Permeable Membrane Vibration for Physiologic BBB Permeation Testing
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Solution Overview
Problem
Existing in vitro models of the brain blood barrier (BBB) fail to accurately replicate the physiological effects of pulsatile blood flow, leading to inadequate permeation rate assessments, which are crucial for understanding and treating neurodegenerative diseases.
Innovation Solution
An apparatus and method that applies a generally vertical oscillating normal force of 90° +/- 45° to a permeable membrane supporting BBB cells, using a shaker device to simulate the pulsatile flow, thereby enhancing permeation rate evaluations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional static membrane models are used, then device simplicity is maintained, but physiological accuracy of permeation rates deteriorates
Solution Approach 1:
The patent applies dynamic oscillating motion to the membrane assembly using an orbital shaker, transforming the static membrane model into a dynamic system that replicates pulsatile blood flow conditions. This dynamic approach enhances permeation rates by four orders of magnitude while maintaining reasonable device complexity through the use of standard laboratory equipment.
Solution Approach 2:
The patent utilizes mechanical vibration through orbital shaking at specific frequencies and amplitudes to simulate the physiological effects of pulsatile blood flow. The vibration applies normal forces to the membrane and cell monolayer, creating conditions that more accurately reflect in vivo permeation processes while keeping the apparatus relatively simple.
2Reliability
If orbital shakers are used to enhance permeation rates, then permeation accuracy improves, but device complexity increases
Solution Approach 1:
The patent employs an orbital shaker, which is a common multi-functional laboratory device, to perform the specific function of simulating pulsatile blood flow. This approach leverages the universality of standard equipment rather than requiring a specialized custom-built apparatus, thereby improving permeation assessment accuracy while minimizing the increase in device complexity.
3Ease of operation
If magnetic micro-stir bars are used to agitate fluid, then fluid mixing improves, but physiological relevance deteriorates
Solution Approach 1:
The patent replaces magnetic stirring with mechanical vibration through orbital shaking. This vibration applies normal forces to the membrane and cell monolayer, creating physiological conditions that more accurately reflect in vivo permeation processes while maintaining ease of operation through the use of standard orbital shaker equipment.
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 method significantly increases permeation rates by four orders of magnitude, providing a more accurate in vitro model that aligns with in vivo conditions, ensuring reliable drug permeability assessments.
Implementation Method 1
a shaker device applies an oscillating normal force of 90° +/- 45° to said permeable membrane and said blood brain barrier cells
Implementation Method 2
evaluate permeation rates of selected drugs through brain blood barrier cells disposed on the membrane
Data Source
Figure 1
Figure 2
Figure 3A~3B
AI summary
An apparatus and method for applying normal forces to a support device including a permeable membrane. More specifically, the present invention provides an apparatus and method to apply normal forces to a porous membrane that provides independent access to both sides of the porous membrane layer to evaluate permeation rates of selected drugs through brain blood barrier cells disposed on the membrane.