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microBrain® 3D Assay Ready

Structure Leads to Improved Cell-Based Assay Outcomes

Neural Network Structure and Cell Maturity

The neural network structure of microBrain cortical spheroids is extensively developed with accelerated maturity and enhanced cell performance. The effectiveness of the network structure and cell maturity level in microBrain spheroids is evident from:

• Expression of key markers of cell maturity, such as synaptic proteins and glutamate transporters
• High density of functional synapses resulting in active neuronal circuitry
• Spontaneous and synchronous activity
• Strong response to neurotransmitters

Click here to read how microBrain 3D Assay Ready is being used in our new technical note.

A Structured Environment for Cell Performance

StemoniX® microBrain® 3D Assay Ready Plates are a human iPSC-derived cortical spheroid screening platform. Each well of this multi-well plate contains a single mature spheroid comprised of neurons and astrocytes from a single source. Delivered to the customer pre-plated under ambient conditions, the plates can be easily implemented as a reliable high throughput screening platform for drug discovery, safety pharmacology and neuro-toxicology, and disease modeling.

microBrain 3D Assay Ready 384-Well Plate

Physiologically Relevant Spheroids

The microBrain cortical spheroids are highly homogenous in size and composition. Derived from a single human donor, the iPSC-derived neural cells in the spheroid develop naturally during the course of differentiation.

Key characteristics of microBrain spheroids:

• ~600 μm diameter
• Balanced composition of cortical neurons and astrocytes, nominally 50/50 ratio
• Cortical neurons include both excitatory (glutamatergic) and inhibitory (GABAergic), nominally 80/20 ratio
• Matured 7 to 10 weeks

MAP2 – GFAP – DAPI

Cross-sectional view of a microBrain spheroid

The relationship between neurons and astrocytes is well documented in the literature. Astrocytes are known to support, protect and enhance the development and function of neurons.  The neurons in microBrain spheroids have a fully developed foundation of astrocytes that have been derived from a single source and display key markers of cellular identity, resulting in a truly physiologically relevant neural model.

MAP2 – Synapsin I – DAPI

Aquaporin4 – GFAP – DAPI

Well-Developed Synapses

A Network of Mature Astrocytes

Responsive to Neurotransmitters

A Powerful High Throughput Screening Platform

The power and effectiveness of microBrain 3D Assay Ready’s enhanced network structure and cell maturity is evident through highly synchronized activity. The microBrain cortical spheroids present quantifiable, robust and uniform spontaneous and synchronized calcium oscillations, measured in kinetic high throughput plate readers (e.g. FLIPR®) and high content imaging systems. The calcium signal can be reproducibly modified with excitatory and inhibitory modulators, confirming the presence of a functionally integrated glutamatergic/GABAergic circuit. microBrain 3D Assay Ready demonstrates remarkably consistent performance, making it ideal for high throughput drug discovery and screening applications.

Uniform spontaneous calcium oscillations measured on FLIPR

Synchronized calcium oscillations across a microBrain spheroid

Consistent performance demonstrated by a heat map of FLIPR activity across a 384-well plate

microBrain® 3D Assay Ready

Assay ready plates are pre-plated with StemoniX cortical spheroids, with each well containing a single mature spheroid. The plates are delivered under ambient conditions and ready for assay use after a brief preparation process.

Structure Leads to Improved Cell Based Assay Outcomes

Safety Pharmacology & Investigative Toxicology

• Neurotoxicity screening
• Compatible with popular cell viability and toxicity kits
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Drug Discovery & Screening

• Mature cortical circuitry allows for the study of normal neural electrophysiological activity
• Image-based screens for key structural features (e.g. formation of synapses, dendrites)

Disease Modeling

• Neuroinflammation
• Effect of hypoxia on the development and function of mature cortical neurons
• Model relevant human disease by modulation of mature cortical circuitry (e.g. seizure)

Platform Compatibility

• High Throughput Kinetic Plate Readers (e.g. FLIPR®)
• High Content Imaging
• Multi-Mode Plate Readers
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