Luminescence Technology Research Articles

Non-Invasive In Vivo Bioimaging in Pigs

Imaging technologies are used to observe the morphology and function of various organs in the body and have become indispensable in a multitude of fields, ranging from basic research to clinical medicine. The luminescence technology based on the luciferin–luciferase reaction has been used in many research fields as an imaging technique, enabling quantitative analysis and detection at high sensitivity. Specifically in gene therapy and cell therapy, it has been developed as an in vivo bioimaging technique mainly for small animal models because of its non-invasive and time-sequential analysis. Currently, translational research using this luminescence imaging technology in pigs for clinical applications is ongoing. In this review, we discuss the progress of these technologies and issues for their clinical application, focusing on pigs, by comparing conventional imaging techniques, including fluorescent probes, with luminescence imaging techniques.

Hybrid metal halide family with color-time-dual-resolved phosphorescence for multiplexed information security applications

Luminescent materials with engineered optical properties play an important role in anti-counterfeiting and information security technology. However, conventional luminescent coding is limited by fluorescence color or intensity, and high-level multi-dimensional luminescent encryption technology remains a critically challenging goal in different scenarios. To improve the encoding capacity, we present an optical multiplexing concept by synchronously manipulating the emission color and decay lifetimes of room-temperature phosphorescence materials at molecular level. Herein, we devise a family of zero-dimensional (0D) hybrid metal halides by combining organic phosphonium cations and metal halide tetrahedral anions as independent luminescent centers, which display blue phosphorescence and green persistent afterglow with the highest quantum yields of 39.9 % and 57.3 %, respectively. Significantly, the luminescence lifetime can be fine-tuned in the range of 0.0968–0.5046 μs and 33.46–125.61 ms as temporary time coding through precisely controlling the heavy atomic effect and inter-molecular interactions. As a consequence, synchronous blue phosphorescence and green afterglow are integrated into one 0D halide platform with adjustable emission lifetime acting as color- and time-resolved dual RTP materials, which realize the multiple applications in high-level anti-counterfeiting and information storage. The color-lifetime-dual-resolved encoding ability greatly broadens the scope of luminescent halide materials for optical multiplexing applications.

In Vivo Luciferin-Luciferase Reaction in Micro-Mini Pigs Using Xenogeneic Rat Bone Marrow Transplantation.

Luminescent technology based on the luciferin-luciferase reaction has been extensively employed across various disciplines as a quantitative imaging modality. Owing to its non-invasive imaging capacity, it has evolved as a valuable in vivo bioimaging tool, particularly in small animal models in fields such as gene and cell therapies. We have previously successfully generated rats with a systemic expression of the luciferase gene at the Rosa26 locus. In this study, we transplanted bone marrow from these rats into micro-mini pigs and used in vivo imaging to non-invasively analyze the dynamics of the transplanted cells. In addition, we established that the rat-to-pig transplantation system is a discordant system, similar to the pig-to-human transplantation system. Thus, rat-to-pig transplantation may provide a clinically appropriate large animal model for pig-to-human xenotransplantation.

Further investigation of spatially resolved single grain quartz OSL and TL signals

The use of luminescence signals from single mineral grains for optical dating has become a valuable and frequently utilised tool in Quaternary Geochronology. Single grain luminescence dating is particularly beneficial in complex depositional settings, however the ability to measure single grain signals also offers the opportunity to assess intrinsic luminescence properties of individual mineral grains. The use of spatially resolved luminescence technologies such as an electron multiplier charge coupled device is of benefit when making luminescence measurements at single grain scales because they allow stimulation with light emitting diodes, and this offers a number of key benefits related to stimulation power when it comes to the assessment of characteristics such as optically stimulated luminescence (OSL) decay rate and the calculation of parameters such as the fast ratio and photo ionisation cross-sections. In this paper, the intra- and inter-sample variability of sensitised single grain thermoluminescence (TL) and OSL signals is considered. A comparison between TL and OSL signals is undertaken, as well as calculation of the fast ratio, OSL component photo ionisation cross-sections, thermal stability, and characteristic dose for a suite of quartz samples from a range of geographic locations and depositional settings. For these heated signals, key findings include the lack of relationship between OSL signal intensity and dominance of the fast component, the fitting of two components (a fast and slow component) is the most common fit for single grain OSL signals, characteristic doses from fast dominated signals suggesting saturation at c. 150 Gy, and the identification of the ultrafast OSL component. Intra-sample variability across all measured parameters is observed, suggesting that for this suite of samples, variability is the norm rather than the exception, and that the intrinsic luminescence characteristics of quartz are variable and diverse.

Enhancing the efficiency of photovoltaic cells through the usage of dye concentrators

Over the past few years, there has been a growing interest in renewable energy sources. Among them, photovoltaic (PV) technology is advancing rapidly. Solar insolation is the most crucial factor for PV installations. Various solutions, such as tracking mechanisms, hybrid systems, and new materials, can enhance the efficiency of PV systems. Concentrators focus solar light onto the surface of solar modules, increasing production of electricity. Implementing such solutions can reduce the number of silicon cells in installations, leading to a decrease in waste generated during production. Dye concentrators have a positive impact on the performance of silicon systems. A two-stage study on the effect of dye concentrator application on PV cell efficiency is carried out. In the first stage, specific types of dye concentrators are tested for their interaction with the silicon system. Tinted and luminescent acrylic glass (polymethyl methacrylate, PMMA) in yellow and red are used as dye concentrators. The experiment included multiple measurement calibrations, such as the temperature of the tested silicon cell and the intensity of illuminance. Results showed absolute increase of efficiency in solar cells ranging from 0.05% to 1.42%, depending on the type of concentrator used. The most significant improvements were observed with luminescent red PMMA, averaging at 1.21%. The potential of this concentrator was further explored in the second stage of the study, investigating the relationship between the surface involvement of the silicon cell and the dye concentrator. Test results indicated the potential of dye concentrators for integrating luminescent dye concentrator technology into PV systems. The effect of this integration is increase in the efficiency of the PV cell. On the other hand, it should be noted that replacing the PV cell with a dye concentrator reduces the efficiency of the entire photovoltaic system. Hence, the use of a PV cell and concentrator system is recommended especially for photovoltaic systems with a large area. As dye concentrators have the ability to operate without direct irradiance, they are also recommended for regions where natural light is dispersed.

Highly Sensitive Immunoassay for Long Forms of Cardiac Troponin T Using Upconversion Luminescence.

Long cardiac troponin T (cTnT) has been proposed to be a promising and more specific biomarker of acute myocardial infarction (AMI). As it represents a subfraction of circulating cTnT, detection of very low concentrations is a requirement. The aim of this study was to develop a novel, highly sensitive immunoassay for long cTnT. A two-step sandwich-type immunoassay for long cTnT was developed, utilizing upconverting nanoparticles (UCNPs) as reporters. The limits of detection and quantitation were determined for the assay. Linearity and matrix effects were evaluated. Performance with clinical samples was assessed with samples from patients with non-ST elevation myocardial infarction (NSTEMI, n = 30) and end-stage renal disease (ESRD, n = 37) and compared to a previously developed time-resolved fluorescence (TRF)-based long cTnT assay and a commercial high-sensitivity cTnT assay. The novel assay reached a 28-fold lower limit of detection (0.40 ng/L) and 14-fold lower limit of quantitation (1.79 ng/L) than the previously developed TRF long cTnT assay. Li-heparin and EDTA plasma, but not serum, were found to be suitable sample matrixes for the assay. In a receiver operating characteristics curve analysis, the troponin ratio (long/total cTnT) determined with the novel assay showed excellent discrimination between NSTEMI and ESRD with an area under the curve of 0.986 (95% CI, 0.967-1.000). By utilizing upconversion luminescence technology, we developed a highly sensitive long cTnT assay. This novel assay can be a valuable tool for investigating the full potential of long cTnT as a biomarker for AMI. ClinicalTrials.gov Registration Number: NCT04465591.

Multi-color and multi-mode luminescence tuning in persistent phosphors by trap engineering

Conventional persistent luminescent phosphors face a significant challenge in developing a single material for multi-color anti-counterfeiting. In this study, a wide range of Cr3+ activated gallium germanate-based persistent phosphors are successfully synthesized using high-temperature solid phase approach. By incorporating Cr3+ and Er3+ as dual emitting centers, and utilizing Yb3+ as a sensitizer and electron traps, the resulting phosphors exhibit an exceptional combination of photoluminescence, up-conversion luminescence, persistent luminescence, photo/thermo-stimulated luminescence, followed by photo-stimulated persistent luminescence in a single material system. Beyond its multi-mode emissions, the luminescence color output can be conveniently controlled by adjusting annealing time, Yb3+ ion doping concentration, excitation wavelength, or excitation power. A systematic study of trap distribution related to PersL has been conducted by regulating annealing temperature, time, doping concentration and type. The responding multi-mode luminescent mechanisms are also proposed. Particularly, these phosphors demonstrated outstanding performance as security labels in advanced anti-counterfeiting applications. This research holds the potential to inspire the design and development of more intricate luminescence anti-counterfeiting materials and technologies.

Development and validation of CYP26A1 inhibition assay for high-throughput screening.

All-trans retinoic acid (atRA) is an endogenous ligand of the retinoic acid receptors, which heterodimerize with retinoid X receptors. AtRA is generated in tissues from vitamin A (retinol) metabolism to form a paracrine signal and is locally degraded by cytochrome P450 family 26 (CYP26) enzymes. The CYP26 family consists of three subtypes: A1, B1, and C1, which are differentially expressed during development. This study aims to develop and validate a high throughput screening assay to identify CYP26A1 inhibitors in a cell-free system using a luminescent P450-Glo assay technology. The assay performed well with a signal to background ratio of 25.7, a coefficient of variation of 8.9%, and a Z-factor of 0.7. To validate the assay, we tested a subset of 39 compounds that included known CYP26 inhibitors and retinoids, as well as positive and negative control compounds selected from the literature and/or the ToxCast/Tox21 portfolio. Known CYP26A1 inhibitors were confirmed, and predicted CYP26A1 inhibitors, such as chlorothalonil, prochloraz, and SSR126768, were identified, demonstrating the reliability and robustness of the assay. Given the general importance of atRA as a morphogenetic signal and the localized expression of Cyp26a1 in embryonic tissues, a validated CYP26A1 assay has important implications for evaluating the potential developmental toxicity of chemicals.

Multi-mode photoluminescence inks based on lanthanide-doped multilevel core-shell microspheres for advanced anti-counterfeiting applications

Development of advanced luminescent nanomaterials and technologies is of great significance for anticounterfeiting applications in global economy, security, and human health. In this work, we have designed two types of anti-counterfeit materials. (1) The dual excitation mode core–shell microsphere is based on SiO2 core, with the GdVO4:Yb,Er upconversion luminescent inner layer, SiO2 shell separator, and Gd2O3:Eu@SiO2 downconversion luminescent layer are sequentially deposited on it via co-precipitation method. The microspheres have a five-layer core–shell structure with an overall diameter of ∼ 146 nm and enables the spatial separation of Er3+ and Eu3+, which prevents the cross-relaxation of Er3+. The microspheres were prepared into an upconversion/downconversion excitation mode luminescent ink, with inkjet-printed patterns that only extract information when excited by 254 nm and 980 nm excitation. (2) The core–shell-shell SiO2@AIPA-S-Si-Tb@SiO2 microspheres have been synthesized by using organic ligands ((HOOC)2C6H3NHCONH(CH2)3Si(OCH2CH3)3) (defined as AIPA-S-Si) connected with Tb3+ ions and silica through covalent bond. The microspheres have a sandwich structure with an overall diameter of ∼ 100 nm and show bright green light. The sandwich structure and five-layer core–shell structure was mixed proportionally to obtain orange-red, white, and yellow emission ink under 254 nm, green emission under 310 nm, and green emission under 980 nm excitation.

Isostructural doping for organic persistent mechanoluminescence.

Mechanoluminescence, featuring light emission triggered by mechanical stimuli, holds immense promise for diverse applications. However, most organic Mechanoluminescence materials suffer from short-lived luminescence, limiting their practical applications. Herein, we report isostructural doping as a valuable strategy to address this challenge. By strategically modifying the host matrices with specific functional groups and simultaneously engineering guest molecules with structurally analogous features for isostructural doping, we have successfully achieved diverse multicolor and high-efficiency persistent mechanoluminescence materials with ultralong lifetimes. The underlying persistent mechanoluminescence mechanism and the universality of the isostructural doping strategy are also clearly elucidated and verified. Moreover, stress sensing devices are fabricated to show their promising prospects in high-resolution optical storage, pressure-sensitive displays, and stress monitoring. This work may facilitate the development of highly efficient organic persistent mechanoluminescence materials, expanding the horizons of next-generation smart luminescent technologies.

Anti-counterfeiting applications of antimony-doped zero-dimensional indium halide with temperature-responsive broad emission

While spatial-resolved luminescent anti-counterfeiting technology has reached maturity, achieving rapid responsiveness and exceptional fatigue resistance remains a challenge for high-security-level applications. Temperature-based multi-stimuli-responsive luminescent solid-state materials offer a promising solution to meet these requirements. In this study, we present a dual stimuli-responsive photoluminescence (PL) switching system that depends on both temperature and excitation wavelength, utilizing a Zero-Dimensional (0D) (PMA)4In0.98Sb0.02Cl7·H2O (PMA = benzylamine). Notably, (PMA)4In0.98Sb0.02Cl7·H2O exhibits orange broad-band emission at room temperature under both low-energy (365 nm) and high-energy (254 nm) irradiation. At 80 K, green light emission is observed under high-energy irradiation (254 nm), transforming into red emission when excited with low-energy wavelength (365 nm) at the same temperature. Moreover, the (PMA)4In0.98Sb0.02Cl7·H2O both in powder and film states demonstrate excellent stimuli-responsive performance, including short response times and superior cyclic reversibility. Therefore, this 0D (PMA)4In0.98Sb0.02Cl7·H2O can serve as a novel quarter-fold turn-on and tuning luminescent switch for encryption/decryption under the stimuli of temperature and excitation with rapid response and excellent fatigue resistance.

Concentration dependence of visible luminescence from Pr3+-doped niobium zinc barium boro-tellurite glasses

This study explored the luminescence properties of a glass with the compositions defined in the formula (30-x)TeO2-30B2O3-10ZnO-20BaO-10Nb2O5, doped with varying concentrations of praseodymium (Pr3+) ions (x = 0.00 to 1.50 mol%). The investigation covers multiple aspects, including the physical, structural, optical, and luminescence properties, to explain the material’s behaviour with respect to its physical attributes. The measured density, molar volume, and refractive index span a range of 3.76-3.86 g/cm3, 35-36 cm3/mol, and 1.71-1.79, respectively. Structural analysis through FTIR spectroscopy demonstrates characteristic stretching vibrations of Te-O (677 cm−1) and B-O (892 cm−1) bonds, providing insight into the molecular arrangement within the glass composition. The optical investigation on transitions from the ground state 3H4 to higher-energy states: 1D2 (590 nm), 1G4 (1008 nm), 3F3 (1529 nm), and 3F2 (1932 nm). These emission peaks furnish crucial information on the material’s electron transitions, which are suitable for curtain potential applications in optical devices. Significantly, our study reveals a quenching effect at a Pr3+ doping concentration of 0.10 mol%, indicating interactions between Pr3+ ions and the glass matrix, affecting luminescence behaviour. This work contributes to an enhanced understanding of material properties and lays the groundwork for potential applications in luminescence and optical technologies.

Comparative analysis between light-emitting diodes using quantum dots and organic light-emitting diodes

Due to its customizable emission peaks, high saturation chromaticity, and low cost, quantum dot luminescence technology has gained significant attention as the most cutting-edge technology in the optoelectronics sector. Whether the technology of making light emitting diodes from solution treatable quantum dots-(QLED)-can emerge and compete with organic light emitting diode (OLED) displays will become the focus of this paper. Through the property and function of the quantum dots and by looking at some waveforms of quantum dots, the essay describes the specific structure of QLED and the preparation technology of QLED. Furthermore, using these properties and functions, quantum dot technology produces displays with a wider color gamut. And compared with OLED, the paper comes to the conclusion that although QLEDs are slightly inferior in stability to OLEDs, they are superior in color gamut, low cost, and temperature according to the studies of quantum dots and organic light emitting diodes at different temperatures, color rendering indices, and energy band structures.

Cyanostyrene derivative with multi-stimuli responsive properties: Multicolor- and high-color-contrast switching in response to force, heat and light

Multi-stimuli responsive luminescent materials are ideal materials for luminescent anti-counterfeiting technology. Currently, it is still challenging to develop excellent multi-stimuli-responsive material that is easy to synthesize and low-cost. Herein, a dicyanostilbenebenzene derivative (α-CFP) with a symmetrical structure was designed and successfully synthesized, which showed obvious AIE and solvent effects in solution. Two polymorphs of it were prepared by controlling the cooling rate, and it was found that green-emitting Form I and blue-emitting Form II can transform into each other by heat and mechanical force. Crystal structure analysis reveals the possible intrinsic mechanism of polymorphism-dependent emission and interconversion. Further studies found that both Form I and Form II could transform into another new polymorph Form III upon heating to 220 °C. Form III can undergo photoinduced [2 + 2] cycloaddition reaction accompanied by discoloration, and it can return to its original state by heating. Finally, three application scenarios were designed and demonstrated, which confirm their potential applications in information encryption and anti-counterfeiting.

Upconverting ultraviolet light source with extended emission wavelengths based on Bi3+-activated phosphor

Upconverted ultraviolet luminescence technology is attracting extensive interest lately due to its potential applications. To date, visible-to-ultraviolet upconversion has been achieved in Pr3+, Gd3+, Er3+, Ho3+ or Tm3+-activated phosphors. We herein report an upconverted ultraviolet emission of Bi3+ in a co-doped phosphor, YBO3:Pr3+,Bi3+, utilizing a 447 nm laser for excitation. Through spectroscopic investigations, we have determined that the blue laser excites the Pr3+ 4f5d state, followed by an energy transfer to the excited state of the Bi3+ ion in the phosphor. Consequently, the upconverted emission spectra do not show the Pr3+ (4f5d→4f2) emission, but rather the ultraviolet emission is completely dominated by the Bi3+ (3P1→1S0) emission. Taking advantage of the ultraviolet emission performance and blue light excitability of the phosphor, we have successfully built and demonstrated a prototype upconverting ultraviolet light source based on phosphor conversion. The introduction of Bi3+-activated upconversion luminescence enriches the bank of upconverting ultraviolet phosphors and provides a novel upconversion strategy for achieving Bi3+-activated ultraviolet light source.

Monte Carlo Dosimetry Validation for X-Ray Guided Endovascular Procedures

Endovascular treatment is continuously gaining ground in vascular surgery procedures. However, current patient radiation dose estimation does not take into account the exact patient morphology and organs' composition. Monte Carlo (MC) simulation can accurately estimate the dose by recreating the irradiation process generated during X-ray-guided interventions. This study aimed to validate the MC simulation models by comparing simulated and measured dose distributions in endovascular aortic aneurysm repair (EVAR) procedures. We conducted a clinical study in patients treated for EVAR. Patient dose measurements were taken with passive dosimeters using Optically Stimulated Luminescence technology in 4 specific anatomical points on the skin: xiphoid process, pubic symphysis, right and left iliac crest. Dose measurements were compared to the corresponding simulated doses with the Geant4 Application for Emission Tomography (GATE) and GPU Geant4-based Monte Carlo Simulations (GGEMS) MC simulations softwares. The MC simulation took as input the computed tomography scan of the patient and the parameters of the imaging system (orientation angles, tube voltage, and aluminum filtration) and gives as output the three-dimensional (3D) dose map for each patient and angulation. A good agreement with real doses was found for doses simulated by the MC GATE method (P<0.0001; r=0.97; 95% confidence interval [CI] [0.96-0.98]), as well as for doses simulated by the GGEMS method (P<0.0001; r=0.96; 95% CI [0.94-0.97]). The mean relative error for all measurements was 5±5% in the MC GATE group and 6±5% in the GGEMS group. Process execution on GGEMS (6sec) was faster than the GATE MC simulation (5hr). Considering the current imaging settings, this study shows the potential of using the GATE and GGEMS MC simulations platforms to model the 3D dose distributions during EVAR procedures.

Wearable Integrated Self‐Powered Electroluminescence Display Device Based on All‐In‐One MXene Electrode for Information Encryption

AbstractAnti‐counterfeiting and visual optical information encryption/decryption technology have attracted widespread attention in the field of information security. Luminescent encryption technologies still face a huge challenge in external high voltage power supply, complex architecture, and expensive decryption equipment, which hinder their broad applications. Herein, a wearable integrated self‐powered electroluminescent (EL) display device (W‐ELD) that consists of MXene/Silicone‐based triboelectric nanogenerator (MS‐TENG) and EL device based on a shared MXene electrode is developed for patterned display and information encryption. The W‐ELD features an all‐in‐one MXene electrode with excellent flexibility and high conductivity of 0.6 kΩ sq−1, which is shared by both MS‐TENG and EL devices. The MS‐TENG demonstrates excellent output performances (output power of 0.9 Wm−2) and high stability and durability (104 cycles), which can directly light up the flexible patterned EL device. More importantly, when dripping conductive electrolyte solution, the W‐ELD based on “中國”‐patterned MXene electrode can precisely reveal the encryption information through self‐powered EL emission for real‐time visualized information interaction. Consequently, the all‐in‐one MXene electrode‐based W‐ELD that integrates both MS‐TENG and EL device demonstrates exceptional patterned EL‐based information encryption features, which offers a potential prospect in wearable self‐powered optoelectronic devices, flexible displays, and encryption technology.

Orange-red persistent luminescence in Mn2+-Doped Sr3Y2Ge3O12 films for dynamic anti-counterfeiting

The research focus in the field of anti-counterfeiting has shifted toward the secure luminescent label technology, which has gained prominence. The exceptional luminescence properties of persistent luminescence materials are important in the achievement of effective anti-counterfeiting measures. It is in this context that Sr3Y2Ge3O12 can serve as an excellent matrix material. In this study, it is found that Sr3Y2Ge3O12: 4.00% Mn2+ exhibits a luminescence intensity, persistence time, and stability that meet the practical requirements for applications. It is shown that the fabricated persistent luminescence film can be used in anti-counterfeiting applications, thereby, demonstrating the possibility to broaden the application scope of persistent luminescence materials. An emission band centered at 634 nm and a high-energy inflection point at 578 nm are observed in the samples excited at 260 nm. Fluorescence emission at 634 nm is also achieved through X-ray excitation. Through thermoluminescence, photoluminescence, and phosphorescence spectroscopy, a comprehensive investigation of the trap characteristics and inherent mechanisms of the long persistent phosphorescence has been conducted. The novel orange-red Sr3Y2Ge3O12: Mn2+ phosphor is extensively examined.

Dual-targeting lanthanide-ICG-MOF nanoplatform for cancer Theranostics: NIR II luminescence imaging guided sentinel lymph nodes surgical navigation.

Sentinel lymph node imaging is important for breast tumor staging and prediction of postoperative metastasis. However, clinical sentinel lymph node imaging has limitations such as low specificity, low contrast, and short retention time. The combination of bio-conjugates chemistry and luminescence technology may achieve the specific targeting effect. In this research, we designed a dual-targeting composite nanoprobe (∼50nm) using a metal-organic framework (MOF) as carrier, loaded with lanthanide and ICG, and combined with hyaluronic acid and folic acid to detect metastatic lymph nodes. The coupled hyaluronic acid and folic acid can target to the tumor cells and dentritic cells with a dual-targeting effect. The FA-HA/ZIF-8@ICG nanoprobes can accumulate rapidly in sentinel lymph node with a stronger luminescence intensity (1.6 times) than that of normal popliteal lymph nodes in vivo, thus distinguish metastatic sentinel lymph node from normal effectively. Furthermore, due to the MOF carrier, the integrated lanthanide and near-infrared dye by transferring the absorbed excitation energy from ICG to Nd3+ can enhance the signal-to-background ratio of NIR II imaging and have long retention time in vivo imaging. Finally, the FA-HA/ICG@Ln@ZIF-8 nanoplatform increased the penetration depth and contrast of imaging, prolonged the retention time, and achieved the sentinel lymph nodes surgical resection. This study has important implications for lymph node imaging and surgical navigation.

Lanthanide-Doped Inorganic Nanoprobes for Luminescent Assays of Biomarkers

ConspectusTremendous progress in nanomaterial and nanotechnology has been made in recent years, which greatly contributes to the development of inorganic nanoparticles (NPs) as luminescent probes in diverse biomedical applications. In particular, these luminescent nanoprobes are widely employed for sensitive assays of biomarkers like disease markers. Generally, the luminescent bioassay technologies mainly rely on conventional molecular probes such as lanthanide (Ln3+) chelates or organic dyes, which suffer from inferior photochemical stability, low photobleaching, potential long-term toxicity, or high background noise. In contrast, Ln3+-doped NPs possess distinct physicochemical properties including better photostability, lower toxicity, and superior optical properties like long photoluminescent (PL) lifetime, narrow emission band, and tunable spectral range from the ultraviolet to the second near-infrared (NIR-II), which make them extremely ideal as luminescent nanoprobes. As such, enormous research enthusiasm has been invested in this fascinating field of Ln3+-doped luminescent nanoprobes in recent years. Accordingly, background-free luminescent bioassays with high signal-to-noise have been achieved by employing Ln3+-doped NPs on the basis of their downshifting luminescence (DSL) with a long PL lifetime, NIR-II luminescence with long-wavelength emissions, or upconverting luminescence (UCL) upon NIR excitation. However, there are still key challenges for Ln3+-doped nanoprobes owing to their low brightness and quantum yield, which restrict their biomedical applications. During the past decade, we have explored efficient approaches for the synthesis and design of highly efficient Ln3+-doped nanoprobes toward ultrasensitive luminescent bioassay of disease markers.In this Account, we summarize our most recent endeavors toward the development of inorganic Ln3+-doped NPs as sensitive nanoprobes for luminescent bioassays. First, we overview the approaches of controlled synthesis and optical manipulation to obtain highly efficient Ln3+-doped NPs with desirable optical properties. Second, we survey the design of Ln3+-doped nanoprobes with outstanding water dispersibility and excellent biocompatibility through surface functional bioconjugation of NPs. By employing these nanoprobes, we propose and exemplify several background-free luminescent bioassay strategies in an effort to suppress the interference of background noise from scattered lights and autofluorescence from biological samples. Third, we highlight the ultrasensitive bioassay of disease markers such as the time-resolved luminescent bioassay, NIR-II luminescent bioassay, and UCL bioassay. Finally, the major challenges, promising emerging trends, and future perspectives on this attractive field are discussed. Through this Account, we aim to offer a series of effective approaches to luminescent bioassay with high sensitivity and excellent specificity based on Ln3+-doped nanoprobes, which may broaden the roadway for clinical bioassays and accelerate the exploration of novel nanoprobes in versatile biomedical applications.