Permeable Membrane Oscillation 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 simulate the physiological effects of pulsatile blood flow, leading to inadequate representation of in vivo BBB and limiting the reliability of drug permeability assessments.
Innovation Solution
An apparatus and method that applies a 90°+/−45° normal force to a permeable membrane supporting BBB cells using a vertical oscillating shaker, replicating the in vivo conditions and enhancing permeation rate assessment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If horizontal shakers or magnetic micro-stir bars are used to agitate fluid around the membrane, then permeation rates are enhanced, but the model fails to accurately simulate the physiological effects of pulsatile blood flow
Solution Approach 1:
The patent applies vertical oscillation at frequencies of 50-200 cycles per minute with amplitudes of 0.5-2.0 mm to the Transwell insert, creating normal force fluctuations that simulate pulsatile blood flow. This mechanical vibration approach enhances permeation rates while maintaining physiological accuracy by replicating the natural pulsatile nature of blood flow through the BBB, unlike horizontal shaking which creates non-physiological shear forces.
Solution Approach 2:
The patent changes the direction and characteristics of mechanical agitation from horizontal to vertical oscillation, matching the physiological parameters of pulsatile blood flow. By adjusting frequency (50-200 cycles/min) and amplitude (0.5-2.0 mm) parameters, the system replicates in vivo conditions while enhancing drug permeation, resolving the contradiction between improved productivity and maintained reliability.
2Productivity
If orbital shakers are used to enhance permeation, then drug transport across the membrane is improved, but the model becomes less representative of in vivo BBB conditions
Solution Approach 1:
The patent inverts the conventional horizontal shaking approach by applying vertical oscillation to the Transwell insert. This inversion creates normal force fluctuations perpendicular to the membrane surface, accurately simulating the pulsatile pressure changes experienced by the BBB in vivo. The vertical oscillation enhances drug transport while maintaining physiological relevance, unlike horizontal shaking which creates non-physiological flow patterns.
Solution Approach 2:
The vertical oscillation mechanism creates pressure fluctuations analogous to pulsatile blood flow through the BBB. By applying rhythmic normal forces through vertical oscillation, the system hydraulically simulates the in vivo pressure changes that drive drug transport across the BBB, thereby enhancing drug transport while maintaining accurate in vivo representation.
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 application of normal forces significantly increases permeation rates through the BBB, providing a more accurate in vitro model that mimics in vivo conditions, thereby improving drug permeability assessments.
Implementation Method 1
a shaker device connected to said support including said permeable membrane wherein said shaker device applies an oscillating normal force of 90°+/−45° to said permeable membrane and said blood brain barrier cells
Implementation Method 2
determining a rate of permeation of said selected drug through said BBB cells and said permeable membrane
Data Source
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.