Optical detection methods for mass spectrometry of macroions.

Detection of macroions has been a challenge in the field of mass spectrometry. Conventional ionization-based detectors, relying on production and multiplication of secondary electrons, are restricted to detection for charged particles of m/z < 1 x 10(6). While both energy-sensitive and charge-sensitive detectors have been developed recently to overcome the limitation, they are not yet in common use. Photon-sensitive detectors are suggested to be an alternative, with which detection of macroions (or charged particles) by either elastic light scattering (ELS) or laser-induced fluorescence (LIF) has been possible. In this article, we provide a critical review on the developments of novel optical detection methods for mass spectrometry of macroions, including both micron-sized and nano-sized synthetic polymers as well as high-mass biomolecules. Design and development of new spectrometers making possible observations of the mass spectra of macroions with sizes in the range of 10-10(3) nm or masses in the range of 1-10(6) MDa are illustrated. The potential and promise of this optical approach toward macroion detection with high efficiency are discussed in practical aspects.

[1]  W. Peng,et al.  Ion trap mass spectrometry of fluorescently labeled nanoparticles. , 2003, Analytical chemistry.

[2]  Zhaozhu Ge,et al.  Simultaneous Elemental Composition and Size Distributions of Submicron Particles in Real Time Using Laser Atomization Ionization Mass Spectrometry , 2000 .

[3]  H. Walther,et al.  Ion/molecule reactions, mass spectrometry and optical spectroscopy in a linear ion trap , 1998 .

[4]  R. Cooks,et al.  Ion trap mass spectrometry , 1991 .

[5]  M. Nielen.  MALDI TIME-OF-FLIGHT MASS SPECTROMETRY OF SYNTHETIC POLYMERS , 1999 .

[6]  L. Friedman,et al.  A study of the formation of high molecular weight water cluster ions (m/e<59 000) in expansion of ionized gas mixtures , 1982 .

[7]  R. March,et al.  Quadrupole ion trap mass spectrometry: a view at the turn of the century , 2000 .

[8]  M. Frank,et al.  Energy-sensitive cryogenic detectors for high-mass biomolecule mass spectrometry. , 1999, Mass spectrometry reviews.

[9]  H. Kraus.  Cryogenic detectors and their application to mass spectrometry , 2002 .

[10]  Nanoparticle Detection by Aerosol Mass Spectrometry , 2001 .

[11]  Robert A. Millikan,et al.  A new modification of the cloud method of measuring the elementary electrical charge, and the most probable value of that charge , 1910 .

[12]  Y. Lee,et al.  Single-particle mass spectrometry of polystyrene microspheres and diamond nanocrystals. , 2002, Analytical chemistry.

[13]  M. Duncan.  Frontiers in the spectroscopy of mass-selected molecular ions , 2000 .

[14]  H. Koizumi,et al.  A sonic spray interface for capillary electrophoresis/mass spectrometry , 1999 .

[15]  P. Perrier,et al.  A dual quadrupole ion trap mass spectrometer , 1999 .

[16]  C. Tropea,et al.  Light Scattering from Small Particles , 2003 .

[17]  M. Seah,et al.  Ion detection efficiency in SIMS:: Dependencies on energy, mass and composition for microchannel plates used in mass spectrometry , 2000 .

[18]  M. Gamero-Castaño,et al.  A CONDENSATION NUCLEUS COUNTER (CNC) SENSITIVE TO SINGLY CHARGED SUB-NANOMETER PARTICLES , 2000 .

[19]  M E Belov,et al.  Rapid quantitative measurements of proteomes by Fourier transform ion cyclotron resonance mass spectrometry , 2001, Electrophoresis.

[20]  Polymerase chain reaction products analyzed by charge detection mass spectrometry , 1999 .

[21]  F. McLafferty,et al.  Unit resolution mass spectra of 112 kDa molecules with 3 Da accuracy , 1997 .

[22]  L. M. Smith,et al.  Charge reduction electrospray mass spectrometry. , 2000, Analytical chemistry.

[23]  W. H. Benner,et al.  Molecular weight determination of megadalton DNA electrospray ions using charge detection time-of-flight mass spectrometry. , 1995, Rapid communications in mass spectrometry : RCM.

[24]  M. Morris,et al.  Plastic microchip electrophoresis with analyte velocity modulation. Application to fluorescence background rejection. , 2000, Analytical chemistry.

[25]  J. Stephenson,et al.  Novel quadrupole ion trap methods for characterizing the chemistry of gaseous macro-ions , 2000 .

[26]  R. March.  Ion trap mass spectrometry , 1992 .

[27]  D. Twerenbold.  Biopolymer mass spectrometer with cryogenic particle detectors , 1996 .

[28]  G. Strouse,et al.  ZnS nanomaterial characterization by MALDI-TOF mass spectrometry. , 2003, Journal of the American Chemical Society.

[29]  John B. Fenn,et al.  Electrospray ionization–principles and practice , 1990 .

[30]  P. Demirev,et al.  Characterization of intact microorganisms by MALDI mass spectrometry. , 2001, Mass spectrometry reviews.

[31]  M. Schabel,et al.  Measurement of individual particle atomic composition by aerosol mass spectrometry. , 2001, Analytical chemistry.

[32]  G. Siuzdak,et al.  Mass spectrometry and viral analysis. , 1996, Chemistry & biology.

[33]  Richard K. Chang,et al.  Aerosol Fluorescence Spectrum Analyzer for Rapid Measurement of Single Micrometer-Sized Airborne Biological Particles , 1998 .

[34]  L. Friedman,et al.  Threshold studies of secondary electron emission induced by macro-ion impact on solid surfaces , 1980 .

[35]  G. Stafford.  Ion trap mass spectrometry: A personal perspective , 2002, Journal of the American Society for Mass Spectrometry.

[36]  W. Benner.  A Gated Electrostatic Ion Trap To Repetitiously Measure the Charge and m/z of Large Electrospray Ions , 1997 .

[37]  W. Peng,et al.  Optical detection and charge-state analysis of MALDI-generated particles with molecular masses larger than 5 MDa. , 2002, Analytical chemistry.

[38]  R. March,et al.  Quadrupole storage mass spectrometry , 1989 .

[39]  K. Prather,et al.  Mass spectrometry of aerosols. , 1999, Chemical reviews.

[40]  S. Kaufman,et al.  DNA analysis using an electrospray scanning mobility particle sizer. , 1997, Analytical chemistry.

[41]  K. Prather,et al.  Improved Lower Particle Size Limit for Aerosol Time-of-Flight Mass Spectrometry , 2001 .

[42]  M. Mann,et al.  Electrospray ionization for mass spectrometry of large biomolecules. , 1989, Science.

[43]  J. Fenn,et al.  Multiple charging in electrospray ionization of poly(ethylene glycols) , 1988 .

[44]  H. V. Hulst.  Light Scattering by Small Particles , 1957 .

[45]  D. Hercules,et al.  MALDI of synthetic polymers—an update , 2003 .

[46]  E. Yeung,et al.  Spatial and temporal imaging of gas phase protein and DNA produced by matrix-assisted laser desorption. , 1994, Analytical chemistry.

[47]  Joseph A. Loo,et al.  Electrospray ionization mass spectrometry: a technology for studying noncovalent macromolecular complexes , 2000 .

[48]  Richard D. Smith,et al.  Trapping, Detection, and Mass Measurement of Individual Ions in a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer , 1994 .

[49]  G. A. Anderson,et al.  Trapping, detection and reaction of very large single molecular ions by mass spectrometry , 1994, Nature.

[50]  R. Zenobi,et al.  Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for identifying the composition of labeled proteins. , 1999, Analytical biochemistry.

[51]  C. Monroe,et al.  Quantum dynamics of single trapped ions , 2003 .

[52]  F Hillenkamp,et al.  Infrared MALDI mass spectrometry of large nucleic acids. , 1998, Science.

[53]  Interaction of electrons and molecules with a single trapped nanoparticle , 2004 .

[54]  S. A. McLuckey,et al.  Performance of a quadrupole ion trap mass spectrometer adapted for ion/ion reaction studies , 2003 .

[55]  P. H. Hemberger,et al.  Operation of a quadrupole ion trap mass spectrometer to achieve high mass/charge ratios , 1991 .

[56]  Richard D. Smith,et al.  Trapping, Detection, and Mass Determination of Coliphage T4 DNA Ions by Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry , 1995 .

[57]  G. Siuzdak,et al.  Mass Spectrometry of an Intact Virus. , 2001, Angewandte Chemie.

[58]  J. Hajdu,et al.  Electrospray time-of-flight mass spectrometry of the intact MS2 virus capsid , 2000 .

[59]  R. C. Mobley,et al.  Molecular Beams of Macroions , 1968 .

[60]  R. Whetten,et al.  Giant Gold−Glutathione Cluster Compounds: Intense Optical Activity in Metal-Based Transitions , 2000 .

[61]  N. Dalal,et al.  Resolution of Individual Component Fluorescence Lifetimes from a Mixture of Trapped Ions by Laser-Induced Fluorescence/Ion Cyclotron Resonance† , 2002 .

[62]  P. Kofel,et al.  Matrix-assisted Laser Desorption/Ionization Using a New Tandem Quadrupole Ion Storage Trap, Time-of-flight Mass Spectrometer , 1996 .

[63]  Lorcan Folan,et al.  Fluorescence spectrometer for a single electrodynamically levitated microparticle , 1986 .

[64]  Yong-Le Pan,et al.  Characterizing and monitoring respiratory aerosols by light scattering. , 2003, Optics letters.

[65]  S. Kaufman,et al.  Macromolecule analysis based on electrophoretic mobility in air:  globular proteins. , 1996, Analytical chemistry.

[66]  Noble,et al.  Real-time single particle mass spectrometry: a historical review of a quarter century of the chemical analysis of aerosols , 2000, Mass spectrometry reviews.

[67]  L. L. Dulcie,et al.  Impact energy measurement in time-of-flight mass spectrometry with cryogenic microcalorimeters , 1998, Nature.

[68]  R. Nelson,et al.  Mass determination of human immunoglobulin IgM using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. , 1994, Rapid communications in mass spectrometry : RCM.

[69]  S. A. McLuckey,et al.  Charge manipulation for improved mass determination of high-mass species and mixture components by electrospray mass spectrometry. , 1998, Journal of Mass Spectrometry.

[70]  M. P. Sinha,et al.  Analysis of individual biological particles by mass spectrometry , 1984 .

[71]  L. M. Smith,et al.  Controlling charge states of large ions. , 1999, Science.

[72]  U. Bahr,et al.  A charge detector for time-of-flight mass analysis of high mass ions produced by matrix-assisted laser desorption/ionization (MALDI) , 1996 .

[73]  B. Luk’yanchuk,et al.  Imaging of Vapor Plumes Produced by Matrix Assisted Laser Desorption: A Plume Sharpening Effect , 1999 .

[74]  D. Gerber,et al.  Detection of single macromolecules using a cryogenic particle detector coupled to a biopolymer mass spectrometer , 1996 .

[75]  R Zenobi,et al.  MALDI mass spectrometry of dye-peptide and dye-protein complexes. , 1998, Analytical chemistry.

[76]  H. Walther,et al.  Photodissociation of MgC60+ complexes generated and stored in a linear ion trap , 1996 .

[77]  R. Bakhtiar,et al.  Charge-state shifting of individual multiply-charged ions of bovine albumin dimer and molecular weight determination using an individual-ion approach. , 1994, Analytical chemistry.

[78]  J. Michael Ramsey,et al.  Detection of single Rhodamine 6G molecules in levitated microdroplets , 1993 .

[79]  P. Barber.  Absorption and scattering of light by small particles , 1984 .

[80]  S. Schlemmer,et al.  Nondestructive high-resolution and absolute mass determination of single charged particles in a three-dimensional quadrupole trap , 2001 .

[81]  G. Siuzdak.  The emergence of mass spectrometry in biochemical research. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[82]  Laser-induced volatilization and ionization of microparticles , 1984 .

[83]  M. McClain,et al.  Flow cytometry of Escherichia coli on microfluidic devices. , 2001, Analytical chemistry.

[84]  Recent Advances and Some Remaining Challenges in Analytical Chemistry of the Atmosphere , 2003 .

[85]  J. Fenn,et al.  Electrospray ion source: another variation on the free-jet theme , 1984 .

[86]  G. Spiteller,et al.  Rapid and Easy Identification of Isomers of Coumaroyl- and Caffeoyl-D-quinic Acid by Gas Chromatography/Mass Spectrometry , 1996 .

[87]  Richard P. Haugland,et al.  Handbook of fluorescent probes and research chemicals , 1996 .

[88]  S. A. McLuckey,et al.  Ion/ion chemistry of high-mass multiply charged ions. , 1998, Mass spectrometry reviews.

[89]  William Charnock,et al.  The apparent activation energy for serrated yielding , 1969 .

[90]  Schlunegger,et al.  Frequency scan for the analysis of high mass ions generated by matrix-assisted laser desorption/ionization in a paul trap , 1999, Rapid communications in mass spectrometry : RCM.

[91]  S. Downey,et al.  Single particle characterization by time-of-flight mass spectrometry , 1995 .

[92]  W. Paul.  Electromagnetic traps for charged and neutral particles , 1990 .

[93]  G. Hárs,et al.  Application of quadrupole ion trap for the accurate mass determination of submicron size charged particles , 1995 .

[94]  Michael Karas,et al.  Ion formation in MALDI: the cluster ionization mechanism. , 2003, Chemical reviews.

[95]  P Zöllner,et al.  Charge-reduced nano electrospray ionization combined with differential mobility analysis of peptides, proteins, glycoproteins, noncovalent protein complexes and viruses. , 2001, Journal of mass spectrometry : JMS.

[96]  Yong-Le Pan,et al.  Single-Particle Fluorescence Spectrometer for Ambient Aerosols , 2003 .

[97]  S. A. McLuckey,et al.  Mass analysis at the advent of the 21st century. , 2001, Chemical reviews.

[98]  J. Parks,et al.  FRET measurements of trapped oligonucleotide duplexes , 2003 .

[99]  S. Arnold,et al.  An absolute method for aerosol particle mass and charge measurement , 1983 .

[100]  I. Waki,et al.  Laser-cooled fluorescence mass spectrometry using laser-cooled barium ions in a tandem linear ion trap , 2001 .

[101]  K. Birkinshaw.  Detectors and the measurement of mass spectra , 2002 .

[102]  S. Nie,et al.  Probing specific sequences on single DNA molecules with bioconjugated fluorescent nanoparticles. , 2000, Analytical chemistry.

[103]  M. Karas,et al.  Matrix-assisted laser desorption/ionisation, an experience , 2000 .

[104]  B. Morrical,et al.  Real-Time Analysis of Individual Atmospheric Aerosol Particles: Design and Performance of a Portable ATOFMS , 1997 .

[105]  G. Siuzdak,et al.  Probing viruses with mass spectrometry. , 1998, Journal of mass spectrometry : JMS.

[106]  Koichi Tanaka,et al.  Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry , 1988 .

[107]  J. Cottrell,et al.  A Faraday cup detector for high‐mass ions in matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry , 1995 .

[108]  J. C. Schultz,et al.  Mass determination of megadalton-DNA electrospray ions using charge detection mass spectrometry , 1998, Journal of the American Society for Mass Spectrometry.

[109]  A. Zelenyuk,et al.  Simultaneous determination of individual ambient particle size, hygroscopicity and composition , 2002 .

[110]  LASER DESORPTION/IONIZATION OF ULTRAFINE AEROSOL PARTICLES , 1997 .

[111]  A. Marshall,et al.  Fourier transform ion cyclotron resonance detection: principles and experimental configurations , 2002 .

[112]  C. Rolando,et al.  Varying the radio frequency: a new scanning mode for quadrupole analyzers , 1998 .

[113]  Yong Cai,et al.  Laser-induced fluorescence/ion trap as a detector for mass spectrometric analysis of nanoparticles , 2003 .

[114]  Michael D. Barnes,et al.  A CCD BASED APPROACH TO HIGH-PRECISION SIZE AND REFRACTIVE INDEX DETERMINATION OF LEVITATED MICRODROPLETS USING FRAUNHOFER DIFFRACTION , 1997 .

[115]  M. Karas,et al.  Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. , 1988, Analytical chemistry.

[116]  G. Fraser.  The ion detection efficiency of microchannel plates (MCPs) , 2002 .

[117]  J. Parks,et al.  Pulsed fluorescence measurements of trapped molecular ions with zero background detection , 2002, Journal of the American Society for Mass Spectrometry.

[118]  J. Michael Ramsey,et al.  Single-molecule detection limits in levitated microdroplets , 1991 .

[119]  C. Dass.  Principles and Practice of Biological Mass Spectrometry , 2000 .

[120]  Y. Rudich,et al.  Ion motion synchronization in an ion-trap resonator. , 2001, Physical review letters.

[121]  S. Schlemmer,et al.  Molecular Hydrogen in Space: Experiments with Trapped Ions and Nanoparticles , 1999 .

[122]  C M Dobson,et al.  Detection and selective dissociation of intact ribosomes in a mass spectrometer. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[123]  J. Reilly,et al.  High-Resolution Time-of-Flight Mass Spectra of Alkanethiolate-Coated Gold Nanocrystals , 1998 .

[124]  T. Hirschfeld,et al.  Virometer: an optical instrument for visual observation, measurement and classification of free viruses. , 1977, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[125]  G. Siuzdak,et al.  Mass spectrometry in viral proteomics. , 2000, Accounts of chemical research.

[126]  S. Kaufman.  Analysis of biomolecules using electrospray and nanoparticle methods: the gas-phase electrophoretic mobility molecular analyzer (gemma) , 1998 .

[127]  A. Bruins,et al.  Atmospheric pressure photoionization: an ionization method for liquid chromatography-mass spectrometry , 2000, Analytical chemistry.

[128]  F. Huisken,et al.  Gas-phase characterization of silicon nanoclusters produced by laser pyrolysis of silane , 1999 .

[129]  R. Zenobi,et al.  Protein structure information from mass spectrometry? Selective titration of arginine residues by sulfonates , 2001, Journal of the American Society for Mass Spectrometry.

[130]  J. Reilly,et al.  Photoionization Studies of Chromophore-Labeled Amino Acids and Peptides† , 2000 .

[131]  F. McLafferty,et al.  Attomole Protein Characterization by Capillary Electrophoresis-Mass Spectrometry , 1996, Science.

[132]  The emergence of mass spectrometry in biochemical research , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[133]  Discrimination between bacterial spore types using time-of-flight mass spectrometry and matrix-free infrared laser desorption and ionization. , 2001, Analytical chemistry.

[134]  Kevin J. McHale,et al.  Atmospheric pressure laser desorption/chemical ionization mass spectrometry: a new ionization method based on existing themes. , 2002, Rapid communications in mass spectrometry : RCM.

[135]  J. Lay,et al.  MALDI-TOF mass spectrometry of bacteria. , 2001, Mass spectrometry reviews.

[136]  R. F. Wuerker,et al.  Electrodynamic Containment of Charged Particles , 1959 .

[137]  R. Cooks,et al.  Instrumentation, applications, and energy deposition in quadrupole ion-trap tandem mass spectrometry , 1987 .

[138]  R. Zenobi,et al.  Direct detection of particles formed by laser ablation of matrices during matrix-assisted laser desorption/ionization. , 2003, Rapid communications in mass spectrometry : RCM.

[139]  Yong Cai,et al.  Calibration of an audio-frequency ion trap mass spectrometer , 2002 .

[140]  S. Cristoni,et al.  Development of new methodologies for the mass spectrometry study of bioorganic macromolecules. , 2003, Mass spectrometry reviews.

[141]  Wineland,et al.  Laser cooling to the zero-point energy of motion. , 1989, Physical review letters.

[142]  Stephen Arnold,et al.  Determination of particle mass and charge by one electron differentials , 1979 .

[143]  M. Johnston.  Sampling and analysis of individual particles by aerosol mass spectrometry. , 2000, Journal of mass spectrometry : JMS.

[144]  W. Whitten,et al.  Real-time detection of individual airborne bacteria , 1997 .

[145]  J. Fenn,et al.  Electrospray mass spectrometry of poly(ethylene glycols) with molecular weights up to five million , 1992 .

[146]  C. D. Hendricks,et al.  Electrostatic Acceleration of Microparticles to Hypervelocities , 1960 .

[147]  C. Robinson,et al.  Detection of the Intact GroEL Chaperonin Assembly by Mass Spectrometry , 1999 .

[148]  D. Schriemer,et al.  Detection of High Molecular Weight Narrow Polydisperse Polymers up to 1.5 Million Daltons by MALDI Mass Spectrometry. , 1996, Analytical chemistry.

[149]  Chemical reaction of sympathetically laser-cooled molecular ions , 2002 .

[150]  W. Moerner,et al.  Illuminating single molecules in condensed matter. , 1999, Science.

[151]  R. Cotter,et al.  Injection of externally generated ions into an increasing trapping field of a quadrupole ion trap mass spectrometer. , 1997, Journal of mass spectrometry : JMS.

[152]  Richard D. Smith,et al.  Observation and implications of high mass-to-charge ratio ions from electrospray ionization mass spectrometry , 1993, Journal of the American Society for Mass Spectrometry.

[153]  Yong-Le Pan,et al.  Application of light-emitting diodes for aerosol fluorescence detection. , 2003, Optics letters.

[154]  D. Russell.  An evaluation of Fourier transform mass spectrometry for high mass applications , 1986 .

[155]  W. H. Benner,et al.  High-efficiency Detection of 66 000 Da Protein Molecules Using a Cryogenic Detector in a Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometer , 1996 .

[156]  S. Arnold,et al.  Spherical void electrodynamic levitator , 1987 .

[157]  A. Marshall,et al.  Fourier transform ion cyclotron resonance mass spectrometry: a primer. , 1998, Mass spectrometry reviews.

[158]  L. Ding,et al.  A simulation study of the digital ion trap mass spectrometer , 2002 .

[159]  R. Whetten,et al.  On-line sampling and intact mass analysis of nanometer-size aerosols via time-of-flight high-mass spectrometry , 1998 .

[160]  A three‐axis spherical void electrodynamic levitator trap for microparticle experiments , 1991 .

[161]  A. Marshall,et al.  Direct optical spectroscopy of gas-phase molecular ions trapped and mass-selected by ion cyclotron resonance: laser-induced fluorescence excitation spectrum of hexafluorobenzene (C6F6+) , 2001 .

[162]  E. James Davis,et al.  A History of Single Aerosol Particle Levitation , 1997 .