Coherent Grid Diffraction for High-Resolution Cell Motility Analysis

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Solution Overview

Problem

Current micro- and nanosensor technologies are inadequate for measuring cell motility with high temporal resolution and flexibility, particularly for investigating large numbers of biological cells, which is crucial for cancer research and diagnostics.

Innovation Solution

A method and device using a grid illuminated by light with a coherence length greater than the grid element spacing, allowing phase objects to move freely and generating a diffraction image that is analyzed for information on cell motility, shape, refractive index, and other characteristics with high temporal resolution without the need for chemical bonding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If elastic elements are used to measure cell force, then force measurement capability is achieved, but device complexity and manufacturing cost increase

Engineering Contradiction:
Improveforce measurement capabilityVSAvoidstructure with elastic elements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical elastic element system with an optical measurement system. Instead of using physical elastic elements that deflect under cell force, the invention uses a grid with illuminated elements and detects phase changes in light passing through or reflecting off the grid. This substitution of mechanical measurement with optical measurement achieves force measurement capability while eliminating the need for complex elastic element structures.

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

2Measurement precision

If two grids with identifying material are used for analyte detection, then analyte detection capability is achieved, but temporal resolution for measuring transient behavior deteriorates

Engineering Contradiction:
Improveanalyte detection capabilityVSAvoidtemporal resolution
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts the identifying material from the grid structure itself, allowing the grid elements to serve dual purposes: both as structural components for diffraction and as carriers of identifying material for analyte detection. This integration eliminates the need for separate identification layers that would slow down transient measurements, thereby maintaining high temporal resolution while achieving analyte detection capability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The grid elements are designed to perform multiple functions simultaneously: they provide the structural framework for optical diffraction, serve as the measurement medium for phase changes, and can incorporate identifying material for analyte detection. This multi-functionality allows the system to achieve both analyte detection and high temporal resolution for transient behavior without requiring separate dedicated components.

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

3Measurement precision

If image analysis of movement sequences is used for cell motility assessment, then cell motility measurement is achieved, but productivity and cost efficiency deteriorate when observing large numbers of cells

Engineering Contradiction:
Improvecell motility measurementVSAvoidobservation speed for large cell populations
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent merges multiple measurement functions into a single optical detection step. Instead of requiring separate image capture, processing, and analysis steps for each cell in a sequence, the system uses a grid-based diffraction approach where phase changes caused by cell movement are directly detected and converted into motility measurements. This consolidation of measurement functions enables simultaneous assessment of large cell populations, dramatically improving productivity while maintaining measurement precision.

Inventive Principle:
Principle #5Merging (Combining)

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 real-time investigation of cell motility and other biological processes with high sensitivity and accuracy, allowing for the observation of large populations of cells and the assessment of pharmaceutical effects, while reducing costs and complexity.

Implementation Method 1

a diffraction image of the illuminating light scattered on the grid is generated

Methodology Applied
Scientific EffectDiffraction: Diffraction

Data Source

PatentUS10295463B2Device and method for investigating one or a plurality of phase objects
Publication Date: 2019.05.21 LUDWIG MAXIMILIANS UNIV MUNCHEN
  • US10295463B2 patent drawing
  • US10295463B2 patent drawing
  • US10295463B2 patent drawing

AI summary

A method for investigating one or a plurality of phase objects is described, in which a grid made up of elements is used, which is illuminated with light of a light source, the coherence length of which is larger than the average spacing of adjacent elements of the grid. A diffraction image of the illuminating light scattered on the grid is generated, whereby the one or the plurality of phase objects are placed in the light path between the light source and the grid and/or in the light path of the illuminating light scattered on the grid. At least a part of the diffraction image is detected by an optical sensor directly or after interaction with further optical components and converted into a signal. The signal is analyzed further in order to ascertain information relating to the one or plurality of phase objects therefrom. A corresponding device is likewise described.