Flow Cytometer Nozzle Design for Sperm Cell Resolution

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Solution Overview

Problem

Conventional flow cytometers face issues with reduced resolution in separating particles or cells, particularly sperm cells, due to disruptions in laminar flow, turbulent fluid movement, non-straight cell source conduits, non-replaceable injector components, connector-induced contamination, rough interior surfaces, large nozzle cross-sections, and difficulties in accurately measuring DNA content with high coefficients of variation.

Innovation Solution

The enhanced flow cytometer design addresses these issues by introducing fluids at a controlled angle to maintain laminar flow, using a symmetrical velocity cell source fluid stream, providing a replaceable particle injector, eliminating connectors, smoothing interior surfaces, and employing a single-piece nozzle with reduced cross-sectional area to enhance resolution and viability of sperm cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional flow cytometers are used to separate sperm cells, then separation can be achieved, but resolution is reduced due to disruptions in laminar flow and turbulent fluid movement

Engineering Contradiction:
ImproveresolutionVSAvoidlaminar flow
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The device segments the fluid stream into discrete droplets containing individual sperm cells, with each droplet forming a isolated unit. This segmentation prevents turbulent interactions between cells while maintaining laminar flow conditions, thereby improving resolution during separation based on DNA content

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The device changes the physical parameters of fluid flow by controlling droplet formation frequency, size, and spacing. By optimizing these parameters, the system maintains stable laminar flow conditions that enhance measurement precision of sperm cell DNA content while preventing turbulent disruptions

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If non-straight cell source conduits are used, then device assembly is simplified, but turbulent fluid movement increases reducing separation quality

Engineering Contradiction:
Improvedevice assemblyVSAvoidseparation quality
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The cell source conduit is designed with smooth curved transitions rather than sharp angles or bends. This curvature minimizes flow disturbances and prevents turbulent movement while maintaining ease of assembly, thereby preserving separation quality without compromising manufacturing simplicity

Inventive Principle:
Principle #14Spheroidality (Curvature)

3Ease of manufacture

If connectors are included in the cell source conduit, then modular assembly is enabled, but connector-induced contamination occurs

Engineering Contradiction:
Improvemodular assemblyVSAvoidcontamination
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The design extracts and eliminates connectors from the cell source conduit system. By removing this potential source of contamination, the system achieves continuous sterile flow paths while maintaining modular assembly capabilities through alternative connection methods that do not compromise fluid integrity

Inventive Principle:
Principle #2Taking out (Extraction)

4Ease of manufacture

If rough interior surfaces are present in conduits, then manufacturing is easier, but particle aggregation and flow disruption occur

Engineering Contradiction:
ImprovemanufacturingVSAvoidflow uniformity
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The interior surface parameters of the conduits are optimized to achieve sufficient smoothness without requiring excessive manufacturing complexity. By controlling surface roughness within specific ranges, the system prevents particle aggregation and flow disruption while maintaining practical manufacturability

Inventive Principle:
Principle #35Parameter changes

5Productivity

If large nozzle cross-sections are used, then fluid flow capacity is increased, but resolution between sperm cell populations is reduced

Engineering Contradiction:
Improvefluid flow capacityVSAvoidresolution
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The nozzle is designed with non-uniform cross-sectional characteristics, where the flow path provides sufficient capacity while the separation region maintains optimized dimensions for high resolution. This local quality variation allows the system to achieve both high fluid flow capacity and excellent separation resolution simultaneously

Inventive Principle:
Principle #3Local quality

6Device complexity

If non-replaceable injector components are used, then device structure is simplified, but maintenance and cleaning become difficult

Engineering Contradiction:
Improvedevice structureVSAvoidmaintenance and cleaning
Core Design Contradiction:
Device complexityVSEase of repair

Solution Approach 1:

The injector components are segmented into replaceable modules that can be individually accessed, removed, and cleaned or replaced as needed. This segmentation maintains relatively simple overall device structure while enabling easy maintenance and cleaning of critical flow paths without requiring disassembly of the entire system

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 design significantly increases the resolution and homogeneity of separated sperm cell populations, achieving purities greater than conventional methods, with improved viability and reduced production costs, and allows for easier maintenance and operation of the flow cytometer.

Implementation Method 1

introducing fluids at a controlled angle to maintain laminar flow

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Implementation Method 2

pressure waves may be established within the nozzle (2) and transmitted to the fluid stream (3) exiting the nozzle (2) at nozzle orifice (5)

Methodology Applied
Scientific EffectPressure waves: Pressure Gradient

Implementation Method 3

irradiation source such as a laser (12) generating an irradiation beam to which the particle or cell (16) can be responsive

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS7855078B2High resolution flow cytometer
Publication Date: 2010.12.21 XY INC
  • US7855078B2 patent drawing
  • US7855078B2 patent drawing
  • US7855078B2 patent drawing

AI summary

High resolution particle differentiation process and separation system that provides enhanced resolution of particles based upon selected particle characteristics. In particular, the system may include an enhanced resolution flow cytometer. In an embodiment, the invention can include at least one fluid source conduit (24) that introduces 0 fluid source stream (24) into an enhanced resolution nozzle (25) at an angle that enhances particle resolution by the cell sensing system (13).