1 Scientific RepoRts | 7:41584 | DOI: 10.1038/srep41584 www.nature.com/scientificreports Ultra-fast cell counters based on microtubular waveguides Cornelius s. Bausch 1,2 , Christian Heyn 1 , Wolfgang Hansen 1 , Insa M. A. Wolf 3 , Björn-philipp Diercks 3 , Andreas H. Guse 3 & Robert H. Blick 1,2 We present a radio-frequency impedance-based biosensor embedded inside a semiconductor microtube for the in-fow detection of single cells. An impedance-matched tank circuit and a tight wrapping of the electrodes around the sensing region, which creates a close, leakage current-free contact between cells and electrodes, yields a high signal-to-noise ratio. We experimentally show a twofold improved sensitivity of our three-dimensional electrode structure to conventional planar electrodes and support these fndings by fnite element simulations. Finally, we report on the diferentiation of polystyrene beads, primary mouse t lymphocytes and Jurkat t lymphocytes using our device. An automated counting of living biological cells in culture populations has become an important tool for many biomedical diagnostic and research applications 1 . Currently prevalent detection schemes comprise of either optical methods such as the widely used fuorescence-activated cell sorting (FACS) technique 2 or electronic sensing mechanisms employed by instruments using the Coulter principle. In contrast to optical methods, impedance-based sensing holds great potential for the ease of downscaling using microfuidics, parallelization and potentially label-free operation. Such on-chip devices allow for on-site diagnostics as required for the sites of virus outbreaks in developing countries 3 . An important goal in building these minituarized particle counters is to achieve a high cell throughput while simultaneously maintaining a high sensitivity. In microfuidic impedance-sensors, the cell passes over elec- trodes, thus inducing a change in the impedance of the device by altering conductivity and capacitance. Typically, electrodes are either embedded on one side of the channel in a coplanar fashion 4–6 or embedded on opposing sides of the channel 7,8 . For both approaches, the impedance measurement depends on the position of the parti- cle in the fow 9 , where the latter design generally promises an increased tolerance to the particle position and a higher sensitivity 10 . Due to a lack of close contact between cell and electrodes, both electrode geometries sufer from leakage currents propagating through the extracellular medium. An approach to solve this problem is the use of constriction channels, whose diameter is smaller than the diameter of the cells. Currently, only rectangular channels have been used for this purpose 11–13 , which sufer from a low throughput and possible clogging due to an incompatibility of the rectangular cross section with the approximately circular cross section of biological cells in suspension. A diferent electrode design with a reported higher sensitivity than coplanar or parallel-facing electrodes was frst introduced by Martinez-Cisneros et al. 14 , who presented a tubular electrode structure. However, their design was limited to test frequencies in the kHz regime and their fuid fow through the microchannel was not confned to the electrode area. Here, we present measurements and simulations of a microfuidic impedance-based fow sensor which allows both for a high measurement bandwidth by the use of radio-frequencies and displays an increased sensitivity as well as a reduced signal dependence on the particle position by the use of a tubular, rolled-up electrode geometry. A tubular coplanar waveguide (T-CPW) is embedded inside a semiconductor microtube, which does not only act as a scafold for the electrodes but also functions as the circularly shaped microfudic channel at the sensing region with the electrodes wrapped tightly around it. Results and Discussion Images of a fabricated T-CPW, a T-CPW integrated into an SU-8 microchannel structure, and the sealed and electrically connected chip are shown in Fig. 1a–c,e. 1 Institute of Nanostructure and Solid State Physics, University of Hamburg, Jungiusstraße 11c, Hamburg, Germany. 2 Center for Hybrid Nanostructures, University of Hamburg, Falkenried 88, Hamburg, Germany. 3 calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, Germany. Correspondence and requests for materials should be addressed to C.S.B. (email: cbausch@physnet.uni-hamburg.de) received: 29 February 2016 accepted: 22 December 2016 Published: 30 January 2017 opeN