title: Multiparametric sensor-chip based technology for monitoring metabolic activity: A proof-of-principle study with live tissue.
abstract: The recent development of an electronic test system based on silicon sensor-chips allows the continuous parallel recording of relative changes in extracellular acidification, oxygen consumption and electric impedance in living cells. The objective of this proof-of-principle study therefore, was to clarify whether this system can also be applied to live tissue slices thus providing a device for an ultimately envisioned chemosensitivity testing apparatus for individualized treatment schemes in cancer therapy. A prototype of the testing apparatus equipped with six individual measuring devices has been used to simultaneously analyze changes in extracellular acidification, oxygen consumption and electronic impedance in live liver tissue and compared to data obtained from a tumor cell line. In contrast to tumor cells, tissue slices showed low rates of extracellular acidification but high rates of oxygen consumption. Monitoring of electrical impedance values, reflecting cellular morphology, revealed that the compact cell structure of the tissue slices was able to function as electric insulator and actively change the impedance values of the system. Exposure of tumor cells to 1 microM cytochalasin B, a fungal metabolite known to interact with the cytoskeleton and influence glucose metabolism, resulted in the rapid decline of extracellular acidification, increased oxygen consumption rates and increased values in capacitance. In tissue slices upon addition of 1 microM cytochalasin B, a decline of both extracellular acidification and electrical impedance was observed within 1 h. Determination of ATP content in the tissue slices revealed that decreasing ATP content paralleled diminishing oxygen consumption. This new technique offers the possibility of generating metabolic profiles for cells and tissues by studying oxygen consumption, extracellular acidification and electrical impedance.
authors.affiliation: Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie der TU München, München, Germany. natter13@gmx.de
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Sprague
authors.forename: Vadim
authors.initials: V
authors.lastname: Beregov
authors.forename: Georg
authors.initials: G
authors.lastname: Von Sternbach
authors.forename: Martin
authors.initials: M
authors.lastname: Brischwein
authors.forename: Angela M
authors.initials: AM
authors.lastname: Otto
authors.forename: Markus
authors.initials: M
authors.lastname: Adam
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wolf
authors.forename: Michael
authors.initials: M
authors.lastname: Molls
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003571:Cytochalasin B / Q000494:pharmacology; D017097:Electric Impedance; D005069:Evaluation Studies as Topic; D045604:Extracellular Fluid / Q000737:chemistry*; D008297:Male; D008660:Metabolism / Q000502:physiology*; D008991:Monitoring, Physiologic / Q000295:instrumentation* / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats
chemical_list: D003571:Cytochalasin B; D000255:Adenosine Triphosphate