Ž . Sensors and Actuators B 63 2000 167–177 www.elsevier.nlrlocatersensorb Femtoliter injector for DNA mass spectrometry Ph. Luginbuhl a, ) , P.-F. Indermuhle a,1 , M.-A. Gretillat a,2 , F. Willemin a,3 , N.F. de Rooij a , ´ D. Gerber b , G. Gervasio b , J.-L. Vuilleumier b , D. Twerenbold c , M. Duggelin d , D. Mathys d , ¨ R. Guggenheim d a Institute of Microtechnology, IMT, UniÕersity of Neuchatel, P.O. Box 3, CH-2007 Neuchatel, Switzerland ˆ ˆ b Institute of Physic, Rue A.-L.Breguet 1, 2000 Neuchatel, Switzerland ˆ c GenSpec SA, P.O. Box 120, 2017 Boudry, Switzerland d REM-Laboratory, UniÕersity of Basel, Bernoullistrasse 32, Basel, Switzerland Received in revised form 1 December 1999 Abstract The fabrication of a front-end injection device based on a fully three-dimensional ring-shaped nozzle as well as the reduction of the nozzle aperture to the micron scale are presented. This new configuration allows to manipulate accurately very small amounts of liquids, Ž y15 . in the femtoliter range 1 fl s10 l . The manipulation of the liquid has been tested with two different operating modes: a dynamic method based on the piezo injection technique and a static method based on the variation of the hydrostatic pressure in the liquid Ž . reservoir. The size distribution of the droplets generated at 0.5 MHz using the piezo technique is centered at 3.6 fl B s1.9 mm and drop Ž . about 25% of the droplets have a volume less than 1 fl B s1.24 mm. drop On the other hand, the free nozzle extremity was used as an ultra-small liquid reservoir for static liquid handling, allowing us to perform a controlled fluid manipulation at the femtoliter level. A syringe connected to the injection device, via a Teflon tube, is used manually to increase quasi-statically the pressure in the nozzle channel. With this simple method it has been possible to monitor and to Ž w . visualize the drop formation at the nozzle extremity in an Environmental Scanning Electron Microscope ESEM . q 2000 Elsevier Science S.A. All rights reserved. Keywords: Micro nozzle; Micro fluidic device; DNA mass-spectrometry; Droplet injector; Piezoelectric actuation 1. Introduction The miniaturization of liquid dispensers based on MEMS technology for the injection and the manipulation Ž . of DNA fragments into a mass spectrometer MS is crucial when only small sample volumes are available. Furthermore, the coupling between MEMS systems and an w x MS becomes an important issue 1–3 . ) Corresponding author. Present address: Microflow Engineering SA, Jaquet-Droz 1, CH-2007 Neuchatel, Switzerland. Tel.: q 41-32-7205-161; ˆ fax: q 41-32-7205-789. Ž . E-mail address: pluginbuhl@microflow.ch Ph. Luginbuhl . 1 Present address: Zyomyx, Inc., 3912 Trust Way, Hayward, CA 94545, USA. 2 Present address: Intersema Sensoric SA Ch. Chapons-des-Pres 11, ´ CH-2022 Bevaix, Switzerland. 3 Present address: Nouvelle Lemania S.A., CH-1341 l’Orient, Switzer- land. Mass spectrometry has the potential to increase throughput, reduce reagent cost and increase accuracy in DNA sizing applications like genotyping and DNA se- quencing. The novel cryodetector technology introduced in w x biopolymer mass spectrometry 4,5 enhances the detection Ž . sensitivity of molecules DNA fragments, proteins with masses beyond 10 kDa as compared to ionizing detectors. We are developing a novel micromachined front-end injec- tion device for our cryodetector mass spectrometer system. The objective is to introduce a controlled volume of liquid Ž . sample DNA and proteins into a geometrically well-de- fined position in order to enhance the performance of our mass spectrometer system. 2. Principle The ejection of droplets into the air through a nozzle aperture requires two types of energies: a surface energy 0925-4005r00r$ - see front matter q 2000 Elsevier Science S.A. All rights reserved. Ž . PII: S0925-4005 00 00354-3