Microchip for Combining Gas Chromatography or Capillary Liquid Chromatography with Atmospheric Pressure Photoionization-Mass Spectrometry Markus Haapala, † Laura Luosuja 1 rvi, ‡ Ville Saarela, § Tapio Kotiaho, †,‡ Raimo A. Ketola, †,⊥ Sami Franssila, § and Risto Kostiainen* ,† Division of Pharmaceutical Chemistry, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland, Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FI-00014 University of Helsinki, Finland, Micro and Nanosciences Laboratory, Helsinki University of Technology, P.O. Box 3500, FI-02015 TKK, Finland, and Drug Discovery and Development Technology Center, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland We present a microfabricated nebulizer chip for combin- ing atmospheric pressure photoionization-mass spectrom- etry (APPI-MS) with gas chromatography (GC) or capillary liquid chromatography (capLC). The chip consists of a silicon plate and a glass plate or two glass plates. The chip includes a sample inlet channel, auxiliary gas and dopant inlet, vaporizer channel, nozzle, and platinum heater. The sample eluted from the capLC or GC is mixed with auxiliary gas and dopant (toluene) in the heated vaporizer. The chip forms a confined jet of the sample vapor, which is photoionized as it exits the chip. The analytical perfor- mance of GC- and capLC-microchip APPI-MS was evalu- ated with some polycyclic aromatic hydrocarbons, am- phetamines, and steroids. The GC-μAPPI-MS method provides high sensitivity down to 0.8 fmol, repeatability (RSD ) 7.5-14%), and linearity (r ) 0.9952-0.9987). The capLC-μAPPI-MS method shows high sensitivity down to 1 fmol, good repeatability (RSD ) 3.6-8.1%), and linearity (r ) 0.9989-0.9992). One of the current trends in development of analytical systems is toward miniature lab-on-a-chip devices, which can have several advantages such as faster operation, better performance, smaller sample consumption, reduced waste production, and lower cost over those of conventional systems. Most lab-on-a-chip systems are based on microfluidics, combining, for example, pumping, mixing, reactions, sample treatment, separation, and detection. Optical or electrochemical methods, which can be miniaturized, are often used for detection. However, mass spec- trometry (MS), due to its high sensitivity and selectivity, has gained increasing interest during the recent years as a detection method used with lab-on-a-chip devices. Although even entire mass spectrometers have been scaled down to centimeter scale, 1 the main interest has been miniaturization of ion sources. Since electrospray ionization (ESI) 2,3 is the ionization method most used in liquid chromatography-mass spectrometry (LC-MS), and it is relatively simple to miniaturize, research on miniaturi- zation has focused almost completely on ESI. Several miniaturized ESI sources produced with various technologies and materials such as glass, 4 silicon, 5 and polymers 6,7 have been presented. Although ESI is usually the method of choice in LC- MS, other ionization methods such as atmospheric pressure photoionization (APPI) and atmospheric pressure chemical ioniza- tion (APCI) have their place in the analysis of less polar and nonpolar compounds. APPI for LC-MS has been increasingly used since its introduction several years ago. 8,9 In APPI, a liquid sample is vaporized by a heated nebulizer and ionized via proton-transfer or charge-exchange reactions using high-energy photons (about 10 eV) for initialization of the ionization process. 10,11 Since commercial APPI and APCI sources are designed to work with flow rates on a scale of 100-1000 μL/min, and miniaturized sources are not available, APPI and APCI have mostly been limited to traditional LC. Nevertheless, in some studies low flow rates have been used with APCI and APPI. APCI has been combined with supercritical fluid chromatography, 12 open tubular liquid chromatography, 13 and capillary electrophoresis (CE). 14 APPI * To whom correspondence should be addressed. E-mail: risto.kostiainen@ helsinki.fi. Phone: +358-9-191 59 134. 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