Microinjection Chip Hydration and Throughput

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Solution Overview

Problem

Traditional microinjection methods for biological reagents into organisms, such as nematodes, face challenges including desiccation, limited throughput, and user fatigue due to manual manipulation and the need for extensive training, while existing microfluidic devices often require complex setups or specialized equipment.

Innovation Solution

A microinjection chip with a fluid-filled channel that can be penetrated by a microinjection pipette without forming an opening, allowing for the stabilization and injection of organisms within a closed system, reducing desiccation and improving throughput by using a silicone polymer side wall that easily allows pipette insertion and resealing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional manual microinjection method is used, then flexibility and adaptability are maintained, but productivity is limited and user fatigue increases

Engineering Contradiction:
Improvenumber of nematodes injected per hourVSAvoidcomplexity of microfluidic system
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The microfluidic chip is divided into distinct functional zones: a loading chamber for nematode introduction, an injection chamber for the microinjection process, and a recovery chamber for post-injection handling. This segmentation allows automated high-throughput injection while keeping each zone simple and focused on a specific task, resolving the contradiction between productivity and device complexity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The injection chamber is designed with a nested structure where the nematode is positioned within a microchannel, and the microinjection pipette is inserted through a port in the chamber wall. This nested arrangement allows the pipette to access the nematode directly without complex positioning mechanisms, enabling high throughput while maintaining relatively simple device architecture.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Reliability

If agarose pad is used to immobilize nematodes, then ease of operation is maintained, but harmful factors increase due to desiccation

Engineering Contradiction:
Improvepost-injection recovery rateVSAvoiddesiccation of nematodes
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The microfluidic chip creates a closed, hydrated microenvironment within its channels and chambers that isolates the nematodes from the external atmosphere. This fluid-filled environment prevents desiccation while maintaining nematode immobilization and physiological viability, directly addressing the contradiction between reliability and harmful desiccation effects.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The chip walls and channel structures act as flexible barriers that contain the hydrated environment while allowing optical access for microscopy. This thin-film enclosure prevents evaporation and maintains the hydrated state necessary for high recovery rates without requiring complex environmental control systems.

Inventive Principle:
Principle #30Flexible shells and thin films

3Measurement precision

If high magnification objective is used for injection, then measurement precision is improved, but loss of time increases due to frequent objective switching

Engineering Contradiction:
Improveprecision of injection positioningVSAvoidtime per injection cycle
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The microfluidic chip translates the three-dimensional positioning problem into a two-dimensional planar problem by confining nematodes to a fixed vertical position within the microchannel. This allows high-magnification imaging to be maintained throughout the injection process without requiring vertical stage adjustment or objective switching, eliminating time loss while preserving precision.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The microchannel structure pre-position s and orients nematodes in a standardized configuration before injection begins. This preliminary positioning eliminates the need for real-time adjustment during injection, allowing consistent high-magnification imaging and precise targeting without time-consuming repositioning operations.

Inventive Principle:
Principle #10Preliminary action

4Productivity

If multiple nematodes are immobilized on a single coverslip, then productivity increases, but harmful factors increase due to desiccation

Engineering Contradiction:
Improvenumber of nematodes processed per coverslipVSAvoidsuccess rate of genetic transformation
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The chip divides the working area into multiple independent microchambers or zones, each capable of holding and processing nematodes in a controlled hydrated environment. This segmentation allows batch processing of multiple nematodes while maintaining individual environmental control, preventing desiccation even when many organisms are processed simultaneously.

Inventive Principle:
Principle #1Segmentation

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 microinjection chip enhances the efficiency and success rate of injecting biological reagents by maintaining organism hydration, reducing pipette breakage and clogging, and simplifying the injection process, thereby increasing the number of organisms that can be injected per hour and improving user safety and productivity.

Implementation Method 1

The microinjection chip comprises an inlet port, an injection channel, that does not comprise a microinjection port, and a post injection reservoir, wherein the inlet port, the injection channel and post injection reservoir are in fluid communication with each other

Methodology Applied
Scientific EffectPhysical containment: Physical Containment

Implementation Method 2

the injection channel comprises a side wall adapted to receive a microinjection pipette without a microinjection port and reseal when the microinjection pipette is removed

Methodology Applied
Scientific EffectElasticity: Elasticity

Data Source

PatentUS11654434B2Microinjection chip, device, system and uses thereof for unicellular or multicellular organisms
Publication Date: 2023.05.23 NEMAMETRIX INC
  • US11654434B2 patent drawing
  • US11654434B2 patent drawing
  • US11654434B2 patent drawing

AI summary

Disclosed herein are microinjection chips, devices, and systems for injection of unicellular or multicellular organisms. The microinjection chip and device disclosed herein include the microfluidic features, inlet port, pre-injection reservoir, injection channel and post injection channel in fluid communication with each other. The inlet port is adapted to sequentially move individual organisms into the injection channel, which is adapted to immobilize the individual organism in fluid. The injection channel features a side wall adapted to receive a microinjection pipette without a microinjection port and to reseal when the microinjection pipette is removed.