Condensed ECM-based nanofilms on highly permeable PET membranes for robust cell-to-cell communications with improved optical clarity.

The properties of a semipermeable porous membrane, including pore size, pore density, and thickness, play a crucial role in creating a tissue interface in a microphysiological system (MPS) because it dictates multicellular interactions between different compartments. The small pore-sized membrane has been preferentially used in an MPS for stable cell adhesion and the formation of tissue barriers on the membrane. However, it limited the applicability of the MPS because of the hindered cell transmigration via sparse through-holes and the optical translucence caused by light scattering through pores. Thus, there remain unmet challenges to construct a compartmentalized MPS without those drawbacks. Here we report a submicrometer-thickness (∼500 nm) fibrous extracellular matrix (ECM) film selectively condensed on a large pore-sized track-etched (TE) membrane (10µm-pores) in an MPS device, which enables the generation of functional tissue barriers simultaneously achieving optical transparency, intercellular interactions, and transmigration of cells across the membrane. The condensed ECM fibers uniformly covering the surface and 10µm-pores of the TE membrane permitted sufficient surface areas where a monolayer of the human induced pluripotent stem cell-derived brain endothelial cells is formed in the MPS device. The functional maturation of the blood-brain barrier (BBB) was proficiently achieved due to astrocytic endfeet sheathing the brain endothelial cells through 10µm pores of the condensed-ECM-coated TE (cECMTE) membrane. We also demonstrated the extravasation of human metastatic breast tumor cells through the human BBB on the cECMTE membrane. Thus, the cECMTE membrane integrated with an MPS can be used as a versatile platform for studying various intercellular communications and migration, mimicking the physiological barriers of an organ compartment.

Attomolar detection of protein biomarkers using biofunctionalized gold nanorods with surface plasmon resonance.

This paper describes an ultrasensitive surface plasmon resonance (SPR) detection method using biofunctionalized gold nanorods for the direct detection of protein biomarkers. Immunoglobulin E (IgE), which has separate antibody and DNA aptamer binding sites, was chosen as a model protein for which a sandwich assay platform was designed. Detection was achieved via the specific adsorption of unlabelled IgE proteins onto the surface immobilized aptamer followed by the specific adsorption of anti-IgE coated gold nanorods (Au-NRs). Using the biofunctionalized nanorods in conjunction with SPR, we were able to directly measure IgE proteins at attomolar concentrations. This is a remarkable 10(8) enhancement compared to conventional SPR measurements of the same surface sandwich assay format 'anti-IgE/IgE/surface bound IgE-aptamer' in the absence of gold nanorod signal amplification.