20
Years of Laser Research in Analytical Chemistry
Major developments and articles published in Analytical Chemistry are chroni-
T
he first paper experimentally demonstrating a ruby laser was published by Theodore Maiman in August 1960 (1).
This event was propitious because it was my first semester
in college—lasers and I were going to grow up together. From then until my senior year, I was rather oblivious to the development of the He–Ne contin-
Fred E. Lytle
Purdue University
uous wave (cw) laser (2), and semiconductor lasers (3–5). I remember a seminar speaker telling us about the wonderful new blue-green laser that would revolutionize underwater communication (6 ). Little did I realize then that the argon-ion laser would be the mainstay of my research program for 20 years. J U LY 1 , 2 0 0 0 / A N A LY T I C A L C H E M I S T R Y
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The laser is con-
tinuing to have
an almost unpar-
alleled impact on the advancement of science in this
decade.
I worked for David Hercules as an undergraduate at Juniata College and followed him to MIT to pursue a Ph.D. Three things came together in graduate school to whet my interest in laser spectroscopy. First, Charles Townes was awarded the 1964 Nobel Prize in Physics for his pioneering work in lasers. Our laboratory was just two doors up the hall from his, and it was exciting to stop by and see what his group was doing. Second, I got to know one of Townes’s graduate students, Raymond Chaio, who told me about the inverse Raman experiment (7), which I used as part of an original proposition. Finally, my thesis research on the photophysics of tris(2,2´-bipyridine) ruthenium(II) dichloride required measuring luminescence lifetimes using a TRW nanosecond spectral source. After Peter Rentzepis and co-workers published the first picosecond paper (8, 9), it was obvious that gas discharge lamps would soon be replaced by lasers. What were the readers of Analytical Chemistry (AC) learning about lasers while I was progressing through eight years of higher education? Not much, if they only read the research papers. In the January 1965 editor’s column, L. T. Hallett wrote, “The laser is continuing to have an almost unparalleled impact on the advancement of science in this decade.” This statement was in marked contrast to the absence of such articles in AC. Fortunately, the A-pages contained editorials, meeting programs, and advertisements that kept readers abreast of advances in the field. Two other sources of information were the biannual Fundamental Reviews and the annual Buyer’s Guide (now the Lab Guide). Also, it is reasonable to assume that readers were scanning other journals.
Instruments, applications, and conference presentations The first article related to lasers appeared in AC in July 1962. Consistent
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with the interest in chemical methods of analysis prevalent at that time, the paper described the analysis of ruby and sapphire crystals for trace metals (consult the reading list on the Web at pubs.acs.org/ac). Coincidentally, an article on Hughes Aircraft appeared in the A-pages of the same issue. The article stated that “one of the main departmental efforts in which analytical chemistry plays a major role is the preparation and investigation of materials . . . for use in laser devices.” The first analytical method involving a laser appeared in December 1965. The authors at Argonne National Laboratory used a 30–35-J ruby laser from Maser Optics to remotely open a metallic container filled with radioactive material. Only a government laboratory would own such a device! My 3-J ruby laser was frightening and constantly destroyed optical components. In 1966, a He–Ne laser was first used in spectroscopy. In May 1966, an article appeared in AC that described the replacement of the tungsten lamp in a Beckman Model B absorption spectrophotometer with a 10-mW laser from Raytheon. The authors demonstrated conformity to Beer’s law for concentrations at which the lamp data deviated from linearity. In December, a description of a laser-based Raman spectrometer appeared. The authors, from Cary Instruments, modified a Model 81 instrument by replacing the Toronto arc lamp with a 30-mW laser from Spectra-Physics. Unfortunately for AC readers, 13 months elapsed between the date of submission and publication. Nine months earlier, Cary had exhibited the instrument at the Pittsburgh Conference. In 1967, an interesting paper appeared that described an absorption measurement that relied on the spatial coherence of a 1mW He–Ne laser. The beam was bounced around a cylindrical cathode surface to monitor solvated electrons. This was the first laser paper written by an academic author, albeit a physical chemist. In July, a capillary Raman technique was described that could obtain spectra from as little as 0.04 µL of sample. This achievement involved modifying the sample chamber of a Perkin-Elmer LR-1 spectrophotometer and using a 10mW He–Ne laser.
Two papers appeared in 1968 that described using the laser as a microsampler. The authors, from Stanford Research Institute and the Stanford University School of Medicine, described modifications to the Jarrell-Ash laser microprobe to improve its performance in monitoring the emission from metals in biological samples. Later that year, a paper described using a pulsed ruby laser from Raytheon to sample a 5-µm-diam area of refractory material. The vaporized sample was collected on a microscope cover plate and analyzed by various nonoptical methods. At the time, the best sources of information on laser-based research were the conferences and the 1966 and 1968 Fundamental Reviews. At the earliest meetings, there were many general talks on laser principles and new spectroscopic techniques. Maurice Windsor spoke on the excitation of organic compounds and Paul Maker on nonlinear light scattering. During this time, many talks focused on either the laser microprobe or laser-excited Raman spectra. The optical microprobe from Jarrell-Ash was the first commercially available analytical instrument to use a laser. It was based on a Q-switched ruby laser and photographically measured atomic emission intensities. The primary person describing this device was Fred Brech of Jarrell-Ash, a constant presence at meetings in the 1960s. A group of researchers from the National Bureau of Standards (NBS, now the National Institute of Standards and Technology) was also frequently at the meetings and talked about their microprobe instrument and experiments. Other groups working on the laser microprobe included Republic Aviation, the Naval Air Engineering Center, the University of Illinois, and Stanford University School of Medicine. The Stanford and Illinois studies were the only ones published in AC in the late 1960s. The NBS study appeared in Applied Optics (10). As best as can be determined, no description of the Jarrell-Ash instrument was ever published. The biannual Fundamental Review
on emission spectrometry covered the optical microprobe starting with a single paragraph in 1964 (the first possible date) and ending with a subject heading by 1968. The laser Raman spectrophotometer was the second commercially available instrument to use a laser. Sergio Porto from Bell Laboratories gave the first talk about it in 1963, and he was the first person to publish on the topic (11). However, the major players were from instrument companies. In 1964, the Applied Physics group discussed the performance of a He–Ne laser with the Cary Model 81 spectrometer. By 1965, PerkinElmer was displaying its own spectrometer at the Pittsburgh Conference and joined the lecture tour the following year. Other notable work involving argonion excitation came from George Walrafen’s group at Bell Laboratories and Don Landon from Spex Industries on the use of a double monochromator. These last two advances were important components of most Raman instrumentation throughout the next two decades. The biannual Fundamental Review on Raman spectrometry started off lukewarm in 1964, mentioned the rapidly developing impact of lasers in 1966, and became dominated by laser applications by 1968. Other notable work came from Brad Moore at the University of California–Berkeley on vibrational fluorescence, Francis Vastola at Pennsylvania State University on laser vaporization in MS, and several on stimulated and inverse Raman spectroscopy.
At Argonne, a
30–35-J ruby
laser was used to remotely open a
container filled
with radioactive
material—my 3-J
ruby laser was
frightening and constantly de-
stroyed optical
Exploring a new field Upon joining the analytical faculty at Purdue University, I decided to explore the general area of time-resolved fluorimetry. At that time, the most popular excitation sources were nitrogen (12) or frequency-doubled ruby
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The characteris-
tic that generated the most interest was the
stunning power
per unit band-
width and the relationship this
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lasers, used with or without a pulsed dye laser (13). Both devices had serious limitations with short-lived fluorophores. The ideal source would have a high, variable repetition rate, picosecond pulse widths, and an adjustable wavelength. We started with a mode-locked argon-ion laser that provided subnanosecond pulses at a fixed, high repetition rate (14). Helping us was Henri Merkelo, an electrical engineer from the University of Illinois, who was using mode-locked lasers with phase fluorimetry (15). After determining that the repetition rate was too high for time-resolved fluorimetry, we investigated cavity-dumped argon-ion lasers that generated nanosecond pulses from the single-shot to the megahertz domain (16). About the same time, Dick Johnson from Radiation, Inc., published a procedure for cavity-dumping a modelocked laser, thereby providing shorter pulse widths (17 ) . His paper clearly showed how the two techniques could be combined. The final piece needed to build the ideal source was a modelocked cw dye laser (18, 19). Because the cavity dumper had to be placed within the resonator, we implemented synchronous pumping, which is an earlier technique used to get picosecond output from pulsed dye lasers (20). At long last, we had the ideal source on which we could base our analytical studies (21). While we were developing skills in laser technology, fundamental studies of and instrumental improvements to the optical microprobe continued. In 1969, Malmstadt and Peipmeier authored the first article in AC by academic analytical chemists. The abundance of microprobe studies was also reflected in the number of talks on the topic at the Pittsburgh Conference. In 1973, an article with a misleading title, “Novel Method of Raman Data Ac-
A N A L Y T I C A L C H E M I S T R Y / J U LY 1 , 2 0 0 0
quisition”, described the first coherent anti-Stokes Raman spectroscopy (CARS) experiment published in AC. In 1974, Rick Van Duyne published the first article describing how temporal resolution could be used to reject fluorescence from Raman spectra. A second paper attracted my attention because of the clever way that high photon counting rates were achieved. Two new applications that appeared during the early 1970s were intracavity absorption enhancement and laser-excited luminescence, both atomic and molecular. Intracavity absorption enhancement was studied by groups at Ohio University, the University of Alberta, and the Illinois Institute of Technology. These efforts extended the original work done at NBS (22). Jim Winefordner’s group at the University of Florida published three papers on atomic fluorescence, an area that would receive attention from many other groups in the years to come. A paper by Mark Kelsey and I reported the inverse of Van Duyne’s experiment by rejecting Rayleigh and Raman scattering from fluorescence spectra, and a landmark paper by Michael Berman and Dick Zare introduced the combination of laser-excited fluorescence and chromatography. These last two published articles describe quite different approaches to improving the detection limit of increasingly selective instruments. Starting in 1969, the format of Ralph Muller’s column on instrumentation in AC drastically changed. Instead of Muller writing his own column, an advisory panel actively sought authors to write tutorial A-page articles on various topics, resulting in several articles on tunable lasers.
Applying knowledge and experience For analytical chemists, the period from 1960 to 1968 primarily involved learning about lasers, and the period from 1969 to 1975 involved the development of the experimental skills necessary to use them. Building on this foundation, scientists devoted the remainder of the 1970s to discovering new applications. The one char-
acteristic of lasers that generated the most interest was the stunning power per unit bandwidth and the relationship this power had to analytical sensitivity (slope of the calibration curve). Spectroscopists who had never worked with a source this intense quickly recognized that optical power was a two-edged sword. Most often, the increased spectroscopic blank and/or chemical blank nullified gains in sensitivity. When looking back over the body of research, it is clear that the most successful use of lasers involved those applications in which additional instrumental selectivity was built into the measurement. This additional “resolving power” could come from the laser or from other parts of the overall analytical methodology, e.g., prior separation of a multicomponent mixture by chromatography. Laser monochromaticity can increase method selectivity as long as the absorption and/or emission line widths are sufficiently narrow. There were several vastly different applications of this principle. Research into atomic fluorescence continued with Ed Yeung’s group at Iowa State, and the laser group at NBS added to the work that Winefordner had already begun. An alternative approach to detecting atomic excited states was laser-enhanced ionization, a technique developed and popularized by NBS. John Wright’s group at Wisconsin applied monochromatic excitation to rare earth determinations in the solid state. In addition, Earl Wehry’s group at the University of Tennessee used matrix isolation to narrow molecular transitions and analyze mixtures of polycyclic aromatic hydrocarbons. Pulsed lasers were natural sources for time-resolved fluorimetry. With this approach, selectivity was increased by utilizing differences in excitedstate lifetimes. The principle was applied to the reduction of the fluorescence background in Raman spectra, the elimination of Raman and Rayleigh scatter from fluorescence spectra, and the analysis of fluorophore mixtures. Looking back from the perspective of
current applications, the most successful strategy for molecular analysis combined laser-excited fluorescence with a second, highly selective technique. The prime example is the combination with chromatography. Zare’s group at Stanford made the natural transition from TLC to LC during this time. They were joined by Yeung’s group and a collaboration between the Jim Callis and Gary Christian groups at the University of Washington. Two alternative approaches to improving detection limits used the chemical specificity of antibodies to determine insulin and enzymes to determine glucose-6-phosphate. Fluorescence has excellent limits of detection because it is not limited by source shot noise. This same advantage can be obtained with nonfluorescent molecules by converting absorbed energy into something other than light. Several papers appeared using this approach. Photoacoustic spectroscopy relies on conversion into sound, whereas the thermal lens technique relies on the creation of a change in refractive index. Several miscellaneous applications are worth noting. CARS uses a spatially isolated signal to remove fluorescence interferences, and inverse Raman spectroscopy uses an absorption measurement to avoid the problem altogether. Two-photon excitation of fluorescence reduced interference from scattered light by moving the laser wavelength farther from the emission. Spatially restricted measurements such as the Raman microprobe and laser desorption MS were also making headway into the examination of complex samples. One of the last papers published in the 1970s was by Rick McCreery’s group at Ohio State using spatially well-defined absorption measurements near an electrode surface. It is
Two new appli-
cations that appeared in the
1970s were intracavity absorption en-
hancement and laser-excited
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Each person
brought some-
thing unique to the area and
freely shared
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fitting to end with this work because it tackled a similar problem as the first electrochemistry article mentioned earlier.
Conclusion The abstract of a talk I gave at the 1979 Summer Symposium stated, “In general, a poor knowledge of optics has retarded the rapid utilization of lasers by analytical chemists. Most of the early methodological developments were centered in industrial and government laboratories, where a broad base of expertise was available. Unlike other areas of analytical chemistry, very few research groups have been willing to undertake the task of building their own equipment. As a result, applications have hinged to a great extent on the availability of commercial hardware directly suited to immediate needs.” I still believe this to be an accurate assessment of the field at that time. The first wave of analytical chemists to develop laser-based research programs most often had some background knowledge that made optical physics easy to learn and adopt. It is also important to realize that many non-analytical chemists participated in pushing the frontiers of applied laser spectroscopy. Some individuals’ involvement was temporary, whereas others included analytical chemistry as part of their overall program. Each person brought something unique to the area and freely shared it with others. It was only when these pioneer groups started to train graduate students and postdoctoral associates that the field entered its phase of rapid expansion. As research applications were developed and refined throughout the 1980s and 1990s, the word laser lost its cachet. The papers shifted orientation toward the chemical or physical property at hand, and the laser-based measurement was no longer the focus. In any event, by 1979 the door was open, and those of us who walked through fully believed
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that laser spectroscopy would revolutionize analytical chemistry. Indeed, the future did justify the enormous effort of these first two decades by producing such stunning achievements as single-molecule detection and the routine analysis of unbelievably complex chemical systems.
References (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22)
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Fred Lytle is a professor at Purdue University. His research interests include applying lasers to time-resolved fluorescence and two-photon absorption. Address correspondence about this article to Lytle at 1393 Brown Laboratory, West Lafayette, IN 47907 (
[email protected]).
