Ion mobility spectrometer

Abstract

An ion mobility spectrometer comprises a drift tube defining a drift tube inlet configured to receive ions and a drift tube outlet. The drift tube is configured to separate ions in time as a function of ion mobility. The drift tube defines a first ion activation region between the drift tube inlet and the drift tube outlet. The first ion activation region is configured to selectively induce structural changes in at least some of the ions.

1 . An ion mobility spectrometer comprising a drift tube defining a drift tube inlet configured to receive ions and a drift tube outlet, the drift tube configured to separate ions in time as a function of ion mobility, the drift tube defining a first ion activation region between the drift tube inlet and the drift tube outlet, the first ion activation region configured to selectively induce structural changes in at least some of the ions.  
   
   
       2 . The ion mobility spectrometer of  claim 1  further comprising a source of buffer gas, 
 wherein the drift tube is configured to receive buffer gas therein from the source of buffer gas.    
   
   
       3 . The ion mobility spectrometer of  claim 2  further including at least one voltage source coupled to the first ion activation region, the at least one voltage source configured to selectively establish an electric field in the first ion activation region that is sufficient to induce structural changes in the at least some of the ions by fragmenting the at least some of the ions via collisions with the buffer gas.  
   
   
       4 . The ion mobility spectrometer of  claim 2  further including at least one voltage source coupled to the first ion activation region, the at least one voltage source configured to selectively establish an electric field in the first ion activation region that is sufficient to induce structural changes in the at least some of the ions by inducing conformational changes in the at least some of the ions via collisions with the buffer gas without fragmenting the at least some of the ions.  
   
   
       5 . The ion mobility spectrometer of  claim 1  further comprising an ion source region configured to supply ions to the drift tube inlet.  
   
   
       6 . The ion mobility spectrometer of  claim 5  further including an ion gate normally impeding passage of ions from the ion source region into the drift tube inlet, the ion gate responsive to an ion gate control signal to allow passage of ions from the ion source region into the drift tube inlet.  
   
   
       7 . The ion mobility spectrometer of  claim 5  wherein the ion source region defines a funnel therein, the funnel having one end defining a first opening with a first cross-sectional area and an opposite end defining a second opening with a second cross-sectional area smaller than the first cross-sectional area, the funnel configured to receive ions in the first opening and to supply ions to the drift tube inlet via the second opening, the funnel defining a cavity between the first and second openings configured to radially focus ions between the first and second openings.  
   
   
       8 . The ion mobility spectrometer of  claim 7  further including a voltage source coupled to the funnel, the voltage source configured to selectively create a second ion activation region within the funnel, the second ion activation region within the funnel configured to induce structural changes in at least some of the ions within the funnel.  
   
   
       9 . The ion mobility spectrometer of  claim 7  further including an ion gate positioned between the second opening of the funnel and the drift tube inlet, the ion gate normally impeding passage of ions from the funnel into the drift tube inlet, the ion gate responsive to an ion gate control signal to allow passage of ions from the funnel into the drift tube inlet.  
   
   
       10 . The ion mobility spectrometer of  claim 9  further including a voltage source coupled to the funnel, the funnel responsive to voltage produced by the voltage source to collect therein ions received via the first opening, 
 wherein the ion gate is responsive to the ion gate control signal to allow passage of at least some of the ions collected in the funnel into the drift tube inlet.    
   
   
       11 . The ion mobility spectrometer of  claim 5  wherein the ion source region is configured to receive ions generated externally thereto.  
   
   
       12 . The ion mobility spectrometer of  claim 5  wherein the ion source region is configured to generate ions from a sample source.  
   
   
       13 . The ion mobility spectrometer of  claim 1  further comprising an ion gate positioned between the drift tube inlet and the drift tube outlet and partitioning the drift tube into a first drift tube region between the drift tube inlet and the ion gate and a second drift tube region between the ion gate and the drift tube outlet, the ion gate responsive to a first control signal to impede passage of ions from the first drift tube region into the second drift tube region and to a second control signal to allow passage of ions from the first drift tube region into the second drift tube region.  
   
   
       14 . The ion mobility spectrometer of  claim 13  further comprising a voltage source configured to produce the first and second control signals, the voltage source programmable to produce the second control signal at a predetermined time relative to passage of ions into the first drift tube region to thereby allow passage into the second drift tube region only of ions having a corresponding predetermined mobility range.  
   
   
       15 . The ion mobility spectrometer of  claim 13  wherein the drift tube defines a funnel therein between the drift tube inlet and the drift tube outlet, the funnel having one end defining a first opening with a first cross-sectional area and an opposite end defining a second opening with a second cross-sectional area smaller than the first cross-sectional area, the funnel configured to receive ions in the first opening and to supply ions via the second opening, the funnel defining a cavity between the first and second openings configured to radially focus ions between the first and second openings.  
   
   
       16 . The ion mobility spectrometer of  claim 15  wherein the first opening of the funnel is positioned adjacent to the ion gate with the ion gate disposed between the first drift tube region and the first opening of the funnel and with the second drift tube region extending between the second end of the funnel and the drift tube outlet.  
   
   
       17 . The ion mobility spectrometer of  claim 16  wherein the ion activation region is positioned between the second end of the funnel and the second drift tube region.  
   
   
       18 . The ion mobility spectrometer of  claim 1  further comprising a third ion activation region positioned adjacent to the drift tube outlet, the third ion activation region configured to selectively induce structural changes in at least some of the ions exiting the drift tube outlet.  
   
   
       19 . The ion mobility spectrometer of  claim 18  further comprising a source of buffer gas, 
 wherein the drift tube is configured to receive buffer gas therein from the source of buffer gas.    
   
   
       20 . The ion mobility spectrometer of  claim 19  further comprising at least one voltage source coupled to the third ion activation region and configured to selectively establish an electric field in the third ion activation region sufficient to induce structural changes in the at least some of the ions exiting the drift tube outlet by fragmenting the at least some of the ions exiting the drift tube outlet via collisions with the buffer gas.  
   
   
       21 . The ion mobility spectrometer of  claim 19  further comprising at least one voltage source coupled to the third ion activation region and configured to selectively establish an electric field in the third ion activation region sufficient to induce structural changes in the at least some of the ions exiting the drift tube outlet by inducing conformational changes in the at least some of the ions exiting the drift tube outlet via collisions with the buffer gas without fragmenting the at least some of the ions exiting the drift tube outlet.  
   
   
       22 . The ion mobility spectrometer of  claim 1  further comprising an ion detector positioned to detect ions exiting the drift tube outlet and produce electrical signals indicative thereof.  
   
   
       23 . The ion mobility spectrometer of  claim 22  further comprising a processor electrically coupled to the ion detector, the processor configured to process the electrical signals produced by the ion detector to determine corresponding ion mobility spectral information.  
   
   
       24 . The ion mobility spectrometer of  claim 1  further comprising an ion mass spectrometer positioned to receive ions exiting the drift tube outlet, the ion mass spectrometer configured to separate in time as a function of ion mass-to-charge ratio at least some of the ions exiting the drift tube outlet.  
   
   
       25 . The ion mobility spectrometer of  claim 24  further comprising an ion detector positioned to detect ions exiting the ion mass spectrometer and produce electrical signals indicative thereof.  
   
   
       26 . The ion mobility spectrometer of  claim 25  further comprising a processor electrically coupled to the ion detector, the processor configured to process the electrical signals produced by the ion detector to determine ion spectral information as a function of ion mobility and of ion mass-to-charge ratio.  
   
   
       27 . An ion mobility spectrometer comprising: 
 an ion source configured to produce ions, and    a drift tube defining a drift tube inlet configured to receive ions from the ion source and a drift tube outlet, the drift tube including an ion gate positioned between the drift tube inlet and the drift tube outlet and partitioning the drift tube into a first drift tube region between the drift tube inlet and the ion gate and a second drift tube region between the ion gate and the drift tube outlet, the ion gate responsive to a first control signal to impede passage of ions from the first drift tube region into the second drift tube region and to a second control signal to allow passage of ions from the first drift tube region into the second drift tube region, the drift tube configured to separate ions in time as a function of ion mobility between the drift tube inlet and the ion gate and also between the gate and the drift tube outlet, the drift tube defining an ion activation region configured to selectively induce structural changes in at least some of the ions exiting the first drift tube region.    
   
   
       28 . The ion mobility spectrometer of  claim 27  further comprising a source of buffer gas, 
 wherein the drift tube is configured to receive buffer gas therein from the source of buffer gas.    
   
   
       29 . The ion mobility spectrometer of  claim 28  further including at least one voltage source coupled to the ion activation region, the at least one voltage source configured to selectively establish an electric field in the ion activation region sufficient to induce structural changes in the at least some of the ions exiting the first drift tube region by fragmenting the at least some of the ions exiting the first drift tube region via collisions with the buffer gas.  
   
   
       30 . The ion mobility spectrometer of  claim 28  further including at least one voltage source coupled to the ion activation region, the at least one voltage source configured to selectively establish an electric field in the ion activation region sufficient to induce structural changes in the at least some of the ions exiting the first drift tube region by inducing conformational changes in the at least some of the ions exiting the first drift tube region via collisions with the buffer gas without fragmenting the at least some of the ions exiting the first drift tube region.  
   
   
       31 . The ion mobility spectrometer of  claim 27  wherein the ion source includes a protein solution, 
 and wherein the ion source is configured to produce protein ions from the protein solution.    
   
   
       32 . The ion mobility spectrometer of  claim 27  further including an ion detector positioned to detect ions exiting the drift tube outlet.  
   
   
       33 . The ion mobility spectrometer of  claim 27  wherein the ion activation region is positioned adjacent to the gate with the ion activation region disposed between the gate and the drift tube outlet.  
   
   
       34 . A method of separating ions in time as a function of ion mobility, the method comprising: 
 introducing ions into a first drift tube,    separating the ions in time as a function of ion mobility in the first drift tube,    inducing structural changes in at least some of the ions exiting the first drift tube, and    separating in time the ions exiting the first drift tube, after inducing structural changes in at least some of the ions exiting the first drift tube, as a function of ion mobility in a second drift tube.    
   
   
       35 . The method of  claim 34  wherein the act of inducing structural changes in at least some of the ions exiting the first drift tube comprises exposing the ions exiting the first drift tube to an electric field in the presence of a buffer gas, the electric field sufficient to fragment the at least some of the ions via collisions with the buffer gas.  
   
   
       36 . The method of  claim 34  wherein the act of inducing structural changes in at least some of the ions exiting the first drift tube comprises exposing the ions exiting the first drift tube to an electric field in the presence of a buffer gas, the electric field sufficient to induce conformational changes in the at least some of the ions via collisions with the buffer gas without fragmenting the at least some of the ions.  
   
   
       37 . The method of  claim 34  further comprising allowing only ions having a predefined ion mobility range to exit the first drift tube region.  
   
   
       38 . The method of  claim 34  further comprising inducing structural changes in at least some of the ions prior to introducing the ions into the drift tube.  
   
   
       39 . The method of  claim 34  further comprising separating in time as a function of ion mass-to-charge ratio at least some of the ions exiting the second drift tube.  
   
   
       40 . The method of  claim 34  further comprising inducing structural changes in at least some of the ions exiting the second drift tube.  
   
   
       41 . The method of  claim 40  further comprising separating in time ions exiting the second drift tube, after inducing structural changes in at least some of the ions exiting the second drift tube, as a function of ion mass-to-charge ratio.  
   
   
       42 . The method of  claim 34  wherein the first drift tube comprises a first region of a single drift tube and the second drift tube comprises a second region of the single drift tube, 
 and wherein the act of inducing structural changes in at least some of the ions exiting the first drift tube is carried out in an ion activation region of the single drift tube that is positioned between the first and second drift tube regions.    
   
   
       43 . The method of  claim 34  further including radially focusing the ions exiting the first drift tube in a funnel structure prior to inducing structural changes in at least some of the ions exiting the first drift tube.  
   
   
       44 . The method of  claim 34  further including radially focusing the ions in a funnel structure prior to introducing the ions into the first drift tube.  
   
   
       45 . The method of  claim 34  further including radially focusing ions in the second drift tube in a funnel structure prior to exiting the second drift tube.  
   
   
       46 . An ion mobility spectrometer comprising: 
 a drift tube defining a drift tube inlet configured to receive ions and a drift tube outlet, the drift tube configured to separate the ions in time as a function of ion mobility,    an ion fragmentation region,    a source of buffer gas configured to supply buffer gas to at least the ion fragmentation region,    a source of doping gas configured to supply doping gas to at least the ion fragmentation region, and    at least one voltage source coupled to the ion fragmentation region, the at least one voltage source configured to selectively establish an electric field in the ion fragmentation region that is sufficient to fragment at least some of the ions via collisions with a mixture of the buffer gas and the doping gas,    wherein the doping gas is selected such that a magnitude of the electric field that can be sustained in the ion fragmentation without breaking down in the presence of the ions and the mixture of the buffer gas and the doping gas is higher than the magnitude of the electric field that can be sustained in the ion fragmentation region without breaking down in the presence of ions and only the buffer gas.    
   
   
       47 . The ion mobility spectrometer of  claim 46  wherein the ion fragmentation region is contained within the drift tube.  
   
   
       48 . The ion mobility spectrometer of  claim 46  wherein the ion fragmentation region is positioned adjacent to the drift tube outlet.  
   
   
       49 . The ion mobility spectrometer of  claim 46  further including an ion source configured to supply ions to the drift tube inlet, 
 wherein the ion fragmentation region is positioned to fragment at least some of the ions prior to entrance into the drift tube.    
   
   
       50 . The ion mobility spectrometer of  claim 46  wherein the buffer gas is helium.  
   
   
       51 . The ion mobility spectrometer of  claim 50  wherein the doping gas is nitrogen.  
   
   
       52 . The ion mobility spectrometer of  claim 51  wherein the mixture of the buffer gas and the doping gas consists of approximately 1-5 mole percent of the nitrogen gas and approximately 95-99 mole percent of the helium gas.  
   
   
       53 . A method of increasing the magnitude of an electric field that can be sustained without breaking down in the presence of ions and a buffer gas, the method comprising: 
 selecting a doping gas to mix with the buffer gas to form a mixture gas such that a magnitude of an electric field that can be sustained without breaking down in the presence of ions and the mixture gas is higher than the magnitude of the electric field that can be sustained without breaking down in the presence of ions and the buffer gas, and    mixing the doping gas with the buffer gas to form the mixture gas.    
   
   
       54 . The method of  claim 53  wherein the buffer gas is helium.  
   
   
       55 . The method of  claim 54  wherein the doping gas is nitrogen.  
   
   
       56 . The method of  claim 55  wherein the mixture gas consists of approximately 1-5 mole percent of the nitrogen gas and approximately 95-99 mole percent of the helium gas.