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Appendix A: Evaluating Detector Signals
Pages 69-78

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From page 71...
... In the section, this simplified illustration of instrument response as a function of target concentration will be exploited to discuss aspects of performance testing for determining minimum detectable concentration in terms of BAULA units. We acknowledge here that in practice instrument response, R(c)
From page 72...
... Consider a procedure for determining a test instrument's detection threshold in BAULA consisting of: • an idealized referee system that accurately measures active agent in a sample; • a test instrument that uses a nucleic acid detection scheme that accurately senses the number of genome equivalent (GE) copies of the target agent to determine agent concentration with an inherent detection limit of 20 GE; and • a target agent pathogenic enough that 1 active organism or molecule exposure or dosage is the LD50.
From page 73...
... Assuming that the intrinsic GE copy detection capability is 20, then the sensor limit of detection would be empirically estimated to be 8 BAULA. In summary, as we decrease the ratio of inactive target agent to active agent from 1:2 in Case 1 to 2:1 in Case 2, the instrument's apparent minimum detectable concentration in BAULA, as experimentally estimated by a perfect referee system at the location of the test instrument, goes from 16 to 8.
From page 74...
... We introduce a matrix construct to help generalize to the different instruments that DOD currently and will potentially test. For a specific target agent define three variables: • A as the concentration of active agent at the referee (and test instrument)
From page 75...
... The referee system estimates and, therefore, the matrix reduces to one experiment: aAk + nNk = Λk As expected, the minimum concentration threshold is biased by a noise term nNk, and scaled by a, which can be interpreted as an instrument efficiency parameter. Since the noise term cannot be removed without a second experiment, it is necessary to change the Ak / Ik ratio and repeat the series of dilutions for the new Ak concentration of target agent and with nonzero inactive component Ik.
From page 76...
... Just as we added previously active agent and compensated for it, we could add columns that represent optical cross-section for a specific wavelength of light, antigen binding, etc. Basically any parameter that the referee estimates can be introduced into the matrix to organize calculation of the limit of detection.
From page 77...
... As before, a series of three experiments is sufficient to solve for a, i, and nNk uniquely. Using this series for the GE test instrument that is biased by a near neighbor contaminant (Λ is increased by 10 in each experiment)


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