Biodefense Applications

Today's modern sensors enable such wide ranging applications as detection of chemical warfare agents, toxic industrial chemicals (TICs) and select agent pathogens.

We have developed technologies around the differential mobility spectrometer (DMS) to be used for advanced threat detection purposes. Sample introduction plays a large role in effective threat determination with any analytical sensor. One method we have used is the pyrolysis technique to analyze biological samples such as endospores, viruses, bacteria and proteins. The cartoon below shows how this process uses heat to deconstruct biological materials into their small constituent building blocks. [from our paper: Krebs MD, Zapata AM, Nazarov EG, Miller RA, Costa IS, Sonenshein AL, Davis CE*. (2005) Detection of biological and chemical agents using differential mobility spectrometry (DMS). IEEE Sensors Journal, Special Edition on Anti-Terrorism 5(4): 696-703.]

When this pyrolysis technique was applied to Bacillus spore samples, we were able to detect differences between endospore species. Below are representative results of principal component analysis for 80,000 spores per sample, 100 samples for each species. [from our paper: Krebs MD, Mansfield B, Yip P, Cohen SJ, Sonenshein AL, Hitt B, Davis CE*. (2006) Spore biomarkers differentiate between closely-related Bacillus species using differential mobility spectrometry. Biomolecular Engineering 23(2): 119-127.]

After applying genetic algorithms to the spectra, we found that some classification features within the signal produce strong differentiation between spore species groups. For example, this feature (below) shows a large difference in raw signal amplitude between B. subtilis and B. thuringiensis -- even when the total spore count is quite low (5k). [from our paper: Krebs MD, Mansfield B, Yip P, Cohen SJ, Sonenshein AL, Hitt B, Davis CE*. (2006) Spore biomarkers differentiate between closely-related Bacillus species using differential mobility spectrometry. Biomolecular Engineering 23(2): 119-127.]

We have also performed experiments using simulant chemical weapon detection with the DMS. The figure below shows: (a) DMS spectra of varying concentrations of MS. The signal intensity is shown as a function of the compensation voltage. (b) DMS signal peak area as a function of mass of MS introduced. Amount of compound introduced corresponds to concentrations ranging from 344 ppb to 45 ppt. Also shown is the molecular structure of MS. (c) DMS spectra of MS and DMMP. Spectra were collected sequentially. (d) Simultaneous detection of nerve and blister agent simulants DMMP and MS. A mixture of DMMP and MS is graphed with signal intensity as a function of compensation voltage (solid line). The spectrum for MS (dashed line) is shown again for reference. [from our paper: Krebs MD, Zapata AM, Nazarov EG, Miller RA, Costa IS, Sonenshein AL, Davis CE*. (2005) Detection of biological and chemical agents using differential mobility spectrometry (DMS). IEEE Sensors Journal, Special Edition on Anti-Terrorism 5(4): 696-703.]

Finally, we have also used the DMS as a way to examine exogenous chemicals found in exhaled breath. We constructed a custom electrospray ionization interface to evaluate a wide range of exhaled breath compounds. [from our paper: Davis CE*, Bogan MJ, Sankaran S, Molina MA, Loyola BR, Zhao W, Benner WH, Schivo M, Farquar GR, Kenyon NJ, Frank M. (2010) Volatile and non-volatile analysis of biomarkers in human breath using differential mobility spectrometry. IEEE Sensors Journal special issue "Sensors for Breath Analysis" 10(1): 114-122.]

Using this ESI/DMS analysis method, we could determine the presence of exogenous compounds in breath down to extremely low concentration levels. [from our paper: Davis CE*, Bogan MJ, Sankaran S, Molina MA, Loyola BR, Zhao W, Benner WH, Schivo M, Farquar GR, Kenyon NJ, Frank M. (2010) Volatile and non-volatile analysis of biomarkers in human breath using differential mobility spectrometry. IEEE Sensors Journal special issue "Sensors for Breath Analysis" 10(1): 114-122.]