Perfluoro-n-Octane Operating Liquid for Mercury-Free Piezo-ICSI

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Solution Overview

Problem

Current Piezo-ICSI methods for intracytoplasmic sperm injection in humans are not approved for clinical use due to inefficiencies and the toxicity of mercury, and there is a need for a safer and more effective operating liquid to improve fertilization rates and standardize the procedure.

Innovation Solution

The use of purified perfluoro-n-octane with an H-value of 1000 ppm or less as the operating liquid in Piezo-ICSI apparatus and kits, which includes injection micropipettes, to facilitate precise and safe piercing of oocytes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mercury is used as operating liquid in Piezo-ICSI, then the success rate of sperm injection is improved, but the toxicity and safety concerns worsen

Engineering Contradiction:
Improvesuccess rate of sperm injectionVSAvoidtoxicity of mercury
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces toxic mercury with perfluoro-n-octane, a safer alternative that can be easily disposed of or degraded. This disposable approach eliminates the need to handle toxic substances long-term, resolving the contradiction between achieving high injection success rates and avoiding toxicity.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent introduces perfluoro-n-octane as an intermediary substance that mediates the piezoelectric effect in the micropipette. This intermediary enables the piercing function while being non-toxic, thus resolving the contradiction between functional effectiveness and safety.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If conventional ICSI is used, then the procedure is well-established, but the labor intensity and skill requirement worsen

Engineering Contradiction:
Improveestablishment of procedureVSAvoidlabor intensity and skill requirement
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanically intensive conventional ICSI procedure with a piezoelectrically-driven system. The piezoelectric effect automatically generates the precise mechanical force needed for piercing, reducing the operator's manual skill requirements while maintaining procedural reliability.

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

Solution Approach 2:

The piezoelectric micropipette system performs the piercing action autonomously through electrical stimulation, eliminating the need for highly skilled manual manipulation. The system serves itself by converting electrical signals into the precise mechanical movements required, reducing labor intensity.

Inventive Principle:
Principle #25Self-service

3Object-affected harmful factors

If piezoelectric effect is used for piercing, then the stress on oocyte is reduced, but the fertilization rate initially worsened

Engineering Contradiction:
Improvestress on oocyteVSAvoidfertilization rate
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent optimizes parameters such as piezoelectric pulse duration, intensity, and frequency to achieve the optimal balance between gentle piercing (reducing oocyte stress) and effective sperm injection (maintaining fertilization rate). By carefully adjusting these parameters, both contradictions are resolved simultaneously.

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

Enhances fertilization success rates, improves embryo development, and simplifies the ICSI procedure, potentially leading to its approval for clinical use and automation in assisted reproduction.

Implementation Method 1

a piezoelectric effect is used to pierce the oocyte. The piezoelectric effect is the phenomenon that certain materials accumulate electric charge in response to mechanical stress, and conversely mechanical stress can be induced by application of electricity. A brief 'Piezo pulse' is applied to the micropipette containing the sperm to produce ultra-fast, sub-micron forward momentum of the micropipette.

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

when the piezo pulse is applied, the micropipette moves forward but the operating liquid does not move due to the laws of inertia and the high specific gravity of the liquid. It is believed that the rapidly moving micropipette and stationary operating liquid generate negative pressure in the micropipette tip which pulls open the zona pellucida.

Methodology Applied
Scientific EffectInertia: Inertia

Data Source

PatentEP4058588B1Use of perfluoro-n-octane for piezo-mediated intracytoplasmic sperm injection
Publication Date: 2025.11.12 VITROLIFE SWEDEN AB
  • EP4058588B1 patent drawingFigure 1
  • EP4058588B1 patent drawingFigure 2A~2B
  • EP4058588B1 patent drawingFigure 3A~3B

AI summary

The present invention relates to an operating liquid for Piezo-mediated microinjection. In particular, the present invention relates to use of purified perfluoron-octane or a composition comprising purified perfluoro-n-octane as operating liquid for Piezo-mediated intracytoplasmic sperm injection (Piezo-ICSI). The present invention further relates to methods of fertilising an oocyte in vitro by Piezo-ICSI using purified perfluoro-n-octane or a composition comprising purified perfluoro-noctane as operating liquid and methods of assisted reproduction using methods of the invention.