Compressible Membrane Sealing for Skin Sample Viability in HTS
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Solution Overview
Problem
Current high throughput screening (HTS) methods for testing skin samples are limited in their ability to maintain the viability and integrity of skin samples, particularly for murine, porcine, and human skin tissues, during the testing process, which affects the accuracy and reliability of drug discovery and biochemical interaction studies.
Innovation Solution
A multiwell skin cell culture device is designed with a base and compression member that secures a compressible skin sheet across channels, forming sealed wells for reagent contact, allowing for tension application and maintaining skin sample viability through controlled compression and tension, suitable for HTS.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a multiwell plate is used for HTS with skin samples, then high throughput screening capability is achieved, but skin sample viability and integrity are compromised
Solution Approach 1:
The patent uses a flexible membrane as the skin sample substrate that can be stretched and secured across well openings. This flexible film approach allows the membrane to conform to the well structure while maintaining skin integrity, enabling HTS format compatibility without compromising sample viability through rigid constraints
Solution Approach 2:
The invention divides a single skin sample into multiple discrete segments or regions, each corresponding to a separate well. This segmentation allows simultaneous testing of multiple conditions across different portions of the same skin sample while maintaining overall sample integrity and viability through proper mounting and sealing
2Reliability
If compression is applied to secure the skin sample, then sealing and sample stability are improved, but skin sample integrity may be compromised
Solution Approach 1:
The compression mechanism applies localized pressure only at specific sealing points around the well openings rather than uniform compression across the entire skin sample. This local quality approach ensures adequate sealing and sample stability at critical interfaces while preserving skin integrity and cellular viability in the test regions
3Manufacturing precision
If tension is applied to stretch the skin sample, then sample flatness and reagent contact are improved, but skin sample integrity may be compromised
Solution Approach 1:
The mounting mechanism applies a controlled amount of tension that is sufficient to achieve adequate flatness and reagent contact for HTS functionality, but carefully limited to avoid excessive stress that would compromise skin integrity. This partial action principle optimizes the balance between sample preparation quality and sample viability
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 effectively maintains skin sample viability and integrity, enabling reliable high throughput screening with minimal leakage and consistent results, as demonstrated by the skin's response to small molecule drugs and gene expression analysis over several days.
Implementation Method 1
parts of the compressible sheet are compressed between the base and the compression member to form a seal between the base and the compression member
Implementation Method 2
A reagent is added to the channels and the reagent, under the action of gravity, is in contact with the compressible sheet at the part which extends across the channel
Data Source
AI summary
An apparatus for high throughput screening which has a base with channels for receiving a reagent. The channels are spaced across the surface of the base and have one or more walls which extend through the base from a first base surface to a second base surface. A compression member containing a plurality of openings which extend through the compression member and which are positioned across the surface of the compression member, one or more o-' said openings being positioned for alignment with a corresponding channel in the base. A grip for removably securing the compression member to the base such that when a compressible sheet s positioned across the channel between the base and the compression member and fixed by the grip, parts of the compressible sheet are compressed between the base and the compression member to form a seal between the base and the compression member such that and the compressible sheet and walls of the base form one or more wels for containing the reagent.