Fluorescent Molecular Patterns for High-Throughput Cell Force Phenotyping

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Solution Overview

Problem

Current methods for studying cell contractile forces, such as traction force microscopy and atomic force microscopy, are not suitable for high-throughput analysis of mixed cell populations with rare phenotypes, requiring high-resolution imaging and precise focusing, which limits their compatibility for screening large numbers of drugs or samples.

Innovation Solution

A system using an optically transparent substrate with a soft material (3 kPa to 100 kPa Young's modulus) and fluorophore-conjugated molecular patterns, allowing for high-throughput analysis of cell forces by measuring dimensional changes of the patterns with an imaging device and computing device, enabling identification and quantification of force phenotypes in cell populations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If high-resolution imaging and precise focusing are used to measure cell forces, then measurement precision is improved, but device complexity and ease of operation deteriorate

Engineering Contradiction:
Improvemeasurement precisionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex optical measurement systems with a simplified mechanical approach using flexible substrates and fluorescent molecular patterns. Instead of using high-resolution imaging to directly measure cell forces, the system uses fluorescently labeled molecules that physically move or change conformation in response to cellular forces, converting mechanical force measurements into optical signal changes that can be detected with simpler, lower-resolution imaging systems.

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

Solution Approach 2:

The patent introduces fluorescent molecular patterns as intermediary elements between the cells and the imaging system. These molecular patterns act as mediators that translate cellular mechanical forces into detectable optical signals. The fluorescent molecules serve as a bridge that converts complex mechanical interactions into simple fluorescence intensity or position changes, eliminating the need for complex optical focusing and high-resolution imaging.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If high-resolution imaging and precise focusing are used to measure cell forces, then measurement precision is improved, but productivity deteriorates

Engineering Contradiction:
Improvemeasurement precisionVSAvoidproductivity
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent replaces time-consuming high-resolution imaging procedures with a rapid fluorescence-based detection method. The fluorescent molecular patterns provide direct optical readouts of cellular forces that can be captured with standard fluorescence microscopy, dramatically reducing measurement time and enabling high-throughput screening of multiple cell samples simultaneously.

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

Solution Approach 2:

The patent changes the measurement parameter from requiring precise spatial resolution to measuring fluorescence intensity or position changes. This parameter transformation allows the same force measurement information to be obtained with lower imaging resolution, enabling faster acquisition times and higher productivity while maintaining measurement precision through the sensitive fluorescent signal response.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If conventional force measurement methods are used, then measurement precision is improved, but adaptability deteriorates

Engineering Contradiction:
Improvemeasurement precisionVSAvoidadaptability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal measurement platform using fluorescent molecular patterns that can be applied to various cell types and force measurement applications. The same basic system architecture—flexible substrate with fluorescent molecular patterns—can measure forces from different cell types (cancer cells, stem cells, immune cells) and can be adapted to study various biological processes, providing both precision and broad adaptability.

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

Solution Approach 2:

The patent enables adaptability by changing the measurable parameters through different fluorescent molecular pattern designs. By varying the type, arrangement, and properties of the fluorescent molecules, the system can be adapted to measure different force magnitudes, directions, and temporal characteristics across diverse cell types and experimental conditions while maintaining measurement precision.

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

Enables efficient and high-throughput measurement of cell forces, facilitating the analysis of drug effects on protein targets and cellular structures, and allowing for the identification of specific cell sub-populations based on force phenotypes, improving the screening process for therapeutic applications.

Implementation Method 1

The system includes at least one light source configured to excite the fluorophore-conjugated patterns... The system includes an imaging device that is configured to capture fluorescent light emitted from the fluorophore-conjugated patterns

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa

Methodology Applied
Scientific EffectElasticity: Elasticity

Data Source

PatentUS11592438B2Device and method for force phenotyping of cells for high-throughput screening and analysis
Publication Date: 2023.02.28 RGT UNIV OF CALIFORNIA
  • US11592438B2 patent drawing
  • US11592438B2 patent drawing
  • US11592438B2 patent drawing

AI summary

A system for assaying forces applied by cells includes an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa. An array of molecular patterns is disposed on a surface of the optically transparent substrate, the molecular patterns include fluorophore-conjugated patterns adherent to cells. The system includes at least one light source configured to excite the fluorophore-conjugated patterns and an imaging device configured to capture fluorescent light emitted from the fluorophore-conjugated patterns. Dimensional changes in the size of the patterns are used to determine contractile forces imparted by cells located on the patterns.