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.SignificanceOrgan-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.

Analysis of the Downscaling Effect and Definition of the Process Fingerprints in Micro Injection of Spiral Geometries

Microinjection moulding has been developed to fulfil the needs of mass production of micro components in different fields. A challenge of this technology lies in the downscaling of micro components, which leads to faster solidification of the polymeric material and a narrower process window. Moreover, the small cavity dimensions represent a limit for process monitoring due to the inability to install in-cavity sensors. Therefore, new solutions must be found. In this study, the downscaling effect was investigated by means of three spiral geometries with different cross sections, considering the achievable flow length as a response variable. Process indicators, called “process fingerprints”, were defined to monitor the process in-line. In the first stage, a relationship between the achievable flow length and the process parameters, as well as between the process fingerprints and the process parameters, was established. Subsequently, a correlation analysis was carried out to find the process indicators that are mostly related to the achievable flow length.

Disposable Optical Stretcher Fabricated by Microinjection Moulding

Microinjection moulding combined with the use of removable inserts is one of the most promising manufacturing processes for microfluidic devices, such as lab-on-chip, that have the potential to revolutionize the healthcare and diagnosis systems. In this work, we have designed, fabricated and tested a compact and disposable plastic optical stretcher. To produce the mould inserts, two micro manufacturing technologies have been used. Micro electro discharge machining (µEDM) was used to reproduce the inverse of the capillary tube connection characterized by elevated aspect ratio. The high accuracy of femtosecond laser micromachining (FLM) was exploited to manufacture the insert with perfectly aligned microfluidic channels and fibre slots, facilitating the final composition of the optical manipulation device. The optical stretcher operation was tested using microbeads and red blood cells solutions. The prototype presented in this work demonstrates the feasibility of this approach, which should guarantee real mass production of ready-to-use lab-on-chip devices.

Polymer based microneedle patch fabricated using microinjection moulding

This paper presents the development of a polymer based microneedle patch for transdermal drug delivery application using plastic microinjection moulding. Design and analysis of the microneedle cavities and mould insert used in the injection moulding process were carried out using Computer-Aided Engineering (CAE) software. A mould insert with low surface roughness was fabricated using Micro Electrical Discharge Machining (μ-EDM). The injection moulding parameters including clamping force, temperature, injection pressure and velocity were characterized in order to obtain the optimum reproducibility. Solid truncated cone microneedles, made of biocompatible polymethyl methacrylate (PMMA), with a round tip radius of 50 μm and 500 μm in height have been realized by microinjection moulding process demonstrating the potential of a low cost, high production efficiency, and suitable for mass production. In addition, a mould insert of cylindrical microneedles fabricated using X-ray LIGA has been proposed.