Separation Well Microplate Embedding for Brain Organoid Hydrogels

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Solution Overview

Problem

Automating the process of embedding embryoid bodies in hydrogels for culturing brain organoids is challenging due to the difficulty in handling the delicate nature of embryoid bodies and the risk of premature hydrogel polymerization when excessive media is used.

Innovation Solution

The use of a separation well microplate with automated methods for embedding embryoid bodies in hydrogels, involving steps such as adding embryoid bodies to a primary well, removing media, adding liquid hydrogel, and suspending the encapsulated embryoid bodies in a secondary well, with controlled tilting and temperature adjustments to ensure efficient encapsulation and transportation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If manual preparation of dimpled parafilm substrate is used for generating Matrigel droplets, then the embryoid bodies can be embedded in hydrogel, but the process is labor-intensive and difficult to automate

Engineering Contradiction:

Improveautomation capabilityVSAvoidmanual preparation requirement

Core Design Contradiction:

Ease of manufactureVSDevice complexity

Solution Approach 1:

The microplate is divided into separate wells: a first well for holding embryoid bodies and a second well for generating and transferring hydrogel droplets. This segmentation allows automated liquid handling to dispense hydrogel into the second well without needing to manually prepare substrates, enabling full automation while maintaining the embedding function.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The second well acts as an intermediary chamber where hydrogel droplets are generated and mature before being transferred to the first well for embedding. This intermediary step eliminates the need for manual substrate preparation by using automated liquid handling to create and transfer the hydrogel-containing droplets.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If excessive media is used to transport embryoid bodies, then the embryoid bodies can be moved efficiently, but the hydrogel may liquify and fail to encapsulate properly

Engineering Contradiction:

Improvetransport efficiencyVSAvoidhydrogel encapsulation stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The transport and embedding processes are segmented into separate steps in different wells. Embryoid bodies are moved to the second well where hydrogel droplets are formed, then the hydrogel is transferred back to the first well with the embryoid bodies. This segmentation allows controlled media usage at each step, preventing hydrogel liquification while maintaining transport efficiency.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The hydrogel is kept in a continuous state of being in the appropriate well with appropriate media volume. By forming hydrogel droplets in the second well and transferring them with embryoid bodies, the system maintains continuous control over media-hydrogel interactions, preventing premature polymerization or liquification throughout the process.

Inventive Principle:

Principle #20Continuity of useful action

3Extent of automation

If automated liquid handling is used to dispense hydrogel, then the process can be automated, but precise control of hydrogel volume and positioning is required

Engineering Contradiction:

Improveembedding automationVSAvoidhydrogel volume and positioning control

Core Design Contradiction:

Extent of automationVSManufacturing precision

Solution Approach 1:

The automated embedding process is segmented into discrete steps: dispensing hydrogel into the second well, allowing droplet formation, and transferring the droplet to the first well. Each step uses automated liquid handling with precise volume control, eliminating the need for manual positioning while maintaining accuracy through programmable liquid handling parameters.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The system uses automated liquid handling to self-regulate hydrogel volume and positioning. The liquid handler automatically dispenses precise volumes of hydrogel into the second well, and the droplet transfer process automatically positions the hydrogel relative to the embryoid bodies, reducing the need for manual intervention and improving precision consistency.

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 allows for delicate and efficient embedding of embryoid bodies in hydrogels, facilitating automated culturing and screening of brain organoids, enhancing the reliability and scalability of the process.

Implementation Method 1

adding a liquid hydrogel to encapsulate the embryoid body

Methodology Applied

Scientific EffectAdhesion: Adhesive

Implementation Method 2

incubating the plate over a first period of time to solidify the hydrogel encapsulating the embryoid body

Methodology Applied

Scientific EffectPolymerization: Photopolymerisation

Data Source

PatentUS20260015575A1Methods of automated embryoid body embedding in hydrogel using separation well microplate

Publication Date: 2026.01.15 MOLECULAR DEVICES AUSTRIA GMBH

AI summary

Methods are provided for automated embedding of embryoid bodies in a hydrogel, media exchange, culturing organoids, and monitoring the development of organoids such as brain organoids. Methods for automated testing of compounds and toxicity effects are also provided.