Probability of real-time detection versus probability of infection for aerosolized biowarfare agents: a model study.

Real-time biosensors are expected to provide significant help in emergency response management should a terrorist attack with the use of biowarfare, BW, agents occur. In spite of recent and spectacular progress in the field of biosensors, several core questions still remain unaddressed. For instance, how sensitive should be a sensor? To what levels of infection would the different sensitivity limits correspond? How the probabilities of identification correspond to the probabilities of infection by an agent? In this paper, an attempt was made to address these questions. A simple probability model was generated for the calculation of risks of infection of humans exposed to different doses of infectious agents and of the probability of their simultaneous real-time detection/identification by a model biosensor and its network. A model biosensor was defined as a single device that included an aerosol sampler and a device for identification by any known (or conceived) method. A network of biosensors was defined as a set of several single biosensors that operated in a similar way and dealt with the same amount of an agent. Neither the particular deployment of sensors within the network, nor the spacious and timely distribution of agent aerosols due to wind, ventilation, humidity, temperature, etc., was considered by the model. Three model biosensors based on PCR-, antibody/antigen-, and MS-technique were used for simulation. A wide range of their metric parameters encompassing those of commercially available and laboratory biosensors, and those of future, theoretically conceivable devices was used for several hundred simulations. Based on the analysis of the obtained results, it is concluded that small concentrations of aerosolized agents that are still able to provide significant risks of infection especially for highly infectious agents (e.g. for small pox those risk are 1, 8, and 37 infected out of 1000 exposed, depending on the viability of the virus preparation) will remain undetected by the present, most advanced, or even future, significantly refined real-time biosensors.

[1]  J. Mandel,et al.  Ultrasensitive quartz crystal microbalance sensors for detection of M13-Phages in liquids. , 2001, Biosensors & bioelectronics.

[2]  Jerome Hauer,et al.  Tularemia as a biological weapon , 2001 .

[3]  Philip K. Russell,et al.  Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. , 1999, JAMA.

[4]  Steven Buchsbaum An introduction to the Homeland Security Advanced Research Projects Agency (HSARPA) , 2004 .

[5]  M Jantunen,et al.  Fine PM measurements: personal and indoor air monitoring. , 2002, Chemosphere.

[6]  Petr I. Nikitin,et al.  Surface plasmon resonance interferometry for biological and chemical sensing , 1999 .

[7]  John M. Walker,et al.  Molecular Biology and Biotechnology , 1988 .

[8]  Jose Melendez,et al.  Detection of Staphylococcus aureus enterotoxin B at femtomolar levels with a miniature integrated two-channel surface plasmon resonance (SPR) sensor. , 2002, Biosensors & bioelectronics.

[9]  W. Petrich MID-INFRARED AND RAMAN SPECTROSCOPY FOR MEDICAL DIAGNOSTICS , 2001 .

[10]  Joseph Wang SURVEY AND SUMMARY From DNA biosensors to gene chips , 2000 .

[11]  V. A. Nefedov,et al.  Detection of trace amounts of explosives and/or explosive related compounds on various surfaces by a new sensing technique/material , 2004 .

[12]  Stephen J. Martin,et al.  Acoustic Wave Microsensors , 1993 .

[13]  Didier Raoult,et al.  Diagnosis of Q Fever , 1998, Journal of Clinical Microbiology.

[14]  K. C Schuster,et al.  FTIR SPECTROSCOPY APPLIED TO BACTERIAL CELLS AS A NOVEL METHOD FOR MONITORING COMPLEX BIOTECHNOLOGICAL PROCESSES , 1999 .

[15]  Barbara Johnson OSHA Infectious Dose White Paper , 2003 .

[16]  Philip K. Russell,et al.  Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. , 1999, JAMA.

[17]  César Milstein,et al.  Man-made antibodies , 1991, Nature.

[18]  M. S. Zubairy,et al.  FAST CARS: Engineering a laser spectroscopic technique for rapid identification of bacterial spores , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  D F Doyle,et al.  Gas phase activity of anti-FITC antibodies immobilized on a surface acoustic wave resonator device. , 2002, Biosensors & bioelectronics.

[20]  S. Peto,et al.  A Dose-Response Equation for the Invasion of Micro-Organisms , 1953 .

[21]  A. Madonna,et al.  Detection of cyclic lipopeptide biomarkers from Bacillus species using atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry. , 2003, Analytical chemistry.

[22]  V K Gupta,et al.  Optical amplification of ligand-receptor binding using liquid crystals. , 1998, Science.

[23]  Jay W. Grate,et al.  Acoustic Wave Microsensors PART II , 1993 .

[24]  J Wang,et al.  From DNA biosensors to gene chips. , 2000, Nucleic acids research.

[25]  Noble,et al.  Real-time single particle mass spectrometry: a historical review of a quarter century of the chemical analysis of aerosols , 2000, Mass spectrometry reviews.

[26]  Philip K. Russell,et al.  Botulinum toxin as a biological weapon: medical and public health management. , 2001, JAMA.

[27]  Günter Gauglitz,et al.  Surface plasmon resonance sensors: review , 1999 .

[28]  J J Valdes,et al.  Recombinant antibodies: a new reagent for biological agent detection. , 2000, Biosensors & bioelectronics.

[29]  Gina Pugliese,et al.  Plague as Biological Weapon , 2000, Infection Control & Hospital Epidemiology.

[30]  Jerome Hauer,et al.  Anthrax as a biological weapon, 2002: updated recommendations for management. , 2002, JAMA.

[31]  E Raber,et al.  Decontamination issues for chemical and biological warfare agents: How clean is clean enough? , 2001, International journal of environmental health research.

[32]  R. Press,et al.  Quantitative real-time PCR with automated sample preparation for diagnosis and monitoring of cytomegalovirus infection in bone marrow transplant patients. , 2004, Clinical chemistry.

[33]  Igor Babkin,et al.  Species-Level Identification of Orthopoxviruses with an Oligonucleotide Microchip , 2002, Journal of Clinical Microbiology.

[34]  L. Laricchia-Robbio,et al.  Comparison between the surface plasmon resonance (SPR) and the quartz crystal microbalance (QCM) method in a structural analysis of human endothelin-1. , 2004, Biosensors & bioelectronics.

[35]  Philip K. Russell,et al.  Tularemia as a biological weapon: medical and public health management. , 2001, JAMA.

[36]  Jian Zhang,et al.  Comparison of surface plasmon resonance spectroscopy and quartz crystal microbalance for human IgE quantification , 2004 .

[37]  Thomas W Graham,et al.  Journal of Homeland Security and Emergency Management How Much Is Enough : Real-Time Detection and Identification of Biological Weapon Agents , 2011 .

[38]  Vladimir M. Doroshenko,et al.  Recent developments in atmospheric pressure MALDI mass spectrometry , 2002 .

[39]  George G. Guilbault,et al.  Commercial quartz crystal microbalances-Theory and applications , 1999 .

[40]  Philip K. Russell,et al.  Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. , 2000, JAMA.

[41]  G. M. Richardson,et al.  Probability Density Functions Describing 24-Hour Inhalation Rates For Use in Human Health Risk Assessments , 1998 .

[42]  Bettina Warscheid,et al.  Characterization of Bacillus spore species and their mixtures using postsource decay with a curved-field reflectron. , 2003, Analytical chemistry.