Sensitivity and detection limit: How ‘little’ of a substance can still be detected?

Sensitivity and the limit of detection (LOD) are two parameters that are often confused, yet are in fact distinct. Sensitivity refers to an instrument’s ability to respond to changes in the concentration of a target substance—in layman’s terms, how much of a signal change a given small change in concentration produces. The stronger and more stable the response, the higher the sensitivity, and the steeper the slope of the corresponding calibration curve. The limit of detection, on the other hand, is the lowest concentration or quantity that an instrument can ‘still reliably detect’; it is usually defined as the quantity corresponding to a signal that is a certain multiple (e.g. three times) higher than the background noise.

The two are closely related but have different focuses: high sensitivity means that even minute quantities can generate a distinct signal; a low detection limit means that the lower limit at which the presence of a substance can be confirmed is lower. To ensure that trace substances can be ‘detected and measured accurately’, both high sensitivity and low noise (a good signal-to-noise ratio) are required — therefore, the detection limit is essentially determined by both sensitivity and noise. This is why simply amplifying the signal is not sufficient; background suppression and ion suppression must also be carried out simultaneously.

In the field of online analysis, Neo Source INSTRUMENT’s ProC series of online time-of-flight mass spectrometers, when combined with flue gas/ in-situ analysis systems, with a nominal sensitivity of 10 ppb (parts per billion). Combined with a high-transmission-efficiency ion lens and an MCP detector (10⁶ gain), they can perform quantitative detection of analytes in the ppb concentration range in ambient air, with a wide dynamic range.

In the field of mass spectrometry imaging, sensitivity is enhanced by eliminating polarity discrimination and supplementing ionisation. Compared to conventional DESI, MSI DPI (DESI+PI) increases signal intensity by 1–4 orders of magnitude; typical examples include a 205-fold increase in cholesterol in rat brains, a 14.5-fold increase in theanine in tea leaves, and a 61-fold increase in caffeine; MSI LDPI offers a signal enhancement of 1–3 orders of magnitude compared to simple laser ablation, with a minimum detectable mass-to-charge ratio as low as approximately 70. This substantial improvement in sensitivity means that more trace metabolites can now be clearly detected rather than remaining undetectable. Both sources can be fitted to mass spectrometers from Agilent, AB SCIEX and Thermo.