Subcellular optochemical nanobiosensors: probes encapsulated by biologically localised embedding (PEBBLEs)

Described here are arguably the world's smallest stand-alone devices/sensors, consisting of multicomponent nano-spheres with radii as small as 10 nm, occupying approximate to 1 ppb of a typical mammalian cell's volume. The probe is prepared from up to seven ingredients and is optimised for selective and reversible analyte detection, as well as sensor stability and reproducibility. Such a sensor probe encapsulated by biologically localised embedding (PEBBLE), is delivered into a cell by a variety of minimally-invasive techniques, including a pico-injector, a gene gun, liposomal incorporation and natural ingestion. These remote nano-optodes (PEBBLEs) have been prepared for pH, calcium, magnesium, potassium and oxygen. The sensor PEBBLEs can be inserted into a cell individually, in clusters (single analyte), in sets (multi-analyte) or in ensembles (single analyte, multiple locations). (C) 1998 Elsevier Science S.A. All rights reserved.