Abstract: 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.

Abstract: A method is provided for controlling a multi-pole charged particle transmission device having rods spaced apart radially about a central axis extending from a particle inlet at one end of the device to a particle outlet at an opposite end. An AC voltage source is controlled to apply an AC voltage having a frequency, a peak amplitude, and a waveform shape to the charged particle transmission device, and a set of charged particles is passed through the device under such conditions. The AC voltage source is then controlled to change at least one of the frequency, peak amplitude or shape of the AC, and another set of the charged particles is then passed through the charged particle transmission device under such conditions.

Abstract: A charged particle guide includes a plurality of electrically conductive segments radially spaced apart from one another about an opening defined axially through the segments, wherein the opening defines a central axis passing centrally and axially therethrough such that charged particles are received at one end of the opening and pass through an opposite end of the opening, at least one voltage source configured to produce and supply separate voltages to each of the segments, and at least one control circuit configured to control supply of selected voltages to the segments to create an electric field within the opening configured to cause charged particles entering the one end of the opening along a first axial path relative to the central axis to exit the opposite end of the opening along a second axial path relative to the central axis, wherein the first and second axial paths are not collinear.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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%.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: An instrument 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 electrostatic linear ion trap (ELIT) positioned to receive ions exiting the at least one ion separation instrument. The ELIT has first and second ion mirrors separated by a charge detection cylinder, and is configured such that an ion trapped therein oscillates 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 ion traversing the charge detection cylinder and total time spent by the trapped ion traversing a combination of the first and second ion mirrors and the charge detection cylinder during one complete oscillation cycle, of approximately 50%.

Abstract: A CDMS may include an ELIT having a charge detection cylinder (CD), a charge generator for generating a high frequency charge (HFC), a charge sensitive preamplifier (CP) having an input coupled to the CD and an output configured to produce a charge detection signal (CHD) in response to a charge induced on the CD, and a processor configured to (a) control the charge generator to induce an HFC on the CD, (b) control operation of the ELIT to cause a trapped ion to oscillate back and forth through the CD each time inducing a charge thereon, and (c) process CHD to (i) determine a gain factor as a function of the HFC induced on the CD, and (ii) modify a magnitude of the portion of CHD resulting from the charge induced on the CD by the trapped ion passing therethrough as a function of the gain factor.

Abstract: 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.

Abstract: A method for reducing heterogeneity of a virus preparation may include generating virus ions from the virus preparation, repeatedly increasing at least one of a temperature and an incubation period at the increased temperature of at least one of the virus preparation and the generated virus ions, measuring mass-to-charge ratios and charge magnitudes of at least some of the generated virus ions at each increase of the at least one of the temperature and the incubation period, determining a mass spectrum at each increase of the at least one of the temperature and the incubation period based on values of the respective mass-to-charge ratios and charge magnitudes, and determining, based on the mass spectrums, optimum ones of the temperature and the incubation period which together minimize, or at least reduce, a heterogeneity of the virus preparation without aggregation of virus capsids in the virus preparation.

Abstract: A charge filter instrument includes a field-free drift region, a plurality of charge detection cylinders in the drift region through which ions drifting axially therethrough pass, a plurality of charge sensitive amplifiers each coupled to at least one charge detection cylinder and configured to produce a charge detection signal corresponding to a charge of one or more of ions passing therethrough, a single inlet, single outlet charge deflector or a single inlet, multiple outlet charge steering device coupled to the outlet end of the drift region, means for determining charge magnitudes or charge states of ions drifting axially through the drift region based on the charge detection signals, and means for controlling the charge deflector or the charge steering device to pass through the single outlet or through a specified one of the multiple outlets only ions having a specified charge magnitude or charge state.

Abstract: A charge detection mass spectrometer may include an ion source, an electrostatic linear ion trap (ELIT) including a charge detection cylinder disposed between a pair of coaxially aligned ion mirrors, means for selectively establishing electric fields within the ion mirrors configured to cause the trapped ions in the ELIT to oscillate back and forth between the ion mirrors each time passing through the charge detection cylinder, and means for controlling a trajectory of the beam of ions entering the ELIT to cause the subsequently trapped ions to oscillate 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.

Abstract: 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.