# US 10,371,665 B2 · Mobility selective attenuation

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- Number: US 10,371,665 B2
- Document ID: US10371665B2
- Status: Granted
- Kind: B2
- Application number: 15/315,148
- Filed: 2015-06-05
- Published: 2017-07-27
- Granted: 2019-08-06
- Earliest claimed: 2014-06-06
- Assignees: Micromass UK Limited
- Applicants: Micromass UK Limited
- Inventors: Martin Raymond Green; Jason Lee Wildgoose
- Web page: https://patentgrep.com/patent/US10371665B2

## CPC

- G01N 27/623: combined with mass spectrometry
- H01J 49/0031: {Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence)}
- H01J 49/004: {Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)

## Abstract

A method of mass spectrometry is disclosed comprising separating a first population of ions according to their ion mobility and selectively attenuating ions in the first population of ions in one or more ion mobility and/or drift time ranges so as to form a second population of ions. The step of selectively attenuating ions comprises applying a varying, increasing or decreasing attenuation factor to ions in different ion mobility and/or drift time ranges. The method further comprises separating the second population of ions according to their ion mobility.

## Claims

### Claim 1

A method of mass spectrometry comprising:
accumulating a first population of ions in a first accumulation device;
separating the first population of ions according to their ion mobility;
selectively attenuating ions in said first population of ions in one or more ion mobility and/or drift time ranges so as to form a second population of ions, wherein said step of selectively attenuating ions comprises applying a varying, increasing or decreasing attenuation factor to ions in different ion mobility and/or drift time ranges, wherein the attenuation factor applied to ions in each of said ion mobility and/or drift time ranges is less than about 90%;
accumulating said second population of ions in a second accumulation device or region; and
separating said second population of ions according to their ion mobility, wherein:
said step of separating said first population of ions is carried out in a first ion mobility separator which is downstream of said first accumulation device;
said step of selectively attenuating ions in said first population of ions is carried out using an attenuation device, wherein the attenuation device is separate to and downstream of said first ion mobility separator;
said second accumulation device or region is downstream of said attenuation device; and
said step of separating said second population of ions is carried out in a second ion mobility separator, wherein said second ion mobility separator is separate to and downstream of said attenuation device and said second accumulation device or region;
wherein said first ion mobility separator is a lower performance device having a first elution, cycle time or resolution and a first space charge tolerance and said second ion mobility separator is a higher performance device having a second elution, cycle time or resolution and a second space charge tolerance, wherein:
said first resolution is lower than said second resolution and said first space charge tolerance is greater than said second space charge tolerance; or
said first elution or cycle time is shorter or faster than said second elution or cycle time and said first space charge tolerance is greater than said second space charge tolerance.

### Claim 2 (depends on 1)

A method as claimed in claim 1, further comprising accumulating said second population of ions in the second accumulation device or region such that said second population of ions is not separated according to ion mobility and/or drift time within the second accumulation device or region and any ion mobility separation from the first ion mobility separator is lost, prior to said step of separating said second population of ions according to their ion mobility.

### Claim 3 (depends on 1)

A method as claimed in claim 1, wherein said step of attenuating ions comprises selectively attenuating only one or more relatively abundant or intense species of ions.

### Claim 4 (depends on 1)

A method as claimed in claim 1, wherein said step of attenuating ions comprises selectively attenuating all ions except one or more relatively abundant or intense species of ions.

### Claim 5 (depends on 1)

A method as claimed in claim 1, further comprising determining one or more ion mobility and/or drift time ranges of said second population of ions that have been accumulated within the second accumulation device or region, and optimising one or more parameters of said second downstream ion mobility separator that will be applied to said second downstream ion mobility separator for said second population of ions based on the determined one or more ion mobility and/or drift time ranges of said second population of ions.

### Claim 6 (depends on 1)

A method as claimed in claim 1, further comprising operating said first upstream ion mobility separator under different operating parameters or conditions to said second downstream ion mobility separator.

### Claim 7 (depends on 1)

A method as claimed in claim 1, wherein said first ion mobility separator is a lower performance device having a first elution, cycle time or resolution and a first space charge tolerance and said second ion mobility separator is a higher performance device having a second elution, cycle time or resolution and a second space charge tolerance, wherein said first elution, cycle time or resolution is lower than said second elution, cycle time or resolution and said first space charge tolerance is greater than said second space charge tolerance.

### Claim 8 (depends on 1)

A method as claimed in claim 1, wherein said first ion mobility separator comprises a plurality of electrodes each having an aperture through which ions are transmitted in use.

### Claim 9 (depends on 8)

A method as claimed in claim 8, further comprising supplying an RF voltage to said electrodes to radially confine ions within said first ion mobility separator.

### Claim 10 (depends on 1)

A method as claimed in claim 1, further comprising applying an attenuation factor of between 10-90%, 20-80%, 30-70% or 40-60% to ions in each of said one or more ion mobility and/or drift time ranges to form said second population of ions.

### Claim 11 (depends on 1)

A method as claimed in claim 1, further comprising recording the amount of attenuation applied for each ion mobility and/or drift time range.

### Claim 12 (depends on 1)

A method as claimed in claim 1, further comprising:
separating one or more further populations of ions according to ion mobility in said first ion mobility separator; and
attenuating ions in said further populations of ions using said attenuation device so as to form further attenuated populations of ions,
wherein the one or more further populations of ions have a composition substantially the same as that of the first population of ions, and an attenuation factor applied by said attenuation device to ions in said further populations of ions in each of said ion mobility and/or drift time ranges is substantially the same as the attenuation factor applied by said attenuation device to ions in said second population of ions in each of said ion mobility and/or drift time ranges.

### Claim 13 (depends on 12)

A method as claimed in claim 12, wherein said step of selectively attenuating ions comprises applying a varying, increasing or decreasing attenuation factor to ions in different populations of ions.

### Claim 14 (depends on 1)

A method as claimed in claim 1, further comprising recording the amount of attenuation applied for each different population of ions or each ion mobility and/or drift time range, and calculating a correction factor to be applied to each ion mobility and/or drift time range in mass spectral data produced from said populations of ions.

### Claim 15 (depends on 12)

A method as claimed in claim 12, further comprising accumulating and mixing said second and further attenuated populations of ions in the second accumulation device or region and subsequently separating said second and further attenuated populations of ions in said second ion mobility separator simultaneously according to ion mobility.

### Claim 16 (depends on 12)

A method as claimed in claim 12, further comprising accumulating and mixing said second and further populations of ions in the second accumulation device or region, wherein said second and further populations of ions are held within the second accumulation device such that said second and further populations of ions are not separated according to ion mobility and/or drift time within the second accumulation device or region and any ion mobility separation from the first ion mobility separator is lost and subsequently separating said second and further attenuated populations of ions simultaneously according to their ion mobility.

### Claim 17 (depends on 1)

A method as claimed in claim 1, further comprising accumulating one or more further populations of ions that have not been attenuated, have not been completely attenuated, or have been attenuated to a lesser degree, in an accumulation device whilst said second population of ions are separated according to their ion mobility.

### Claim 18 (depends on 1)

A method as claimed in claim 1, further comprising fragmenting or reacting said second population of ions prior to separating said second population of ions according to their ion mobility.

### Claim 19

A mass spectrometer comprising:
a first accumulation device or region arranged and adapted to accumulate a first population of ions;
a first ion mobility separator downstream of said first accumulation device and arranged and adapted to separate the first population of ions according to their ion mobility;
an attenuation device separate to and downstream of said first ion mobility separator, the attenuation device being arranged and adapted to apply a varying, increasing or decreasing attenuation factor to ions in different ion mobility and/or drift time ranges, so as to attenuate ions in said first population of ions in one or more ion mobility and/or drift time ranges and to form a second population of ions, wherein the attenuation factor applied to ions in each of said ion mobility and/or drift time ranges is less than about 90%;
a second accumulation device or region downstream of said attenuation device; and
a second ion mobility separator separate to and downstream of said second accumulation device or region, the second ion mobility separator being arranged and adapted to subsequently separate said second population of ions according to their ion mobility;
wherein said first ion mobility separator is a lower performance device having a first elution, cycle time or resolution and a first space charge tolerance and said second ion mobility separator is a higher performance device having a second elution, cycle time or resolution and a second space charge tolerance, wherein:
said first resolution is lower than said second resolution and said first space charge tolerance is greater than said second space charge tolerance; or
said first elution or cycle time is shorter or faster than said second elution or cycle time and said first space charge tolerance is greater than said second space charge tolerance.
