Abstract: The human brain exhibits exceptional computational efficiency, integrating sensory information and solving complex problems with minimal energy consumption. This efficiency arises from neuronal parallel processing and synaptic plasticity, presenting a promising alternative to conventional silicon-based computing, which has limitations related to power consumption and scalability. However, the performance improvement of three-dimensional (3D) organoid-based bioprocessor is constrained by the structural limitations inherent to 3D organoids. Increasing the number of cells and synapses to enhance bioprocessor performance often leads to inadequate oxygen and nutrient delivery to the inner regions of the three-dimensional organoid structure. This insufficient supply causes cell death, ultimately resulting in a decline in processor performance. To address this challenge, we propose a novel 3D packaging strategy for bioprocessor, wherein uniformly cultured brain organoids are systematically stacked within a structured matrix to enhance network scalability while mitigating necrotic core cellular apoptosis. Layered architecture significantly increases the number of neurons and synapses while improving inter-organoid connectivity, enabling richer neural signal processing. These findings suggest that 3D organoid integration approach can surpass the performance of conventional two-dimensional (2D) neuron-based bioprocessor, providing a foundation for the development of next-generation energy-efficient and high-performance neuron cell-based computing systems.
Funding Source: This work was supported by NRF and MFDS grants funded by the Korean government (RS-2024-00441103 and RS-2024-00331678).