Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats

Eunseop Yeom,Hye Mi Kim,Jun Hong Park,Woorak Choi,Sang Joon Lee,Junsang Doh

doi:10.1038/s41598-017-01985-w

Eunseop Yeom, Hye Mi Kim + Show 4 more

Open Access

https://doi.org/10.1038/s41598-017-01985-w

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Abstract

Sepsis causes multiple organs failures and eventually death. Changes in blood constituents due to sepsis lead to alterations in hemorheological properties, and cell adhesiveness. In this study, a new microfluidic system is proposed to measure temporal variations in biophysical properties of blood after injecting lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition. To measure blood viscosity, the interfacial line between blood and a reference fluid is formed in a Y-shaped channel. Based on the relation between interfacial width and pressure ratio, the temporal variation in blood viscosity is estimated. Optical images of blood flows are analyzed by decreasing flow rate for examination of red blood cell (RBC) aggregation. Platelets initiated by shear acceleration around the stenosis adhere to the post-stenosed region. By applying a correlation map that visualizes the decorrelation of the streaming blood flow, the area of adhered platelets can be quantitatively attained without labeling of platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8) are also monitored. The increasing tendency for blood viscosity, RBC aggregation, platelet adhesion, and septic biomarkers are observed after LPS injection. This microfluidic system would be beneficial for monitoring the changes in hemorheological properties and platelet activation caused by sepsis.

Highlights

Sepsis is the most frequent cause of mortality in numerous intensive care units[1]
We propose a microfluidic system for monitoring temporal variations in biophysical properties including blood viscosity, red blood cell (RBC) aggregation, and platelet adhesion, in the rat extracorporeal sepsis model after injecting LPS
The inflammatory response of sepsis is induced through high-dose injection (3 mg/kg) of LPS into the rat extracorporeal model

Summary

Introduction

Sepsis is the most frequent cause of mortality in numerous intensive care units[1]. This complex and impetuous illness induces alterations in microcirculation and changes in biochemical and physiological characteristics of blood constituents[2]. Molecules such as RANTES, IL1-β, monocyte chemoattactant factor (MCP-1), platelet factor 4 (PF4), and platelet activating factor (PAF), to regulate inflammation and tissue repair processes in patients with sepsis[14]. These molecules may promote platelet–immune cell adhesion[15]. The readouts of platelet activation have been suggested as biomarkers to indicate the infectious state of sepsis complications and the related prognosis[14, 16]

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