Oberschleißheim, Germany
Oberschleißheim, Germany

Time filter

Source Type

Pfister C.,TU Munich | Pfister C.,HP Medizintechnik GmbH | Forstmeier C.,TU Munich | Biedermann J.,TU Munich | And 6 more authors.
Medical and Biological Engineering and Computing | Year: 2015

We estimated the dynamic cell metabolic activity and the distribution of the pH value and oxygen concentration in tissue samples cultured in vitro by using real-time sensor records and a numerical simulation of the underlying reaction–diffusion processes. As an experimental tissue model, we used chicken spleen slices. A finite element method model representing the biochemical processes and including the relevant sensor data was set up. By fitting the calculated results to the measured data, we derived the spatiotemporal values of the pH value, the oxygen concentration and the absolute metabolic activity (extracellular acidification and oxygen uptake rate) of the samples. Notably, the location of the samples in relation to the sensors has a great influence on the detectable metabolic rates. The long-term vitality of the tissue samples strongly depends on their size. We further discuss the benefits and limitations of the model. © 2015 International Federation for Medical and Biological Engineering


PubMed | TU Munich, HP Medizintechnik GmbH and Institute For Tierphysiologie
Type: Journal Article | Journal: Medical & biological engineering & computing | Year: 2016

We estimated the dynamic cell metabolic activity and the distribution of the pH value and oxygen concentration in tissue samples cultured in vitro by using real-time sensor records and a numerical simulation of the underlying reaction-diffusion processes. As an experimental tissue model, we used chicken spleen slices. A finite element method model representing the biochemical processes and including the relevant sensor data was set up. By fitting the calculated results to the measured data, we derived the spatiotemporal values of the pH value, the oxygen concentration and the absolute metabolic activity (extracellular acidification and oxygen uptake rate) of the samples. Notably, the location of the samples in relation to the sensors has a great influence on the detectable metabolic rates. The long-term vitality of the tissue samples strongly depends on their size. We further discuss the benefits and limitations of the model.


Demmel F.,TU Munich | Brischwein M.,TU Munich | Wolf P.,HP Medizintechnik GmbH | Huber F.,TU Munich | And 2 more authors.
Physiological Measurement | Year: 2015

The response of two well-characterized human breast cancer cell lines (MCF-7 and MDA-MB-231) to a series of nutrient deficiencies is investigated with a label-free cell assay platform. The motivation of the research is to analyze adaptive responses of tumor cell metabolism and to find limiting conditions for cell survival. The platform measures extracellular values of pH and dissolved oxygen saturation to provide data of extracellular acidification rates and oxygen uptake rates. Additional electric cell substrate impedance sensing and bright-field cell imaging supports the data interpretation by providing information about cell morphological parameters. A sequential administration of nutrient depletions does not cause metabolic reprogramming, since the ratios of oxygen uptake to acidification return to their basal values. While the extracellular acidification drops sharply upon reduction of glucose and glutamine, the oxygen uptake is not affected. In contrast to other published data, cell death is not observed when both glucose and glutamine are depleted and cell proliferation is not inhibited, at least in MCF-7 cultures. It is assumed that residual concentrations of nutrients from the serum component are able to maintain cell viability when delivered regularly by active flow like in the cell assay platform, and, in a similar way, under physiological conditions. © 2015 Institute of Physics and Engineering in Medicine.


Schwarzenberger T.,TU Munich | Schwarzenberger T.,HP Medizintechnik GmbH | Demmel F.,TU Munich | Demmel F.,HP Medizintechnik GmbH | And 10 more authors.
Journal of Physics: Conference Series | Year: 2010

Living cells react to external influences such as pharmacological agents in an intricate manner due to their complex internal signal processing. Cell reactions are an impact on vitality, cell-cell or cell-matrix interaction and morphological changes. A number of published techniques on impedance spectroscopy (IS) of adherent cells with planar electrodes address these changes. However, IS can merely serve as an indicator of cellular events rather than provide detailed information on a specific cell process. Thus our approach is a 24-microwell sensor-plate with impedance-electrodes in parallel to pH-and O2-sensors, capable of being integrated into a fully automated screening system. For the purpose of IS, high precision impedance-electronics have been developed based on integrated circuits and validated against a Solartron 1260 impedance analyzer. IS data is correlated to the metabolic-sensors and additionally compared with cell images shot by an inverse optical microscope which is also part of the screening system. Proof of principle is demonstrated by experimental growth monitoring of a MCF-7 culture and cellular response to chemotherapeutics. Furthermore, the potential to monitor living tissue probes is presented for the first time. © 2010 IOP Publishing Ltd.


Schwarzenberger T.,TU Munich | Wolf P.,TU Munich | Wolf P.,HP Medizintechnik GmbH | Brischwein M.,TU Munich | And 7 more authors.
Physiological Measurement | Year: 2011

Living cultured cells react to external influences, such as pharmaceutical agents, in an intricate manner due to their complex internal signal processing. Impedance sensing of cells on microelectrodes is a favored label-free technology to indicate cellular events, usually ascribed to morphologic alteration or changes in cellular adhesion, which is usually found in stand-alone systems that do not incorporate life support or additional sensor systems. However, only in symbiosis with metabolic activity sensing and picture documentation may a complete insight into cellular vitality be provided. This complement was created within the framework of an automated high-content screening system previously developed by our group, monitoring 24 cell culture chambers in parallel. The objective of this paper is the development of miniaturized electronics for impedance measurements and its system integration as a modular unit. In addition, it is shown how sensor electrodes were optimized by impedance matching such that spectroscopy and raw data analysis become feasible for every culture well. Undesired mechanical stress on cultured cells may arise from the medium and agent support system of the autonomous screening apparatus. This paper demonstrates how this hazard is treated with the simulation of microfluidics and impedance measurements. Physiological data are subsequently derived from the exemplary tumor cell line MCF-7 both during treatment with the agent doxorubicin and through the impact of natural killer cells. This correlates the information content of complex impedance spectra with cellular respiration as well as data from microscopy. © 2011 Institute of Physics and Engineering in Medicine.


Wolf P.,TU Munich | Wolf P.,HP Medizintechnik GmbH | Brischwein M.,TU Munich | Kleinhans R.,TU Munich | And 6 more authors.
Biosensors and Bioelectronics | Year: 2013

Cellular assays have become a fundamental technique in scientific research, pharmaceutical drug screening or toxicity testing. Therefore, the requirements of technical developments for automated assays raised in the same rate. A novel measuring platform was developed, which combines automated assay processing with label-free high-content measuring and real-time monitoring of multiple metabolic and morphologic parameters of living cells or tissues. Core of the system is a test plate with 24 cell culture wells, each equipped with opto-chemical sensor-spots for the determination of cellular oxygen consumption and extracellular acidification, next to electrode-structures for electrical impedance sensing. An automated microscope provides the optical sensor read-out and allows continuous cell imaging. Media and drugs are supplied by a pipetting robot system. Therefore, assay can run over several days without personnel interaction. To demonstrate the performance of the platform in physiologic assays, we continuously recorded the kinetics of metabolic and morphologic parameters of MCF-7 breast cancer cells under the influence of the cytotoxin chloroacetaldehyde. The data point out the time resolved effect kinetics over the complete treatment period. Thereby, the measuring platform overcomes problems of endpoint tests, which cannot monitor the kinetics of different parameters of the same cell population over longer time periods. © 2013 Elsevier B.V.


Pfister C.,TU Munich | Pfister C.,HP Medizintechnik GmbH | Bozsak C.,TU Munich | Wolf P.,HP Medizintechnik GmbH | And 3 more authors.
Physiological Measurement | Year: 2015

Flow-induced shear stress on adherent cells leads to biochemical signaling and mechanical responses of the cells. To determine the flow-induced shear stress on adherent cells cultured in a micro-scaled reaction chamber, we developed a suitable finite element method model. The influence of the most important parameters - cell shape, cell density, shear modulus and fluid velocity - was investigated. Notably, the cell shape strongly influences the resulting shear stress. Long and smooth cells undergo lower shear stress than more rounded cells. Changes in the curvature of the cells lead to stress peaks and single cells experience higher shear stress values than cells of a confluent monolayer. The computational results of the fluid flow simulation were validated experimentally. We also analyzed the influence of flow-induced shear stress on the metabolic activity and shape of L929, a mouse fibroblast cell line, experimentally. The results indicate that threshold stress values for continuous flow conditions cannot be transferred to quasi static flow conditions interrupted by short fluid exchange events. © 2015 Institute of Physics and Engineering in Medicine.


Pfister C.,TU Munich | Wolf P.,HP Medizintechnik GmbH
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2015

We present an automated analysis of the cellular dynamic metabolic activity in combination with live cell imaging, an essential factor for understanding the fundamental cellular physiological responses. For that purpose, we utilized the Intelligent Microplate Reader, a new analysis platform for marker-free cell-based assays in real-time. To demonstrate the benefit of the platform, we analyzed the relationship between various dynamic cell parameters (extracellular acidification, oxygen uptake, cell morphology, cell density and cell migration) of L929, a mouse fibroblast cell line, under the influence of sodium dodecyl sulfate. The dynamic kinetics of the monitored parameters are consistent and revealing much information about the activity occurring in the cells. © 2015 IEEE.


Kleinhans R.,TU Munich | Brischwein M.,TU Munich | Wang P.,TU Munich | Becker B.,TU Munich | And 7 more authors.
Medical and Biological Engineering and Computing | Year: 2012

Personalized tumor chemotherapy depends on reliable assay methods, either based on molecular ''predictive biomarkers'' or on a direct, functional ex vivo assessment of cellular chemosensitivity. As a member of the latter category, a novel high-content platform is described monitoring human mamma carcinoma explants in real time and label-free before, during and after an ex vivo modeled chemotherapy. Tissue explants are sliced with a vibratome and laid into the microreaction chambers of a 24-well sensor test plate. Within these ≈23 μl volume chambers, sensors for pH and dissolved oxygen record rates of cellular oxygen uptake and extracellular acidification. Robot-controlled fluid system and incubation are parts of the tissue culture maintenance system while an integrated microscope is used for process surveillance. Sliced surgical explants from breast cancerous tissue generate well-detectable ex vivo metabolic activity. Metabolic rates, in particular oxygen consumption rates have a tendency to decrease over time. Nonetheless, the impact of added drugs (doxorubicin, chloroacetaldehyde) is discriminable. Sensor-based platforms should be evaluated in explorative clinical studies for their suitability to support targeted systemic cancer therapy. Throughput is sufficient for testing various drugs in a range of concentrations while the information content obtained from multiparametric real-time analysis is superior to conventional endpoint assays. © International Federation for Medical and Biological Engineering 2011.

Loading HP Medizintechnik GmbH collaborators
Loading HP Medizintechnik GmbH collaborators