Magnetic microspheres impregnated with chromophoric dyes or Quantum Dots (QD) could be used to develop sensitive tests for chem-bio-threat agents (CB-Agent). Sensor development is further facilitated through the specific and very high affinity (Kd = 10-15M) interaction between streptavidin and biotin. A variety of magnetic microspheres (mbeads) may be impregnated with QD or dyes for barcoding. The surface of the microspheres are functionalized with streptavidin protein. Biotinylated antibodies to various chem-bio-threat agents may then be stably anchored to the mbeads. A complete "sandwich" is generated when the CB-Agent binds to the antibody followed by the binding of a second antibody that has an optical signature. The ratio of the optical signature (fluorescence, chemiluminescence or absorption) in the presence and absence of the CB-Agent is an indicator for a particular agent. Multiple antibodies anchoring to the same mbead or mixing mbeads containing several different antibodies directed toward various CB-Agents and internal barcoding confers multiplexing capabilities.
Terrorism has been called “war in the 21st Century”. There is clearly a need for a rapid, accurate, threat vector detection platform that can handle many threats, sample types and physical scales (nano-to-macro, NTM). Yet detection methods that are conventionally or currently relied upon seek to extend the traditional effort rather than develop the new methods that this new world situation requires. What is required is a new agent identification solution, capable of quickly detecting multiple threats, and a new metric to quantify the effectiveness of the new required solution. Metrics must also be adopted that allow the quantization of not only the sensitivity but the time to identify (TTI) a change in a threat state and the system design trade offs that weight the time to make an accurate identification with the threat detection level.
Sandia is developing a new battlefield adaptable agent detection platform capable of sensing multiple threat agents (chemical, biological and nuclear) simultaneously in diverse media, and a performance model of the detection platform. A new performance metric, time-to-identify (TTI), is presented, which is the time required to identify the presence of a given target analyte at an operationally-relevant concentration. This model and metric are used to predict the detection platform’s sensitivity and speed for several CONcepts of OPeration (CONOP): (1) agent detection (chemical or biological) in clinical samples, (2) botulinum toxin detection in milk, and (3) pathogen detection in airplane cabin air. Application of the model in these CONOPs indicates that the proposed platform can be optimized to reduce TTI, thereby minimizing the impact of chem-bio events. The reaction schema below chem-bio-threat agent detection using "sandwich" immunoassays:
Our crucial platform elements are sets of specialized beads and bead-handling and sensing components. Elements defining the TTI and multiplexed detection are described:
The results for detecting ovalbumin as a simulant for botulinum toxin A (BoNT/A) in raw milk are shown below:
For additional information or questions, please email us at Biosensors and Nanomaterials