Patent Abstract:
A method for automatically verifying the existence of a target compound comprises generating a total ion chromatogram. The total ion chromatogram comprises a plurality of peaks, each peak representing one or more compounds in a sample matrix, each peak comprising at least two compounds. The method also comprises deconvoluting each peak to isolate each target compound present in the peak, and automatically verifying the identity of each target compound against a target compound library.

Full Description:
BACKGROUND 
   A gas chromatograph/mass spectrometer (typically abbreviated as “GC/MS”) analyzes a sample of material to determine the constituent compounds thereof. For example, a GC/MS can be used to determine the compounds that are in a sample of food. In one application, a GC/MS analyzes food products to detect the presence of contaminants, such as a pesticide, a chemical warfare agent (CWA), or other contaminants present in the sample. The sample is also referred to as a “matrix” or “sample matrix.” Typically, a GC/MS analyzes a sample using both time-based parameters (for example, identifying a target compound based on a time window, referred to as “retention time”) and on mass-to-charge ratio, referred to as “m/z,” that identifies ions present in the target compound. For a sample having multiple components, the GC/MS outputs a signal that is represented by a pulse train having multiple peaks. The position of each peak relates to the identity of the components in the mixture while the area of the peak relates to the quantity (also referred to as abundance) of that component in the mixture. 
   When a target compound is detected in the sample matrix, the identity of the target compound must be verified. Verification of the target compound is typically automated, but manual review of the analysis results is required to validate the results. 
   Typically, a number of different software programs may be used to process the results of the analysis performed by the GC/MS. A first program can be used to analyze the results of the GC portion of the GC/MS and to analyze the results of the MS portion of the GC/MS. A second program may be used to confirm the results by comparison with a known database. 
   Typically, an analyst who must be proficient in the use of the above-mentioned software may require on the order of 20–30 minutes to perform peak averaging and background subtraction to confirm a target compound found by a retention time window analysis and four (4) ion identification. Unfortunately, this confirmation process is time consuming and burdensome, due to matrix interferences. As known by those skilled in the art, matrix interferences are those compounds present in a sample in which one is not interested. They have similar retention times and/or similar ion fingerprints that obscure correct identification of the compounds in which one is interested, which are referred to as the target compounds. 
   Therefore, it would be desirable to automate the identification and verification of a target compound detected in a sample. 
   SUMMARY OF THE INVENTION 
   The invention provides a system and method for automatically identifying a target compound. In one embodiment, a method for automatically identifying a target compound comprises generating a total ion chromatogram. The total ion chromatogram comprises a plurality of peaks, each peak representing one or more compounds in a sample matrix. The method also comprises deconvoluting each peak to isolate each compound present in the peak, and automatically verifying the identity of each compound against a target compound library. 
   Other systems, methods and advantages in addition to or in lieu of the foregoing are provided by certain embodiments of the invention, as is apparent from the description below with reference to the following drawings. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The present invention, as defined in the claims, can be better understood with reference to the following drawings. The components within the drawings are not necessarily to scale relative to each other, emphasis instead being placed upon clearly illustrating the principles of the present invention. 
       FIG. 1  is a graphical view illustrating the data provided from a gas chromatograph/mass spectrometer (GC/MS). 
       FIG. 2  is a graphical view illustrating a “total ion chromatogram” (TIC) of a sample, including one or more compound(s) plus the sample matrix. 
       FIG. 3  is a block diagram illustrating a system including a GC/MS and a controller/computer. 
       FIG. 4  is a block diagram illustrating an exemplary controller/computer constructed in accordance with an embodiment of the invention. 
       FIG. 5  is a functional block diagram illustrating the interaction among the deconvolution reporting software, the GC/MSD software, the AMDIS software and the NIST02 library software of  FIG. 4 . 
       FIGS. 6A and 6B  are a graphical representation collectively illustrating the total ion concentration and mass spectrum for a particular target sample. 
       FIGS. 7A and 7B  are a graphical representation collectively illustrating the deconvolution of the peak “P” of  FIG. 6B  into its constituent compounds. 
       FIG. 8  is a graphical view illustrating a report generated by the deconvolution reporting software in accordance with an embodiment of the invention. 
       FIG. 9  is a flow chart describing the operation of one embodiment of the invention. 
   

   DETAILED DESCRIPTION OF THE INVENTION 
     FIG. 1  is a graphical view illustrating the data provided from a gas chromatograph/mass spectrometer (GC/MS). The graph  10  includes a horizontal axis  12  representing time and a vertical axis  14  representing quantity, or abundance, of a compound detected and identified in a sample matrix. The z axis  16  represents the mass spectrum, also referred to as the “ion fingerprint” of the compound identified from the sample matrix. The data provided from the GC/MS are three dimensional. The x, y and z axes are used to completely identify a compound in a sample matrix. The GC portion of the GC/MS resolves compounds with respect to time while the MS portion of the GC/MS detects resolved components based on a mass spectrum of each component. 
   Ideally, every compound has a unique mass spectrum by which it can be identified. However, many compounds have similar structures, so their mass spectra are similar. To aid in compound identification, a GC is first used to attempt to separate similar compounds with respect to time. For example, different compounds in a sample matrix resolve differently based on what is referred to as “retention time.” The retention time of a compound can be identified by a GC and can be used to preliminarily identify a compound. After the GC portion of a GC/MS identifies compounds in a sample matrix according to retention time, a mass spectrum of the compound, or compounds, is generated by the MS portion of the GC/MS. A complete mass spectrum of a compound can contain from one (1) to hundreds of ions. The exact number of ions that can be used is not exact. 
   A mass spectrum can comprise a single ion, if that&#39;s all the system is configured to search for. Alternatively, if the system is configured to search for all ions, a mass spectrum can contain 50 or 100 or 150+ ions. The number of ions depends on the compound being analyzed. However, due to the availability of processing resources, such as the speed and memory capacity of a processor located in a computing system, it is generally impractical to analyze all of the possible ions. Therefore, in this example, and in a typical GC/MS, a subset of ions, in this example four (4), are analyzed to confirm the existence of a target compound. Using retention time and four ion analysis, a target compound, which is (are) one or more compounds from a subset of all compounds in the universe, can be identified. A different number of ions can be analyzed, depending on the application. By identifying a target compound first using the retention time of a target compound using the GC portion of the GC/MS, and then by using the MS portion of the GC/MC to perform the ion analysis, a reasonably certain analysis identifying the target compound in the sample can be obtained. These analyses are combined by the GC/MSD software (to be described below) to produce a first “result.” The first result is generated from what is referred to as a total ion chromatogram (TIC), which will be described in  FIG. 2 . 
   The TIC can then be supplied to a software program, referred to as the Automated Mass Spectral Deconvolution and Identification Software (AMDIS), to be described below, that is used to deconvolute compounds and compare the resultant deconvoluted mass spectra to a database of known target compound spectra. This produces a second result, and a list of possible target compounds found. The results (deconvoluted mass spectra) are then supplied to a database containing a different set of mass spectra for comparison. Such a database is referred to as the NIST02 library and contains a library of target compounds. The NIST02 library is available from the National Institute of Standards and Technology (NIST) and is generated using all ions. The NIST02 database can be used to verify the identity of a target compound identified using the GC/MS as described above, thus generating a third result. A shortcoming of the above-described identification procedure is that to completely verify the identity of the target compound, the three results must be manually analyzed by an individual familiar with all three procedures and the associated software. 
     FIG. 2  is a graphical view illustrating a “total ion chromatogram” (TIC)  20  of a sample, including one or more target compounds plus the sample matrix. The horizontal axis corresponds to time, while the vertical axis corresponds to the quantity, or abundance, of a compound in the sample matrix. In  FIG. 2 , the z axis, which represents the mass spectrum of a compound extends into the page. The total ion chromatogram  20  includes a plurality of peaks, exemplary ones of which are illustrated using reference numerals  22 ,  24 ,  26  and  28 . Each peak represents one or more compounds, which are identified by the gas chromatograph, in the sample matrix based on retention time (shown on the horizontal axis). The characteristic “ion fingerprint” of each peak, which is not directly shown in  FIG. 2 , corresponds to the mass spectrum of each of the peaks  22 ,  24 ,  26  and  28 . 
     FIG. 3  is a block diagram illustrating a system  100  including a GC/MS  110  and a controller/computer  200 . The GC/MS  110  is coupled to the controller/computer  200  by a bi-directional connection  102 . The GC/MS  110  separates and detects compounds in a sample matrix, as described above, and creates retention time data and mass spectra for each compound. The controller/computer  200  controls data acquisition and data processing relating to the GC/MS  110 . The controller  200  can be, for example, a computer, a computerized controller, or other type of computing device that includes processing, interface, and software components that are used to control all aspects of the GC/MS  110 . Alternatively, the functionality of the controller/computer  200  can be located in the GS/MS 110 . 
     FIG. 4  is a block diagram illustrating an exemplary controller/computer  200  constructed in accordance with an embodiment of the invention. Generally, in terms of hardware architecture, as shown in  FIG. 4 , the computer  200  includes a processor  204 , memory  206  (one or more random access memory (RAM) elements, read only memory (ROM) elements, etc.), an optional removable media disk drive  212 , a gas chromatograph/mass spectrometer interface  208 , referred to as a “GC/MS interface  208 ,” an input/output controller  222  and a power module  265  that are connected together and that communicate with each other via a local interface  218 . The local interface  218  can be, for example but not limited to, one or more buses or other wired or wireless connections, as is known to those having ordinary skill in the art. The local interface  218  may have additional elements, which are omitted for simplicity, such as buffers (caches), drivers, and controllers, to enable communications. Further, the local interface  218  includes address, control, and data connections to enable appropriate communications among the aforementioned components. 
   The processor  204  is a hardware device for executing software that can be stored in memory  206 . The processor  204  can be any suitable processor for implementing the functionality of the controller/computer  200 . In one embodiment, the controller/computer  200  executes on a personal computer (PC). 
   The memory  206  can include any one or a combination of volatile memory elements (e.g., random access memory (RAM, such as DRAM, SRAM, etc.)) and nonvolatile memory elements (e.g., NVRAM, ROM, hard drive, tape, CDROM, etc.). Moreover, the memory  206  may incorporate electronic, magnetic, optical, and/or other types of storage media. Note that the memory  206  can have a distributed architecture, where various components are situated remote from one another, but can be accessed by the processor  204 . 
   The software in memory  206  may include one or more separate programs, each of which comprise one or more code segments, which are an ordered listing of executable instructions for implementing logical functions. In the example of  FIG. 4 , the software in the memory  206  includes software in the form of gas chromatograph/mass selective detector (GC/MSD) software  236  (the term “mass selective detector” is synonymous with the term “mass spectrometer”), AMDIS software  237  and NIST02 library software  238 . The GC/MSD software  236  can be, for example, a proprietary software module that performs the GC/MS analysis described above using retention time analysis and four ion mass spectra analysis. The AMDIS software  237  can be, for example, compound identification software available from the National Institute of Standards and Technology (NIST). The AMDIS software  237  uses all ions to separate, also referred to as “deconvolute,” co-eluting compounds detected by the GC/MSD software  236 . Co-eluting compounds are those compounds that have similar retention times when they are analyzed by the GC/MS. The NIST02 library software  238  is also available from the National Institute of Standards and Technology and includes a library of mass spectra formed using all ions. 
   The GC/MSD software  236  generates a first result  241 , including the results of the GC/MS analysis of the sample matrix. The first result can be generated from the information contained in the TIC  20  of  FIG. 2 . The GC/MSD software  236 , under the control of the deconvolution reporting software (DRS)  250 , supplies the first result to the AMDIS software  237 , which generates a second result  242 , further identifying/confirming the identity of the target compounds in the first result  241 . The second result  242  is supplied to the NIST02 library software  238 , which generates a third result  243  further confirming the identity of the target compounds. 
   The memory  206  also includes a graphical user interface (GUI)  249 . The GUI  249  provides a graphical user interface for the controller/computer  200  and also displays information to a user on the display  280 . The memory also includes deconvolution reporting software  250 . The deconvolution reporting software  250  generates a first list  261  corresponding to the first result  241 , a second list  262  corresponding to the second result  242 , and a third list  263  corresponding to the third result  243 . The deconvolution reporting software  250  combines the data from the GC/MSD software  236 , AMDIS software  237  and the NIST02 library software  238  and generates a sorted combined result  255 . The deconvolution reporting software  250  then generates a report  260  for display on the display  280 . The deconvolution reporting software  250  generates the sorted combined result by, for example, sorting the lists  261 ,  262  and  263  based on retention time and/or based on a chemical abstracts service number (CAS #). A CAS number is a unique, universally recognized number assigned to each target compound. 
   The memory  206  also includes one or more operating software modules, collectively referred to as operating system (O/S)  210 . The O/S  210  may include software modules that perform some of the functionality of the controller/computer  200  not specifically described herein. 
   In a preferred embodiment, the O/S  210  is the commonly available Microsoft 2000 or XP operating system available from Microsoft. However, other operating systems may be used. The operating system  210  essentially controls the execution of other computer programs, such as the GC/MSD software  236 , AMDIS software  237 , NIST02 software  238  and the deconvolution reporting software  250 . The processor  204  and operating system  210  define a computer platform, for which application programs, such as the GC/MSD software  236 , AMDIS software  237 , NIST02 software  238  and the deconvolution reporting software  250 , are written in higher level programming languages. The GC/MSD software  236 , AMDIS software  237 , NIST02 software  238  and the deconvolution reporting software  250  include the executable instructions that allow the controller/computer  200  to detect, separate and rapidly and automatically identify target compounds in a sample matrix. 
   The input/output controller  222  includes a network interface  224 , an input interface  245  and an output interface  256  each in communication with the local interface  218 . The network interface  224  couples the controller/computer  200  to an external network  228  via connection  226 . The external network can be any network to which the controller/computer  200  may couple to exchange information. The input interface  245  is coupled to an internal keypad  246  via connection  244  and to an external keypad  252  via connection  248 . The internal keypad  246  is located on the controller/computer  200  while the external keypad  252  is an auxiliary keypad to which the controller/computer  200  may be coupled. 
   The output interface  256  is coupled to a printer  267  via connection  258 . The printer  267  can be used to provide a permanent record of the analysis results obtained by the controller/computer  200 . The output interface  256  also couples to a video controller  270  via connection  264 . The video controller  270  couples to a display  280  via connection  272 . The display  280  can be an LCD touch screen display capable of receiving input from a user, but may be any type of suitable display. 
   The disk drive  212  can be any storage element or memory device, and as used herein, generally refers to flash memory, sometimes referred to as compact flash (CF) or PC card. 
   The power module  265  can power the controller/computer  200  from an AC power source, or can include batteries and a built in charger to provide portable DC power. The GC/MS  208  provides both electrical and mechanical interfaces to a GC/MS device. 
   When the controller/computer  200  is in operation, the processor  204  is configured to execute software stored within the memory  206 , to communicate data to and from the memory  206  and to generally control operations of the controller/computer  200  and the GC/MS  110  ( FIG. 3 ) pursuant to the software. 
   When portions of the controller/computer  200  are implemented in software, as is shown in  FIG. 4 , it should be noted that the O/S  210 , GC/MSD software  236 , AMDIS software  237 , NIST02 software  238  and the deconvolution reporting software  250  can be stored on any computer readable medium for use by or in connection with any computer related system or method. In the context of this document, a computer readable medium is an electronic, magnetic, optical, or other physical device or means that can contain or store a computer program for use by or in connection with a computer related system or method. The O/S  210 , GC/MSD software  236 , AMDIS software  237 , NIST02 software  238  and the deconvolution reporting software  250  can be embodied in any computer-readable medium for use by or in connection with an instruction execution system, apparatus, or device, such as a computer-based system, processor-containing system, or other system that can fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions. In the context of this document, a “computer-readable medium” can be any means that can contain, store, communicate, propagate, or transport the program for use by or in connection with the instruction execution system, apparatus, or device. 
   The computer readable medium can be, for example but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, device, or propagation medium. More specific examples (a non-exhaustive list) of the computer-readable medium include the following: an electrical connection (electronic) having one or more wires, a portable computer diskette (magnetic), a random access memory (RAM) (electronic), a read-only memory (ROM) (electronic), an erasable programmable read-only memory (EPROM or Flash memory) (electronic), an optical fiber (optical), and a portable compact disc read-only memory (CDROM) (optical). Note that the computer-readable medium could even be paper or another suitable medium upon which the program is printed, as the program can be electronically captured, via for instance optical scanning of the paper or other medium, then compiled, interpreted or otherwise processed in a suitable manner if necessary, and then stored in a computer memory. 
   The hardware components of the controller/computer  200  can be implemented with any or a combination of the following technologies, which are each well known in the art: a discrete logic circuit(s) having logic gates for implementing logic functions upon data signals, an application specific integrated circuit (ASIC) having appropriate combinational logic gates, a programmable gate array(s) (PGA), a field programmable gate array (FPGA), etc. 
     FIG. 5  is a functional block diagram illustrating the interaction among the deconvolution reporting software  250 , the GC/MSD software  236 , the AMDIS software  237  and the NIST02 library software  238  of  FIG. 4 . The GC/MSD software  236  receives the results of the analysis performed by the GC/MS  110  ( FIG. 3 ), identifies compounds first by time, then by ion (i.e., mass-to-charge “m/z”) ratios using, in this example, four ions, and provides a first result  241  to the deconvolution reporting software  250 . The deconvolution reporting software  250  receives the first result  241  and generates a corresponding first list  261 . The first list  261  represents portions of the data contained in a TIC  20  and corresponds to the first result  241 . The AMDIS software  237  also receives the results of the analysis performed by the GC/MS  110  ( FIG. 3 ). The AMDIS software  237  deconvolutes the mixed spectra and identifies compounds first by ion ratios using a database containing complete ion identification criteria, and then by time. The AMDIS software  237  then provides a second result  242  to the deconvolution reporting software  250 . 
   The deconvolution reporting software  250  receives the second result  242  and develops a second list  262  corresponding to the second result  242 . The second list  262  is then provided to the NIST02 library software  238 , which confirms the results by comparison to a NIST02 database, or library of target compounds. The NIST02 library software  238  then provides a third result  243  to the deconvolution reporting software  250 . The deconvolution reporting software  250  receives the third result  243  and develops a third list  263 , corresponding to the third result  243 . 
   The deconvolution reporting software  250  combines the data from the first list  261 , the second list  262 , and the third list  263  into one report referred to as a sorted combined result  255 . The sorted combined result  255  can be sorted by, for example, the retention time and the CAS number of the target compound. The sort can be performed in a fraction of the time that it would take an individual to analyze and verify the results provided by the GC/MSD software  236 , the AMDIS software  237  and the NIST02 library software  238 . The deconvolution reporting software  250  then generates a report  260  that can be sorted by, for example, the retention time or the CAS number of the target compound. A sample report  260  is illustrated below in  FIG. 8 . 
     FIGS. 6A and 6B  are a graphical representation  500  collectively illustrating the total ion concentration and mass spectrum for a particular target sample. The graph  505  illustrates the total ion chromatogram having a peak  507 . The peak  507  will likely include unresolved components in the sample. The mass spectrum  510  graphically illustrates the components that are present in the peak  507 . In  FIG. 6B , the peak  507  is illustrated as comprising three components, represented as peaks  530 ,  535 , and  540 . The peak  530  corresponds to a first component of the peak  507 , the peak  535  corresponds to a second component of the peak  507 , and the peak  540  corresponds to a third component of the peak  507 . The mass spectrum  550  illustrated in  FIG. 6B , includes compounds from the three peaks  530 ,  535  and  540 . It is difficult to isolate and identify the separate components of the peak  507  when the compounds are not completely separated (i.e., resolved in time) as illustrated in  FIG. 6B . 
     FIGS. 7A and 7B  are a graphical representation  600  collectively illustrating the deconvolution of the peak “P”  507  of  FIG. 6B  into its constituent compounds. The peak  507 , after being operated on by the AMDIS software  237  ( FIGS. 4 and 5 ), is deconvoluted into peak  530  (peak  1 ), peak  535  (peak  2 ), and peak  540  (peak  3 ). The term deconvolution refers to a mathematical process that resolves unresolved compounds. Furthermore, the AMDIS software  237  resolves the peak  507  not only in time, but also by mass spectrum. This is illustrated by the individual mass spectra associated with each peak. For example, the mass spectrum  610  is associated with peak  530 , the mass spectrum  620  is associated with the peak  535 , and the mass spectrum  630  is associated with the peak  540 . In this example, the peak  530  represents the sample matrix, the peak  535  represents matrix interference, and the peak  540  represents the target compound that is sought to be isolated. The three mass spectra  610 ,  620  and  630  are collectively shown in  FIG. 7A  as mass spectrum  550 . 
   In accordance with an embodiment of the invention, the deconvolution reporting software  250  combines the results of the GC/MSD software  236 , the AMDIS software  237 , and the NIST02 library software  238  and automatically generates a sorted combined result  255  ( FIGS. 4 and 5 ) and a report  260 , an example of which is shown in  FIG. 8 . 
     FIG. 8  is a graphical view  800  illustrating a report  260  generated by the deconvolution reporting software  250 . The deconvolution reporting software  250  combines the data from the GC/MSD software  236 , the AMDIS software  237 , and the NIST02 library software  238  into one report by building three lists  261 ,  262  and  263  ( FIGS. 4 and 5 ) of results. The deconvolution software  250  then sorts the lists based on, for example, retention time and CAS number, generates the sorted combined result  255 , and generates the report  260  shown in  FIG. 8 . For example, the report  260  can be sorted by retention time  801 , or by CAS number  802 . By combining the result of the GC/MSD software  236 , shown in column  806 , with the result from the AMDIS software  237 , shown in column  808 , and by combining the result from the NIST02 library software  238 , shown in column  810 , the report  260  can be sorted and can be used to verify target compounds in significantly less time than that required by manual operation to review the results  241 ,  242  and  243  ( FIG. 4 ). 
   In an alternative application, the GC/MS  110  ( FIG. 3 ) can also simultaneously acquire data from one or more additional GC detectors mounted on the GC/MS system. This data is represented as one or more signals additional to the TIC  20 . The data are 2-dimensional, that is time and abundance only, no z-axis, and hence no ion data. The detectors are typically element specific, such as a dual flame photometric detector (DFPD) or an electron capture detector (ECD). An ECD detects compounds with halogen atoms present, such as chlorine, bromine, fluorine etc. This data can be used to further confirm the identity of a target compound. The report in  FIG. 8  could be modified to include an additional column. For example, the entry “p,p′-DDE” contains chlorine and shows a response by ECD. That response could be noted in this additional column. If the ECD is calibrated, that response could be noted as an amount. Compounds that do not contain halogens would not show a response, hence the entries for those compounds would be blank in this additional column. As an additional benefit, the NIST02 search results,  810 , could be further sorted to report only those compounds that showed a response dependent on the specific detector used. 
     FIG. 9  is a flow chart  900  describing the operation of one embodiment of the invention. The blocks in the flowchart  900  illustrate the operation of one embodiment of the deconvolution reporting software  250 . The blocks may be performed in the order shown, out of the order shown, or may be performed concurrently. In block  902  the gas chromatograph/mass spectrometer  110  is operated to detect, isolate and analyze target compounds. In block  904  the GC/MSD software  236 , the AMDIS software  237 , and the NIST02 library software  238  generate their respective results  241 ,  242  and  243 . In block  906 , the results  241 ,  242  and  243  are transferred to the deconvolution reporting software  250 . In block  908 , the deconvolution reporting software  250  generates lists  261 ,  262  and  263 . 
   In block  912 , the deconvolution reporting software  250  analyzes the data in the lists  261 ,  262  and  263  by, for example, sorting the lists  261 ,  262  and  263  based on retention time and/or CAS number. In block  914 , the deconvolution reporting software  250  generates a sorted combined result  255 . In block  916 , the deconvolution reporting software  250  generates the report  260 . In block  918 , the deconvolution reporting software  250  determines whether additional samples are to be analyzed. If additional samples are to be analyzed, then the process returns to block  902 . If it is determined in block  918  that no additional samples are to be analyzed, the process ends. 
   It will be apparent to those skilled in the art that many modifications and variations may be made to the preferred embodiments of the present invention, as set forth above, without departing substantially from the principles of the present invention. For example, the present invention can be used with a number of different GC/MS analysis devices and with a number of different liquid chromatograph/mass spectrometer (LC/MS) devices. All such modifications and variations are intended to be included herein within the scope of the present invention, as defined in the claims that follow.

Technology Classification (CPC): 6