Interdigitated impedance sensors for analysis of biological cells in microfluidic biochips

Abstract

In the presented work we describe the novel combination of contact-less dielectric microsensors and microfluidics for quantitative cell analysis. The lab-on-a-chip system consists of microfluidic channels and chambers together with integrated and passivated interdigitated electrode structures. In contrast to existing bioimpedance methods implemented for cell analysis, the dielectric microsensors are completely insulated and physically removed from the liquid sensing environment using defined multi-passivation layer of distinct size and composition. Consequently, these structures act as contact-less microsensors for the characterization of in vitro cultivated cells. The overall performance of the system is demonstrated on various bacterial and yeast strains. Due to the high sensitivity of the contact-less dielectric microsensors it is possible to directly identify microbial strains, based on morphological differences and biological composition in the absence of any indicators or labels. Additionally, dielectric changes occurring in sub-cellular structures such as membranes can be directly monitored over a wide frequency range. As a result, microfluidic biochips are developed to continuously monitor cell morphology changes in a non-invasive manner over long periods of time.Mikrofluidische Lab-on-a-Chip-Systeme zur Analyse biologischer Zellen mittels integrierter planarer Impedanzsensoren.Ein neuartiges miniaturisiertes Analysesystem zur quantitativen Zellanalyse, auf Basis dielektrischer Mikrosensoren und Mikrofluidik, wird in dieser Arbeit vorgestellt. Das realisierte Lab-on-a-Chip beinhaltet in Kammern eingebettete, passivierte interdigitale Elektrodensysteme. Die Einfü hrung einer Multilagen-Passivierung ermö glicht, im Gegensatz zu herkö mmlichen Bioimpedanz-Systemen, die Isolation und somit die rä umliche Trennung der dielektrischen Mikrosensoren von der Flü ssigkeitsumgebung in den Analysekammern. Anhand von unterschiedlichen, in vitro kultivierten, Bakterien und Hefezellen wird das Lab-on-a-Chip charakterisiert. Es zeigt sich, dass mikrobiologische Substanzen aufgrund morphologischer Unterschiede bzw. ihrer biologischen Zusammensetzung ohne Verwendung von Markern oder Indikatoren identifiziert werden kö nnen. Dielektrische Variationen in subzellularen Strukturen, wie beispielsweise der Membranen, sind ü ber einen weiten Messfrequenzbereich beobachtbar. Der prä sentierte mikrofluidische Biochip wurde speziell fü r die kontinuierliche und nicht-invasive Beobachtung der Zellmorphologie ü ber lange Zeiträ ume entwickelt.Schlü sselwö rter: Lab-on-a- IntroductionThe application of impedance techniques for cell analysis is a well established and widely used non-destructive methodology. Interdigitated electrode structures (IDES) have long been employed, in addition to two and three electrode systems, to monitor impedance changes (Giaever, Keese 1984) of biological samples. A comprehensive introduction into the theory and applications of IDES can be found e.g. in a review of (Mamishev et al., 2004). In brief, impedan...

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