3D Brain Organoids

CNS-3D Brain Organoids are human brain microtissues derived from induced pluripotent stem cells (iPSCs) differentiated into neural progenitor cells (NPCs). The resulting cortical organoids mature to 500–600 µm in diameter, exhibit spontaneous, electrically driven network activity, and display transcriptomic profiles consistent with human cortical tissue.

Cell Types

Each CNS-3D Brain Organoid contains a balanced mix of neurons (~50%) astrocytes (~50%), along with small population of progenitor cells. Within the neuronal population, ~90%are glutamatergic (excitatory) and ~5% are GABAergic (inhibitory). This cellular composition is highly consistent across batches, ensuring stable excitatory/inhibitory balance, metabolic support, and consistent functional outcomes.

Reproducibility

CNS-3D Brain Organoids deliver consistent results across experiments, production batches, and time. Each brain organoid displays highly consistent size, cell composition, and functional response, enabling reproducible results from the first experiment onward. Performance is stable across a validated, 4-week assay window, supporting longitudinal (weeks-long) treatment paradigms.

Quality Control

Every batch of CNS-3D Brain Organoids is produced and tested under a rigorous quality control framework to support consistent biological performance. Each shipment includes a Certificate of Analysis verifying organoid size (<5% VC, 98% presence), neuron-to-astrocyte ratios, sterility (mycoplasma, bacterial, fungal), and functional assay performance for 8 reference compounds (EC/IC₅₀ and robust Z’ values for FLIPR screening).

Assays

FLIPR Functional Modulation

CNS-3D Brain Organoids exhibit spontaneous functional activity quantifiable viahigh-throughput FLIPR using a calcium-sensitive fluorophore. Consistent waveform profiles across replicates enable reliable neurotoxicity and neuromodulation screening with as few as four replicates per condition.

Cell Viability Assessment

Cell viability assays such as CellTiter-Glo and LDH-Glo can be run alone or multiplexed with FLIPR to distinguish between neuromodulatory and cytotoxic effects.

3D High-content Imaging

High-resolution imaging and custom analysis algorithms enable precise quantification of treatment-induced morphological changes in specific brain cell types at cellular and subcellular levels.

Multiplexed Sample Collection

Post-treatment CNS-3D Brain Organoids and media can be frozen to preserve RNA, proteins, and secreted factors for downstream analyses, including transcriptomics, proteomics, and ELISA-based biomarker assays.

Additional Assays

CNS-3D Brain Organoids support a wide range of standard fluorescence, luminescence, and colorimetric assays, including JC-10 (mitochondrial health), Live/Dead imaging, cytokine profiling, and enzymatic activity (e.g., AChE).

Use Case 01

Neurotoxicity

By incorporating human cells, cellular diversity, and functional neural activity, CNS-3D Brain Organoids detect a range of seizurogenic and neurodegenerative side effects, while keeping safe compounds in play. A peer-reviewed study (ALTEX 2022, Takeda) demonstrates that CNS-3D is 7.4x more predictive of clinical neurotoxicity than animal models, with 93% specificity and 53% sensitivity.

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Dose response data of 8 representative compounds with various degrees of toxicity as assessed by potency of neuromodulation (peak count) relative to clinically relevant concentrations (Cmax).

Use Case 02

Disease Modeling

CNS-3D Brain Organoids can be adapted to model rare diseases and provide unique insights into disease mechanisms and potential therapeutic efficacy. It has been used to model Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD) with patient-derived iPSCs, revealing distinct disease-specific functional network signatures despite overlapping clinical phenotypes.

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CNS-3D Brain Organoids modeling two distinct neurodevelopmental disorders Rett Syndrome (orange) and CDKL5 Deficiency Disorder (teal) display unique functional phenotypes and can be grown in 384-well plate formats.

Use Case 03

Combined Safety & Efficacy Assessment

CNS-3D Brain Organoids enable simultaneous, high-throughput assessment of drug safety and efficacy. Using CDKL5 deficiency brain organoids, 28bio screened >5,000 compounds and identified 22 that restored neural function without toxicity—using FLIPR calcium imaging for functional activity and a custom, image-based assay for cytotoxicity. This integrated approach can accelerate the identification of safe, efficacious drug candidates.

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Dose response data demonstrating disease-selective rescue without impacts to cell viability (predicted CTG). Compound restores aberrant CDD organoid function (teal) to Control levels (white).

Use Case 04

Neuromodulator Profiling

CNS-3D Brain Organoids enable high-throughput functional profiling of compounds that modulate neural network activity—revealing excitatory, inhibitory, and mixed effects before overt cytotoxicity occurs. In a 2019 study of 87 compounds (Sirenko et al.,Toxicological Sciences), FLIPR and CellTiter-Glo assays detected subtle, dose-dependent responses to pharmaceuticals, pesticides, and industrial chemicals, demonstrating the value of CNS-3D for early safety pharmacology and mechanism-of-action studies.

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CNS-3D Brain Organoids treated with nine representative compounds cause unique functional phenotypes to appear in fluorescence over time calcium imaging experiments.

Engineered brain organoids: 7.4x more predictive of human clinical outcomes.

A Complex in vitro Model of the human brain

Neurotoxicity

Disease Modeling

Combined Safety & Efficacy Assessment

Neuromodulator Profiling

Products & Services

CNS-3D Brain Organoid Resources