1230 Anal. zyxwvutsrq Chem. 1987, zyxwvut 59, zyxwvuts 1230-1232 surements. Though linear dynamic ranges (LDR) are poor, excellent sensitivity and detectability are achievable over a narrow interval of analyte concentrations. We are presently investigating antibody-sandwich and direct assays in order to extend FIS applications. Manipulation of these techniques, along with the preincubation competitive assay, will allow full exploitation of the in situ measurement possibilities offered by fiber-optic sensor instrumentation. ACKNOWLEDGMENT The authors thank C. J. Wust of the University of Ten- nessee for his valuable advice and R. N. Compton of Oak Ridge National Laboratory for his loan of laboratory equip- ment and space. Registry zyxwvutsrqp No. GOPS, 2530-83-8. LITERATURE CITED Munkholrn, C.; Walt, D. R.; Mllanovich, F. P.; Klainer, S. M. Anal. Chem. 1986, 58, 1427-1430. Seitz. W. R. Anal. Chem. 1984, 56, 16A-34A. Milanovich, F. P. Environ. Sci. Technol. 1986, 20, 441-442. Arnold, M. 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This work has been supported by the National Institutes of Health (GM 34730) and the Office of Health and Environmental Research, U.S. Department of Energy, under Contract Number DE-AC05-840R21400 with Martin Mar- ietta Energy Systems, Inc. CORRESPONDENCE On-Line Mass Spectrometric Detection for Capillary Zone Electrophoresis Sir: Mikkers, Jorgenson, and co-workers (I, 2) have re- ported on the use of capillary zone electrophoresis (CZE) for high-resolution separations of amino acids, peptides, proteins, and complex salt mixtures. This technique has been shown to provide separation efficiencies of up to lo6 theoretical plates, often in less than 20 min (3). Capillary zone electrophoresis is particularly useful in the separation of ionized and partially ionized species in aqueous solvents, although nonaqueous solvents have also been used (4). In CZE separation occurs in a capillary tube filled with a buffer and immersed in buffer reservoirs at each end (Figure 1). The sample is typically introduced as a sample plug by electromigration from a sep- arate sample reservoir (2). Electroosmotic flow in the capillary is caused by the migration of ions from the diffusive layer of the electrical double layer at the capillary surface, under the influence of an electrical field imposed tangentially to the surface, causing the ions to migrate toward the oppositely charged electrode (5). The resulting bulk electroosmotic flow can be sufficiently fast so that positively charged ions, neutral species, and negatively charged ions elute in short times, with the separation due to differences in the electrophoretic mo- bilities of the analytes. Detection of the eluting species in CZE is usually performed by on-line fluorescence or UV absorbance detection. Such detection techniques have been adequate for species that fluoresce, absorb, or are amenable to derivatization with fluorescing or absorbing chromophores (I, 2). However these detectors impose difficult cell volume and sample size limi- tations if high separation efficiencies are to be realized. These limitations constitute a major drawback in the use of CZE for the separation and identification of complex mixtures. The ideal detector for CZE would provide universal detection, selectivity, and sensitivity without degrading separation ef- f ic i en cy . We have developed a viable alternative to CZE detection based on mass spectrometric interfacing. A capillary zone electrophoresis-mass spectrometry (CZE-MS) interface ob- viously requires a substantial departure from the conventional CZE arrangement; it is clear that the interface design and ionization method are crucial to success. The liquid flow rate in CZE (- 1 pL/min) is highly compatible with conventional mass spectrometers even if the total column effluent was introduced directly. The direct liquid introduction interfaces developed for LC-MS suffer from orifice plugging at low flow rates and the thermal degradation of high mass-low volatility components (6,7). Thermospray ionization, though attractive, has not been shown to be effective for liquid flow rates below a few tenths of a mL/min. Therefore, our evaluation of the requirements for a mass spectrometer interface suggested an approach that incorporates the electrospray ionization tech- nique developed by Dole et al. (8) and the more recent work reported by Fenn and co-workers (9). In this communication, we report the successful development of CZE-MS instru- mentation for the separation and analysis of ionic species in aqueous solutions. EXPERIMENTAL SECTION Apparatus. A schematic of the CZE-MS instrument is given 0003-2700/67/0359-1230$01.50/0 1967 American Chemical Society