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RESEARCH FEATURES Autofuorescence-free biological imaging A new class of photon-upconvertng nanopartcles has emerged as luminescent probes for biological imaging with substantally diminished background noise Introducton Over the past decade, the feld of optcal imaging has witnessed a rapid growth in using luminescent labels to unravel the complexites of cell signalling, neuroscience and cancer. Despite various microscopic techniques being available, it remains a big challenge to identfy a collecton of suitable luminescent probes that Figure 1: Typical luminescent materials for biological imaging. In a typical Stokes- meet biologists’ increasing demand for shifed imaging, an organic dye (Lef panel) or a quantum dot (Middle panel) is microscopy. Stokes-shifed materials used as the probe to generate visible light (Vis) with the excitaton of an ultraviolet (e.g. organic fuorophores, quantum (UV) or Vis light. (Right panel) For upconversion imaging, a lanthanide-doped dots and carbon dots) are generally nanopartcle is excited by near-infrared light, followed by visible emission. used as imaging probes. Unfortunately, typically consists of an inorganic host of an energy migraton process in host these commonly used imaging probes and lanthanide dopants embedded latces, the upconversion emission ofen sufer from limited brightness in the host latce. In general, the comes from a broad range of lanthanide and photo-stability, which are not upconversion emission originates from actvators. This includes Tb , Eu , 3+ 3+ suitable for long-term imaging studies. the electronic transiton within the 4f n Dy , Sm , Ce and Mn . In a follow- 3+ 3+ 2+ 3+ In additon, high energy light (typically confguratons of lanthanide dopants. up work, this energy migraton process ultraviolet or the blue end of the has been proven to be efectve in Tb - 3+ visible spectrum) required to excite There are signifcant research eforts on based nanopartcles. Unfortunately, these probes may cause unwanted upconversion on the emission tuning almost all of these nanopartcles rely on background fuorescence from of lanthanide-doped nanopartcles. oil-based synthetc approaches, which biological molecules and induce photo- We are able to design and synthesise makes the resultng nanopartcles damage to the biological tssues (see upconversion nanopartcles to display unsuitable for biological applicatons. Figure 1). a wide range of colours from a single wavelength excitaton. As the emission Our recent research breakthrough Lanthanide-doped upconversion comes from the lanthanide dopant, shows that the combinaton of nanopartcles that can convert one commonly used approach is to caton exchange reacton and energy near-infrared (NIR) excitaton into have diferent combinatons and migraton can provide a simple visible emissions have emerged as a concentratons of dopants to produce method for the multcolour synthesis promising luminescent alternatve (see multcolour emissions. Some host of partcles in water, opening a new Figure 1). In additon to their inherent materials can exchange excitaton avenue for potental applicatons in nature of high chemical stability and energy with dopants. Manipulaton of bioimaging. low cytotoxicity, these nanopartcles host matrices provides another way of exhibit unique optcal propertes modulatng emissions. However, these Biomedical Applicatons such as large ant-Stokes shif, narrow colour tuning strategies are limited to emission bandwidths, long lifetmes only Er , Tm , and Ho ions. The use of upconversion nanopartcles 3+ 3+ 3+ and high photo-stability. Furthermore, for bioimaging enables non-invasive the near-IR excitaton for photon My group has invented a new type detecton and real-tme visualisaton of upconversion ofers high penetraton of photon upconversion process many important biological processes depth in biological tssue, with less called “energy migraton-mediated within a living organism. Over the photo damage to the biological sample upconversion” to solve this issue. past 10 years, considerable eforts and minimal autofuorescence [1]. It uses a gadolinium-based core- have been devoted to developing shell nanopartcle, in which a upconversion nanoprobes for a Partcle Design for Multcolour set of lanthanide ions at defned diverse range of biological applicatons Emission concentratons is incorporated into the ranging from high sensitvity molecule diferent layers. By taking advantage detecton to cellular imaging, deep- An upconversion nanopartcle ADVANCES IN SCIENCE | VOL. 22 | NUMBER 1 | JUNE 2017 8
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