Signaling Molecules in the Brain

“…By creating discrete aqueous analyte plugs that are surrounded by an oil phase, diffusion broadening is limited to the droplet, and temporal resolution is improved overall. This technique has been used to study both amino acids ) and acetylcholine (Song et al, 2012) from the rat brain. Furthermore, by coupling this segmented flow system to a push-pull perfusion system, Glu was detected with 7 s temporal resolution and a spatial resolution of 0.016 mm 2 , an 80-fold improvement over traditional microdialysis (Slaney et al, 2011).…”

“…CE-MS (see Figure 3a) is widely used to measure and identify bioactive peptides (Ye et al, 2011), metabolites (Nemes et al, 2011(Nemes et al, , 2012Nautiyal et al, 2012;Gholipour et al, 2013), classical neurotransmitters (Lapainis et al, 2009), and amino acids (Moini, 2013). Alternatively, microdialysis sampling can be directly coupled to ESI-MS via nanodroplet segmented flow for in vivo chemical monitoring of neurotransmitters, metabolites, and drugs in the live brain (Song et al, 2012). As another hyphenation solution, CE separations have been integrated into microfluidic devices that also serve as electrospray emitters, although sample loading for small-volume analysis remains a barrier to high-throughput analysis (Mellors et al, 2008;Sun et al, 2010;.…”

Quantitative Metabolome Analysis Based on Chromatographic Peak Reconstruction in Chemical Isotope Labeling Liquid Chromatography Mass Spectrometry

“…Chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) uses differential isotope mass tags to label a metabolite in two comparative samples (e.g., 12 Clabeling of an individual sample and 13 C-labeling of a pooled sample), followed by mixing and LC-MS analysis. Individual metabolites are detected as peak pairs in mass spectra.…”