The µSiM

This page has background about the µSiM and contains posts to guide users in assembly and use of the latest version of the µSiM – the modular µSiM.

ALine Modular Device Geometry

ALine Modular Device Assembly

The µSiM

Definition: microphysiological system or microfluidic device enabled by a silicon membrane

The µSiM platform has been used by several laboratories across the world, primarily to study a variety of vascular barriers. The devices feature an ultra-thin, highly porous silicon membrane, ideal for co-culture studies and in situ analyses requiring excellent optical properties. There have been several versions of the µSiM, as discussed below. The latest, modular version is designed for rapid assembly, ease of use by any laboratory, and the ability to easily adapt the device based on the specific needs of the user.

First Generation

First generation devices are made primarily of PDMS and are assembled layer-by layer using traditional bonding methods of UV ozone exposure and thermal incubation. The devices generally have a “Transwell”-style layout, with an open well architecture and a bottom channel separated by a porous membrane. However, µSiM devices have also been assembled in a microfluidic style with a top and bottom channel that can be connected to tubing for addition of fluid flow. This generation of devices has been used to study osteomyelitis, vascular transmigration, and to develop models of the cerebrovascular and blood-brain barrier.

Fig. 1. Examples of first generation µSiM devices. Devices are assembled by layer-by-layer assembly using UV ozone bonding and are either “Transwell” mimetics or designed as microfluidic devices.

References:

  • Bentley, K., Trombetta, R., Nishitani, K, Bello-Irizarry, S.N., Ninomiya, M, Chung, H.L., McGrath, J.L., Daiss, J.L., Awad, A.A., Kates, S.L., Schwarz, E.M. (2017) Evidence of Staphylococcus aureus deformation, proliferation and migration in surgery-induced microcracks and canaliculi of live cortical bone in murine models of osteomyelitis. Journal of Bone and Mineral Research, 32:985-990
  • Masters, E.A., Salminen, A.T., Begolo, S., Luke, E.N., Barrett, S., Overby, O.T., Gill, A.L., de Mesy Bentley, K.L., Awad, H.A., Gill, S.R., Schwarz,, E.S., McGrath, J.L. (2019) An in vitro platform for elucidating the molecular genetics of S. aureus invasion of the osteocyte lacuno-canalicular network during chronic osteomyelitis. Nanomedicine 21:102039
  • Salminen, A.T., Zhang, J., Madejski, G.R., Khire, T.S, Waugh, R.E., McGrath, J.L., Gaborski T.R. (2019) Ultrathin Dual-Scale Nano- and Micro-Porous Membranes for Vascular Transmigration Models. Small 5(6):e1804111
  • Mossu, A., Rosito, M., Khire, T., Chung, H.H., Nishihara, H., Gruber, I., Luke, E., Dehouck, L., Sallusto, F., Gosselet, F., McGrath, J.L., Engelhardt, B.  (2019) A Silicon Nanomembrane Platform for the Visualization of Immune Cell Trafficking Across the Human Blood-brain Barrier Under Flow. Journal of Cerebral Blood Flow & Metabolism 39(3):395-410
  • Hudecz, H., Khire, K., Chung, H.L., Adumeau, L., Glavin, D., Luke, E.N., Nielsen, M.S., Dawson, K.A., McGrath, J.L., Yan, Y. (2020) Porous Silicon Nitride Membranes for in situ Optical Analysis of Translocation of Nanoparticles across the Blood-Brain Barrier ACS Nano 14: 1111-1122

Second Generation

After teaming up with ALine, experts in microfluidic device production, the second generation of µSiM devices were developed. Devices transitioned from PDMS to acrylic-based to avoid the concerns associated with PDMS, such as absorption of small hydrophobic molecules. They retained the “Transwell”-style layout. Devices were manufactured by ALine and shipped back to our laboratory for use or distribution. Thus far, this generation of devices has been used as a platform for a microvascular mimetic. In particular, the device was used to develop a novel in situ assay to quantify changes in endothelial permeability and junctional integrity.

Fig. 2. Second generation µSiM device, manufactured by ALine in a “Transwell”-style layout.

References:

  • Khire, T.S., Salminen, A.T., Swamy, H., Lucas, K.S., McCloskey, M.C., Ajalik, R.E., Chung, H.H, Gaborski, T.R., Waugh, R.E., Glading, A.J., McGrath, J.L., (2020) Microvascular Mimetics for the Study of Leukocyte-Endothelial Interactions  Cell and Molecular Bioengineering 13, 125–139

Third Generation

In order to improve both the distribution and adaptability of µSiM devices, the modular µSiM was developed with ALine. Easy-to-use kits enable assembly of devices by any laboratory. The device has a core “Transwell”-style architecture, with plug-and-play modules to adapt the device for the needs of the user. Modules will include a fluid flow system and TEER measurements, among others. These devices are described in greater detail in the links provided at the beginning of this page.

Fig. 3. Example of third generation, modular µSiM device. Components are manufactured by ALine and assembly is done in-house. This is the core, “Transwell”-style layout.

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