Optoelectronic Tweezers for Non-Damaging Cell Sorting

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Solution Overview

Problem

Current cell sorting technologies are labor-intensive, often damage cells due to mechanical forces or chemical exposures, and are limited in their ability to sort cells based on viability, chromosome number, and genetic mutations, while also being inefficient in throughput and specificity.

Innovation Solution

The use of optical pattern-driven light-induced dielectrophoresis (DEP) to create virtual electrodes that can be manipulated in location, time, and field intensity, allowing for the separation and extraction of cells based on their dielectric properties, enabling high-throughput sorting and retrieval of viable cells and embryos.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cell sorting methods (flow cytometry, mechanical sorting) are used, then cells can be sorted based on viability and other characteristics, but the cells are damaged due to mechanical forces or chemical exposures

Engineering Contradiction:
Improvecell viabilityVSAvoidmechanical damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces mechanical sorting systems with an optical field-based system. Optical patterns are projected onto a photoconductive surface to create dielectrophoretic fields that selectively move cells based on their dielectric properties. This substitution eliminates mechanical contact and force-based separation, thereby preventing mechanical damage to cells while maintaining sorting capability.

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

Solution Approach 2:

The patent introduces an optical field as an intermediary between the sorting system and cells. The optical pattern drives dielectrophoretic forces that indirectly manipulate cells without direct mechanical contact. This intermediary approach allows cell separation based on dielectric properties while avoiding harmful mechanical interactions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If conventional sorting technologies are used, then cells can be separated into groups, but the throughput is low and the process is labor-intensive

Engineering Contradiction:
Improvesorting throughputVSAvoidprocessing time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent implements continuous cell sorting through automated optical pattern projection and dielectrophoretic manipulation. The system continuously processes cell samples without interruption, eliminating the batch processing limitations of conventional methods. This continuous operation significantly increases throughput and reduces processing time while maintaining high sorting accuracy.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent uses optical patterns as copies or representations of sorting criteria. By projecting optical patterns that encode sorting information, the system can rapidly identify and separate cells based on their dielectric properties without requiring manual intervention or time-consuming conventional sorting procedures.

Inventive Principle:
Principle #26Copying

3Reliability

If existing sorting modalities are used, then cells can be sorted into viable and non-viable groups, but the same cells cannot be used for fertilization due to lethality or genetic damage risk

Engineering Contradiction:
Improveviability assessment accuracyVSAvoidgenetic damage risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces harmful mechanical and chemical sorting methods with optical field-based dielectrophoresis. This substitution eliminates the lethality and genetic damage risks associated with conventional modalities while maintaining accurate viability assessment through dielectric property measurement. The non-contact optical approach ensures cells remain suitable for subsequent fertilization procedures.

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

4Measurement precision

If complex sorting systems are used to achieve high specificity, then cells can be sorted based on multiple characteristics, but the device complexity increases

Engineering Contradiction:
Improvesorting specificityVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent creates a universal sorting platform where a single optical pattern projection system can sort cells based on multiple characteristics by varying the optical pattern parameters. This multi-functional approach eliminates the need for multiple specialized sorting devices, thereby reducing overall system complexity while maintaining high sorting specificity across different cell types and characteristics.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 method allows for non-invasive, accurate discrimination and selection of viable cells and embryos, improving the success rate of artificial fertilization techniques by sorting cells based on viability and health, and enabling the exclusion of defective gametes, thereby enhancing implantation success rates.

Implementation Method 1

optical pattern-driven light induced dielectrophoresis (DEP) to create virtual electrodes

Methodology Applied
Scientific EffectPhotoconductivity: Photoconductivity

Implementation Method 2

light induced dielectrophoresis (DEP) to create virtual electrodes that can be manipulated in location, time, and field intensity, allowing for the separation and extraction of cells based on their dielectric properties

Methodology Applied
Scientific EffectDielectrophoresis:

Data Source

PatentEP2414539B1Apparatus and method for sorting cells and other biological particulates
Publication Date: 2020.12.16 RGT UNIV OF CALIFORNIA
  • EP2414539B1 patent drawingFigure 1
  • EP2414539B1 patent drawingFigure 2
  • EP2414539B1 patent drawingFigure 3

AI summary

An optical pattern-driven light induced dielectrophoresis (DEP) apparatus and separation methods are described which provide for the manipulation of particles or cells and selection based on traits correlated with the DEP response. Embodiments of the apparatus use DEP electric field patterns in combination with microfluidic laminar flows to measure response, separate, segregate and extract particles from heterogeneous mixtures according to the relative response of the particles to one or more DEP fields without damaging living cells. The preferred OET-DEP devices generally comprise a planar liquid-filled structure having one or more portions which are photoconductive to convert incoming light to a localized virtual electrode with a DEP electric field gradient of selected intensity along with input and a plurality of output fluidic channels. The light patterns are dynamically generated to provide a number of manipulation structures that can manipulate single particles and cells or groups of particles/cells. The methods are particularly suited for selecting and extracting the best sperm and embryo candidates based on fitness for use with existing artificial reproduction procedures and excluding defective or non-viable gametes.