Micromass UK Limited

The University of British Columbia

Jeffery Mark Brown

Martin Raymond Green

Jason Lee Wildgoose

Steven Derek Pringle

Paul Robert Murray

Keith George Richardson

Daniel James Kenny

David John Langridge

Kevin Giles

Robert Harold Bateman

Anthony James Gilbert

John Brian Hoyes

John Charles Gebler

Weibin Chen

Asish B Chakraborty

Jonathan P Williams

Richard Chapman

Stevan Bajic

Michael Raymond Morris

Damon Robb

Emmy Maria Hoyes

Christopher Clarkson Jones

David Gordon

Emrys Jones

Richard Denny

Boris Kozlov

Emmanuelle Claude

Farnoush Salarzaei

Kieran Neeson

Mark McDowall

Mark Williams Towers

Rainer Cramer

Steve Bajic

Steven Foster

Kevil Giles

Iain Campuzano

Christopher Jones

Malcolm Anderson

Brian Green

Keith Richardson

Jonathan Paul Williams

Craig Dorschel

Disclosed herein are various methods and apparatus for performing charge detection mass spectrometry (CDMS). In particular, techniques are disclosed for monitoring a detector signal from a CDMS device to determine how many ions are present in the ion trap () of the CDMS device. For example, if no ions are present the measurement can then be terminated early. Similarly, if more than one ion is present, the measurement can be terminated early, or ions can be removed from the trap () until only a single ion remains. Techniques are also provided for increasing the probability of there being a single ion in the trap (). A technique for attenuating an ion beam is also provided.

Charge detection mass spectrometry

A method of ionising a sample is disclosed comprising nebulising a sample which includes first biomolecules such as bovine insulin comprising one or more disulphide (S&#x2014;S) bonds. A stream of droplet or charged droplets comprising one or more disulphide (S&#x2014;S) bonds is directed so as to impact upon a target () or electrode so as to cause the breaking of a portion of the disulphide bonds. Alternatively, charged droplets may pass through an electric field region determined by an electrode () arranged downstream of a nebuliser or electrospray probe and an ion inlet () of a mass spectrometer so as to cause the breaking of a portion of the disulphide bonds.

Breaking of disulfide bonds of a nebulized analyte

An ion source is provided comprising a nebuliser or electrospray probe () for nebulising a sample and an impact surface or target electrode (). The impact surface or target electrode () comprises a tarnishable or oxidisable metal or an alloy comprising a tarnishable or oxidisable metal. Also provided is an ion source comprising a nebuliser or electrospray probe with a central wire comprising a tarnishable or oxidisable metal or an alloy comprising a tarnishable or oxidisable metal or an alloy comprising a tarnishable or oxidisable metal. Adducts with relatively heavy metals result in simplified multiply-charged mass spectra that are easier to interpret.

Impact ionisation ion source

A method of producing ions from a sample is disclosed. The method comprises directing a spray of droplets onto a sample, and causing droplets comprising analyte from the sample to impact upon a surface so as to generate analyte ions.

Method of producing ions using spray droplets onto a sample

A method of mass spectrometry determines if a mutated variant of a target protein is present in a sample. The method includes subjecting the sample to fragmentation so as to cause the target protein to fragment to form second generation fragment ions, and then mass analysing these fragment ions to obtain spectral data. The method determines if a mutated variant is present in the sample by determining that an ion in the spectral data has a mass to charge ratio that differs from the mass to charge ratio of an ion that would be observed if the target protein was a normal unmutated version of the target protein, and by an amount that corresponds to a mass difference that would be caused by the target protein being a mutated variant of the target protein.

Mass spectrometry for determining if a mutated variant of a target protein is present in a sample

A mass spectrometer comprising: a multi-reflecting time of flight (MRTOF) mass analyser or mass separator having two gridless ion mirrorsthat are elongated in a first dimension (Z-dimension) and configured to reflect ions multiple times in a second orthogonal dimension (X-dimension) as the ions travel in the first dimension; the spectrometer configured to operate in: (i) a first mode for ions having a first rate of interaction with background gas molecules in the mass analyser or separator, such that the ions are reflected a first number of times between the ion mirrors; and (ii) a second mode for ions having a second, higher rate of interaction with background gas molecules in the mass analyser or separator, such that ions are reflected a second, lower number of times between the ion mirrors

Multi-reflecting time of flight mass analyser

A MALDI ion source is disclosed comprising: a target plate () having a front surface (), a rear surface (), and at least one sample receiving well () for receiving a liquid sample or at least one sample receiving channel () extending from an opening () in the rear surface () to an opening () in the front surface () for receiving a liquid sample (), wherein each well () or channel () has a volume of &#x2265;1 &#x3bc;L. The ion source also comprise a laser () for ionising a liquid sample () on or in the target plate (), wherein the laser () is a pulsed laser set up and configured to have a pulsed repetition rate of &#x2265;20 Hz, or is a continuous laser.

MALDI target plate

An ambient or atmospheric pressure ion source is disclosed that comprises a laser source () that generates ions and/or neutral particles from a target (). A transfer device () causes the ions and/or neutral particles to pass along a first path or axis within the transfer device (), while a secondary activation device () directs laser radiation or photons along, across or over at least a portion of the first path or axis to cause secondary activation of the ions and/or neutral particles.

Axial atmospheric pressure photo-ionization imaging source and inlet device

Disclosed herein is an ion analysis instrument comprising a Time of Flight ('TOF') mass analyser comprising a reflectron. The instrument is operable in at least a first mode and a second mode, wherein in said first mode ions are caused to turn around at a first point in the reflectron and wherein in said second mode ions are caused to turn around at a second point in the reflectron such that the distance traveled by ions within the Time of Flight mass analyser is greater in the second mode than the distance traveled by ions within the Time of Flight mass analyser in the first mode. In this way, the operating modes can be selectively optimised for the analysis of ions of different masses.

Dual mode mass spectrometer

A method of mass or ion mobility spectrometry is disclosed that uses the Leidenfrost effect to cause a liquid to be repelled away from a heated surface so as to levitate above there-above. The repelled liquid is urged so as to move along the surface in a predetermined direction, for example, by the geometric configuration of the heated surface.

Sample introduction system for spectrometers

A mass spectrometer is disclosed comprising a glow discharge device within the initial vacuum chamber of the mass spectrometer. The glow discharge device may comprise a tubular electrode located within an isolation valve, which is provided in the vacuum chamber. Reagent vapour may be provided through the tubular electrode, which is then subsequently ionised by the glow discharge. The resulting reagent ions may be used for Electron Transfer Dissociation of analyte ions generated by an atmospheric pressure ion source. Other embodiments are contemplated wherein the ions generated by the glow discharge device may be used to reduce the charge state of analyte ions by Proton Transfer Reaction or may act as lock mass or reference ions.

Glow discharge ion source

A method of screening or testing a sample is disclosed that comprises ionising a native human hemoglobin sample to generate parent or precursor ions, subjecting the parent or precursor ions to Electron Transfer Dissociation fragmentation so as to generate a plurality of fragment ions, mass analysing the fragment ions and determining whether or not the fragment ions include fragment ions which are indicative of a variant of hemoglobin.

Fast method to analyse blood samples for the identification of hemoglobin variants using electron transfer dissociation

A mass spectrometer is disclosed wherein highly charged fragment ions resulting from Electron Transfer Dissociation fragmentation of parent ions are reduced in charge state within a Proton Transfer Reaction cell by reacting the fragment ions with a neutral superbase reagent gas such as Octahydropyrimidolazepine.

Method of charge reduction of electron transfer dissociation product ions

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Hyde, United Kingdom

Jeffery Mark Brown