Hanging Drop Array Plate for Stable 3D Cell Culture
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Solution Overview
Problem
Current methods for creating and handling three-dimensional (3D) cell cultures, such as spheroids, are labor-intensive, not scalable, and not compatible with high-throughput screening, due to issues like drop perturbation, media exchange difficulties, and equipment requirements.
Innovation Solution
A system comprising an array plate with holes and plateaus that stabilizes hanging drops, allowing for efficient formation, maintenance, and analysis of spheroids, compatible with high-throughput screening and automated instruments, using a configuration that includes a reservoir plate and a lid to maintain humidity and facilitate liquid transfer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional hanging drop method on Petri dish lid is used, then spheroid formation is achieved, but drops are susceptible to perturbation, falling, spreading, and merging
Solution Approach 1:
The invention divides the culture system into modular components: a base plate with recesses for individual drop containment, a separate lid for sealing, and optional reservoir plates for media storage. This segmentation allows each drop to be isolated and stabilized in its own recess, preventing merging while enabling standardized handling and automation compatibility.
Solution Approach 2:
The recesses in the base plate act as intermediary structures between the hanging drops and the plate surface. These recesses provide physical support and confinement for the drops, stabilizing their position and preventing spreading or merging, while maintaining the hanging drop configuration needed for spheroid formation.
2Ease of operation
If conventional hanging drop method is used, then spheroid culture is achieved, but media exchange is difficult without damaging spheroids
Solution Approach 1:
The culture system separates media storage (in reservoir plates) from spheroid culture (in the base plate with recesses). This segmentation allows media to be exchanged in the reservoir plates without direct contact with spheroids, while controlled delivery mechanisms enable gentle media replacement in each recess, preventing spheroid damage.
Solution Approach 2:
Media is pre-loaded into reservoir plates before the culture experiment begins. This preliminary action allows for easy media exchange by simply replacing reservoir plates or dispensing fresh media from reservoirs, without needing to manually handle or disturb the spheroids in the base plate.
3Productivity
If traditional hanging drop method is used, then spheroid formation is achieved, but the process is labor-intensive and not scalable
Solution Approach 1:
The base plate with recesses serves multiple functions: it contains and stabilizes hanging drops, provides a standardized format compatible with automated liquid handlers and plate readers, and interfaces with reservoir plates for media management. This multi-functionality enables the system to scale from manual to automated operations without requiring specialized equipment.
Solution Approach 2:
The invention standardizes the culture format by defining specific recess geometries and plate dimensions that match standard automation equipment parameters. This parameter standardization allows the system to be integrated with high-throughput screening instruments, enabling scalable production from dozens to thousands of spheroids simultaneously.
4Ease of manufacture
If microwell structures and planar micropatterns are used, then spheroid production is achieved, but specialized and expensive equipment is required
Solution Approach 1:
The base plate with recesses can be manufactured as a disposable or reusable component using simple molding techniques, eliminating the need for expensive specialized microwell fabrication equipment. The recesses provide sufficient mechanical support and drop containment without requiring complex micropatterned structures, reducing manufacturing costs while maintaining spheroid uniformity.
5Productivity
If microwell structures with multiple spheroids in one compartment are used, then spheroid culture is achieved, but individual monitoring and treatment is not possible
Solution Approach 1:
The base plate divides the culture system into numerous small, isolated recesses, each containing a single hanging drop and spheroid. This segmentation enables individual monitoring and treatment of each spheroid while maintaining high throughput, as each recess can be independently accessed by automated liquid handlers and observed by plate readers or microscopes.
Solution Approach 2:
The invention transitions from planar micropatterns to a three-dimensional recess structure that extends below the plate surface. This dimensional change provides physical isolation for each spheroid while maintaining a compact, high-density array format that supports both individual analysis and high-throughput screening.
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 the formation of uniformly sized spheroids in a high-throughput manner, allowing for long-term culture and accurate drug testing, with reduced labor and costs, while maintaining stable osmolality and humidity, and being compatible with existing screening instruments.
Implementation Method 1
Traditional spheroid formation involves cultivation of suspended cells in hanging drops on the underside of a Petri dish lid
Implementation Method 2
One way to create 3D cell culture models is through the formation of spheroids, or 3D clusters or aggregates of cells
Data Source
AI summary
The present disclosure relates general to devices, systems, and methods of using such devices in creating and handling hanging drops of fluid. The present disclosure also relates to cell culture devices, methods and/or systems of using such devices as well as the use of cell culture devices, for example, for research and high throughput screening.