listen to your cells hp-med.com High-content cell based assays

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1 listen to your cells

2 ... listen to your cells Living cells are the main components of nature and human life. Understanding of cellular evolution and interaction with their microenvironment is essential to find remedies for diseases such as cancer or diabetes. Living cells also have to be investigated in fields of application like environmental monitoring, regenerative medicine or as an alternative for animal experiments. Modern elaborate research at the Heinz Nixdorf Lehrstuhl für Medizinische Elektronik at the Technische Universität München evolved a mature technology to record different parameters regarding the vitality of cells non-invasively, online and for long term experiments. After more than 10 years of scientific work, implementation of such systems by cellasys GmbH and HP Medizintechnik GmbH resulted. Here, microsensors for monitoring respiration, acidification and morphological changes of the cells are used. Such systems are now produced maintaining industrial quality standards and are available for a variety of applications. Different research groups are working on the development of new assays incorporating those systems. Now, unique information about cellular metabolism can be gained to develop new therapies, alternative approaches or early warning systems. So, listen to your cells. 2

3 content applications Oncology 4 Drug development 5 Toxicokinetics 6 Quality control 7 Environmental monitoring 8 Biofuel production research 9 Diabetes research 10 Risk assessment 11 Functional food research 12 FCS tests 13 Food testing 14 Basic research 15 page systems IMOLA-IVD 16 IMR 18 software IMOLA-IVD 20 IMROS 20 DALiA 21 service Assay development 22 Training 22 System integration 22 Consultancy 22 Tested cells 23 content 3

4 applications Oncology To test the efficiency of a drug prior to the beginning of a therapy, the drug can be tested on the basis of a patient s biopsy. The example shows a dose response curve of the chemotherapeutic agent Cisplatin tested on cancer cells. The displayed parameter of cellular vitality is normalized to the time of drug addition. Thanks to: B. Becker, Heinz Nixdorf Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany 4

5 applications and operational area Drug development The effect of new drugs on cellular metabolism and cellular morphology can be investigated. The example shows the influence of the anti cancer drug Arctigenin on a PANC-1 cell line. Both aspects of bioimpedance monitoring (real and imaginary part) are recorded. Thanks to: K. Kami, Institute for Advanced Biosciences, Keio University, Japan applications 5

6 applications Toxicokinetics Monitoring of the vitality of cultured living cells is the key toward the reduction of animal experiments in the field of toxicology. The example shows the toxic effect of mercury toward 3T3 fibroblasts and also the recovery of the cells after the toxin is removed. Thanks to: J. Frank, BioMed zet Life Science GmbH, Austria 6

7 applications and operational area Quality control In the field of regenerative medicine the vitality of the used cells can be determined. With the vitality information only the healthiest cells can be selected for e.g. transplantation. The example shows 3T3 fibroblast with different vitality status. Thanks to: R. Kleinhans, Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany applications 7

8 applications Environmental monitoring With algae as signal converters the systems can be used to monitor water quality. The example shows the reduced photosynthetic activity of chlorella kessleri after contamination with Metamitron and the recovery after removal of the toxin. Thanks to: T. Stadthagen, Limnologische Station Iffeldorf Department of Ecology, Technische Universität München, Germany 8

9 applications and operational area Biofuel production research To investigate the potential of algae for biofuel production the vitality of the algae can be monitored during changing environmental conditions. The example shows photosynthetic active algae in an enlighted environment and oxygen consuming algae in a dark environment. Thanks to: N. Ohi, Institute for Advanced Biosciences, Keio University, Japan applications 9

10 applications Diabetes research Pancreatic islets, and in particular insulin producing beta-cells, can be monitored under different conditions of nutrient supply. The metabolic measurement of beta-cells or islets can provide basic information on their viability and functional capacity in regenerative medicine. The test example shows changes in metabolic activity of the beta-cell line INS-1E when exposed to glucose concentrations mimicking physiologically low and high glucose levels in blood, i.e. under conditions which regulate insulin secretion. Thanks to: A.M. Otto, Institute for Medical Engineering, Technische Universität München, Germany 10

11 applications and operational area Risk assessment New ingredients of daily products like cosmetics or detergents have to be classified in their harmlessness as well as in their degradabillity and exposure time. The example shows the oxygen consumption rate of cells after treatment with different concentrations of an unknown substance. Thanks to: M. Zottmann, Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany applications 11

12 applications Functional food research To investigate e.g. anti-inflammatory properties of food additives interactions between cells and additive can be monitored. The example shows the interference between an additive and escherrichia coli bacteria after 9 h of interaction. Thanks to: M. Brischwein, D. Grundl, Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany and DIL - German Institute Of Food Technologies, Quakenbrück, Germany 12

13 applications and operational area FCS tests If new fetal calve serum (FCS) has to be tested in a cell culture laboratory, the evaluation using a cell based assay gives better information about cellular vitality than e.g. cell counting. The example shows the acidification rate of cells when treated with cell culture media containing different FCS. Thanks to: Heraeus Sensor Technology GmbH, Kleinostheim, Germany applications 13

14 applications Food testing To check if food is free of toxins a probe of the food or the washing water can be investigated. The example shows the reduced vitality of yeast due to a fungicide. Thanks to: M. Schmidhuber, Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany 14

15 applications and operational area Basic research Cell based assays are useful tools in basic research in the field of cell biology. The example shows the interaction between the drug Cytochalasin B and living cells. Thanks to: J. Fredebohm, German cancer research center, Heidelberg, Germany applications 15

16 systems IMOL A - IVD Low priced disposable BioChip-C for ph, po 2, bioimpedance and temperature Electro-chemical sensors for ph and po 2, bioimpedance and temperature In conformity with directive 98/97/EC on in vitro medical devices Closed fluid system Continuous long term monitoring of cell vitality Marker-free assays with living cells Online data analysis and visualization Automated six channel fluid system Ready to use set up in incubator Advantages Low priced disposable BioChip-C Closed fluid system Continuous long term monitoring Integrated PC-System BioChip-C Description The intelligent mobile lab for in vitro diagnostics (IMOLA-IVD) is a flexible modular device for monitoring extracellular acidification, mitochondrial activity or cellular respiration and bioimpedance (detects changes in cell number, density and morphology) of living cells. 16

17 systems and units Technical data Measurement parameters Liquid handling system Extracellular acidification (ph) Oxygen consumption (po 2 ) Cell morphology (bioimpedance) Temperature 6 channel closed fluid system Modular reservoir and waste flasks Interfaces Power supply Product changes and new accessories will be made public on our website in due course. Wireless Serial CAN Ethernet 230 V (50 Hz), 115 V (60 Hz) Conformity to directive 98/97/EC on in vitro diagnostic medical devices. systems 17

18 systems IMR Low priced disposable 24 well sensor plates detecting ph, po 2, bioimpedance Glass substrate for imaging capability Sensor plate observes standard SBS format Opto-chemical sensors for ph and po 2 Bioimpedance sensor utilizes platinum thin film technology All wells with own independent robot interfaced micro-fluidics Continuous long term monitoring of cell vitality Marker-free assays with living cells Imaging with computer controlled microscope Online data analysis and visualization Liquid handling robot Multiple storage and waste volumes Environmental control (temperature, humidity) Description The Intelligent Microplate Reader (IMR) is a fully automated system for cell based assays. After the experiment setup, the system runs autonomously, yet measurement data and acquired microscope images can be observed in real-time. Due to the liquid handling robot, drugs can be added anytime, therefore enabling flexible experiments. The micro-fluidics in the sensor plate assure a nearly 100% disposal of used fluids, thus even allowing the removal of drugs from cell growth area. The sensor plate contains opto-electronic sensors for ph (extracellular acidification), po 2 (mitochondrial activity cellular respiration) and bioimpedance (detects changes in cell number, density and morphology). Through the glass substrate of the plate, continuous imaging of cells is possible. Modular setup Measurement systems can be customer chosen Metabolics (ph, po 2 ) Morphology (bioimpedance) Imaging (microscope) All systems are field upgradeable Corresponding sensor plates available 18

19 systems and units HP Medizintechnik GmbH Bruckmannring Oberscheißheim Made in Germany Advantages Easy experiment setup Robot allows flexible experiments Experiment length is not limited Standard laboratory dimensions Side-by-side mounting without any clearance Integrated PC-System Autofocus Technical data Measurement parameters Imaging Liquid handling system Interfaces Power supply Product changes and new accessories will be made public on our website in due course. Interdigital electrode structure on sensor plate, image taken with a bright field microscope (imic Till Photonics) settings: 40x magnification, numerical aperture(na) = 0.75 Extracellular acidification (ph) Oxygen consumption (po 2 ) Cell morphology 4x 40x magnification Fluorescence and transmitted light microscopy Automated microscope moving on xy-stage 24 channel pipetting (up to 250 μl each) 7 storage / waste positions (SBS standard) 1 measurement position (sensor plate) Ethernet (100 Mbit) 230 V (50 Hz), 115 V (60 Hz) systems 19

20 software IMOLA-IVD IMROS The user interface for the IMOLA system is integrated in a local client version of the DALiA software package. With a user-based configuration modul it is possible to predefine different tests for researchers, laboratory personnel or automated tests. The user interface (IMROS IMR Operating System) provides a comfortable and easy-touse interface for handling experiment runs. Different expansion stages depending on the application are supported. Easy to use configuration software Quick start by using predefined protocols Setup instructions shown for each experiment Password protection against unauthorized use Local or centralized user management Messenger system via and SMS Data export to remote servers Remote update for latest software features Image analysis Automatic cell count 3D image stack Time lapse Visualisation of fluorescence data Measurements of length, area and volume 20

21 software DALiA The Data Acquisition and Link Application (DALiA) allows secure storage and online access to your data. With the import/export interfaces data can be exchanged with other software packages. Analysis Views Statistics Storage User management Application management BioChip management Device management software 21

22 service Service We are ready to assist you as a service partner to perform your tests or studies using our cell based assays. We have different service laboratories with trained personnel to perform your tests in a reliable and efficient way. Please find some of the cells we already investigated on the opposite page. Assay development We help to develop particular assays to address your specific questions. Together with the scientists of the Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik our experienced team of biologists, engineers and quality representatives assure valid assays which are compliant to regulatory laws. Training Different tasks need different knowledge. Ask for training in the usage of cell based assays, system integration or assay development. Our interdisciplinary team is happy to share their experience with you. System integration The skills of our engineers include broadcasting, miniaturization, parallelization, analysis and data management. Please ask for an extension of your existing technology or laboratories by our team. Consultancy We performed studies ranging from future trends of cell based assays and marketing research to the optimization of fluidic parameters for specific cell lines. If you need consultancy in the field of cell based assays our knowledge and the experience at the Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik may be valuable. 22

23 service Tested cells MDA Human breast adenocarcinoma cell line Caco-2 Human epithelial colorectal adenocarcinoma cell line HeLa Human cervical cancer cell line MIA PaCa-2 Human pancreatic carcinoma cell line PANC-1 Human pancreatic carcinoma cell line BxPC3 Human pancreatic adenocarcinoma cell line K562 Human myelogenous leukaemia line INS-1E Rat insulinoma cells L929 Mouse fibroblast cell line 3T3 Mouse fibroblast cell line Primary cells Primary human breast carcinoma slice Primary human laryngeal carcinoma slice Primary murine neuron cells Primary murine liver slice Primary ovine pancreatic slice Yeast Baker s yeast Escherrichia coli Gram-negative facultative anaerobic bacterium Chromera velia Microalgae Chlorella kessleri Algae All technical details are state of the technology from March 2010 and are subject to change without notice. No liability is assumed for pictures, descriptions or any content of this brochure. All descriptions, pictures, technical drawings and all other illustrations are protected by copyright and unless otherwise marked property of cellasys GmbH. Any subsequent use needs prior written allowance by cellasys GmbH. service 23

24 Contact Tel: Fax: System development and marketing cellasys GmbH - R&D Karlstrasse Munich - Germany Tel: HP Medizintechnik GmbH Bruckmannring Oberschleissheim - Germany Tel: www. Partner Supported by Technische Universität München Heinz Nixdorf-Lehrstuhl für Medizinische Elektronik Prof. Dr. Bernhard Wolf Tel: Supported by Supported by

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