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Methods and apparatus for the ion mobility based separation and collection of molecules

a technology of ion mobility and method, applied in the field of methods and apparatus for the ion mobility based separation and collection of molecules, can solve the problems of difficult rapid and efficient separation and collection of chiral compounds, time-consuming process, and many drawbacks of traditional enantiomer preparation processes, so as to achieve enhanced separation and collection

Inactive Publication Date: 2008-07-24
EXCELLIMS CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]In various aspects, the present inventions provide apparatus and method for separating and collecting chiral molecules using ion mobility, preferably in the gas phase. In comparison to chromatographic separations, gas phase separations can be conducted rapidly, e.g. on the order of milliseconds to tens of seconds as opposed to the tens of minutes typically found in chromatographic approaches. In the case of other compounds which are very similar to each other, for example very similar proteins. These compounds may contain two or more chiral centers that are not related as an object and its mirror image, separation and collection can be enhanced by adding a separating substance where their physical properties are nearly identical.
[0008]In various embodiments, the ion source employs electrospray ionization (ESI) to form ions. Other methods of ionization and suitable ionization sources include, but are not limited to, matrix assisted laser desorption ionization (MALDI), electrospray ionization (ESI), secondary electrospray ionization (SESI), desorption electrospray ionization (DESI), surface ionization, corona discharge ionization, electron beam ionization, radioactive ionization, photo ionization, laser ionization, laser ablation ionization, direct analysis in real time (DART) ionization and possible combination of multiple ionization principles. In various embodiments, the combined ionization source disclosed in this invention may eliminate ionization suppression in the primary ionization source and enhance over all ionization efficiency.

Problems solved by technology

The rapid and efficient separation and collection of chiral compounds is difficult since they have the same physical properties.
The processes traditionally employed for enantiomer preparation, however, suffer from several drawbacks.
In this process, the analysis mixture is mixed with an externally prepared carrier medium and separated in a separating column as a function of the different affinity of the enantiomers for the stationary phase of the chromatographic column; and thus, the individual components pass in succession through the chromatography column as a function of their different retention times. This process, however, can be very time consuming when multiple samples (such as might be desired in high-throughput screening) are to be analyzed as elution times of 20-30 minutes for one sample, are relatively common.
A further disadvantage of the chromatographic process is that the enantiomeric molecules can often have very similar retention times, leading to poor separation per pass.
The first analytical separation of two enantiomers occurred with gas chromatography, but due to the required analyte volatility for gas chromatography, its applications are limited.
Both CE and HPLC have received considerable attention, however, a major difficulty with both techniques is that prediction of the separation conditions remains difficult.
For example, in HPLC, there are over 200 CSP's commercially available, yet no clear method to determine which CSP will provide a good separation.
This can lead to both time-consuming and costly method development.

Method used

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  • Methods and apparatus for the ion mobility based separation and collection of molecules
  • Methods and apparatus for the ion mobility based separation and collection of molecules
  • Methods and apparatus for the ion mobility based separation and collection of molecules

Examples

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example 1

[0103]FIG. 13 shows superimposed ion mobility spectra of racemic mixtures in a pure nitrogen drift gas (no chiral modifier added). Each enantiomer in the electrospray solution was at a concentration of 100 ppm. Samples were introduced into the IMS via the electrosprayer with a flow rate of 1 μL / min. The enantiomeric mixtures showed in FIG. 13 are D- and L-valinol, D and L-threonine, D- and L-penicillamine, D and L-tryptophan, D- and L-methyl-α-glucopyranoside and R- and S-atenolol. These spectra represent data that can be obtained using a conventional ion mobility spectrometer. Even though these test enantiomeric mixtures could be separated from each other in the IMS, no enantiomeric separation was observed for the racemates in nitrogen drift gas without chiral modifier.

example 2

[0104]Atenolol is from a class of drugs called beta-blockers mainly prescribed alone or in combination with other medications to treat high blood pressure and lower heart rate, to prevent angina and to reduce the risk of recurrent heart attacks. Chiral Ion Mobility Separator (CIMS) separation of S- and R-atenolol enantiomeric mixture is illustrated in FIG. 14. When no chiral modifier was introduced to the drift gas, drift times for the S- and R-enantiomers were almost identical at 24.56 and 24.51 ms, respectively. In the CIMS, The drift times of S- and R-atenolol were 24.61 ms and 25.04 ms respectively when analyzed individually; the drift times of S- and R-atenolol were 24.66 ms and 25.06 ms when analyzed as a mixture. It was observed that drift time shift of R-atenolol was more significant compared to S-atenolol.

example 3

[0105]To illustrate how a chiral modifier affects separation in a CIMS, the drift times of individual enantiomers, L- and D-methionine, were recorded as a function of infusion flow rate of the chiral modifiers introduced into the drift gas. In the experiments, μL / min of a liquid chiral modifier, S-(+)-2-butanol or R-(−)-2-butanol, was pumped into and volatilized in the preheated nitrogen gas stream. The results of this investigation are shown in FIG. 15.

[0106]The drift times of methionine enantiomers increased with the introduction of chiral modifier, S-(+) or R-(−)-2-butanol. When S-(+)-2-butanol was used as the chiral modifier the drift time of both enantiomers, D- and L-methionine increased as a function of the concentration of the chiral modifier in the nitrogen drift gas. However, no difference in the drift time of the enantiomers could be seen until the chiral modifier flow rate reached about 30 μL / min. With only nitrogen as the drift gas, the drift time of both methionine ena...

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Abstract

This invention describes an apparatus for the separation and collection of components in a sample of interest comprising: an ionization source; an ion mobility separator and an ion collector positioned to receive ions leaving the ion mobility separator. The ion mobility separator having an inlet to supply at least one separating substance which comprises particles which selectively interact with at least one analyte component of interest to certain degree different from the others. The analyte component of interest may be enantiomers, diastereomers, stereoisomers, isomers, etc. The ion collector can be used to conduct analytical, preparative, and semi-preparative separation. In addition, a combined primary electrospray and secondary electrospray ionization source is disclosed to enhance ionization efficiency of interest.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims the benefit of and priority to corresponding U.S. Provisional Patent Application No. 60 / 807,031 and 60 / 891,532, filed Jul. 11, 2006 and Feb. 26, 2007 respectively, the entire content of the applications are herein incorporated by referenceBACKGROUND OF THE INVENTION[0002]Enantiomerically pure compounds are of great interest in the pharmaceutical industry and other fields. The rapid and efficient separation and collection of chiral compounds is difficult since they have the same physical properties. All of their physical properties correspond, except the direction in which they rotate plane-polarized light, i.e. they differ in a specific optical activity. Furthermore, all of their chemical properties correspond, except the reactivity toward other chiral compounds. Note that the term chiral compounds are also often used as a general term that refers to the molecules with a chiral center. Development of both pr...

Claims

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Application Information

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IPC IPC(8): H01J49/26
CPCG01N27/622C07B63/00H01J49/165
Inventor WU, CHING
Owner EXCELLIMS CORP
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