3d comsol simulation model  (COMSOL Inc)

Journal: bioRxiv

Article Title: Computational modeling of necrosis in neural organoids

doi: 10.1101/2025.04.30.651571

Figure Lengend Snippet: (A) Schematic illustrating 2D vs 3D tissue cultures. (B) Schematic diagram showing that while necrosis is not a concern for smaller organoids, it occurs in the dense core regions of larger organoids. (C) Workflow of our overall strategy for computational modeling of necrosis within 3D culture using NOs. We identify necrosis in stained slices of NOs ( left ) and fit the percentage (%) of necrotic area to get the respective Damköhler number ( Da ) ( middle ) and proceed with parametric studies for the NO in our 3D CAD models ( right ).

Article Snippet: We developed a 3D computational model (COMSOL Multiphysics) to investigate the progression of necrosis in NO culture.

Techniques: Staining

Journal: bioRxiv

Article Title: Computational modeling of necrosis in neural organoids

doi: 10.1101/2025.04.30.651571

Figure Lengend Snippet: ( A ) Confocal microscopy of NO cultures at ( i-vi ) static state, ( vii-xii ) oOrbital shaking at 88 RPM. Nuclei stained with Hoechst 33342 ( blue ), neuronal staining with HMGB-1 ( green ) and βIII-tubulin ( red ), and apoptosis markers with TUNEL ( pink ). A yellow dotted line indicates the necrotic area. The scale bar is 50 μm. ( B ) Experimental estimation of percentage (%) necrotic area of NO. The sample size used was n=3. ( C ) Geometry and mesh of the calibration model; ( D ) Calibration curve of % percentage necrotic area vs Da across diffusion and reaction dominated regions. Using the % necrotic area of NO at static state and 88 RPM as shown in ( B ), we find a corresponding Da . We found reasonable agreement with both experimental ranges at Da≈ 8.1. ( E ) 3D simulation showing oxygen consumption and necrosis across an irregular NO (like experimental sample) with equivalent radius (650 μm) at Da = 8.1. Critical oxygen concentration is assumed to be 0.05 mol/m .

Article Snippet: We developed a 3D computational model (COMSOL Multiphysics) to investigate the progression of necrosis in NO culture.

Techniques: Confocal Microscopy, Staining, TUNEL Assay, Diffusion-based Assay, Concentration Assay

Journal: bioRxiv

Article Title: Computational modeling of necrosis in neural organoids

doi: 10.1101/2025.04.30.651571

Figure Lengend Snippet: (A-C) 3D geometry of NO culture strategy using (A) static culture, (B) orbital shaking, and (C) microfluidic flow around the NO. (D) Visualization of the necrotic area by plotting O 2 concentration in a NO slice. The core area marked by the dotted yellow line has an O 2 concentration below the critical O 2 concentration of 0.05 mol/m and is necrotic. (D-F) Computational estimation of necrosis in a NO by plotting O 2 concentration across an NO between 500-1000 μ m (diameter). ( D ) For a 500 μ m NO cultured using, (i) static culture (ii) orbital shaking, and (iii) microfluidic flow around NO. (iv) O 2 concentration across NO on a cutline at y=0 for all three cases. The blue-shaded region represents the area below the critical O 2 concentration, which determines the necrotic area. We observe viable NOs with no necrosis in all culture strategies. (E) For a 650 μ m NO cultured using (i) static culture (ii) orbital shaking, and (iii) microfluidic flow around NO. (iv) O 2 concentration across NO on a cutline at y=0 for all three cases. The blue-shaded region represents the area below the critical O 2 concentration, which determines the necrotic area. We observe that orbital shaking improves the NO viability in comparison to the other two culture strategies. (F) For a 1000 μ m NO cultured using, (i) static culture, (ii) orbital shaking, and (iii) microfluidic flow around NO. (iv) O 2 concentration across the NO on a cutline at y=0 for all three cases. The blue-shaded region represents the area below the critical O 2 concentration, which determines the necrotic area. We observe that all strategies show significant necrotic cores.

Article Snippet: We developed a 3D computational model (COMSOL Multiphysics) to investigate the progression of necrosis in NO culture.

Techniques: Concentration Assay, Cell Culture, Comparison

Journal: bioRxiv

Article Title: Computational modeling of necrosis in neural organoids

doi: 10.1101/2025.04.30.651571

Figure Lengend Snippet: (A-C) Varying synthetic capillary density to determine optimal layout to eliminate necrosis. We varied the density in the grid layout containing (A) 1, (B) 4, and (C) 9 capillaries. We maintain a flow rate of 200 μL/min. (D-F) O 2 concentration across NO on a cutline at z=0 for the three capillary densities. (G-I) Stacked 3D visual representation of O 2 concentration across the NO for the three capillary densities. (D&G) 1 capillary system causes high necrosis. ( E&H ) 4 capillary system necrosis reduces, but the organoid is not viable. (F&I) We observe no necrosis in the 9-capillary system.

Article Snippet: We developed a 3D computational model (COMSOL Multiphysics) to investigate the progression of necrosis in NO culture.

Techniques: Concentration Assay