Semi-permeable Arrays for Biological Analysis
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Solution Overview
Problem
Current microwell technologies face challenges in efficiently isolating individual wells to prevent cross-contamination and allow for efficient exchange of buffers, which limits their ability to capture and analyze biological molecules effectively.
Innovation Solution
The method involves functionalizing the surfaces of microwells with affinity resins and ionic functional groups, using a porous membrane for molecular bonding to isolate each well, and employing a semipermeable membrane for buffer exchange and reagent delivery, enabling efficient biochemical analysis and multiplexing reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a microwell array is used to load beads into each well, then loading efficiency is greatly increased, but cross-contamination between adjacent wells occurs and buffer exchange is limited
Solution Approach 1:
The microwell array is segmented into individual isolated wells by inserting physical partitions or membranes between adjacent wells. This segmentation maintains the high loading efficiency of the array while preventing cross-contamination between wells and enabling independent buffer exchange for each well.
Solution Approach 2:
An intermediary membrane or partition is introduced between adjacent wells to act as a barrier. This intermediary structure allows each well to be isolated for biochemical analysis while still being part of the integrated microwell array platform, preventing molecular cross-contamination between neighboring wells.
2Measurement precision
If wells are isolated to prevent cross-contamination, then biochemical analysis accuracy is improved, but buffer exchange efficiency decreases
Solution Approach 1:
Thin film membranes or flexible partitions are used to isolate wells while maintaining permeability to buffers and reagents. These thin films allow efficient buffer exchange through diffusion and convection while still preventing cross-contamination between adjacent wells, thus maintaining both accuracy and productivity.
Solution Approach 2:
Porous membranes or porous partitions are inserted between wells to provide isolation while maintaining porosity for buffer and reagent exchange. The porous structure allows molecules and buffers to pass through while physically separating adjacent wells, enabling accurate biochemical analysis with efficient buffer exchange.
3Reliability
If a porous membrane is used for molecular bonding to isolate wells, then cross-contamination is reduced, but device complexity increases
Solution Approach 1:
The porous membrane isolation structures are merged with the existing microwell array manufacturing process, combining the isolation function with the well formation process. This integration reduces device complexity by eliminating separate assembly steps while maintaining reliable well isolation through the porous membrane structure.
Solution Approach 2:
The porous membrane structure is designed to self-assemble or self-position within the microwell array, reducing the need for complex external assembly mechanisms. The membrane may be pre-formed to fit the well geometry or automatically positioned during manufacturing, simplifying the overall device assembly while maintaining reliable isolation.
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 approach allows for high-throughput parallel single-cell biochemical analysis with reduced cross-contamination, efficient capture of biological molecules, and the ability to perform multiple biochemical reactions in a single platform, enhancing data acquisition and analysis capabilities.
Implementation Method 1
employing a semipermeable membrane for buffer exchange and reagent delivery
Implementation Method 2
performing molecular bonding of a porous membrane on an apical surface of an array having a plurality of wells
Implementation Method 3
functionalizing the surfaces of microwells with affinity resins and ionic functional groups
Implementation Method 4
performing molecular bonding of a porous membrane on an apical surface of an array
Data Source
AI summary
The present application provides a method of assembling a container for one or multiple parallel steps of biochemical analysis on one or more cells comprising performing molecular bonding of a porous membrane on an apical or basal surface of an array having a plurality of wells, wherein the molecular bonding substantially isolates each well from adjacent wells.