Hydrogel Spheroid Manufacturing via Liquid Bath Dipping

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Solution Overview

Problem

Existing methods for manufacturing spheroids, such as aggregation and hanging-drop methods, face challenges in achieving uniformity and are prone to errors due to their complexity and difficulty in processing.

Innovation Solution

A method involving the use of a liquid bath composition for dipping hydrogel droplets, where hydrogel is prepared with cells or drugs, and extracellular matrix materials, and discharged through a nozzle to form a spheroid, which is then cured and separated to maintain a uniform spherical shape, allowing for reproducible and high-throughput production of spheroids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If the aggregation method is used to manufacture spheroids, then the process is simple, but the uniformity of spheroid size is poor

Engineering Contradiction:

Improveprocess simplicityVSAvoidspheroid size uniformity

Core Design Contradiction:

Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent introduces a liquid bath as an intermediary medium between the hydrogel droplet and the substrate. The liquid bath composition (containing surfactant and thickener) mediates the interaction, allowing the droplet to be dipped and separated while maintaining spherical shape and uniform size. This resolves the contradiction by providing a simple dipping process that achieves high uniformity through the mediating liquid environment.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical parameters of the liquid environment by introducing a liquid bath with specific composition (surfactant concentration 0.1-10% w/v, thickener concentration 0.01-1% w/v). These parameter changes enable the hydrogel droplet to maintain spherical shape during processing, achieving both simplicity and uniformity in spheroid manufacturing.

Inventive Principle:

Principle #35Parameter changes

2Manufacturing precision

If the hanging-drop method is used to manufacture uniform spheroids, then the uniformity is improved, but the processing difficulty and error rate increase

Engineering Contradiction:

Improvespheroid size uniformityVSAvoidprocessing difficulty

Core Design Contradiction:

Manufacturing precisionVSEase of operation

Solution Approach 1:

Instead of hanging the droplet from above (hanging-drop method), the patent inverts the approach by dipping the droplet into a liquid bath from below. This inversion simplifies the operation while maintaining uniformity, as the liquid bath supports the droplet and enables easy separation without the complexity of hanging-drop positioning and manipulation.

Inventive Principle:

Principle #13The other way round (Inversion)

3Ease of manufacture

If conventional methods are used, then manual handling is required, but handling errors increase and automation is difficult

Engineering Contradiction:

Improvemanual handling capabilityVSAvoidhandling error rate

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The liquid bath system enables the hydrogel droplet to self-maintain its spherical shape through the dipping and separation process. The surfactant and thickener in the liquid bath create conditions where the droplet naturally forms and maintains uniform spheres without requiring precise manual manipulation, thereby reducing handling errors and enabling automation.

Inventive Principle:

Principle #25Self-service

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 enables the efficient and uniform production of spheroids with a 3D spherical shape, overcoming the limitations of conventional methods by minimizing handling errors and allowing for automated high-throughput screening, and can be applied in 3D cell culture and bioprinting applications.

Implementation Method 1

a composition for a liquid bath for dipping a droplet

Methodology Applied

Scientific EffectSurface tension: Surface Tension

Implementation Method 2

dipping the formed hydrogel droplet in the composition for a liquid bath for dipping a droplet

Methodology Applied

Scientific EffectBuoyancy: Archimedes' Principle (Buoyancy)

Data Source

PatentUS11154506B2Method of manufacturing spheroid having uniform size

Publication Date: 2021.10.26 PENSEES INC

AI summary

The present invention relates to a method of manufacturing a spheroid using a composition for a liquid bath for dipping a hydrogel droplet and to a spheroid manufactured thereby. The method of manufacturing the spheroid according to the present invention is capable of successfully forming a spheroid having a 3D spherical shape that is difficult to implement on a planar substrate and also of realizing a spheroid having a uniform size, and thus can be effectively used as a technique for obtaining a spheroid having a 3D spherical shape and a uniform size in the field of cell culture.