Porous Filter for Intracellular Payload Delivery
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Solution Overview
Problem
Current technologies face challenges in efficiently delivering payloads such as small molecule drug candidates, proteins, and nucleic acids into cells on a large scale, often causing negative impacts on cell viability and resulting in biologically meaningless assays.
Innovation Solution
A high-throughput system comprising a liquid handler configured with a filter having a plurality of pores for perturbing cell membranes, allowing for the intracellular delivery of payloads by mechanically perturbing cells and distributing them to multiple samples, while maintaining cell viability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional delivery techniques are used to deliver payloads to cells, then delivery efficiency is improved, but cell viability deteriorates
Solution Approach 1:
The invention employs a porous filter with controlled pore sizes (e.g., 3-10 μm) that allows mechanical perturbation of cell membranes to facilitate payload delivery. The porous structure enables cells to pass through while experiencing controlled membrane disruption, achieving efficient delivery without excessive damage to cell viability.
2Manufacturing precision
If mechanical perturbation is applied to deliver payloads, then intracellular delivery is achieved, but cell damage increases
Solution Approach 1:
The invention optimizes multiple parameters including pore size (3-10 μm), flow rate (e.g., 5-50 mL/min), and pressure gradients to control the degree of mechanical perturbation. By carefully adjusting these parameters, the system achieves sufficient membrane disruption for payload delivery while minimizing cell damage and maintaining viability.
Solution Approach 2:
The system maintains continuous flow of cell-containing solution through the porous filter, ensuring consistent mechanical perturbation and payload delivery. The continuous action allows for controlled, uniform treatment of cells without intermittent stress that could cause excessive damage.
3Productivity
If high-throughput processing is implemented, then productivity is improved, but system complexity increases
Solution Approach 1:
The porous filter system serves multiple functions simultaneously: it acts as a flow regulator, a mechanical perturbation device, and a delivery platform. This multi-functionality reduces the need for separate components, thereby managing system complexity while achieving high-throughput processing capability.
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 system enables efficient intracellular delivery of payloads to a large number of cells with minimal impact on cell viability, facilitating high-throughput cellular assays such as drug screening and gene editing.
Implementation Method 1
a filter configured to be placed in fluidic communication with the cell reservoir, the filter comprising a plurality of pores therethrough for perturbing cell membranes of the plurality of cells
Data Source
AI summary
The present disclosure, in some aspects, is directed to high-throughput systems, and methods of use thereof, for intracellular delivery of one or more payloads to separate cell samples. For example, in certain aspects, provided is a high-throughput liquid handler configured for distribution of mechanically perturbed cells in formats suitable for high-throughput cellular assays. In certain other aspects, the present disclosure is directed to components of said high-throughput systems, e.g., liquid handlers and cartridges comprising a filter comprising a plurality of pores therethrough for perturbing cell membranes, and uses of said high-throughput systems.


