Endocrine Abstracts

“Ligand” (or “binding”) assays – a class of methods of which for many years immunoassay long constituted the most widely used example – were first applied (in the late 50 s/early 60 s) to measurements of hormone concentrations in body fluids, but were later extended to the assay of other substances present in samples at low concentrations. This presentation reviews the main developments in this field, including those presently occurring (which are likely to revolutionize medical research and diagnosis in the next decade). The history of these methods evolution may be divided into three principal stages:

i. the development of “competitive” assays, relying on observation of what is viewed as a competition between the analyte and a labelled analogue for a limited amount of a specific binding agent (e.g. antibody);

ii the emergence of ultrasensitive “non-competitive” assays, relying on observation of the binding of the specific binding agent (labelled, and widely thought to be optimally present in large excess vis-à-vis the target analyte) which now dominate the field;

iii the current development of miniaturized microarray-based assay methods relying on the use of arrays of “microspots”, each comprising a minute area of a specific binding agent located on a solid support.

Amongst factors which have contributed to these techniques’ widespread use are their ubiquity, simplicity, sensitivity and speed. Surprisingly, their development has nevertheless often been impeded by misunderstandings regarding fundamental concepts such as assay sensitivity, precision and accuracy, some of these terms’ meanings remaining controversial. Other misconceptions have centred on the difference between “analytical” and “comparative” assays. Such misunderstandings have greatly influenced views on assay design, delaying recognition of, e.g., the usefulness of monoclonal antibodies, and the feasibility of ultrasensitive microarray methods.

This presentation will attempt to clarify these misconceptions in tracing the development of the ligand assay field over the past 50 years.