Indiana University

Advanced Research & Technology Institute

The Texas A&m University System

Ecole Polytechnique Federale De Lausanne

Ecole Polytechnique Féderale De Lausanne (epfl)

David E Clemmer

Michael A Ewing

Martin F Jarrold

Steven M Zucker

Christopher R P Conant

Stephen J Valentine

Samuel I Merenbloom

James P Reilly

Ruwan T Kurulugama

Stormy L Koeniger

Tarick J El-baba

Corinne A Lutomski

Fabiane M Nachtigall

Zachary Henson

David H Russell

Evan R Williams

Thomas Rizzo

Tarik J El-Baba

Michael Zachary Kamrath

Daniel R Fuller

Daniel W Woodall

Neelam Khanal

C Ray Sporleder

Chiara Masellis

Brooke A Brown

A method for purifying particles generates charged particles from a sample, measures at least at least one of masses, charge magnitudes and mobilities of the generated charged particles, and selectively passes to a particle collection target each of the measured charged particles having at least one of (a) a measured mass equal to a selected mass or within a selected range of particle masses, (b) a measured charge magnitude equal to a selected charge magnitude or within a selected range of charge magnitudes, (c) a mass-to-charge ratio equal to a selected mass-to-charge ratio or within a selected range of mass-to-charge ratios, and (d) a measured mobility equal to a selected mobility or within a selected range of mobilities. In some embodiments, the collected particles may be harvested and amplified.

System and method for identifying, selecting and purifying particles

A mass spectrometer may have an ion source region including an ion generator configured to generate ions from a sample, an ion detector configured to detect ions and produce corresponding ion detection signals, an electric field-free drift region disposed between the ion source region and the ion detector through which the generated ions drift axially toward the ion detector, a plurality of spaced-apart charge detection cylinders disposed in the drift region and through which the ions drifting axially through the drift region pass, and a plurality of charge amplifiers each coupled to a different one of the plurality of charge detection cylinders and each configured to produce a charge detection signal corresponding to a magnitude of charge of one or more of the generated ions passing through a respective one of the plurality of charge detection cylinders.

Mass spectrometer with charge measurement arrangement

A method for analyzing charged particles may include generating, in or into an ion source region, charged particles from a sample of particles, causing the charged particles to enter a mass spectrometer from the ion source region at each of a plurality of differing physical and/or chemical conditions in a range of physical and/or chemical conditions in which the sample particles undergo structural changes, controlling the mass spectrometer to measure at least the charge magnitudes of the generated charged particles at each of the plurality of differing physical and/or chemical conditions, determining, with a processor, an average charge magnitude of the generated charged particles at each of the plurality of differing physical and/or chemical conditions based on the measured charge magnitudes, and determining, with the processor, an average charge magnitude profile over the range of physical and/or chemical conditions based on the determined average charge magnitudes.

Identification of sample subspecies based on particle charge behavior under structural change-inducing sample conditions

Identification of sample subspecies based on particle mass and charge over a range of sample temperatures

An instrument for energizing molecules contained in a sample solution may include a droplet generator configured to generate droplets of the sample solution. The droplet generator illustratively has an elongated nozzle defining an orifice at one end thereof from which the droplets exit the droplet generator, and the orifice illustratively defines a first longitudinal axis centrally therethrough. A molecule energizing source is configured to produce a molecule energizing field, and is positioned relative to the nozzle orifice such that the molecule energizing field extends into at least some of the generated droplets along a direction non-parallel with the first longitudinal axis. The molecule energizing field illustratively carries energy which heats at least one of the generated droplets sufficiently to induce structural changes in at least one molecule contained in the at least one of the generated droplets.

Instrument and method for energizing molecules in charged droplets

A method for a structural characterization of polysaccharides, comprising steps of characterizing a polysaccharide by physical measurements comprising a determination of a mass of the polysaccharide by means of mass spectrometry, a further determination of a rotationally averaged cross section of the polysaccharide by means of ion mobility spectrometry, and an infrared spectrum of the polysaccharide by means of cryogenic, messenger-tagging IR spectroscopy.

Method for characterizing polysaccharides

An ion mobility spectrometer includes a drift tube responsive to application of at least a first voltage to establish a first electric field therein configured to cause ions within the drift tube to move along and about the drift tube while separating from one another as a function of ion mobility, and a transition region coupled to opposed ends of the first drift tube such that the drift tube and the transition region together define a closed path. The transition region is responsive to application of at least a second voltage to cause the ions to move along and about the closed path, to application of at least a third voltage to selectively pass ions into the drift tube and to application of at least a fourth voltage to selectively pass ions out of the drift tube.

Closed path ion mobility spectrometer having a common ion inlet and outlet

A hybrid ion mobility spectrometer includes a single-pass drift tube having an ion inlet and an ion outlet, a multiple-pass drift tube having an ion inlet and an ion outlet each coupled to the single pass drift tube between the ion inlet and the ion outlet thereof, and at least one ion steering channel controllable to selectively pass ions traveling through the single-pass drift tube into the multiple-pass drift tube via the ion inlet of the multiple-pass drift tube and to selectively pass ions traveling through the multiple-pass drift tube into the single-pass drift tube via the ion outlet of the multiple-pass drift tube. The single-pass drift tube separates in time ions traveling therethrough according to a first function of ion mobility, and the multiple-pass drift tube separates in time ions traveling one or more times therethrough according to the first or a second function of ion mobility.

Hybrid ion mobility spectrometer

An ion mobility spectrometer instrument has a drift tube that is partitioned into a plurality of cascaded drift tube segments. A number of electric field sources may each be coupled to one or more of the plurality of drift tube segments. A control circuit is configured to control operation of the number of the electric field sources in a manner that sequentially applies electric fields to the drift tube segments with a magnitude of at least one being different than the others to allow only ions having a predefined ion mobility or range of ion mobilities to travel through the drift tube. Alternatively, the length of at least one of the drift tube segments may be made different from those of the others to produce the same result. The drift tube segments may define a linear drift tube or a closed drift tube with a continuous ion travel path.

Ion mobility spectrometer and method of operating same

In a linear drift tube partitioned into a plurality of cascaded drift tube segments each followed by an ion elimination region, a system and method of separating ions includes repeatedly establishing electric drift fields in the drift tube segments and in some of the ion elimination regions while establishing electric repulsive fields in others of the ion elimination regions such that ions having a predefined mobility or range of mobilities are transmitted through the drift tube in one direction, and when the ions reach the end of the drift tube the electric drift fields are reversed and the process is repeated to transmit the ions to the opposite end of the drift tube. Ions may be made to pass back and forth through the drift tube any number of times before being drawn out of the drift tube to an ion detector or into another drift tube.

A hybrid ion mobility spectrometer includes a single-pass drift tube having an ion inlet at one end and an ion outlet at an opposite end, a multiple-pass drift tube having an ion inlet and an ion outlet each coupled to the single pass drift tube between the ion inlet and the ion outlet thereof, and a set of ion gates each controllable between an open position to pass ions therethrough and a closed position to block ions from passing therethrough. The set of ion gates may be controlled to pass at least some ions traveling through the single-pass drift tube into the multiple-pass drift tube via the ion inlet of the multiple-pass drift tube and to pass at least some ions traveling through the multiple-pass drift tube into the single-pass drift tube via the ion outlet of the multiple-pass drift tube.

In a drift tube partitioned into a plurality of cascaded drift tube segments each followed by an ion elimination region, a method of separating ions as a function of ion mobility includes repeatedly, and alternating between at least two different time durations, establishing electric drift fields in the drift tube segments and in some of the ion elimination regions while establishing electric repulsive fields in others of the ion elimination regions such that ions having a predefined mobility or range of mobilities are transmitted through the drift tube at one or more frequencies which include one or more overtones of a fundamental frequency at which ions having the predefined mobility or range of mobilities are transmitted through the drift tube with the electric drift fields and electric repulsive fields repeatedly established with uniform time durations.

In a drift tube partitioned into a plurality of cascaded drift tube segments each followed by an ion elimination region, for any integer M greater than 1, a method of separating ions repeats the following multiple times to cause only ions entering the drift tube that have a predefined ion mobility or range to traverse the drift tube: for each integer N beginning with 1 and sequentially advancing to M, establishing for a time duration an Nth electric repulsive field in the Nth ion elimination region and in every following Mth ion elimination region and an Nth electric drift field in each remaining ion elimination region and in each drift tube segment while deactivating for the time duration all non-Nth electric drift fields and non-Nth electric repulsive fields in each of the ion elimination regions and drift tube segments.

An ion mobility spectrometer instrument has a drift tube that is partitioned into a plurality of cascaded drift tube segments. A number of electric field activation sources may each be coupled to one or more of the plurality of drift tube segments. A control circuit is configured to control operation of the number of electric field activation sources in a manner that sequentially applies electric fields to the drift tube segments with a activation duration of at least one of the electric field activation sources different than that of the others to allow only ions having a predefined ion mobility or range of ion mobilities to travel through the drift tube. The drift tube segments may define a linear drift tube or a closed drift tube with a continuous ion travel path.

An ion mobility spectrometer comprises a drift tube defining a drift tube inlet configured to receive ions and a drift tube outlet. The drift tube is configured to separate ions in time as a function of ion mobility. The drift tube defines a first ion activation region between the drift tube inlet and the drift tube outlet. The first ion activation region is configured to selectively induce structural changes in at least some of the ions.

Growing community of inventors

Gosport, IN, United States of America

David E Clemmer