KOLUMNE 417 CHIMIA 44 (1990) Nr.I~ (Ikzem""r) Chimia 44 (/990) 417 424 <&') Schll'ei=. Chemiker- Verhand; ISSN 0009 4293 Recent Progress in Laser Analytics Analytical methods are on their way to mass spectrometry (MS). In 1946, William penetrate the biological sciences. In this E. Stephens (University of Pennsylvania in trend, laser technology plays an important Philadelphia) described a mass spectrome- role, especially in the form of laser-desorp- ter with time dispersion, followed by the tion mass spectrometry (LD-MS). ion velocitron of A.E. Cameron and D.£. The remarkable progress made in this Eggers. These devices represented early field is nicely demonstrated by a statement forms of the time-of-flight mass spectrom- made in 1986 by Frank H. Field, a specialist eter (TOF-MS) first described by the Swiss in the mass spectrometric investigation of R. Keller in 1949. biomolecules and Professor at Rockefeller The first commercially successful TOF- University in New York. Citing Professor MS was introduced by Bendix Corpora- In dieser Kalwnne schreibl Field: 'The mass region of real interest for tion, and it was based on the design re- Prof Dr. H. M. Widmer proteins lies between 40000 and 100000 ported in 1955 by William C. Wile)' and Forse/lUng Analylik Da, and one can only speculate as to l. H. McLaren (Bendix Aviation Corpom- Ciha-Geigy AG. FO 3.2 CH 4{)()2 Basel whether such monster gaseos ions could be tion). In these early days of TOF-MS, the regelmiissig eigene Meinungsarlike/ oder liidl Giiste produced. My personal feeling is that to do ions were generated by electron impact ein. lI11gemein inreressierende Ange/egenheilen der so may well require the discovery of some (El). The Bendix instrument had a 2 m long ",odemen Analyrik =u kOlllmenlieren. Eilllvendwl- flight tube and its mass range was limited xen aus dem Leserpl/hlikl/m sind nichtl/nerlV</nsclJ/ new technique.' ( A dresse: siehe ohen) </lidwerden in angemessener This statement represented the state-of- to 400 Da when operated at 10 kHz. Origi- Weise hen/chicl/tigt. the-art in 1986, but only less than two nally this instrument was used to study years later the predicted new discovery was ion-molecule and molecule-molecule inter- made. The novel method is calIed matrix- actions. assisted laser desorption/ionization (LDI), An important improvement in the TOF- and was introduced by Michael Karas and MS instrumentation was introduced in Franz Hillenkamp (Institute for Medical 1973 by B.A. Mamyrin, v.J. Karatajeo, Physics, University of Munster) in 1987/ D. V. Shmikk, and V. Zagulin (Physical 88. Their invention made it possible to in- Technical Institute loffe, Leningrad) the vestigate biomolecules up to 300000 Da in inventors of the reflectron. Their mass re- the gas phase of a time-of-flight mass spec- flector enabled the focussing of ions with trometer (TOF-MS). the same mass, and, therefore, inhanced It is interesting to recall the different the mass resolution ofTOF·MS. steps that made this success come true. It is Parallel to these instrumental develop- again one of these cases demonstrating the ments, attempts were made to desorb and necessity of interdisciplinary influences for ionize nonvolatile and polar substances to Dr. Klaus Olaf Bomsell is the laser program project the advancement of analytical methodol- make them accessible for MS. The idea was leader in the Central Analytical Research Depart- ogies. At the same time, it is a typical to desorb such molecules directly from the ment of Ciha-Geixy Ltd., Basel. He studied at the Christian-Albrechts University in Kiel. Under model case for the instrumental develop- solid state into the gas phase and to ionize Prof. Edward M. Schlag at the Technical Univer- ments from a complicated physical instru- them in a second step in the gas phase. sity in Munich, hc rcceived his Ph. D. in 1987. He ment to a widely used analytical tool. It In 1960, Hans D. Beckel' and P. Schult: joined Ciha-Geigy in 1988 as a postdoctoral fellow and became a permanent cmployee in 1989. needed a fine-tuning through chemical ex- (University of Bonn) introduced thejield- perience to improve the efficiency of the desorption (FD) technique. Field desorp- method and to simplify the instrumental tion creates a direct and combined desorp- device, so that it became economical and tion and ionization from the condensed may be operated by relative unskilled per- phase. The primary excitation is achieved sonnel, a prerequisite for the wide-spread through low-energy ions and neutral parti- use of a technology, especially in medical cles such as Xe· and Xe. applications. In 1964, Joseph Berkowitz and William Laser techniques have long been used in A. Chupka used a laser beam directed at the analytical research, but seldom has a laser surface of graphite to study the mass spec- method reached whide applications. It re- trum of the vapor ejected from the solid mained the domain of specialists, partially material. Kenneth A. Lincoln (Naval due to the fact, that for many years lasers Radiological Defense Laboratory, San remained expensive and delicate to handle. Francisco) also used laser radiation to Dr. Martin Se/,iir rcccived his Ph. D. in 1988 from However, in the last few years, novel laser flash evaporate solid materials for the University of Berne, where he studied under instruments became available, among mass spectrometric investigations. Other Prof. Ernst Schumacher. He spent a postdoctoral them the simple diode and semiconductor desorption methods followed shortly. In year at the c:.lifornia Institute of Technology in Pasadcna, wherc hc investigated the photoelec- lasers, which found many applications in 1976, D. MacFarlane and D.£. Torgerson tronic spectra of van der Waals clusters in molecu- fiber optical sensors and other analytical (Cyclotron Institute, Texas A and M Uni- lar beams. He joined the Laser Laboratory of the fields. versity, College Station) published work Oha-Geigy, Ccntral Analytical Rescarch Depart- The most important analytical applica- on the plasma desorption (PO) of large ment, in July 1990. tions of laser methods are connected with molecules, based on the analyte surface KOLUMNE 4]8 CHIMIA 44 (1990) Nr.12 (DelClllher) bombardment with high-energy heavy par- MPI and analyzed in a TOF-MS system. technology. The most astonishing results ticle fission products of mCf, and in the In an earlier Columna Analytica article were published by the groups around same year Alfred Benninghoven, D. Jaspers, (Chimia, 1988, 42, 147), Renato Zenobi, Michael Karas and Franz Hillenkamp and and W. Sichtermann (University of Kaln) Jong Hoon Hahn, and Richard N. Zare by Ronald C. Beavis and Brian T. Chait used lighter particles, such as fast alkali or (Department of Chemistry, Stanford Uni- (Department of Mass Spectrometry and rare-gase ions, to desorb ions form the versity) reviewed and illustrated the feasi- Gas Phase Ion Chemistry, The Rockefeller solid surface. The method was called sec- bility of such technologies. University, New York) and Robert J. Cot- ondary-ion mass spectrometry (SIMS). An The classical ionization, i.e. electron-im- ter (Department of Pharmacology of extension of these techniques was intro- pact (£1) and chemical-ionization (CI) Molecular Sciences, The John Hopkins duced in 1981 by Michael Barber, Robert techniques for gas-phase molecules are University, Baltimore). S. Bordoli, R. Donald Sedgwick, and An- suitable only for relatively small species. In Matrix-assisted LDI-MS is character- drew N. Tyler (Chemistry Department, contrast, the laser desorption techniques ized by several typical features. Singly University of Manchester), called fast- are applicable to large polar and thermo- charged molecular ions are in all cases the atom-hombardment (F AB). For many labile molecules, such as antibiotica, en- base peak of the analyte signal, and no years, SIMS and FA B were the most popu- zymes, and carbohydrates. fragments are observed above 1000 Da. lar methods for the desorption oflarge and In the early 1980's, laser desorption of Sometimes, multiple charged ions are ob- nonvolatile molecules, since these tech- intact organic molecules evolved. Al- served, which has not been reported before niques were easily adapted to the existing though various mass analyzers were used for the laser desorption, though for plasma sector and quadrupole mass spectrometers for this purpose, the time-of-flight ana- desorption MS of high-mass proteins. of numerous MS laboratories. Although lyzer proved to be the most suitable, since Multimers and doubly charged molecular FAB and SIMS were extended to desorb TOF-MS can record ions over a broad ions generally improve the molecular ion compounds above 10000 Da, these investi- mass range, therefore, extending the mass detection. A remarkable sensitivity is gations were generally handicapped by the range of previous laser-desorption mass demonstrated and only small samples are resulting week signals and the sensitivity spectrometry. However, laser desorption required for multiple analysis (sub- remained unsatisfactory for this upper also fits well with ion-cyclotron-resonance nanogram range). Furthermore, matrix- mass range. (lCR). David A. McCreary, E. B. Ledford, assisted LDI is also characterized by a low Around 1975 laser microprobe instru- Jr., and M. L Gross conducted some of the chemical-noise level. ments became available and were widely very first experiments in which samples The matrix material plays a crucial role used. Their characteristics is that they fo- were analyzed by ICR, also called Fourier- in the successful desorption and ionization cus the laser to a very small spot size on a Transform MS (FT-MS). of the macromolecules. Whereas Michael thin foil on which the sample is deposited In 1987, Kuni Tanaka, Y. ldo, S. Akita, Karas and Franz Hillenkamp used nicotinic on the opposite side of the foil.