Development of a Lab-on-a-Chip for the Characterization of Human Cells
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1004-P05-05
Development of a Lab-on-a-Chip for the Characterization of Human Cells Peter Ertl, Lukas Richter, Andy Mak, Christoph Stepper, Michael Kast, and Hubert Br¸ckl Nano-System-Technologies, Austrian Research Centers GmbH (ARC), Donau-City-Str. 1, Vienna, 1220, Austria ABSTRACT Microfabricated biochips are developed to continuously monitor cellular phenotype dynamics in a non-invasive manner. In the presented work we describe the novel combination of contact-less dielectric microsensors and microfluidics for quantitative cell analysis. The cell chip consists of a polymeric fluidic (PDMS) system bonded to a glass wafer containing the electrodes while temperature and fluid flow are controlled by external heating and pumping stations. Additionally, the cell chip contains an integrated reference arm providing a low-noise detection environment by eliminating background signals and interferences. The high-density interdigitated capacitors (µIDC) are designed to monitor living cells in a space of approximately 10 nL volume by controlling critical electrode characteristics, such as size, shape and passivation composition as well as thickness. The integrated µIDCs are isolated by a 300 nm multipassivation layer of defined dielectric property and provide non-invasive, stable, robust and nondrifting measurement conditions. The performance of this detector is evaluated using various bacterial and yeast strains. INTRODUCTION Understanding the complex interaction between cells and their environment is fundamental to medicine and biology because it provides insight into how cellular systems dynamically respond to changing conditions (1-3). As a result, the study of cellular dynamics in the context of cell populations is highly desirable because of its physiological relevance and practical applications (4,5). Despite the potential of cellular phenotype analysis, recent advances fail to overcome the limitations of existing detection methodologies (e.g. lengthy analysis time, low sensitivity, reproducibility, and etc.). Consequently, to understand a cellís dynamic system, new technologies are needed to rapidly assess these phenotypic changes. Microchip technology is ideally suited to address these requirements since it allows the creation of biological niches by providing relevant fluidic conditions such as physiological flow velocities (1 ñ 50 µm/s) and low fluid-to-cell volume ratios (e.g. 1:1), and maintaining stable temperature profiles over long periods of time (6-10). The technique employed to continuously measure cell viability and morphology changes is called cellular dielectric spectroscopy (CDS). In contrast to existing bioimpedance methods implemented for cell analysis (11-15), the dielectric microsensors are completely insulated and physically removed from the liquid sensing environment using defined multi-passivation layer of distinct size and composition. Dielectric spectroscopy makes use of the electrical properties of cells exposed to a radio-frequency electrical field of small magnitude (± 15 mV) (16-21). We h
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