IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 60, NO. 12, DECEMBER 2013 3269 Electrokinetic Analysis of Cell Translocation in Low-Cost Microfluidic Cytometry for Tumor Cell Detection and Enumeration Jinhong Guo, Tze Sian Pui, Yong-Ling Ban, Abdur Rub Abdur Rahman, and Yuejun Kang ∗ Abstract—Conventional Coulter counters have been introduced as an important tool in biological cell assays since several decades ago. Recently, the emerging portable Coulter counter has demon- strated its merits in point of care diagnostics, such as on chip detection and enumeration of circulating tumor cells (CTC). The working principle is based on the cell translocation time and am- plitude of electrical current change that the cell induces. In this paper, we provide an analysis of a Coulter counter that evaluates the hydrodynamic and electrokinetic properties of polystyrene mi- croparticles in a microfluidic channel. The hydrodynamic force and electrokinetic force are concurrently analyzed to determine the translocation time and the electrical current pulses induced by the particles. Finally, we characterize the chip performance for CTC detection. The experimental results validate the numerical analysis of the microfluidic chip. The presented model can provide critical insight and guidance for developing micro-Coulter counter for point of care prognosis. Index Terms—Circulating tumor cell, Coulter counter, electroki- netic, hydrodynamic, point of care. I. INTRODUCTION C OULTER counter has emerged as a powerful tool for the detection and enumeration of biological particles or cells in fluidic electrolyte solution [1]. Their applications range widely from the analysis of pollen [2], human cells [3], bac- teria [4], viruses [5], DNA, and other biomolecules [6], [7], to ion detection for some industrial applications. When micropar- ticles or cells translocate through a micro/nanosensing aperture, Manuscript received February 14, 2013; revised May 8, 2013; accepted Au- gust 5, 2013. Date of publication August 15, 2013; date of current version November 18, 2013. The work of Y. Kang was supported by a start-up grant from the College of Engineering and Academic Research Fund, Nanyang Tech- nological University, Ministry of Education of Singapore under Grant RG 26/11. The work of T. S. Pui and A. R. A. Rahman was supported by A*STAR under JCO Grant #11/3/06/ASC/02. The work of J. Guo was supported by the Ph.D. scholarship from Nanyang Technological University. Asterisk indicates the cor- responding author. J. Guo is with the School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459 (e-mail: jguo002@e.ntu.edu.sg). T. S. Pui and A. R. A. Rahman are with the A*STAR, Institute of Micro- electronics, Singapore 117685 (e-mail: puits@ime.a-star.edu.sg; abdurr@ime. a-star.edu.sg). Y.-L. Ban is with the Institute of Electromagnetics, University of Elec- tronic Science and Technology of China, Chengdu 611731, China (e-mail: byl@uestc.edu.cn). ∗ Y. Kang is with the School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459 (e-mail: yuejun.kang@ ntu.edu.sg). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TBME.2013.2278014 the aperture is electrically blocked because these nonconduct- ing particles displace the conducting electrolyte solution. This results in significant electrical current change across the aper- ture. By analyzing the change of electrical pulse amplitude and pulse bandwidth, the information of size and numbers of the microparticles can be obtained. Recently, due to the fast de- velopment of micro/nanofabrication technology, micro-Coulter counters have been developed for point of care analysis of whole blood cells and cancer cells at low cost [1]. It is well known that the circulating tumor cells (CTCs) are shed from primary tumor and transported in circulatory blood to a distant organ form- ing metastasis, which is the major cause of mortality in most cancer patients. Since the number density of CTCs in blood is proportionally correlated to metastases, accurate enumera- tion of CTCs in the circulatory blood is critical for monitoring disease progression and assessing the patient response to treat- ment. However, it is of great challenge to detect and quantify the CTCs in the early cancer stage, which is due to the fact that the CTCs are extremely rare compared with other blood cells. There are many current methods for CTC detection using their unique physical properties, or fluorescent nanobioprobes based on the immunoreactions between the antibodies and the cancer biomarkers expressed on their cell surface [8], [9]. The conven- tional flow cytometry technique that is based on the fluorescent tag and laser optical detection is limited due to high opera- tion cost and bulky instruments. Meanwhile, the microfluidic impedance cytometry can provide a rapid and less costly solu- tion for the characterization of CTCs. The next generation of Coulter counters will have multiple channels which are expected to achieve much higher detection efficiency in a very short time. Therefore we present, in this paper, a numerical model for a comprehensive analysis of a microfluidic impedance flow cy- tometer for point of care CTC detection and enumeration. II. THEORY AND METHOD A. Mathematical Theory The structure of the microfluidic cytometer consists of four reservoirs (A, B, C, D). A/B are for sample inlet and outlet, re- spectively. C/D are the liquid channels that act as the conducting electrodes [see Fig. 1(a)]. The widths of the main channel and the conducting liquid channel are 160 and 300 μm, respectively [see Fig. 1(b)]. The length and width of the sensing aperture are 150 and 25 μm, respectively. The entire channel has the same height of 30 μm. 0018-9294 © 2013 IEEE