Blood Viscoelasticity Measurement Using Interface Variations in Coflowing Streams under Pulsatile Blood Flows

Figure 1. Proposed method for measuring blood viscoelasticity by monitoring the interface of both fluids in coflowing streams under a pulsatile blood flow rate. (A) Schematic diagram of the proposed method, including a microfluidic device, two syringe pumps, and an image acquisition system. (a) Microfluidic device composed of two inlets (a, b), one outlet (a), two guiding channels (blood sample channel (BC) and reference-fluid channel (RC)), and a coflowing channel (CC). (b) Two syringe pumps employed to supply blood sample and reference fluid into the corresponding inlets. (c) High-speed camera with a frame rate of 5 kHz employed to capture microscopic images at an interval of 1 s. (B) Quantification of interface in coflowing channel and its mathematical model with a discrete fluidic circuit. (a) Region of interest (ROI, 150 × 750 pixels) selected in coflowing channel for evaluating interface (αB) and ROI (300 × 150 pixels) selected in blood sample channel for evaluating averaged blood velocity (<UBC>) or averaged image intensity (<IBC>). (b) Image conversion from gray-scale image to binary-scale image by using digital image processing. Interface (αB) was obtained as αB = WB/W. WB and W…

Figure 2. Estimation of correction factor (CF) and two approximate factors (F1, F2) with numerical simulation. (A) Variations of interface (αB) through numerical simulation with respect to flow-rate ratio (QR/QB): (a) QR/QB = 1, (b) QR/QB = 0.8, (c) QR/QB = 0.6, (d) QR/QB = 0.4, (e) QR/QB = 0.2, and (f) QR/QB = 0.1. For convenience, the flow rate of the blood sample was assumed to be QB = 1 mL/h. The viscosities of both fluids were given as μB = 1 cP and μR = 1 cP, respectively. (B) Variations of estimated normalized viscosity (μn) of blood sample and CF with respect to interface (0.1 < αB < 0.9). The CF was obtained as CF = 4.2162 αB4 – 8.4325 αB3 + 7.0763 αB2 − 2.86 αB2 + 1.4599 (R2 = 0.9912). (C) Variations of CF (αB)/(1 − αB), F1/(1 − αB), and normalized difference (ND) over αB. (D) Variations of CF (αB) × αB/(1 −αB), F2 × αB/(1 − αB), and ND over αB.

Figure 3. Evaluation of the effect of period (T) on viscoelasticity (blood viscosity and compliance). (A) Temporal variations of αB and βB with respect to period (T) ((a) T = 120 s, (b) T = 240 s, (c) T = 360 s, and (d) T = 480 s). (B) Quantification of viscosity (μB) and compliance (CB) with respect to period. (a) variations of β0 and β1 with respect to T, (b) variations of λB with respect to T, and (c) variations of μB and CB with respect to T.

Figure 4. Contribution of hematocrit (Hct) to viscoelasticity and ESR. Blood samples (Hct = 30%, 40%, 50%, and 60%) were prepared by adding normal RBCs into plasma. (A) Temporal variations of βB with respect to hematocrit ((a) Hct = 30%, (b) Hct = 40%, (c) Hct = 50%, and (d) Hct = 60%). (B) Temporal variations of μB and CB with respect to hematocrit ((a) Hct = 30%, (b) Hct = 40%, (c) Hct = 50%, and (d) Hct = 60%). (C) Evaluation of ESR occurring in driving syringe. (a) Microscopic images of blood sample (Hct = 30%) flowing in blood channels over time (t = 0, 480, 960, 1440, and 1920 s). (b) Side view of a driving syringe over time (t = 0, 480, 960, 1440, and 1920 s). (c) Temporal variations of <IBC> with respect to Hct. (d) Variations of SESR with respect to Hct.

Figure 5. Contribution of fixed blood sample to viscoelasticity of blood sample. Fixed RBCs were prepared chemically with GA solution (CGA) (CGA = 4, 8, and 12 µL/mL). A fixed blood sample (Hct = 50%) was then prepared by adding fixed RBCs into plasma: (A) temporal variations of βB with respect to CGA, (B) temporal variations of <IBC> with respect to CGA, (C) variations of β0 and β1 with respect to CGA, and (D) variations of μB and CB with respect to CGA.

Figure 6. Mathematical representation and quantification of contributions of channel depth and air cavity to compliance. (A) Mathematical representation of conventional viscometer and microfluidic system. (a) Mathematical representation of conventional viscometer. (b) Mathematical representation of microfluidic system. (B) Evaluation of channel depth (H) on compliance. Here, 1x PBS as test fluid was infused into a microfluidic system. (a) Variations of λB with respect to H. (b) Variations of RWB and CB with respect to H. (C) Evaluation of air cavity on compliance.

Figure 7. Quantitative compliance of GB and CB with respect to previous study [18] and present study. (A) Variation of GB and CB with respect to Hct. (B) Variations of GB and CB with respect to CGA.