microelectronic meets medicine (m 3 ) From Sensorarray to intelligent pills
source: www.cochlea-implantat.ch source: www.dr-severe.de Reality and Visions source www.memagazine.org source: www.pharmazeutische-zeitung.de source: www.charite.de
Health care: Where the money goes Health expenditure in Germany in the year 2003: for (in billion Euro): total 239,7 billion Euro Differences due to rounding Source: Stat. Bundesamt
R&D spendings and NME licenses (pharma) year R&D spendings of the PhRMA-member-companies [billion USD] NME licenses NME licenses R&D spendings
Costs and life span
Improvement of processors
entire output of processing industries in the G7-states* persons employed in processing industries in the G7-states* period of time development in microelectronic transistors per unit of area *USA, France, Great Britain, Germany, Japan, Italy, Canada
Trends in technology
Nanostructures in a biological cell surface membrane vesicles endoplasmatic reticulum (protein synthesis and modification) nucleus Electron micrograph of human colon cancer cells ( B. Wolf) 1 µm cell-cell contact Mitochondrium (energy production)
Oscillations in cell communication
Membrane potentials of cells -40 Binggeli, R, Weinstein, R.C., J. theor. Biol. 1986, 123, pp. 377-401
Signal transduction systems of a cell Input molecules of adhesion antigen/antibody (CEA) Growth factors (EGF,PDGF, insulin ) hormone (vasopressin) hormone (adrenalin) adhesion and morphology modulators enzyme cytostatic drugs proliferation metabolism O 2, ion transfer potential of the membrane, ions (Na, K, Ca, Cl ) dielectric properties of the cell membran phregulation ph of micro environment Output vesicular transport metabolite, lactic acid, CO 2, heat of reaction Multiparametric Chips as signal transducer
Design of cell-chip-interfaces
Cells on an ISFET-gate (electron micrograph of tumor cells, B. Wolf)
A cell-chip workstation
Multielectrode arrays for detection of action potentials CNNS,University of North Texas, Denton, Texas, USA
Analysis of electric cell communication in neuronal networks Realtime analysis of neuronal signals (unterstützt durch Fluoreszenzmikroskopie) Action potential waveslopes Time response of activity: Online data analysis cellchip
A portable cell-chip workstation for metabolic analysis Integrated life support system allows online measurement on living cells Tumor cells are cultivated on a ceramic based multi-parametic sensor chip Cellassys Tumor cells have to be cultivated on the sensor chip. The cost-saving ceramic substrate includes all sensors for the measurement of vital parameters
An automated multi-well cell-chip workstation e) top view bottom view Intelligent Microplate Reader (Prototype) System components: a) digital inverted microscope (TILL-Photonics), b) robot (H&P Labortechnik AG, ), c) sterile warm able Housing (schematic), d) external PC, e) multi sensor array microtestplate
Measurements of tumor cell vitality: Chemosensitivity testing of primary breast cancer cells Metabolic rates (scaled) 1,5 1,0 0,5 +50 µm CAA Extracellular Acidification (+CAA) Extracellular Acidification (control) Oxygen Consumption (control) Oxygen Consumption (+CAA) Triton-X-100 0,0 0 5 10 15 20 25 Time [h]
Measurements of tumor cell vitality: Detection of drug resistance Legend: Colon carcinoma cells (LS174T) were grown on glass chips. The test agent (gray bars) was added and removed with the perfusion medium.
Developments for localized drug therapy: Smart Drugs
Developments for localized drug therapy: Smart Drugs source: Headlines@Hopkins der Johns Hopkins University, Baltimore
Developments for localized drug therapy: Manipulation of magnetic nanobeads
Developments for localized drug therapy: Magnetic Drug Targeting Magnetic drug targeting uses magnetic particles loaded with a drug to establish a high concentration of the substance in a diseased region. Dames, P, Gleich, B. et. al., Nature Nanotech, 2,8 (2007), pp. 495-499
Developments for localized drug therapy: Magnetic Neurostimulation Mag n More GmbH, www.magnandmore.de
Developments in Telemedicine: Detection of bruxism BioBite - sleep guard system for diagnosis and therapy of bruxism
Developments in Telemedicine: Monitoring of pulse and exposure with on single device 1-channel ECG acceleration altimeter detection of movement patterns Sendsor GmbH
Developments in Telemedicine: Biometric authentification via detection of footstep pattern 2 test persons; histogram of vertical and horizontal acceleration values (1024 values)
Developments in Telemedicine: Virtual telemedicine Testing of personalized therapies in a virtual lab.
Developments in Telemedicine: Project SyCare producer provider data center clinic Heinz Nixdorf-Lehrstuhl für Medizinische Elektronik Prof. Dr. B. Wolf SyCare ist eingetragenes Warenzeichen der Firma Synergy Systems GmbH internet
Mitarbeiter des Heinz Nixdorf-Lehrstuhls für Medizinische Elektronik Prof. Dr. Bernhard Wolf Dr.Helmut Grothe Dr. Martin Brischwein Dr. Angela Otto Dr. Thomas Weyh Dr. Jochen Peter Dipl.-Ing. Carlos do Amaral Dipl.-Ing. Eléonore Cabala Dipl.-Ing. Johannes Clauss Dipl.-Ing. Petra Friedrich Dr.-Ing. Thomas Geisler Dr.-Ing. Bernhard Gleich Dipl.-Ing. Hans-Georg Gruber Dipl.-Ing. Florian Ilchmann Dipl.-Ing. Volker Lob Dipl.-Ing. Jochen Meyer Dipl.-Ing. Johann Ressler Dipl.-Ing. Michael Schmidhuber Dipl.-Ing. Alexander Scholz B. Sc. Adonay da Silva Dipl.-Biol. Torsten Stadthagen Dr.-Ing. Kerstin Wendicke Dipl.-Ing. Joachim Wiest Dr.-Ing. Hannes Zantow Robert Arbogast Ingrid Franz Alfred Michelfelder Margarethe Remm Wolfgang Ruppert Ildiko Szabados Gudrun Teschner Jeannette Toldrian