Microplate Well Geometry for Spheroid Centering and Assay Sensitivity
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Solution Overview
Problem
Current spheroid microplates are laborious and prone to failure due to manual transfer processes, lack centering during metabolic analysis, and have large microchamber volumes that reduce assay sensitivity, making them unsuitable for sophisticated applications like organ-on-chip assays.
Innovation Solution
A microplate design with a central indentation and concentric lips that facilitates in-situ generation and centering of three-dimensional cellular materials, reducing microchamber volume and enabling efficient metabolic analysis without manual transfer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If manual transfer process is used to move spheroids from culture plate to metabolic analysis plate, then spheroids can be analyzed metabolically, but the process is laborious, time-consuming, and prone to failure due to loss or damage of spheroids
Solution Approach 1:
The patent combines the culture plate and metabolic analysis plate into a single integrated plate design. The well geometry features a broad base for culture that transitions to a narrow neck for analysis, eliminating the need for manual transfer between separate plates while maintaining both culture and metabolic analysis functions
Solution Approach 2:
The plate is designed to serve multiple functions: it can be used for both spheroid culture and metabolic analysis without requiring separate specialized plates. The universal design allows the same plate to perform both functions effectively, reducing workflow complexity and time
2Measurement precision
If current spheroid microplates are used for metabolic analysis, then analysis can be performed, but spheroids do not stay centered during mixing cycles leading to erratic measurements or complete loss of signal
Solution Approach 1:
The well geometry employs asymmetric design with a broad base that transitions to a narrow neck. This asymmetric shape creates a natural centering effect where the spheroid is funneled into a consistent position at the narrow end, ensuring stable positioning during mixing cycles and improving measurement precision
3Measurement precision
If current spheroid microplates with large microchamber volume are used, then metabolic analysis can be performed, but the large volume reduces sensitivity of the metabolic assay
Solution Approach 1:
The patent changes the geometric parameters of the well, specifically reducing the microchamber volume at the analysis end by designing a narrow neck portion. This parameter change increases the concentration of metabolites in the smaller volume, thereby improving assay sensitivity while still accommodating the spheroid
4Measurement precision
If current spheroid microplates are used, then metabolic analysis is possible, but larger spheroids with diameter of about 500 micrometers are required to generate measurable signal
Solution Approach 1:
By changing the microchamber volume parameter to a smaller value through the narrow neck design, the patent enables detection of metabolic signals from smaller spheroids (100-250 micrometers) that would previously be below the detection threshold in larger volume chambers
5Ease of operation
If current spheroid microplates with broad base are used, then culture capacity is adequate, but spheroids move out of focal plane during imaging
Solution Approach 1:
The asymmetric well design with broad base transitioning to narrow neck provides both adequate culture area and improved imaging. The narrow neck portion creates a natural focal zone that keeps the spheroid centered and within the focal plane during imaging, while the broad base provides sufficient culture volume
Data Source
AI summary
An apparatus for containing a three-dimensional cellular material surrounded by a medium that facilitates and maintains the centering of the three-dimensional cellular material throughout an assay is provided. The apparatus includes a well having an open proximal end and a closed distal end. Further, the well defines a compartment having an interior surface and a sample nesting site for containing the three-dimensional cellular material surrounded by the medium. A central indentation is located at the closed distal end of the well, a first concentric lip is located above the central indentation in a y-direction towards the open proximal end of the well, and a second concentric lip is located above the first concentric lip in the y-direction towards the open proximal end of the well. Additionally, the first concentric lip and the second concentric lip define a groove therebetween. A method of forming a three-dimensional cellular material is also provided.