ORIGINAL PAPER Monitoring of cell cultures with LTCC microelectrode array P. Ciosek & K. Zawadzki & J. Łopacińska & M. Skolimowski & P. Bembnowicz & L. J. Golonka & Z. Brzózka & W. Wróblewski Received: 2 December 2008 / Revised: 22 January 2009 / Accepted: 23 January 2009 / Published online: 14 February 2009 # Springer-Verlag 2009 Abstract Monitoring of cell cultures in microbioreactors is a crucial task in cell bioassays and toxicological tests. In this work a novel tool based on a miniaturized sensor array fabricated using low-temperature cofired ceramics (LTCC) technology is presented. The developed device is applied to the monitoring of cell-culture media change, detection of the growth of various species, and in toxicological studies performed with the use of cells. Noninvasive monitoring performed with the LTCC microelectrode array can be applied for future cell-engineering purposes. Keywords Sensor array . Cell cultures . LTCC . Ion-selective electrodes Introduction Cultured mammalian cells under laboratory conditions have become indispensable research tool in understanding the unity of living systems, including the human body. Culture of mammalian cells enables the development of advanced cell biology, which offers the possibility of investigating the mechanisms of cell-cell interactions, cell-extracellular matrix (ECM) interactions, and transport phenomena [1]. The early stages of drug development most frequently involve the testing of compounds on cells, using defined in-vitro cell-based assays. Cultured mammalian cells play all-important roles as the fundamental components of tissue culture and tissue engineering [2, 3]. Moreover, cell cultures are fundamental tools in the manufacture of vaccines, enzymes, hormones, and monoclonal antibodies, etc. Cells are permanently exposed to a multiplicity chemical or mechanical stimuli, which strongly influence their physiological functions and their properties. The complex intercellular communication network, which coordinates the proliferation, differentiation, and metabolism of the multitude of cells in diverse tissues and organs, is a necessary condition for the proper performance of a multicellular organism. Aberrations in signal transduction underlie many different diseases, including the majority of cancers [4]. Understanding the establishment of specific cell-cell and cell-extracellular matrix interactions has several advantages for research on fundamental aspects of cell biology. The tendency of animal cells in vivo to interact with one another and with surrounding extracellular matrix is mimicked in their growth in culture. It is recognized that for anchorage- dependent cells microenvironmental conditions such as the topology of the substrate, the composition of the extracel- lular matrix, and the signals of neighboring cells have significant effects on the results obtained from cell-based assays [5]. Chemical and mechanical signals in the cell microenvironment are sensed by cells and subsequently transformed into biochemical responses [6]. According to these facts, cellomics [7], i.e. the study of cells, is nowadays a rapidly developing branch of science. Usually, prokaryotic, eucariotic, and plant cells are grown in cell-culture flasks and maintained under controlled Anal Bioanal Chem (2009) 393:2029–2038 DOI 10.1007/s00216-009-2651-x P. Ciosek (*) : K. Zawadzki : J. Łopacińska : M. Skolimowski : Z. Brzózka : W. Wróblewski Warsaw University of Technology, Faculty of Chemistry, Noakowskiego 3, 00-664 Warsaw, Poland e-mail: pciosek@ch.pw.edu.pl P. Bembnowicz : L. J. Golonka Faculty of Microsystem Electronics and Photonics, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland