Search

Cerebral organoids provide unparalleled access to human brain development in vitro. However, variability induced by current culture methodologies precludes using organoids as robust disease models. To address this, we developed an automated Organoid Culture and Assay (ORCA) system to support longitudinal unbiased phenotyping of organoids at scale across multiple patient lines. We then characterized organoid variability using novel machine learning methods and found that the contribution of donor, clone, and batch is significant and remarkably consistent over gene expression, morphology, and cell-type composition. Next, we performed multi-factorial protocol optimization, producing a directed forebrain protocol compatible with 96-well culture that exhibits low variability while preserving tissue complexity. Finally, we used ORCA to study tuberous sclerosis, a disease with known genetics but poorly representative animal models. For the first time, we report highly reproducible early morphological and molecular signatures of disease in heterozygous TSC+/− forebrain organoids, demonstrating the benefit of a scaled organoid system for phenotype discovery in human disease models.

New closed cell composite metal foam has been processed using both casting and powder metallurgy (PM) techniques. The foam is comprised of steel hollow spheres packed into a dense arrangement, with the interstitial spaces between spheres occupied with a solid metal matrix. Using the casting technique, an aluminum alloy infiltrates the interstitial spaces between steel spheres. In the PM technique, steel spheres and steel powder are sintered to form a solid, closed cell structure. The measured densities of the Al-Fe composite foam, low carbon steel foam, and stainless steel foam are 2.4, 2.6, and 2.9 g/cm 3 with relative densities of 42, 34, and 37%, respectively. The composite metal foams composite materials developed in this study displayed superior compressive strength as compared to any other foam being produced with similar materials. The compressive strength of the cast Al-Fe foam averaged 67 MPa over a region of 10 to 50% strain, while the low carbon steel PM foam averaged 76 MPa over the same strain region, and the stainless steel PM foam averaged 136 MPa over the same region. Densification began at approximately 50% for the cast foam and ranged from 50 to 55% for the PM foams. The strength to density ratio of the product of both techniques exceeded twice that of foams processed using other techniques with similar materials.