Whole Cell Biosensors

to obtain functi does this substance act on other aspects of cellular metabolism, such as second messenger pathways, or enzymes? Cholera or pertussis toxins act on G proteins, for instance. Recognizing this action on cellular metabolism would be a general screen of agents of this type. is this substance toxic to cells? This question can be answered by monitoring bacterial cells, but more recently methods to use mammalian cells have also been investigated [3-51. The advantage of using mammalian cells is that those are a closer proxy to the toxicity in humans than bacteria. is this environmental sample polluted? This is to some extent an analytical question, but the ultimate issue of damage to the environment is a functional one. Biosensors based on a bacterial component have been used for a long time in this application; for recent reviews see Refs. [6,7]. Measurements such as biological oxygen demand (BOD) [8,9] or mutagenicity [IO] are by definition functional rather than analytical. The second reason to use a living component is to obtain analytical information, whether quantitative or qualitative. In its simplest form it tells us whether a given substance is present, and in what concentration. Cells with a given type of receptor can be considered as sensors for agonists, with a sensitivity related to the binding constant of that receptorAigand combination [ 1,111. Another large body of work uses bacteria, often genetically engineered to respond to specific substances. Examples are the detection of herbicides [ 121, naphtalene and salicylate [ 131, benzene [14], alcohol [15] trimethylamine gas [16], and various heavy metals [7]. It is important to note, however, that one of the advantages invoked for the use of cells in environmental applications is that it allows the measurement of the total bioavailability of a given pollutant rather than its free form [7,13]. For instance, a bioluminescent bacteria detector specific for copper also detects insoluble copper sulfide [7]. Thus, the analytical question really becomes a functional one, namely how bioavailable is a given substance. When used for environmental applications, a further potential advantage of biosensor devices is that they are capable of continuous monitoring, and can be made small enough to use in the field. The main potential problem is the handling and lifetime of the living component.