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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.

The nature of the material to be employed is one of the first factors manufacturers must take into account when embarking upon the design and production of a new microfluidic device. Silicon and glass have traditionally been used for manufacturing micro-features but polymeric materials, including thermoplastics, have recently been explored. The required microfluidic functions, degree of integration and application are the principal issues that must be considered when choosing a material. However, environmental sustainability is another concern that is of increasing importance due to the dramatic rise in the amount of medical plastic waste produced globally, largely driven by the use of single-use, disposable medical equipment. The advent of point-of-care diagnostics, in labon-chip format, is likely to add further to the amount of healthcare waste generated and, therefore, embedding sustainability at the research stage is essential. This thesis describes the possibility of making research prototypes and future products more sustainable across their entire lifecycle, from raw material to the finished article, by proposing the use of chemically recycled and natural origin polymers. First, a safe and cost effective protocol to bond conventional polymethyl metacrylate, PMMA, based microfluidic devices is investigated and the possibility to use chemically recycled PMMA taken into consideration. Polylactic acid, PLA, is introduced as environmentally sustainable solution and the CO2 laser cut workability improved to microstructure microfluidic devices. PLA material properties are investigated to assess material suitability for point-of-care and microfluidic cell culture applications.

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. Competing Interest Statement The authors have declared no competing interest.

Organ-on-chips are miniaturised devices aiming at replacing animal models for drug and toxicity studies 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 PDMS, a material widely used in microfluidic prototyping, but which has proven difficult to use in industrial settings and poses a number of challenges to experimentalists, including loss 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 such as microinjection moulding. The polymer can be formed into sheets and prototyped into the desired devices in the research lab. The aim of this paper is to assess and prove the suitability of Polylactic acid as substrate material for Organ-on-a-chip applications. Surface properties, biocompatibility, small molecules adsorption and optical properties of PLA are investigated and compared with PDMS and other reference polymers.