The zinc(II)-protoporphyrin IX (ZnPPIX) fluorophore binds to G-quadruplexes, and this results in the enhanced fluorescence of the fluorophore. This property enabled the development of DNA sensors, aptasensors, and a sensor following telomerase activity. The DNA sensor is based on the design of a hairpin structure that includes a "caged" inactive G-quadruplex sequence. Upon opening the hairpin by the analyte DNA, the resulting fluorescence of the ZnPPIX/G-quadruplex provides the readout signal for the sensing event (detection limit 5 nM). Addition of Exonuclease III to the system allows the recycling of the analyte and its amplified analysis (detection limit, 200 pM). The association of the ZnPPIX to G-quadruplex aptamer-substrate complexes allowed the detection of adenosine-5'-triphosphate (ATP, detection limit 10 μM). Finally, the association of ZnPPIX to the G-quadruplex repeat units of telomers allowed the detection of telomerase activity originating from 380 ± 20 cancer 293T cell extract.

The anti-cocaine aptamer was fragmented into two nucleic acids, (1) and (2). The nucleic acid (1) was tethered at its 5'-end to aminoethyl nicotinamide adenine dinucleotide, amino-NAD(+), or to horseradish peroxidase, HRP. The nucleic acid (2) was functionalized at its 3'-end with alcohol dehydrogenase, AlcDH, or with glucose oxidase, GOx. In the presence of cocaine, the supramolecular NAD(+)/AlcDH/cocaine-aptamer complex is formed, and the biocatalytic oxidation of ethanol is activated. Similarly, in the presence of cocaine, the GOx/HRP/cocaine-aptamer complex is formed, and this activates the biocatalytic cascade where glucose is oxidized by GOx to yield gluconic acid and H(2)O(2), and the resulting hydrogen peroxide activates the HRP-biocatalyzed oxidation of 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate), ABTS(2-). The systems may be considered as biomimetic prototypes for systems biology.

The self-assembly of labeled aptamer sub-units in the presence of their substrates provides a method for the optical (fluorescence) or electrochemical detection of the substrate. One of the sub-units is linked to CdSe/ZnS quantum dots (QDs), and the self-assembly of the dye-functionalized second sub-unit with the modified QDs, in the presence of cocaine, stimulates fluorescence resonance energy transfer (FRET). This enables the detection of cocaine with a detection limit corresponding to 1 x 10(-6) M. Alternatively, the aptamer fragments are modified with pyrene units. The formation of a supramolecular aptamer-substrate complex allosterically stabilizes the formation of excimer supramolecular structure, and its characteristic emission is observed. In addition, the thiolated aptamer sub-unit is assembled on an Au electrode. The Methylene Blue-labeled sub-unit binds to the surface-confined fragment in the presence of cocaine. The amperometric response of the system allows the detection of cocaine with a detection limit of 1 x 10(-5) M. The approach is generic and can be applied to other substrates, e.g. adenosine triphosphate.

The luminescence of CdSe/ZnS QDs is quenched via electron transfer by hemin/G-quadruplex associated with the particles. This phenomenon is implemented to develop DNA sensors or aptasensors by tailoring hairpin-functionalized QDs that generate the hemin/G-quadruplex quenchers upon sensing of the respective analytes.

Luminescent Ag nanoclusters (NCs) stabilized by nucleic acids are implemented as optical labels for the detection of the explosives picric acid, trinitrotoluene (TNT), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The sensing modules consist of two parts, a nucleic acid with the nucleic acid-stabilized Ag NCs and a nucleic acid functionalized with electron-donating units, including L-DOPA, L-tyrosine and 6-hydroxy-L-DOPA, self-assembled on a nucleic acid scaffold. The formation of donor-acceptor complexes between the nitro-substituted explosives, exhibiting electron-acceptor properties, and the electron-donating sites, associated with the sensing modules, concentrates the explosives in close proximity to the Ag NCs. This leads to the electron-transfer quenching of the luminescence of the Ag NCs by the explosive molecule. The quenching of the luminescence of the Ag NCs provides a readout signal for the sensing process. The sensitivities of the analytical platforms are controlled by the electron-donating properties of the donor substituents, and 6-hydroxy-L-DOPA was found to be the most sensitive donor. Picric acid, TNT, and RDX are analyzed with detection limits corresponding to 5.2 × 10(-12) M, 1.0 × 10(-12) M, and 3.0 × 10(-12) M, respectively, using the 6-hydroxy-L-DOPA-modified Ag NCs sensing module.