Analytical aspects of biosensors

The aims of simplifying biochemical measurement and of extending assay reliability outside the con®nes of a central laboratory are present in many applied biology sectors, not just clinical chemistry. An increasing range of desktop analysers are commercially available that are economical both of sample and of operator time. A common theme running through many approaches is the exploitation of biological reagents, with the ultimate in simpli®cation being integration of biological and measurement elements into a simple, monolithic device. This is the basic concept of the biosensor, a biological sample-interactive phase in close contact with a physical or chemical transducer. A typical biosensor construct has three features ± a recognition element, a signal transducing structure and an ampli®cation/processing element (see Fig. 1). Various transduction mechanisms have been used: electrochemical, electrical, optical, thermal and piezoelectric, as summarized in Table 1. Most commonly, in a biosensor, a biorecognition phase (e.g. enzyme, antibody, receptor, single-stranded DNA) interacts with the analyte of interest to produce some chargebased or optical change at the local sensor± transducer interface. Through signal processing this interaction is converted into digital values that relate to the build-up of concentration or activity of the analyte in the vicinity of the device, which in turn relates to the ambient levels in the bulk sample under investigation. A biosensor is not necessarily a stand-alone entity, but should be considered as part of a general development in instrumentation, designed to address generic medical and non-medical measurement science problems. Biosensors, when deployed in a clinical setting, offer the advantage of extra-laboratory analysis of a variety of relevant substances, including hormones, drugs of abuse and metabolites (both in vivo and in vitro). Continuous realtime monitoring of analytes is also a possibility; for example, monitoring of metabolites in blood (where the sample matrix is inevitably optically opaque) in the critical care situation. Generally, biosensors permit the use of low cost, `clean’ technologywith reduced requirements for sample pre-treatment and large sample volume; ultimately, the user can be someone without prior laboratory skills. The `niche’ application is therefore extra-laboratory testing, as realized with conventional dry reagent dipsticks. This review provides basic descriptions of the main subtypes of biosensorwith an indication of their operational capability from a clinical chemistry perspective. Owing to a greater appreciation of the capabilities and limitations of biosensors and new input from the microfabrication and materials science ®elds, the direction of biosensor research is undergoing rapid change. The descriptions that follow are intended to re ect this change and illustrate the shift in emphasis from a preoccupation with bioreagent immobilization and chemistry to a renewed effort towards total system integration. A functionally ef®cient juxtaposition of sample and sensor remains essential for proper function, and the descriptions given provide some relevant examples.