title: Microcavity array (MCA)-based biosensor chip for functional drug screening of 3D tissue models.
abstract: Multicellular tumour spheroids that mimic a native cellular environment are widely used as model systems for drug testing. To study drug effects on three-dimensional cultures in real-time we designed and fabricated a novel type of sensor chip for fast, non-destructive impedance spectroscopy and extracellular recording. Precultured spheroids are trapped between four gold electrodes. Fifteen individual 100microm deep square microcavities with sizes from 200 to 400microm allow an optimised positioning during the measurement. Although apoptosis was induced in human melanoma spheroids by Camptothecin (CTT), treated cultures did not show disintegration but displayed increased impedance magnitudes compared to controls after 8h resulting from an altered morphology of the outer cells. Contractions in cardiomyocyte spheroids were monitored when the innovative chip was used for recording of extracellular potentials. The silicon-based electrode array is used as an acute test system for the monitoring of any kind of 3D cell cultures. Since no adherence of cells or labelling is necessary the multifunctional sensor chip provides a basis for improved drug development by high content screenings with reduced costs and assay times. Additional improvements for parallel testing of different substances on one chip are presented.
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kloss
authors.forename: Randy
authors.initials: R
authors.lastname: Kurz
authors.forename: Heinz-Georg
authors.initials: HG
authors.lastname: Jahnke
authors.forename: Michael
authors.initials: M
authors.lastname: Fischer
authors.forename: Andrée
authors.initials: A
authors.lastname: Rothermel
authors.forename: Ulf
authors.initials: U
authors.lastname: Anderegg
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Robitzki
mesh_terms: D001681:Biological Assay / Q000295:instrumentation* / Q000379:methods; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D017097:Electric Impedance; D004867:Equipment Design; D019544:Equipment Failure Analysis; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D018213:Neoplasms, Bone Tissue; D013057:Spectrum Analysis / Q000379:methods*; D046888:Tissue Array Analysis / Q000295:instrumentation* / Q000379:methods