High-throughput microfluidic chip having parallelized constrictions for perturbing cell membranes
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Solution Overview
Problem
Existing systems for intracellular payload delivery suffer from clogging issues, insufficient throughput rates, and complexity in fabrication, particularly in microfluidic cell-constricting chips.
Innovation Solution
The development of high-throughput microfluidic chips with parallelized constrictions, featuring deep, narrow, rectangular channels etched into a substrate, which maintain uniform flow velocity and minimize clogging by optimizing the cross-sectional area to perimeter ratio, ensuring efficient deformation of cell membranes for payload delivery.
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 suffers from clogging and insufficient throughput rates
Solution Approach 1:
The invention divides a single constriction into multiple parallel constrictions (e.g., arrays of 2-1000 constrictions per chip). This segmentation allows cell suspensions to flow through multiple pathways simultaneously, increasing overall throughput while reducing the likelihood of clogging in any single constriction. The parallel architecture enables high-volume payload delivery without the bottlenecks of conventional single-constriction designs.
Solution Approach 2:
The invention transitions from two-dimensional planar constrictions to three-dimensional deep constrictions etched into substrates. These vertical constrictions extend through the substrate thickness, creating a third dimension for flow. This dimensional change increases the effective constriction area and improves cell deformation efficiency while maintaining compact chip footprints and reducing clogging from debris accumulation.
2Productivity
If deep, narrow, rectangular constrictions are etched into substrates to increase cross-sectional area, then per-constriction throughput increases and clogging decreases, but manufacturing precision requirements increase
Solution Approach 1:
The invention optimizes constriction geometry parameters including depth, width, and aspect ratio to balance throughput and manufacturability. By controlling etch depth to extend through the substrate and designing rectangular cross-sections with specific width-to-depth ratios, the system achieves high per-constriction throughput while maintaining compatibility with standard semiconductor fabrication processes. The geometric parameters are tuned to ensure cell deformation effectiveness without requiring ultra-precision manufacturing.
3Productivity
If multiple parallelized constrictions are implemented to increase throughput, then productivity improves, but device complexity increases
Solution Approach 1:
The invention merges multiple constrictions into integrated arrays on single chips, combining the functionality of many individual constrictions into one unified device. This merging approach increases overall throughput by providing parallel flow pathways while avoiding the complexity of multi-chip systems. The constrictions are arranged in systematic patterns (grids, arrays, or parallel channels) that simplify fabrication and reduce interconnect complexity compared to separate chip assemblies.
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 enhances throughput and reduces clogging rates while maintaining efficient payload delivery and cell viability, addressing the limitations of previous designs.
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.