Ongaro, A. E. | bioRxiv Science

bioRxiv2020

Engineered membranes for residual cell trapping on microfluidic blood plasma separation systems. A comparison between porous and nanofibrous membranes.

Blood-based clinical diagnostics require challenging limit-of-detection for low abundance, circulating molecules in plasma. Micro-scale blood plasma separation (BPS) has achieved remarkable results in terms of plasma yield or purity, but rarely achieving both at the same time. Here, we proposed the first use of electrospun polylactic-acid (PLA) membranes as filters to remove residual cell population from continuous hydrodynamic-BPS devices. The membranes hydrophilicity was improved by adopting a wet chemistry approach via surface aminolysis as demonstrated through Fourier Transform Infrared Spectroscopy and Water Contact Angle analysis. The usability of PLA-membranes was assessed through degradation measurements at extreme pH values. Plasma purity and hemolysis were evaluated on plasma samples with residual red blood cell content (1, 3, 5% hematocrit) corresponding to output from existing hydrodynamic BPS systems. Commercially available membranes for BPS were used as benchmark. Results highlighted that the electrospun membranes are suitable for downstream residual cell removal from blood, permitting the collection of up to 2 mL of pure and low-hemolyzed plasma. Fluorometric DNA quantification revealed that electrospun membranes did not significantly affect the concentration of circulating DNA. PLA-based electrospun membranes can be combined with hydrodynamic BPS in order to achieve high volume plasma separation at over 99% plasma purity.

bioengineering↗

bioRxiv2019

Polylactic acid, a sustainable, biocompatible, transparent substrate material for Organ-On-Chip and Microfluidic applications

Organ-on-chips are miniaturised devices aiming at replacing animal models for drug discovery, toxicology and studies of complex biological phenomena. The field of Organ-On-Chip has grown exponentially, and has led to the formation of companies providing commercial Organ-On-Chip devices. Yet, it may be surprising to learn that the majority of these commercial devices are made from Polydimethylsiloxane (PDMS), a silicone elastomer that is widely used in microfluidic prototyping, but which has been proven difficult to use in industrial settings and poses a number of challenges to experimentalists, including leaching of uncured oligomers and uncontrolled adsorption of small compounds. To alleviate these problems, we propose a new substrate for organ-on-chip devices: Polylactic Acid (PLA). PLA is a material derived from renewable resources, and compatible with high volume production technologies, such as microinjection moulding. PLA can be formed into sheets and prototyped into desired devices in the research lab. In this article we uncover the suitability of Polylactic acid as a substrate material for Microfluidic cell culture and Organ-on-a-chip applications. Surface properties, biocompatibility, small molecule adsorption and optical properties of PLA are investigated and compared with PDMS and other reference polymers.\n\nSignificanceOrgan-On-Chip (OOC) technology is a powerful and emerging tool that allows the culture of cells constituting an organ and enables scientists, researchers and clinicians to conduct more physiologically relevant experiments without using expensive animal models. Since the emergence of the first OOC devices 10 years ago, the translation from research to market has happened relatively fast. To date, at least 28 companies are proposing body and tissue on-a chip devices. The material of choice in most commercial organ-on-chip platforms is an elastomer, Polydymethyloxane (PDMS), commonly used in microfluidic R&D. PDMS is however subject to poor reproducibility, and absorbs small molecule compounds unless treated. In this study we show that PLA overcomes all the drawbacks related to PDMS: PLA can be prototyped in less than 45 minutes from design to test, is transparent, not autofluorescent, and biocompatible. PLA-based microfluidic platforms have the potential to transform the OOC industry as well as to provide a sustainable alternative for future Lab-On-Chip and point-of-care devices.

bioengineering↗