A Review of Design Considerations for Hemocompatibility within Microfluidic Systems

Abstract

The manipulation of blood within in vitro environments presents a persistent challenge, due to the highly reactive nature of blood, and its multifaceted response to material contact, changes in environmental conditions, and stimulation during handling. Microfluidic Lab-on-Chip systems offer the promise of robust point-of-care diagnostic tools and sophisticated research platforms. The capacity for precise control of environmental and experimental conditions afforded by microfluidic technologies presents unique opportunities that are particularly relevant to research and clinical applications requiring the controlled manipulation of blood. A critical bottleneck impeding the translation of existing Lab-on-Chip technology from laboratory bench to the clinic is the ability to reliably handle relatively small blood samples without negatively impacting blood composition or function. This review explores design considerations critical to the development of microfluidic systems intended for use with whole blood from an engineering perspective. Material hemocompatibility is briefly explored, encompassing common microfluidic device materials, as well as surface modification strategies intended to improve hemocompatibility. Operational hemocompatibility, including shear-induced effects, temperature dependence, and gas interactions are explored, microfluidic sample preparation methodologies are introduced, as well as current techniques for on-chip manipulation of the whole blood. Finally, methods of assessing hemocompatibility are briefly introduced, with an emphasis on primary hemostasis and platelet function.

Challenge of material haemocompatibility for microfluidic blood-contacting applications

“…Until now the focus has been primarily on the mechanical experience of the blood and blood-processing functionalities, with the material interactions remaining an afterthought. Although it is true that haemodynamic forces contribute hugely to damage experienced by blood in microfluidic networks, and the methods of protective design have been previously reviewed ( Szydzik et al, 2020 ; Astor and Borenstein, 2022 ; Feaugas et al, 2023 ), devices will not achieve acceptable haemocompatibility without appropriate coating of microchannel surfaces. This review provides a foundational understanding of the significance of material-blood interactions in microfluidic channels and the formation of thrombi, and how coatings can improve haemocompatibility.…”

Microfluidic Systems for Blood and Blood Cell Characterization

“…Looking ahead, there is a growing trend toward using neural networks, machinelearning systems, artificial intelligence, and edge computing to characterize blood cells. We believe that progress in the study of the physical properties of blood will be associated with the use of new hemocompatible materials [193], hydrogels [194,195], and 4D printing technology [196,197]. Self-driven micro-/nanorobots may be involved in cell and particle manipulations [198,199].…”