Microfluidic device with embedded cell culture chambers for high throughput biological assays
Inventors
Yang, Ruiguo • Jaberi, Arian • Esfahani, Amir Monemian • TAMAYOL, Ali
Assignees
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Publication Number
US-12064759-B2
Publication Date
2024-08-20
Expiration Date
Abstract
Microfluidic gradient generators that can create robust platforms that can not only be used for creating co-cultures of cells with various ratios, but also can simultaneously generate gradients of mechanical and chemical stresses. A chip utilizes microchambers embedded within channels to provide space for 3D cell culture and exposes these cells to gradients of mechanical shear stress and a chemical treatment.
Core Innovation
The invention relates to an integrated microfluidic gradient generator for high-throughput biological assays that combines a microfluidic chemical/drug concentration gradient across embedded 3D cell culture chambers with an associated mechanical shear-stress gradient correlated with inlet flow rates. The device uses microchannels arranged in a “Christmas tree”-like network and microchambers arranged in increasing numbers of chambers per row to generate gradients across the array of chambers.
The integrated architecture includes microchamber-embedded “Christmas tree” configurations and optional micropillars and microchamber flow-resistor structures, with manifold coupling. The microchannels and coupled microchambers are configured to form first and second gradients of different materials, and, with micropillars, to further create a shear-stress distribution within each microchamber in addition to the inter-chamber shear-stress gradient.
The disclosure uses the device for 3D co-culture in GelMA hydrogel encapsulating two cell types, and evaluates drug response including doxorubicin dose response and viability. The results are described as correlating drug concentration gradients with shear-stress gradients to evaluate synergy, and the gradient generation is validated by simulation versus experiments, with comparative viability confirmation in petri dishes.
Claims Coverage
The claims coverage is not explicitly described in the patent text provided; no independent inventive features are set out here.
Not explicitly described in patent.
Stated Advantages
Generates chemical/drug concentration gradients across embedded 3D cell culture chambers in a high-throughput biological assay format.
Generates mechanical shear-stress gradients correlated with inlet flow rates across the chamber array.
Enables, with micropillars, shear-stress gradients within each microchamber in addition to inter-chamber shear-stress gradients.
Supports evaluation of 3D co-culture viability and doxorubicin dose response under controlled gradients, including assessment of synergy between drug concentration and shear stress.
Provides validation of gradient generation using COMSOL simulation compared with experiments, and compares viability with petri dish results.
Documented Applications
High-throughput biological assays using integrated microfluidic chemical/drug concentration gradients and mechanical shear-stress gradients in embedded 3D cell culture chambers.
3D co-culture of two cell types in GelMA hydrogel in the microchambers, including evaluation of doxorubicin dose response, viability, and synergy with shear stress.
Validation of generated gradients by comparing COMSOL simulation results with experimental measurements, and confirmation of viability comparisons in petri dishes.
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