Microfluidic Sperm Segregation and Cryopreservation

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Solution Overview

Problem

Current methods for microsurgical testicular sperm extraction (mTESE) are inefficient in isolating and cryopreserving non-motile sperm from testicular tissue, leading to low sperm recovery rates and limited opportunities for men with non-obstructive azoospermia to father offspring, as existing technologies rely on manual inspection and bulk tissue storage, which are time-consuming and labor-intensive, and unsuitable for non-motile sperm.

Innovation Solution

A microfluidic tissue sample processing system that includes a fluid channel with outlets for segregating materials by size, allowing for the separation and cryopreservation of non-motile sperm cells, enabling efficient segregation, sorting, and concentration of sperm cells, and allowing for multiple aliquot storage and thawing without impairing sperm viability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If manual microscopic inspection is used to identify sperm in testicular tissue, then sperm can be located, but the process is time-consuming and labor-intensive, often taking up to 12 hours

Engineering Contradiction:
Improvesperm identification accuracyVSAvoidtime required for sperm identification
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces manual microscopic inspection with a microfluidic device that uses flow dynamics and size-based separation to automatically identify and isolate sperm cells. The device channels tissue suspension through microchannels where sperm are separated from other cells based on their unique size and shape characteristics, eliminating the need for manual inspection while maintaining identification accuracy.

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

Solution Approach 2:

The microfluidic device enables self-service by allowing the tissue sample to undergo automatic separation and identification processes without human intervention. The flow-based separation system autonomously sorts sperm cells from other tissue components based on their physical properties, and the system automatically captures and stores identified sperm in cryopreservation chambers.

Inventive Principle:
Principle #25Self-service

2Reliability

If bulk tissue storage is used for cryopreservation, then sperm can be preserved, but it is difficult to relocate sperm after thawing and multiple freeze/thaw events are detrimental to sperm viability

Engineering Contradiction:
Improvesperm preservationVSAvoidsperm retrieval difficulty
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent divides the bulk tissue sample into individual cell-level segments using microfluidic flow separation. Each sperm cell is isolated and placed in its own micro-chamber or small group within the device, creating discrete, addressable units rather than a homogeneous bulk sample. This segmentation allows precise retrieval of specific sperm-containing chambers after thawing without affecting other samples.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microfluidic device creates locally optimized cryopreservation conditions in each micro-chamber, allowing different storage conditions or retrieval priorities for different sperm samples. Each chamber can be independently thawed and accessed, enabling selective retrieval based on clinical needs while maintaining overall sample integrity.

Inventive Principle:
Principle #3Local quality

3Productivity

If existing microfluidic devices utilize sperm motility for separation, then motile sperm can be separated from non-motile sperm, but these devices are not suitable for isolating non-motile testicular sperm

Engineering Contradiction:
Improvesperm separation efficiencyVSAvoidapplicability to non-motile sperm
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent changes the separation parameter from sperm motility to physical dimensions (size and shape). The microfluidic device is designed with channel geometries and flow rates that exploit the unique aspect ratio and size of sperm cells compared to other testicular cells. This parameter change allows the same device architecture to effectively separate non-motile testicular sperm based on their distinctive morphological characteristics rather than movement properties.

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

The system significantly increases sperm recovery rates and efficiency, automating the processing steps, reducing human error, and enabling multiple thawing cycles, thus improving IVF outcomes for men with non-obstructive azoospermia.

Implementation Method 1

Flow of the tissue sample in the fluid channel can facilitate segregation of materials in the tissue sample based on size into a plurality of size fractions

Methodology Applied
Scientific EffectSize-based segregation:

Implementation Method 2

a cryopreservation system associated with at least one of the plurality of outlets to freeze the material in the tissue sample associated with the at least one of the plurality of outlets

Methodology Applied
Scientific EffectCryopreservation: Freezing

Data Source

PatentUS11708556B2Tissue sample processing system and associated methods
Publication Date: 2023.07.25 UNIV OF UTAH RES FOUND
  • US11708556B2 patent drawing
  • US11708556B2 patent drawing
  • US11708556B2 patent drawing

AI summary

A tissue sample processing system and associated methods is disclosed and described. The tissue sample processing system (100) can include a microfluidic separating system (110). The microfluidic separating system (110) can include a fluid channel to receive a carrier fluid (104) and a tissue sample (102), and a plurality of outlets. Flow of the carrier fluid (104) and the tissue sample (102) in the fluid channel can facilitate segregation of materials in the tissue sample (102) based on size into a plurality of size fractions, such that each one of the plurality of outlets receives a different size fraction of the materials in the tissue sample. In addition, the sample processing system (100) can comprise a cryopreservation system (120) associated with at least one of the plurality of outlets to freeze the material in the tissue sample (102) associated with the at least one of the plurality of outlets.