Recent Advancements in Ln‐Ion‐Based Upconverting Nanomaterials and Their Biological Applications

Upconversion nanoparticles (UCNPs) convert low‐energy infrared (IR) or near‐infrared (NIR) photons into high‐energy emission radiation ranging from ultraviolet to visible through a photon upconversion process. In comparison to conventional fluorophores, such as organic dyes or semiconductor quantum dots, lanthanide‐ion‐doped UCNPs exhibit high photostability, no photoblinking, no photobleaching, low cytotoxicity, sharp emission lines, and long luminescent lifetimes. Additionally, the use of IR or NIR for excitation in such UCNPs reduces the autofluorescence background and enables deeper penetration into biological samples due to reduced light scattering with negligible damage to the samples. Because of these attributes, UCNPs have found numerous potential applications in biological and medicinal fields as novel fluorescent materials. Different upconversion mechanisms commonly observed in UCNPs, various methods that are used in their synthesis, and surface modification processes are discussed. Recent applications of Ln‐UCNPs in the biological and medicinal fields, including in vivo and in vitro biological imaging, multimodal imaging, photodynamic therapy, drug delivery, and antibacterial activity, are also presented.     

Hybrid Rayleigh,Raman and two‐photon excited fluorescence spectral confocal microscopy of living cells

A hybrid fluorescence–Raman confocal microscopy platform is presented, which integrates low‐wavenumber‐resolution Raman imaging, Rayleigh scatter imaging and two‐photon fluorescence (TPE) spectral imaging, fast ‘amplitude‐only’ TPE‐fluorescence imaging and high‐spectral‐resolution Raman imaging. This multi‐dimensional fluorescence–Raman microscopy platform enables rapid imaging along the fluorescence emission and/or Rayleigh scatter dimensions. It is shown that optical contrast in these images can be used to select an area of interest prior to subsequent investigation with high spatially and spectrally resolved Raman imaging. This new microscopy platform combines the strengths of Raman ‘chemical’ imaging with light scattering microscopy and fluorescence microscopy and provides new modes of correlative light microscopy. Simultaneous acquisition of TPE hyperspectral fluorescence imaging and Raman imaging illustrates spatial relationships of fluorophores, water, lipid and protein in cells. The fluorescence–Raman microscope is demonstrated in an application to living human bone marrow stromal stem cells. Copyright © 2009 John Wiley & Sons, Ltd.     

Highly Bright and Photostable Li(Gd,Y)F4:Yb,Er/LiGdF4 Core/Shell Upconversion Nanophosphors for Bioimaging Applications

Intense green‐emitting Li(Gd,Y)F₄:Yb,Er/LiGdF₄ core/shell (C/S) upconversion nanophosphors (UCNPs) with a tetragonal bipyramidal morphology are synthesized. The morphology and UC luminescence of the Li(Gd,Y)F₄:Yb,Er UCNPs are significantly affected by the Li precursors, and bright UC green‐emitting Li(Gd,Y)F₄:Yb,Er UCNPs with a tetragonal bipyramidal shape, i.e., UC tetragonal bipyramids (UCTBs), are synthesized using LiOH·H₂O as a Li precursor. A LiGdF₄ shell is grown on the Li(Gd,Y)F₄:Yb,Er UCTBs, and the C/S UCNPs exhibit 4.7 times higher luminescence intensity than core UCTBs. The C/S UCNPs show a high absolute UC quantum yield of 4.6% under excitation with 980 nm near infrared (NIR) light, and the UC luminescence from the C/S UCNPs is stable under continuous irradiation with the 980 nm NIR laser for 1 h. The hydrophobic surfaces of the as‐synthesized C/S UCNPs are modified to hydrophilic surfaces by using poly(acrylic acid) (PAA) for bioimaging applications. They are applied to human cervical adenocarcinoma (HeLa) cell imaging and SK‐MEL‐2 melanoma cell imaging and in vivo imaging, including subcutaneous and intramuscular imaging, and UC luminescence images with high signal‐to‐noise ratio are obtained. Furthermore, sentinel‐lymph‐node imaging is successfully conducted with the PAA‐capped Li(Gd,Y)F₄:Yb,Er/LiGdF₄ C/S UCNPs under illumination with NIR light.     

Construction of a Dual Drug Carrier on the Basis of Hollow Structured Upconversion Nanoparticles for pH‐Responsive Drug Delivery and UCL/MRI Dual Mode Imaging

A series of Gd³⁺ doping hollow upconversion nanoparticles NaYF₄:Yb,Gd,Tm (h‐UNCP) are prepared successfully. The hollow NaYF₄:Yb,Gd,Tm possess excellent upconversion luminescence (UCL) and large longitudinal relativity (r₁ = 128.3 mm ^?1 s^?1), which can be potentially used for UCL/magnetic resonance imaging (MRI) dual mode imaging. On the basis of the optimal h‐UCNP, doxorubicin hydrochloride (DOX) and methotrexate (MTX) are used as drug models to prepare a dual drug carrier. After the encapsulation of DOX on the h‐UCNP, chitosan (CS) is further wrapped and then used to load MTX to obtain a dual drug carrier h‐UCNPs/DOX/CS/MTX. The pH responsive release of DOX and MTX is discussed. The MTX release climbs from 33% to 100% by regulating the pH from 5.8 to 7.4. The DOX release is different at different pH conditions. The synergistic effect of DOX and MTX on the cancer cells is confirmed by cell viability. The h‐UCNPs/DOX/CS/MTX are tracked by cells UCL imaging and vivo MRI imaging. The excellent performance of UCL imaging and positive MRI images demonstrates that h‐UCNPs/DOX/CS/MTX can be used for UCL/MRI dual mode imaging. All the results show the potential application of h‐UCNPs/DOX/CS/MTX in pH responsive release and UCL/MRI dual imaging.     

铌酸钇里Bi~(3+)敏化Tm~(3+)的近红外量子剪裁发光的浓度效应

寻找新能源为全球目前面临着的重要课题,其中最理想的新能源为太阳能。近红外量子剪裁发光方法可以把硅或锗太阳能电池响应不够灵敏的大能量光子成倍的转换成为太阳能电池响应灵敏的小能量光子,能够解决光谱失配的问题,较大幅度的提高太阳能电池的效率。很有意义。报道了掺Tm~(3+)Bi~(3+)的铌酸钇磷光粉样品材料的近红外量子剪裁发光的浓度效应。通过测量激发谱与发光谱,发现Tm_(0.058)Bi_(0.010)Y_(0.932)NbO_4有很强的1 820.0 nm近红外量子剪裁发光;进一步的分析发现,它们是由交叉能量传递过程导致的多光子量子剪裁发光;还发现了有着很强的Bi~(3+)对Tm~(3+)的敏化近红外量子剪裁发光,302.0 nm光激发导致的Tm_(0.058)Bi_(0.010)Y_(0.932)NbO_4相对Tm_(0.058)Y_(0.995)NbO_4的1820.0 nm近红外量子剪裁发光的增强达到175.5倍。该结果对探索多光子近红外量子剪裁锗太阳能电池比较有意义。     

新型BODIPY荧光染料的合成及光谱性质研究

传统的BODIPY荧光染料具有荧光量子效率高、摩尔消光系数大、紫外吸收和荧光发射峰窄等优点,然而这类荧光染料普遍存在荧光发射波长短和Stokes位移小的缺点,因而限制了它们在体内生物传感及成像方面的广泛应用。为了得到荧光发射波长较长和Stokes位移大的BODIPY荧光染料,以BODIPY母核为基本结构,通过在它的8位连接吸电子性质的酯基来增加分子内电荷转移程度,同时在其3,5位引入供电子的芳香取代基增加分子的π共轭结构,合成得到了一类8位酯基取代的新型BODIPY荧光染料。所得到的新型BODIPY荧光染料的化学结构经过1H NMR, 13C NMR和HR-MS得以确认。光谱测试结果表明,这类染料的紫外吸收光谱(λ_abs=536 nm)和荧光发射光谱(λ_em=592 nm)与普通的BODIPY相比都发生显著红移(80 nm),并且保持了较高的荧光量子效率(Ф=0.43)。此外,这类BODIPY荧光染料的紫外可见吸收光谱和荧光发射光谱几乎完全分开,Stokes位移长达60 nm,可以有效地避免自吸收和生物样品的背景干扰。密度泛函理论计算结果表明,这种相对较大的Stokes位移主要是由于染料分子在基态和激发态下不同的几何构型所造成的。该类化合物的光物理性能受溶剂的影响小,是一类性能优良的新型荧光染料。细胞成像结果表明,染料1具有良好的细胞渗透性和光稳定性,可以实现对细胞的荧光成像。     

Two‐photon absorption induced anti‐Stokes emission in single InGaN/GAN quantum‐dot‐like objects

We observed crossed transitions and anti‐Stokes emissions in single quantum‐dot‐like objects embedded in the active layer of InGaN/GaN quantum disks by two‐photon absorption techniques. We proposed a phenomenological model based on the interplay between Auger effect and crossed transitions to explain the origin of anti‐Stokes emissions and the preferential excitation of 0D objects at the expense of their surroundings. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Colour tunability in a bimodal fluorescent hybrid nanostructure UCNPs@AuNPs@QDs

In the present work, lysine modified NaY_0.78Er_0.02Yb_0.2F₄ upconversion nanoparticles (UCNPs, positively charged) and lysine modified ZnSe:Mn²⁺ quantum dots (QDs, positively charged) are attached onto the surface of citrate reduced gold nanoparticles (AuNPs, negatively charged). The gold nanoparticles not only entangle the QDs and the UCNPs, through electrostatic interaction, but also tune the optical properties of UCNPs through the effect of surface plasmon resonance. The hybrid nanostructure gives green emission both through photoluminescence (under UV excitation) and through photon upconversion (under IR light excitation) process. The colour tuning is observed through variation in the size of QDs and through plasmonic effect of gold nanoparticles. In both the cases, the colour of emission gradually changes from green to red. The colour tunability and bi-modal photon conversion property of this material could be useful for its application in the field of bio-imaging and solar energy harvesting.     

Red Emissive Biocompatible Nanoparticles from Tetraphenylethene‐Decorated BODIPY Luminogens for Two‐Photon Excited Fluorescence Cellular Imaging and Mouse Brain Blood Vascular Visualization

BODIPY (4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene) is an emissive chromophore in solutions but suffers from fluorescence quenching when aggregated due to its flat molecular conformation and small Stokes shift. To create aggregate‐state emissive BODIPY luminogens, tetraphenylethene (TPE), which is a popular luminogen with intriguing aggregation‐induced emission (AIE) characteristic, is introduced as periphery to a methylated BODIPY core. Three TPE‐BODIPY adducts are synthesized and characterized, and their photophysical properties and electronic structures are investigated. The incorporation of AIE‐active TPE units alleviates aggregation‐caused quenching of BODIPY core, furnishing emissive nanoparticles based on TPE‐BODIPY adducts. Significantly, the two‐photon absorption (TPA) and two‐photon excited fluorescence (TPEF) properties are improved as more TPE units are attached. The luminogens with 3TPE units (3TPE‐BODIPY) shows the strongest TPA and TPEF in the wavelength range of 750–830 nm, with cross‐section values of 264 and 116 GM at 810 nm, respectively. Red emissive nanoparticles with a Stokes shift of 60 nm and a fluorescence quantum yield of 16% are attained by encapsulating 3TPE‐BODIPY with 1,2‐sistearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000]. The nanoparticles are biocompatible and function well in TPEF cellular imaging and mouse brain blood vascular visualization.     

Optical hybrid approaches to quantum information

This article reviews recent hybrid approaches to optical quantum information processing, in which both discrete and continuous degrees of freedom are exploited. There are well‐known limitations to optical single‐photon‐based qubit and multi‐photon‐based qumode implementations of quantum communication and quantum computation, when the toolbox is restricted to the most practical set of linear operations and resources such as linear optics and Gaussian operations and states. The recent hybrid approaches aim at pushing the feasibility, the efficiencies, and the fidelities of the linear schemes to the limits, potentially adding weak or measurement‐induced nonlinearities to the toolbox.     

Surface plasmon mediated near-field imaging and optical addressing in nanoscience

We present an overview of recent progress in "plasmonics". We focus our study on the observation and excitation of surface plasmon polaritons (SPPs) with optical near-field microscopy. We discuss in particular recent applications of photon scanning tunnelling microscope (PSTM) for imaging of SPP propagating in metal and dielectric wave guides. We show how near-field scanning optical microscopy (NSOM) can be used to optically and actively address remote nano objects such as quantum dots. Additionally we compare results obtained with near-field microcopy to those obtained with other optical far-field methods of analysis such as leakage radiation microscopy (LRM).     

From anti‐Stokes photoluminescence to resonant Raman scattering in GaN single crystals and GaN‐based heterostructures

The progress on anti‐Stokes photoluminescence and Stokes and anti‐Stokes Raman scattering in GaN single crystals and GaN/AlN heterostructures is reviewed. Anti‐Stokes photoluminescence investigated in the past was primarily attributed to two‐photon absorption, three‐photon absorption, and phonon‐assisted absorption. On the other hand, anti‐Stokes Raman scattering was used to determine electron‐phonon scattering time and decay time constant for longitudinal‐optical phonons. In a typical high electron mobility transistor based on GaN/AlN heterostructures, strong resonances were reached for first‐order and second‐order Raman scattering processes. Therefore, both Stokes and anti‐Stokes Raman intensities were dramatically enhanced. The feasibility of laser cooling of a nitride structure has been demonstrated. Anti‐Stokes photoluminescence and Raman scattering have potential applications in upconversion lasers and laser cooling of nitride ultrafast electronic and optoelectronic devices.     

Photoacoustic microscopy

Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (∼1 mm in soft tissue). With its excellent scalability, PAM can provide high‐resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering‐based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence‐based methods, such as wide‐field, confocal, and multi‐photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state‐of‐the‐art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.     

Correcting lateral photon scattering in an InSb infrared detector

Both luminescence and lock‐in thermography imaging, which are also evaluated quantitatively, are valuable methods for characterizing solar cells. For luminescence imaging of silicon solar cells it was recently discovered that photon scattering in the detector of the used camera leads to a certain amount of blurring, which may be corrected by image deconvolution for enabling a correct quantitative image interpretation. In this work the same effect is investigated for an infrared camera employing a cooled InSb‐based quantum detector. It is found that also here the photon scattering effect exists, though its influence is weaker than for luminescence imaging.     

Nonlinear optical microscopy for drug delivery monitoring and cancer tissue imaging

A multimodal nonlinear optical microscope that combines coherent anti‐Stokes Raman scattering (CARS), two‐photon excitation fluorescence (TPEF), second‐harmonic generation (SHG) and sum‐frequency generation (SFG) was developed and applied to image breast cancer tissue and MCF‐7 cells as well as monitoring anticancer drug delivery in live cells. TPEF imaging showed that drugs are preferentially localized in the cytoplasm and the nuclear envelope in resistant cells. Moreover, the extracellular matrix was observed by TPEF signals arising from elastin's autofluorescence and SHG signals from collagen fibrils in breast tissue sections. Additionally, CARS signals arising from proteins and (PO₂)⁻ allowed identification of tumors. Label‐free imaging with chemical contrast of significant components of cancer cells and tissue suggests the potential of multimodal nonlinear optical microscopy for early detection and diagnosis of cancer. Copyright © 2010 John Wiley & Sons, Ltd.     

原子系综中光学腔增强的Duan-Lukin-Cirac-Zoller写过程激发实验

原子系综中的Duan-Lukin-Cirac-Zoller(DLCZ)过程是产生光与原子(量子界面)量子关联和纠缠的重要手段.当一束写光与原子发生作用时,将会产生斯托克斯(Stokes)光子的自发拉曼散射,并同时产生一个自旋波(spin-wave)存储在原子系综中,上述过程即为DLCZ量子记忆产生过程.这一过程被广泛地研究.本文将87Rb原子系综放入驻波腔,并使Stokes光子与光学腔共振,我们观察到有腔且锁定的情况下Stokes光子产生概率比无腔时增大了8.7倍.在此条件下研究了Stokes光子产生概率和写光功率的关系,Stokes光子产生概率随写光功率线性增大.     

Detecting lateral interfaces with focus‐engineered coherent anti‐Stokes Raman scattering microscopy

Focus‐engineered coherent anti‐Stokes Raman scattering (FE‐CARS) microscopy is used to highlight the lateral interfaces between chemically distinct media. Interface highlighting is achieved by using a HG10 mode for the Stokes laser beam and a HG00 mode for the pump laser beam in the forward detection scheme. The spectral and the orientation dependence of FE‐CARS are found to be in agreement with theoretical predictions. A brief discussion on the relevance of this technique for imaging third‐order nonlinear susceptibility interfaces in thin samples of biological or chemical importance is presented. Copyright © 2008 John Wiley & Sons, Ltd.     

Development of fast,simultaneous and multi‐technique scanning hard X‐ray microscopy at Synchrotron Soleil

A distributed fast‐acquisition system for synchronized multi‐technique experiments is presented, in which the collection of metadata and the asynchronous merging of large data volumes from multiple detectors are managed as part of the data collection process. This fast continuous scanning scheme, named FLYSCAN, enables measurement of microscopy data on a timescale of milliseconds per pixel. Proof‐of‐principle multi‐technique experiments, namely scanning X‐ray fluorescence spectrometry combined with absorption, differential phase contrast and dark‐field imaging, have been performed on biological and geological samples.     

High‐Fidelity Hybrid Quantum Gates between a Flying Photon and Diamond Nitrogen‐Vacancy Centers Assisted by Low‐Q Single‐Sided Cavities

High‐fidelity universal quantum gates are crucial in quantum computing. Three high‐fidelity universal quantum gates, namely the hybrid controlled NOT gate, the hybrid Toffoli gate, and the hybrid Fredkin gate, on a flying photon qubit and diamond nitrogen‐vacancy (NV) centers, assisted by low‐Q single‐sided cavities, are presented. Errors due to the imperfection of the practical input–output process are detected to improve the fidelity of these quantum gates, which therefore relaxes the requirement on their implementation, since strong coupling is no longer mandatory. In addition, quantum gates have the advantage that they can work faithfully even when the resonant condition among the NV center, the photon, and the cavity is not strictly satisfied, or the NV centers are not identical. The performance and success probability of these quantum gates are analyzed, finding that these schemes are feasible with current technology.     

Two Photon Spectroscopy Can Serve as a Marker of Protein Denaturation Pathway

Rhodamine group of molecules are widely used dyes for imaging of biological molecules. Application of these dyes however includes a limitation that these molecules absorb in the visible range of the spectrum, which does not fall in the ‘biologically transparent window’ (BTW). Two photon absorption (TPA) process could come up with an alternate solution to this as these dyes could be excited in the near infrared (NIR) window to extract similar information. To validate this we have investigated TPA cross section (TPACS, σ₂) of two rhodamine dyes, namely Rhodamine 6G (R6G), Rhodamine B (RhB), site selectively bound with a model protein, bovine serum albumin (BSA), by exciting at 800 nm. Two photon spectroscopy and imaging confirms the binding of the dye to the protein. The decreases in TPACS with increasing temperature at a fixed BSA concentration excellently follows the temperature induced structural transition of BSA as the protein transforms from a molten globule to unfolded conformation beyond 60 °C, which has previously been established through circular dichroism (CD) measurements. The thus established resemblance in TPACS and CD measurement trends thus strongly affirms the suitability of TPA process in protein imaging and as an alternative marker to tracking its conformational transformations using NIR radiation.