Micropatterned macroporous structures in microfluidic devices for viral separation from whole blood

Abstract

Separation and enrichment of bio-nanoparticles from cell suspensions and blood are critical steps in many chemical and biomedical practices. We demonstrate here the design and fabrication of a microfluidic immunochromatographic device incorporating regular and multiscale monolithic structures to capture viruses from blood. The device contains micropatterned arrays of macroporous materials to perform size-exclusion and affinity chromatography in a simple flow-through process. The microscale gaps in the array allow the passage of cells while the macroporous matrices promote viral capture. Computational analyses reveal that fluid permeation into the porous matrices is controllable by the micropattern shape, separation distance and dimensions. Experimental analyses using blood samples containing human immunodeficiency viruses (HIV) as a model system further prove significantly improved viral capture efficiency using devices incorporating multiscale structures than those containing solid micropatterns. Such microfluidic devices with regular and multiscale structures have a potential for the separation and concentration of a wide range of bio-nanoparticles as well as macromolecules from complex mixtures containing both nano- and micro-sized species.

Porous Structural Microfluidic Device for Biomedical Diagnosis: A Review

“…Microfluidic devices also have the ability to capture, align and manipulate cells. Cell separation and capture can be achieved by preparing arrays of porous microstructures, such as separating cancer cells from healthy cells for cancer diagnosis [ 224 , 225 , 226 , 227 ]. Yin et al prepared the first pyramidal porous array to capture specific cells [ 225 ] ( Figure 6 a).…”

Characterizing Extracellular Vesicles and Their Diverse RNA Contents

“…Affinity columns have an advantage of biochemical flexibility over SEC columns: stationary phase materials have extensive flexibility with regard to their composition, and functionalization by antibodies, aptamers, and other moieties (Block et al, 2009 ; Urh et al, 2009 ; Acquah et al, 2015 ; Tanaka and McCalley, 2016 ). Low-input chromatographic systems have also been demonstrated and we expect to see future development in microfluidic, chromatography-based modules with further specialization for handling clinical samples and extracting RNA (Chirica et al, 2006 ; Millet et al, 2015 ; Surawathanawises et al, 2017 ). Overall we find that chromatographic EV separations, especially those prepared using commercial kits, have a high applicability to discovery- and EV-based RNA studies where purity and reproducibility are paramount.…”

Microfluidic and Paper-Based Devices for Disease Detection and Diagnostic Research

“…The detection of viruses in blood samples can be difficult due to their dilute concentration requiring sample enrichment steps. Surawathanawises et al used semi-circular traps composed of porous silica beads and polystyrene to trap viruses and remove RBCs and WBCs [ 14 ]. This method was tested using human blood infected with HIV and was capable of efficiently detecting the virus in concentrations of approximately 10 6 virions per mL.…”

“…Similarly, the ability to remotely confirm a viral infection in low income areas or underdeveloped countries would provide essential information to slow the progression of diseases. Examples include the rapid and accurate detection of influenza [ 7 , 8 , 9 , 10 ], Zika virus [ 11 , 12 , 13 ], or sexually transmitted diseases [ 11 , 14 , 15 ]. To this extent, the first part of this review will highlight some recent microfluidic devices developed to provide early and accurate detection of diseases by confirming the presence or absence of specific precursors and identifiers.…”