Microfluidic Device With Sealable Port for Low-Shear Cell Handling
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Solution Overview
Problem
Microfluidic devices face challenges in connecting the micro-components to the macro-environment, leading to issues such as high shear stress on cells due to fluid flow, difficulty in accurately introducing cells, and inefficient macro-to-micro interface, especially for high-throughput applications and sensitive cell types like hESC.
Innovation Solution
A microfluidic device with a sealable port, chamber design, and interconnect system that allows precise material insertion/removal, reduces shear stress, and enhances the macro-to-micro interface, featuring a chamber with optimized dimensions and flow control mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Use of energy by moving object
If a constant perfusion system is used to supply medium to cells, then nutrient supply and oxygen delivery are improved, but high shear stress is generated which is detrimental to sensitive cells
Solution Approach 1:
The system transitions from constant perfusion to a dynamic intermittent perfusion system where medium flow is pulsed rather than continuous. This allows nutrient delivery while reducing average shear stress exposure on sensitive cells like hESC
Solution Approach 2:
The perfusion system operates in periodic cycles with defined on/off intervals. During the on-phase, medium flows to supply nutrients; during the off-phase, flow stops to minimize shear stress. This periodic action resolves the contradiction between adequate nutrient supply and shear stress reduction
2Productivity
If high flow rates are used for perfusion, then medium supply efficiency is improved, but cells are washed out of the microfluidic device
Solution Approach 1:
The system uses dynamic flow rate adjustment rather than constant high flow. Flow rate is modulated in sync with the intermittent perfusion cycles, delivering adequate medium supply during active phases while preventing cell washout during low-flow or rest phases
Solution Approach 2:
By implementing periodic perfusion cycles with controlled duration and intensity, the system achieves cumulative medium supply equivalent to high continuous flow while allowing cells to remain anchored during off-phases, thus preventing washout
3Ease of operation
If cells are flushed into the chamber from upstream inlets, then cell introduction is simplified, but the number of cells becomes undefined and phenotype may be affected
Solution Approach 1:
The invention extracts the cell introduction step from the main perfusion flow path. Instead of flushing cells through the upstream inlet with high-flow medium, cells are introduced through a separate dedicated inlet, allowing precise control and counting independent of the perfusion dynamics
Solution Approach 2:
A separate cell introduction inlet acts as an intermediary pathway, decoupling cell delivery from the main perfusion system. This allows cells to be introduced in a controlled manner without exposure to high shear stress from the main flow, preserving phenotype while enabling accurate cell number control
4Productivity
If the device is designed for high-throughput applications, then productivity is improved, but manual manipulation becomes uneconomical and the macro-to-micro interface must be developed
Solution Approach 1:
The device incorporates standardized macro-to-micro interface components such as universal connectors and ports that can be repeatedly opened and closed. This allows automated or semi-automated manipulation while maintaining ease of operation, bridging the scale gap between manual handling and high-throughput requirements
Data Source
Figure 1A~1C
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AI summary
The invention relates to a microfluidic device comprising a chamber having a fluid inlet, a fluid outlet and a sealable port, wherein the fluid inlet and the fluid outlet are positioned to direct fluid flowing from the fluid inlet to the fluid outlet through the chamber, and wherein the sealable port is aligned with the chamber to allow material to be placed directly into, or removed from, the chamber from the exterior of the device when the sealable port is open, and to prevent fluid escaping through the sealable port when the port is sealed.