This paper reports the first study of stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at the single cell level, leukemic metastasis progresses are accompanied by biophysical property alterations. A microfluidic device was utilized to electrically measure cell volume and transit time of single lymphocytes from healthy and CLL patients. The results from testing thousands of cells reveal that lymphocytes from CLL patients have higher stiffness (i.e., lower deformability), as compared to lymphocytes in healthy samples, which was also confirmed by AFM indentation tests. This observation is in sharp contrast to the known knowledge on other types of metastatic cells (e.g., breast and lung cancer cells) whose stiffness becomes lower as metastasis progresses.
Sickle cell trait (SCT) is a condition in which an individual inherits one sickle hemoglobin gene (HbS) and one normal beta hemoglobin gene (HbA). It has been hypothesized that under extreme physical stress, the compromised mechanical properties of the red blood cells (RBCs) may be the underlying mechanism of clinical complications of sickle cell trait individuals. However, whether sickle cell trait (SCT) should be treated as physiologically normal remains controversial. In this work, the mechanical properties (i.e., shear modulus and viscosity) of individual RBCs were quantified using a microsystem capable of precisely controlling the oxygen level of RBCs' microenvironment. Individual RBCs were deformed under shear stress. After the release of shear stress, the dynamic cell recovery process was captured and analyzed to extract the mechanical properties of single RBCs. The results demonstrate that RBCs from sickle cell trait individuals are inherently stiffer and more viscous than normal RBCs from healthy donors, but oxygen level variations do not alter their mechanical properties or morphology.
This paper presents a microfluidic device with wide channels and embedded AgPDMS electrodes for measuring the electrical properties of single cells. The work demonstrates the feasibility of using a large channel design and embedded electrodes for impedance spectroscopy to circumvent issues such as channel clogging and limited device re-usability. AgPDMS electrodes were formed on channel sidewalls for impedance detection and cell electrical properties measurement. Equivalent circuit models were used to interpret multifrequency impedance data to quantify each cell's cytoplasm conductivity and specific membrane capacitance. T24 cells were tested to validate the microfluidic system and modeling results. Comparisons were then made by measuring two leukemia cell lines (AML-2 and HL-60) which were found to have different cytoplasm conductivity values (0.29 ± 0.15 S m −1 versus 0.47 ± 0.20 S m −1) and specific membrane capacitance values (41 ± 25 mF m −2 versus 55 ± 26 mF m −2) when the cells were flown through the wide channel and measured by the AgPDMS electrodes.
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