Abstract:
A detector for time of flight mass spectroscopy uses a microwave resonant cavity excited into resonance by the passage of charged particles as an ion detector. With proper configuration of the frequency of resonance of the cavity, its modes and its quality factor, nanosecond time resolution, should be possible.

Description:
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
       [0001]    This invention was made with United States government support awarded by the following agencies:
       USAF/AFOSR FA9550-08-1-0337       
 
         [0003]    The United States government has certain rights to this invention. 
     
    
     CROSS REFERENCE TO RELATED APPLICATION 
       [0004]    - - 
       BACKGROUND OF THE INVENTION 
       [0005]    The present invention relates to mass spectrometers and in particular to a high-resolution detector for time of flight spectrometers. 
         [0006]    Mass spectrometers are analytic instruments that may provide for the precise measurement of the mass of molecules. Generally, the molecules to be measured are given an electrical charge and then accelerated by an electrical field. The velocity of their acceleration will be generally proportional to the mass to charge ratio (m/z) and so for a given and known charge the mass may be precisely determined by a velocity measurement. 
         [0007]    One method of determining velocity is the use of a “sector” type analyzer which bends the trajectories of the charged particles using a magnetic field. When the particles exit the magnetic field, the angle of their trajectories (and spatial separation at a measurement point) will be in proportion to m/z and may be measured by a series of spatially separated collectors. 
         [0008]    An alternative detection system uses a “time of flight” analyzer in which relative velocities of different molecular species are deduced based on the time it takes them to reach a detector. Common detectors used for time of flight analysis include so-called “Faraday cups” which are conductive metal cups, which catch charged particles and are attached to sensitive electrical amplifiers and “dynode” detectors which provide an amplification of received charge through electron multiplier techniques. 
         [0009]    Mass spectrometry is increasingly applied to extremely large molecules, for example proteins, that may be ionized by various techniques such as matrix assisted laser desorption/ionization (MALDI) in which the fragile proteins are protected with a matrix material that is struck by a laser beam. The matrix absorbs the energy of the beam and is removed from the protein while transferring a charge to the protein. 
         [0010]    The large mass of protein molecules decreases the sensitivity of a time of flight spectrometer to the extent that the velocity of the proteins is lower and thus the difference between velocities of similar masses is less. This requires that the difference in measured times of flight must be resolved more precisely. Conventional spectrometer detectors can exhibit latencies that hide small mass differences for large molecules thus limiting the mass resolving power of the spectroscope. 
       SUMMARY OF THE INVENTION 
       [0011]    The present invention provides a detector for mass spectrometers employing a tuned microwave cavity. Charged particles passing through the cavity create an electrical field that can be detected by an cavity coupled to the cavity. With high quality factor cavities, time resolutions on the order of 1-ns should be possible. 
         [0012]    Specifically, the present invention provides a detector for use in a mass spectrometer of a type providing a source of ionized molecules, for analysis, that are then accelerated in an acceleration field before reaching the detector. The detector includes a cavity of conductive material providing an electromagnetically tuned cavity, the cavity having an opening positioned to receive molecules after acceleration by the acceleration field along an axis into the cavity. An antenna communicates with the cavity to receive an electrical signal caused by electromagnetic resonance of the cavity; and detection electronics receive the electrical signal to distinguish a time of arrival of the ionized molecule in the cavity. 
         [0013]    It is thus a feature of at least one embodiment of the invention to provide a novel detector for time of flight mass spectrometry providing potentially high temporal resolution. 
         [0014]    The cavity may have a resonant frequency in the TM-010 mode of no less than 500 GHz and preferable in no less than 1.5 GHz. The cavity may have a quality factor (Q) in excess of 4000 or preferably in excess of 7000. 
         [0015]    It is thus a feature of at least one embodiment of the invention to provide time resolutions suitable for time of flight measurements of large molecules such as proteins. 
         [0016]    The antenna may be a first conductive stub placed at a first anti-node for the TM110 mode and referenced to a second conductive stub placed at a second anti-node for the TM110 mode having a phase shift with respect to the first anti-node of an odd multiple of π. 
         [0017]    It is thus a feature of at least one embodiment of the invention to provide an antenna system effectively capturing energy generated by small charges passing through the cavity. 
         [0018]    The cavity may be radially symmetric about the axis and/or may be a reentrant resonant cavity. 
         [0019]    It is thus a feature of at least one embodiment of the invention to provide a manufacturable high-Q cavity suitable for ion detection. 
         [0020]    The cavity may provide a through passage along the axis from the opening to a cavity exit. 
         [0021]    It is thus a feature of at least one embodiment of the invention to provide a cavity that can be used in a mass spectrometer without accumulation of material in the cavity. 
         [0022]    The detector may further include an isolator providing for an isolation of direct current voltages between the antenna and the detector circuitry. 
         [0023]    It is thus a feature of at least one embodiment of the invention to provide a sensitive electrical measurement device that can be biased with the necessary field voltages needed in a mass spectrometer. 
         [0024]    The conductive material may be copper. 
         [0025]    It is thus a feature of at least one embodiment of the invention to provide an extremely high Q resonant cavity suitable for high-speed ion measurements. 
         [0026]    These particular objects and advantages may apply to only some embodiments falling within the claims and thus do not define the scope of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0027]      FIG. 1  is a simplified diagram of a matrix assisted laser desorption/ionization, time of flight (MALDI-TOF) mass spectrometer using a detector of the present invention; 
           [0028]      FIG. 2  is a perspective view of the detector of  FIG. 1 ; 
           [0029]      FIG. 3  is a fragmentary cross-sectional view of the detector of  FIG. 2  taken along line  3 - 3 ; and 
           [0030]      FIG. 4  is a plot of the radiofrequency (RF) characteristics of the detector of  FIG. 2  showing its high quality value and tuning. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0031]    Referring now to  FIG. 1 , an example mass spectrometer  10  suitable for use with the present invention may include an ion generator  12 , for example, providing an introduction zone  14  into which matrix treated molecules  16  may be introduced and targeted by a laser  18  to provide a source of ions  20 . 
         [0032]    The ions  20  may be accelerated along a travel axis  22  by means of various accelerating plates, for example, a repeller plate  24  position on a rear side of the introduction zone  14  and an attractor plate  26  position on the front side of the introduction zone  14  (in the direction of desired ion travel) with the attractor plate  26  having a relatively lower electrical potential than the repeller plate  24  (for positive ions). An accelerator plate  28  in front of the attractor plate  26  may further accelerate the ions  20  to a desired speed. The ions  20  may be focused by a set of steering plates  30  as understood in the art to enter a flight tube  32  providing a zone when the ions  20  of different velocities may further separate improving the resolution of the system. The ions may then enter a detector  34 . 
         [0033]    Referring now to  FIG. 2 , the detector  34  of the present invention may be an electrically resonant microwave cavity, for example, having a conductive copper body  36  defining a cavity volume  37 . In one embodiment, the cavity volume  37  may have rotational symmetry about the axis  22  and provide an inlet port  38  and exit port  39  aligned with and opposed along the axis  22  to receive and expel ions  20 . Ions  20 , as they pass along the axis  22  through the detector  34 , excite the resonant microwave cavity to produce an electrical signal that may be detected as a voltage generated across leads  40  connected to internal antennas within the detector  34  as will be described. 
         [0034]    Referring now to  FIG. 3 , the detector  34  may, for example, be machined from one or more solid blocks of conductive material for dimensional stability, for example an oxygen free copper, assembled together to provide a central cylindrical cavity  44  and a cylindrical annular side cavity  46  concentric about axis  22  and communicating with the central cylindrical cavity by means of a radially extending slot  48  joining the central cylindrical cavity  44  with a rear base of the annular side cavity  46 . The cavity so formed provides a so-called reentrant resonant cavity. 
         [0035]    The ions  20  passing through the cavity along axis  22  excite a monopole resonance in the TM010 mode  50  as well as a TM 110 mode resonance  52 . This latter resonance may be detected by means of stub antennas  56  extending radially inward into the annular side cavities  46  at the front end of the annular cavities diametrically opposed across axis  22 . The stub antennas  56  are short conductors supported by feedthrough insulators  57  in the body  36  of the detector  34  and connected to coaxial cable leads  40 . 
         [0036]    These antennas  56  are positioned to couple to the anti-nodes of the TM110 mode. The energy in the TM110, like the TM010 mode, will largely be proportional only to the molecular ion beam intensity and not the ion velocity. 
         [0037]    Referring now also to  FIG. 4 , a plot  47  of antenna gain for the detector  34  as a function of frequency shows a preferred design characteristic where the cavity is tuned to have a fundamental TM010 mode in microwave frequencies, for example, 1.5 GHz and a quality factor calculated to be 7400 or higher. 
         [0038]    The resolution of the cavity will be generally given by the following formula: 
         [0000]    
       
         
           
             τ 
             = 
             
               1 
               
                 π 
                  
                 
                     
                 
                  
                 B 
               
             
           
         
       
     
         [0039]    where B is the bandwidth defined by the relationship: 
         [0000]    
       
         
           
             B 
             = 
             
               
                 f 
                 d 
               
               
                 Q 
                 ld 
               
             
           
         
       
     
         [0040]    where f d  is the frequency of the resonant cavity and Q ld  is the quality factor for the cavity. With a calculated intrinsic quality factor of 7400, nanosecond time resolution should be obtained with this cavity. 
         [0041]    Referring again to  FIG. 1 , one lead  40  may be referenced to a signal ground through a terminating resistor  58  (e.g. 50 ohms) and the other lead  40  may be connected to a DC isolator  60 , for example a blocking capacitor, isolating the detection circuitry to be described from the voltages of the spectrometer. In this way the body  36  of the detector  34  may be electrically biased with respect to the plates  24 ,  26  and  28  as necessary, for example at a ground point different from the signal ground. 
         [0042]    A band pass filter  62  centered about the desired modal frequency (e.g. 1.5 GHz) may receive the signal from the isolator  60  to reduce other frequencies outside of the resonance of the cavity to improve signal-to-noise ratio. The output of the band pass filter  62  may be connected to a detector  64  (for example, a square law or diode type detector) to extract an amplitude value of the cavity resonance that may be used to signal passage of an ion  20 , for example, by threshold detection. 
         [0043]    In one embodiment the output of the detector  64  they be provided to a high-speed oscilloscope  66  used to measure time of arrival of the ion  20  and hence the time of flight of the ion  20 . Alternatively the signal from detector  64  may be provided to a microprocessor system  68  typically associated with such spectrometers receiving an ion initiation time signal, for example from the laser  18 , to provide a spectrographic output  70 . 
         [0044]    The present invention is not limited to a mass spectrometer of the MALDI-TOF design as described in simplified form above but may be used in any time of flight mass spectrometers including those that provide for reflection of the ions and other features well known in the art. It is anticipated that other configurations of resonant cavities may be also be used provided they exhibit the necessary frequency and Q characteristics. Although the present detector is particularly desirable for large molecules such as proteins where high temporal resolution is required, it may find use in general-purpose spectroscopy as well. 
         [0045]    Certain terminology is used herein for purposes of reference only, and thus is not intended to be limiting. For example, terms such as “upper”, “lower”, “above”, and “below” refer to directions in the drawings to which reference is made. Terms such as “front”, “back”, “rear”, “bottom” and “side”, describe the orientation of portions of the component within a consistent but arbitrary frame of reference, which is made clear by reference to the text and the associated drawings describing the component under discussion. Such terminology may include the words specifically mentioned above, derivatives thereof, and words of similar import. Similarly, the terms “first”, “second” and other such numerical terms referring to structures do not imply a sequence or order unless clearly indicated by the context. 
         [0046]    When introducing elements or features of the present disclosure and the exemplary embodiments, the articles “a”, “an”, “the” and “said” are intended to mean that there are one or more of such elements or features. The terms “comprising”, “including” and “having” are intended to be inclusive and mean that there may be additional elements or features other than those specifically noted. It is further to be understood that the method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional or alternative steps may be employed. 
         [0047]    References to “a microprocessor” and “a processor” or “the microprocessor” and “the processor,” can be understood to include one or more microprocessors that can communicate in a stand-alone and/or a distributed environment(s), and can thus be configured to communicate via wired or wireless communications with other processors, where such one or more processors can be configured to operate on one or more processor-controlled devices that can be similar or different devices. Furthermore, references to memory, unless otherwise specified, can include one or more processor-readable and accessible memory elements and/or components that can be internal to the processor-controlled device or external to the processor-controlled device, and can be accessed via a wired or wireless network. 
         [0048]    It is specifically intended that the present invention not be limited to the embodiments and illustrations contained herein and the claims should be understood to include modified forms of those embodiments including portions of the embodiments and combinations of elements of different embodiments as come within the scope of the following claims. All of the publications described herein, including patents and non-patent publications, are hereby incorporated herein by reference in their entireties.