Presentation at the 7th Ion Channel Retreat 2009 in Vancouver

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