Conventional biosensors and bioehips rely on a "lock-and-key" recognition principle, for which specific ligands, such as aptamers, antibodies, or mimetics are needed. In contrast, electronic nose/tongue devices (eN/eT) use the differential binding of analytes, either alone or in mixtures, to an array of cross-reactive receptors (CRRs) whose combined responses create a characteristic pattern for each component. As a result, none of the CRRs need to be highly specific for any given analyte and the time-consuming design and generation of specific sensors may be circumvented. Based on this principle, CRR arrays associated with appropriate detection have been developed. For example, synthetic tetraphenylporphyrin derivatives, whose fluorescence quenching upon protein binding was used for detection, or a receptor library, integrating a peptide cavity coupled with indicator-uptake colorimetric detection, were developed for protein sensing above concentrations of ten micromolar. A sensor array composed of gold nanoparticles, grafted with different amino-functionalized thiols and conjugated with an anionic fluorescent polymer (poly(p-phenyleneethynylene. PPE), allowed detection of proteins in the low nanomolar range, as well as detection of bacteria or discrimination oi normal cells from their cancerous counterparts. Furthermore, replacing PPE with green fluorescent protein led tc a concentration-sensitive CRR array able to discriminate different proteins in human serum at physiologically relevant concentrations.
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