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Lower Limit of Detection

The lower limit of detection (LLOD) is the smallest amount of an analyte that can reliably be detected. LLOD is also called analytic sensitivity. In practical terms, LLOD is the lowest level of analyte that can be statistically distinguished from a blank sample. LLOD is a function of the variability of the blank sample and the sensitivity of the assay.

A zero calibrator is often used for the blank sample because it is difficult to find patient samples totally lacking the analyte of interest. The zero calibrator is tested 20 times within the same run and the mean and standard deviation of the results are calculated. LLOD is considered to be 3 standard deviations above the mean of the blank. Using this formula the chance of misclassification is 7%. If 2 standard deviations are used the chance of misclassification is 16%.

Another way to validate LLOD is to run the blank sample 20 times. Fewer than 3 of the results should exceed the manufacturer's published analytic sensitivity. Then, 20 patient samples containing the analyte at a concentration slightly above the manufacturer's stated analytic sensitivity are run. If at least 17 of them are above the blank value, the manufacturer's LLOD can be accepted.

Once the LLOD has been established, all patient values measuring less than the LLOD should be reported as "less than the LLOD value" rather than a finite value. Patient values below the LLOD cannot be reliably differentiated from zero. For example, the LLOD for serum ethanol may be 5 mg/dL. If a patient result is measured as 4 mg/dL, it should be reported as <5mg/dL. The method is not sensitive enough to determine if the result is really 4 or zero. 

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