Microfluidic Constriction for Intracellular Biomolecule Delivery

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Solution Overview

Problem

Current methods for intracellular delivery of molecules are inefficient, particularly for cells with cell walls such as plant, yeast, fungal, algal, and prokaryotic cells, due to non-specific delivery, molecule modification or damage, high cell death, and low throughput, making them unsuitable for large-scale applications.

Innovation Solution

A method involving passing a cell suspension through a constriction to deform the cell, allowing a compound to enter, where the constriction can be within a microfluidic channel or a surface with pores, and the cell suspension can be treated with enzymes or ultrasound to modify the cell wall before passing through.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If electrical fields, nanoparticles, or pore-forming chemicals are used for intracellular delivery, then molecule delivery can be achieved, but non-specific delivery, molecule modification or damage, high cell death, and low throughput occur

Engineering Contradiction:
Improvedelivery effectivenessVSAvoidcell damage and molecule damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces electrical fields, chemical agents, and nanoparticle-based methods with a mechanical system consisting of a microfluidic device with a constriction. The mechanical deformation of cells as they pass through the constriction creates transient pores that allow compound entry, eliminating the harmful effects of electrical fields, chemical toxicity, and nanoparticle non-specific delivery while maintaining effective intracellular delivery

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the physical state and geometry parameters of the cell by deforming it through a constriction with a specific diameter (smaller than the cell diameter). This geometric constraint causes mechanical stress and transient pore formation, changing the membrane permeability parameter dynamically to enable compound entry while preserving cell viability

Inventive Principle:
Principle #35Parameter changes

2Reliability

If existing intracellular delivery methods are used, then some molecule delivery is achieved, but throughput is low and implementation is difficult

Engineering Contradiction:
Improvedelivery effectivenessVSAvoidthroughput
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The microfluidic device enables high-throughput delivery by allowing continuous flow of cell suspensions through the constriction. The system processes cells in a self-sustaining flow regime without requiring manual intervention for each cell, achieving scalable throughput while maintaining consistent delivery effectiveness across large cell populations

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The constriction-based delivery system serves multiple functions: it deforms cells to create transient pores, enables compound entry, and can be integrated with microfluidic networks for cell sorting and delivery. This multi-functionality simplifies implementation compared to specialized equipment required for electrical field or nanoparticle methods

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If existing delivery methods are used, then molecule delivery can occur, but delivery to cells with cell walls is ineffective

Engineering Contradiction:
Improvedelivery effectivenessVSAvoidcell type compatibility
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The mechanical deformation approach changes the physical state of the cell wall and membrane under stress, creating transient pores that allow compound entry. This parameter change mechanism is universally applicable to different cell types including those with cell walls, as the mechanical stress effect occurs regardless of cell wall composition, enabling delivery to plant, yeast, fungal, and prokaryotic cells

Inventive Principle:
Principle #35Parameter changes

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

This method enables effective and efficient delivery of compounds into cells with cell walls, including plant, yeast, fungal, and prokaryotic cells, improving throughput and reducing cell damage, making it suitable for various applications including drug screening and manufacturing.

Implementation Method 1

passing a cell suspension through a constriction, wherein said constriction deforms the cell comprising a cell wall, thereby causing a perturbation of the cell such that the compound enters the cell

Methodology Applied
Scientific EffectMechanical deformation: Deformation

Implementation Method 2

the cell suspension can be treated with enzymes or ultrasound to modify the cell wall before passing through

Methodology Applied
Scientific EffectEnzymatic degradation: Enzyme

Implementation Method 3

the cell suspension can be treated with enzymes or ultrasound to modify the cell wall before passing through

Methodology Applied
Scientific EffectUltrasonic vibration: Ultrasonic Vibration

Data Source

PatentUS20230357782A1Intracellular delivery of biomolecules to cells comprising a cell wall
Publication Date: 2023.11.09 STEMCELL TECHNOLOGIES CANADA INC
  • US20230357782A1 patent drawing
  • US20230357782A1 patent drawing
  • US20230357782A1 patent drawing

AI summary

The present disclosure pertains to methods for delivering a compound into a cell comprising a cell wall, including passing a cell suspension through a constriction, wherein said constriction deforms the cell comprising a cell wall, thereby causing a perturbation of the cell such that the compound enters the cell, wherein said cell suspension is contacted with the compound.