Microfluidic Vortex-Assisted Electroporation for Single-Cell Control

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Solution Overview

Problem

Current electroporation techniques, including conventional and microfluidic systems, face challenges in precisely and individually controlling molecular delivery and are inefficient for samples with large cell diameter heterogeneity, as they rely on bulk stochastic processes and lack multi-molecule delivery capabilities.

Innovation Solution

A microfluidic electroporation system utilizing inertial focusing and vortex-assisted trapping to isolate cells of uniform size, followed by sequential delivery of molecules with precise control over electric field strength and duration for efficient and controlled molecular uptake.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional electroporation techniques using cuvettes or micro-capillaries are used, then molecular delivery can be achieved, but precise and individual control of transferred molecular doses cannot be obtained

Engineering Contradiction:
Improvemolecular delivery controlVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system divides the cell population into individual cells, each trapped separately in its own vortex within a microfluidic array. This segmentation enables independent molecular delivery control to each cell, transforming the bulk stochastic process into individually controllable events while maintaining manageable system complexity through parallel processing

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a microfluidic vortex trap array as an intermediary structure between the electroporation electrodes and the cells. This intermediary enables precise positioning and individual control of molecular delivery to each cell while simplifying the overall control mechanism through standardized trap designs and uniform electric field application

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If bulk electroporation processes are used, then throughput can be maintained, but precise dosage control and multi-molecule delivery capabilities are lost

Engineering Contradiction:
ImprovethroughputVSAvoiddosage control
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system segments the bulk electroporation process into individual cell events within a parallel array of vortex traps. Each trap handles one cell at a time with precise molecular dosage control, while the overall throughput is maintained through simultaneous processing of multiple cells across the array

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microfluidic vortex trap array serves multiple functions: it traps individual cells, controls molecular delivery dosage, enables multi-molecule delivery sequences, and maintains cell viability. This universal structure replaces multiple separate functions that would otherwise be needed, achieving both precision and productivity

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

3Productivity

If high electric field strength is applied to cells with large heterogeneity in diameter, then molecular delivery efficiency may improve, but cell viability decreases

Engineering Contradiction:
Improvemolecular delivery efficiencyVSAvoidcell viability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The system creates local uniformity within each vortex trap, where cells are positioned in a consistent manner relative to the electric field. This local quality control ensures that each cell receives a standardized electric field exposure appropriate for its size, improving delivery efficiency while maintaining viability through optimized field parameters for each trapped cell

Inventive Principle:
Principle #3Local quality

4Adaptability or versatility

If single-directional flow-through scheme is used, then system simplicity is maintained, but multiple different molecule delivery and dosage control are not achieved

Engineering Contradiction:
Improvemulti-molecule delivery capabilityVSAvoidflow control complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The system employs periodic action by sequentially delivering different molecules to the trapped cells in a time-dependent manner. Each molecule is delivered in a separate flow phase while maintaining the same physical trap structure, enabling multi-molecule delivery without requiring complex spatial reconfiguration or additional trapping mechanisms

Inventive Principle:
Principle #19Periodic action

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

Enables precise and independent molecular delivery into pre-selected target cells with enhanced viability and efficiency, overcoming the limitations of bulk stochastic processes and cell size heterogeneity, achieving three-fold higher electroporation efficiency compared to conventional methods.

Implementation Method 1

A first channel has an inertial focusing region to move cells in a solution travelling through the first channel towards sides of the channel

Methodology Applied
Scientific EffectInertial focusing: Inertia

Implementation Method 2

maintaining a vortex flow in the traps to trap the cells of interest in the traps

Methodology Applied
Scientific EffectVortex flow: Vortex Ring

Implementation Method 3

providing an electric field across the traps to perform electroporation of the first molecules of interest into the cells of interest in the traps

Methodology Applied
Scientific EffectElectroporation: Electric Field

Data Source

PatentUS9029109B2Microfluidic vortex-assisted electroporation system and method
Publication Date: 2015.05.12 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US9029109B2 patent drawing
  • US9029109B2 patent drawing
  • US9029109B2 patent drawing

AI summary

A system and method include delivering cells of interest to multiple traps via a channel connecting the traps, maintaining a vortex flow in the traps to trap the cells of interest in the traps, providing first molecules of interest to the traps, and providing an electric field across the traps to perform electroporation of the first molecules of interest into the cells of interest in the traps.