Luminescent bioassay techniques have been widely adopted in a variety of research and medical institutions. However, conventional luminescent bioassays utilizing traditional bioprobes like organic dyes and quantum dots often suffer from the interference of background noise from scattered lights and autofluorescence from biological matrices. To eliminate this disadvantage, the use of inorganic lanthanide (Ln 3+ )-doped nanoparticles (NPs) is an excellent option in view of their superior optical properties, such as the long-lived downshifting luminescence, near-infrared triggered anti-Stokes upconverting luminescence and excitation-free persistent luminescence. In this review, we summarize the latest advances in the development of inorganic Ln 3+ -doped NPs as sensitive luminescent bioprobes from their fundamental physicochemical properties to biodetection, including the chemical synthesis, surface functionalization, optical properties and their promising applications for background-free luminescent bioassays. Future efforts and prospects towards this rapidly growing field are also proposed.
INTRODUCTIONSensitive and specific bioassay of trace amount of target analytes is essential for a variety of biomedical applications ranging from pharmaceutical preparation to disease diagnosis and therapy [1][2][3]. Among various bioassay methods, luminescent bioassay has received particular attention because of its high sensitivity and good specificity [4,5]. Conventional luminescent bioassay techniques such as enzyme-linked immunosorbent assay (ELISA), time-resolved (TR) fluoroimmunoassay (TRFIA), Förster resonance energy transfer (FRET) and TR-FRET assays have laid the foundation for many modern clinical applications [6][7][8][9][10][11]. However, these bioassays are impeded by the availability of traditional bioprobes like organic dyes, lanthanide (Ln 3+ ) chelates and quantum dots (QDs). The use of these bioprobes has a number of limitations. Organic dyes commonly possess poor photochemical stability and suffer from serious photobleaching [12]. The applicability of QDs is compromised by photoblinking and high toxic- ity of heavy metal elements like cadmium and selenium, especially for in vivo biosensing [13,14]. Moreover, both organic dyes and QDs may induce high background noise and considerable photodamage to the biological samples under ultraviolet (UV) excitation, which deteriorates their detection sensitivity for bioassays [15,16]. Although such background noise can be suppressed by the technique of TR photoluminescence (PL) through the use of the longlived luminescence of Ln 3+ -chelates, the poor photochemical stability, long-term toxicity and high cost of Ln 3+ -chelates remain a major issue [17]. These concerns fuel a crucial demand for the development of a new generation of luminescent bioprobes to circumvent the limitations of traditional ones.Recently, with the explosion of nanoscience and nanotechnology, there is a growing dedication towards the development of diverse luminescent nanoprobes for biodetection ...