listen to your cells - lbe.ei.tum.de · 6 high-content cell based assays hp-med.com toxicokinetics...

… listen to your cells

High-content cell based assays

hp-med.com

2


hp-med.com

... 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 fi nd remedies for diseases such as cancer or diabetes. Living cells also have to be investigated in fi elds 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 diff erent parameters regarding the vitality of cells non-invasively, online and for long term experiments. After more than 10 years of scientifi c work, implementation of such systems by cellasys GmbH and HP Medizintechnik GmbH resulted. Here, microsensors for monitoring respiration, acidifi cation 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. Diff erent 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.

3


hp-med.com cont

ent

page

applicationsOncology 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

systemsIMOLA-IVD 16

IMR 18

softwareIMOLA-IVD 20

IMROS 20

DALiA 21

serviceAssay development 22

Training 22

System integration 22

Consultancy 22

Tested cells 23

content

4


hp-med.com

Oncology To test the effi ciency 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.

applications

Thanks to: B. Becker, Heinz Nixdorf – Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany

5


hp-med.com appl

icat

ions

applications and operational area

Drug development The eff ect of new drugs on cellular metabolism and

cellular morphology can be investigated.

The example shows the infl uence 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

6


hp-med.com

Toxicokinetics Monitoring of the vitality of cultured living cells is the key toward the reduction

of animal experiments in the fi eld of toxicology.

The example shows the toxic eff ect of mercury toward 3T3 fi broblasts and also the recovery of the cells after the toxin is removed.

Thanks to: J. Frank, BioMed – zet Life Science GmbH, Austria

applications

7


hp-med.com


appl

icat

ions

Quality control In the fi eld 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 fi broblast with diff erent vitality status.

Thanks to: R. Kleinhans, Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany

8


hp-med.com

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 Iff eldorf Department of Ecology, Technische Universität München, Germany

9


hp-med.com


appl

icat

ions

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

10


hp-med.com

applications

Diabetes research Pancreatic islets, and in particular insulin producing beta-cells, can be monitored

under diff erent 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

11


hp-med.com


appl

icat

ions

Risk assessment New ingredients of daily products like cosmetics or detergents have to be classifi ed

in their harmlessness as well as in their degradabillity and exposure time.

The example shows the oxygen consumption rate of cells after treatment with diff erent concentrations of an unknown substance.

Thanks to: M. Zottmann, Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik, Technische Universität München, Germany

12


hp-med.com

applications

Functional food research To investigate e.g. anti-infl ammatory 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

13


hp-med.com appl

icat

ions

hp-med.com

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 acidifi cation rate of cells when treated with cell culture media containing diff erent FCS.

Thanks to: Heraeus Sensor Technology GmbH, Kleinostheim, Germany


14


hp-med.com

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

15


hp-med.com


Basic research Cell based assays are useful tools in basic research in the fi eld 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

appl

icat

ions

16


hp-med.com

IMOL A - IVD Low priced disposable BioChip-C for

pH, pO2, bioimpedance and temperature

Electro-chemical sensors for pH and pO2, bioimpedance and temperature

In conformity with directive 98/97/EC on in vitro medical devices

Closed fl uid system

Continuous long term monitoring of cell vitality

Marker-free assays with living cells

Online data analysis and visualization

Automated six channel fl uid system

Ready to use set up in incubator

BioChip-C

DescriptionThe intelligent mobile lab for in vitro diagnostics (IMOLA-IVD) is a fl exible modular device for monitoring extracellular acidifi cation, mitochondrial activity or cellular respiration and bioimpedance (detects changes in cell number, density and morphology) of living cells.

Advantages Low priced disposable BioChip-C

Closed fl uid system

Continuous long term monitoring

Integrated PC-System

systems

17


hp-med.com

systems and units

syst

ems

Technical data

Measurement parameters

Extracellular acidifi cation (pH)Oxygen consumption (pO2)

Cell morphology (bioimpedance)Temperature

Liquid handling system 6 channel closed fl uid systemModular reservoir and waste fl asks

Interfaces

WirelessSerialCAN

Ethernet

Power supply 230 V (50 Hz), 115 V (60 Hz)

Product changes and new accessories will be made public on our website in due course.

Conformity to directive 98/97/EC on in vitro diagnostic medical devices.

18


hp-med.com

systems

IMR Low priced disposable 24 well sensor plates

detecting pH, pO2, bioimpedance

Glass substrate for imaging capability

Sensor plate observes standard SBS format

Opto-chemical sensors for pH and pO2

Bioimpedance sensor utilizes platinum thin fi lm technology

All wells with own independent robot interfaced micro-fl uidics

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)

DescriptionThe 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 fl exible experiments. The micro-fl uidics in the sensor plate assure a nearly 100% disposal of used fl uids, thus even allowing the removal of drugs from cell growth area.

The sensor plate contains opto-electronic sensors for pH (extracellular acidifi cation), pO2 (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, pO2)

Morphology (bioimpedance)

Imaging (microscope)

All systems are fi eld upgradeable

Corresponding sensor plates available

19


hp-med.com

systems and units

syst

ems

Advantages Easy experiment setup

Robot allows fl exible experiments

Experiment length is not limited

Standard laboratory dimensions

Side-by-side mounting without any clearance

Integrated PC-System

Autofocus

Technical data

Measurement parametersExtracellular acidifi cation (pH)

Oxygen consumption (pO2)Cell morphology

Imaging4x – 40x magnifi cation

Fluorescence and transmitted light microscopyAutomated microscope moving on xy-stage

Liquid handling system24 channel pipetting (up to 250 μl each)

7 storage / waste positions (SBS standard)1 measurement position (sensor plate)

Interfaces Ethernet (100 Mbit)

Power supply 230 V (50 Hz), 115 V (60 Hz)

Product changes and new accessories will be made public on our website in due course.

HP Medizintechnik GmbHBruckmannring 1985764 Oberscheißheim

Made in Germany

Interdigital electrode structure on sensor plate, image taken with a bright fi eld microscope (iMic Till Photonics)settings: 40x magnifi cation, numerical aperture(NA) = 0.75

20


hp-med.com

IMROSThe user interface (IMROS – IMR Operating System) provides a comfortable and easy-to-use interface for handling experiment runs. Diff erent expansion stages depending on the application are supported.

Easy to use confi guration software Quick start by using predefi ned

protocols Setup instructions shown for

each experiment Password protection against

unauthorized use Local or centralized user

management Messenger system via email

and SMS Data export to remote servers Remote update for latest

software features

IMOLA-IVDThe user interface for the IMOLA system is integrated in a local client version of the DALiA software package. With a user-based confi guration modul it is possible to predefi ne diff erent tests for researchers, laboratory personnel or automated tests.

software

Image analysis Automatic cell count 3D image stack Time lapse Visualisation of fl uorescence data Measurements of length,

area and volume

21


hp-med.com

software

DALiAThe 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

soft

war

e

22


hp-med.com

ServiceWe are ready to assist you as a service partner to perform your tests or studies using our cell based assays. We have diff erent service laboratories with trained personnel to perform your tests in a reliable and effi cient way. Please fi nd some of the cells we already investigated on the opposite page.

Assay developmentWe help to develop particular assays to address your specifi c 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.

TrainingDiff erent tasks need diff erent 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 integrationThe 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.

ConsultancyWe performed studies ranging from “future trends of cell based assays” and “marketing research” to the “optimization of fl uidic parameters for specifi c cell lines”. If you need consultancy in the fi eld of cell based assays our knowledge and the experience at the Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik may be valuable.

service

23


hp-med.com serv

ice

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 fi broblast cell line

3T3 Mouse fi broblast 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

[email protected]

Tel: +49 89 2000110-74Fax: +49 89 2000110-76


System development and marketing

Supported by

hp-med.comHP Medizintechnik GmbH

Bruckmannring 1985764 Oberschleissheim - Germany

Tel: +49 89 30 666 47 -0

[email protected]

cellasys GmbH - R&D

Karlstrasse 9680335 Munich - Germany

Tel: +49 89 2000110-74

[email protected]

Technische Universität München

Heinz Nixdorf-Lehrstuhl für Medizinische Elektronik

Prof. Dr. Bernhard Wolf

Tel: +49 89 289-22947

www.lme.ei.tum.deSupported by

www.ime-muenchen.de www.shz-software.com

Supported by

www.heraeus-sensor-technology.com

Partner

listen to your cells - lbe.ei.tum.de · 6 high-content cell based assays hp-med.com toxicokinetics...

Documents