Enhanced Cell Stiffness Evaluation by Two-phase Decomposition

This work proposes an enhanced method for cell stiffness evaluation by eliminating the effect from cell viscosity. While the passing time of cell through a μ-channel is used for evaluating cell stiffness in the conventional method, the time includes both the effects of cell stiffness and cell viscosity. The key idea is that we separate the cell motion inside a μ-channel into two phases, the phases of deformation and constant velocity. We evaluate the cell stiffness by focusing on the cell motion in the phase of constant velocity. The results of experimental study are presented and discussed. KEYWORD cell stiffness, μ-channel, stiffness evaluation INTRODUCTION It is documented that there are human diseases associating with stiffening/softening of red blood cells [1,2]. As a result, it is important to develop a fast and accurate method to evaluate cell stiffness for medical practices. There are different approaches for evaluating biomechanical properties of cells [3]. The method of evaluating cell stiffness by a μ-channel [4] is much faster than most of conventional methods, such as micropipette aspiration [5], optical tweezers [6] and atomic force microscope [7]. However, the accuracy of the μ-channel method is sacrificed for its high sensing speed. In this work, we proposed a novel idea for improving the accuracy of the stiffness evaluation with a μ-channel. As far as we know that this is the first work of eliminating viscosity effect for the cell stiffness evaluation. MODELING AND KEY IDEA A spring is used for modeling the cell in the conventional method, while a spring and a damper are used for modeling the cell in the proposed model, as shown Figure 1(a). The spring and damper represent the stiffness and internal viscosity of a cell, respectively. The cell is pushed through the μ-channel by the pressure difference between two sides of the channel, and it deforms in order to squeeze into the channel. We defined Phase I as the duration while the spring and damper both react to the deformation, as left two cells illustrated in the lower diagram of Figure 1(a). After the cell fully entered the channel and reached to an equilibrium state, the shape of the cell becomes constant, as well as the velocity. Hence, only the spring is still responding to the deformation, and we defined this duration as Phase II, as right two cells illustrated in the lower diagram of Figure 1(a). According to this idea, the motion of the cell inside a μ-channel can be separated into two phases based on the motion profile. Phase I is the region where the motion profile is nonlinear, as the red curve in Figure 1(b). Phase II is the region where the motion profile is linear, as the green line in Figure 1(b). Figure 1: Comparison between the conventional and proposed μ-channel methods. (a) The cell is modeled with a spring in conventional method, but is modeled with a spring and a damper. Phase I is defined as both the spring and damper reacting to the deformation, while only the spring is in effect in Phase II. (b) Comparison between conventional methods and the proposed method. 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 28 November 1, 2012, Okinawa, Japan 978-0-9798064-5-2/μTAS 2012/$20©12CBMS-0001 1009 In conventional μ-channel method, it is assumed the cell reaches equilibrium immediately, and moves in a constant velocity through the channel, as the black line illustrated in Figure 1(b). From the comparison in Figure 1(b), we can clearly see the difference of equilibrium velocities between the conventional method (black) and the proposed method (green). We believe that the difference is the reason for the inaccuracy of the conventional μ-channel method.