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微束X射线荧光成像方法及其在纳米材料生物学效应研究中的应用
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摘要
纳米材料生物学效应研究是将纳米技术与生物、化学、物理、毒理学与医学等领域的实验技术结合起来,研究纳米尺度物质与生命过程相互作用及其结果的一个新兴科学领域。为了完全评估纳米材料的潜在危险,新的研究方法和手段是解决纳米材料生物学效应问题的关键。同步辐射X射线荧光成像方法,由于具有灵敏度高、无损分析、制样简单、能分析含水样品、能同时探测多种元素、不需要真空条件等优点,非常适合纳米材料生物学效应领域的研究。
     硬X射线微探针光束线站是上海光源首批建设的七条线站中唯一的一条硬X射线微束线站,提供微束X射线荧光分析、微束X射线吸收精细结构、微束X射线衍射等多种实验方法。虽然能够提供高通量的硬X射线微束,当用户进行细胞样品或其它微米级样品实验研究时,BL15U1线站现有的实验条件已略显不足。例如微区扫描时,样品定位方法不便捷,可见显微镜粗略划定的扫描范围与实际扫描范围有20μm的误差,需要预扫描才能获得精确的微区位置,费时费力。还有,1.5μm×1.5μm的微束已不能满足细胞样品的实验要求,微束对细胞样品的成像结果,只能看到大概的轮廓结构,不能区分细胞内微机构和亚细胞器。因此,发展更快速的样品定位方法、提高X射线束的空间分辨率,既是用户实验过程中对线站的要求,也是线站自身研究方法发展的必然。
     本论文设计并应用了硬X射线微米探针高精度样品定位系统,实现了样品的微米级快速离线定位,使用户能够快速、准确地定位微区研究对象。将定位系统应用于研究纳米TiO2在小鼠肺部毒性的工作中,研究了肺组织对纳米TiO2的排除机制,及纳米TiO2的入侵对肺组织内K、Ca、Fe、Cu、Zn等原生元素的影响。参与设计和搭建了BL15U1线站基于波带片的亚微米聚焦系统,主要工作为亚微米光斑的调试和实验应用工作,得到亚微米聚焦光,并对亚微米光斑的焦深、聚焦效率、通量、通量密度、元素探测限、细胞实验结果等进行了研究。将亚微米光斑应用到量子点免疫荧光染色后细胞的X射线荧光成像工作中,成功对Hela细胞内的微管蛋白进行了CdSe/ZnS量子点的免疫荧光染色,并取得了染色后细胞亚微米X射线荧光成像工作的初步结果。
     第一章,首先从纳米材料生物学效应、X射线荧光成像方法、上海光源硬X射线微探针线站三个方面进行了综述,介绍了本论文工作的背景,然后总结提出了本论文的研究内容。第一小节介绍了纳米材料生物学效应的概念、当前面临的挑战和各种研究方法,及X射线荧光成像方法在纳米材料生物学效应研究中的优势;第二小节介绍了X射线荧光物理学基础、同步辐射X射线荧光分析、X射线荧光定量分析方法、及定量分析软件PyMCA和GeoPIXE;第三小节介绍了上海光源硬X射线微探针线站、线站开展的实验方法、及当前线站的优势和不足;最后提出了本论文的研究内容。
     第二章,设计应用了硬X射线微米探针高精度样品定位系统。该系统由离线样品显微镜系统、在线样品实验系统和高精度定位样品架三部分组成,首次在国内同步辐射装置上实现样品在微米范围内的定位。实验验证了该系统在X方向的平均误差为1.3μm,Z方向的平均误差为2.5μm,系统快速、准确可靠。
     第三章,应用样品定位系统和微米级的光斑,研究纳米TiO2作用于小鼠肺组织的毒性。研究了肺组织对纳米TiO2的排除机制,及纳米TiO2的入侵对肺组织内K、Ca、Fe、Cu、Zn等原生元素的影响。
     第四章,介绍了BL15U1基于波带片的硬X射线亚微米聚焦系统。介绍了X射线波带片聚焦的原理、亚微米聚焦系统的设计和构成、聚焦系统的安装与准直、以及聚焦系统的调试和实验。得到亚微米聚焦光,并对亚微米光斑的焦深、聚焦效率、通量、通量密度、元素探测限、细胞实验结果等进行了研究。
     第五章,将亚微米光斑应用到量子点免疫荧光染色后细胞的X射线荧光成像工作中。介绍了量子点的性能及其在细胞成像中的应用、细胞内量子点的免疫荧光染色、以及量子点染色后细胞的亚微米光斑X射线荧光成像工作。
     第六章,总结本论文工作,并进行了展望。
Biological effects of nanomaterials is a new scientific field studying theinteraction of nanoscale materials and life processes, combining nanotechnology withthe experimental techniques in biology, chemistry, physics, medicine and toxicology.In order to fully assess the potential dangers of nanomaterials, new research methodsand techniques are the key of solving the problem of biological effects ofnanomaterials. Because of its high sensitivity, non-destructive analysis, simple samplepreparation, analyzing aqueous samples, detecting multiple elements simultaneously,needless vacuum conditions, etc, synchrotron radiation X-ray fluorescence imagingmethod is an ideal tool for the research of biological effects of nanomaterials.
     BL15U1hard X-ray microprobe beamline is the only hard X-ray microfocusbeamline among the first seven beamline in Shanghai Synchrotron Radiation Facitity(SSRF), providing multiple experimental methods, including micro X-rayfluorescence analysis, micro X-ray absorption fine structure, micro X-ray diffraction.Though it provides high flux hard X-ray beam, the existing experimental conditionsof BL15U1beamline have been slightly less, when users do research into cells orother microscale samples. For example, when doing micro-scanning, the samplepositioning method is not convenient. There is an error of20μm between the roughscan scope delineated by the visible light microscope and the actual scan scope. Apre-scan is needed to get the exact micro location, which spends lots of research time.In addition, the microbeam of1.5μm×1.5μm can not satisfy the requirements of cellsample experiments. From the cell sample imaging results using microbeam, we onlyget the outline of the structure in cells, instead of clear microstructure and subcellularorganelles. Therefore, developing a rapid sample positioning method, and improvingthe spatial resolution of X-ray beam, are not only the requirements of doingexperiment for users, but also the necessary trend of research methods developing forbeamline.
     In this paper, a new kind of hard X-ray microprobe precision sample positioningsystem is designed and applied to achieve fast offline sample positioning, helpingusers to locate micro studying objects quickly and accurately. The positioning system was used to study pulmonary toxicity of nanoscale titanium dioxide in mice. Theexclusion mechanism of nano TiO2from lung tissue, and the effects of the nativeelements (K, Ca, Fe, Cu, Zn) in lung tissue because of the exposing of nano TiO2,were studied. I took part in the design and construction of the BL15U1beamlinesubmicron focusing system based on zone plates. The main work of mine isdebugging and experiment of submicron X-ray spot. A submicron spot was gotten.Many features of submicron spot were studied, such as depth of focus, focusingefficiency, flux, flux density, detection limit, cell experiments and so on. Thesubmicron spot was applied to image the cells after quantum dotsimmunofluorescence staining, using X-ray fluorescence. The tubulin of Hela cells wasimmunofluorescence stained successfully by CdSe/ZnS quantum dots. Thepreliminary results of research of submicron X-ray fluorescence image to stained cellswere gotten.
     In the first chapter, we reviewed the biological effects of namomaterials, X-rayfluorescence imaging method, and the hard X-ray microprobe beamline station inSSRF, described the background of the work. In the first section, we introduced theconcept of biological effects of nanomaterials, current challenges and researchmethods, the advantages of X-ray fluorescence imaging method to study thebiological effects of nanomaterials. In the second section, we introduced the physicsprinciple of X-ray fluorescence, synchrotron radiation X-ray fluorescence analysis,quantitative X-ray fluorescence analysis, and quantitative analysis software (PyMCA,GeoPIXE). In the third section, we introduced the hard X-ray microprobe beamlinestation, the experimental methods provided by BL15U1, current advantages anddisadvantages. At last, we presented the research content.
     In the second chapter, a new kind of hard X-ray microprobe precision samplepositioning system is designed and applied. The positioning system is composed ofthree parts: off-line sample microscope system, on-line sample experiment system,high-precision positioning sample holder. It’s the first time in the domesticsynchrotron radiation devices to achieve sample offline positioning in micron scalequickly. The experiment results showed that the average errors of X-axis and Z-axiswere1.3μm and2.5μm respectively, using the positioning method. The sample offlinepositioning system is fast, accurate, reliable.
     In the third chapter, the positioning system and micro X-ray spot were used to study pulmonary toxicity of nanoscale titanium dioxide in mice. The exclusionmechanism of nano TiO2from lung tissue, and the effects of the native elements (K,Ca, Fe, Cu, Zn) in lung tissue because of the exposing of nano TiO2, were studied.
     In the fourth chapter, we introduced the BL15U1hard X-ray submicron focussystem based on zone plates. X-ray focusing principle of zone plates, design andcomposition of submicron focusing system, collimating and installation of submicronfocusing system, debugging and experiment of focusing system were introduced. Asubmicron spot was gotten. Many features of submicron spot were studied, such asdepth of focus, focusing efficiency, flux, flux density, detection limit, cell experimentsand so on.
     In the fourth chapter, the submicron X-ray spot was applied to image thequantum dots immunofluorescence staining cells using X-ray fluorescence. Theproperties of quantum dots and their application in cell imaging, intracellularimmunofluorescence staining of quantum dots, the submicron spot X-ray fluorescenceimaging of the quantum dot staining cells were introduced.
     In the sixth chapter, we summarized the work and prospected.
引文
[1] CHEN C, LI Y-F, QU Y, et al. Advanced nuclear analytical and relatedtechniques for the growing challenges in nanotoxicology [J]. Chemical SocietyReviews,2013,42(21):8266-303.
    [2] COLVIN V L. The potential environmental impact of engineerednanomaterials [J]. Nat Biotech,2003,21(10):1166-70.
    [3] NEL A, XIA T, M DLER L, et al. Toxic Potential of Materials at theNanolevel [J]. Science,2006,311(5761):622-7.
    [4] OBERDORSTER G, OBERDORSTER E, OBERDORSTER J.Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles[J]. Environmental Health Perspectives,2005,113(7):823-39.
    [5]ZHAO Y, XING G, CHAI Z. Nanotoxicology: Are carbon nanotubes safe?[J].Nat Nano,2008,3(4):191-2.
    [6] CAMPAGNOLO L, MASSIMIANI M, PALMIERI G, et al. Biodistributionand toxicity of pegylated single wall carbon nanotubes in pregnant mice [J]. Part FibreToxicol,2013,10(
    [7] WANG H F, WANG J, DENG X Y, et al. Biodistribution of carbonsingle-wall carbon nanotubes in mice [J]. J Nanosci Nanotechno,2004,4(8):1019-24.
    [8] MENG H, CHEN Z, XING G, et al. Ultrahigh reactivity provokesnanotoxicity: Explanation of oral toxicity of nano-copper particles [J]. ToxicologyLetters,2007,175(1–3):102-10.
    [9] WANG B, FENG W, WANG M, et al. Transport of Intranasally Instilled FineFe2O3Particles into the Brain: Micro-distribution, Chemical States, andHistopathological Observation [J]. Biol Trace Elem Res,2007,118(3):233-43.
    [10] WANG J X, CHEN C Y, YU H W, et al. Distribution of TiO2particles inthe olfactory bulb of mice after nasal inhalation using microbeam SRXRF mappingtechniques [J]. J Radioanal Nucl Chem,2007,272(3):527-31.
    [11] LAO F, CHEN L, LI W, et al. Fullerene Nanoparticles Selectively EnterOxidation-Damaged Cerebral Microvessel Endothelial Cells and Inhibit JNK-RelatedApoptosis [J]. ACS Nano,2009,3(11):3358-68.
    [12] MENG H, XING G, SUN B, et al. Potent Angiogenesis Inhibition by theParticulate Form of Fullerene Derivatives [J]. ACS Nano,2010,4(5):2773-83.
    [13] ZHAO F, ZHAO Y, LIU Y, et al. Cellular Uptake, IntracellularTrafficking, and Cytotoxicity of Nanomaterials [J]. Small,2011,7(10):1322-37.
    [14] FISCHER H C, CHAN W C W. Nanotoxicity: the growing need for invivo study [J]. Current Opinion in Biotechnology,2007,18(6):565-71.
    [15] NEL A E, MADLER L, VELEGOL D, et al. Understandingbiophysicochemical interactions at the nano-bio interface [J]. Nat Mater,2009,8(7):543-57.
    [16] DHAWAN A, SHARMA V. Toxicity assessment of nanomaterials:methods and challenges [J]. Anal Bioanal Chem,2010,398(2):589-605.
    [17] WANG L, LI Y-F, ZHOU L, et al. Characterization of gold nanorods invivo by integrated analytical techniques: their uptake, retention, and chemical forms[J]. Anal Bioanal Chem,2010,396(3):1105-14.
    [18] TETARD L, PASSIAN A, FARAHI R H, et al. Atomic force microscopyof silica nanoparticles and carbon nanohorns in macrophages and red blood cells [J].Ultramicroscopy,2010,110(6):586-91.
    [19] PORTER A E, GASS M, MULLER K, et al. Visualizing the Uptake ofC60to the Cytoplasm and Nucleus of Human Monocyte-Derived Macrophage CellsUsing Energy-Filtered Transmission Electron Microscopy and Electron Tomography[J]. Environmental Science&Technology,2007,41(8):3012-7.
    [20] SERDA R E, FERRATI S, GODIN B, et al. Mitotic trafficking of siliconmicroparticles [J]. Nanoscale,2009,1(2):250-9.
    [21] QU Y, LI W, ZHOU Y, et al. Full Assessment of Fate and PhysiologicalBehavior of Quantum Dots Utilizing Caenorhabditis elegans as a Model Organism [J].Nano Letters,2011,11(8):3174-83.
    [22] ASHARANI P V, LOW KAH MUN G, HANDE M P, et al. Cytotoxicityand Genotoxicity of Silver Nanoparticles in Human Cells [J]. ACS Nano,2008,3(2):279-90.
    [23] SNIGIREVA I, SNIGIREV A. X-Ray microanalytical techniques basedon synchrotron radiation [J]. Journal of Environmental Monitoring,2006,8(1):33-42.
    [24] BERTRAND M, WEBER G, SCHOEFS B T. Metal determination andquantification in biological material using particle-induced X-ray emission [J]. TrACTrends in Analytical Chemistry,2003,22(4):254-62.
    [25] WELZ B, BORGES D L G. Atomic Spectrometry and ElementalAnalysis [M]. digital Encyclopedia of Applied Physics. Wiley-VCH Verlag GmbH&Co. KGaA.2003.
    [26] PRZYBY OWICZ W J, MESJASZ-PRZYBY OWICZ J, PINEDA C A,et al. Elemental mapping using proton-induced x-rays [J]. X-Ray Spectrom,2001,30(3):156-63.
    [27] KARYDAS A-G, SOKARAS D, ZARKADAS C, et al.3D MicroPIXE-a new technique for depth-resolved elemental analysis [J]. J Anal AtomSpectrom,2007,22(10):1260-5.
    [28] LI Y, CHEN C, LI B, et al. Elimination efficiency of different reagentsfor the memory effect of mercury using ICP-MS [J]. J Anal Atom Spectrom,2006,21(1):94-6.
    [29] BECKER J S, ZORIY M, BECKER J S, et al. Laser ablation inductivelycoupled plasma mass spectrometry (LA-ICP-MS) in elemental imaging of biologicaltissues and in proteomics [J]. J Anal Atom Spectrom,2007,22(7):736-44.
    [30] DRESCHER D, GIESEN C, TRAUB H, et al. Quantitative Imaging ofGold and Silver Nanoparticles in Single Eukaryotic Cells by Laser Ablation ICP-MS[J]. Analytical Chemistry,2012,84(22):9684-8.
    [31] WU B, BECKER J S. Imaging techniques for elements and elementspecies in plant science [J]. Metallomics,2012,4(5):403-16.
    [32] ADAMS F, VAN VAECK L, BARRETT R. Advanced analyticaltechniques: platform for nano materials science [J]. Spectrochimica Acta Part B:Atomic Spectroscopy,2005,60(1):13-26.
    [33] SHON H K, PARK J, CHOI I, et al. Mass Imaging of Iron OxideNanoparticles Inside Cells for In Vitro Cytotoxicity [J]. J Nanosci Nanotechno,2011,11(1):638-41.
    [34] CHO N-H, CHEONG T-C, MIN J H, et al. A multifunctional core-shellnanoparticle for dendritic cell-based cancer immunotherapy [J]. Nat Nano,2011,6(10):675-82.
    [35] FARRER R A, BUTTERFIELD F L, CHEN V W, et al. Highly EfficientMultiphoton-Absorption-Induced Luminescence from Gold Nanoparticles [J]. NanoLetters,2005,5(6):1139-42.
    [36] DURR N J, LARSON T, SMITH D K, et al. Two-Photon LuminescenceImaging of Cancer Cells Using Molecularly Targeted Gold Nanorods [J]. NanoLetters,2007,7(4):941-5.
    [37] CHAO W, KIM J, REKAWA S, et al. Demonstration of12nmResolution Fresnel Zone Plate Lens based Soft X-ray Microscopy [J]. Opt Express,2009,17(20):17669-77.
    [38] WU X, SCHULTZ P G. Synthesis at the Interface of Chemistry andBiology [J]. J Am Chem Soc,2009,131(35):12497-515.
    [39] SCHROER C G, KURAPOVA O, PATOMMEL J, et al. Hard x-raynanoprobe based on refractive x-ray lenses [J]. Appl Phys Lett,2005,87(12):-.
    [40] BUSSY C, CAMBEDOUZOU J, LANONE S, et al. Carbon Nanotubesin Macrophages: Imaging and Chemical Analysis by X-ray Fluorescence Microscopy[J]. Nano Letters,2008,8(9):2659-63.
    [41] UCHIDA M, MCDERMOTT G, WETZLER M, et al. Soft X-raytomography of phenotypic switching and the cellular response to antifungal peptoidsin Candida albicans [J]. Proceedings of the National Academy of Sciences,2009,106(46):19375-80.
    [42] CHAO W, HARTENECK B D, LIDDLE J A, et al. Soft X-raymicroscopy at a spatial resolution better than15[thinsp]nm [J]. Nature,2005,435(7046):1210-3.
    [43] CHEN N, HE Y, SU Y, et al. The cytotoxicity of cadmium-basedquantum dots [J]. Biomaterials,2012,33(5):1238-44.
    [44] MAJUMDAR S, PERALTA-VIDEA J R, CASTILLO-MICHEL H, et al.Applications of synchrotron mu-XRF to study the distribution of biologicallyimportant elements in different environmental matrices: A review [J]. Anal Chim Acta,2012,755(1-16.
    [45] PAUNESKU T, VOGT S, MASER J, et al. X-ray fluorescencemicroprobe imaging in biology and medicine [J]. J Cell Biochem,2006,99(6):1489-502.
    [46] FAHRNI C J. Biological applications of X-ray fluorescence microscopy:exploring the subcellular topography and speciation of transition metals [J]. Curr OpinChem Biol,2007,11(2):121-7.
    [47]吉昂,陶光仪,卓尚军, et al. X射线荧光光谱分析[M].北京:化学工业出版社,2003.
    [48]罗立强,詹秀春,李国会. X射线荧光光谱仪[M].北京:化学工业出版社,2008.
    [49]吴应荣,巢志瑜,潘巨详, et al.同步辐射微束X射线荧光分析实验站[J].高能物理与核物理,1997,21(5):475-80.
    [50]马礼敦,杨福家.同步辐射应用概论(第二版)[M].上海:复旦大学出版社,2005.
    [51] SHIRAIWA T, FUJINO N. Theoretical Calculation of Fluorescent X-RayIntensities in Fluorescent X-Ray Spectrochemical Analysis [J]. Jpn J Appl Phys,1966,5(10):886-&.
    [52] LEMBERGE P, VAN ESPEN P J. Quantitative energy-dispersive x-rayfluorescence analysis of liquids using partial least-squares regression [J]. X-RaySpectrom,1999,28(2):77-85.
    [53] ADAMS M J, ALLEN J R. Quantitative X-ray fluorescence analysis ofgeological materials using partial least-squares regression [J]. Analyst,1998,123(4):537-41.
    [54] SHERMAN J. The Theoretical Derivation of Fluorescent X-RayIntensities from Mixtures [J]. Spectrochim Acta,1955,7(5):283-306.
    [55]张延乐.无标样X射线荧光定量分析方法在BL15U1的实现[D];中科院上海应用物理研究所,2010.
    [56] CRISS J W, BIRKS L S. Calculation Methods for Fluorescent X-RaySpectrometry-Empirical Coefficients Vs Fundamental Parameters [J]. AnalyticalChemistry,1968,40(7):1080-&.
    [57] GREAVES E D, BERNASCONI G, WOBRAUSCHEK P, et al. Directtotal-reflection X-ray fluorescence trace element analysis of organic matrix materialswith a semiempirical standard [J]. Spectrochimica Acta Part B-Atomic Spectroscopy,1997,52(7):923-33.
    [58] YAP C T, AYALA R E, WOBRAUSCHEK P. QuantitativeTrace-Element Determination in Thin Samples by Total ReflectionX-Ray-Fluorescence Using the Scattered Radiation Method [J]. X-Ray Spectrom,1988,17(5):171-4.
    [59] OJEDA N, GREAVES E D, ALVARADO J, et al. Determination of V, Fe,Ni and S in Petroleum Crude-Oil by Total-Reflection X-Ray-Fluorescence [J].Spectrochimica Acta Part B-Atomic Spectroscopy,1993,48(2):247-53.
    [60] MARCO L M, GREAVES E D, ALVARADO J. Analysis of humanblood serum and human brain samples by total reflection X-ray fluorescencespectrometry applying Compton peak standardization [J]. Spectrochimica Acta PartB-Atomic Spectroscopy,1999,54(10):1469-80.
    [61] WANG H-J, WANG M, WANG B, et al. Quantitative imaging ofelement spatial distribution in the brain section of a mouse model of Alzheimer'sdisease using synchrotron radiation X-ray fluorescence analysis [J]. J Anal AtomSpectrom,2010,25(3):328-33.
    [62] DEVRIES J L, VREBOS B. Quantification by XRF analysis of infinitelythick samples [M]//GRIEKEN R V, MARKOWICZ A. Handbook of X-raySpectrometry, Methods and Techniques. New York; Marcel Dekker inc.1993.
    [63] MARKOWICZ A, VANGRIEKEN R. Quantification in XRF analysis ofintermediate-thickness samples [M]//GRIEKEN R V, MARKOWICZ A. Handbook ofX-ray Spectrometry, Methods and Techniques. New York; Marcel Dekker INC.1993.
    [64]余笑寒,李爱国.上海光源硬X射线微聚焦光束线站设计报告[J].2006,
    [65]闫芬.基于EPICS的同步辐射微探针实验站控制和数据采集系统[D];中科院上海应用物理研究所,2011.
    [66]毛成文.上海光源硬X射线微聚焦线站微聚焦系统研究[D];中科院上海应用物理研究所,2009.
    [67] ZHENG M Z, CAI C, HU Y, et al. Spatial distribution of arsenic andtemporal variation of its concentration in rice [J]. New Phytol,2011,189(1):200-9.
    [68] FAN X P, HARBOTTLE G, GAO Q, et al. Brass before bronze? Earlycopper-alloy metallurgy in China [J]. J Anal Atom Spectrom,2012,27(5):821-6.
    [69] WANG H J, WANG M, WANG B, et al. The distribution profile andoxidation states of biometals in APP transgenic mouse brain: dyshomeostasis with ageand as a function of the development of Alzheimer's disease [J]. Metallomics,2012,4(3):289-96.
    [70] ZHANG J, TIAN S K, LU L L, et al. Lead tolerance and cellulardistribution in Elsholtzia splendens using synchrotron radiation micro-X-rayfluorescence [J]. J Hazard Mater,2011,197(264-71.
    [71] WANG J, QIN H Y, LIU J B, et al. Atomic Structure ofPolypyrrole-Modified Carbon-Supported Cobalt Catalyst [J]. J Phys Chem C,2012,116(38):20225-9.
    [72] ZHANG L J, LI J, DU Y P, et al. Lattice distortion and its role in themagnetic behavior of the Mn-doped ZnO system [J]. New J Phys,2012,14(
    [73] CONG Y H, HONG Z H, ZHOU W M, et al. Conformational Orderingon the Growth Front of Isotactic Polypropylene Spherulite [J]. Macromolecules,2012,45(21):8674-80.
    [74] SUN L L, CHEN X J, GUO J, et al. Re-emerging superconductivity at48kelvin in iron chalcogenides [J]. Nature,2012,483(7387):67-9.
    [75] WU Y, WU X, QIN S, et al. Compressibility and phase transition ofintermetallic compound Fe2Ti [J]. J Alloy Compd,2013,558(160-3.
    [76] QIU J K, DENG B A, YANG Q, et al. Internal elemental imaging byscanning X-ray fluorescence microtomography at the hard X-ray microprobebeamline of the SSRF: Preliminary experimental results [J]. Nucl Instrum Meth B,2011,269(22):2662-6.
    [77] COREZZI S, URBANELLI L, CLOETENS P, et al. Synchrotron-basedX-ray fluorescence imaging of human cells labeled with CdSe quantum dots [J]. AnalBiochem,2009,388(1):33-9.
    [78] FINNEY L, MANDAVA S, URSOS L, et al. X-ray fluorescencemicroscopy reveals large-scale relocalization and extracellular translocation ofcellular copper during angiogenesis [J]. P Natl Acad Sci USA,2007,104(7):2247-52.
    [79]孙鑫,余安萍. VC++深入详解[M].电子工业出版社,2006.
    [80]毛成文.硬X射线纳米尺度聚焦方法研究[D];中科院上海应用物理研究所,2012.
    [81] XUE C F, WANG Y, GUO Z, et al. High-performance soft x-rayspectromicroscopy beamline at SSRF [J]. Rev Sci Instrum,2010,81(10):
    [82] KIRZ J. Phase Zone Plates for X-Rays and Extreme Uv [J]. J Opt SocAm,1974,64(3):301-9.
    [83] SERVICE R F. Nanotoxicology: Nanotechnology grows up [J]. Science,2004,304(5678):1732-4.
    [84] FADEEL B, KAGAN V, KRUG H, et al. There's plenty of room at theforum: Potential risks and safety assessment of engineered nanomaterials [J].Nanotoxicology,2007,1(2):73-84.
    [85] ROGUEDA P G A, TRAINI D. The nanoscale in pulmonary delivery.Part1: deposition, fate, toxicology and effects [J]. Expert Opinion on Drug Delivery,2007,4(6):595-606.
    [86] SUN D, MENG T T, LOONG T H, et al. Removal of natural organicmatter from water using a nano-structured photocatalyst coupled with filtrationmembrane [J]. Water Science and Technology,2004,49(1):103-10.
    [87] WAKEFIELD G, STOTT J. Photostabilization of organic UV-absorbingand anti-oxidant cosmetic components in formulations containing micronizedmanganese-doped titanium oxide [J]. Journal of Cosmetic Science,2006,57(5):385-95.
    [88] GUARINO M, COSTA A, PORRO M. Photocatalytic TiO2coating-toreduce ammonia and greenhouse gases concentration and emission from animalhusbandries [J]. Bioresource Technology,2008,99(7):2650-8.
    [89] CHEN H W, SU S F, CHIEN C T, et al. Titanium dioxide nanoparticlesinduce emphysema-like lung injury in mice [J]. Faseb Journal,2006,20(13):2393-+.
    [90] WARHEIT D B, WEBB T R, REED K L, et al. Pulmonary toxicity studyin rats with three forms of ultrafine-TiO2particles: Differential responses related tosurface properties [J]. Toxicology,2007,230(1):90-104.
    [91] WARHEIT D B, BROCK W J, LEE K P, et al. Comparative pulmonarytoxicity inhalation and instillation studies with different TiO2particle formulations:Impact of surface treatments on particle toxicity [J]. Toxicological Sciences,2005,88(2):514-24.
    [92] OBERDORSTER G, FERIN J, LEHNERT B E. Correlation betweenParticle-Size, in-Vivo Particle Persistence, and Lung Injury [J]. Environmental HealthPerspectives,1994,102(173-9.
    [93] WARHEIT D B, WEBB T R, SAYES C M, et al. Pulmonary instillationstudies with nanoscale TiO2rods and dots in rats: Toxicity is not dependent uponparticle size and surface area [J]. Toxicological Sciences,2006,91(1):227-36.
    [94] KEMNER K M, KELLY S D, LAI B, et al. Elemental and redox analysisof single bacterial cells by X-ray microbeam analysis [J]. Science,2004,306(5296):686-7.
    [95] KORBAS M, BLECHINGER S R, KRONE P H, et al. Localizingorganomercury uptake and accumulation in zebrafish larvae at the tissue and cellularlevel [J]. P Natl Acad Sci USA,2008,105(34):12108-12.
    [96] BUSH A I. Metals and neuroscience [J]. Curr Opin Chem Biol,2000,4(2):184-91.
    [97] VAN RAVENZWAAY B, LANDSIEDEL R, FABIAN E, et al.Comparing fate and effects of three particles of different surface properties:Nano-TiO2, pigmentary TiO2and quartz [J]. Toxicology Letters,2009,186(3):152-9.
    [98] SONG Y L, FUKUDA N, BAI C X, et al. Role of aquaporins in alveolarfluid clearance in neonatal and adult lung, and in oedema formation following acutelung injury: studies in transgenic aquaporin null mice [J]. Journal ofPhysiology-London,2000,525(3):771-9.
    [99] LAM C W, JAMES J T, MCCLUSKEY R, et al. Pulmonary toxicity ofsingle-wall carbon nanotubes in mice7and90days after intratracheal instillation [J].Toxicological Sciences,2004,77(1):126-34.
    [100] SEMMLER-BEHNKE M, TAKENAKA S, FERTSCH S, et al. Efficientelimination of inhaled nanoparticles from the alveolar region: Evidence for interstitialuptake and subsequent reentrainment onto airway epithelium [J]. EnvironmentalHealth Perspectives,2007,115(5):728-33.
    [101] BERMUDEZ E, MANGUM J B, WONG B A, et al. Pulmonaryresponses of mice, rats, and hamsters to subchronic inhalation of ultrafine titaniumdioxide particles [J]. Toxicological Sciences,2004,77(2):347-57.
    [102] DAL-SECCO D, CUNHA T M, FREITAS A, et al. Hydrogen sulfideaugments neutrophil migration through enhancement of adhesion molecule expressionand prevention of CXCR2internalization: Role of ATP-sensitive potassium channels[J]. Journal of Immunology,2008,181(6):4287-98.
    [103] ELFERINK J G R, DE KOSTER B M. Inhibition ofinterleukin-8-activated human neutrophil chemotaxis by thapsigargin in a calcium-and cyclic AMP-dependent way [J]. Biochemical Pharmacology,2000,59(4):369-75.
    [104] KRAUSE K H, CAMPBELL K P, WELSH M J, et al. The CalciumSignal and Neutrophil Activation [J]. Clinical Biochemistry,1990,23(2):159-66.
    [105] SARAIVA R M, MASUDA M O, OLIVEIRACASTRO G M. Outwardpotassium current oscillations in macrophage polykaryons: extracellular calcium entryand calcium-induced calcium release [J]. Brazilian Journal of Medical and BiologicalResearch,1997,30(11):1349-57.
    [106] TOYAMA K, SAITO T, FUJIWARA Y, et al. Intermediate conductancecalcium-activated potassium channel, KCa3.1, plays an important role in macrophage(MO) migration in atheroscierosis [J]. Faseb Journal,2007,21(6): A854-A.
    [107] GOVEN D, BOUTTEN A, LECON-MALAS V, et al. Induction of HemeOxygenase-1, Biliverdin Reductase and H-Ferritin in Lung Macrophage in Smokerswith Primary Spontaneous Pneumothorax: Role of HIF-1alpha [J]. Plos One,2010,5(5):-.
    [108] WARD P P, MENDOZA-MENESES M, PARK P W, et al.Stimulus-dependent impairment of the neutrophil oxidative burst response inlactoferrin-deficient mice [J]. American Journal of Pathology,2008,172(4):1019-29.
    [109] JOSHI P C, RAYNOR R, FAN X, et al. HIV-1-transgene expression inrats decreases alveolar macrophage zinc levels and phagocytosis [J]. AmericanJournal of Respiratory Cell and Molecular Biology,2008,39(2):218-26.
    [110] JOSHI P C, MEHTA A, JABBER W S, et al. Zinc Deficiency MediatesAlcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats [J].American Journal of Respiratory Cell and Molecular Biology,2009,41(2):207-16.
    [111] WHITE C, LEE J, KAMBE T, et al. A Role for the ATP7ACopper-transporting ATPase in Macrophage Bactericidal Activity [J]. Journal ofBiological Chemistry,2009,284(49):33949-56.
    [112] BABU U, FAILLA M L. Respiratory Burst and Candidacidal Activity ofPeritoneal-Macrophages Are Impaired in Copper-Deficient Rats [J]. Journal ofNutrition,1990,120(12):1692-9.
    [113] BABU U, FAILLA M L. Copper Status and Function of Neutrophils AreReversibly Depressed in Marginally and Severely Copper-Deficient Rats [J]. Journalof Nutrition,1990,120(12):1700-9.
    [114] LIANG P, QIN Y C, HU B, et al. Study of the adsorption behavior ofheavy metal ions on nanometer-size titanium dioxide with ICP-AES [J]. FreseniusJournal of Analytical Chemistry,2000,368(6):638-40.
    [115] LEE S, FURDYNA J K, DOBROWOLSKA M. Optical properties ofII-VI-based magnetic semiconductor self-assembled quantum dots [J]. CompoundSemiconductors2004, Proceedings,2005,184(455-62.
    [116] FERREIRA R, VERZELEN O, BASTARD G. Optical properties ofexcitonic polarons in semiconductor quantum dots [J]. Physica E,2004,21(2-4):164-70.
    [117] ARTEMYEV M V, BIBIK A I, GURINOVICH L I, et al. Opticalproperties of dense and diluted ensembles of semiconductor quantum dots [J]. PhysStatus Solidi B,2001,224(2):393-6.
    [118] YOFFE A D. Semiconductor quantum dots and related systems:electronic, optical, luminescence and related properties of low dimensional systems[J]. Adv Phys,2001,50(1):1-208.
    [119] WOGGON U. Optical properties of semiconductor quantum dots-Introduction [J]. Springer Tr Mod Phys,1997,136(1-5.
    [120] NOMURA S, SEGAWA Y, MISAWA K, et al. Optical properties ofsemiconductor quantum dots in magnetic fields [J]. J Lumin,1996,70(144-57.
    [121] EKIMOV A I. Optical-Properties of Semiconductor Quantum Dots inGlass Matrix [J]. Phys Scripta,1991, T39(217-22.
    [122]李晓明.镉系量子点引发的细胞学毒性及其机制研究[D];中科院上海应用物理研究所,2013.
    [123] CONE R L, THIEL C W, SUN Y, et al. Rare-earth-doped materials withapplication to optical signal processing, quantum information science, and medicalimaging technology [J]. Proc Spie,2012,8272(
    [124] DE RINALDIS S, RINALDI R, CINGOLANI R, et al. Intrinsicdipole-dipole excitonic coupling in GaN quantum dots: application to quantuminformation processing [J]. Physica E,2002,13(2-4):624-9.
    [125] BIOLATTI E, D'AMICO I, ZANARDI P, et al. Electro-optical propertiesof semiconductor quantum dots: Application to quantum information processing [J].Phys Rev B,2002,65(7):
    [126] HIROTA O. Quantum information theory and its application to quantuminformation processing [J]. Cleo(R)/Pacific Rim2001, Vol I, Technical Digest,2001,626-7.
    [127] JIE G F, YUAN J X, ZHANG J. Quantum dots-based multifunctionaldendritic superstructure for amplified electrochemiluminescence detection of ATP [J].Biosens Bioelectron,2012,31(1):69-76.
    [128] ANTONELLO A, BRUSATIN G, GUGLIELMI M, et al. Novelmultifunctional nanocomposites from titanate nanosheets and semiconductor quantumdots [J]. Opt Mater,2011,33(12):1839-46.
    [129] SMITH A M, NIE S. Minimizing the hydrodynamic size of quantumdots with multifunctional multidentate polymer ligands [J]. J Am Chem Soc,2008,130(34):11278-+.
    [130] SUSUMU K, UYEDA H T, MEDINTZ I L, et al. Enhancing the stabilityand biological functionalities of quantum dots via compact multifunctional ligands [J].J Am Chem Soc,2007,129(45):13987-96.
    [131] RHYNER M N, SMITH A M, GAO X H, et al. Quantum dots andmultifunctional nanoparticles: new contrast agents for tumor imaging [J].Nanomedicine-Uk,2006,1(2):209-17.
    [132] SANTRA S, YANG H S, HOLLOWAY P H, et al. Synthesis ofwater-dispersible fluorescent, radio-opaque, and paramagnetic CdS: Mn/ZnSquantum dots: A multifunctional probe for bioimaging [J]. J Am Chem Soc,2005,127(6):1656-7.
    [133] CHAN W C W, NIE S M. Quantum dot bioconjugates for ultrasensitivenonisotopic detection [J]. Science,1998,281(5385):2016-8.
    [134] WU X Y, LIU H J, LIU J Q, et al. Immunofluorescent labeling of cancermarker Her2and other cellular targets with semiconductor quantum dots (vol21, pg41,2003)[J]. Nat Biotechnol,2003,21(4):452-.
    [135] SOLE V A, PAPILLON E, COTTE M, et al. A multiplatform code forthe analysis of energy-dispersive X-ray fluorescence spectra [J]. Spectrochimica ActaPart B-Atomic Spectroscopy,2007,62(1):63-8.
    [136] PALLON J, RYAN C G, MARRERO N A, et al. STIM evaluation inGeoPIXE to complement the quantitative dynamic analysis [J]. Nucl Instrum Meth B,2009,267(12-13):2080-4.
    [137] RYAN C G, VAN ACHTERBERGH E, YEATS C J, et al. QuantitativePIXE trace element imaging of minerals using the new CSIRO-GEMOC NuclearMicroprobe [J]. Nucl Instrum Meth B,2002,189(400-7.
    [138] RYAN C G. Quantitative trace element imaging using PIXE and thenuclear microprobe [J]. Int J Imag Syst Tech,2000,11(4):219-30.
    [139] RYAN C G, COUSENS D R, SIE S H, et al. Quantitative PixeMicroanalysis of Geological Material Using the Csiro Proton Microprobe [J]. NuclInstrum Meth B,1990,47(1):55-71.
    [140] RYAN C G, VAN ACHTERBERGH E, JAMIESON D N. Advances inDynamic Analysis PIXE imaging: Correction for spatial variation of pile-upcomponents [J]. Nucl Instrum Meth B,2005,231(162-9.
    [141] RYAN C G, VAN ACHTERBERGH E, YEATS C J, et al. Quantitative,high sensitivity, high resolution, nuclear microprobe imaging of fluids, melts andminerals [J]. Nucl Instrum Meth B,2002,188(18-27.
    [142] RYAN C G, ETSCHMANN B E, VOGT S, et al. Nuclearmicroprobe-synchrotron synergy: Towards integrated quantitative real-time elementalimaging using PIXE and SXRF [J]. Nucl Instrum Meth B,2005,231(183-8.

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