Evaluation of
Ready-to-Use
Quick-Neuron™
Plate - MEA 48

Society for Neuroscience 2021

Tomoaki Nakayama1, Manabu Seo2, Tomoyuki Aratani1, Motoki Azuma1
1.RICOH COMPANY, Ltd.
2.Elixirgen Scientific, Inc.

(C)2021 Ricoh Company, Ltd. All rights reserved.

How can we evaluate neuralactivities?
§ Detection methods
Multi-electrode array

https://www.waisman.wisc.edu/cellular-and-molecularneuroscience/axion-maestro-pro-mea-multi-electrode-array/

Patch-Clamp

https://www.leica-microsystems.com/science-lab/the-patchclamp-technique/

Ca transient assay

https://www.moleculardevices.com/en/assets/app-note/dd/flipr/compound-effects-uponcalcium-transients-in-beating-axiogenesis-cor.4u-human-ips-cell-derived-cardiomyocytes§ Features of MEA(Multi-electrode Arrays)
Detection :Extracellular electrodeFormat:Well-plate format

Advantages
ü Damageless for cells
ü High time-resolution
ü Easy to assay

iPSC-derived neuron

Multi-electrode Array

Neural activities measured
with MEAChallenge of MEA Assays withiPSC-derived neurons§ Challenge• The spontaneous firing rate is unstable.
• Cumbersome to prepare and culture cells for months.
• Itʼs difficult to optimize culture conditions for obtaining
good responsibility to pharmacological drugs.

§ Our solution
Providing a Ready-to-use MEA plate!!
Users can evaluate drug efficacy and toxicity.
• Stable firing rate
• Assay immediately after receiving the plate• Expected responses to typical compounds

What is Quick-NeuronTM Plate?
“Quick-Neuron™ Plate frees users
from experiment preparation!!”
CytoView MEA 48

Human iPSC–derivedNeurons

Product Specifications
Cell︓
・Elixirgen Scientific
Human iPSC-derived Neurons
・Thermo Fisher
Human Astrocytes
Plate︓

・Axion Biosystems
CytoView MEA 48

Objective in this study
Evaluate Quick-Neuron™ Plate can be use as Ready-to-use
・Stability of firing rate
・Assay immediately after receiving the plate
・To show expected responses to typical compounds-Receptor agonist and antagonists-Anti-epileptic drugs
4How stable is Quick-Neuron™
Plate?
The spontaneous firing rate of Quick-Neuron™
Plate was more stable than the platewith non-optimized condition.
Mean firing ratedSooGNo
optimization

Optimized culture methodtas !!
eitib il

Network burst frequency

Nooptimization

Optimized culture method

Are the plates functional after
long-distance transportation?
The plate transported from Tokyo to Baltimore showed
the good response to 4AP, K+ channel blocker.
From Tokyo to Baltimore, 33 hours
32 hour

Before transportation(In Japan)

Goodsp onartry !!
tilita b

Drug response after transportation
Control (DMSO)

After transportation(In America)

4AP (3 μM)

4AP (30 μM)

Can the plate be used forneuroscience research?
The plate showed robust responses to compounds
that affect majore!receptors!
Goodonpsers

ModeReceptors / Ion channelsCompounds

Testing density

Changes of spike
number

Negative control-Acetaminophen

1-100 μM

No change

Glutamate receptors
GABA receptors

Glutamate
GABA

1-100 μM
0.1-10 μM↗↘
↘

Dopamine receptors

Dopamine

0.1-10 μM↘↗

Muscarine receptors

Pilocarpine(HCl)0.1-10 μM↗

Histamine receptors

Histamine

0.3-30 μM↗

2.3 μM
2.8 μM
0.122 μM（D1)
2.76 μM (D2)
1.66 μM (D5)18 μM(M1,3)
4.5 μM(M2)
24 μM

AMPA, Kainate receptors

CNQX

0.5-50 μM↘

0.92/6.1μM

GABA(A) receptors
Dopamine D2 receptors
NMDA receptors
GABA(A) receptors
Histamine H1 receptors

Gabazine
Chlorpromazine
D-AP5
Picrotoxin
Ketotifen

0.3-30 μM
0.1-10 μM
0.5-50 μM
0.1-10 μM
0.1-10 μM↗
↗↘
No change↗
↗↘

0.2 μM
0.363 μM
4.1 μM
2.4 μM-NeuroTransmitter

Receptor
Antagonist

Ref: IC50

The plate can be also used for antiepileptic screening.
Negative control
DMSO

Anti-epileptic drugs(Na+ channel blocker)

Acetaminophen

droo
G

0.2%

0.4%

se!!Phenytoinno(IC50:16.6 μM)
esp

Carbamazepine(IC50:131 μM)

Control

Control

Control

100 μM

100 μM

50 μM

Relative change of MFR to Control
50 μM

*

10 μM

5 μM

*

1 μM

0.5 μM

0.4%

100 μM

100 μM

0.3%

10 μM

0.2%

1 μM

*

*︓p<0.05*︓p<0.05

Conclusions
Quick-Neuron™ Plate is expected to be a useful toolfor nervous system drug discovery.
Ø We developed Quick-Neuron™ Plate, which is Ready-to-use MEA
plate for iPSC based neuronal assays
Ø Quick-Neuron™ Plate can be used for Ready-to-use plate.
• Stable firing rate
• Assay immediately after receiving the plate• Expected responses to typical compounds

E-mail: tomoaki.nakayama@jp.ricoh.com