Multiplexed LC-MS system

FIGURE 6.4 Schematic of a four-channel, staggered parallel multiplexed LC-MS system. 

Fig. 4. Schematic representation of a commercial parallel LC/MS system. Liquid flow is delivered to eight columns by a pump and a flowsplitter. Peaks are detected by a multichannel UV detector and a TOF mass spectrometer with a multiplexed electrospray source...

The MS instrumentation is the most expensive part of the LC-MS system, hence efforts to improve the throughput of the LC-MS analysis often involve the use of parallel multiple columns that feed into a single mass spectrometer. Zeng and Kassel [99] developed an automated parallel analytical/preparative LC-MS workstation to increase the throughput for the characterization and purification of combinatorial libraries. The system incorporates two columns operated in parallel for both LC-MS analytical and preparative LC-MS purifications. A multiple-sprayer ESI interface was designed to support flows from multiple columns. The system is under complete software control and delivers the crude samples to the two HPLC columns from a single autosampler. The authors demonstrated characterization of more than 200 compounds per instrument per day, and purification of more than 200 compounds per instrument per night. De Biasi et al. [100] described a four-channel multiplexed... 

The first reported case of timesharing for a mass spectrometer9 involved the design of an Ionspray interface with multiple sprayers to support the analysis of effluents from multiple columns. This approach led to the development of a multiplexed electrospray interface (MUX)10 using an LC/MS interface and multiple (identical) sprayers linked to a HPLC system and a spinning screen to allow the output of only a single sprayer to enter the MS (Figure 4.5). The injections of the HPLC systems... 

FIGURE 3 A multiplex LC/UV/MS system for Log P measurement. (Copyright 2002 John Wiley Sons Limited. Reproduced with permission.)... 

Figure 4.16. (a) Pictures of an Eksigent Parallel LC system and (b) Waters 2488 eight-channel UV/Vis detector, (c) Schematic diagram of a multiplexed parallel LC/MS analysis. Diagrams courtesy of Eksigent and Waters Corporation. 

Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discoveiy of classes of protein biomarkers that were previously undetectable. Multiplexed LC systems are coupled to MS to analyze affinity-tagged cellular lysates and protein mixtures and someday might replace 2-D gel-based systems. 

Bayliss and co-workers [10] combined ultra-high flow rates, parallel LC columns, a multiplex electrospray source, and mass spectrometric detection for the rapid determination of pharmaceuticals in plasma using four narrow bore (50 mm x 1 mm, 30 pm Oasis HLB) or capillary (50 mm x 0.18 mm, 25 pm Oasis HLB) HPLC columns with large particle sizes (to avoid high system back-pressure) in parallel with a multiple probe injector and a MUX MS interface. Small sample aliquots were injected directly into the system without sample pre-treatment procedure, obtaining very low limits of quantification (from 1 to 5 ng/mL). 

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