The present invention relates to particle detection systems and methods of analysis. The invention relates more particularly to a rapid detection method and system for determining the identity in real time of individual aerosol particles by comparing bipolar test spectra per individual particle to a database of known particle types, such as biological and chemical threat agents.
The potential threat of biological and chemical agent warfare is an ever-increasing national security concern. Of the known biological and chemical warfare agents it has been suggested that those capable of being deployed as aerosols are of greatest concern. Four of the five Centers for Diseases Control and Prevention Category A bioterrorism agents are capable of being transmitted as bio-aerosols, including Bacillus anthracis, more commonly known as “anthrax.” Unfortunately, the detection of such biological attacks is inherently difficult due to the small sample sizes. For example, a lethal dose of Bacillus anthracis spores weighs only 4 ng. In addition, these small samples can be widely dispersed within the air and may be found mixed with many other aerosol particles present in concentrations thousands of times larger than the bio-aerosol of interest. These demanding sampling conditions and other detection issues such as the unreliability of real time particle source analysis, let alone identification, have been problematic for the rapid screening of packages, letters, baggage, passengers, and shipping containers for biological and/or chemical agents.
While various particle detection methods have been and are currently employed, such as PCR or immuno-assay techniques, they are incapable of real-time analysis and onsite identification of particle source, including threat agents. Moreover, many “online” and “real time” particle detection and analysis systems simply provide sorting of spectral data into similar groups (e.g. via fuzzy logic algorithms) for subsequent visual identification by an expert user. Thus, current methods and systems of “real-time” particle detection, analysis and identification may present too substantial a disruption of commerce to be used as a pragmatic alternative. There is therefore a need for a truly real time particle detection system providing rapid or virtually instantaneous identification of a single aerosol particle from among known particle types or sources, and which goes beyond a simple determination of a particle's chemical composition from mass spectra. Moreover, the ability to rapidly detect and screen bio and chemical aerosols within a complex mixture of background particles would aid in the detection and interdiction of bioterrorist attack.
One aspect of the present invention includes a method of identifying individual aerosol particles in real time comprising: receiving sample aerosol particles; producing positive and negative test spectra of an individual aerosol particle using a bipolar single particle mass spectrometer; comparing each test spectrum to spectra of the same respective polarity in a database of predetermined positive and negative spectra for known particle types to obtain a set of substantially matching spectra; and determining the identity of the individual aerosol particle from the set of substantially matching spectra by determining a best matching one of the known particle types having both a substantially matching positive spectrum and a substantially matching negative spectrum associated therewith from the set.
Another aspect of the present invention includes a method of detecting in real time chemical and/or biological threat agents from a test specimen comprising: placing the test specimen in an enclosure defining a sampling volume; collecting sample aerosol particles from the sampling volume; receiving the sample aerosol particles into a bipolar single particle mass spectrometer; producing positive and negative test spectra of an individual aerosol particle using the bipolar single particle mass spectrometer; comparing each test spectrum to spectra of the same respective polarity in a database of predetermined positive and negative spectra for known particle types including threat agents, to produce a similarity score for each predetermined spectrum and obtain a set of substantially matching spectra based on a predetermined vigilance factor for similarity scores; determining the identity of the individual aerosol particle from the set of substantially matching spectra by determining a best matching one of the known particle types having both a substantially matching positive spectrum and a substantially matching negative spectrum associated therewith from the set, with at least one of the substantially matching positive and negative spectra having the highest order similarity score of all substantially matching spectra of the same respective polarity; and notifying a user upon identifying the individual aerosol particle as a threat agent from the known particle types.
And still another aspect of the present invention includes a system for identifying individual aerosol particles in real time comprising: a bipolar single particle mass spectrometer adapted to receive sample aerosol particles and produce positive and negative test spectra of individual aerosol particles; a data storage medium; a database of predetermined positive and negative spectra for known particle types stored on the data storage medium; and a data processor having a first data processing module adapted to compare each test spectra to spectra of the same respective polarity in the database to obtain a set of substantially matching spectra, and a second data processing module adapted to determine the identity of the individual aerosol particle from the set of substantially matching spectra by determining a best matching one of the known particle types having both a substantially matching positive spectrum and a substantially matching negative spectrum associated therewith from the set.
The accompanying drawings, which are incorporated into and form a part of the disclosure, are as follows:
The present invention is a general aerosol rapid detection (GARD) system and method which interrogates individual aerosol particles in an effort to characterize a sample that might be of interest either scientifically, medically, commercially, or as an indication of a terrorist threat, or in the interest of law enforcement. In particular, the system and method of the present invention serves to achieve more than a simple determination of a particle's chemical composition or further grouping into similar clusters. Instead, the system operates to analyze and positively identify an individual aerosol particle (not in aggregate) of unknown origin from a database of known particle types, with each known particle type associated with both a positive spectrum profile and a negative spectrum profile. Furthermore, the analysis and identification is achieved online and in real time, with the identification results rapidly communicated to a user in a virtually instantaneous manner.
In this manner, the system may be used to characterize and identify particular substances, such as bioterrorist agents and their surrogates, surrogates of plant, animal and human disease-causing microorganisms, cells in various stages of their life cycles, microorganism growth media, illegal drugs and samples likely to be confused with other threat agents by the casual observer. It is appreciated that the present invention may also be used to characterize and identify samples containing explosives or to monitor an industrial process for a detrimental byproduct. And other applications may include the monitoring of open air for threat agents, the rapid diagnosis of transmissible disease, the rapid and noninvasive detection of explosives, drugs or biological threat agents in packages, envelopes or shipping containers, the rapid biopsy of individual cells for medical diagnoses, real-time building monitoring, and the scientific investigation of single cells and their responses to drugs or other stimuli in cultures, among others.
Turning now to the drawings,
Alternatively, at block 102, sample aerosol particles may also be obtained from a test specimen or other object under inspection (not shown), such as a letter, potentially laden with a threat agent or other target particle type. In contrast to open air monitoring where the particles are already in the aerosol phase, particles must be resuspended from the test specimen for sampling. In this regard, the system may also include an aerosol generator serving to aerosolize particles found on the test specimen. The aerosol generator may operate by blowing compressed air on or in the test specimen to aerosolize and reentrain the particles either from the surface or from within the test specimen. Or aerosol generation may involve the deliberate nebulization of the sample by means of a collision nebulizer or bubble aerosol generator. Alternatively, the aerosol generator may operate by agitating the test specimen, such as by direct manipulation, and then sampling the headspace for aerosol particles that have been resuspended. In any case, once the particles are aerosolized by the aerosol generator, a suitable sample collection apparatus, such as the hose and vacuum arrangement described above, may be utilized for sample collection from the test specimen. It is notable that the test specimen may be first placed within a sampling enclosure serving to restrict generated aerosol particles to within the enclosed sampling volume. And a “test specimen” may be any physical object or sample which is the subject of inspection and testing, including, but not limited to, letters, parcels, containers, baggage, and even people, e.g. airline passengers.
Next, at block 104, the acquired sample aerosol particles are transmitted to a bipolar single particle mass spectrometer for spectral analysis, such as an aerosol time-of-flight mass spectrometer (ATOFMS) shown in
At block 105 of
Details of the normalization process for test spectra are shown in
Following the normalization of the positive test spectrum in step 203 in
Details of the substantially matching process for test spectra are shown in
Next, at step 403 “substantial similarity” between the test spectra and the database spectra of the same respective polarity is determined from the resulting similarity scores, with the determining criterion for substantial similarity being based on a similarity score threshold, also referred as a vigilance factor. For example, a predetermined positive database spectrum may be determined to be “substantially similar” to the positive test spectrum if the dot product exceeds a predetermined vigilance factor, such as 0.7. In other words, the vigilance factor is considered to be the minimum degree of similarity acceptable to call the test spectrum substantially similar to the standard. And at step 404 the names of the particle types associated with substantially matching database spectra of a given polarity are sorted in order of similarity score, such as in decreasing order, for output at step 405.
Following the finding of substantially matching positive and negative spectra at steps 204 and 205, respectively, in
Generally, if both polarities “match” spectra profiles with the same particle type, then the test spectrum is identified as that particle type, i.e. assigned that particle label. In situations encountering multiple matches within database spectra of a given polarity, then the best match is considered to be the particle type associated with the highest order similarity score for the positive spectrum that has any corresponding substantial match with the negative spectrum. For example, if there were matches of 0.8 for “Bacillus Spores” and 0.75 for “Growth Medium” for the positive spectrum and matches of 0.9 for “Growth Medium” and 0.75 for “Bacillus Spores” for the negative, then the spectrum would be identified as “Bacillus Spores”. If there is no match that matches both polarities, then the particle is labeled “Other”.
It is notable here that in the exemplary embodiment of
Upon completion of the spectrum identification algorithm of 105 in
While particular operational sequences, materials, temperatures, parameters, and particular embodiments have been described and or illustrated, such are not intended to be limiting. Modifications and changes may become apparent to those skilled in the art, and it is intended that the invention be limited only by the scope of the appended claims.
This application claims priority in provisional application filed on Oct. 25, 2001, entitled “General Aerosol Rapid Detection System” Ser. No. 60/335,598 by inventors Eric E. Gard and David P. Fergenson.
The United States Government has rights in this invention pursuant to Contract No. W-7405-ENG-48 between the United States Department of Energy and the University of California for the operation of Lawrence Livermore National Laboratory.
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