Sociedad Europea De Analisis Diferencial De Movilidad

Other

Yale University

Nanoengineering Corporation

Fernandez De La Mora, Juan

Labowsky, Michael J.

De La Mora, Juan Fernandez

Juan Fernandez De La Mora

Michael J Labowsky

Gonzalo Fernandez De La Mora

Alejandro Casado

Joan Rosell

Thilo Eichler

Luis De Juan

Guillermo Vidal-de-Miguel

Jerome J Schmitt, Iii

Alessandro Gomez

Juan Rus

Jerome J Schmitt

Keqi Tang

Mario Amo

Francisco Estevez-Molinero

Juan Rus-Perez

Daoiz Zamora

Pablo Martinez-Lozano Sinues

G Wayne Neilson

Achieving high conversion of large multiply charged biological ions into low charge states involves requirements difficult to reconcile when high transmission and good spray quality (resulting in narrow mobility distributions) are sought. These multiple goals are achieved in this invention by partially isolating different regions from each other with electrostatic barriers relatively transparent to ions, such as metallic grids. One such region requires high electric fields for ion generation. The other region, used for ion recombination, is approximately field-free. In an alternative arrangement intended for charge reduction in sub-millisecond times, two sources of ions with opposite polarities are placed contiguously, with a grid in between. In all cases, ion crossing through grids into field free regions is effectively driven by space charge.

High resolution mobility analysis of large charge-reduced electrospray ions

Improvements are provided in the detection of atmospheric vapors by ionizing them near ambient pressure, and analyzing them as ions. Lowest detection limits of parts per quadrillion (ppq) concentrations are enabled by a combination of improvements, including the use of a filter to remove occasional intense signal from explosive particles. Several sources of chemical background are identified and solutions for their reduction or elimination are presented. Gains in response time may be achieved by operating at elevated temperature. When the ionizer is an electrospray source, the use of high boiling point solvents is indicated. An increased selectivity is achieved by operating a differential mobility analyzer (DMA) in series with a mass spectrometer. However, ppq sensitivities require various improvements in the DMA system including a special coupling to the ionizer, controlling the temperature in the DMA pump circuit, avoidance of induction on the DMA electrodes from heating devices, etc.

Method for detecting atmospheric vapors at parts per quadrillion (PPQ) concentrations

A rapid method of volatile analysis and interpretation is taught enabling inferences on the surrounding environment as sophisticated as commonly achieved by dogs via olfaction. The method is based on rapid analysis of vapors released by persons or other organisms into a gas, correction of said analysis due to competing ambient volatiles, extraction of abundance patterns of certain preselected metabolites present in said vapor analysis, and classification of said persons or organisms by comparison of said abundance patterns with preestablished standard metabolite patterns. A preferred approach for rapid analysis involves an atmospheric pressure ionization, such as an electrospray cloud, followed by a mass spectrometer with an atmospheric pressure source. A preferred method for background correction is subtraction of the background signal from the sample signal when both are ionized at similar humidity levels. A preferred comparison pattern involves the abundance of fatty acids and other common metabolites. Preferred classification criteria include recognition of individuals, or species, or health state.

Method to analyze and classify persons and organisms based on odor patterns from released vapors

The present invention is based on the observation that radio frequency (RF) electric fields in multi-pole lenses with small rod diameters in the range of 1 mm enables strongly concentrating ions suspended in a gas at pressures much higher than previously used for ion manipulation, including atmospheric pressure. Other lens configurations are described, including one based on the funnels of U.S. Pat. No. 6,107,628, and another on the coiled wire system of Hutchins et al. (1999). The finding provides a method to increase the concentration of ions transmitted to mass spectrometers and other analyzers, both from volatile or involatile species in solution, hence increasing their analytical sensitivity. It also enables improved charging efficiencies of neutral volatile species existing in the gas phase.

Use ion guides with electrodes of small dimensions to concentrate small charged species in a gas at relatively high pressure

A method for fast and accurate recognition of species contained in trace amounts in complex mixtures such as ambient air or biological fluids is taught based on the use in tandem of one or several differential mobility analyzers (DMAs) and possibly also a mass spectrometer (MS), all arranged in series. The two DMAs operate in different regions of the ion drag versus drift velocity curve (for instance, linear versus nonlinear regions), hence separating according to more than one independently discriminating parameters of the ion. Very high discrimination can be achieved even with a single stage of mass spectrometric separation by selecting a narrow range of ions with the DMA, and analyzing them in the MS, first without fragmentation, and then with fragmentation. This process does not require necessarily a tandem MS when fragmentation takes place in the inlet region of the MS. Fast and accurate discrimination is possible in single ion monitoring mode (SIM) for a large number of targeted species, even with relatively inexpensive and light single quadrupole MS systems, where the various filters placed in series would open pre-configured narrow windows suitable for passage of each ion in a list.

Method and apparatus to accurately discriminate gas phase ions with several filtering devices in tandem

Prior work on differential mobility analysis (DMA) combined with mass spectrometry (MS) has shown how to couple the output of a planar DMA with the atmospheric pressure inlet of an atmospheric pressure ionization mass spectrometer (APCI-MS). However, because the ion inlet to APCI-MS instruments is a round orifice, while conventional DMA geometries make use of elongated slits, the coupling of both has attained less resolving power or tolerated a smaller sample flow rate than a DMA alone. The present invention overcomes these limitations with an axial DMA of cylindrical symmetry using more than two electrodes. The configuration is related to that previously proposed by Labowsky and Fern&#xe1;ndez de la Mora (2004, 2006), where ions with a critical electrical mobility are brought into the symmetry axis of the DMA. Ions with this critical mobility are now optimally transmitted into the MS, with much higher resolution than possible in planar DMAs. In a preferred embodiment of this DMA facilitating DMA-MS coupling, one DMA electrode intersecting the symmetry axis is relatively planar.

Coupling between axisymmetric differential mobility analyzers and mass spectrometers or other analyzers and detectors

Prior work on differential mobility analysis (DMA) combined with mass spectrometry (MS) has shown how to couple the output of the DMA with the inlet of an atmospheric pressure ionization mass spectrometer (APCI-MS). However, the conventional ion inlet to an APCI-MS is a round orifice, while conventional DMA geometries make use of elongated slits. The coupling of two systems with such different symmetries limits considerably the resolutions attainable by the DMA in a DMA-MS combination below the value of the DMA alone. The purpose of this invention is to overcome this limitation in the case of a parallel plate DMA. One solution involves use of an elongated rather than a circular MS sampling hole, with the long dimension of the MS inlet hole aligned with that of the DMA slit. Another involves use of a more elongated orifice in the DMA exit and a more circular hole on the MS inlet, the two being connected either through a short transfer conduit or through an ion guide. The DMAs described can also be coupled profitably to detectors and analyzers other than mass spectrometers.

Resolution improvement in the coupling of planar differential mobility analyzers with mass spectrometers or other analyzers and detectors

The invention describes a system and method to separate ions (and charged particles) suspended in gas based on their ion electrical mobility. Most common ion mobility analyzers involve two parallel plate (or concentric cylinder) elements (electrodes) between which is imposed an electrical field perpendicular to a sheath gas flow field between the cylinders. Separation occurs because high mobility ions tend to follow the electrical field while low mobility ions tend to follow the flow field. This invention describes various configurations of electrical elements and sheath gas flow fields for ion mobility separation devices with unique performance characteristics. These characteristics include devices in which: the ion inlet and outlet are on the same element; the inlet and outlet are at the same voltage; the outlet is upstream from the inlet; the outlet is on the axis; the inlet is on the axis; and the ions are focused on the outlet.

Ion mobility separation devices

A differential mobility analyzer (DMA) for separating charged particles or ions suspended in a gas and a method of using the DMA for separating such particles. The invention includes various means for increasing the resolution of the DMA by stabilizing the laminar flow within the DMA and by allowing unusually large flow velocities.

Method and apparatus to increase the resolution and widen the range of differential mobility analyzers (DMAs)

The present invention concerns the formation of a stable electrospray of a volatile liquid at reduced pressures by limiting its tendency to evaporate. In a first approach, multi-component capillary jets are produced, comprising a thin layer of low volatility liquid, which is not necessarily a good conductor, surrounding a core of volatile and conducting liquid such as water, so as to minimize direct exposure of the volatile liquid to the region of low pressure. In a second approach, the diameter of the meniscus of a Taylor cone is reduced to a critical diameter, below which no evaporative freezing occurs.

Method and apparatus to produce ions and nanodrops from Taylor cones of volatile liquids at reduced pressures

An analytical apparatus provides for the separation and analysis of a subset of ions from a mixture of ions in a gas. The apparatus includes an ion supply, such as an electrospray, which provides a population of variously charged ions. An analyzing chamber is coupled to the ion supply and includes a first wall with an inlet orifice for receiving the flow of variously charged ions, and a second wall opposed to the first wall. A laminar gas flow is established within the analyzing chamber along a flow axis. The second wall is provided with an outlet orifice that is displaced by a determined distance along the gas flow axis from the inlet orifice. A potential difference is applied between the first and second walls which causes the flow of ions, introduced via the inlet orifice, to migrate towards the outlet orifice. The laminar gas flow displaces ion flight trajectories along the flow axis, so that only the ions with a mobility near a specific value reach the second wall close enough to the outlet orifice to be sampled through it. The outlet orifice is coupled to the inlet of a mass spectrometer to enable analysis of the ions emerging from the outlet orifice.

Method and apparatus for separation of ions in a gas for mass

An electrospray apparatus incorporating the invention includes a capillary with an exit for ejecting a fluid, and an electrode positioned downstream from the exit. A gas source is used to establish a region of gas, at least immediately about the exit. A voltage supply creates a potential difference between the capillary exit and the electrode, the potential difference being sufficient to both establish a cone jet mode of operation at the exit of the capillary, to ionize the region of gas about the exit and create a current flow between the exit and the electrode. The current flow exhibits an increased value upon the gas becoming ionized, thus enabling detection of the establishment of a corona. This action creates a corona-assisted cone jet mode of electrospray operation which enables the fluid to disperse into highly uniform sized particles. The preferred gas is carbon dioxide.

Growing community of inventors

New Haven, CT, United States of America

Juan Fernandez De La Mora