636results about "Spectrometer combinations" patented technology

A mass spectrometer is configured with individual multipole ion guides, configured in an assembly in alignment along a common centerline wherein at least a portion of at least one multipole ion guide mounted in the assembly resides in a vacuum region with higher background pressure, and the other portion resides in a vacuum region with lower background pressure. Said multipole ion guides are operated in mass to charge selection and ion fragmentation modes, in either a high or low pressure region, said region being selected according to the optimum pressure or pressure gradient for the function performed. The diameter, lengths and applied frequencies and phases on these contiguous ion guides may be the same or may differ. A variety of MS and MS / MSn analysis functions can be achieved using a series of contiguous multipole ion guides operating in either higher background vacuum pressures, or along pressure gradients in the region where the pressure drops from high to low pressure, or in low pressure regions. Individual sets of RF, + / −DC and resonant frequency waveform voltage supplies provide potentials to the rods of each multipole ion guide allowing the operation of ion transmission, ion trapping, mass to charge selection and ion fragmentation functions independently in each ion guide. The presence of background pressure maintained sufficiently high to cause ion to neutral gas collisions along a portion of each multiple ion guide linear assembly allows the conducting of Collisional Induced Dissociation (CID) fragmentation of ions by axially accelerating ions from one multipole ion guide into an adjacent ion guide. Alternatively ions can be fragmented in one or more multipole ion guides using resonant frequency excitation CID. A multiple multipole ion guide assembly can be configured as the primary mass analyzer in single or triple quadrupole mass analyzers with or without mass selective axial ejection. Alternatively, the multiple multipole ion guide linear assembly can be configured as part of a hybrid Time-Of-Flight, Magnetic Sector, Ion Trap or Fourier Transform mass analyzer.

To provide comprehensive (i.e. rapid and sensitive) MS-MS analysis, the inventor employs a time-nested separation, using two time-of-flight (TOF) mass spectrometers. Parent ions are separated in a slow and long TOF1, operating at low ion energy (1 to 100 eV), and fragment ions are mass analyzed in a fast and short TOF2, operating at much higher keV energy. Low energy fragmentation cell between TOF1 and TOF2 is tailored to accelerate fragmentation and dampening steps, mostly by shortening the cell and employing higher gas pressure. Since separation in TOF1 takes milliseconds and mass analysis in TOF2—microseconds, the invention provides comprehensive MS-MS analysis of multiple precursor ions per single ion pulse. Slow separation in TOF1 becomes possible with an introduction of novel TOF1 analyzers. The TOF-TOF could be implemented using a static TOF1, here described on the examples of spiratron, planar and cylindrical multi-pass separators with griddles spatial focusing ion mirrors. Higher performance is expected with the use of novel hybrid TOF1 analyzers, combining radio frequency (RF) and quadratic DC fields. RF field retains low-energy ions within TOF1 analyzer, while quadratic DC field improves resolution by compensate for large relative energy spread.

A mass spectrometer is disclosed wherein ions having a particular desired charge state are selected by operating an ion mobility spectrometer in combination with a quadrupole mass filter. Precursor ions are fragmented or reacted to form product ions in a collision cell ion trap and sent back upstream to an upstream ion trap. The fragment or product ions are then passed through the ion mobility spectrometer wherein they become temporally separated according to their ion mobility. Fragment or product ions are then re-trapped in the collision cell ion trap before being released therefrom in packets. A pusher electrode of a time of flight mass analyzer is energized a predetermined period of time after a packet of ions is released from the collision cell ion trap. Accordingly, it is possible to select multiply charged precursor ions from a background of singly charged ions, fragment them, and mass analyze the fragment ions with a near 100% duty cycle across the whole mass range.

During the structural analysis of a protein or peptide by tandem mass spectroscopy, a peptide ion derived from a protein that has already been measured and that is expressed in great quantities is avoided as a tandem mass spectroscopy target. A peptide derived from a minute amount of protein, which has heretofore been difficult to analyze, can be automatically determined as a tandem mass spectroscopy target within the real time of measurement. Data concerning a protein that has already been measured and a peptide derived from the protein is automatically stored in an internal database. The stored data is collated with measured data with high accuracy to determine an isotope peak. In this way, the process of selecting a peptide peak that has not been measured as the target for the next tandem analysis can be performed within the real time of measurement and a redundant measurement of peptides derived from the same protein can be avoided. The information contained in the MSn spectrum is effectively utilized in each step of the MSn involving a multi-stage dissociation and mass spectroscopy (MSn), so that the flows for the determination of the next analysis content and the selection of the parent ion for the MSn+1 analysis, for example, can be optimized within the real time of measurement and with high efficiency and accuracy. Thus, a target of concern to the user can be subjected to tandem mass spectroscopy without wasteful measurement.

This invention relates to tandem mass spectrometry and, in particular, to tandem mass spectrometry using a linear ion trap and a time of flight detector to collect mass spectra to form a MS / MS experiment. The accepted standard is to store and mass analyze precursor ions in the ion trap before ejecting the ions axially to a collision cell for fragmentation before mass analysis of the fragments in the time of flight detector. This invention makes use of orthogonal ejection of ions with a narrow range of m / z values to produce a ribbon beam of ions that are injected into the collision cell. The shape of this beam and the high energy of the ions are accommodated by using a planar design of collision cell. Ions are retained in the ion trap during ejection so that successive narrow ranges may be stepped through consecutively to cover all precursor ions of interest.

To provide comprehensive MS—MS analysis, a time-nested separation is employed using two time-of-flight (TOF) mass spectrometers. Parent ions are separated in a slow and long TOF1, operating at low ion energy (1 to 100eV), and fragment ions are mass analyzed in a fast and short TOF2, operating at much higher keV energy. A low energy fragmentation cell between TOF1 and TOF2 is tailored to accelerate fragmentation and dampening steps, mostly by shortening the cell and employing higher gas pressure. Slow separation in TOF1 becomes possible with an introduction of novel TOF1 analyzers. Higher performance is expected with the use of novel hybrid TOF1 analyzers, combining radio frequency (RF) and quadratic DC fields. An RF field retains low-energy ions within a TOF1 analyzer, while a quadratic DC field improves resolution by compensating for a large relative energy spread.

A system and method for detecting an analyte of interest in a sample is provided. The method includes passing a set of ions obtained from the sample through an ion mobility spectrometer to filter out ions that are not ions of interest and to generate an ion mobility spectrum. A mass spectrum of at least some of the ions is generated using a mass spectrometer. The method also includes determining that the analyte of interest is in the sample when peaks of interest are found in one or more of the ion mobility spectrum and the mass spectrum, and the peaks of interest follow a predetermined pattern of peaks associated with the analyte of interest or are confirmed by ion mobility spectrometry.

The present invention provides methods for the determination of the structure of biomolecular targets, as well as the site and nature of the interaction between ligands and biomolecular targets. The present invention also provides methods for the determination of the relative affinity of a ligand for the biomolecular target it interacts with. Also provided are methods for screening ligand or combinatorial libraries of compounds against one or more than one biological target molecules. The methods of the invention also allow determination of the relative binding affinity of combinatorial and other compounds for a biomolecular target. The present invention further provides methods for the use of mass modifying tags for screening multiple biomolecular targets. In a preferred embodiment, ligands which have great specificity and affinity for molecular interaction sites on biomolecules, especially RNA can be identified. In preferred embodiments, such identification can be made simultaneously with libraries of ligands.

An imbalanced radio frequency (RF) field creates a retarding barrier near the exit aperture of a multipole ion guide, in combination with the extracting DC field such that the barrier provides an m / z dependent cut of ion sampling. Contrary to the prior art, the mass dependent sampling provides a well-conditioned ion beam suitable for other mass spectrometric devices. The mass selective sampling is suggested for improving duty cycle of o-TOF MS, for injecting ions into a multi-reflecting TOF MS in a zoom mode, for parallel MS-MS analysis in a trap-TOF MS, as well as for moderate mass filtering in fragmentation cells and ion reactors. With the aid of resonant excitation, the mass selective ion sampling is suggested for mass analysis.

Provided are methods of detecting the presence or amount of a vitamin D metabolite in a sample using mass spectrometry. The methods generally comprise ionizing a vitamin D metabolite in a sample and detecting the amount of the ion to determine the presence or amount of the vitamin D metabolite in the sample. Also provided are methods to detect the presence or amount of two or more vitamin D metabolites in a single assay.

The present invention is an improved apparatus and method for mass spectrometry using a dual ion trapping system. In a preferred embodiment of the present invention, three "linear" multipoles are combined to create a dual linear ion trap system for trapping, analyzing, fragmenting and transmitting parent and fragment ions to a mass analyzer-preferably a TOF mass analyzer. The dual ion trap according to the present invention includes two linear ion traps, one positioned before an analytic quadrupole and one after the analytic multipole. Both linear ion traps are multipoles composed of any desired number of rods-i.e. the traps are quadrupoles, pentapoles, hexapoles, octapoles, etc. Such arrangement enables one to maintain a high "duty cycle" while avoiding "memory effects" and also reduces the power consumed in operating the analyzing quadrupole.

An imbalanced radio frequency (RF) field creates a retarding barrier near the exit aperture of a multipole ion guide, in combination with the extracting DC field such that the barrier provides an m / z dependent cut of ion sampling. Contrary to the prior art, the mass dependent sampling provides a well-conditioned ion beam suitable for other mass spectrometric devices. The mass selective sampling is suggested for improving duty cycle of o-TOF MS, for injecting ions into a multi-reflecting TOF MS in a zoom mode, for parallel MS-MS analysis in a trap-TOF MS, as well as for moderate mass filtering in fragmentation cells and ion reactors. With the aid of resonant excitation, the mass selective ion sampling is suggested for mass analysis.

A system for analyzing one or more ion species of a sample including a first ion mobility filter associated with a first flow path for passing first ions of the sample, a second ion mobility filter associated with a second flow path for passing second ions of the sample, a first outlet from the first flow path for passing a portion of the first ions from the first flow path to the second flow path, and a first outlet from the second flow path for removing neutral particles from the second flow path where the first outlet from the second flow path is upstream of the second ion mobility filter in relation to the ion flow in the second flow path.

An ion separation instrument includes an ion source coupled to at least a first ion mobility spectrometer having an ion outlet coupled to a mass spectrometer. Instrumentation is further included to provide for passage to the mass spectrometer only ions defining a preselected ion mobility range. In one embodiment, the ion mobility spectrometer is provided with electronically controllable inlet and outlet gates, wherein a control circuit is operable to control actuation of the inlet and outlet gates as a function of ion drift time to thereby allow passage therethrough only of ions defining a mobility within the preselected ion mobility range. In another embodiment, an ion trap is disposed between the ion mobility spectrometer and mass spectrometer and is controlled in such a manner so as to collect a plurality of ions defining a mobility within the preselected ion mobility range prior to injection of such ions into the mass spectrometer. In yet another embodiment, an ion inlet of the ion trap may be electronically controlled relative to operation of the ion mobility spectrometer as a function of ion drift time to thereby allow passage therein only of ions defining a mobility within the preselected ion mobility range. The mass spectrometer is preferably a Fourier Transform Ion Cyclotron Resonance mass spectrometer, and the resulting ion separation instrument may further include therein various combinations of ion fragmentation, ion mass filtering, ion trap, charge neutralization and / or mass reaction instrumentation.

A mass spectrometer is disclosed wherein ions are passed through an ion mobility separator and are then mass analysed by a Time of Flight mass analyzer. Multiple sets of mass spectral data are obtained which are then post-processed so that mass spectral data relating to ions having undesired charge state(s) is filtered out. The resultant mass spectrum comprises ions having a desired charge state.

An apparatus (100) for sequentially analyzing particles such as single cells or single beads, by spectrometry. The apparatus, an elemental flow cytometer, includes means (102) for sequential particle introduction, means (104) to vaporize, atomize and excite or ionize the particles, or an elemental tag associated with an analyte on the particles, and means (106) to analyze the elemental composition of the vaporized, atomized and excited or ionized particles, or an elemental tag associated with the particles. Methods for sequentially analyzing particles such as singe cells or single beads by spectrometry are also described.

Multipole ion guides configured with one or mote segments and positioned in a higher pressure vacuum region, are operated in mass to charge selection and ion fragmentation modes. Individual multipole ion guides are mounted in a linear assembly with no electrodes configured in between each multipole ion guide. At least a portion of each multipole ion guide mounted in a linear assembly resides in a vacuum region with higher background pressure. At least one ion guide can be configured to extend continuously from one vacuum stage into another. Individual sets of RF, + / − DC and secular frequency voltage supplies provide potentials to the rods of each multipole ion guide allowing the operation of ion transmission, ion trapping, mass to charge selection and ion fragmentation functions independently in each ion guide. The presence of higher background pressure along a portion of the multiple ion guide linear assembly allows the Collisional Induced Dissociation (CID) fragmentation of ions by axially accelerating ions from one multipole ion guide to an adjacent ion guide, analogous to a triple quadrupole function. A variety of MS and MS / MSn analysis functions can be achieved with a mass analyzer configured with multiple ion guide linear assembly operated in a higher background pressure.

A novel high ion storage / ion mobility separation mass spectrometer that provides for a high duty cycle of operation is presented herein. In particular, the example embodiments, as disclosed herein, provides for a high ion storage / ion mobility instrument that beneficially includes a two-dimensional (2D) plurality of adjacently arranged ion confinement channels to provide a high storage bank of a desired mass range of ions. Such ions, via ion mobility transport, are separated into smaller fractions of an overall mass window into desired confinement regions of the disclosed 2D confinement channels and thereafter transferred out in a manner so as to enable the aforementioned novel high-duty cycle of sequential operation.

The invention relates to ions guided by gas flows in mass spectrometers, particularly in RF multipole systems, and to RF quadrupole mass filters and their operation with gas flows in tandem mass spectrometers. The invention provides a tandem mass spectrometer in which the RF quadrupole mass filter is operated at vacuum pressures in the medium vacuum pressure regime, utilizing a gas flow to drive the ions are through the mass filter. Vacuum pressures between 0.5 to 10 pascal are maintained in the mass filter. The mass filter may be enclosed by a narrow enclosure to guide the gas flow. The quadrupole mass filter may be followed by an RF multipole system, operated at the same vacuum pressure, serving as fragmentation cell to fragment the selected parent ions. The fragmentation cell may be enclosed by the same enclosure which already encloses the mass filter, so the ions may be driven by the same gas flow at the same vacuum pressure, greatly simplifying the required vacuum pumping system in tandem mass spectrometers. There are many other applications utilizing gas flows including supersonic gas jets in mass spectrometry.

The invention relates to time-of-flight mass spectrometers for the measurement of daughter ion spectra (also called fragment ion spectra or MS / MS spectra) and corresponding measurement methods.According to the invention, the ions of an ion source are initially accelerated only to an intermediate level of energy, allowing them to decompose at that energy level by metastable decomposition or by collisionally induced fragmentation (CID). The ions are then accelerated in a second step to a high energy level. Light fragment ions gain a higher velocity than heavier fragment ions or non-decomposed parent ions. The spectrum of fragment ions can be detected separated by mass in either linear or reflector mode. An ion selector at the low energy level selects a single type of parent ion in order to avoid superpositions with fragment ions of other parent ions. A particularly preferred embodiment raises the potential of ions, for there second acceleration, during their flight through a small electrically isolated flight path chamber.

A mass spectrometer includes an ion source and at least one vacuum stage, a means for delivering ions from the ion source to the vacuum stage, a collision cell, a detector, at least two multipole ion guide segments, and independent RF frequency and DC voltage sources applied to the multipole ion guide segments, the RF frequency and DC voltage sources being controlled independently of each other.

The invention “Ion Trap Array (ITA)” pertains generally to the field of ion storage and analysis technologies, and particularly to the ion storing apparatus and mass spectrometry instruments which separate ions by its character such as mass-to-charge ratio. The aim of this invention is providing an apparatus for ion storage and analysis comprising at least two or more rows of parallel placed electrode array wherein each electrode array includes at least two or more parallel bar-shaped electrodes, by applying different phase of alternating current voltages on different bar electrodes to create alternating electric fields inside the space between two parallel electrodes of different rows of electrode arrays, multiple linear ion trapping fields paralleled constructed in the space between the different rows of electrode arrays which are open to adjacent each other without a real barrier. This invention also provides a method for ion storage and analysis involving with the trapping, cooling and mass-selected analyzing of ions by this apparatus mentioned which constructs multiple conjoint linear ion trapping fields in the space between the different rows of electrode arrays

A mass analysis system including a low pressure dissociation region and a differential mobility spectrometer. The differential mobility spectrometer including at least one pair of filter electrodes defining an ion flow path where the filter electrodes generate an electric field for passing through a selected portion of the sample ions based on the mobility characteristics of the sample ions. The differential mobility spectrometer also includes a voltage source that provides DC and RF voltages to at least one of the filter electrodes to generate the electric field, an ion inlet that receives sample ions that have passed through the low pressure dissociation region, and an ion outlet that outputs the selected portion of the sample ions. A mass spectrometer receives some or all of the selected portion of the sample ions.

A multi-reflection mass spectrometer is provided comprising two ion-optical mirrors, each mirror elongated generally along a drift direction (Y), each mirror opposing the other in an X direction, the X direction being orthogonal to Y, characterized in that the mirrors are not a constant distance from each other in the X direction along at least a portion of their lengths in the drift direction. In use, ions are reflected from one opposing mirror to the other a plurality of times while drifting along the drift direction so as to follow a generally zigzag path within the mass spectrometer. The motion of ions along the drift direction is opposed by an electric field resulting from the non-constant distance of the mirrors from each other along at least a portion of their lengths in the drift direction that causes the ions to reverse their direction.

An apparatus (100) for sequentially analyzing particles such as single cells or single beads, by spectrometry. The apparatus, an elemental flow cytometer, includes means (102) for sequential particle introduction, means (104) to vaporize, atomize and excite or ionize the particles, or an elemental tag associated with an analyte on the particles, and means (106) to analyze the elemental composition of the vaporized, atomized and excited or ionized particles, or an elemental tag associated with the particles. Methods for sequentially analyzing particles such as singe cells or single beads by spectrometry are also described.

A mass spectrometer is disclosed wherein a relatively energetic pulse of ions having a relatively narrow spread of mass to charge ratios are ejected from a quadrupole ion trap and received in an ion trap upstream of a Time of Flight mass analyser. The ions are collisionally cooled within the ion trap and are pulsed out of the ion trap and into an extraction region of the Time of Flight mass analyser without substantially exciting the ions. This enables improved operation with the Time of Flight mass analyser. According to another embodiment, parent ions are fragmented and the resulting fragment ions are stored in two ion traps having different low mass cut-offs. The trapping system enables MS / MS experiments to be performed with a very high duty cycle.

This invention describes an ion mobility spectrometer system for chemical detection in the field. The system allows: a high throughput operation, an interface to new ionization methods, and an interface to a mass spectrometer.

In a tandem mass spectrometer ions are created only once and stored in an ion reservoir. A particular ion species to be analyzed is then exported from the reservoir through a mass selective ion gate without damaging the other ion species remaining in the reservoir. All subsequent analyses are conducted on these stored ions, without adding further ions so that no changes in the concentrations of the stored ion species occur. The exported ions are fragmented, and a fragment ion mass spectrum is measured in a mass analyzer, preferably in a time-of-flight mass analyzer with orthogonal ion injection. The processes of exporting a selected ion species with subsequent fragmentation and the acquisition of the fragment ion spectrum can be repeated for any number of ion species stored in the reservoir.