Microfluidic Sperm Sorting via Impedance Analysis

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Solution Overview

Problem

Current sperm sorting systems are unable to effectively differentiate and separate morphologically normal from abnormal sperm cells, particularly those with cytoplasmic droplets, due to their similar characteristics, leading to the discard of healthy sperm cells during artificial insemination processes.

Innovation Solution

A microfluidic system utilizing a fluid flow channel with electrodes to measure impedance changes over time, allowing for the discrimination and sorting of sperm cells based on morphological characteristics such as cytoplasmic droplets, through the comparison of time-dependent impedance data with predefined reference data, using dielectrophoretic forces for cell positioning and sorting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional sperm sorting systems are used, then the process is simple and fast, but the systems cannot differentiate morphologically normal from abnormal sperm cells

Engineering Contradiction:
Improvediscrimination accuracyVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system divides the sperm cell analysis into multiple measurement stages: initial impedance measurement, secondary impedance measurement after re-suspension, and comparative analysis. This segmentation allows differentiation of morphologically abnormal sperm cells through multi-step characterization without requiring overly complex single-step detection

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary re-suspension step where sperm cells are re-suspended in medium after initial measurement. This intermediary action enables secondary measurement that provides additional discriminatory information about morphological abnormalities, improving detection accuracy without directly complicating the core measurement system

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If morphologically abnormal sperm cells are discarded, then the quality of insemination should improve, but healthy sperm cells with similar characteristics are also discarded

Engineering Contradiction:
Improveinsemination success rateVSAvoidloss of healthy sperm cells
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The system employs feedback through comparative analysis of impedance measurements taken at different stages. By comparing initial and secondary impedance data, the system generates feedback information that characterizes morphological abnormalities, enabling more accurate identification and reduction of false positives among healthy sperm cells

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent applies partial action by using only the discriminatory information derived from impedance changes rather than complete morphological analysis. This partial measurement approach sufficiently identifies abnormal sperm cells while avoiding the need for more complex and potentially more restrictive sorting criteria that would discard additional healthy cells

Inventive Principle:
Principle #16Partial or excessive action

3Measurement precision

If impedance measurement is used to differentiate sperm cells, then discrimination capability improves, but the measurement time and complexity increase

Engineering Contradiction:
Improvecell differentiation accuracyVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The system uses periodic action by taking impedance measurements at distinct time points: initial measurement and secondary measurement after re-suspension. This periodic measurement approach provides time-dependent impedance data that reveals morphological characteristics without requiring continuous monitoring, balancing accuracy with time efficiency

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent applies preliminary action by performing the re-suspension and secondary measurement as a preparatory step before final sorting decisions. This preliminary characterization of sperm cells through multi-stage impedance measurement ensures accurate differentiation is achieved before the sorting process, preventing re-measurement needs

Inventive Principle:
Principle #10Preliminary 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

The system achieves a discrimination success rate of over 65% for sperm cells, reducing the discard of healthy, morphologically normal sperm cells and enabling high-quality screening, with the potential for scaling up through parallel processing.

Implementation Method 1

measuring an impedance as a function of time of the fluid between the pair of electrodes

Methodology Applied
Scientific EffectElectrical impedance measurement: Electrical Resistance

Implementation Method 2

using dielectrophoretic forces for cell positioning and sorting

Methodology Applied
Scientific EffectDielectrophoresis: Dielectric

Data Source

PatentEP3356792B1Microfluidic device for selection of semen
Publication Date: 2020.04.29 SEMEN REFINEMENT BV
  • EP3356792B1 patent drawingFigure 1A
  • EP3356792B1 patent drawingFigure 1B
  • EP3356792B1 patent drawingFigure 2

AI summary

The invention provides a system (1) for performing sperm analysis and selection based on sperm cell morphology of sperm cells (6) in a fluid (5), the system (1) comprising: (i) a fluid flow channel (2) for transport of said fluid (5), the fluid flow channel (2) comprising an inlet (10) an analyzing zone (40) configured downstream from said inlet (10) and comprising a first pair of electrodes (41) comprising a first intra-electrode distance (dl), a sorting zone (50) configured downstream from said analyzing zone (40) and comprising a sorting device (51), and outlets (80, 90,...) configured downstream from said sorting zone (50); (ii) an electric source (140) configured to provide an electric signal to the first pair of electrodes (41); (iii) a measuring device (150) functionally coupled to the first pair of electrodes (41) and configured to measure a first impedance as a function of time of the fluid (5) between the first pair of electrodes, and to provide time-dependent impedance data; wherein the sorting device (51) is configured to sort sperm cells (6) by directing the sperm cell (6) in the sorting zone (50) to one of the outlets (80, 90,...) based on a comparison in a comparison stage of the time dependent impedance data with predefined reference data.