Ultra-fast cell counters based on microtubular waveguides

Cornelius S Bausch,Wolfgang Hansen,Robert H Blick,Insa M A Wolf,Björn-Philipp Diercks,Andreas H Guse,Christian Heyn

doi:10.1038/srep41584

Cornelius S Bausch, Wolfgang Hansen + Show 5 more

Open Access

https://doi.org/10.1038/srep41584

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Abstract

We present a radio-frequency impedance-based biosensor embedded inside a semiconductor microtube for the in-flow 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 findings by finite element simulations. Finally, we report on the differentiation of polystyrene beads, primary mouse T lymphocytes and Jurkat T lymphocytes using our device.

Highlights

We present a radio-frequency impedance-based biosensor embedded inside a semiconductor microtube for the in-flow detection of single cells
Only rectangular channels have been used for this purpose[11,12,13], which suffer 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
While flowing phosphate buffered saline solution (PBS) through our device and measuring the S-Parameter during the transition from air to PBS, this tubular geometry yields an increase in sensitivity by a factor of about 2.7 when compared to a planar electrode structure

Summary

Introduction

We present a radio-frequency impedance-based biosensor embedded inside a semiconductor microtube for the in-flow detection of single cells. In contrast to optical methods, impedance-based sensing holds great potential for the ease of downscaling using microfluidics, 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]. A different electrode design with a reported higher sensitivity than coplanar or parallel-facing electrodes was first introduced by Martinez-Cisneros et al.[14], who presented a tubular electrode structure Their design was limited to test frequencies in the kHz regime and their fluid flow through the microchannel was not confined to the electrode area. We present measurements and simulations of a microfluidic impedance-based flow 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 act as a scaffold for the electrodes and functions as the circularly shaped microfludic channel at the sensing region with the electrodes wrapped tightly around it

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