MS inlet

LC-MS inlet probes support all conventional HPLC column diameters from mobile phase must be eliminated, either before entering or from inside the mass spectrometer, so that the production of ions is not adversely affected. The problem of removing the solvent is usually overcome by direct-liquid-introduction (DLI), mechanical transport devices, or particle beam (PB) interfaces. The main disadvantages of transport devices are that column... 

Configure the LC instrument with a 5-pL injection loop (or autosampler) a precolumn (for endogenous samples) a column (ca. 2.1x30 mm, 3.5 pm particle size C18 column) two solvent reservoirs, Reservoir A 0.05% TFA in H20 and Reservoir B 95% MeCN and 5% a soln of 0.05% TFA in H20 a mobile phase gradient (e.g., 5% A for 3min, increase to 90% A over 8min, hold at 90% A for 3min, at 0.5 mL-min 1 flow rate) and an MS inlet flow appropriate for the mass spectrometer. Dissolve sample (preferably 1 pmol-pL-1) in 20% MeCN with 0.05% TFA. Inject 10 pL of sample into LC-MS and aquire the spectra. 

The other arrangement is called open split and is shown in Figure 11.7. The space between the column and the MS inlet is maintained at about atmospheric pressure by the use of a second source of gas and a separate vacuum. By controlling the amount of purge gas in this region, the column can be disconnected without shutting down the MS, and, alternatively, undesirable sample components such as large quantities of solvent can be removed before they enter the MS. 

Commercially, Agilent Technologies produces chips for both direct infusion into a mass spectrometer and for HPLC-MS applications. The chips accommodate nanoflow rates with an electrospray ionisation source, are about the size of a credit card and are rensable. The infusion chip is for collecting direct MS or tandem MS data. The protein HPLC chip has both a sample enrichment and CIS separation column on the chip, as well as the connections and spray nozzles for electrospray. There are also a small molecule chip and a glycan chip. The chip being used is placed in a Chip Cube MS interface which positions the sprayer tip perpendicular to the MS inlet (Figure 10.7). 

This is sometimes employed as a process MS inlet. Process GC-MS presents more fault and routine maintenance issues, and the delay associated with a chromatographic separation often negates the significant speed advantage of process MS. However, few analytical techniques are as powerful as GC-MS, especially for pilot plants and processes with very complex matrices or with frequent production of unknown byproducts. Commercial process GC-MS instrumentation is available, and is being ruggedized and made more rapid with further advances in the area of fast-GC . 

GC-MS is the most widely used hyphenated technique and there have been many comprehensive reviews. This description will only be a brief overview and touch on specific issues relevant to the coupling of the GC to the MS. The interfacing of the GC outlet to the MS inlet usually requires some type of selective carrier gas removal. Although direct connection of the GC to the MS is feasible (if large enough vacuum pumps are used), this is rarely done. This is because the vacuum at the outlet of the column can affect the separation efficiency, making most calculations of column retention parameter or efficiency calculations impossible, and the MS... 

Figure 10.2 shows schematically the coupling of a GC system to an MS system. Both systems are heated (200-300°C), both deal with compounds in the vapor state, and both require small samples (micro- or nano-grams). GC and MS systems are very compatible, lite only problem is that the atmospheric pressure output of the GC must be reduced to a vacuum of 10" to 10" torr for the MS inlet. The coupling of the two must be done with a reduction of pressure, and is accomplished with an interface. 

Figure 1.7 Top-down (a) and bottom-up (b) flow path for minimizing the connection tubing length between LC column outlet and MS inlet (ion source).

Keep your eyes on the shortest distance possible between LC outlet and MS inlet already while setting up your UPHPLC system. 

The predecessor of PI-ESI was ultrasonication-assisted spray ionization (UASI) [107, 108]. In that early version, one end of a sample capillary was dipped in the sample vial held in an ultrasonicator (frequency 40 kHz) while the other (tapered) end was placed close ( 3 mm) to the MS inlet. Although no electric potential was applied to the tapered end of the capillary, electrospray could be observed, and mass spectra of analytes with... 

Later, it was discovered that a short tapered capillary ( 1 cm), placed in proximity ( 1 mm) to the MS inlet, could also support electrospray - even in the absence of a power supply, electrical grounding, or ultrasound [109]. Since there was no direct electric contact at the sample capillary, this method was named contactless atmospheric pressure ionization (C-API) [109] or contactless ESI [110]. Figure 2.15 shows the putative mechanism of the ion formation in C-API. Rearrangement of electric charges at the end of the tapered capillary is induced by the electric field present near the MS inlet. 

The charges, with the signs opposite to the sign of the electric potential applied to the MS inlet, accumulate on the liquid meniscus at the capillary outlet. This process is followed by the formation of a Taylor cone and Coulomb explosions which lead to the formation of fine droplets. The mechanism responsible for generation of charged droplets and ions in Pl-ESI appears to be similar to that found in the conventional ESI process (Section 2.4). 

---