Challenge of material haemocompatibility for microfluidic blood-contacting applications

Abstract

Biological applications of microfluidics technology is beginning to expand beyond the original focus of diagnostics, analytics and organ-on-chip devices. There is a growing interest in the development of microfluidic devices for therapeutic treatments, such as extra-corporeal haemodialysis and oxygenation. However, the great potential in this area comes with great challenges. Haemocompatibility of materials has long been a concern for blood-contacting medical devices, and microfluidic devices are no exception. The small channel size, high surface area to volume ratio and dynamic conditions integral to microchannels contribute to the blood-material interactions. This review will begin by describing features of microfluidic technology with a focus on blood-contacting applications. Material haemocompatibility will be discussed in the context of interactions with blood components, from the initial absorption of plasma proteins to the activation of cells and factors, and the contribution of these interactions to the coagulation cascade and thrombogenesis. Reference will be made to the testing requirements for medical devices in contact with blood, set out by International Standards in ISO 10993-4. Finally, we will review the techniques for improving microfluidic channel haemocompatibility through material surface modifications-including bioactive and biopassive coatings-and future directions.

Keywords: biomaterials; coating; haemocompatibility; medical devices; microfluidics; surface modification; thrombosis.

FIGURE 1

Number of publications (including patents) per year from 2012 until 2022 from searching Google Scholar with the term “microfluidics + blood −brain”. The results including the word “brain” were removed to exclude irrelevant organ-on-chip papers focussing on the blood-brain barrier.

FIGURE 2

Virchow’s Triad of interacting factors which contribute to an increased risk of thrombosis. Adapted from Wolberg et al. (2012) combined with Virchow’s original translation.

FIGURE 3

Process of plasma protein adsorption to a blood-contacting biomaterial surface and ensuing platelet activation and coagulation response leading to thrombus formation.

FIGURE 4

Differing coating applications to open (left side) and sealed (right side) microchannels, with practical features of each: benefits and challenges.