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Electrophysiological imaging
for advanced pharmacological screening
Imaging at different spatio-temporal scales
Macro- Meso- Micro-
100 billion neurons 2D/3D cultures, organoids,
tens of thousands of cells
Neurons and sub-elements
Competing technology
1.5mm
Main limitations
• temporal resolution
• field of view / spatial resolution
• indirect measurement: use of dyes
(averaging, bleaching, interference with
network parameters)
0.1mm
Main limitations:
• very low spatial resolution (electrode pitch
~100 μm)
• large under-sampling of network activity
(~20,000 neurons per 100 electrodes)
Optical imaging Extracellular electrophysiology
3Brain’s BioCAM – BioChip Advantages
>0.5
0
Values[mV]
Spontaneous retinal waves of a P10 mouse under bicuculline effect
Standard MEAHigh-density MEA
Dissociated Cultures Acute Brain Tissue Retina Tissue
HD-MEA Probes
• 4,096 electrodes
• new 3D models coming
soon
BioCAM Line
• single- and multi- well
models
BrainWave 4
• data recording, analysis
and compression tools
Services
• data analysis, training,
protocols and
experimental design
Products and services
Solutions
Help
Care
Khíron chip
3D high-density multielectrode array – available from 2019 Q3
Khíron chip
3D high-density multielectrode array – available from 2019 Q3
Pharmaceutical applications
First 6-well prototype
coming soon
• Multi-well configuration
• Advanced data compression strategies
• Roadmap to increase # on wells: 12, 96, 384 and
more
From single-well… …to multi-well
Case studies
Dissociated cultures
Tissues
24 Days In Vitro (DIV)
100nM
Oligomer Aβ-42
26 Hours of monitoring
H. Amin et al., Sci Report 2017
Dissociated hippocampal
neuronal network
In vitro model of induced Alzheimer’s disease
Human neuronal cultures on HD-MEA
validated for more than 3 months with
spontaneous and electrically evoked
recordings
Amin et al., Front. Neurosci. 2016
Several adhesion factors (PDLO,
PEI) promote different
maturation stages
Human-derived stem cell neuronal networks
Dissociated cultures
Tissues
Case studies
Epileptic model for anticonvulsant compound testing
Ferrea et al. 2012, Front. Neural Circuits
0.0
0.2
0.4
0.6
0.8
1.0
THIP
Control
CA1CA3DG
**
*
0.0
0.2
0.4
0.6
0.8
1.0
THIP
Control
CA1CA3DG
*
CLASS1
CLASS2
4-AP THIP 4-AP THIP
LTP protocols: D-Cycloserine effects on functional activity
A Maccione et al. – SFN 2016
LTP
Compound effect on purkinje activity in cerebellum slice (I)
Ca2+-activated K+
channels modulators
alter PCs firing
0 10 20 30 40 50 60 70 80 900
50
200
150
100
Meannorm.frequency(%)
Time (min)
Basal
0 40 80 120
0
80
120
40
Basal (Hz)
Final(Hz)
Vehicle
Final
0 10 20 30 40 50 60 70 80 90
Time (min)
0 40 80 120
Basal (Hz)
CyPPA
0 10 20 30 40 50 60 70 80 90
Time (min)
0 40 80 120
Basal (Hz)
NS 309
0 10 20 30 40 50 60 70 80 90
Time (min)
0 40 80 120
Basal (Hz)
Apamin
A Ugolini et al. – Fens 2018
Compound effect on purkinje activity in cerebellum slice (II)
Light responsive human-derived
retinal organoids
D Hallam et al. – Stem Cells 2018
Electrophysiological imaging for advanced pharmacological screening

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Electrophysiological imaging for advanced pharmacological screening

  • 1. Electrophysiological imaging for advanced pharmacological screening
  • 2. Imaging at different spatio-temporal scales Macro- Meso- Micro- 100 billion neurons 2D/3D cultures, organoids, tens of thousands of cells Neurons and sub-elements
  • 3. Competing technology 1.5mm Main limitations • temporal resolution • field of view / spatial resolution • indirect measurement: use of dyes (averaging, bleaching, interference with network parameters) 0.1mm Main limitations: • very low spatial resolution (electrode pitch ~100 μm) • large under-sampling of network activity (~20,000 neurons per 100 electrodes) Optical imaging Extracellular electrophysiology
  • 4. 3Brain’s BioCAM – BioChip Advantages >0.5 0 Values[mV] Spontaneous retinal waves of a P10 mouse under bicuculline effect Standard MEAHigh-density MEA
  • 5. Dissociated Cultures Acute Brain Tissue Retina Tissue
  • 6. HD-MEA Probes • 4,096 electrodes • new 3D models coming soon BioCAM Line • single- and multi- well models BrainWave 4 • data recording, analysis and compression tools Services • data analysis, training, protocols and experimental design Products and services Solutions Help Care
  • 7. Khíron chip 3D high-density multielectrode array – available from 2019 Q3
  • 8. Khíron chip 3D high-density multielectrode array – available from 2019 Q3
  • 9. Pharmaceutical applications First 6-well prototype coming soon • Multi-well configuration • Advanced data compression strategies • Roadmap to increase # on wells: 12, 96, 384 and more From single-well… …to multi-well
  • 11. 24 Days In Vitro (DIV) 100nM Oligomer Aβ-42 26 Hours of monitoring H. Amin et al., Sci Report 2017 Dissociated hippocampal neuronal network In vitro model of induced Alzheimer’s disease
  • 12. Human neuronal cultures on HD-MEA validated for more than 3 months with spontaneous and electrically evoked recordings Amin et al., Front. Neurosci. 2016 Several adhesion factors (PDLO, PEI) promote different maturation stages Human-derived stem cell neuronal networks
  • 14. Epileptic model for anticonvulsant compound testing Ferrea et al. 2012, Front. Neural Circuits 0.0 0.2 0.4 0.6 0.8 1.0 THIP Control CA1CA3DG ** * 0.0 0.2 0.4 0.6 0.8 1.0 THIP Control CA1CA3DG * CLASS1 CLASS2 4-AP THIP 4-AP THIP
  • 15. LTP protocols: D-Cycloserine effects on functional activity A Maccione et al. – SFN 2016 LTP
  • 16. Compound effect on purkinje activity in cerebellum slice (I) Ca2+-activated K+ channels modulators alter PCs firing
  • 17. 0 10 20 30 40 50 60 70 80 900 50 200 150 100 Meannorm.frequency(%) Time (min) Basal 0 40 80 120 0 80 120 40 Basal (Hz) Final(Hz) Vehicle Final 0 10 20 30 40 50 60 70 80 90 Time (min) 0 40 80 120 Basal (Hz) CyPPA 0 10 20 30 40 50 60 70 80 90 Time (min) 0 40 80 120 Basal (Hz) NS 309 0 10 20 30 40 50 60 70 80 90 Time (min) 0 40 80 120 Basal (Hz) Apamin A Ugolini et al. – Fens 2018 Compound effect on purkinje activity in cerebellum slice (II)
  • 18. Light responsive human-derived retinal organoids D Hallam et al. – Stem Cells 2018