Bone Marrow Microfluidic Device with Multi-Chamber Segmentation
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Solution Overview
Problem
Current microfluidic devices are limited in their ability to effectively mimic complex biological systems, such as bone marrow, as they often rely on a simple two-microchannel configuration separated by a membrane, which does not accurately represent the complexity of in vivo conditions.
Innovation Solution
The development of microfluidic devices with an upper and lower chamber separated by a porous membrane, where the upper chamber is filled with a matrix of bone marrow cells and hematopoietic media, and the lower chamber is lined with endothelial cells, allowing for the simulation of bone marrow environments through controlled media flow and sampling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If a simple two-microchannel configuration separated by a membrane is used, then the device structure is simple and easy to manufacture, but it cannot accurately represent the complexity of in vivo bone marrow conditions
Solution Approach 1:
The device is divided into multiple chambers (first chamber, second chamber, third chamber) with distinct functional zones. The first chamber contains endothelial cells lining the microchannel, the second chamber contains the extracellular matrix with bone marrow cells, and the third chamber provides additional culture space. This segmentation allows each zone to perform its specific biological function while collectively mimicking the complex in vivo bone marrow environment.
Solution Approach 2:
The invention transitions from a simple two-channel planar configuration to a three-dimensional multi-chamber structure with vertical layering. The chambers are stacked with porous membranes separating them, creating a z-dimension that enables complex cell-cell and cell-matrix interactions throughout the volume, better representing the three-dimensional architecture of bone marrow tissue.
2Reliability
If a multi-chamber configuration with extracellular matrix is used, then the biological system mimicry accuracy is improved, but the device structure becomes more complex
Solution Approach 1:
The porous membranes serve multiple functions: they physically separate different chambers while allowing nutrient and signal molecule diffusion, provide structural support for the extracellular matrix, and enable mechanical coupling between chambers. The extracellular matrix in the second chamber simultaneously provides structural scaffolding, biochemical signaling, and mechanical properties necessary for bone marrow cell function, consolidating multiple requirements into a single component.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This configuration enables the successful culture and expansion of bone marrow cells, including CD34+ progenitor cells, and allows for the simulation of bone marrow environments in vitro, including responses to radiation, demonstrating the ability to mimic in vivo conditions and facilitate new research possibilities.
Implementation Method 1
a porous membrane separating the upper chamber from the lower chamber
Implementation Method 2
a porous membrane separating the upper chamber from the lower chamber
Data Source
AI summary
The present disclosure relates to a microfluidic devices and methods for culturing bone marrow cells. Aspects include methods of preparing microfluidic devices and culturing bone marrow cells with the microfluidic devices. In some aspects, a method includes providing a microfluidic device having an upper chamber, a lower chamber, and a porous membrane separating the upper chamber from the lower chamber. The method further includes seeding walls of the lower chamber and a bottom surface of the membrane with endothelial cells. The method further includes providing a matrix within the upper chamber. The matrix includes fibrin gel and bone marrow cells. The method further includes filling or perfusing the upper chamber with a media.