Parallel Microfluidic Constrictions for High-Throughput Cell Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing systems for intracellular payload delivery are prone to clogging, have insufficient throughput rates, and are not efficiently manufactured.
Innovation Solution
High-throughput microfluidic chips with parallelized constrictions, featuring deep, narrow, rectangular channels etched into a substrate, ensuring uniform flow velocity and minimizing clogging by maintaining a high cross-sectional area to perimeter quotient, thereby enhancing throughput and reducing clogging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional microfluidic constricting channels are used for intracellular payload delivery, then cell membrane perturbation is achieved, but the system is prone to clogging and has low throughput rates
Solution Approach 1:
The invention divides a single constriction into multiple parallel constrictions (e.g., arrays of 5-50 parallel channels). This segmentation allows cell suspensions to flow through multiple paths simultaneously, increasing throughput while reducing the likelihood of clogging in any single channel. The parallel architecture maintains effective cell membrane perturbation while solving the throughput-clogging contradiction.
Solution Approach 2:
The invention transitions from a single-constriction design to a multi-dimensional parallel array, adding the dimension of parallelism to the constriction architecture. By arranging constrictions in parallel across multiple channels, the system achieves higher throughput without compromising reliability, as cells can distribute across multiple flow paths.
2Ease of manufacture
If conventional constricting channels are used, then cell membrane perturbation is achieved, but the manufacturing process is complex and inefficient
Solution Approach 1:
The constriction array is designed as a modular segmented structure that can be fabricated using standard microfluidic manufacturing techniques. The parallel channels are created through systematic division of the flow path, allowing for simplified manufacturing compared to complex single-constriction designs. Each parallel channel is identical and can be produced through repetitive patterning processes.
Solution Approach 2:
The invention optimizes constriction parameters including width, height, and spacing between parallel channels to achieve effective cell membrane perturbation. By controlling these parameters within specific ranges, the design maintains manufacturability while achieving the desired biological effect. The standardized parameter set facilitates efficient fabrication using conventional methods.
3Productivity
If constrictions with high cross-sectional area are used to increase throughput, then per-constriction throughput improves, but the perimeter increases which may increase clogging risk
Solution Approach 1:
Instead of increasing the cross-sectional area of a single constriction, the invention segments the total flow area into multiple parallel constrictions. Each individual constriction maintains a moderate cross-sectional area that minimizes clogging risk, while the collective array of parallel constrictions provides high overall throughput. This segmentation strategy decouples the relationship between single-constriction size and total productivity.
Solution Approach 2:
The invention applies different geometric characteristics to different parts of the constriction array. Each parallel constriction is optimized with specific dimensions and spacing to achieve uniform flow distribution and minimize local clogging hotspots. The local geometry of each channel is tailored to balance throughput and clogging resistance, while the overall array configuration maximizes total productivity.
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
The solution achieves improved throughput and reduced clogging rates while maintaining payload delivery effectiveness and cell viability, facilitating efficient intracellular payload delivery.
Implementation Method 1
the chips comprise a plurality of parallelized constrictions through which a cell suspension may be forced under pressure
Implementation Method 2
The cells of the cell suspension may be deformed and their membranes perturbed due to passage through a cell-deforming constriction
Data Source
AI summary
A microfluidic chip for causing the delivery of a payload to a cell comprises a plurality of constrictions configured to allow a cell suspension to flow through one or more of the plurality of constrictions from a first fluid flow region to a second fluid flow region within the microfluidic chip, wherein a cross-sectional width of each of the plurality of constrictions is less than a diameter of cells in the cell suspension, such that membranes of the cells are perturbed when passing through the constrictions such that a payload is able to pass through the perturbed cell membranes, and wherein a quotient of a cross-sectional area over a cross-sectional perimeter of each of the plurality of constrictions is greater than greater than or equal to 0.5 μm.