Microfluidic Cervix Model with Protrusion Barriers
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Solution Overview
Problem
Current methods for investigating cellular and tissue functions in the human cervix, such as animal models and two-dimensional Transwell-based in vitro models, fail to accurately replicate the complex three-dimensional structure and dynamic microenvironments of the cervix, limiting their ability to mimic physiological and pathological processes.
Innovation Solution
A microdevice with a compartmentalized three-dimensional microfluidic design that includes an upper channel for cervical epithelial cells and a lower channel with parallel lanes for stromal tissue formation, featuring a porous membrane for nutrient exchange and protrusion structures to prevent hydrogel spillage, allowing for co-culture of multiple cervical cell types and simulation of physiological and pathological processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If animal models are used to investigate cervical tissue functions, then physiological and pathological processes can be studied, but genetic and structural divergence from humans limits accuracy
Solution Approach 1:
The microdevice is divided into multiple compartments including an upper microchannel for epithelial cells, a lower microchannel with three parallel lanes for stromal tissue, and intermediate lanes for immune cells. This segmentation allows each compartment to be optimized for specific cell types and functions while maintaining overall physiological accuracy.
Solution Approach 2:
The device employs nested structures where protrusion structures are integrated into the lower microchannel to create physical barriers, which are in turn surrounded by hydrogel matrices containing cells. This nested arrangement enables complex tissue architecture within a compact device footprint.
2Reliability
If two-dimensional Transwell-based in vitro models are used, then simplicity is maintained, but ability to replicate three-dimensional cervical structure and dynamic microenvironments is greatly limited
Solution Approach 1:
The invention transitions from two-dimensional Transwell models to a three-dimensional microfluidic system with vertical stacking of upper and lower microchannels connected by porous membranes. This adds the vertical dimension, enabling true 3D tissue architecture and improved mass transport.
Solution Approach 2:
The device incorporates microfluidic channels with controlled fluid flow through porous membranes, enabling dynamic delivery of nutrients, growth factors, and mechanical forces to cells in three-dimensional culture, thereby replicating physiological microenvironments.
3Reliability
If hydrogel precursor solution is injected into the first parallel lane, then stromal tissue formation is enabled, but hydrogel spillage into second and third parallel lanes occurs
Solution Approach 1:
Protrusion structures are pre-formed in the lower microchannel before hydrogel injection. These structures create physical barriers that confine the hydrogel precursor solution to the first parallel lane during injection, preventing spillage into adjacent lanes and ensuring precise tissue compartmentalization.
4Reliability
If porous membrane is positioned between upper and lower microchannels, then nutrient and gas exchange is enabled, but structural integrity must be maintained
Solution Approach 1:
A porous membrane is positioned between the upper and lower microchannels to enable diffusion of nutrients, oxygen, and waste products while maintaining structural separation. The porous structure provides sufficient mechanical strength to support tissue formation while allowing efficient mass transport.
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
Enables faithful recreation of the complex interplay between cervical tissue types, allowing direct visualization and quantitative analysis of structural and functional alterations, and serves as a research tool for investigating biological processes and drug development.
Implementation Method 1
The porous membrane can be configured to pass nutrients, oxygen, growth factors, cytokines, chemokines, pathogens, particulates, chemicals, and drug compounds from the upper microchannel to the lower microchannel (or vice versa)
Implementation Method 2
the protrusion structures can be configured to pin the menisci of a hydrogel precursor solution injected into the first parallel lane of the lower microchannel and prevent the hydrogel precursor from spilling into the second and third parallel lanes
Data Source
AI summary
The presently disclosed subject matter provides systems and methods for producing a three-dimensional model of a human cervix. A microdevice is provided for culturing human cervical cells. The microdevice can include an upper microchannel including live ectocervical epithelial cells. The microdevice can include a lower microchannel including a first parallel lane and a second parallel lane including stromal media. The first and the second parallel lanes can be lined with live vascular endothelial cells. The lower microchannel can include a third parallel lane including uterine fibroblasts and live smooth muscle cells embedded in hydrogel. The first, second, and third lanes of the lower microchannel can be separated by protrusion structures. The third parallel lane can be positioned in the lower microchannel in between the first and the second parallel lanes. The microdevice can further include a porous membrane positioned in between the upper microchannel and the lower microchannel.