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EP-3246700-B1 - METHOD OF SEPARATING IONS

EP3246700B1EP 3246700 B1EP3246700 B1EP 3246700B1EP-3246700-B1

Inventors

  • GREEN, MARTIN RAYMOND
  • GILES, KEVIN
  • LANGRIDGE, DAVID J.

Dates

Publication Date
20260506
Application Date
20170517

Claims (8)

  1. A method of separating ions according to their ion mobility, comprising: (i) accumulating a first population of ions in a first region (12) of an ion mobility separator (10), wherein said ion mobility separator (10) comprises a second region (16) downstream of said first region (12); (ii) separating said first population of ions according to their ion mobility in said first region (12) and said second region (16) of said ion mobility separator (10); (iii) accumulating a second population of ions in an accumulation region (14) upstream of said first region (12) whilst said first population of ions are being separated according to their ion mobility in said first region (12) of said ion mobility separator (10), said accumulation region (14) being arranged and adapted to trap or accumulate a population of ions and then transfer the population of ions from the accumulation region (14) into the first region (12); and (iv) accumulating said second population of ions in said first region (12) of said ion mobility separator (10) whilst said first population of ions are being separated according to their ion mobility in said second region (16) of said ion mobility separator (10) and after said first population of ions have exited said first region (12) of said ion mobility separator (10), wherein said step of accumulating said second population of ions in said first region (12) of said ion mobility separator (10) comprises transferring said second population of ions from said accumulation region (14) into said first region (12); and continuing to pass ions through said accumulation region (14) and into said first region (12) during said transferring of said second population of ions from said accumulation region (14) into said first region (12); wherein said first region (12) of said ion mobility separator (10) switches between a trapping mode, in which ions are substantially trapped within said first region (12), and an ion mobility separation mode, in which ions are separated according to their ion mobility within said first region (12).
  2. A method as claimed in claim 1, further comprising: (v) separating said second population of ions according to their ion mobility in said ion mobility separator (10); and (vi) accumulating a third population of ions in said first region (12) of said ion mobility separator whilst said second population of ions are being separated according to their ion mobility.
  3. A method as claimed in claim 2, further comprising: repeating steps (ii) to (vi) for said third and further populations of ions, such that subsequent populations of ions are accumulated in said first region (12) of said ion mobility separator (10) whilst preceding populations of ions are being separated according to their ion mobility.
  4. A method as claimed in any preceding claim, further comprising directing a beam of ions continuously into the accumulation region (14).
  5. A method as claimed in any preceding claim, wherein said ion mobility separator (10) comprises an RF-confined ion mobility separator (10).
  6. A method as claimed in claim 5, wherein said ion mobility separator (10) comprises a plurality of electrodes (18) stacked adjacent to one another, wherein alternate phases of an RF voltage are applied to adjacent electrodes (18), wherein optionally each of said plurality of electrodes (18) comprise apertures through which ions travel in use.
  7. A method as claimed in any preceding claim, wherein said first region (12) and/or said second region (16) of said ion mobility separator (10) and/or said accumulation region (14) comprise RF-confined regions.
  8. An ion mobility spectrometer or separation device comprising: an ion mobility separator (10) comprising: a first region (12) arranged and adapted to accumulate consecutive populations of ions and to switch between a trapping mode, in which ions are substantially trapped within said first region (12), and an ion mobility separation mode, in which ions are separated according to their ion mobility within said first region (12); and a second region (16) downstream of said first region (12); an accumulation region (14) upstream of said first region, arranged and adapted to trap or accumulate a population of ions and then transfer the population of ions from the accumulation region (14) into the first region (12); and a control system arranged and adapted: (i) to accumulate a first population of ions in said first region (12) of said ion mobility separator (10); (ii) to separate said first population of ions according to their ion mobility in said first region (12) and said second region (16) of said ion mobility separator (10); (iii) to accumulate a second population of ions in said accumulation region (14) upstream of said first region (12) whilst said first population of ions are being separated according to their ion mobility in said first region (12) of said ion mobility separator (10); and (iv) to accumulate said second population of ions in said first region (12) of said ion mobility separator (10) whilst said first population of ions are being separated according to their ion mobility in said second region (16) of said ion mobility separator (10) and after said first population of ions have exited said first region (12) of said ion mobility separator (10), wherein to accumulate said second population of ions in said first region (12) of said ion mobility separator (10) comprises said control system being arranged and adapted to transfer said second population of ions from said accumulation region (14) and into said first region (12); and wherein during said transfer of said second population of ions from said accumulation region (14) into said first region (12), ions continue to pass through said accumulation region (14) and into said first region (12)

Description

FIELD OF THE INVENTION The present invention relates generally to methods of separating ions, for example according to mass or ion mobility, and ion separators such as ion mobility separators or mass separators. BACKGROUND A single ion trap may be used upstream of an ion mobility separator in order to improve the duty cycle when transferring successive populations of ions into the ion mobility separator. Application of relatively high voltage extraction field is typically required to ensure rapid transfer of ions from the ion trap to the ion mobility separator with minimal dispersion. Application of such a high voltage field can cause heating of the ions, resulting in undesired fragmentation (e.g., of labile compounds). However, slower transfer of ions from the ion trap can lead to a lower duty cycle. In addition, the ion cloud may not be driven far enough into the ion mobility separator, and may not experience the desired ion mobility separation force during subsequent operation. In this case ions can be lost or remain trapped at the front region of the ion mobility separator. US2003/0141446 (Blanchard) discloses an ion detecting apparatus and methods. WO 99/47912 (Spangler) discloses an ion mobility storage trap and method. US 7838826 (Park) discloses an apparatus and method for parallel flow ion mobility spectrometry combined with mass spectrometry. WO 2014/140579 (Micromass) discloses a method of mass and/or ion mobility spectrometry comprising: trapping ions in an annular or co-axial ion trap and then axially ejecting at least some of said ions from said annular or co-axial ion trap into an annular ion guide. Ions trapped in the ion trap are distributed around the entire circumference of the annular or co-axial ion trap. As the ions travel along at least a portion of the length of the ion guide their motion around the circumference of the annular ion guide is unrestricted and the ions separate axially as they travel along the ion guide. It is desired to provide an improved method of separating ions according to their ion mobility. SUMMARY According to an aspect of the present disclosure there is provided a method of separating ions according to their ion mobility as claimed in claim 1. The above method provides a first region of an ion mobility separator that acts as both an accumulation region and an ion mobility separation region. Successive populations of ions are accumulated in the first region and then separated according to their ion mobility in the first region. This avoids having to rapidly transfer successive populations of ions from an accumulation region (e.g., an external ion trap) into the ion mobility separator to be separated, as they are already present within it. Conventional arrangements, for example those described in US2003/0141446 (Blanchard), do not disclose an accumulation region that is also used as an ion mobility separation region. The separation of the first population of ions is not limited to the first region. As discussed herein, the ion mobility separation region includes the first region and a second region downstream thereof. The ion mobility separation region may include eefurther ion mobility separation regions downstream thereof. In embodiments the first region acts in a trapping mode during step (i) and then switch to an ion mobility separation mode in step (ii). The switching may be instantaneous or substantially instantaneous. The above method comprises accumulating the second population of ions in an accumulation region upstream of the first region, whilst the first population of ions are being separated according to their ion mobility in the ion mobility separator (e.g., in the first region). The upstream accumulation region may be or form part of an ion trap, for example an ion trap external to the ion mobility separator. The use of two accumulation regions has been found to improve upon arrangements that involve only a single accumulation region, for example where an accumulating ion trap is located upstream of an ion mobility separator. This avoids, for example, transferring ions into the ion mobility separator (or ion mobility separation region) suddenly, which can lead to ion losses and/or fragmentation. The above method comprises transferring the second population of ions from the upstream accumulation region to the first region. Step (iii) further comprises continuing to pass ions through the upstream accumulation region and into the first region, for example to add to and/or increase the number of ions in the second population of ions (now accumulating in the first region). The ion mobility separator comprises a second region downstream of the first region, and step (ii) comprises separating the first population of ions according to their ion mobility in the first and second regions of the ion mobility separator. Upon initiation of step (ii), the first population of ions are all located within the first region, and a driving force may be applied to drive