An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation

Abstract

An on-chip deformability checker is proposed to improve the velocity–deformation correlation for red blood cell (RBC) evaluation. RBC deformability has been found related to human diseases, and can be evaluated based on RBC velocity through a microfluidic constriction as in conventional approaches. The correlation between transit velocity and amount of deformation provides statistical information of RBC deformability. However, such correlations are usually only moderate, or even weak, in practical evaluations due to limited range of RBC deformation. To solve this issue, we implemented three constrictions of different width in the proposed checker, so that three different deformation regions can be applied to RBCs. By considering cell responses from the three regions as a whole, we practically extend the range of cell deformation in the evaluation, and could resolve the issue about the limited range of RBC deformation. RBCs from five volunteer subjects were tested using the proposed checker. The results show that the correlation between cell deformation and transit velocity is significantly improved by the proposed deformability checker. The absolute values of the correlation coefficients are increased from an average of 0.54 to 0.92. The effects of cell size, shape and orientation to the evaluation are discussed according to the experimental results. The proposed checker is expected to be useful for RBC evaluation in medical practices.

Spring‐network model of red blood cell: From membrane mechanics to validation

“…To further validate the model, we simulated a device described in Reference and depicted in Figure . The height of the device is 3.5 μm which means that RBCs travel flat (in x ‐direction from left to right) and the deformation in slits as viewed from above is not determined by cell rotation.…”

“…In the following we thus study the dependence of the cell velocity on the cell deformation. We simulate the experiment using our model with elastic parameters taken from Section 4 and we compare the velocity‐deformation correlation to the experimental results provided in Reference .…”

On-chip cell manipulation and applications to deformability measurements

“…Most popular strategy was the quantification of the passage through a narrow channel under a constant pressure difference between the inlet and the outlet as shown in Fig. 2 [40][41][42][43][44][45]. Note that the widths of the narrow channels used here were comparable or less than the size of a single cell to confine the degree of freedom of the cell motion to one-dimensional line for the simple and defined experimental situations.…”

“…Note that the widths of the narrow channels used here were comparable or less than the size of a single cell to confine the degree of freedom of the cell motion to one-dimensional line for the simple and defined experimental situations. In this context, various biological and mechanical aspects have been quantified: ATP-release under wall shear stress [46], passing velocity through the narrow part [43] and the channel-width dependence [45], aspect ratio [47], circularity [48,49], elastic constants [49][50][51], and viscoelastic recovery time [52]. In those studies, RBCs exhibit stiffness (shear modulus) of the order of 10 −6 N/m, time constant of the order of 0.1 s for shape recovery, and large dispersions of the measured values as their typical mechanical responses.…”

Temporal Transition of Mechanical Characteristics of HUVEC/MSC Spheroids Using a Microfluidic Chip with Force Sensor Probes

“…Moreover, when the micropipette moves to the target point, disturbance flow occurs, so it is difficult to reduce the time interval of measurement. On the other hand, methods using a microfluidic chip have been proposed for mechanical characterization of single cells [ 18 , 19 , 20 , 21 , 22 , 23 ]. These methods deliver the target cells to the measurement point by flow and they can reduce the time interval of measurement.…”