Abstract:
Analysis of biological small molecules such as toxins, spores or cells is achieved by miniature mass spectrometer apparatus and apparatus attached thereto for vaporizing and ionizing a liquid sample fed into an evacuated vaporization chamber as an electrospray. The mass spectrometer apparatus includes: a collimation chamber, a repeller assembly, an internal ionization chamber, a mass filter and ion separation chamber, a drift space region, and a multi-channel ion detection array so as to permit the collection and analysis of ions formed over a wide mass range simultaneously. The vaporization chamber includes an output port adjacent the input to the collimation chamber so as to maximize the amount of vaporized material being fed into the mass spectrometer apparatus.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This invention is related to the invention shown and described in U.S. Ser. No. 11/802,196 (Northrop Grumman Case No. 001283-078) entitled “Miniature Mass Spectrometer For The Analysis Of Chemical And Biological Solid Samples” filed in the name of Carl B. Freidhoff, the present inventor, on May 21, 2007. 
     This invention is also related to the invention shown and described in U.S. Ser. No. 11/260,106 (Northrop Grumman case No. 000810-078) entitled “A MEMs Mass Spectrometer”, filed in the name of Carl B. Freidhoff, on Oct. 28, 2005. 
     The teachings of the above cross-referenced patent applications are intended to be incorporated herein by reference for any and all purposes. 
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to solid state miniature mass spectrometers, and more particularly to a miniature mass spectrometer test system for the analysis of biological small molecules such as toxins, spores or cells by a nanoelectrospray fed into a vacuum. 
     2. Description of Related Art 
     A mass spectrometer is a device that permits rapid analysis of an unknown sample of material to be analyzed. A small amount of the sample is introduced into the mass spectrometer where it is ionized, focused and accelerated by means of magnetic and/or electric fields toward a detector array. Different ionized constituents of the sample travel along different paths to the detector array in accordance with their mass to charge ratios. The outputs from the individual detector elements of the array provide an indication of the sample&#39;s constituents. 
     Industrial mass spectrometers are generally large, heavy and expensive, and therefore, a need exists for a miniature, relatively inexpensive light-weight solid state mass spectrometer for use by the military, homeland security personnel, hazmat crews, industrial concerns and the like to test for the presence of dangerous substances in the immediate environment. 
     A typical miniature mass spectrometer is shown and described in the present assignee&#39;s U.S. Pat. No. 5,386,115 entitled “Solid State Micro-Machined Mass Spectrograph Universal Gas Detection Sensor”, issued to Carl B. Freidhoff et al. on Jan. 31, 1995. Basically such a device is comprised of two semiconductors substrates joined together by an epoxy seal. Each half includes intricate cavities formed by a lithograph process. Although the device meets the requirements for small size, due to the depth and intricacy of the cavities, the lithographic process is extremely expensive. Further, under vacuum conditions, the epoxy seal tends to add gas into the device thus contaminating the readings obtained and thereby limiting its sensitivity. 
     In the above-referenced U.S. application Ser. No. 11/260,106, entitled “A MEMs Mass Spectrometer”, there is disclosed an improved MEMs mass spectrometer for analyzing a gas sample. 
     SUMMARY OF THE INVENTION 
     The present invention is directed to the analysis of biological small molecules by a device consisting of a miniature mass spectrometer test system which is adapted to operate with a minimum of support equipment and includes a nanoelectrospray of a test sample into a vacuum ionizing chamber. The vacuum ionizing chamber is affixed to the front end of the mass spectrometer apparatus and vaporizes a fluid i.e. liquid sample into an atomized spray without heat and drying gas. The vacuum environment comprises an external electrospray-ionization chamber and provides a nanospray fluid flow rate, which is adapted to provide a sufficient number of ions for detection without requiring a large pump or power expenditure. The mass spectrometer includes a differentially pumped front end, which allows the mass spectrometer to sample a higher pressure regime and analyze ions formed at a lower pressure. 
     In a preferred aspect of the present invention there is provided a mass imaging spectrometer test system for analyzing biological small molecules of a liquid sample, comprising: an evacuated liquid sample input chamber including apparatus for vaporizing and ionizing a liquid sample being fed into the chamber; mass spectrometer apparatus connected to the input chamber and having an ionized vapor input port for receiving ionized vapor of the liquid sample from the input chamber, and wherein the spectrometer includes: a collimation chamber having a vapor collimation sub-assembly connected to the input port and having at least one vacuum pumping aperture for evacuating and drawing said ionized vapor from the evacuated chamber into the collimation chamber; a repeller member located adjacent the vapor collimation sub-assembly; an ionizer sub-assembly located adjacent the repeller member for further ionizing the ionized vapor; an ion optics chamber located adjacent the ionizer sub-assembly; at least one evacuated ion filter and separation chamber located adjacent the ion optics chamber and including means for generating an electromagnetic field therein for separating ions therein by their respective mass/charge ratio; and, a detector array for detecting ions separated in the mass filter and ion separation chamber and located a predetermined distance therefrom by an intermediate drift space region. 
     Further scope of applicability of the present invention will become apparent from the detailed description provided below. It should be understood, however, that the detailed description and the specific example, while indicating the preferred embodiment of the invention is provided by way of illustration only, since changes and modifications coming within this scope the spirit of the invention will become apparent to those skilled in the art from this detailed description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present invention will become more fully understood from the detailed description provided hereinafter and the accompanying drawings which are provided by way of illustration only, and thus are not meant to be considered in a limiting sense, and wherein: 
         FIG. 1  is a block diagram broadly illustrative of the preferred embodiment of the subject invention; 
         FIG. 2  is an exploded view of two halves of the preferred embodiment of the subject invention including an electrospray ionizer chamber; 
         FIG. 3  is a perspective plan view illustrative of the base portion and support member of the subject invention shown in  FIG. 2 ; 
         FIG. 4  is a fragmented top planar view further illustrative of the base portion of the subject invention shown in  FIG. 3 ; and, 
         FIG. 5  is a partial perspective view illustrative of an enlarged portion of the front end section of the subject invention shown in  FIG. 2 . 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Referring now to the drawing figures wherein like reference characters refer to like parts, the block diagram of  FIG. 1  is illustrative of miniature mass spectrometer apparatus  10  for the analysis of biological small molecules by nanoelectrospray into a vacuum by means of a device fabricated on a chip. Reference numeral  12  denotes an electrospray-ionizer input chamber located in a separate housing  14  ( FIG. 2 ) which is physically attached to a semiconductor chip  16  and in which is located a collimator section  18 , an ionizer chamber  20 , first and a second ion optics chambers  22  and  24 , an ion separation chamber  26 , field generating means  28  for generating an electromagnetic field in the ion separation chamber  26  and draft space region  27 , an array  30  of detector elements and a readout chip  32 . Further, as shown in  FIG. 1 , a pair of vacuum pumps  33  are connected to the electrospray ionizer chamber  12  and the mass spectrometer chip  16  for separately evacuating the two elements. 
     Electrospray of a liquid input sample is performed at reduced pressure (vacuum) in the subject invention so as to dissolve large molecules of biological materials such as toxins, spores or cells. Electrospray allows multiple charges to be placed on large biological molecules so as to bring down the effective mass of the ion and with antibody capture or other clean-up techniques to remove background clutter. Thus, the small mass spectrometer of the subject invention is used to sense and separate out different toxins. 
     Considering now the invention in greater detail, ions produced in the electrospray-ionizer chamber  12  are fed into the collimator  18  which is differentially pumped by a pumping arrangement shown in  FIG. 4 , described hereinafter, so as to sample a higher pressure regime and analyze ions formed at a lower pressure inside of the electrospray chamber  12 . The vacuum environment acts to dry the fluid in the atomized spray without heat and drying gas. 
     The mass spectrometer apparatus  10  of the subject invention is fabricated in an elongated semiconductor chip as shown in  FIGS. 2 ,  3  and  4  and is comprised of a top section  34  and a bottom section  36 . The bottom section  36  forms part of a base member  35  shown in  FIG. 3 . Both sections  34  and  36  each include opposing collimator elements  18   1  and  18   2 , repeller members  19   1  and  19   2 , ionizer chamber elements  20   1  and  20   2 , first and second optics chambers  22   1 ,  22   2  and  24   1 ,  24   2 , upper and lower ion separation chamber portions  26   1  and  26   2 , a pair of drift space regions  27   1  and  27   2 . 
     Electromagnetic field generation apparatus  28   1  and  28   2  associated with the ion separation chamber elements  26   1  and  26   2  and the drift space regions  27   1  and  27   2  generate orthogonal magnetic and electric fields which operate to separate ions passing through the upper and lower portions  26   1  and  26   2  of the ionization separation chamber and drift space portions  27   1  and  27   2  and strike the detector array  30  which are comprised of multiple detector elements. The readout chip  32  converts detected analog signals to digital form which is then fed via a set of signal leads  34  to a digital signal processor  36  which generates output signals for a readout in the form of a visible display  38 . 
     Referring now to  FIGS. 3 and 4 , shown thereat is the lower half portion  16   2  of the mass spectrometer apparatus  10  and corresponds to the structure shown in  FIG. 2 , but now there is additionally shown in  FIG. 3  two sets of electrical signal leads  40  and  42  along with eight solder bumps  44   1 ,  44   2  . . .  44   8  surrounding respective apertures  46   1 ,  46   2  . . .  46   8  which are connected to eight individual evacuation pumps  48   1 ,  48   2  . . .  48   8  shown in  FIG. 4 , via pneumatic pipe members  50   1 ,  50   2  . . .  50   8  and  52   1 ,  52   2  . . .  52   8 . Electrical power is provided to the individual pumps  48   1 ,  48   2  . . .  48   8  by way of connector elements  54   1 ,  54   2  . . .  54   8 . Further, as shown in  FIG. 3 , three sets of electrical signal leads  56 ,  58  and  60  are located on a support member  62  for connection of the spectrometer  10  to external apparatus, not shown. 
     Referring now to  FIG. 5 , shown thereat are the structural details of the front end portion of the bottom section  16   2  of the mass spectrometer apparatus  10  and is intended to further illustrate the structure of the collimator section  18   2  and the details of the electrospray-ionizer chamber  12 . In  FIG. 5 , the electrospray-ionizer chamber  12  comprises a generally rectangular housing having an input port  13  to accommodate a commercially available nanoelectrospray member  14  having a tip  16  located in a front wall FW for injecting a liquid input sample into the chamber  12 . A nanoelectrospray output port  21  is located in a rear wall RW of the chamber  12  so as to mate with the collimator section  18   2  of the bottom section  36  of the spectrometer  10 . The collimator section  18   2  is comprised of three mutually aligned outwardly diverging pairs of collimator elements  23   1 ,  23   2 , and  23   3  terminating in a tip pointing to the output port  21  of the electrospray-ionizer chamber  12  so as to allow ions formed of the liquid sample to enter to the collimator portion  18   2  of the mass spectrometer apparatus  10 . The foremost pair of collimator elements  23   1  project into the output port  21  of the electrospray-ionizer chamber  12  toward an opening  25  between a pair of elongated bar members  27   1  and  27   2  which are spaced approximately 1 centimeter away from the tip  15  of the electrospray sample input member. A voltage from a voltage source  29   1  of two voltage sources  29   1  and  29   2  is applied between the elongated bar members  27   1  and  27   2  and the nanoelectrospray member  14  and is poled so as to attract ions having a positive polarity to the opening  25  and then into the collimator portion  18   2 . The second voltage source  29   2  is shown connected between the bar members  27   1  and  27   2  and the lower section  36  of the spectrometer  10 . Accordingly, positive ions travel into the collimator section  18   2  where they pass into a second ionizer chamber  20   2  and the lower portions  22   2  and  24   2  of the ion optics chambers  22  and  24  and then into the ion separation chamber  26 , the lower portion thereof being shown by reference numeral  26   2 . 
     Although small molecules of a liquid sample will be vaporized in the interior of the electrospray-ionizer chamber  12 , this operation can be carried out in a pressure regime that can be as high as atmospheric pressure but is preferably carried out in a vacuum. To this end, a vacuum port  31  is shown located in the front wall FW of the chamber  12  to accommodate a vacuum pump shown, for example in  FIG. 1  by reference numeral  33 . 
     Furthermore a differential vacuum pumping scheme is provided in the collimator section  18   2  of the spectrometer  10  and as such includes four small circular openings  35   1 ,  35   2 ,  35   3  and  35   4  which are respectively coupled, for example, to pumps  48   1 ,  48   2 ,  48   5  and  48   6  as shown in  FIG. 4 . Additional stages of vacuum pumping are also provided by the pumps  48   3 ,  48   4 ,  48   7  and  48   8  to provide proper vacuum levels in the nanoelectrospray and mass separation regions of the spectrometer apparatus  10 . The differentially pumped front end allows the apparatus to sample a higher pressure regime and analyze ions formed at a lower pressure. 
     Thus what has been shown described is a structure for use in a miniature mass spectrometer in sampling biological small molecule ions that are vaporized and ionized through the use of nanoelectrospray in a vacuum. 
     The foregoing detailed description merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are thus within its spirit and scope.