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090630 Ion Cannel Retreat

  1. Pluripotent Stem Cell-derived Cardiomyocytes as Suitable Substrates For Automated Ion Channel and Electrophysiological Analysis Systems Dr. Ralf Kettenhofen Axiogenesis AG 7th Ion Channel Retreat June 29th, Vancouver
  2. Content
  3. Content Introduction Transgenic Pluripotent Stem Cells Selection of Cardiomyocytes from Differentiated mouse ES Cells
  4. Content Introduction Transgenic Pluripotent Stem Cells Selection of Cardiomyocytes from Differentiated mouse ES Cells Automated Recording and Pharmacology of Cardiac Ion Currents
  5. Content Introduction Transgenic Pluripotent Stem Cells Selection of Cardiomyocytes from Differentiated mouse ES Cells Automated Recording and Pharmacology of Cardiac Ion Currents Automated Recording and Pharmacology of Cardiac Action Potentials
  6. Content Introduction Transgenic Pluripotent Stem Cells Selection of Cardiomyocytes from Differentiated mouse ES Cells Automated Recording and Pharmacology of Cardiac Ion Currents Automated Recording and Pharmacology of Cardiac Action Potentials Automated Analyses and Pharmacology of Cardiac Na+/K+-ATPases
  7. Content Introduction Transgenic Pluripotent Stem Cells Selection of Cardiomyocytes from Differentiated mouse ES Cells Automated Recording and Pharmacology of Cardiac Ion Currents Automated Recording and Pharmacology of Cardiac Action Potentials Automated Analyses and Pharmacology of Cardiac Na+/K+-ATPases Summary
  8. Content Introduction Transgenic Pluripotent Stem Cells Selection of Cardiomyocytes from Differentiated mouse ES Cells Automated Recording and Pharmacology of Cardiac Ion Currents Automated Recording and Pharmacology of Cardiac Action Potentials Automated Analyses and Pharmacology of Cardiac Na+/K+-ATPases Summary Conclusion
  9. The Optimal Cellular Model
  10. The Optimal Cellular Model Physiological properties
  11. The Optimal Cellular Model Physiological properties Ready-to-use availability
  12. The Optimal Cellular Model Physiological properties Ready-to-use availability Lot-to-lot reproducibility
  13. The Optimal Cellular Model Physiological properties Ready-to-use availability Lot-to-lot reproducibility No inter lab-differences
  14. The Optimal Cellular Model Physiological properties Ready-to-use availability Lot-to-lot reproducibility No inter lab-differences Purity
  15. The Optimal Cellular Model Physiological properties Ready-to-use availability Lot-to-lot reproducibility No inter lab-differences Purity Relevant and predictive
  16. The Optimal Cellular Model Physiological properties Ready-to-use availability Lot-to-lot reproducibility No inter lab-differences Purity Relevant and predictive
  17. Puromycin Selection of Cardiomyocytes from Genetically Engineered Embryonic Stem Cells
  18. Puromycin Selection of Cardiomyocytes from Genetically Engineered Embryonic Stem Cells
  19. Puromycin Selection of Cardiomyocytes from Genetically Engineered Embryonic Stem Cells Differentiation of ES cells and selection of cardiomyocytes
  20. Puromycin Selection of Cardiomyocytes from Genetically Engineered Embryonic Stem Cells Differentiation of ES cells and selection of cardiomyocytes 9d Puro 0d
  21. Puromycin Selection of Cardiomyocytes from Genetically Engineered Embryonic Stem Cells Differentiation of ES cells and selection of cardiomyocytes 9d 10d 12d Puro 0d Puro 1d Puro 3d
  22. Puromycin Selection of Cardiomyocytes from Genetically Engineered Embryonic Stem Cells Differentiation of ES cells and selection of cardiomyocytes 9d 10d 12d Puro 0d Puro 1d Puro 3d Quality control Freezing Dissociation
  23. Puromycin Selection of Cardiomyocytes from Genetically Engineered Embryonic Stem Cells Differentiation of ES cells and selection of cardiomyocytes 9d 10d 12d Puro 0d Puro 1d Puro 3d Quality control Freezing Dissociation
  24. Specificity and In Vivo Relevance?
  25. Specificity and In Vivo Relevance? Fleischmann M. et al. FEBS Lett. 1998 Dec 4;440(3):370-6
  26. Specificity and In Vivo Relevance? Kolossov E. J Exp Med. 2006 Oct 2;203(10):2315-27. Fleischmann M. et al. FEBS Lett. 1998 Dec 4;440(3):370-6
  27. ES Cell-derived, Genetically Selected and Purified Cardiomyocytes 17d in culture after thawing
  28. ES Cell-derived, Genetically Selected and Purified Cardiomyocytes 17d in culture after thawing Frozen ES cell-derived and purfied cardiomyocytes are viable and retain their autonomous contractile phenotype for at least 3 weeks after thawing when cultured in monolayer.
  29. Gene Expression Analysis P =Present A = Absent Cor.At Cardiomyocytes Cor.At Cardiomyocytes Gene symbol days in culture after thawing Protein Gene symbol days in culture after thawing Protein 2d 20d 2d 20d SCN5a P P Nav1.5 ABCC8 P P SUR1 CACNA1c P P Cav1.2 (!1c) Pias3 P P KChAP, PIAS3 CACNA1h P P Cav3.2 (!1h) AKAP6 P P AKAP 6 KCNA1 P P Kv1.1 AKAP9 P P Yotiao KCNA4 P P Kv1.4 AKAP10 P P D-AKAP2 KCNA5 P A Kv1.5 AKAP12 P P Gravin KCNA7 P P Kv1.7 AKAP7 P P AKAP 7 KCNB1 P P Kv2.1 Slc8a1 P P NCX1 KCND2 A P Kv4.2 Slc12a2 P P ENCC3, BSC2, NKCC1 KCND3 P P Kv4.3 Slc9a1 P P SLC9A1, APNH, NHE1 KCNG2 P P Kv subfamily G, member 2 ATP1A1 P P Na+/K+-ATPase !1 KCNV2 A P Kv8.2 ATP1A2 P P Na+/K+-ATPase !2 KCNH2 P P erg1 (LQT2), Kv11.1 KvLQT1 (Kv7.1, JLN-1) ATP1A3 P P Na+/K+-ATPase !3 KCNQ1 P P ATP1B1 P P Na+/K+-ATPase "1 CLCN3 P P ClC-3 ATP1B2 P P Na+/K+-ATPase "2 clcn4-2 P P ClC-4 CLCN6 P P ClC-6 ATP1B3 P P Na+/K+-ATPase "3 CLCN7 P P ClC-7 ATP2A2 P P SERCA2, cardiac muscle, slow twitch 2 CLCA1 P P ClCa-1 RYR2 P P ryanodine receptor , RYR2 KCNJ12 P P Kir2.2 Ank2 P P Akyrin B (LQT-4) KCNJ3 P P Kir3.1 Gja1 P P Connexin 43 KCNJ5 P P Kir3.4 Gja3 P P Connexin 46 KCNJ6 P P Kir3.2 Gja7 P P Connexin 45 KCNJ11 P P Kir6.2 Slc4a3 P P anion exchanger 3 brain + cardiac isoforms KCNK6 P P TWIK-2 Vdac2 P P voltage-dependent anion channel 2 HCN1 P P HCN-1 Vdac1 P P voltage-dependent anion channel 1 HCN2 P P HCN-2 Pacsin2 P P Kv Shab-related subfamily, member 1 SCN1b P P SCN1B KCNN1 A P calcium-activated SK1 CACNB2 P P CACNB2 KCNN2 P P calcium-activated SK2 CACNA2d1 P P CACNA2d1 Slc24a3 P P Slc24a (Na/K/Ca exchanger), member 3 KCNE1 P P minK Slc24a6 P P Slc24a (Na/K/Ca exchanger), member 6 KCNIP2 A P KChIP2 Slc12a9 P P Slc12a (Na/K/Ca exchanger), member 9
  30. Manual Voltage Clamp of Cardiac Ion Currents
  31. Manual Voltage Clamp of Cardiac Ion Currents INa I/V Diagram (Normalized to Maximum Amplitude) 0 -70 -50 -30 -10 10 30 50 70 -0,2 Normalized current -0,4 -0,6 -0,8 -1 -1,2 voltage [mV]
  32. Manual Voltage Clamp of Cardiac Ion Currents INa ICa I/V Diagram I/V Diagram (Normalized to Maximum Amplitude) (Normalized to Maximum Amplitude) 0 0 -70 -50 -30 -10 10 30 50 70 -70 -50 -30 -10 10 30 50 70 -0,2 -0,2 Normalized current Normalized current -0,4 -0,4 -0,6 -0,6 -0,8 -0,8 -1 -1 -1,2 -1,2 voltage [mV] voltage [mV]
  33. Manual Voltage Clamp of Cardiac Ion Currents INa ICa IK I/V Diagram I/V Diagram I/V Diagram (Normalized to Maximum Amplitude) (Normalized to Maximum Amplitude) (Normalized to Maximum Amplitude) 1,2 0 0 -70 -50 -30 -10 10 30 50 70 -70 -50 -30 -10 10 30 50 70 1 Normalized current -0,2 -0,2 Normalized current Normalized current 0,8 -0,4 -0,4 0,6 -0,6 -0,6 0,4 -0,8 -0,8 0,2 -1 -1 0 -1,2 -1,2 -60 -40 -20 0 20 40 60 80 voltage [mV] voltage [mV] voltage [mV]
  34. Manual vs. Automated Patch - Chip replaces Pipette Pipette: “Aperture towards the 2 µm
  35. Manual vs. Automated Patch - Chip replaces Pipette Pipette: “Aperture towards the Chip: “Cell towards the 2 µm 20 µm
  36. Prerequisites for Automated Patch Clamp
  37. Prerequisites for Automated Patch Clamp Homogeneous cell population
  38. Prerequisites for Automated Patch Clamp Homogeneous cell population No contamination with other cell types (e.g. fibroblasts)
  39. Prerequisites for Automated Patch Clamp Homogeneous cell population No contamination with other cell types (e.g. fibroblasts) Round morphology
  40. Prerequisites for Automated Patch Clamp Homogeneous cell population No contamination with other cell types (e.g. fibroblasts) Round morphology Relatively high amount of cells.
  41. ® Cor.At Cardiomyocytes and PatchXpress 7000A ® MDS - Analytical Technologies
  42. ® Cor.At Cardiomyocytes and PatchXpress 7000A ® MDS - Analytical Technologies Dr. Xin Jiang
  43. ® PatchXpress 7000A - Cardiac Ion Currents
  44. ® PatchXpress 7000A - Cardiac Ion Currents INa 1 nA 2 ms I/V Diagram
  45. ® PatchXpress 7000A - Cardiac Ion Currents INa ICa 1 nA 100 pA 50 ms 2 ms I/V Diagram
  46. ® PatchXpress 7000A - Cardiac Ion Currents INa ICa IK 1 nA 100 pA 50 ms 2 ms I/V Diagram I/V Diagram
  47. Statistics Subject Number of cells Result ± SEM High resistance seals (> 1GΩ), (%) 96 45 ± 12 Successful whole cell (%) 96 49 ± 16 Peak INa (nA) (at -20 mV) 6 1.52 ± 0.23 Peak ICa (nA) (at +10 mV) 11 0.067 ± 0.008 Peak IK (nA) (at +20 mV) 21 0.49 ± 0.11
  48. ® PatchXpress 7000A: Potassium Current Pharmacology 4-Aminopyridine Control 10 µM
  49. ® PatchXpress 7000A: Potassium Current Pharmacology 4-Aminopyridine Control 10 µM
  50. ® PatchXpress 7000A: ß-adrenergic modulation of I(Ca,L)
  51. ® PatchXpress 7000A: ß-adrenergic modulation of I(Ca,L) Epinephrine (Adrenaline)
  52. ® PatchXpress 7000A: ß-adrenergic modulation of I(Ca,L) Epinephrine (Adrenaline) Epi, 10 µM
  53. ® PatchXpress 7000A: ß-adrenergic modulation of I(Ca,L) Epinephrine (Adrenaline) Epi, 10 µM
  54. ® Cor.At Cardiomyocytes and QPatch ® Sophion Bioscience A/S
  55. ® Cor.At Cardiomyocytes and QPatch ® Sophion Bioscience A/S Dr. Rikke Schrøder
  56. ® QPatch - Ion Currents
  57. ® QPatch - Ion Currents INa I/V Diagram
  58. ® QPatch - Ion Currents INa ICa I/V Diagram I/V Diagram
  59. ® QPatch - Ion Currents INa ICa IK I/V Diagram I/V Diagram I/V Diagram
  60. Statistics
  61. Statistics Avergage of 4 QPlates 16
  62. Statistics Subject Number of cells Result Viability after harvest procedure (%) 87± 3 Size of cell (pF) 112 17 ± 7 Cells with recordable INa amplitude (%) 15 of 22 68 Current density INa (pA/pF) 52 104 ± 129 Peak INa (pA) (at -30 mV) 52 1842 ± 2521 Cells with recordable ICa amplitude (%) 12 of 22 55 Current density ICa (pA/pF) 32 2 ± 1.5 Avergage of 4 QPlates 16 Peak ICa (nA) (at +10 mV) 32 0.035 ± 0.027
  63. ® QPatch - Sodium Current Pharmacology INa block with TTX
  64. ® QPatch - Sodium Current Pharmacology INa block with TTX
  65. ® QPatch - Sodium Current Pharmacology INa block with TTX
  66. ® QPatch - Sodium Current Pharmacology INa block with TTX A) baseline
  67. ® QPatch - Sodium Current Pharmacology INa block with TTX B) 50 nM A) baseline
  68. ® QPatch - Sodium Current Pharmacology INa block with TTX C) 5 µM B) 50 nM A) baseline
  69. ® QPatch - ß-adrenergic modulation of I(Ca,L) Voltage protocol
  70. ® QPatch - ß-adrenergic modulation of I(Ca,L) Isoproterenol
  71. ® QPatch - ß-adrenergic modulation of I(Ca,L) Isoproterenol
  72. ® QPatch - ß-adrenergic modulation of I(Ca,L) Isoproterenol 1) baseline
  73. ® QPatch - ß-adrenergic modulation of I(Ca,L) Isoproterenol 1) baseline 2) 1 µM Iso
  74. ® QPatch - ß-adrenergic modulation of I(Ca,L) Isoproterenol 1) baseline 2) 1 µM Iso 3) 10 µM Iso
  75. ® QPatch - ß-adrenergic modulation of I(Ca,L) Isoproterenol 4) 10 µM Nifedipine 1) baseline 2) 1 µM Iso 3) 10 µM Iso
  76. ® QPatch - ß-adrenergic modulation of I(Ca,L) Isoproterenol 4) 10 µM Nifedipine 1) baseline 2) 1 µM Iso 3) 10 µM Iso
  77. ® Cor.At Cardiomyocytes and ® Port-a-Patch and Patchliner ® Nanion Technologies
  78. ® Cor.At Cardiomyocytes and ® Port-a-Patch and Patchliner ® Nanion Technologies Dr. Sonja Stölzle
  79. Voltage Clamp
  80. Voltage Clamp INa I/V Diagram
  81. Voltage Clamp INa ICa I/V Diagram I/V Diagram
  82. Voltage Clamp INa ICa IK I/V Diagram I/V Diagram I/V Diagram
  83. Automated Current Clamp Recording
  84. Automated Current Clamp Recording Port-a-Patch® Stimulation Protocol (500 ms stimuli at 0.2 Hz) -40 pA I(memb) 150 ms 20 mV
  85. Automated Current Clamp Recording Port-a-Patch® Patchliner ® Stimulation Protocol (500 ms stimuli at 0.2 Hz) Screen Shot from a 4 channel Patchliner -40 pA I(memb) 150 ms 20 mV
  86. Preliminary Statistical Data Subject Result Patched Cells in 2.5 days 45 Success rate for gigaseal and whole cell (%) about 80 Cells with recordable action potentials amplitude (%) 50 Cells with recordable INa amplitude (%) 50 Cells with recordable ICa amplitude (%) 100 Cells with recordable IK amplitude (%) 60
  87. ® Port-a-Patch - Sodium Channel Pharmacology Tetrodotoxin (TTX)
  88. ® Port-a-Patch - Sodium Channel Pharmacology Tetrodotoxin (TTX) control TTX 20 µM 150 ms 20 mV washout
  89. ® Patchliner - Sodium Channel Pharmacology
  90. ® Patchliner - Sodium Channel Pharmacology min
  91. ® Patchliner - Sodium Channel Pharmacology min
  92. ® Port-a-Port - Identification of hERG blocker
  93. ® Port-a-Port - Identification of hERG blocker Dofetilide
  94. ® Port-a-Port - Identification of hERG blocker Dofetilide control Dofetilide, 1µM 150 ms 20 mV 150 ms 20 mV washout
  95. ® Patchliner - Potassium Channel Pharmacology
  96. ® Patchliner - Potassium Channel Pharmacology Quinidine
  97. ® Patchliner - Potassium Channel Pharmacology Quinidine min stimulation interval: 0.1 Hz
  98. ® Patchliner - Potassium Channel Pharmacology Quinidine min stimulation interval: 0.1 Hz 150 ms
  99. Why is it possible to identify hERG blocker effects in mouse ES cell-derived cardiomyocytes?
  100. Developmental Changes of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  101. Developmental Changes of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  102. Developmental Changes of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  103. Developmental Changes of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  104. Developmental Changes of Mouse Cardiac Repolarization Change of the Dofetilide Sensitivity of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  105. Developmental Changes of Mouse Cardiac Repolarization Change of the Dofetilide Sensitivity of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  106. Developmental Changes of Mouse Cardiac Repolarization Change of the Dofetilide Sensitivity of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  107. Developmental Changes of Mouse Cardiac Repolarization Change of the Dofetilide Sensitivity of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  108. Developmental Changes of Mouse Cardiac Repolarization Change of the Dofetilide Sensitivity of Mouse Cardiac Repolarization Wang et al. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res. 1996 Jul;79(1):79-85.
  109. + + Cardiac Na /K -ATPases as Important Drug Targets
  110. + + Gene Expression of Na /K ATPase Subunits
  111. + + Gene Expression of Na /K ATPase Subunits Cor.At Cardiomyocytes days in culture after Gene symbol thawing Protein 2d 20d ATP1A1 P P Na+/K+-ATPase α1 ATP1A2 P P Na+/K+-ATPase α2 ATP1A3 P P Na+/K+-ATPase α3 ATP1A4 A A Na+/K+-ATPase α4 ATP1B1 P P Na+/K+-ATPase β1 ATP1B2 P P Na+/K+-ATPase β2 ATP1B3 P P Na+/K+-ATPase β3
  112. + + Na /K ATPase Subunits Homology between Mouse and Human Amino Acid Sequences Na+/K+ ATPase catalytic alpha subunits: ATP1A1 Identities = 963/992 (97%), Positives = 979/992 (98%), Gaps = 0/992 (0%) Identities = 991/1023 (96%), Positives = 1008/1023 (98%), Gaps = 0/1023 (0%) ATP1A2 Identities = 1011/1020 (99%), Positives = 1018/1020 (99%), Gaps = 0/1020 (0%) ATP1A3 Identities = 1001/1005 (99%), Positives = 1003/1005 (99%), Gaps = 0/1005 (0%) Na+/K+ ATPase regulatory beta subunits: ATP1B1 Identities = 285/304 (93%), Positives = 298/304 (98%), Gaps = 1/304 (0%) Identities = 282/302 (93%), Positives = 295/302 (97%), Gaps = 1/302 (0%) ATP1B2 Identities = 282/290 (97%), Positives = 287/290 (98%), Gaps = 0/290 (0%)
  113. ® Cor.At Cardiomyocytes and Pharmacological Studies with the ICR 8000 ® Aurora Biomed
  114. ® Cor.At Cardiomyocytes and Pharmacological Studies with the ICR 8000 ® Aurora Biomed Dr. Sikander Gill
  115. + ICR 8000 - Rb Uptake Assay
  116. + ICR 8000 - Rb Uptake Assay Monitoring of cardiac Na+/K+ ATPases
  117. + ICR 8000 - Rb Uptake Assay Monitoring of cardiac Na+/K+ ATPases Activity
  118. + ICR 8000 - Rb Uptake Assay Monitoring of cardiac Na+/K+ ATPases Activity Pharmacology
  119. Summary
  120. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current:
  121. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current: PatchXpress® 7000A from MDS-AT
  122. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current: PatchXpress® 7000A from MDS-AT QPatch® from Sophion
  123. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current: PatchXpress® 7000A from MDS-AT QPatch® from Sophion Port-a-Patch® and Patchliner® from Nanion
  124. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current: PatchXpress® 7000A from MDS-AT QPatch® from Sophion Port-a-Patch® and Patchliner® from Nanion I(Ca,L) beta-adrenergic stimulation was revealed
  125. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current: PatchXpress® 7000A from MDS-AT QPatch® from Sophion Port-a-Patch® and Patchliner® from Nanion I(Ca,L) beta-adrenergic stimulation was revealed For the first time recording of action potentials from primary-like cardiomyocytes were established in the the Port-a-Patch® and Patchliner® from Nanion.
  126. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current: PatchXpress® 7000A from MDS-AT QPatch® from Sophion Port-a-Patch® and Patchliner® from Nanion I(Ca,L) beta-adrenergic stimulation was revealed For the first time recording of action potentials from primary-like cardiomyocytes were established in the the Port-a-Patch® and Patchliner® from Nanion. hERG and I(Na) blocker effects on action potentials have been revealed recorded with the Port-a-Patch and Patchliner.
  127. Summary Cor.At® cardiomyocytes were successsfully applied to automated patch clamp systems from three different companies to analyse cardiac ion current: PatchXpress® 7000A from MDS-AT QPatch® from Sophion Port-a-Patch® and Patchliner® from Nanion I(Ca,L) beta-adrenergic stimulation was revealed For the first time recording of action potentials from primary-like cardiomyocytes were established in the the Port-a-Patch® and Patchliner® from Nanion. hERG and I(Na) blocker effects on action potentials have been revealed recorded with the Port-a-Patch and Patchliner. Cor.At® cells have been validated to be suitable for HTS applications for the analyses of Na+/K+-ATPase activity and pharmacology in the ICR 8000 from Aurora.
  128. Conclusion
  129. Conclusion ® Cor.At cells are primary-like cardiomyocytes predictive and relevant for pharmacological studies.
  130. Conclusion ® Cor.At cells are primary-like cardiomyocytes predictive and relevant for pharmacological studies. ® Cor.AT cells are suitable for automated electrophysiology and are validated on leading systems
  131. Conclusion ® Cor.At cells are primary-like cardiomyocytes predictive and relevant for pharmacological studies. ® Cor.AT cells are suitable for automated electrophysiology and are validated on leading systems ® Cor.At cells capable for scalable HTS and HCS applications
  132. Conclusion ® Cor.At cells are primary-like cardiomyocytes predictive and relevant for pharmacological studies. ® Cor.AT cells are suitable for automated electrophysiology and are validated on leading systems ® Cor.At cells capable for scalable HTS and HCS applications One relevant cell for all information
  133. Conclusion ® Cor.At cells are primary-like cardiomyocytes predictive and relevant for pharmacological studies. ® Cor.AT cells are suitable for automated electrophysiology and are validated on leading systems ® Cor.At cells capable for scalable HTS and HCS applications One relevant cell for all information ® Cor.At cardiomyocytes are available now.
  134. Acknowledgment
  135. Acknowledgment MDS Analytical Technologies: Dr. Xin Jiang Dr. Jan Dolzer Dr. James Costantin Dr. David Yamane
  136. Acknowledgment MDS Analytical Technologies: Dr. Xin Jiang Dr. Jan Dolzer Dr. James Costantin Dr. David Yamane Sophion SA Dr. Rikke Schrøder-Perrier Dr. Morten Sunesen
  137. Acknowledgment MDS Analytical Technologies: Dr. Xin Jiang Dr. Jan Dolzer Dr. James Costantin Dr. David Yamane Sophion SA Dr. Rikke Schrøder-Perrier Dr. Morten Sunesen Nanion Technologies: Dr. Sonja Stölzle Dr. Niels Fertig Dr. Cecilia Farre Dr. Claudia Haarmann
  138. Acknowledgment MDS Analytical Technologies: Aurora Biomed: Dr. Xin Jiang Dr. Sikander Gill Dr. Jan Dolzer Sophia Liang Dr. James Costantin Saranna Brugger Dr. David Yamane Sophion SA Dr. Rikke Schrøder-Perrier Dr. Morten Sunesen Nanion Technologies: Dr. Sonja Stölzle Dr. Niels Fertig Dr. Cecilia Farre Dr. Claudia Haarmann
  139. Acknowledgment MDS Analytical Technologies: Aurora Biomed: Dr. Xin Jiang Dr. Sikander Gill Dr. Jan Dolzer Sophia Liang Dr. James Costantin Saranna Brugger Dr. David Yamane Sophion SA Institute for Neurophysiology, Dr. Rikke Schrøder-Perrier University of Colone: Dr. Morten Sunesen Alexey Kuzmenkin Huamin Liang Prof. Jürgen Hescheler Nanion Technologies: Dr. Sonja Stölzle Dr. Niels Fertig Dr. Cecilia Farre Dr. Claudia Haarmann
  140. Acknowledgment MDS Analytical Technologies: Aurora Biomed: Dr. Xin Jiang Dr. Sikander Gill Dr. Jan Dolzer Sophia Liang Dr. James Costantin Saranna Brugger Dr. David Yamane Sophion SA Institute for Neurophysiology, Dr. Rikke Schrøder-Perrier University of Colone: Dr. Morten Sunesen Alexey Kuzmenkin Huamin Liang Prof. Jürgen Hescheler Axiogenesis AG: Nanion Technologies: Dr. Heribert Bohlen Dr. Sonja Stölzle Dr. Eugen Kolossov Dr. Niels Fertig Dr. Silke Schwengberg Dr. Cecilia Farre Dr. Andreas Ehlich Dr. Claudia Haarmann Josef Tenelsen Peter Metzger
  141. Acknowledgment
  142. Acknowledgment North America: www.reachbio.com
  143. Acknowledgment North America: Special thanks to: Dr. Eric Atkinson Lynn MacIntyre www.reachbio.com
  144. Acknowledgment North America: Special thanks to: Dr. Eric Atkinson Lynn MacIntyre www.reachbio.com Japan: Dr. Junya Koda Dr. Chie Kodama www.veritastk.com
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