The electrodynamic ion funnel has enabled the manipulation and focusing of ions in a pressure regime (0.1-30 Torr) that has challenged traditional approaches, and provided the basis for much greater mass spectrometer ion transmission efficiencies. The initial ion funnel implementations aimed to efficiently capture ions in the expanding gas jet of an electrospray ionization interface and radially focus them for efficient transfer through a conductance limiting orifice. We review the improvements in fundamental understanding of ion motion in ion funnels, the evolution in its implementations that have brought the ion funnel to its current state of refinement, as well as applications of the ion funnel for purposes such as ion trapping, ion cooling, low pressure electrospray, and ion mobility spectrometry. #

The ionization and transmission efficiencies of an electrospray ionization (ESI) interface were investigated to advance the understanding of how these factors affect mass spectrometry (MS) sensitivity. In addition, the effects of the ES emitter distance to the inlet, solution flow rate, and inlet temperature were characterized. Quantitative measurements of ES current loss throughout the ESI interface were accomplished by electrically isolating the front surface of the interface from the inner wall of the heated inlet capillary, enabling losses on the two surfaces to be distinguished. In addition, the ES current lost to the front surface of the ESI interface was spatially profiled with a linear array of 340-m-diameter electrodes placed adjacent to the inlet capillary entrance. Current transmitted as gas-phase ions was differentiated from charged droplets and solvent clusters by measuring sensitivity with a single quadrupole mass spectrometer. The study revealed a large sampling efficiency into the inlet capillary (Ͼ90% at an emitter distance of 1 mm), a global rather than a local gas dynamic effect on the shape of the ES plume resulting from the gas flow conductance limit of the inlet capillary, a large (Ͼ80%) loss of analyte ions after transmission through the inlet arising from incomplete desolvation at a solution flow rate of 1.0 L/min, and a decrease in analyte ions peak intensity at lower temperatures, despite a large increase in ES current transmission efficiency. -6]. The sensitivity of ESI-MS is largely determined by the effectiveness of producing gas-phase ions from analyte molecules in solution (ionization efficiency) and the ability to transfer the charged species from atmospheric pressure to the low-pressure region of the mass analyzer (transmission efficiency) [7][8][9][10].Ionization efficiency is affected by a number of factors, such as flow rate, interface design, solvent composition, and analyte properties. In general, ionization efficiency increases as the liquid flow to the ES emitter decreases [11][12][13]. The primary reason for this increase is the production of smaller charged droplets at the lower flow rates [11,14]. The smaller droplets enable more efficient solvent evaporation and fewer coulombic fission events are required to create gasphase ions [11,14]. Also, the ES current in cone-jet mode increases approximately as the square root of the volumetric flow rate [14], increasing the number of available charges per analyte molecule as the flow rate decreases. Finally, smaller initial droplets and increased amount of charge available per analyte molecule improve the ionization of analytes with lower surface activity, improving quantitation and reducing matrix suppression effects [15,16]. In addition to its importance for transmission efficiency, the ESI interface on the mass spectrometer also plays a key role in ionization efficiency [17]. Adding energy to the charged droplets-such as using heated nitrogen as a background gas-enhances desolvation and liberates more analyte ions [17][18][...

We have developed a new procedure for fabricating fused silica emitters for electrospray ionizationmass spectrometry (ESI-MS) in which the end of a bare fused silica capillary is immersed into aqueous hydrofluoric acid, and water is pumped through the capillary to prevent etching of the interior. Surface tension causes the etchant to climb the capillary exterior, and the etch rate in the resulting meniscus decreases as a function of distance from the bulk solution. Etching continues until the silica touching the hydrofluoric acid reservoir is completely removed, essentially stopping the etch process. The resulting emitters have no internal taper, making them much less prone to clogging compared to e.g. pulled emitters. The high aspect ratios and extremely thin walls at the orifice facilitate very low flow rate operation; stable ESI-MS signals were obtained for model analytes from 5-μm-diameter emitters at a flow rate of 5 nL/min with a high degree of inter-emitter reproducibility. In extensive evaluation, the etched emitters were found to enable approximately four times as many LC-MS analyses of proteomic samples before failing compared with conventional pulled emitters. The fabrication procedure was also employed to taper the ends of polymer monolith-containing silica capillaries for use as ESI emitters. In contrast to previous work, the monolithic material protrudes beyond the fused silica capillaries, improving the monolith-assisted electrospray process.

An experimental investigation and theoretical analysis are reported on charge competition in electrospray ionization (ESI) and its effects on the linear dynamic range of ESI mass spectrometric (MS) measurements. The experiments confirmed the expected increase of MS sensitivities as the ESI flow rate decreases. However, different compounds show somewhat different mass spectral peak intensities even at the lowest flow rates, at the same concentration and electrospray operating conditions. MS response for each compound solution shows good linearity at lower concentrations and levels off at high concentration, consistent with analyte "saturation" in the ESI process. The extent of charge competition leading to saturation in the ESI process is consistent with the relative magnitude of excess charge in the electrospray compared to the total number of analyte molecules in the solution. This ESI capacity model allows one to predict the sample concentration limits for charge competition and the on-set of ionization suppression effects, as well as the linear dynamic range for ESI-MS. has become a widely used analytical technique in modern biological research due to its high sensitivity and broad applicability [2,3]. Because of the extreme complexity of many biological samples (e.g., proteomics analyses), the effectiveness of ESI-MS depends substantially on both its achievable sensitivity and dynamic range. It has been recognized that optimization of ESI processes has a great effect on MS sensitivity [4]. Operating electrosprays in a so called nanoelectrospray [5] mode, with flow rates ranging from 10 to 100 nl/min, has been shown to significantly increase MS sensitivity compared with more conventional electrospray operation (Ͼ1 l/min) [6]. The much smaller charged droplets (nanometer range) generated by nanoelectrosprays [7,8] lead to increased ionization efficiency. It has also been shown that effects upon the analyte ionization efficiency resulting from ionic contaminants (matrix effects) or multiple analytes (ionization suppression) decrease significantly for nano-electrosprays compared to conventional electrosprays [5,9]. Although many advantages have been recognized in principle for nano-electrospray operation, a firm quantitative experimental evaluation in terms of its achievable MS sensitivity is still not available due to factors that include difficulties in reliably operating nano-electrosprays [10]. The most effective nano-electrospray operation requires the interface to be optimized for the significantly smaller sample infusion rate, more facile droplet desolvation, and the lower electrospray current [8].The linear dynamic range for ESI-MS measurements has been previously investigated resulting in somewhat differing conclusions [11][12][13][14][15][16][17]. The upper concentration limit was originally defined by Kebarle and Tang [11,12] as the one corresponding to the maximum analyte charge limit for a given total electrospray current. Above this concentration limit, the ESI response to the analyte concentration...