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

Abstract

<jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:sec><jats:title>Significance</jats:title><jats:p>Organ-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&amp;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.</jats:p></jats:sec>

A new microfluidic concept for successfulin vitroculture of mouse embryos

“…Alternative materials, such as poly methyl methacrylate, polycarbonate, cyclic olefin polymers and copolymers and the most common polystyrene are common thermoplastic materials used in industrial manufacturing of disposable plastic. Most of these are used for microfluidic manufacturing with cheap and fast processes but published evidences do not exclude their long term toxicity [29]. In 2004, Wheeler [30] compared the development of embryos cultured in a microfluidic channel under static conditions, manufactured in silicon/borosilicate and PDMS/borosilicate.…”

Tailoring Electrospun Poly(l-lactic acid) Nanofibers as Substrates for Microfluidic Applications

“…Various strategies can be used to modify the surface properties and thus tailor the polymer wettability, such as chemical grafting, self-assembly and surface hydrolysis 21 . Another reported strategy involves the integration of specific fillers (such as polyethylene glycol 22 , hydrophilic zeolites 23 , superhydrophilic metal-organic frameworks 24 , wet-chemistry treatment 25 , among others) on the polymer matrix in order to reduce the hydrophobic behaviour of polymers 26 .…”

“…The major drawback of PLLA-based electrospun membranes is associated with its inherent hydrophobicity, poor wettability, and low surface energy that must be overcome so that it can be used as a substrate, similar to paper, for the fabrication of microfluidic systems. Various strategies can be used to modify the surface properties and thus tailor the polymer wettability, such as chemical grafting, self-assembly, and surface hydrolysis . Another reported strategy involves the integration of specific fillers (such as polyethylene glycol, hydrophilic zeolites, superhydrophilic metal–organic frameworks, and wet chemistry treatment, among others) on the polymer matrix in order to reduce the hydrophobic behavior of polymers …”

“…Various strategies can be used to modify the surface properties and thus tailor the polymer wettability, such as chemical grafting, self-assembly, and surface hydrolysis. 21 Another reported strategy involves the integration of specific fillers (such as polyethylene glycol, 22 hydrophilic zeolites, 23 superhydrophilic metal−organic frameworks, 24 and wet chemistry treatment, 25 among others) on the polymer matrix in order to reduce the hydrophobic behavior of polymers. 26 Nevertheless, plasma treatment is one of the most extensively used methods to tailor surface adhesion and wetting properties by the insertion of chemically reactive functional groups on the polymer surface, modifying its composition without affecting their bulk characteristics.…”

A New Microfluidic Concept for Successful in Vitro Culture of Mouse Embryos

“…Alternative materials, such as poly methyl methacrylate, polycarbonate, cyclic olefin polymers and copolymers and the most common polystyrene are common thermoplastic materials used in industrial manufacturing of disposable plastic. Most of these are used for microfluidic manufacturing with cheap and fast processes but published evidence does not exclude their long term toxicity [31]. In 2004, Wheeler [32] compared the development of embryos cultured in a microfluidic channel under static conditions, manufactured in silicon/borosilicate and PDMS/borosilicate.…”