US 10,373,817 B2 · Method for determining the structure of a macromolecular assembly

Abstract

A method of determining the structure of a macromolecular assembly (MMA) comprises the steps of (a) generating precursor ions of an MMA species to be investigated; (b) transporting the MMA precursor ions to a fragmentation zone; (c) carrying out pulsed fragmentation of the MMA precursor ions in the fragmentation zone; (d) for a first plurality of MMA precursor ions, detecting both a spatial distribution of the resultant MMA fragment ions, and an m/z distribution of the MMA fragment ions; (e) analyzing the spatial and m/z distributions of fragment ions formed from the said first plurality of precursor ions of the MMA species to be investigated, to determine the relative positions of those fragment ions within the structure of the precursor MMA; and (f) reconstructing the three dimensional (3D) structure of the MMA from the analysis of the spatial and m/z distributions of fragment ions.

Claims15

Dependent claims

A method of analyzing a molecular species, comprising the steps of:

(a) generating precursor ions of a molecular species to be investigated;
(b) directing the precursor ions toward a fragmentation zone;
and
(c) switching between a first mode and a second mode of operation, wherein the first mode includes steps of:
(i) performing a plurality of fragmentation/detection events, wherein for each fragmentation/detection event, a m/z distribution of fragment ions is detected at an ion detector arrangement;
and
(ii) controlling a flow of the precursor ions into the fragmentation zone such that, averaged over the plurality of fragmentation/detection events, no more than one precursor ion is present within the fragmentation zone for each fragmentation/detection event;
and
wherein the second mode includes steps of:
(iii) performing a plurality of fragmentation events;
(iv) accumulating fragment ions formed during the plurality of fragmentation events;
and
(v) mass analyzing the accumulated fragment ions in a high-resolution mass analyzer.

10 more elements

A mass spectrometer comprising:

an ion source for generating precursor ions of a molecular species;
an ion detector arrangement having detector ion optics;
pulsed fragmentation means for fragmenting the precursor ions in a fragmentation zone positioned between the ion detector arrangement and the ion source;
ion optics for transporting the precursor ions from the ion source to the fragmentation zone;
a high-resolution mass analyzer;
and
a controller configured to switch the mass spectrometer between first and second modes of operation;
wherein, in the first mode, the controller causes the mass spectrometer to perform a plurality of fragmentation/detection events, each fragmentation/detection event including operating the fragmentation means to generate fragment ions within the fragmentation zone and detecting the fragment ions at the ion detector arrangement, and to control the flow rate of precursor ions into the fragmentation zone and the pulse rate of the fragmentation means such that, averaged over the plurality of fragmentation/detection events, no more than one precursor ion is present within the fragmentation zone;
and
wherein, in the second mode, the controller causes the mass spectrometer to perform a plurality of fragmentation events, each fragmentation event including operating the fragmentation means to generate fragment ions within the fragmentation zone, to accumulate the fragment ions generated in the plurality of fragmentation events, and to mass analyze the accumulated fragment ions in the high-resolution mass analyzer.

7 more elements

Dependencies are inferred from the claim text.

Method for determining the structure of a macromolecular assembly

Life of this patent

Method for determining the structure of a macromolecular assembly

Life of this patent

Abstract

Claims15