Nanopipette Cell Patterning and Injection via Electroosmosis

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Solution Overview

Problem

Current methods for cell patterning and injection are limited by the need for photolithography and semiconductor fabrication, which are inflexible and require restarting the process for pattern changes, and traditional micropipettes are large, cause cell damage, and require skilled operators.

Innovation Solution

A multi-barreled nanopipette system with a xyz controller and voltage control circuit for precise mechanical movement and electroosmotic injection, allowing for real-time pattern modification and high-throughput cell injection with minimal damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If photolithography and semiconductor fabrication are used for cell patterning, then manufacturing precision is improved, but adaptability deteriorates because the process must be restarted for pattern changes

Engineering Contradiction:
Improvepatterning precisionVSAvoidpattern flexibility
Core Design Contradiction:
Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The patent replaces static photolithography masks with a dynamic inkjet printing system that can change patterns in real-time through software control. The inkjet printer deposits adhesion molecules (e.g., poly-L-lysine) in programmable patterns directly onto the substrate, allowing immediate pattern modification without physical mask changes or process restarts, thus achieving both high precision and full adaptability

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent substitutes the mechanical photolithography process (requiring mask fabrication, alignment, and physical contact) with a non-contact inkjet printing system that uses controlled liquid deposition. This electronic/software-controlled approach eliminates the inflexibility of mechanical mask systems while maintaining submicron patterning precision through digitally controlled droplet placement

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

2Ease of manufacture

If traditional micropipettes are used for cell injection, then ease of manufacture is improved, but object-affected harmful factors worsen due to cell damage from large size

Engineering Contradiction:
Improvepipette fabricationVSAvoidcell damage
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the mechanical micropipette injection system with an electroosmotic injection system. The nanopipette (50-200 nm tip diameter) uses electroosmotic flow generated by applying voltage to its inner surface to eject liquid containing adhesion molecules or injection materials. This eliminates the need for manual micropipette manipulation and reduces mechanical stress on cells, significantly reducing cell damage while maintaining ease of operation through automated voltage control

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

Solution Approach 2:

The patent changes the critical parameter of pipette tip diameter from micrometer scale (traditional micropipettes) to nanometer scale (nanopipettes with 50-200 nm tips). This parameter change enables precise targeting of single cells or even subcellular structures while minimizing mechanical disruption. The electroosmotic injection mechanism further modifies the delivery parameters, allowing controlled material ejection without large-scale mechanical insertion

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

Enables flexible and precise cell patterning and injection with submicron resolution, allowing for controlled cell growth and high cell viability, and the ability to detect biomolecules within single cells without the need for labeling.

Implementation Method 1

applying an ejection voltage to a liquid at a desired location where the liquid in the nanopipette is to be deposited

Methodology Applied
Scientific EffectElectroosmosis: Electro-Osmosis

Data Source

PatentEP2681304B1Method of patterning cells on a substrate
Publication Date: 2020.05.27 RGT UNIV OF CALIFORNIA
  • EP2681304B1 patent drawingFigure 1~2
  • EP2681304B1 patent drawingFigure 3
  • EP2681304B1 patent drawingFigure 4A~4B

AI summary

Disclosed herein are methods and systems for controlled ejection of desired material onto surfaces including single cells using nanopipettes, as well as ejection and into cells. Some systems are directed to a method and system comprising nanopipettes combined with an xyz controller for depositing a user defined pattern on an arbitrary substrate for the purpose of controlled cell adhesion and growth. Alternate embodiments are directed to a method and system comprising nanopipettes combined with an xyz controller and electronic control of a voltage differential in a bore of the nanopipette electroosmotically injecting material into a cell in a high-throughput manner and with minimal damage to the cell. Yet other embodiments are directed to method and system comprising functionalized nanopipettes combined with scanning ion conductance microscopy for studying molecular interactions and detection of biomolecules inside a single living cell.