Receiver Plate Non-Uniform Cross-Section Wicking Reduction
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Solution Overview
Problem
Conventional receiver plates used in non-cell based PAMPA assays suffer from capillary wicking and cross-contamination, limited media volume, evaporation issues, and difficulties in automated assembly and disassembly, which affect the accuracy and efficiency of drug absorption assays.
Innovation Solution
A multi-well assembly with non-uniform receiver plate wells that increase the gap between filter and receiver plate wells to reduce wicking, feature a transition from square to circular cross-section to accommodate larger media volumes, and include lead-in features and positioning ribs for improved assembly and evaporation reduction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional receiver plates with uniform circular cross-section wells are used, then the device structure is simple and easy to manufacture, but capillary wicking and cross-contamination occur between filter and receiver plate wells
Solution Approach 1:
The receiver plate wells are designed with non-uniform cross-sections, transitioning from square at the top to circular at the bottom. This asymmetric geometry creates an enlarged gap between the filter plate and receiver plate walls in the upper portion, preventing capillary wicking and cross-contamination, while the lower circular portion maintains proper nesting and positioning.
2Reliability
If the gap between filter plate and receiver plate wells is increased to reduce wicking, then capillary action is minimized, but the media volume capacity in the lower section is reduced
Solution Approach 1:
The receiver plate well is segmented into two distinct functional zones: an upper portion with enlarged gap for preventing wicking, and a lower portion with reduced cross-section for maintaining media volume capacity. This segmentation allows each zone to optimize its specific function without compromising the other.
Solution Approach 2:
Different cross-sectional geometries are applied to different portions of the well: the upper portion uses a square cross-section with larger gap dimensions to prevent capillary action, while the lower portion uses a circular cross-section with smaller dimensions to maintain adequate media volume. Each local region has optimized properties for its specific function.
3Reliability
If conventional uniform cross-section wells are used, then the device is compatible with standard ANSI/SBS Microplate Standards, but evaporation of media occurs during incubation and shaking
Solution Approach 1:
The filter plate is nested within the receiver plate with the non-uniform cross-section design. The upper square portion creates a sealed interface that prevents evaporation during incubation and shaking, while the overall plate dimensions and well positioning maintain compatibility with ANSI/SBS Microplate Standards for automation compatibility.
4Quantity of substance
If the receiver plate wells have larger cross-section throughout, then media volume capacity is increased, but the gap between plates is reduced increasing wicking risk
Solution Approach 1:
The solution addresses the contradiction by changing the dimensional characteristics at different vertical levels. The upper portion has larger horizontal dimensions (square cross-section) to prevent wicking, while the lower portion has smaller horizontal dimensions (circular cross-section) to maintain media volume. This vertical dimensionality change resolves the contradiction between gap size and media volume.
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 solution minimizes capillary wicking and cross-contamination, reduces media volume requirements, and enhances the repeatability and automation compatibility of the assembly, while maintaining the membrane in liquid contact and reducing evaporation, thereby improving the accuracy and efficiency of drug absorption assays.
Implementation Method 1
The primary cause of cross contamination is the wicking of liquid in the small gap between each filter well and receiver well when the two plates are nested together
Implementation Method 2
The majority of drugs enter the blood stream by passive diffusion through the intestinal epithelium. Consequently, permeability assays that measure passive transport through lipophilic barriers correlate with human drug absorption values
Implementation Method 3
a method known as PAMPA (Parallel Artificial Membrane Permeability Assay), which uses a lipid filled membrane to simulate the lipid bilayer of various cell types, including intestinal epithelium
Implementation Method 4
This creates hydrostatic equilibrium and minimized pressure differentials, which can cause uncontrolled or forced diffusion through the membrane
Data Source
AI summary
A multi-well assembly including a filter plate and receiver plate. Each plate includes a plurality of wells, which, when the filter plate is placed in nesting relationship with the receiver plate, each filter plate well has a corresponding receiver plate well into which it extends. The receiver plate wells are of a non-uniform cross-section in order to increase the gap between the outer walls of the filter plate wells and the inner walls of a corresponding receiver plate well when the receiver plate and filter plate are in nesting relationship. The increased gap size reduces wicking and cross-contamination. A multi-section well of maximum cross-section in an upper region and a minimized cross-section in a lower region, with a gradual transition between the regions, is thus provided. The multi-well assembly of the present invention also improves the repeatability of positioning the filter plate and receiver plate in proper nesting relationship and provides stability during handling, mixing and shaking operations.