The design principles of fluorescence-based siderophore sensor molecules for detection of heavy transition-metal (HTM) ions are first reviewed. As an example, fluorescein-desferrioxamine (FlDFO), a highly efficient fluorophore molecule combining a specific Fe ion receptor and a fluorescence-sensitive signalling site has been designed, synthesized, and used for dosing with Fe ions. Its response test shows its high selectivity and sensitivity to Fe III ions and its potential for nanobiosensor design. This work clearly identified that among two FlDFO positional isomers differing by the attachment of DFO at the 5-or 6-position of the bottom benzene ring of Fl, the fluorescence of 6-FlDFO is insensitive to the complexation with Fe ions. This is independent of the linkage used between Fl and DFO. Only 5-FlDFO could be a highly potential sensor molecule since it has been revealed that in a free state without complexation with Fe ions, this fluoroionophore sensor molecule gave a maximum fluorescent signal. With successive Fe ion complexing, the fluorescence of 5-FlDFO decreased very sensitively and proportionally with ion concentration. The response speed has been evaluated as a function of Fe ion concentration. Responses to other metal ions present in the solution, such as Cu 2+ , Ca 2+ , Ni 2+ , and Al 3+ , and the effect of pH value on the efficiency of the sensor molecules have also been investigated.processes. Furthermore, some metal ions such as mercury, lead, and cadmium are known to be toxic for the organisms. Early detection in the environment is becoming a priority for society.The quantification of metal ions can be achieved by a series of chemical and analytic methods such as colorimetry, flame photometry, UV-vis spectrophotometry, atomic absorption spectrometry, ion-sensitive electrodes (ISEs), electron microprobe analysis, neutron activation analysis, inductively coupled plasma-mass spectrometry (ICP-MS), etc. However, these methods have certain shortcomings because they are generally expensive and voluminous and often require samples of large size and sometimes the destruction of the samples. Furthermore, these methods do not allow continuous monitoring.The development of sensitive and selective fluorescent nanosensors for dosing with heavy transition-metal (HTM) ions has recently attracted great attention due to their importance in the fields of environ mental monitoring, clinical toxicology, wastewater treatment, and industrial process monitoring [1][2][3][4]. The principle advantages of this technology rely on its high sensitivity, which allows easy measurement of low analyst concentrations and its selectivity due to the excitation and emission wavelengths of each fluorescent species [1][2][3][4]. Fluorescent organic chelators, proteins, and peptides have emerged as powerful receptors for dosing with HTM ions, and remarkable progress has been made in developing fluorophore molecules for metal ions such as Ca ++ , Zn ++ , Pb ++ , Hg ++ , Cu ++ , and Ag + ions [5][6][7][8][9][10][11][12][13][14][15][16][17...