Single-Cell Metal Profiling for Male Infertility Diagnosis

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Solution Overview

Problem

Current methods for diagnosing male infertility are inadequate, as they primarily focus on physical and biochemical parameters, leading to a high diagnostic failure rate and misclassification of idiopathic infertility cases, with a need for a more effective assessment of sperm functional quality.

Innovation Solution

The use of single-cell inductively coupled plasma mass spectrometry (sc-ICP-MS) to detect the concentration and dynamic or kinetic parameters of specific metals in spermatozoa, such as sodium, potassium, calcium, magnesium, zinc, iron, copper, and others, to differentiate between fertile and infertile spermatozoa by analyzing metal levels outside predetermined ranges or abnormal signal spikes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional semen analysis and physical-based sperm parameters are used for diagnosis, then the diagnostic process is simple and easy to perform, but the diagnostic accuracy is low with a failure rate of 30% to 70%

Engineering Contradiction:
Improvediagnostic accuracyVSAvoiddiagnostic method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent transitions from conventional physical and biochemical parameters to elemental composition parameters (metal concentrations) for sperm characterization. By measuring metal concentrations such as zinc, calcium, magnesium, and other trace elements in single sperm cells using sc-ICP-MS, the diagnostic method achieves higher accuracy in identifying fertile versus infertile sperm, resolving the limitation of conventional methods that fail to detect functional quality differences.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If single-cell inductively coupled plasma mass spectrometry (sc-ICP-MS) is used to detect metal concentrations in spermatozoa, then the diagnostic accuracy improves significantly, but the device complexity and measurement difficulty increase

Engineering Contradiction:
Improvemetal concentration detection accuracyVSAvoidsingle-cell metal detection difficulty
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent replaces conventional mechanical and optical detection methods with inductively coupled plasma mass spectrometry (ICP-MS) technology. This substitution enables precise measurement of metal concentrations at the single-cell level by ionizing the sample in a plasma environment and detecting metal isotopes through mass spectrometry, achieving attogram-level sensitivity for elements like zinc, calcium, and trace metals that are critical for sperm function.

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

Solution Approach 2:

The patent introduces an intermediary processing system that includes sample introduction devices, nebulization systems, and plasma generation components. These intermediary systems prepare single sperm cells for ICP-MS analysis by converting them into a form suitable for plasma ionization, thereby enabling the detection of intracellular metal concentrations without direct manipulation of the single cells during measurement.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If traditional biochemical component analysis of seminal plasma is performed, then the analysis is relatively simple, but it cannot identify functional quality differences in sperm leading to idiopathic infertility misclassification

Engineering Contradiction:
Improveinfertility diagnosis reliabilityVSAvoidanalysis method complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the analysis from population-level seminal plasma measurement to single-sperm-cell level analysis. By analyzing metal concentrations in individual sperm cells rather than averaging across the entire seminal plasma sample, the method can identify functional heterogeneity within the sperm population and detect subtle differences in cellular metal content that correlate with fertilization capability, thereby improving diagnostic reliability for idiopathic infertility cases.

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

This approach allows for precise identification of infertile spermatozoa by quantifying metal concentrations and kinetic parameters, improving diagnostic accuracy and enabling targeted infertility therapies.

Implementation Method 1

single cell inductively coupled plasma mass spectrometry (sc-ICP-MS)

Methodology Applied
Scientific EffectInductively coupled plasma: Electromagnetic Induction

Implementation Method 2

single cell inductively coupled plasma mass spectrometry (sc-ICP-MS)

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS20240230630A1Uses and methods for elementomic characterization analysis in diagnosis and prognosis of medical diseases and conditions
Publication Date: 2024.07.11 SHANGHAI TECH UNIV
  • US20240230630A1 patent drawing
  • US20240230630A1 patent drawing
  • US20240230630A1 patent drawing

AI summary

The present application provides a method for detecting infertile spermatozoa in a sample, the method comprising: detecting a concentration of at least one metal in the sample that falls outside of a predetermined range using single cell inductively coupled plasma mass spectrometry (sc-ICP-MS). It also provides a method for detecting infertile spermatozoa in a sample, which comprising: detecting a dynamic or kinetic parameter of a signal spike of at least one metal selected from the group of several metallic elements by sc-ICP-MS.