Multiphoton Upconversion Research Articles

Rare Earth Doped Nanoparticles for Theranostics

In the biomedical field, research has recently focused on nanoparticle-based “theranostic” agents for the treatment of diverse diseases, including cancer. This new paradigm in personalized medicine intends to exploit nanoplatforms that carry both therapeutic and diagnostic (theranostic) modalities. Compared with delivering drugs or imaging agents separately, theranostic agents can simultaneously deliver them to specific sites, enabling detection and treatment of disease in a single procedure. Many theranostic nanoplatforms are triggered by light, however, the vast majority of these are limited in that the ultraviolet or visible excitation light used has minimal applicability in biological applications. Rare earth doped nanoparticles, on the other can be excited with biologically friendly near-infrared light (in the biological windows) and can emit in the ultraviolet, visible or near-infrared regions through a multiphoton upconversion process while simultaneously emitting in the near-infrared region (also in the 3 biological windows) through a Stokes or downshifted process. Hence, the upconversion luminescence can be used to trigger the therapeutic application (drug delivery, photodynamic therapy, etc.) while the near-infrared luminescence can be used for the diagnostic modality (bioimaging, nanothermometry/temperature sensing, etc).In this presentation, we will introduce rare earth doped nanoparticles and demonstrate their usefulness in theranostics. In particular, we will show that complex nanoparticle architectures can endow further functionality to these nanoparticles and discuss how they can be used for temperature sensing (nanothermometry) in biological systems.

(Invited) Theranostics with Lanthanide Doped Nanoparticles

In recent years, a significant amount of research has focused on nanoparticle-based “theranostic” agents for the treatment of a wide array of diseases, including cancer. This new paradigm in personalized medicine intends to exploit nanoplatforms that carry both therapeutic and diagnostic (theranostic) modalities. Compared with delivering drugs or imaging agents separately, theranostic agents can simultaneously deliver them to specific sites, enabling detection and treatment of disease in a single procedure. Many theranostic nanoplatforms are triggered by light, however, the vast majority of these are limited in that the ultraviolet or visible excitation light used has minmal applicability in biological applications. Lanthanide doped nanoparticles, on the other can be excited with biologically friendly near-infrared light (in the biological windows) and can emit in the ultraviolet, visible or near-infrared regions through a multiphoton upconversion process while simultaneously emitting in the near-infrared region through a Stokes or downshifted process. Hence, the upconversion luminescence can be used to trigger the therapeutic application (drug delivery, photodynamic therapy, etc.) while the near-infrared luminescence can be used for the diagnostic modality (bioimaging, nanothermometry, etc).In this presentation, we will introduce lanthanide doped nanoparticles and demonstrate their usefulness in theranostics. In particular, we will show complex nanoparticle architectures can endow further functionality to these nanoparticles including the ability to decouple the theranostic processes that are conventionally delivered simultaneously.

MUTE-SIM: multiphoton up-conversion time-encoded structured illumination microscopy

Multiphoton microscopy (MPM) plays important role in biological imaging for its low scattering nature, yet it typically requires high illumination intensity. Although time-stretch of the ultrashort pulse can achieve ultrahigh speed scanning and deep penetration, the near-infrared illumination yields a compromised resolution because of its long wavelength. Here, by combining structured illumination with up-conversion materials, a multiphoton up-conversion time-encoded structured illumination microscopy (MUTE-SIM) with the scanning rate of 50 MHz is developed, which overcomes the limitation on the resolution. The resolution limit of near-infrared light is surpassed by a factor of 223.3% with low illumination intensity. This imaging strategy provides an ultrafast, low intensity, super-resolution MPM approach imaging, which has great potential in deep-tissue with high spatial resolution.

Enhancing multiphoton upconversion through interfacial energy transfer in multilayered nanoparticles

Photon upconversion in lanthanide-doped upconversion nanoparticles offers a wide variety of applications including deep-tissue biophotonics. However, the upconversion luminescence and efficiency, especially involving multiple photons, is still limited by the concentration quenching effect. Here, we demonstrate a multilayered core-shell-shell structure for lanthanide doped NaYF4, where Er3+ activators and Yb3+ sensitizers are spatially separated, which can enhance the multiphoton emission from Er3+ by 100-fold compared with the multiphoton emission from canonical core-shell nanocrystals. This difference is due to the excitation energy transfer at the interface between activator core and sensitizer shell being unexpectedly efficient, as revealed by the structural and temperature dependence of the multiphoton upconversion luminescence. Therefore, the concentration quenching is suppressed via alleviation of cross-relaxation between the activator and the sensitizer, resulting in a high quantum yield of up to 6.34% for this layered structure. These findings will enable versatile design of multiphoton upconverting nanoparticles overcoming the conventional limitation.

Tuning epitaxial growth on NaYbF4 upconversion nanoparticles by strain management.

Core-shell structural engineering is a common strategy for tuning upconversion luminescence in lanthanide-doped nanoparticles. However, epitaxial growth on hexagonal phase NaYbF4 nanoparticles typically suffers from incomplete shell coverage due to the large and anisotropic interfacial strain. Herein, we explore the effects of core particle size and morphology as well as reaction temperature on controlling the epitaxial growth of NaGdF4 shells on NaYbF4 nanoparticles with misfit parameters of fa = 1.58% and fl = 2.24% for axial and lateral growth, respectively. Rod-like core particles with a long length and a large diameter are found to promote shell growth with high surface coverage by facilitating the relaxation of lattice strains. Furthermore, the primary NaGdF4 shell can serve as a transition layer to mediate the growth of additional NaNdF4 coating layers that display an even larger lattice misfit with the core (fa = 2.98%; fl = 4.32%). The resultant NaYbF4@Na(Gd/Nd)F4 core-shell nanostructures simultaneously show strong multiphoton upconversion luminescence and superior magnetic resonance T1 ionic relaxivity. Our findings are important for the rational design of core-shell upconversion nanoparticles with optimized properties and functionality for technological applications.

Perceiving Linear-Velocity by Multiphoton Upconversion.

Up to now, the rising edge of the upconversion process does not receive due attention. Herein, a demonstration utilizing the feature of the rising edge to practically detect the linear-velocity of an object is presented. Typically, upconversion processes with different numbers of participant photons would exhibit diversity in the rising edge. On this account, when the emitter is moving, the emission intensity ratio of different multiphoton processes will vary with changing linear-velocity, which enables accurate speed detection through spectral analysis. To illustrate this principle, in this work, the modeling and numerical simulation were first performed, and then experimental demonstration was carried out in which core-shell upconversion nanocrystals were elaborately designed and fabricated as the speed sensing probe to calibrate the speed of a homemade turnplate. It is believed that the present work will exploit a novel speed sensing method and find a new application for lanthanide-doped upconversion materials.

Two-Photon Up-Conversion Photoluminescence Realized through Spatially Extended Gap States in Quasi-2D Perovskite Films.

A new approach to generate a two-photon up-conversion photoluminescence (PL) by directly exciting the gap states with continuous-wave (CW) infrared photoexcitation in solution-processing quasi-2D perovskite films [(PEA)2 (MA)4 Pb5 Br16 with n = 5] is reported. Specifically, a visible PL peaked at 520 nm is observed with the quadratic power dependence by exciting the gap states with CW 980 nm laser excitation, indicating a two-photon up-conversion PL occurring in quasi-2D perovskite films. Decreasing the gap states by reducing the n value leads to a dramatic decrease in the two-photon up-conversion PL signal. This confirms that the gap states are indeed responsible for generating the two-photon up-conversion PL in quasi-2D perovskites. Furthermore, mechanical scratching indicates that the different-n-value nanoplates are essentially uniformly formed in the quasi-2D perovskite films toward generating multi-photon up-conversion light emission. More importantly, the two-photon up-conversion PL is found to be sensitive to an external magnetic field, indicating that the gap states are essentially formed as spatially extended states ready for multi-photon excitation. Polarization-dependent up-conversion PL studies reveal that the gap states experience the orbit-orbit interaction through Coulomb polarization to form spatially extended states toward developing multi-photon up-conversion light emission in quasi-2D perovskites.

Pressure-Induced Multiphoton Excited Fluorochromic Metal-Organic Frameworks for Improving MPEF Properties.

In multiphoton excited fluorescence (MPEF), high-energy upconversion emission is obtained from low-energy excitation by absorbance of two or more photons simultaneously. In a pressure-induced fluorochromic process, the emission energy is switched by outer pressure stimuli. Now, five metal-organic frameworks containing the same ligand with simultaneous multiphoton absorption and pressure-induced fluorochromic attributes were studied. One-, two-, and three-photon excited fluorescence (1/2/3PEF) can be achieved in the frameworks, which exhibit pressure-induced blue-to-yellow fluorochromism. The performances are closely dependent with the topologies, flexibilities, and packing states of the frameworks and chromophores therein. The multiphoton upconversion performance can be intensified by pressure-related structural contraction. Over ten-fold increment in the 2PA active cross-section up to 2217 GM is achieved in pressed LIFM-114 compared with the 210 GM for pristine sample at 780 nm.

Pressure‐Induced Multiphoton Excited Fluorochromic Metal–Organic Frameworks for Improving MPEF Properties

AbstractIn multiphoton excited fluorescence (MPEF), high‐energy upconversion emission is obtained from low‐energy excitation by absorbance of two or more photons simultaneously. In a pressure‐induced fluorochromic process, the emission energy is switched by outer pressure stimuli. Now, five metal–organic frameworks containing the same ligand with simultaneous multiphoton absorption and pressure‐induced fluorochromic attributes were studied. One‐, two‐, and three‐photon excited fluorescence (1/2/3PEF) can be achieved in the frameworks, which exhibit pressure‐induced blue‐to‐yellow fluorochromism. The performances are closely dependent with the topologies, flexibilities, and packing states of the frameworks and chromophores therein. The multiphoton upconversion performance can be intensified by pressure‐related structural contraction. Over ten‐fold increment in the 2PA active cross‐section up to 2217 GM is achieved in pressed LIFM‐114 compared with the 210 GM for pristine sample at 780 nm.

Color modulation and temperature sensing investigation of Gd2O3: 1 mol% Er3+, 1 mol% Yb3+ phosphors under different excitation condition

Recently, modulating emission color and increasing temperature sensing sensitivity of rare earth doped materials are imperative because of their applications in colorful display, multiplexed labeling and temperature sensing. In this work, the emission color, radiated from Gd2O3: 1 mol% Er3+/1 mol% Yb3+ phosphors, is modulated through co-excitation condition, which is attributed to the additional co-excited up-conversion processes. The validity of co-excited up-conversion processes are demonstrated via the multi-photon up-conversion processes. More importantly, the temperature-dependent green emissions from Gd2O3: 1 mol%Er3+/1 mol%Yb3+ phosphors under different excitation condition are investigated. The fluorescence intensity ratio (FIR) of 522 and 562 nm (R522/562) exhibits relatively high sensing sensitivities among that of R522/538, R522/553, R522/562 due to the big energy gap. The maximal sensing sensibility (4.1 %K−1) is obtained as the sample is co-excited under 980 and 1550 nm lasers, which is 37% improvement over single 980 nm laser excitation (3.0 %K−1). The results confirm that the co-excited method is promising to serve as an alternative approach for tuning the emission color and enhancing the temperature sensing sensibility of up-conversion materials.

Oleylamine-Mediated Synthesis of Small NaYbF4 Nanoparticles with Tunable Size

Hexagonal phase NaYbF4 has recently been reorganized as a more efficient host material than NaYF4 for constructing multiphoton upconversion nanoparticles. However, the synthesis and size control of...

Integrating temporal and spatial control of electronic transitions for bright multiphoton upconversion

The applications of lanthanide-doped upconversion nanomaterials are limited by unsatisfactory brightness currently. Herein, a general strategy is proposed for boosting the upconversion efficiency in Er3+ ions, based on combined use of a core−shell nanostructured host and an integrated optical waveguide circuit excitation platform. A NaErF4@NaYF4 core−shell nanoparticle is constructed to host the upconversion process for minimizing non-radiative dissipation of excitation energy by surface quenchers. Furthermore, an integrated optical microring resonator is designed to promote absorption of excitation light by the nanoparticles, which alleviates quenching of excited states due to cross-relaxation and phonon-assisted energy transfer. As a result, multiphoton upconversion emission with a large anti-Stokes shift (greater than 1150 nm) and a high energy conversion efficiency (over 5.0%) is achieved under excitation at 1550 nm. These advances in controlling photon upconversion offer exciting opportunities for important photonics applications.

Coherent metamaterial absorption of two-photon states with 40% efficiency

Multi-photon absorption processes have a nonlinear dependence on the amplitude of the incident optical field i.e. the number of photons. However, multi-photon absorption is generally weak and multi-photon events occur with extremely low probability. Consequently, it is extremely challenging to engineer quantum nonlinear devices that operate at the single photon level and the majority of quantum technologies have to rely on single photon interactions. Here, we demonstrate experimentally and theoretically that exploiting coherent absorption of N = 2 N00N states makes it possible to enhance the number of two-photon states that are absorbed. An absorbing metasurface placed inside a Sagnac-style interferometer into which we inject an N = 2 N00N state, exhibits two-photon absorption with 40.5% efficiency, close to the theoretical maximum. This high probability of simultaneous absorption of two photons holds the promise for applications in fields that require multi-photon upconversion but are hindered by high peak intensities.

Multi-photon up-conversion enhancement from Gd2(MoO4)3:Er/Yb thin film via the use of sandwich structure

Lanthanide-doped up-converting nano-particles reveal significant promise for data storage, biological imaging, and temperature sensing, but have not been extensively used due to their low emission intensity. Here, we investigate the up-conversion emissions of Gd2(MoO4)3:Er/Yb thin films that are sandwiched by Gd2(MoO4)3:Yb thin films. Our results show that the sandwiched thin films possess significant enhancement of emission intensities. The enhancement factors of the green and red emissions, radiated from Gd2(MoO4)3:Er/Yb films, reach 9.5 and 5, respectively. Moreover, the ability of sandwich structured thin films in multi-photon up-conversion enhancement is more excellent than that of laser power, attributed to the suppression of undesired radiative/non-radiative recombination of the intermediate states. In addition, the intensity-based temperature absolutely sensitivity of sandwich structured Gd2(MoO4)3:Er3+/Yb3+ reaches 0.013 K−1 at 498 K, which indicate this sandwich structured thin films have larger potential in thermal sensors. This sandwich structure might extend the applications of Ln3+-doped materials in super-resolution imaging and temperature sensing.

Carbon Dots Based Fluorescence Nanoprobe for Cell Imaging and Single Particle Tracking

School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164 Advances in real-time imaging in living cells have enabled tracking of individual molecules over time and space. Single particle tracking (SPT) technique enables the imaging and mapping of functional biomolecules directly in living cells at unprecedented spatial and temporal resolution [1-4]. This technique has provided a powerful tool to reveal the dynamic structure-function relationships in complex biological systems and dramatically advanced the fundamental understanding of biological systems and medical diagnose [5-7]. The fluorescent probe, which tags the molecules of interest and allows the fluorescent emission, is crucial for intercellular imaging. The considerable interest in intercellular trafficking sparked sustained research efforts on developing of fluorescent probes with high quantum yield, excellent stability and biocompatibility. Carbon dots (CDs) exhibit controlling size and shape, surface heteroatom doping, tunable photoluminescence (PL) and efficient multiphoton up-conversion. These CDs exhibit excellent biocompatibility, high photostability, enhanced brightness and high quantum yields [8]. Therefore, CDs will provide a new platform as versatile probes for single particle tracking (SPT) in various biological and medical areas. In our previous studies [9-10], we synthesis the CDs with optimized remarkable quantum confinement effect, surface effect and surface defect state are expected to present (1) low cytotoxicity and excellent biocompatibility. (2) Capability of precisely controlling the functional-group and feasible labeling of biomolecule for enhanced specificity. (3) Enhanced optical properties. (4) High stability. The CDs are highly chemically and thermally stable. We found that the endosome escape most probably because that the untreated surface group of CDs could provide high buffering capacity to trigger the osmotic swelling and physical rupture of the lysosomes in acid vesicle [9]. This technology can be easily extended to the mobility of molecules and proteins in the cell membrane with the same principle. This new technology will be a major breakthrough of real-time, high resolution of intercellular imaging.

Nonlinear Photoacoustic Imaging by in situ Multiphoton Upconversion and Energy Transfer.

In recent years, photoacoustic tomography (PAT) is increasingly used in biomedical research, as it allows for direct visualization of optical absorption in deep tissue. In addition to vascular and hemodynamic imaging using endogenous contrasts, PAT is also capable of imaging neural and molecular dynamics with extrinsic contrasts. While near-infrared (NIR)-absorbing contrasts are preferred for deep tissue imaging, compared to visible-light-absorbing contrasts, they are much harder to design and synthesize with good environmental stability. We introduce here a new PAT mode which utilizes nonlinear multiphoton upconversion of NIR light in situ to visible light, thus exciting locally a dye that can generate strong photoacoustic signal. This approach allows to take advantage of a large library of visible-light-absorbing dyes that can enable functional imaging, such as imaging of voltage, oxygen, pH, and ion channel activities. Two types of upconversion materials are utilized in this work: 1) a two-photon absorbing and emitting dye that is efficiently excited by NIR nanosecond laser pulses to enable pulsed laser-based PAT (pulsed-PAT); and 2) rare-earth containing inorganic nanocrystals that absorb continuous-wave (CW) NIR light by sequential multiphoton absorption through real intermediate states to enable intensity-modulated CW laser-based PAT (CW-PAT). Since both cases produce highly localized nonlinear photoacoustic signal, which has very weak scattering in tissue, we can achieve high contrast 3-D volume imaging of deep tissues. In this study, we validated the principle of our approach in different PAT modes and successfully detected enhanced photoacoustic signals from a visible-light-absorbing dye embedded deep in tissue. With vast variety of functionalized organic dyes operating in the visible range, our mode of nonlinear photoacoustic imaging will find great applications in preclinical and clinical researches.

Enhanced light harvesting with chromium in NaLu0.70−xGd0.10F4:Yb0.18Er0.02Crx (0 ≤ x ≤ 0.25) upconversion system

Cr3+-doped NaLu0.70−xGd0.10F4:Yb0.18Er0.02Crx nanoparticles were synthesized by one step solvothermal method. The structural, emission properties were studied by XRD, FT-IR, emission spectra. The doping of 15mol% Cr3+ into NaLu0.70−xGd0.10F4:Yb0.18Er0.02Crx induced cubic-hexagonal phase transition, with a consequent 20 times improvement in the upconversion fluorescence quantum yield. The roles of Cr3+ in the phase transition as well as the mechanism of the multi-photon upconversion process in the material were discussed. The Yb3+-Cr3+ dimer could play the role of as a sensitizer by transferring energy to Er3+. The Cr3+ ions result an asymmetry in the environment surrounding the rare-earth ions, which would favor the hypersensitive transitions. This research may open up a new perspective to prepare high upconversion luminescent materials.

Magneto-Photoluminescence Based on Two-Photon Excitation in Lanthanide-Doped Up-Conversion Crystal Particles.

Experimental studies on magneto-photoluminescence based on two-photon excitation in up-conversion Y2 O2 S:Er, Yb crystal particles are reported. It is found that the up-conversion photoluminescence generated by two-photon excitation exhibits magnetic field effects at room temperature, leading to a two-photon excitation-induced magneto-photoluminescence, when the two-photon excitation exceeds the critical intensity. By considering the spin selection rule in electronic transitions, it is proposed that spin-antiparallel and spin-parallel transition dipoles with spin mixing are accountable for the observed magneto-photoluminescence. Specifically, the two-photon excitation generates spin-antiparallel electric dipoles between 4 S3/2 -4 I15/2 in Er3+ ions. The antiparallel spins are conserved by exchange interaction within dipoles. When the photoexcitation exceeds the critical intensity, the Coulomb screening can decrease the exchange interaction. Consequently, the spin-orbital coupling can partially convert the antiparallel dipoles into parallel dipoles, generating a spin mixing. Eventually, the populations between antiparallel and parallel dipoles reach an equilibrium established by the competition between exchange interaction and spin-orbital coupling. Applying a magnetic field can break the equilibrium by disturbing spin mixing through introducing spin precessions, changing the spin populations on antiparallel and parallel dipoles and leading to the magneto-photoluminescence. Therefore, spin-dependent transition dipoles present a convenient mechanism to realize magneto-photoluminescence in multiphoton up-conversion crystal particles.

Enhancing Multiphoton Upconversion from NaYF4:Yb/Tm@NaYF4 Core-Shell Nanoparticles via the Use of Laser Cavity.

We discover that emission efficiency of Tm3+-doped upconversion nanoparticles can be enhanced through the use of a laser cavity. With suitable control of the lasing conditions, the population of the intermediate excited states of the Tm3+ can be clamped at a required value above the excitation threshold. As a result, upconversion efficiency for the 300-620 nm emission band of the Tm3+-doped nanoparticles under 976 nm excitation can be enhanced by an order of magnitude over the case without a laser cavity. This is because the intrinsic recombination process of the intermediate excited states is suppressed and the surplus of excitation power directly contributes to the enhancement of multiphoton upconversion. Furthermore, our theoretical investigation has shown that the improvement of upconversion emission efficiency is mainly dependent on the cavity loss, so that this strategy can also be extended to other lanthanide-doped systems.

Spectral evidence for multi-pathway contribution to the upconversion pathway in NaYF4:Yb3+,Er3+ phosphors.

Although upconversion phosphors have been widely used in nanomedicine, laser engineering, bioimaging, and solar cell technology, the upconversion luminescence mechanism of the phosphors has been fiercely debated. A comprehensive understanding of upconversion photophysics has been significantly impeded because the number of photons incorporated in the process in different competitive pathways could not be resolved. Few convincing results to estimate the contribution of each of the two-, three-, and four-photon channels of near-infrared (NIR) energy have been reported in yielding upconverted visible luminescence. In this study, we present the energy upconversion process occurring in NaYF4:Yb3+,Er3+ phosphors as a function of excitation frequency and power density. We investigated the upconversion mechanism of lanthanide phosphors by comparing UV/VIS one-photon excitation spectra and NIR multi-photon spectra. A detailed analysis of minor transitions in one-photon spectra and luminescence decay enables us to assign electronic origins of individual bands in multi-photon upconversion luminescence and provides characteristic transitions representing the corresponding upconversion channel. Furthermore, we estimated the quantitative contribution of multiple channels with respect to irradiation power and excitation energy.