This paper reviews the field of biosensors in which the biological com
ponent consists of living cells. One of the most important reasons for
using living cells is to obtain functional information, i.e. informat
ion about the effect of a stimulus on a living system. In many cases,
functional rather than analytical information is ultimately desired. W
hole-cell biosensors provide the opportunity to elicit such informatio
n, for applications such as pharmacology, cell biology, toxicology, an
d environmental measurements. One particularly important application i
s drug discovery, where the binding assays that are commonly used to p
rovide high throughput need to be complemented with a functional assay
. A micromachined silicon chip that is capable of providing a high thr
oughput functional assay based on extracellular acidification is descr
ibed.