Full utilization of a mass spectrometer using on-demand sharing with multiple LC units.
The applicability of liquid chromatography-mass spectrometry (LC/MS) is often limited by throughput. The sharing of a mass spectrometer with multiple LCs significantly improves throughput; however, the reported systems have not been designed to fully utilize the MS duty cycle, and as a result to achieve maximum throughput. To fully utilize the mass spectrometer, the number of LC units that a MS will need to recruit is application dependent and could be significantly larger than the current commercial or published implementations. For the example of a single analyte, the number may approach the peak capacity to a first degree approximation. Here, the construction of a MS system that flexibly recruits any number of LC units demanded by the application is discussed, followed by the method to port a previously developed LC/MS method to the system to fully utilize a mass spectrometer. To demonstrate the performance and operation, a prototypical MS system of eight LC units was constructed. When 1-min chromatographic separations were performed in parallel on the eight LCs of the system, the average LC/MS analysis time per sample was 10.5 s when applied to the analysis of samples in 384-well plate format. This system has been successfully used to conduct large-volume biochemical assays with the analysis of a variety of molecular entities in support of drug discovery efforts. Allowing the recruitment of the number of LC units appropriate for a given application, this system has the potential to be a plug-and-play system to fully utilize a mass spectrometer.
Analytical Sciences, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA. Shu-1.Li@novartis.com
Shu
S
Li
Qin
Q
Hao
John
J
Gounarides
Y Karen
YK
Wang
D000818:Animals; D002417:Cattle; D002853:Chromatography, Liquid / Q000295:instrumentation*; D004075:Diglycerides / Q000737:chemistry; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000737:chemistry; D013058:Mass Spectrometry / Q000295:instrumentation* / Q000379:methods*; D008956:Models, Chemical; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014867:Water / Q000737:chemistry
D004075:Diglycerides; D014867:Water; D012710:Serum Albumin, Bovine; C021650:hydrocortisone acetate; D006854:Hydrocortisone; C013965:diolein