Other

Chem-space Associates, Inc.

Perkinelmer Health Sciences, Inc.

Georgia Tech Research Corporation

Extrel Corporation

Science Applications International Corporation

Biomicom Incorporated

Waters Investments Limited

Ross Clark Willoughby

Edward William Sheehan

Craig M Whitehouse

Thomas P White

Richard F Browner

James D Buchner, Jr

John C Berends, Jr

Timothy Paul Karpetsky

Joseph A Jarrell

David M Strand

Ed Sheehan

Carolyn A Fries

Cell and organ (or tissue) cultures provide a micro-environment with respect to nutrients, gas exchange, and scaffolding in order to encourage specific cell function, and in some cases to mimic in-vivo cellular expression under in-vitro conditions. We describe apparatus and methods to chemically, spatially, and temporally measure diffusible molecules produced, or used by cells or tissues in culture. In this manner, mechanisms of cell-cell interaction and other chemical signaling, detailed biochemical pathways, and the action of potential pharmaco-therapy agents can be better understood at a molecular level. In addition to basic science, the technical advantages of process monitoring and control can be applied to optimize culture products in bioreactors. Embodiments of this device are intended to simulate and monitor [input and output] the behavior of vascular capillary beds in higher species vascular systems.

Micro-sampling for cell, tissue, and micro-organism monitoring

The current invention describes in vivo and vitro (cultured) sampling technologies that allow direct temporal and spatial sampling from living ecosystems such as those associated with marine ecology. The optional use of parallel sampling methods, observatory design, provides for the ability to measure the response of individual organisms to a variety of both biotic and abiotic stresses. Sampling in small volumes and close proximity to living organisms has allowed direct measurement of various invertebrate and other aquatic species in marine ecosystems. These sampling techniques are intended to apply to any liquid based ecosystem in an attempt to minimize sampling as a dependent variable in measuring the chemical and biological behavior of the ecosystem. If is intended that this sampling technology be used to directly measure the chemical behavior of a wide variety of organisms; including, plants, animals, and micro-organisms (e.g. algae, plankton). These probes facilitate the direct measurement of metabolism, decomposition, pollution, and stress or stimuli from the local environment. A variety of sampling tips and probes have been developed for discrete and continuous sampling. A variety of sampling probe geometries, sizes, and sampling capabilities are disclosed that enable both contact and non-contact sampling of the chemical environment. The liquid sampling has been optimized for chemical analysis with liquid chromatography mass spectrometry. Fatty acid and lipid profiling have been demonstrated on a number of species from a cultured aquatic using these techniques.

Micro-sampling for aquatic chemical analysis

A multiple function atmospheric pressure ion source interfaced to a mass spectrometer comprises multiple liquid inlet probes configured such that the sprays from two or more probes intersect in a mixing region. Gas phase sample ions or neutral species generated in the spray of one probe can react with reagent gas ions generated from one or more other probes by such ionization methods as Electrospray, photoionization, corona discharge and glow discharge ionization. Reagent ions may be optimally selected to promote such processes as Atmospheric Pressure Chemical Ionization of neutral sample molecules, or charge reduction or electron transfer dissociation of multiply charged sample ions. Selected neutral reagent species can also be introduced into the mixing region to promote charge reduction of multiply charged sample ions through ion-neutral reactions. Different operating modes can be performed alternately or simultaneously, and can be rapidly turned on and off under manual or software control.

Atmospheric pressure ion source for mass spectrometry

An apparatus for generating ions includes an Electrospray ionization source configured to provide a spray of charged droplets from a sample solution during operation of the apparatus; an atmospheric pressure chemical ionization (APCI) source including a corona discharge needle configured to produce a corona discharge that further ionizes the spray during operation of the apparatus; and a gas delivery system configured to deliver a gas flow to the corona discharge needle during operation of the apparatus, wherein the gas flow comprises a reagent ion gas which facilitates ionization of the spray by the corona discharge.

An improved ion sampling tube designed to increase the amount of current delivered into the vacuum system of a mass spectrometer or other gas-phase ion or particle detectors or collectors. A device and method is disclosed that utilizes a tube with a high flow of ion entrained gas passing through the said tube. Said ions are directed from the tubular gas flow through an ion selective aperture and into an adjacent region and subsequently directed into a lower pressure region for detection or collection. The method is useful for enhancing the detection of analytes in solutions that are either nebulized or electrosprayed, and analytes present in gases. The method is also useful for isolating ionic species from the ion source from neutral gases and particles that may interfere or interact with analyte species. The method also decouples the high flow of the atmospheric pressure ion source from the low flow ion transmission into vacuum.

High-flow tube for sampling ions from an atmospheric pressure ion source

Ions carried in a flowing gas stream are transferred to another gas stream of different composition or purity through an ion selective aperture communicating between the gas streams. The ion selective aperture is formed of a central layer which has an electrically conductive layer on each of its surfaces. One or more open channels extend through the central layer and surface layers allowing physical movement of ions therethrough under the urging and influence of an electric field created by imposing a voltage differential between the conductive surface layers of the ion selective aperture. The gas flow rates of the different gas streams may be independently varied to allow adjustment of ion concentration and flow rate to meet the needs of the ion destination. This device can control sample ion introduction into gas-phase ion detectors, such as ion mobility analyzers, differential mobility analyzers, mass spectrometers, and combinations thereof.

Ion transfer device

An improved electrospray ion source for increasing the current generated from the electrospray process and of the type having a needle (), a counter-electrode (), a saddle or outer electrode (), and concurrent flow of gas (). A method and device is disclosed that utilizes a controlled electrospray nebulizer where an aerosol comprised of charged droplets and gas-phase ions is sprayed into a field-free or near field-free desolvation or reaction region (). This process results in the production and ultimate destination of charged aerosols and gas-phase ions in field-free or near field-free regions () where they can be directed towards and into a sampling aperture or tube; directed into a reaction region resulting in to the production of reaction products; or directed and deposited on surfaces resulting in the production of desorbed products by means of a concurrent flow of gas or nebulizing gas (), a potential difference between the regions of production and destination, counter-current flow of gas, or a combination thereof. The method is useful for increasing the detection of analytes in solutions that are electrosprayed and analyzed with mass spectrometry.

Field-free electrospray nebulizer

Atmospheric pressure, intermediate pressure and vacuum laser desorption ionization methods and ion sources are configured to increase ionization efficiency and the efficiency of transmitting ions to a mass to charge analyzer or ion mobility analyzer. An electric field is applied in the region of a sample target to accumulate ions generated from a local ion source on a solid or liquid phase sample prior to applying a laser desorption pulse. The electric field is changed just prior to or during the desorption laser pulse to promote the desorption of charged species and improve the ionization efficiency of desorbed sample species. After a delay, the electric field may be further changed to optimize focusing and transmission of ions into a mass spectrometer or ion mobility analyzer. Charged species may also be added to the region of the laser desorbed sample plume to promote ion-molecule reactions between the added ions and desorbed neutral sample species, increasing desorbed sample ionization efficiency and/or creating desired product ion species. The cycling of electric field changes is repeated in a timed sequence with one or more desorption laser pulse occurring per electric field change cycle. Embodiments of the invention comprise atmospheric pressure, intermediate pressure and vacuum pressure laser desorption ionization source methods and devices for increasing the analytical flexibility and improving the sensitivity of mass spectrometric analysis.

Laser desorption ion source

An improved ion source and means for collecting and focusing dispersed gas-phase ions from a remote reagent chemical ionization source (R2CIS) at atmospheric or intermediate pressure is described. The R2CIS is under electronic control and can produce positive, negative, or positive and negative reagent ions simultaneously. This remote source of reagent ions is separated from a low-field sample ionization region by a stratified array of elements, each element populated with a plurality of openings, wherein DC potentials are applied to each element necessary for transferring reagent ions from the R2CIS into the low-field sample ionization region where the reagent ions react with neutral and/or ionic sample forming sample ionic species. The resulting sample ionic species are then introduced into a mass spectrometer, ion mobility spectrometer or other sensor capable of detecting the sample ions. Embodiments of this invention are methods and devices for improving sensitivity of mass spectrometry when gas and liquid chromatographic separation techniques are coupled to atmospheric and intermediate pressure photo-ionization, chemical ionization, and thermospray ionization sources; and improving the sensitivity of chemical detectors or probes.

Remote reagent ion generator

Atmospheric pressure, intermediate pressure and vacuum laser desorption ionization methods and ion sources are configured to increase ionization efficiency and the efficiency of transmitting ions to a mass to charge analyzer or ion mobility analyzer. An electric field is applied in the region of a sample target to accumulate ions generated from a local ion source on a solid or liquid phase sample prior to applying a laser desorption pulse. The electric field is changed just prior to or during the desorption laser pulse to promote the desorption of charged species and improve the ionization efficiency of desorbed sample species. After a delay, the electric field may be further changed to optimize focusing and transmission of ions into a mass spectrometer or ion mobility analyzer. Charged species may also be added to the region of the laser desorbed sample plume to promote ion-molecule reactions between the added ions and desorbed neutral sample species, increasing desorbed sample ionization efficiency and/or creating desired production species. The cycling of electric field changes is repeated in a timed sequence with one or more desorption laser pulse occurring per electric field change cycle. Embodiments of the invention comprise atmospheric pressure, intermediate pressure and vacuum pressure laser desorption ionization source methods and devices for increasing the analytical flexibility and improving the sensitivity of mass spectrometric analysis.

An improved ion source for collecting and focusing dispersed gas-phase ions from a reagent source at sub-atmospheric or intermediate pressure, having a remote source of reagent ions separated from a low-field sample ionization region by a barrier, comprised of alternating laminates of metal and insulator, populated with a plurality of openings, wherein DC potentials are applied to each metal laminate necessary for transferring reagent ions from the remote source into the low-field sample ionization region where the reagent ions react with neutral and/or ionic sample forming ionic species. The resulting ionic species are then introduced into the vacuum system of a mass spectrometer or ion mobility spectrometer. Embodiments of this invention are methods and devices for improving sensitivity of mass spectrometry when gas and liquid chromatographic separation techniques are coupled to sub-atmospheric and intermediate pressure photo-ionization, chemical ionization, and thermal-pneumatic ionization sources.

Remote reagent chemical ionization source

An improved ion source and portable analyzer for collecting and focusing dispersed gas-phase ions from a reagent source at atmospheric or intermediate pressure, having a remote source of reagent ions generated by direct or alternating currents, separated from a low-field sample ionization region by a stratified array of elements, each element populated with a plurality of openings, wherein DC potentials are applied to each element necessary for transferring reagent ions from the remote source into the low-field sample ionization region where the reagent ions react with neutral and/or ionic sample forming ionic species. The resulting ionic species are then introduced into the vacuum system of a mass spectrometer or ion mobility spectrometer. Embodiments of this invention are methods and devices for improving sensitivity of mass spectrometry when gas and liquid chromatographic separation techniques or probes containing samples are coupled to atmospheric and intermediate pressure photo-ionization, chemical ionization, and thermospray ionization sources.

A thin laminated high transmission electro-optical lens populated with a plurality of apertures in communication with its laminates used to improve the collection, focusing, and selection of ions generated from atmospheric pressure sources, such as electrospray, atmospheric pressure chemical ionization, inductively coupled plasma, discharge, photoionization and atmospheric pressure matrix assisted laser desorption ionization. The laminated lens is made of alternating layers of electrically insulating and metal laminates. The geometry of the lens may be planar or shaped into various curve shapes, any of which act to optimize both the direct current (DC) and alternate current (AC) electric field geometries and strengths across the lens for transferring virtually all the ions from the ion source into an ion-focusing region adjacent and upstream of a high pressure or atmospheric pressure interface to a mass spectrometer, ion mobility analyzer, or combination thereof. Embodiments of this invention are methods and devices for improving sensitivity of mass spectrometry when coupled to high pressure or atmospheric pressure ionization sources.

Growing community of inventors

Pittsburgh, PA, United States of America

Ross Clark Willoughby