Picoliter Droplet Formation on Thin Optical Fiber Tips Suguru Uemura Department of Mechanical Engineering, Tokyo UniVersity of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan Mårten Stjernstro ¨m,* Johan Sjo ¨dahl, and Johan Roeraade Department of Analytical Chemistry, KTH, School of Chemical Science and Engineering, SE 100 44 Stockholm, Sweden ReceiVed May 15, 2006. In Final Form: August 28, 2006 In this paper, we present experimental results on how minute droplets are formed on fiber optic end faces. Results show that reproducible picoliter volumes can be generated when fibers are retracted from an aqueous phase contained under an inert fluorinated immiscible liquid, with a coefficient of variation (CV) of 0.7-2.3%. The droplet formation was analyzed as a function of the fiber diameter, retraction speed, and wettability. Experiments reveal a volume- determining critical equilibrium contact angle between 60° and 75°, defining the onset of fiber end-face dewetting. The dynamics of the droplet snap-off progression was characterized using high-speed imaging in order to explain the observed wettability-volume dependency. Introduction Manipulation of microvolumes has attracted a great deal of attention in the fields of life science 1 and drug discovery. 2 Important advantages relating to sample size reduction (e.g., reaction kinetics, throughput, space, and cost issues) can now be utilized to address complex biological problems, 3,4 previously unreachable using conventional methods. An extensive number of technologies exist for microdroplet formation on solid planar substrates, including inkjet, 5-8 mi- crocontact, 9 nanopipet, 10 and pin printing 2 sample transfer. Inkjet sample delivery has acquired a lot of consideration due to its ability to dispense minute picoliter (pL) droplets at high speed (10 m/s) and frequency (kHz) in an inherent noncontact mode. However, its robustness is often impaired by delicate sample- specific surface interactions, gas bubbles, particulates, and solvent evaporation. Moreover, inkjet printers have been observed to impose critical damage to labile biological material. 11 Pins are currently the most established sample carriers used for printing sample molecules. The deposition procedure normally includes minute volume sample transfer from a sample container via the tip of a stainless steel pin onto a planar substrate surface. Extreme downscaling of this technology for the production of high-density arrays with nanometer features has been shown to be possible using dip-pen nanolithography. 12 The collected volume is mainly determined by the pin geometry, surface characteristics, and properties of the sample. Hence, on account of material defects and variations in surface chemistry, the spot variance can be substantial. 13 To optimize pin-printed microarray patterns, the effect of the solid sample recipient and solution characteristics has been investigated. 14 Less focus has been directed toward the details of the influence of the properties of the pin in the sample transfer process. The number of involved liquid-handling and deposition steps can be diminished by performing assays directly on optical fibers. The fiber tip can concurrently act as a liquid sample holder and a reaction vessel, a technique often exploited in optical biosensors. 15 The fiber optic arrangement offers flexible ma- nipulation, and enables light guiding and sensitive detection. 16 Interestingly, bundled optical fiber arrays have been developed as alternatives to conventional planar microarray substrates. 17 However, the possibility to generate picoliter droplets directly on end faces of optical fibers for precise volumetric control in assay miniaturization has not been explored. In this context, a key requirement is to understand the fundamental fluid and surface processes occurring at the fiber end. Considerable fundamental fluid mechanics research has been devoted to the stability and rupture of liquid columns 18,19 and the linked study of droplet generation from jets, dripping faucets, and liquid bridges. The experimental and theoretical investigations dealing with solid-supported liquid bridges 20,21 mainly focus on * To whom correspondence should be addressed. E-mail: marten@ analyt.kth.se (1) FitzGerald, S. P.; Lamont, J. V.; McConnell, R. I.; Benchikh, E. O. Clin. Chem. 2005, 51, 1165-1176. (2) Dunn, D. A.; Feygin, I. Drug Discuss. Today 2000, 5, S84-S91. (3) Mao, R.; Wang, X.; Spitznagel, E. L.; Frelin, L. P.; Ting, J. C.; Ding, H.; Kim, J. W.; Ruczinski, I.; Downey, T. J.; Pevsner, J. Genome Biol. 2005, 6, R107. (4) Jones, R. B.; Gordus, A.; Krall, J. A.; MacBeath, G. Nature 2006, 439, 168-174. (5) Ekstro ¨m, S.; Ericsson, D.; O ¨ nnerfjord, P.; Bengtsson, M.; Nilsson, J.; Marko- Varga, G.; Laurell, T. Anal. Chem. 2001, 73, 214-219. (6) Mohebi, M. M.; Evans, J. R. G. J. Comb. Chem. 2002, 4, 267-274. (7) Lemmo, A. V.; Rose, D. J.; Tisone, T. C. I. Curr. Opin. Biotechnol. 1998, 9, 615-617. (8) Litborn, E.; Stjernstro ¨m, M.; Roeraade, J. Anal. Chem. 1998, 70, 4847- 4852. (9) Kane, R. S.; Takayama, S.; Ostuni, E.; Ingber, D. E.; Whitesides, G. M. Biomaterials 1999, 20, 2363-2376. (10) Rodolfa, K. T.; Bruckbauer, A.; Zhou, D.; Schevchuk, A. I.; Korchev, Y. E.; Klenerman, D. Nano Lett. 2006, 6, 252-257. (11) Nishioka, G. M.; Markey, A. A.; Holloway, C. K. J. Am. Chem. Soc. 2004, 126, 16320-16321. (12) Ginger, D. S.; Zhang, H.; Mirkin, C. A. Angew. Chem., Int. Ed. 2004, 43, 30-45. (13) McQuain, M. K.; Seale, K.; Peek, J.; Levy, S.; Haselton, F. R. Anal. Biochem. 2003, 320, 281-291. (14) Smith, J. T.; Reichert, W. M. Langmuir 2003, 19, 3078-3080. (15) Magrisso, M.; Etzion, O.; Pilch, G.; Novodvoretz, A.; Perez-Avraham, G.; Schlaeffer, F.; Marks, R. Biosens. Bioelectron. 2006, 21, 1210-1218. (16) Rissin, D. M.; Walt, D. R. Nano Lett. 2006, 6, 520-523. (17) Walt, D. R. Science 2000, 287, 451-452. (18) Eggers, J. ReV. Mod. Phys. 1997, 69, 865-929. (19) Marmottant, P.; Villermaux, E. Phys. Fluids 2004, 16, 2732-2741. (20) Yildirim, O. E.; Basaran, O. A. Chem. Eng. Sci. 2001, 56, 211-233. 10272 Langmuir 2006, 22, 10272-10276 10.1021/la0613732 CCC: $33.50 © 2006 American Chemical Society Published on Web 10/18/2006