Indiana University

The University of North Carolina at Chapel Hill

Martin F Jarrold

Daniel Botamanenko

Andrew W Alexander

Aaron R Todd

David E Clemmer

Staci N Anthony

Benjamin E Draper

Joanna A Hogan

Deven L Shinholt

Corrine A Lutomski

Aaron A Todd

Tarick J El-baba

Corinne A Lutomski

Aravind Asokan

David Keifer

Brooke A Brown

Elizabeth Pierson

A charge detection mass spectrometer includes an ion trap configured to store ions therein and to release stored ions therefrom, and an electrostatic linear ion trap (ELIT) array, in the form of at least two ELITs or ELIT regions each spaced apart from the ion trap, each ELIT or ELIT region including first and second ion mirrors and a charge detection cylinder positioned therebetween. The ion trap is controlled to release at least some of the stored ions to travel toward and into each of the ELITs or ELIT regions, and the first and second ion mirrors of each of the ELITs or ELIT regions is controlled in a manner which traps one or more ions traveling therein and causes the trapped ion(s) to oscillate back and forth between the first and second ion mirrors each time passing through and inducing a corresponding charge on the charge detection cylinder.

Apparatus and method for pulsed mode charge detection mass spectrometry

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

An instrument for analyzing ions may include an ion source to generate ions, at least one ion processing instrument to process the generated ions by one or both of filtering the ions according to a molecular characteristic and dissociating the ions, and an electrostatic linear ion trap (ELIT) to receive and trap ions exiting the at least one ion processing instrument. The ELIT has first and second ion mirrors separated by a charge detection cylinder, and is configured such that trapped ions oscillate back and forth through the charge detection cylinder between the first and second ion mirrors with a duty cycle, corresponding to a ratio of time spent by the trapped ions traversing the charge detection cylinder and total time spent by the trapped ions traversing a combination of the first and second ion mirrors and the charge detection cylinder during one complete oscillation cycle, of approximately 50%.

Instrument, including an electrostatic linear ion trap, for analyzing ions

A charge detection mass spectrometer may include an ion source to generate ions, a mass spectrometer to separate the generated ions as a function of ion mass-to-charge ratio to produce beam of separated ions, an electrostatic linear ion trap (ELIT) including a charge detection cylinder disposed between a pair of coaxially aligned ion mirrors, and means for controlling a trajectory of the beam of separated ions entering the ELIT to cause the ions subsequently trapped in the ELIT to oscillate therein with different planar ion oscillation trajectories angularly offset from one another about the longitudinal axis with each extending along and crossing the longitudinal axis in each of the ion mirrors or with different cylindrical ion oscillation trajectories radially offset from one another about the longitudinal axis to form nested cylindrical trajectories each extending along the longitudinal axis.

Instrument for separating ions including an electrostatic linear ion trap to simultaneously trap multiple ions

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

A charge detection mass spectrometer (CDMS) includes an electrostatic linear ion trap (ELIT), a processor, and a memory having instructions stored therein executable by the processor to (a) control the ELIT to trap an ion, (b) collect ion measurement information as the trapped ion oscillates back and forth through the ELIT, the ion measurement information including charge induced by the ion on a charge detector of the ELIT during each pass of the ion through the ELIT and timing of the induced charges relative to one another, (c) process the ion measurement information in the time-domain for each of a plurality of sequential time windows of the ion measurement information to determine a charge magnitude of the ion during each time window, and (d) determine the magnitude of charge of the trapped ion based on the charge magnitudes of each of the time windows.

Time-domain analysis of signals for charge detection mass spectrometry

An electrostatic linear ion trap (ELIT) array includes a plurality of ion mirrors and a plurality of elongated charge detection cylinders each defining an axial passageway centrally therethrough, the ion mirrors and the charge detection cylinders arranged relative to one another such that each charge detection cylinder is positioned between a different respective pair of the ion mirrors with the respective axial passageways of each coaxial with one another, wherein the axial passageways of the ELITs are not coaxial with one another, means for selectively directing at least one ion into each of the plurality of ELITs, and means for controlling each of the ion mirrors in a manner which causes the at least one ion in at least two of the ELITs to become trapped therein and to simultaneously oscillate back and forth between the respective ion mirrors each time passing through the respective charge detection cylinder.

Ion trap array for high throughput charge detection mass spectrometry

A charge detection mass spectrometer includes an ion trap configured to receive and store ions therein and to selectively release stored ions therefrom, and an electrostatic linear ion trap (ELIT) spaced apart from the ion trap, the ELIT including first and second ion mirrors and a charge detection cylinder positioned therebetween, and means for selectively controlling the ion trap to release at least some of the stored ions therefrom to travel toward and into the ELIT, and for controlling the first and second ion mirrors in a manner which traps in the ELIT a single one of the ions traveling therein and causes the trapped ion to oscillate back and forth between the first and second ion mirrors each time passing through and inducing a corresponding charge on the charge detection cylinder.

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

The present disclosure relates to methods of identifying components present in intact lipoprotein particles. Methods provided include single particle mass spectrometry, such as charge detection mass spectrometry (CDMS). Distinct subtypes and subpopulations that exist within lipoprotein density classes are determined based on simultaneously measured m/z and charge of ionized lipoprotein particles.

Methods for resolving lipoproteins with mass spectrometry

A CDMS may include an ion source to generate ions from a sample, a mass spectrometer to separate the generated ions as a function of ion mass-to-charge ratio, an electrostatic linear ion trap (ELIT) having a charge detection cylinder disposed between first and second ion mirrors, wherein ions exiting the mass spectrometer are supplied to the ELIT, a charge generator for generating free charges, a field free region between the charge generator and the charge detection cylinder, and a processor configured to control the charge generator, with no ions in the charge detection cylinder, to generate a target number of free charges and cause the target number of free charges to travel across the field-free region and into contact with the charge detection cylinder to deposit the target number of free charges thereon and thereby calibrate or reset the charge detection cylinder to a corresponding target charge level.

Instrument, including an electrostatic linear ion trap with charge detector reset or calibration, for separating ions

A charge detection mass spectrometer may include an electrostatic linear ion trap (ELIT) or orbitrap, a source of ions to supply ions to the ELIT or orbitrap, a processor operatively coupled to the ELIT or orbitrap, a display monitor coupled to the processor, and a memory having instructions stored therein executable by the processor to produce a control graphic user interface (GUI) on the display monitor, the control GUI including at least one selectable GUI element for at least one corresponding operating parameter of the ELIT or orbitrap, receive a first user command, via user interaction with the control GUI, corresponding to selection of the at least one selectable GUI element, and control the ELIT or orbitrap to control the at least one corresponding operating parameter of the ELIT or orbitrap in response to receipt of, and based on, the first user command.

Charge detection mass spectrometry with real time analysis and signal optimization

A system for separating ions may include an ion source configured to generate ions from a sample, at least one ion separation instrument configured to separate the generated ions as a function of at least one molecular characteristic, and an orbitrap in which a rotating and oscillating ion induces charges on inner and outer electrode halves of the orbitrap, and wherein charge detection circuitry is configured to detect the charges induced on each of the inner electrode halves and on each of the outer electrode halves, and to combine the detected charges for each oscillation to produce a measured ion charge signal.

System for separating ions including an orbitrap for measuring ion mass and charge

The present disclosure relates to a method of identifying components present in a lipoprotein. Methods provided include single particle mass spectrometry, such as charge detection mass spectrometry (CDMS). Distinct subpopulations that exist within lipoprotein classes are determined by correlating m/z and mass.

Growing community of inventors

Bloomington, IN, United States of America

Martin F Jarrold