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研究生:林煥彰
研究生(外文):Huan-Chang Lin
論文名稱:質譜儀新技術的開發及其在病毒與細胞的分析
論文名稱(外文):Novel Mass Spectrometry Technology Development for Virus/nanoparticle and Cell/microparticle Analysis
指導教授:陳力騏
指導教授(外文):Richie L. C. Chen
口試委員:林俊利王亦生鄭宗記陳林祈
口試委員(外文):Jung-Lee LinYi-Sheng WangTzong-Jih ChengLin-Chi Chen
口試日期:2013-07-25
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生物產業機電工程學研究所
學門:工程學門
學類:機械工程學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:177
中文關鍵詞:質譜儀雷射脫附病毒細胞奈米粒子微米粒子
外文關鍵詞:Mass SpectrometryLIADVirusCellNanoparticleMicroparticle
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近年來,質譜技術已成功擴展到尺度小於奈米的巨大有機與生物分子的偵測,例如:巨大蛋白質聚合物、有機聚合物等,為了針對量測各種不同的巨大分子衍伸發展出各式的質譜技術。但是尺度介於奈米至微米之間的粒子,其質量範圍約為107 ~ 1016 Da,例如:病毒、細胞等,對於質譜學的探測而言,是一個很艱難的挑戰。本論文目的在研究開發直接且快速量測奈米與微米粒子之新穎質譜技術。第一章節中,介紹傳統質譜學的種類與技術。第二章節中,我們闡述為了直接且快速量測細胞與微米顆粒的質量分佈而自行開發的雷射激發音波脫附游離源(laser-induced acoustic desorption, LIAD)、頻率掃描式離子阱及電荷偵測器,這些技術的整合使細胞與微米顆粒質量分佈之偵測更有效率。並將其應用於不同類型的細胞鑑定與定量分析細胞吞噬奈米/微米粒子的數量,未來可將此技術應用於奈米/微米粒子在藥物傳遞的研究。第三章節中,我們開發對病毒質量量測的技術。病毒與奈米顆粒因為體積比細胞小,表面積能攜帶的電荷數相對很少,加上我們開發的電荷偵測器約有500個電子的雜訊,所以要直接量測單一病毒的質譜訊號是不可行的。另外,病毒相較於小分子的飛行速度慢,也無法撞擊出二次電子或離子來做偵測。最後,我們利用相位固定技術累積增加離子阱捕捉的數量,讓相同電荷數的粒子同時拋出,增加其總電荷數以利電荷偵測器感應。得到的圖譜再利用類似電灑脫附質譜儀(ESI-MS)的分析方法,將單一病毒質量成功地定義出來。基於我們開發的細胞與病毒偵測之質譜技術,讓整個質譜儀的偵測範圍可以從單一原子(1 Da)到單一細胞(1016 Da),可以說是質譜學的一大躍進。

Recently, mass spectrometry was extended to detect large organic- and bio-particles in sub-nano scale. In this work, different novel technologies have been developed to aim at the detection of even larger organic- and bio-particles, such as cells/microparticles and virus/nanoparticles. The sizes ranging from nano- to micro-scale are very difficult to detect by conventional mass spectrometry. In chapter I, I give the brief introduction on the technology development. Some future perspectives on the applications are also included. In chapter II, laser induced acoustic desorption (LIAD) to desorb cells and microparticles inside a quadrupole ion trap is presented. Measurements of the masses of mammalian and poultry erythrocytes, organic microparticle and cells were achieved by the combination of LIAD frequency scanning ion trap and charge detection into one facility. The mass distributions of these particles were also determined. For virus and nanoparticles, the number of charges on each particle is too low to be accurately determined by the current charge detector. The detection of virions/nanoparticles directly by a charge amplification detector is also not feasible due to the low velocities of these nanoparticles. A novel approach was developed based on the simultaneous measurement of different sizes and different number of charges of each nanoparticle to derive the mass of nanoparticles. The details are presented in chapter III. Due to the aforementioned achievements, mass spectrometry can now be used to detect the mass region from atom to cell.

誌謝 i
摘要 iii
Abstract v
Table of Contents vii
List of Figures ix
List of Tables xvi
Nomenclature xvii
1. Overview 1
2. Mass Measurement of Cell and Microparticle 11
2.1 Introduction 11
2.2 Experimental Section 17
2.2.1 Instrumentation 17
2.2.2 Ion Source: Laser-Induced Acoustic Desorption (LIAD) 20
2.2.3 Corona Discharge and Trapping 21
2.2.4 Mass Analyzer: Quadrupole Ion Trap 25
2.2.5 Detection Method: Charge Detector 33
2.2.6 Resolution 39
2.2.7 Monitoring of Trapped Cells / Microparticles by Light Scattering 43
2.2.8 Software: LabVIEW Programs 44
2.2.9 Sample Preparation 48
2.3 Results and Discussion 51
2.3.1 System Calibration (C60 and CEM cells) and Accuracy 51
2.3.2 Measurement of Standard Microparticles and Their Mass Distributions 55
2.3.3 Mass Measurements of cells 57
2.3.4 Red Blood Cells 64
2.3.5 Quantity of Nanoparticles Uptake into Mammalian Cells 67
2.4 Brief Summary 74
3. Virus and Nanoparticles mass measurement 77
3.1 Introduction 77
3.2 Experimental Section 82
3.3 Sample Preparation 86
3.4 Results and Discussion 88
3.4.1 Measurements of Standard Nanoparticles and Their Mass Distributions 88
3.4.2 Human Immunodeficiency Virus (HIV) 91
3.4.3 Influenza Virus 94
3.5 Brief Summary 96
4. Conclusions 97
5. Perspective 99
6. References 102
7. Appendices 113
8. Publications List 122
9. Patents List 124
10. Academic Awards 125

Aksenov, A. and M. Bier. 2008. The analysis of polystyrene and polystyrene aggregates into the mega dalton mass range by cryodetection MALDI TOF MS. Journal of the American Society for Mass Spectrometry 19:219-230.
Aksenov, A. A. and M. E. Bier. 2008. The Analysis of Polystyrene and Polystyrene Aggregates into the Mega Dalton Mass Range by Cryodetection MALDI TOF MS. Journal of the American Society for Mass Spectrometry 19:219-230.
Allen, J. S. 1939. The Detection of Single Positive Ions, Electrons and Photons by a Secondary Electron Multiplier. Physical Review 55:966-971.
Allen, T. M. and P. R. Cullis. 2013. Liposomal drug delivery systems: From concept to clinical applications. Advanced Drug Delivery Reviews 65:36-48.
Aoyama, Y., T. Kanamori, T. Nakai, T. Sasaki, S. Horiuchi, S. Sando and T. Niidome. 2003. Artificial Viruses and Their Application to Gene Delivery. Size-Controlled Gene Coating with Glycocluster Nanoparticles. Journal of the American Chemical Society 125:3455-3457.
Aston, F. W. 1919. LXXIV. A positive ray spectrograph. Philosophical Magazine Series 6 38:707-714.
Bahr, U., U. Rohling, C. Lautz, K. Strupat, M. Schurenberg and F. Hillenkamp. 1996. A charge detector for time-of-flight mass analysis of high mass ions produced by matrix-assisted laser desorption/ionization (MALDI). International Journal of Mass Spectrometry and Ion Processes 153:9-21.
Bandura, D. R., V. I. Baranov, O. I. Ornatsky, A. Antonov, R. Kinach, X. Lou, S. Pavlov, S. Vorobiev, J. E. Dick and S. D. Tanner. 2009. Mass Cytometry: Technique for Real Time Single Cell Multitarget Immunoassay Based on Inductively Coupled Plasma Time-of-Flight Mass Spectrometry. Analytical Chemistry 81:6813-6822.
Bank, A., R. A. Rifkind and P. A. Marks. 1975. The Red Blood Cell, 2nd ed. Chapter 22.
Barber, M., R. S. Bordoli, R. D. Sedgwick and A. N. Tyler. 1981. Fast atom bombardment of solids as an ion source in mass spectrometry. Nature 293:270-275.
Beckey, H. D., E. Hilt and H. R. Schulten. 1973. High temperature activation of emitters for field ionization and field desorption mass spectrometry. Journal of Physics E: Scientific Instruments 6:1043.
Benner, W. H. 1997. A Gated Electrostatic Ion Trap To Repetitiously Measure the Charge and m/z of Large Electrospray Ions. Analytical Chemistry 69:4162-4168.
Beynon, J. H., D. O. Jones and R. G. Cooks. 1975. Imaging detector for mass spectrometry. Analytical Chemistry 47:1734-1738.
Bich, C., M. Scott, A. Panagiotidis, R. J. Wenzel, A. Nazabal and R. Zenobi. 2008. Characterization of antibody–antigen interactions: Comparison between surface plasmon resonance measurements and high-mass matrix-assisted laser desorption/ionization mass spectrometry. Analytical Biochemistry 375:35-45.
Bier Mark, E. and J. Grabowski Joseph. 2007. Active Learning Using the Virtual Mass Spectrometry Laboratory. 13. American Chemical Society.
Bleakney, W. 1930. The Ionization of Hydrogen by Single Electron Impact. Physical Review 35:1180-1186.
Boesl, U., J. Grotemeyer, K. Walter and E. W. Schlag. 1987. A High-Resolution Time-of-Flight Mass Spectrometer With Laser Desorption and a Laser Ionization Source. Instrumentation Science & Technology 16:151-171.
Campbell, J. L., M. N. Fiddler, K. E. Crawford, P. P. Gqamana and H. I. Kenttamaa. 2005. Analysis of Polyethylene by Using Cyclopentadienyl Cobalt Chemical Ionization Combined with Laser-Induced Acoustic Desorption/Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Analytical Chemistry 77:4020-4026.
Champion, J. A. and S. Mitragotri. 2006. Role of target geometry in phagocytosis. Proceedings of the National Academy of Sciences of the United States of America 103:4930-4934.
Chen, C.-H., J.-L. Lin, M.-L. Chu and C.-H. Chen. 2010. MALDI Ion Trap Mass Spectrometer with Charge Detector for Large Biomolecule Detection. Analytical Chemistry 82:10125-10128.
Chen, C. H. W., L. J. Sammartano, N. R. Isola and S. L. Allman. 2001. Laser desorption mass spectrometry for biomolecule detection and its applications. AIP Conference Proceedings 584:96-105.
Chithrani, B. D. and W. C. W. Chan. 2007. Elucidating the Mechanism of Cellular Uptake and Removal of Protein-Coated Gold Nanoparticles of Different Sizes and Shapes. Nano Letters 7:1542-1550.
Chithrani, B. D., A. A. Ghazani and W. C. W. Chan. 2006. Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells. Nano Letters 6:662-668.
Cho, K., X. Wang, S. Nie, Z. Chen and D. M. Shin. 2008. Therapeutic Nanoparticles for Drug Delivery in Cancer. Clinical Cancer Research 14:1310-1316.
Conrad, M. E. 1990. Clinical Methods: The History, Physical and Laboratory Examinations, 3rd ed. Chapter 147.
Cooper, M. A., F. N. Dultsev, T. Minson, V. P. Ostanin, C. Abell and D. Klenerman. 2001. Direct and sensitive detection of a human virus by rupture event scanning. Nat Biotech 19:833-837.
D. M. Sipe, A. O., B. Firek, R. Hendrix, M. E.Bier,. 2008. ASMS2008, Proteomics: Applications 571.
Damian, T. 1996. Cryogenic particle detectors. Reports on Progress in Physics 59:349.
de la Fuente, J. M., C. C. Berry, M. O. Riehle and A. S. G. Curtis. 2006. Nanoparticle Targeting at Cells. Langmuir 22:3286-3293.
Dull, T., R. Zufferey, M. Kelly, R. J. Mandel, M. Nguyen, D. Trono and L. Naldini. 1998. A Third-Generation Lentivirus Vector with a Conditional Packaging System. J. Virol. 72:8463-8471.
Elbakry, A., A. Zaky, R. Liebl, R. Rachel, A. Goepferich and M. Breunig. 2009. Layer-by-Layer Assembled Gold Nanoparticles for siRNA Delivery. Nano Letters 9:2059-2064.
Fauquet, C. M., M. A. Mayo, J. Maniloff, U. Desselberger and L. A. Ball. 2005. Virus Taxonomy: Classification and Nomenclature of Viruses. p421-425. San Diego, California, USA:Elsevier Academic Press.
Fraser, G. W. 2002. The ion detection efficiency of microchannel plates (MCPs). International Journal of Mass Spectrometry 215:13-30.
Fuerstenau, S. D. 2003. Whole Virus Mass Analysis by Electrospray Ionization. Journal of the Mass Spectrometry Society of Japan 51:50-53.
Fuerstenau, S. D. and W. H. Benner. 1995. Molecular weight determination of megadalton DNA electrospray ions using charge detection time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 9:1528-1538.
Gamero-Castano, M. 2007. Induction charge detector with multiple sensing stages. Review of Scientific Instruments 78:043301.
Geno, P. W. and R. D. Macfarlane. 1989. Secondary electron emission induced by impact of low-velocity molecular ions on a microchannel plate. International Journal of Mass Spectrometry and Ion Processes 92:195-210.
Giaever, I., H. R. Hart, Jr. and K. Megerle. 1962. Tunneling into Superconductors at Temperatures below 1°K. Physical Review 126:941-948.
Glish, G. L. and R. W. Vachet. 2003. The basics of mass spectrometry in the twenty-first century. Nat Rev Drug Discov 2:140-150.
Goeringer, D. E., W. B. Whitten, J. M. Ramsey, S. A. McLuckey and G. L. Glish. 1992. Theory of high-resolution mass spectrometry achieved via resonance ejection in the quadrupole ion trap. Analytical Chemistry 64:1434-1439.
Golovlev, V. V., S. L. Allman, W. R. Garrett and C. H. Chen. 1997. Laser-induced acoustic desorption of electrons and ions. Applied Physics Letters 71:852-854.
Golovlev, V. V., S. L. Allman, W. R. Garrett, N. I. Taranenko and C. H. Chen. 1997. Laser-induced acoustic desorption. International Journal of Mass Spectrometry and Ion Processes 169-170:69-78.
Griffiths, J. 2008. A Brief History of Mass Spectrometry. Analytical Chemistry 80:5678-5683.
Gupta, A., D. Akin and R. Bashir. 2004. Single virus particle mass detection using microresonators with nanoscale thickness. Applied Physics Letters 84:1976-1978.
Hogan, C. J., E. M. Kettleson, B. Ramaswami, D.-R. Chen and P. Biswas. 2006. Charge Reduced Electrospray Size Spectrometry of Mega- and Gigadalton Complexes:  Whole Viruses and Virus Fragments. Analytical Chemistry 78:844-852.
Ilic, B., Y. Yang and H. G. Craighead. 2004. Virus detection using nanoelectromechanical devices. Applied Physics Letters 85:2604-2606.
Imrie, D. C., J. M. Pentney and J. S. Cottrell. 1995. A Faraday cup detector for high-mass ions in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 9:1293-1296.
Jelkmann, W. and C. Lundby. 2011. Blood doping and its detection. Blood 118:2395-2404.
Jespersen, S., W. M. A. Niessen, U. R. Tjaden, J. van der Greef, E. Litborn, U. Lindberg, J. Roeraade and F. Hillenkamp. 1994. Attomole detection of proteins by matrix-assisted laser desorption/ionization mass spectrometry with the use of picolitre vials. Rapid Communications in Mass Spectrometry 8:581-584.
Jimenez, J. L., J. T. Jayne, Q. Shi, C. E. Kolb, D. R. Worsnop, I. Yourshaw, J. H. Seinfeld, R. C. Flagan, X. Zhang, K. A. Smith, J. W. Morris and P. Davidovits. 2003. Ambient aerosol sampling using the Aerodyne Aerosol Mass Spectrometer. Journal of Geophysical Research: Atmospheres 108:8425.
Jin, H., D. A. Heller, R. Sharma and M. S. Strano. 2009. Size-Dependent Cellular Uptake and Expulsion of Single-Walled Carbon Nanotubes: Single Particle Tracking and a Generic Uptake Model for Nanoparticles. ACS Nano 3:149-158.
Johnston, H. J., M. Semmler-Behnke, D. M. Brown, W. Kreyling, L. Tran and V. Stone. 2010. Evaluating the uptake and intracellular fate of polystyrene nanoparticles by primary and hepatocyte cell lines in vitro. Toxicology and Applied Pharmacology 242:66-78.
Kaddis, C., S. Lomeli, S. Yin, B. Berhane, M. Apostol, V. Kickhoefer, L. Rome and J. Loo. 2007. Sizing large proteins and protein complexes by electrospray ionization mass spectrometry and ion mobility. Journal of the American Society for Mass Spectrometry 18:1206-1216.
Kaddis, C. S., S. H. Lomeli, S. Yin, B. Berhane, M. I. Apostol, V. A. Kickhoefer, L. H. Rome and J. A. Loo. 2007. Sizing Large Proteins and Protein Complexes by Electrospray Ionization Mass Spectrometry and Ion Mobility. Journal of the American Society for Mass Spectrometry 18:1206-1216.
Karas, M. and F. Hillenkamp. 1988. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Analytical Chemistry 60:2299-2301.
Karas, M., A. Ingendoh, U. Bahr and F. Hillenkamp. 1989. Ultraviolet–laser desorption/ionization mass spectrometry of femtomolar amounts of large proteins. Biological Mass Spectrometry 18:841-843.
Knight, R. D. 1983. The general form of the quadrupole ion trap potential. International Journal of Mass Spectrometry and Ion Physics 51:127-131.
Knochenmuss, R., F. Dubois, M. J. Dale and R. Zenobi. 1996. The Matrix Suppression Effect and Ionization Mechanisms in Matrix-assisted Laser Desorption/Ionization. Rapid Communications in Mass Spectrometry 10:871-877.
Koichi Tanaka, Hiroaki Waki, Yutaka Ido, Satoshi Akita, Yoshikazu Yoshida, Tamio Yoshida and T. Matsuo. 1988. Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 2:151-153.
Ladislas Wiza, J. 1979. Microchannel plate detectors. Nuclear Instruments and Methods 162:587-601.
Lee, J., H. Chen, T. Liu, C. E. Berkman and P. T. A. Reilly. 2011. High Resolution Time-of-Flight Mass Analysis of the Entire Range of Intact Singly-Charged Proteins. Analytical Chemistry 83:9406-9412.
Lin, H.-C., H.-H. Lin, C.-Y. Kao, A. L. Yu, W.-P. Peng and C.-H. Chen. 2010. Quantitative Measurement of Nano-/Microparticle Endocytosis by Cell Mass Spectrometry. Angewandte Chemie International Edition 49:3460-3464.
Lindner, B. 1991. On the desorption of electrosprayed organic compounds from supporting metal foils by laser induced pressure waves. International Journal of Mass Spectrometry and Ion Processes 103:203-218.
Liu, Y., K. Li, J. Pan, B. Liu and S.-S. Feng. 2010. Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of Docetaxel. Biomaterials 31:330-338.
Llic, B., D. Czaplewski, M. Zalalutdinov, and H. G. Craighead. 2001. Single cell detection with micromechanical oscillators. Journal of Vacuum Science & Technology B 19:2825-2828.
Ludwig, K., S. Habbach, J. Krieglstein, S. Klumpp and S. Konig. 2011. MALDI-TOF High Mass Calibration up to 200 kDa Using Human Recombinant 16 kDa Protein Histidine Phosphatase Aggregates. PLoS ONE 6:e23612.
Macfarlane, R. and D. Torgerson. 1976. Californium-252 plasma desorption mass spectroscopy. Science 191:920-925.
March, R. E. 1997. An Introduction to Quadrupole Ion Trap Mass Spectrometry. Journal of Mass Spectrometry 32:351-369.
March, R. E. and R. J. Hughes. 1989. Quadrupole Storage Mass Spectrometer. New York: Wiley.
McKay, A. R., B. T. Ruotolo, L. L. Ilag and C. V. Robinson. 2006. Mass Measurements of Increased Accuracy Resolve Heterogeneous Populations of Intact Ribosomes. Journal of the American Chemical Society 128:11433-11442.
Minko, T., R. I. Pakunlu, Y. Wang, J. J. Khandare and M. Saad. 2006. New Generation of Liposomal Drugs for Cancer. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 6:537-552.
Miyoshi, H., U. Blomer, M. Takahashi, F. H. Gage and I. M. Verma. 1998. Development of a Self-Inactivating Lentivirus Vector. J. Virol. 72:8150-8157.
Munson, M. S. B. and F. H. Field. 1966. Chemical Ionization Mass Spectrometry. I. General Introduction. Journal of the American Chemical Society 88:2621-2630.
Nie, Z., F. Cui, M. Chu, C.-H. Chen, H.-C. Chang and Y. Cai. 2008. Calibration of a frequency-scan quadrupole ion trap mass spectrometer for microparticle mass analysis. International Journal of Mass Spectrometry 270:8-15.
Nie, Z., F. Cui, Y.-K. Tzeng, H.-C. Chang, M. Chu, H.-C. Lin, C.-H. Chen, H.-H. Lin and A. L. Yu. 2007. High-Speed Mass Analysis of Whole Erythrocytes by Charge-Detection Quadrupole Ion Trap Mass Spectrometry. Analytical Chemistry 79:7401-7407.
Nie, Z., Y.-K. Tzeng, H.-C. Chang, C.-C. Chiu, C.-Y. Chang, C.-M. Chang and M.-H. Tao. 2006. Microscopy-Based Mass Measurement of a Single Whole Virus in a Cylindrical Ion Trap. Angewandte Chemie International Edition 45:8131-8134.
Nikolaev, E., I. Boldin, R. Jertz and G. Baykut. 2011. Initial Experimental Characterization of a New Ultra-High Resolution FTICR Cell with Dynamic Harmonization. Journal of the American Society for Mass Spectrometry 22:1125-1133.
Osaki, F., T. Kanamori, S. Sando, T. Sera and Y. Aoyama. 2004. A Quantum Dot Conjugated Sugar Ball and Its Cellular Uptake. On the Size Effects of Endocytosis in the Subviral Region. Journal of the American Chemical Society 126:6520-6521.
Perez, J., L. E. Ramı́rez-Arizmendi, C. J. Petzold, L. P. Guler, E. D. Nelson and H. I. Kenttamaa. 2000. Laser-induced acoustic desorption/chemical ionization in Fourier-transform ion cyclotron resonance mass spectrometry. International Journal of Mass Spectrometry 198:173-188.
Patolsky, F., G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang and C. M. Lieber. 2004. Electrical detection of single viruses. Proceedings of the National Academy of Sciences of the United States of America 101:14017-14022.
Pau, S., C. S. Pai, Y. L. Low, J. Moxom, P. T. A. Reilly, W. B. Whitten and J. M. Ramsey. 2006. Microfabricated Quadrupole Ion Trap for Mass Spectrometer Applications. Physical Review Letters 96:120801.
Peng, W.-P., Y. T. Lee, J. W. Ting and H.-C. Chang. 2005. Averaging peak-to-peak voltage detector for absolute mass determination of single particles with quadrupole ion traps. Review of Scientific Instruments 76:023108.
Peng, W.-P., H.-C. Lin, M.-L. Chu, H.-C. Chang, H.-H. Lin, A. L. Yu and C.-H. Chen. 2008. Charge Monitoring Cell Mass Spectrometry. Analytical Chemistry 80:2524-2530.
Peng, W.-P., H.-C. Lin, H.-H. Lin, M. Chu, A. L. Yu, H.-C. Chang and C.-H. Chen. 2007. Charge-Monitoring Laser-Induced Acoustic Desorption Mass Spectrometry for Cell and Microparticle Mass Distribution Measurement. Angewandte Chemie International Edition 46:3865-3869.
Peng, W.-P., Y.-C. Yang, M.-W. Kang, Y. T. Lee and H.-C. Chang. 2004. Measuring Masses of Single Bacterial Whole Cells with a Quadrupole Ion Trap. Journal of the American Chemical Society 126:11766-11767.
Peng, W.-P., Y.-C. Yang, M.-W. Kang, Y.-K. Tzeng, Z. Nie, H.-C. Chang, W. Chang and C.-H. Chen. 2006. Laser-Induced Acoustic Desorption Mass Spectrometry of Single Bioparticles. Angewandte Chemie International Edition 45:1423-1426.
Peng, W.-P., Y.-C. Yang, C.-W. Lin and H.-C. Chang. 2005. Molar Mass and Molar Mass Distribution of Polystyrene Particle Size Standards. Analytical Chemistry 77:7084-7089.
Philip, M. A., F. Gelbard and S. Arnold. 1983. An absolute method for aerosol particle mass and charge measurement. Journal of Colloid and Interface Science 91:507-515.
Radhakrishnan, A., D. Yeo, G. Brown, M. Z. Myaing, L. R. Iyer, R. Fleck, B.-H. Tan, J. Aitken, D. Sanmun, K. Tang, A. Yarwood, J. Brink and R. J. Sugrue. 2010. Protein Analysis of Purified Respiratory Syncytial Virus Particles Reveals an Important Role for Heat Shock Protein 90 in Virus Particle Assembly. Molecular & Cellular Proteomics 9:1829-1848.
Reid, G. E., J. Mitchell Wells, E. R. Badman and S. A. McLuckey. 2003. Performance of a quadrupole ion trap mass spectrometer adapted for ion/ion reaction studies. International Journal of Mass Spectrometry 222:243-258.
Riek, U., R. Scholz, P. Konarev, A. Rufer, M. Suter, A. Nazabal, P. Ringler, M. Chami, S. A. Muller, D. Neumann, M. Forstner, M. Hennig, R. Zenobi, A. Engel, D. Svergun, U. Schlattner and T. Wallimann. 2008. Structural Properties of AMP-activated Protein Kinase: DIMERIZATION, MOLECULAR SHAPE, AND CHANGES UPON LIGAND BINDING. Journal of Biological Chemistry 283:18331-18343.
Rose, R. J., E. Damoc, E. Denisov, A. Makarov and A. J. R. Heck. 2012. High-sensitivity Orbitrap mass analysis of intact macromolecular assemblies. Nat Meth 9:1084-1086.
Ryan, J. A., K. W. Overton, M. E. Speight, C. N. Oldenburg, L. Loo, W. Robarge, S. Franzen and D. L. Feldheim. 2007. Cellular Uptake of Gold Nanoparticles Passivated with BSA−SV40 Large T Antigen Conjugates. Analytical Chemistry 79:9150-9159.
Sarma, P. R. 1990. Clinical Methods: The History, Physical and Laboratory Examinations, 3rd ed. Chapter 152.
Schlag, E. W., J. Grotemeyer and R. D. Levine. 1992. Do large molecules ionize? Chemical Physics Letters 190:521-527.
Schlemmer, S., J. Illemann, S. Wellert and D. Gerlich. 2001. Nondestructive high-resolution and absolute mass determination of single charged particles in a three-dimensional quadrupole trap. Journal of Applied Physics 90:5410-5418.
Schlemmer, S., S. Wellert, F. Windisch, M. Grimm, S. Barth and D. Gerlich. 2004. Interaction of electrons and molecules with a single trapped nanoparticle. Appl Phys A 78:629-636.
Schlunegger, U. P., M. Stoeckli and R. M. Caprioli. 1999. Frequency scan for the analysis of high mass ions generated by matrix-assisted laser desorption/ionization in a Paul trap. Rapid Communications in Mass Spectrometry 13:1792-1796.
Schultz, J. C., C. A. Hack and W. H. Benner. 1998. Mass Determination of Megadalton-DNA Electrospray Ions Using Charge Detection Mass Spectrometry. Journal of the American Society for Mass Spectrometry 9:305-313.
Schultz, J. C., C. A. Hack and W. H. Benner. 1999. Polymerase chain reaction products analyzed by charge detection mass spectrometry. Rapid Communications in Mass Spectrometry 13:15-20.
Sharp, D. G., A. R. Taylor, I. W. Mclean, D. Beard and J. W. Beard. 1944. Density and Size of Influenza Virus A (PR8 STRAIN) in Solution. Science 100:151-153.
Shaw, M. L., K. L. Stone, C. M. Colangelo, E. E. Gulcicek and P. Palese. 2008. Cellular Proteins in Influenza Virus Particles. PLoS Pathog 4:e1000085.
Shea, R. C., S. C. Habicht, W. E. Vaughn and H. I. Kenttamaa. 2007. Design and Characterization of a High-Power Laser-Induced Acoustic Desorption Probe Coupled with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer. Analytical Chemistry 79:2688-2694.
Shea, R. C., C. J. Petzold, J. L. Campbell, S. Li, D. J. Aaserud and H. I. Kenttamaa. 2006. Characterization of Laser-Induced Acoustic Desorption Coupled with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer. Analytical Chemistry 78:6133-6139.
Shockley, W. and J. R. Pierce. 1938. A Theory of Noise for Electron Multipliers. Radio Engineers, Proceedings of the Institute of 26:321-332.
Singh, P., M. J. Gonzalez and M. Manchester. 2006. Viruses and their uses in nanotechnology. Drug Development Research 67:23-41.
Siuzdak, G., B. Bothner, M. Yeager, C. Brugidou, C. M. Fauquet, K. Hoey and C.-M. Change. 1996. Mass spectrometry and viral analysis. Chemistry & Biology 3:45-48.
Somers, C. M., B. E. McCarry, F. Malek and J. S. Quinn. 2004. Reduction of Particulate Air Pollution Lowers the Risk of Heritable Mutations in Mice. Science 304:1008-1010.
Squires, G. 1998. Francis Aston and the mass spectrograph. Journal of the Chemical Society, Dalton Transactions 0:3893-3900.
Stadler, K., V. Masignani, M. Eickmann, S. Becker, S. Abrignani, H.-D. Klenk and R. Rappuoli. 2003. SARS [mdash] beginning to understand a new virus. Nat Rev Micro 1:209-218.
Stephen D. Fuerstenau, W. H. B., John J. Thomas, Christophe Brugidou, Brian Bothner, Gary Siuzdak,. 2001. Mass Spectrometry of an Intact Virus13. Angewandte Chemie International Edition 40:541-544.
Tanaka, K., H. Waki, Y. Ido, S. Akita, Y. Yoshida, T. Yoshida and T. Matsuo. 1988. Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 2:151-153.
Tang, X., R. Beavis, W. Ens, F. Lafortune, B. Schueler and K. G. Standing. 1988. A secondary ion time-of-flight mass spectrometer with an ion mirror. International Journal of Mass Spectrometry and Ion Processes 85:43-67.
Thomas, J. J., B. Bothner, J. Traina, W. H. Benner and G. Siuzdak. 2004. Electrospray ion mobility spectrometry of intact viruses. Spectroscopy: An International Journal 18:31-36.
Tito, M. A., K. Tars, K. Valegard, J. Hajdu and C. V. Robinson. 2000. Electrospray Time-of-Flight Mass Spectrometry of the Intact MS2 Virus Capsid. Journal of the American Chemical Society 122:3550-3551.
Trivedi, P. C., S. Pandey and S. Bhadauria. 2010. Text Book of Microbiology. p196-198. Jaipur, India:Aavishkar Publishers.
Tsivou, M., N. Kioukia-Fougia, E. Lyris, Y. Aggelis, A. Fragkaki, X. Kiousi, P. Simitsek, H. Dimopoulou, I. P. Leontiou, M. Stamou, M. H. Spyridaki and C. Georgakopoulos. 2006. An overview of the doping control analysis during the Olympic Games of 2004 in Athens, Greece. Analytica Chimica Acta 555:1-13.
Twerenbold, D., D. Gerber, D. Gritti, Y. Gonin, A. Netuschill, F. Rossel, D. Schenker and J.-L. Vuilleumier. 2001. Single molecule detector for mass spectrometry with mass independent detection efficiency. PROTEOMICS 1:66-69.
van den Heuvel, R. H. H., E. van Duijn, H. Mazon, S. A. Synowsky, K. Lorenzen, C. Versluis, S. J. J. Brouns, D. Langridge, J. van der Oost, J. Hoyes and A. J. R. Heck. 2006. Improving the Performance of a Quadrupole Time-of-Flight Instrument for Macromolecular Mass Spectrometry. Analytical Chemistry 78:7473-7483.
Wenzel, R. J., U. Matter, L. Schultheis and R. Zenobi. 2005. Analysis of Megadalton Ions Using Cryodetection MALDI Time-of-Flight Mass Spectrometry. Analytical Chemistry 77:4329-4337.
Westmacott, G., W. Ens and K. G. Standing. 1996. Secondary ion and electron yield measurements for surfaces bombarded with large molecular ions. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 108:282-289.
Westmacott, G., M. Frank, S. E. Labov and W. H. Benner. 2000. Using a superconducting tunnel junction detector to measure the secondary electron emission efficiency for a microchannel plate detector bombarded by large molecular ions. Rapid Communications in Mass Spectrometry 14:1854-1861.
Whitten, W. B., P. T. A. Reilly and J. M. Ramsey. 2004. High-pressure ion trap mass spectrometry. Rapid Communications in Mass Spectrometry 18:1749-1752.
Wong, S. F., C. K. Meng and J. B. Fenn. 1988. Multiple charging in electrospray ionization of poly(ethylene glycols). The Journal of Physical Chemistry 92:546-550.
Yang, P.-H., X. Sun, J.-F. Chiu, H. Sun and Q.-Y. He. 2005. Transferrin-Mediated Gold Nanoparticle Cellular Uptake. Bioconjugate Chemistry 16:494-496.
Zhang, B., Y. Li, C.-Y. Fang, C.-C. Chang, C.-S. Chen, Y.-Y. Chen and H.-C. Chang. 2009. Receptor-Mediated Cellular Uptake of Folate-Conjugated Fluorescent Nanodiamonds: A Combined Ensemble and Single-Particle Study. Small 5:2716-2721.
Zhao, X., L. R. Hilliard, S. J. Mechery, Y. Wang, R. P. Bagwe, S. Jin and W. Tan. 2004. A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles. Proceedings of the National Academy of Sciences of the United States of America 101:15027-15032.
Zhu, Z.-J., P. S. Ghosh, O. R. Miranda, R. W. Vachet and V. M. Rotello. 2008. Multiplexed Screening of Cellular Uptake of Gold Nanoparticles Using Laser Desorption/Ionization Mass Spectrometry. Journal of the American Chemical Society 130:14139-14143.
Zufferey, R., T. Dull, R. J. Mandel, A. Bukovsky, D. Quiroz, L. Naldini and D. Trono. 1998. Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery. J. Virol. 72:9873-9880.

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