Hydrogel Microplate for Individual Platelet Force Measurement

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Solution Overview

Problem

Current methods for measuring mechanical interactions between platelets and fibrin during clot formation are limited, as they primarily assess bulk clot retraction rather than individual platelet behavior, obscuring the underlying mechanical changes that contribute to thrombotic conditions like cardiovascular disease and stroke.

Innovation Solution

A device with a hydrogel layer featuring a pattern of cell interaction regions is used to measure force properties of individual cells, such as platelets, by reducing cell-cell interactions and enabling precise determination of contraction forces through microfluidic systems and high-resolution imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If bulk clot retraction measurement methods are used, then measurement simplicity is maintained, but measurement precision is insufficient to capture individual platelet behavior

Engineering Contradiction:
Improveindividual platelet measurement precisionVSAvoiddevice structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The device segments the measurement process by creating multiple discrete wells, each containing a hydrogel layer with specific mechanical properties. This segmentation allows individual platelet measurements in isolated environments while maintaining overall device manageability through modular architecture.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The hydrogel layers are engineered with locally optimized mechanical properties (different stiffness values) to match specific experimental requirements. Each well's hydrogel can be tailored with distinct acrylamide concentrations to create localized mechanical environments that enhance measurement precision for different platelet populations or conditions.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If individual platelet measurement is implemented, then measurement precision improves, but the number of measurable cells decreases

Engineering Contradiction:
Improveindividual cell measurement capabilityVSAvoidnumber of measurable cells
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The device incorporates multiple wells (e.g., 6-24 wells per device) to increase the total number of individual cell measurements that can be performed simultaneously. Each well acts as an independent measurement chamber, collectively providing high statistical power while maintaining individual cell resolution.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from two-dimensional bulk measurements to three-dimensional hydrogel-based measurements with controlled porosity and mechanical properties. This dimensional change allows cells to be measured in their native-like 3D environment while maintaining optical accessibility for high-resolution imaging.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Ease of operation

If computational methods are simplified, then ease of operation improves, but measurement precision may be compromised

Engineering Contradiction:
Improvedata analysis simplicityVSAvoidforce property determination accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The device replaces complex computational mechanics models with direct optical measurement of hydrogel deformation. By using hydrogels with known mechanical properties and measuring their physical displacement under cell force, the system converts complex biomechanical calculations into straightforward optical readings that are easier to analyze while maintaining precision.

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

Solution Approach 2:

The hydrogel layers are designed with specific mechanical parameters (stiffness, elasticity) that optimize the relationship between cell force and observable deformation. By carefully selecting hydrogel composition and crosslinking density, the device creates a linear, predictable relationship between applied force and displacement, simplifying data analysis while preserving measurement accuracy.

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 device allows for the individual measurement of contraction forces of platelets, increasing the number of measurable cells while reducing computational complexity and enabling the use of small patient samples, providing insights into the mechanical properties of clots and their role in thrombotic conditions.

Implementation Method 1

a hydrogel layer disposed in the at least one well, the hydrogel layer including a hydrogel

Methodology Applied
Scientific EffectElasticity: Elasticity

Implementation Method 2

polymerizing the hydrogel; and discarding the coverslip

Methodology Applied
Scientific EffectPolymerization: Photopolymerisation

Data Source

PatentUS10168341B2Devices for determining cell force properties and methods of manufacturing the devices
Publication Date: 2019.01.01 CHILDRENS HEALTHCARE OF ATLANTA INC
  • US10168341B2 patent drawing
  • US10168341B2 patent drawing
  • US10168341B2 patent drawing

AI summary

A device may be configured to allow individual measuring of at least one property of at least one cell, such as measuring a contraction force of a platelet. The device may include a plurality of wells. Each well may include a hydrogel layer, the hydrogel layer including a hydrogel having a top surface that includes a pattern of cell interaction regions. The wells may differ in stiffness properties of the hydrogel and/or biochemical conditions. Each cell interaction region may include a group of at least two cell interaction sites. The spacing between each cell interaction region may be greater than a spacing between the at least two cell interaction sites of each cell interaction region. In this way, cell-cell interactions may be reduced and thereby increasing number of individual cells capable of being measured.