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

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.

1 . An apparatus for the separation of analyte components in a sample comprising:
 (a) an ionization source;   (b) an ion mobility separator in fluid communication with the ionization source; comprising a separating substance inlet to supply at least one separating substance which interacts with at least one analyte component of interest to a degree different than the separating substance interacts with at least one other analyte component of interest; and   (c) an ion collector in fluid communication with the ion mobility separator and positioned to receive ions leaving the ion mobility separator.   
   
   
       2 . The apparatus of  claim 1 , wherein the analyte components are isomers. 
   
   
       3 . The apparatus of  claim 1 , wherein the analyte components are stereoisomers. 
   
   
       4 . The apparatus of  claim 1 , wherein the analyte components are diastereomers. 
   
   
       5 . The apparatus of  claim 1 , wherein the analyte components are enantiomers. 
   
   
       6 . The apparatus of  claim 1 , wherein the separating substance is chiral and/or nonchiral. 
   
   
       7 . The apparatus of  claim 1 , wherein the separating substance further comprises a plurality of components that interact with the analyte components to different degrees. 
   
   
       8 . The apparatus of  claim 7 , wherein the plurality of components are supplied sequentially or simultaneously. 
   
   
       9 . The apparatus of  claim 1 , wherein the ion mobility separator comprises a symmetric ion mobility separator. 
   
   
       10 . The apparatus of  claim 1 , wherein the ion mobility separator comprises an asymmetric ion mobility separator. 
   
   
       11 . The apparatus of  claim 10 , wherein the asymmetric ion mobility separator is a field asymmetric ion mobility spectrometer. 
   
   
       12 . The apparatus of  claim 10 , wherein the asymmetric ion mobility separator is a differential mobility spectrometer. 
   
   
       13 . The apparatus of  claim 1 , wherein the ionization source comprises a single or plurality of primary ionization sources combined with a single or a plurality of secondary ionization sources. 
   
   
       14 . The apparatus of  claim 13 , wherein the primary ionization source may include but is not limited to: electron beam, MALDI, electrospray, secondary electrospray, surface, corona discharge, radioactive, photo, laser, laser ablation/desorption, DESI, DART. 
   
   
       15 . The apparatus of  claim 13 , wherein the secondary ionization source may include but is not limited to: electron beam, secondary electrospray, surface, corona discharge, radioactive, photo, laser, DESI, DART. 
   
   
       16 . The apparatus of  claim 1 , further comprising at least one sample inlet for supplying samples that are gas, liquid or solid. 
   
   
       17 . The apparatus of  claim 16 , wherein the samples are from other separation devices, including but not limited to gas chromatograph, supercritical fluid chromatograph, liquid chromatograph, electrophoresis, on solid surface, or in a medium. 
   
   
       18 . The apparatus of  claim 1 , wherein the separating substance comprises one or more of: (R)-(−)-α-(Trifluoromethyl)benzyl alcohol, (S)-(+)-α-(Trifluoromethyl)benzyl alcohol, (R)-Tetrahydrofuran-2-carbonitrile, (S)-Tetrahydrofuran-2-carbonitrile, (2R,6R)-2,6-Heptanediol, (+)-Ethyl D-lactate, and (−)-Ethyl L-lactate. 
   
   
       19 . The apparatus of  claim 1 , wherein the separating substance comprises one or more of S-(+)-2-butanol and R-(−)-2-butanol. 
   
   
       20 . The apparatus of  claim 1 , wherein the ion collector comprises a static ion collector. 
   
   
       21 . The apparatus of  claim 20 , wherein the static ion collector comprises a Faraday plate. 
   
   
       22 . The apparatus of  claim 20 , wherein the static ion collector comprises a non-flowing liquid. 
   
   
       23 . The apparatus of  claim 1 , wherein the ion collector comprises a dynamic ion collector. 
   
   
       24 . The apparatus of  claim 23 , wherein the dynamic ion collector comprises one or more of a moving belt and a moving Faraday plate. 
   
   
       25 . The apparatus of  claim 23 , wherein the dynamic ion collector comprises a flowing liquid. 
   
   
       26 . The apparatus of  claim 20  and  23 , wherein ion collectors are segmented. 
   
   
       27 . The apparatus of  claim 1 , further comprising:
 a mass spectrometer disposed at the end of the ion mobility separator; and   an interface structure disposed between the ion mobility separator and the mass spectrometer.   
   
   
       28 . The apparatus of  claim 27 , wherein the mass spectrometer may include but is not limited to: a quadrupole, an ion trap, a time of flight mass analyzer. 
   
   
       29 . A method for the separation of analyte components in a sample comprising the steps of:
 (a) ionizing the sample of interest comprising two or more analyte components of interest to produce an ionized sample; and   (b) transporting under the influence of an electrical field at least a portion of the ionized sample through a neutral medium containing at least one separating substance, the separating substance interacting with at least one analyte component of interest to a degree different than the separating substance interacts with at least one other analyte component of interest; and   (c) collecting with an ion collector at least a portion of the ionized sample transported through the neutral medium containing the separating substance.   
   
   
       30 . The method of  claim 29 , wherein the step of ionizing comprises ionizing the sample with a primary ionization source followed by ionizing a un-ionized neutral sample with a secondary ionization source. 
   
   
       31 . The method of  claim 29 , wherein the electrical field is a substantially static electrical field during the step of transporting. 
   
   
       32 . The method of  claim 29 , wherein the electrical field is a substantially dynamic electrical field during the step of transporting. 
   
   
       33 . The method of  claim 32 , wherein the electrical field comprise an AC component and a DC component. 
   
   
       34 . The method of  claim 33 , wherein the DC component is applied for a time period; after which at least two analyte components of interest acquire different drift times. 
   
   
       35 . The method of  claim 29 , wherein the separating substance comprises one or more of: (R)-(−)-α-(Trifluoromethyl), (S)-(+)-α-(Trifluoromethyl), (R)-Tetrahydrofuran-2-carbonitrile, (S)-Tetrahydrofuran-2-carbonitrile, (2R,6R)-2,6-Heptanediol, (+)-Ethyl D-lactate, and (−)-Ethyl L-lactate. 
   
   
       36 . The method of  claim 29 , wherein the separating substance comprises one or more of S-(+)-2-butanol and R-(−)-2-butanol. 
   
   
       37 . The method of  claim 29 , wherein the step of collecting comprises impinging at least a portion of the ionized sample, that was transported through the neutral medium containing the separating substance, upon a surface. 
   
   
       38 . The method of  claim 37 , wherein the surface is a solid surface. 
   
   
       39 . The method of  claim 38 , wherein the solid surface is a moving surface. 
   
   
       40 . The method of  claim 37 , wherein the surface is a liquid surface. 
   
   
       41 . The method of  claim 40 , wherein the liquid surface is flowing liquid surface. 
   
   
       42 . An apparatus for the separation of analyte components in a sample comprising:
 (a) an ionization source;   (b) an ion mobility separator in fluid communication with the ionization source; and   (c) an ion collector in fluid communication with the ion mobility separator and positioned to receive ions leaving the ion mobility separator.   
   
   
       43 . The apparatus of  claim 42 , wherein the ion mobility separator comprises a symmetric ion mobility separator. 
   
   
       44 . The apparatus of  claim 42 , wherein the ion mobility separator comprises an asymmetric ion mobility separator. 
   
   
       45 . The apparatus of  claim 44 , wherein the asymmetric ion mobility separator is a field asymmetric ion mobility spectrometer. 
   
   
       46 . The apparatus of  claim 44 , wherein the asymmetric ion mobility separator is a differential mobility spectrometer. 
   
   
       47 . The apparatus of  claim 42 , wherein the ion collector comprises a static ion collector. 
   
   
       48 . The apparatus of  claim 47 , wherein the static ion collector comprises a Faraday plate. 
   
   
       49 . The apparatus of  claim 47 , wherein the static ion collector comprises a non-flowing liquid. 
   
   
       50 . The apparatus of  claim 42 , wherein the ion collector comprises a dynamic ion collector. 
   
   
       51 . The apparatus of  claim 50 , wherein the dynamic ion collector comprises one or more of a moving belt and a moving Faraday plate. 
   
   
       52 . The apparatus of  claim 47  and  50 , wherein the ion collectors are segmented. 
   
   
       53 . The apparatus of  claim 50 , wherein the dynamic ion collector comprises a flowing liquid. 
   
   
       54 . An apparatus for the ionization of samples comprising:
 (a) at least one primary ionization source;   (b) at least one secondary ionization source;   (c) a ionization chamber containing a electric field that guides charged particles from the secondary ionization source into a ionization chamber and/or extracts ionized analyte components from the ionization chamber;   (d) at least one sample inlet;   (e) a gas flow that carries neutral analyte components;   (f) at least one analyzer in fluid communication with the ionization chamber.   
   
   
       55 . The apparatus of  claim 54 , wherein the analyzer is an ion mobility separator or a mass analyzer. 
   
   
       56 . The apparatus of  claim 55 , wherein the mass analyzer may include but is not limited to: a quadrupole, an ion trap, a time of flight mass analyzer. 
   
   
       57 . The apparatus of  claim 54 , wherein the sample inlet is for a gas phase sample. 
   
   
       58 . The apparatus of  claim 57 , wherein the gas phase sample comprises elutents from a GC or SFC. 
   
   
       59 . The apparatus of  claim 54 , wherein the sample inlet is for a liquid phase sample. 
   
   
       60 . The apparatus of  claim 54 , wherein the analyzer is interfaced to the ionization chamber between substantially zero and substantially one hundred eighty degrees from the direction ion traveling axis. 
   
   
       61 . The apparatus of  claim 55 , wherein the primary ionization source and the secondary ionization source may include but is not limited to: electron beam, MALDI, secondary electrospray, surface, corona discharge, radioactive, photo, laser, laser ablation/desorption, DESI, DART, SESI, APCI. 
   
   
       62 . The apparatus of  claim 61 , wherein the ionization source further comprises chemical modifiers. 
   
   
       63 . The apparatus of  claim 54 , wherein the sample inlet is an open inlet that allows direct ionization of samples from a surface with the primary ionization source and introduction neutral samples into the ionization chamber with the gas flow. 
   
   
       64 . A method for the ionization of samples comprising the steps of:
 (a) introducing a sample into a ionization chamber;   (b) ionizing the sample by a primary ionization source;   (c) ionizing a neutral sample in a gas flow by a secondary ionization source; and   (e) extracting an ionized sample into an analyzer with a electric field.   
   
   
       65 . The method of  claim 64 , wherein the step of ionizing comprises introducing a chemical modifiers into the ionization source. 
   
   
       66 . The method of  claim 64 , wherein the step of introducing the sample comprises a continuous or pulsed flow. 
   
   
       67 . The method of  claim 64 , wherein the step of ionizing the neutral sample comprises bringing charged particles generated by the secondary ionization source into the ionization chamber continuously or as pulses 
   
   
       68 . The method of  claim 64 , further comprises
 (a) ionizing at least a portion of the sample in the ionization chamber   (b) separating the ionized sample from an un-ionized sample with the electric field   (c) introducing the charged particles into the ionization chamber to ionize the un-ionized sample   (d) extracting the ionized samples into the analyzer   
   
   
       69 . The method of  claim 68 , wherein the steps of (b) and (c) are repeated until all the sample is ionized 
   
   
       70 . The method of  claim 64 , further comprises directly ionizing samples from a surface and introducing neutral samples on the surface into the ionization chamber with the gas flow. 
   
   
       71 . An apparatus of ion gate for an ion mobility separator comprising a segmented Bradbury-Nielson that contains multiple sections of Bradbury-Nielson gate. 
   
   
       72 . The apparatus of  claim 71 , wherein the segmented Bradbury-Nielson gate is a second gate in a time-of-flight type ion mobility separator. 
   
   
       73 . The apparatus of  claim 71 , wherein the segmented Bradbury-Nielson gate comprises a variety of geometries which may include but is not limited to: parallel, rectangular, concentric. 
   
   
       74 . The apparatus of  claim 71 , wherein the ion mobility separator further comprises a segmented ion collector where a plurality of sections of ion collector is inline with the sections of the segmented Bradbury-Nielson gate. 
   
   
       75 . A apparatus for the interface between an IMS and MS comprising:
 a resistance tube; and   a high voltage power supply operatively connected to the resistance tube.   
   
   
       76 . The apparatus of  claim 75 , wherein:
 the resistance tube has an inner diameter in the range between about 1 micrometer and about 2 mm and   the high voltage power supply is configured to apply a voltage gradient in the range between about 1 and about 40,000 volts across the inner diameter of the resistance tube.   
   
   
       77 . A apparatus for the interface between an IMS and MS comprising:
 a first conductive member;   a second conductive member, wherein the first and second conductive members are substantially symmetrically arranged about an ion transport axis and wherein the distance between the ends of the first and second conductive members proximal to an ion mobility separator is equal or less than the distance between the ends of the first and second conductive members distal to the ion mobility separator;   a DC and RF power supply operatively connected to one or more for the first and second conductive members.   
   
   
       78 . The apparatus of  claim 77 , wherein the first and second conductive members are plates. 
   
   
       79 . The apparatus of  claim 77 , wherein the DC and RF power supply is configured to apply voltages between the first and second conductive members in a means that is resemble to the operation of an asymmetric ion mobility separator with two parallel plates, where the first and second conductive members are closest. 
   
   
       80 . A method for operating an ion mobility separator and a mass spectrometer comprising:
 (a) measuring ion mobility of an analyte component using an ion detector/collector at the end of the ion mobility separator;   (b) measuring ion mobility and mass to charge ratio using ion detector of mass spectrometer;   (c) correlating the ion mobility data obtained from mass spectrometer with the ion mobility dada from the ion mobility separator.   
   
   
       81 . The method of  claim 80 , wherein mass identifying ions collected on the ion collector at the end of the IMS using the correlated ion mobility data.