Rapid and label-free screening of enzyme inhibitors using segmented flow electrospray ionization mass spectrometry

Abstract

Electrospray ionization mass spectrometry (ESI-MS) is an attractive analytical tool for high-throughput screening because of its rapid scan time and ability to detect compounds without need for labels. Impediments to the use of ESI-MS for screening have been the relatively large sample consumed and slow sample introduction rates associated with commonly used flow injection analysis. We have previously shown that by segmenting nanoliter plugs of sample with air, an array of discrete samples can be delivered to a platinum-coated emitter tip for ESI-MS analysis with throughput as high as 0.8 Hz and carry-over between samples less than 0.1%. This method was applied to screening for inhibitors of acetylcholinesterase as a demonstration of the potential of segmented flow ESI-MS for such applications. Each enzyme assay consumed 10 nL of sample. At 1 L/min infusion rate, 102 samples were analyzed, corresponding to a 0.65 Hz sample analysis rate. Linear quantification of choline was achieved from 200 M to 10 mM using this method and Z= values were over 0.8 for the assay. Detailed pharmacologic dose-response curves of selected inhibitors were also measured in high-throughput fashion to validate the method. (J Am Soc

Successful Management of a Possible Antibiotic-Related Acquired Factor V Inhibitor: A Case Report and Review of the Literature

“…Equally rare is acquired factor V deficiency which is due to the development of antibodies against factor V. There have been several case reports and case series describing this rare disorder. Most of these case reports have been associated with antibiotics (cephalosporins, aminoglycosides and penicillins) [3,4], infections, malignancy and surgery with exposure to bovine factor V. Similar to other reported cases, our patient was receiving a cephalosporin antibiotic.…”

Continuous Droplet-Based Liquid-Liquid Extraction of Phenol from Oil

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Swan Probe: A Nanoliter-Scale and High-Throughput Sampling Interface for Coupling Electrospray Ionization Mass Spectrometry with Microfluidic Droplet Array and Multiwell Plate

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