Choosing an analytical methods requires a consideration of three potential limitations: the amount of sample available for the analysis, the expected concentration of analyte in the samples, and the minimum amount of analyte that will produce a measurable signal. Collectively, these limitations define an analytical method’s scale of operations, as shown here.
The x-axis gives the sample’s size and the y-axis provides the analyte’s concentration. For convenience, we divide samples into macro (>0.1 g), meso (10 mg–100 mg), micro (0.1 mg–10 mg), and ultramicro (<0.1 mg) sizes, and we divide analytes into major (>1% w/w), minor (0.01% w/w–1% w/w), trace (10-7% w/w–0.01% w/w), and ultratrace (<10‑7% w/w) components. The analyte’s concentration and the sample’s size provide a characteristic description for an analysis. For example, in a microtrace analysis the sample weighs between 0.1 mg–10 mg and contains a concentration of analyte between 10–2% w/w and 10–7% w/w.
The diagonal lines connecting the two axes show combinations of sample size and analyte concentration containing the same mass of analyte. For example, a 1-g sample that is 1% w/w analyte has the same amount of analyte (10 mg) as a 100-mg sample that is 10% w/w analyte, or a 10-mg sample that is 100% w/w analyte.
We can use this scale of operations to establish limits for analytical methods. If a method’s minimum detectable signal is equivalent to 10 mg of analyte, then it is best suited to a major analyte in a macro or meso sample. Extending the method to an analyte with a concentration of 0.1% w/w requires a sample of 10 g, which is rarely practical due to the complications of carrying such a large amount of material through the analysis. On the other hand, small samples containing trace amounts of analyte place significant restrictions on an analysis. For example, 1-mg sample with an analyte present at 10–4% w/w contains just 1 ng of analyte. If we can isolate the analyte in 1 mL of solution, then we need an analytical method that can reliably detect it at a concentration of 1 ng/mL.
