A microfluidic erythrocyte sedimentation rate analyzer using rouleaux formation kinetics

Red blood cells form face-to-face linear or branched structures, called as rouleaux, under static conditions or low shear rates in the presence of appropriate macromolecules (Baskurt et al. 2011a; Chien 1975; Merrill 1969; Neu and Meiselman 2007). This process is reversible, and cells can be dispersed individually when a disaggregating shear rate is applied to the cells (Baskurt et al. 2011b; Lim et al. 2010; Mehri et al. 2014; Shin et al. 2009). Aggregation is a critical factor for the determination of blood viscosity (Chien et al. 1967) and hematocrit level (Deng et al. 1993; Xu et al. 2008); hence, it is physiologically relevant to in vivo microcirculation of blood (Baskurt et al. 2011a; Baskurt and Meiselman 2013; Tuma et al. 2011). Red blood cell aggregation associated disorders include hypertension (Lominadze et al. 1998) and thrombosis (Andrews and Low 1999). In addition to (1) the shear forces applied to the cells (Baskurt et al. 2011b; Lim et al. 2010; Shin et al. 2009) and (2) the cellular factors (electrostatic repulsion, membrane strain) (Chien and Jan 1973; Jan and Chien 1973; Nash and Meiselman 1983; Rampling et al. 2004), the aggregation process is affected by the presence and concentrations of macromolecules in the suspending medium (fibrinogen or dextran) (Armstrong et al. 2001; Barshtein et al. 1998; Neu et al. 2008). Two hypotheses are proposed for the explanation of the aggregation dynamics, Abstract Red blood cell aggregation is an intrinsic property of red blood cells that form reversible stacked structures, also called rouleaux, under low shear rates. Erythrocyte sedimentation rate (ESR), commonly performed in clinics, is an indirect inflammation screener and a prognostic test for diseases. We have recently developed a microfluidic system for rapid measurement of ESR from 40 μl whole blood employing the aggregation dynamics. In this work, we propose the use of an aggregation inducer, dextran polyglucose, for the preparation of multiple blood samples with differing aggregation dynamics. Using these samples, we characterized the performance of the system with three aggregation indices and under varying experimental conditions. Additionally, using the same underlying principle, we improved the system for ESR measurement using both venipuncture and fingerprick whole blood samples depending on the user needs. The results demonstrate that the system performs equally well with both samples, which validates the compatibility of the system for both laboratory and point-of-care applications where venous and capillary blood are the primary samples, respectively. The detailed characterization presented in this study legitimates the feasibility of the system for ultrafast and facile