the topic micro TAS conference S Di USA 2008 San Diego, USA 2008 Cheju, Korea 2009 impact factor 5.8 1,000 attendees annually p f Reviews on Micro total analysis systems in Anal.Chem. 2002, 2004, 2006 and 2008 cited over 1,900 times
amino acids c e [ a r b . u n i t s ] 1 2 3 4 c y c l e # t 7 s s y n c h r . c e [ a r b . u n i t s ] 1 2 3 4 c y c l e # t 7 s s y n c h r . c e [ a r b . u n i t s ] 1 2 3 4 c y c l e # t 7 s s y n c h r . f l u o r e s c e n 0 4 0 8 0 1 2 0 1 6 0 5 6 7 8 f l u o r e s c e n 0 4 0 8 0 1 2 0 1 6 0 5 6 7 8 f l u o r e s c e n 0 4 0 8 0 1 2 0 1 6 0 5 6 7 8 D J H i K Fl K S il Z F C S Eff h A M S i 261 895 897 D.J.Harrison, K.Flury, K.Seiler, Z.Fan, C.S.Effenhauser, A.Manz, Science 261, 895-897 (1993) C.S.Effenhauser, A.Manz, H.M.Widmer, Anal. Chem. 65, 2637-2642 (1993)
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i Brain Blood vessels Ear Tooth 1. Take stem cells from any origin Hair Lung Heart Pancraes Liver Kidney Kidney Cartilage 2. Induce differentiation by: Soluble Immobi- lised C ge Bone factors lised factors Muscle 3. Count and find model cell type to test the device 43 Cell Programming by Nanoscaled Devices
Inner cell group In vitro ESC Stem cell (SC) sources tial of ntiation higher embryonic adult Single ESC In vitro ESC (no. of passage?) In vitro adult SC (passage?) Potent differen lower adult on low Morphology only Specific marker (images only) Statistics ifferentiati Specific markers (quantitatively) Proteome- charac- Quality of d Functionality Functionality and cell interaction Complete epigenetic h t i ti terisation Q high characterisation Long-term stable implantation 44 Cell Programming by Nanoscaled Devices
differentiation depends on many factors. Not constant! 2 No 100% no 0% differentiation ] 70 80 90 Embryonic SC Adult SC 2. No 100%, no 0% differentiation. 3. Suppressing any differentiation in the case of ESC only. ells in [% 50 60 70 differentiation fferentiation 4. Frequently many factors are changed simultaneously. ntiated ce n tion 30 40 pontaneous d Induced di 5. Isotrope versus cluster differentiation. of differe differentiation ed differentiat 10 20 Sp erentiation Amount o Spontaneous Induce ? 0 ppressed diffe S ? 45 Cell Programming by Nanoscaled Devices Sup
lt f t ll In vitro-culture of stem cells A li i f Application of factors SPARC Variant 1: X Variant 2: Variant n: SPARC + X Variant 3: X + Y SPARC X SPARC + X + Y X + Y … … … Actual single factor induction of cell differentiation! Application of different media! pp Unphysiological high concentration of factors! In addition undefined substances (e.g. FCS, Trypsin …)! 46 Cell Programming by Nanoscaled Devices
b Principle of MagnaLab Bild MagnaLab 20 Carrier 120 Microcarriers in one cultivation unit 20 Carrier 20 Carrier unit 20 Carrier 20 Carrier 20 Carrier Cultivation for more than 20 days! ! Inlet and outlet tubes removed ! 51 Cell Programming by Nanoscaled Devices Cultivation for more than 20 days!
beating (synchronised) clusters/cm2 Y = Number of stem cell clusters/cm2 50 up to 100 synchronized 54 Cell Programming by Nanoscaled Devices 50 up to 100 synchronized cardiomyocytes
Ch Prof.Günter Fuhr, St. Ingbert Lin Chen Helke Reinhardt g Dr.Daniel Schmidt, St.Ingbert Prof Claude Leclerq Paris Kaoru Tachikawa Claus Schumann Prof.Claude Leclerq, Paris Dr.Richard Loman, Paris Prof Philippe Renaud Lausanne Dr.Joachim Franzke Prof Philip Day Prof.Philippe Renaud, Lausanne Dr.Martin Heule, Lausanne i i Prof.Philip Day Ying Cai P f K i hi Oh Dr.Luc Bousse, Mountain View Prof.Ken-ichi Ohno