To the flexible tripod platform tren (tris(2-aminoethyl)amine), a Rhodamine and two naphthalene fluorophores were introduced. The resulting fluorescence probe named TRN was fully characterized and employed in cell imaging. Probe TRN exhibited high selectivity and excellent sensitivity for the simultaneous fluorescence detection of Zn 2+ / Hg 2+ / Al 3+ / Cu 2+ . The significant changes in the fluorescence color make naked-eye detection possible. Furthermore, fluorescence imaging experiments of Zn 2+ / Hg 2+ / Al 3+ / Cu 2+ in living PC3 cells demonstrated its value for practical applications in biological systems.Key words: flexible tripod probe, Zn 2+ / Hg 2+ / Al 3+ / Cu 2+ ions detection, cells imaging increasing demands for sensors in these fields. Among these, the metal ion s of mercury, zinc, aluminium and copper are synonymous with various prominent neurological conditions and biological processes. For instance, mercury is a well-known human toxin, capable of serious harm to the skin, nervous and renal systems even at very low levels [1][2][3][4] . Zinc is the second most abundant transition-metal ion and plays important roles in a variety of physiological and pathological processes [5][6][7] , and disorder associated with zinc metabolism in biological systems may lead to a variety of diseases such as Alzheimer's disease, diabetes, epilepsy [8][9][10][11] . Moreover, Al 3+ has been associated with conditions such as neuro dementia, Parkinson's disease, Alzheimer's disease and dialysis encephalopathy. Copper ions, as the third most abundant essential trace element after iron and zinc in the human body, also play an important role in various physiological and enzymatic processes [12][13][14] , such as in transforming melanin in skin pigments, assisting cross-linking in collagen, as well as tissue maintenance and repair [15][16][17] . Excessive copper is also toxic and a major cause for oxidative stress and disorders associated with neurodegenerative diseases including Alzheimer's, Parkinson's, Menkes, Wilson's and prion diseases [18][19][20] . Thus, there is an urgent need to develop sensors capable of detecting low concentrations of Hg 2+ , Al 3+ , Zn 2+ and Cu 2+ ions in biological samples.Fluorescent probes are ideal candidates for both the detection and monitoring of metal ions in a wide variety of samples. This is due to their high sensitivity, fast response, and ability to provide in situ and real-time information with high spatial-temporal resolution, and non-destructive detection. During the past two decades, many fluorescent probes have been developed for a variety of biological ly and environment ally related targets. However, most of the fluorescent probes that have been reported are of two-or three-ion sensor types that detect for example Fe 3+ / Cu 2+ [21] , Ba 2+ / Hg 2+ [22] , Zn 2+ / Cd 2+ [23] , Cu 2+ / Hg 2+ [24, 25] , Pb 2+ / Hg 2+ [26] , Zn 2+ / Hg 2+ / Cu 2+ [27] , Cu 2+ / Cysteine [28] , Zn 2+ / Cd 2+ / Hg 2+ [29] , Cr 3+ / Al 3+ / Fe 3+ [30, 31] . However, it remains a great ch...