Abstract: Binding proteins comprising a VL region paired with a VH region, and a CH1 region paired with a CL region, wherein the VL region and VH region comprise opposite charged mutations to facilitate pairing, and wherein the CH1 region and CL region comprise mutations to facilitate pairing, are provided. Binding proteins comprising one or more cysteine residues engineered into the VH/VL pair to form one or more disulfide bonds, are also provided. Multispecific binding proteins, nucleic acids encoding binding proteins and multispecific binding proteins, expression vectors, host cells, pharmaceutical composition and methods of treatment administering the binding proteins or multispecific binding proteins described herein are also provided.

Abstract: An isotope ratio mass spectrometer has an ion source, a static field mass filter, a reaction cell to induce a mass shift reaction, and a sector field mass analyser for spatially separating ions from the reaction cell according to their m/z. A detector platform detects a plurality of different ion species separated by the sector field mass analyser. The static field mass filter has a first Wien filter that deflects ions away from a longitudinal symmetry axis of the spectrometer in accordance with the ions' m/z, and a second Wien filter that deflects ions back towards the longitudinal symmetry axis in accordance with the ions' m/z. An inverting lens is positioned along the longitudinal axis between the Wien filters to invert the direction of deflection of the ions from the first Wien filter. The static field mass filter provides high transmission and improved spectrometer sensitivity. The first and second Wien filters permit simple tuning.

Abstract: An ion optical arrangement (1) for use in a mass spectrometer comprises a collision cell defining an ion optical axis along which ions may pass, electrodes comprising a set of parallel poles (11A, 11B, 11C) arranged in the collision cell, and a voltage source for providing voltages to the electrodes to produce electric fields. The ion optical arrangement is arranged for switching between a first operation mode in which the collision cell is pressurized and a second operation mode in which the collision cell is substantially evacuated. The ion optical arrangement is further arranged for producing a radio frequency electric focusing field in the first operation mode and a static electric focusing field in the second operation mode.

Abstract: An ion optical arrangement (1) for use in a mass spectrometer comprises electrodes (11, 12, 14) comprising a multipole arrangement defining an ion optical axis, and a voltage source for providing voltages to the electrodes to produce electric fields. The ion optical arrangement is configured for producing a radio frequency electric focusing field for focusing ions on the ion optical axis. The radio frequency electric focusing field has a varying frequency so as to reduce any mass dependence of ion trajectories through the ion optical arrangement. The ion optical arrangement may further he configured for producing a static electric field in response to a DC bias voltage applied to the multipole arrangement. A superimposed varying electric field may be produced by superimposing an AC voltage upon the DC bias voltage.

Abstract: An isotope ratio mass spectrometer has an ion source, a static field mass filter, a reaction cell to induce a mass shift reaction, and a sector field mass analyser for spatially separating ions from the reaction cell according to their m/z. A detector platform detects a plurality of different ion species separated by the sector field mass analyser. The static field mass filter has a first Wien filter that deflects ions away from a longitudinal symmetry axis of the spectrometer in accordance with the ions' m/z, and a second Wien filter that deflects ions back towards the longitudinal symmetry axis in accordance with the ions' m/z. An inverting lens is positioned along the longitudinal axis between the Wien filters to invert the direction of deflection of the ions from the first Wien filter. The static field mass filter provides high transmission and improved spectrometer sensitivity. The first and second Wien filters permit simple tuning.

Abstract: An ion optical arrangement (1) for use in a mass spectrometer comprises electrodes (11, 12, 14) comprising a multipole arrangement defining an ion optical axis, and a voltage source for providing voltages to the electrodes to produce electric fields. The ion optical arrangement is configured for producing a radio frequency electric focusing field for focusing ions on the ion optical axis. The radio frequency electric focusing field has a varying frequency so as to reduce any mass dependence of ion trajectories through the ion optical arrangement. The ion optical arrangement may further be configured for producing a static electric field in response to a DC bias voltage applied to the multipole arrangement. A superimposed varying electric field may be produced by superimposing an AC voltage upon the DC bias voltage.

Abstract: An isotope ratio mass spectrometer has an ion source, a static field mass filter, a reaction cell to induce a mass shift reaction, and a sector field mass analyser for spatially separating ions from the reaction cell according to their m/z. A detector platform detects a plurality of different ion species separated by the sector field mass analyser. The static field mass filter has a first Wien filter that deflects ions away from a longitudinal symmetry axis of the spectrometer in accordance with the ions' m/z, and a second Wien filter that deflects ions back towards the longitudinal symmetry axis in accordance with the ions' m/z. An inverting lens is positioned along the longitudinal axis between the Wien filters to invert the direction of deflection of the ions from the first Wien filter. The static field mass filter provides high transmission and improved spectrometer sensitivity. The first and second Wien filters permit simple tuning.

Abstract: An ion optical arrangement (1) for use in a mass spectrometer comprises a collision cell defining an ion optical axis along which ions may pass, electrodes comprising a set of parallel poles (11A, 11B, 11C) arranged in the collision cell, and a voltage source for providing voltages to the electrodes to produce electric fields. The ion optical arrangement is arranged for switching between a first operation mode in which the collision cell is pressurized and a second operation mode in which the collision cell is substantially evacuated. The ion optical arrangement is further arranged for producing a radio frequency electric focusing field in the first operation mode and a static electric focusing field in the second operation mode.

Abstract: An ion optical arrangement (1) for use in a mass spectrometer comprises electrodes (11, 12, 14) comprising a multipole arrangement defining an ion optical axis, and a voltage source for providing voltages to the electrodes to produce electric fields. The ion optical arrangement is configured for producing a radio frequency electric focusing field for focusing ions on the ion optical axis. The radio frequency electric focusing field has a varying frequency so as to reduce any mass dependence of ion trajectories through the ion optical arrangement. The ion optical arrangement may further be configured for producing a static electric field in response to a DC bias voltage applied to the multipole arrangement. A superimposed varying electric field may be produced by superimposing an AC voltage upon the DC bias voltage.

Abstract: An isotope ratio mass spectrometer has an ion source, a static field mass filter, a reaction cell to induce a mass shift reaction, and a sector field mass analyser for spatially separating ions from the reaction cell according to their m/z. A detector platform detects a plurality of different ion species separated by the sector field mass analyser. The static field mass filter has a first Wien filter that deflects ions away from a longitudinal symmetry axis of the spectrometer in accordance with the ions' m/z, and a second Wien filter that deflects ions back towards the longitudinal symmetry axis in accordance with the ions' m/z. An inverting lens is positioned along the longitudinal axis between the Wien filters to invert the direction of deflection of the ions from the first Wien filter. The static field mass filter provides high transmission and improved spectrometer sensitivity. The first and second Wien filters permit simple tuning.

Abstract: An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U?(r, ?, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U?(r, ?, z) is the result of a perturbation W to an ideal field U(r, ?, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, ?, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2? radians over an ion detection period Tm.

Abstract: A method of calibrating a mass spectrometer is disclosed. The mass spectrometer includes a first quadrupole, a second mass analyzer and a detection means. The method includes calibrating the second mass analyzer at a first time, calibrating the first quadrupole at a second time later than the first including a) determining for each of several selected masses a corresponding value of the amplitude of the RF voltage and DC voltage applied to the electrodes of the first quadrupole, b) fitting a function of the selected mass to the values of the amplitude of the RF voltage and DC voltage corresponding to the several selected masses, c) detecting the selected mass in a filter window width over a mass range, d) evaluating a shift of the peak position and/or a deviation of the filter window width, and e) repeating the calibration steps under certain conditions.

Abstract: An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U?(r, ?, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U?(r, ?, z) is the result of a perturbation W to an ideal field U(r, ?, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, ?, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2? radians over an ion detection period Tm.

Abstract: An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U?(r, ?, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U?(r, ?, z) is the result of a perturbation W to an ideal field U(r, ?, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, ?, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2 ? radians over an ion detection period Tm.

Abstract: A method of calibrating a mass spectrometer is disclosed. The mass spectrometer includes a first quadrupole, a second mass analyzer and a detection means. The method includes calibrating the second mass analyzer at a first time, calibrating the first quadrupole at a second time later than the first including a) determining for each of several selected masses a corresponding value of the amplitude of the RF voltage and DC voltage applied to the electrodes of the first quadrupole, b) fitting a function of the selected mass to the values of the amplitude of the RF voltage and DC voltage corresponding to the several selected masses, c) detecting the selected mass in a filter window width over a mass range, d) evaluating a shift of the peak position and/or a deviation of the filter window width, and e) repeating the calibration steps under certain conditions.

Abstract: An electrostatic dual-mode lens assembly is provided for selectively transmitting or reflecting an ion beam in a mass spectrometer. The assembly comprises at least one electrode that provides a switchable electric field that, during a first mode of operation, directs an ion beam that enters the assembly along a first path so that the beam is transmitted through the assembly along the first path, and during a second mode of operation, directs an ion beam that enters the assembly along the first path so that the ion beam is reflected by the electric field and exits the assembly along a second path. Methods for operating a mass spectrometer using an electrostatic lens are also provided.

Abstract: An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U?(r, ?, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U?(r, ?, z) is the result of a perturbation W to an ideal field U(r, ?, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, ?, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2 ? radians over an ion detection period Tm.

Abstract: An electrostatic dual-mode lens assembly is provided for selectively transmitting or reflecting an ion beam in a mass spectrometer. The assembly comprises at least one electrode that provides a switchable electric field that, during a first mode of operation, directs an ion beam that enters the assembly along a first path so that the beam is transmitted through the assembly along the first path, and during a second mode of operation, directs an ion beam that enters the assembly along the first path so that the ion beam is reflected by the electric field and exits the assembly along a second path. Methods for operating a mass spectrometer using an electrostatic lens are also provided.

Abstract: An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U?(r, ?, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U?(r, ?, z) is the result of a perturbation W to an ideal field U(r, ?, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, ?, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2 ? radians over an ion detection period Tm.

Abstract: Mass spectrometer collision/reaction cell multipole and method. The multipole may have first and second portions and an intermediate portion therebetween, the first and second portions operating at first and second q values lower than a third q value at the intermediate portion. A low-mass cut-off of the multipole may be controlled by varying a q value from a first to at least a second value. The multipole may have multipole electrodes disposed about a central axis and having a respective first portion, second portion, and intermediate portion therebetween which is radially closer to the central axis. This offers relatively high acceptance and ion transmission, while providing low-mass cut-off for removing undesired/interfering ions and helping reduce background count.