In Part 1 we explained that the composite barrier in our model of the post-capillary NVU is determined by RBBB = RBlB + R2 + RBrB where is R2 is the resistance of the ‘perivascular space’ in our chip. Unlike the other two, the perivascular space is not a regulated cellular barrier that we need…
Introduction The modular μSiM is based on a 96-well plate format with a 100 μl open well. While these devices have proven extremely useful for various barrier models including the blood-brain barrier1 and the tendon-vascular interface2, there is a need to transform the open well into a fluidic channel. A closed channel device would enable…
Introduction Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by accumulation of amyloid beta (Aβ) peptides and neurofibrillary tangles (NFTs) made of aggregates of the protein tau (1,2). It results in the destruction of neurons and their connections due to this accumulation of amyloid beta and tau (3). Tau is a microtubule associated…
Introduction Sepsis refers to an uncontrolled systemic inflammatory response which can result from bacterial blood infections. We have long been interested in developing a sepsis model using the μSiM-BBB platform because the neuroinflammation stemming from sepsis can cause severe BBB disruption. For the majority of our stimulation experiments we have relied on cytomix, a cocktail…
The two barrier anatomy of the post-capillary NVU and why it matters At the post-capilliary venule, the blood-brain barrier (BBB) is actually two barriers in series: 1) one created by the pericyte/BMEC layer at the blood interface and 2) one created by astrocytes and the astrocyte-produced glia limitans at the interface with the brain. We’ll…
Introduction Many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are associated with an early breakdown of the blood brain barrier (BBB). This includes an increase in permeability and pericyte degradation [1]. We hypothesize that using dual-scale (nanoporous and microporous) membranes in the µSiM-BBB model will create an inherently ‘leaky’ BBB which can be used…
Introduction As discussed in a previous post, we are working to adapt a PDMS flow insert as a manufacturable component. While our priority was maintaining the original flow channel geometry as Mansouri et al. designed, we slightly changed the channel length (5 mm –> 4.6 mm) to accommodate an extra bonding area for the pressure-sensitive…
Introduction A recent collaborative publication from RIT developed a modular µSiM to address the lack of physiological fluid flow in conventional open-well devices (Figure 1). The magnetic latching assembly of this design allows for quick configuration into a fluidic setup. The flow module is a microfabricated PDMS insert that contains a channel over the membrane…
Introduction: Many applications of the µSiM require fluid to be continuously supplied to the microfluidic devices. We use laboratory tubing (typically Cole-Parmer/Tygon Tubing with I.D = 1/16″) that is connected to syringes or peristaltic pumps to do so. However, interfacing the tubing with the current entry and exit ports for the bottom channel is not…
Introduction The basement membrane (BM) is a critical component of a healthy blood-brain barrier (BBB) model. Further, the BM breaks down in several diseases. Both pericytes and endothelial cells can contribute to basement membrane production. This post will explore a method to localize basement membrane components – collagen type IV (Col IV), fibronectin (FN), and…