Automated Parallel Electrical Characterization of Cells Using Optically-Induced Dielectrophoresis

This article reports an automated optically-induced dielectrophoresis (ODEP) system for characterizing the specific membrane capacitance (SMC) of individual cells. The simulation of cell motion is conducted to analyze the electrokinetic forces acting on the cell. A self-developed visual tracking algorithm for multicells is used to realize an automated process for determining the frequency-sweeping range, crossover frequencies, and cell radii. The SMC values of malignant bladder cancer cells (T24 and RT4) and normal urothelial cells (SV-HUC-1) were quantified using the automated system, demonstrating that the system has a measurement speed of ~1 cell/s, an accuracy of 1 kHz for the crossover frequency determination, and an accuracy of $0.2~\mu \text{m}$ for the cell radius measurement. Note to Practitioners—The current manual optically-induced dielectrophoresis (ODEP) quantification of the specific membrane capacitance (SMC) values of the cells requires a tedious and time-consuming procedure for measuring the cell size and crossover frequency. The automated ODEP approach presented in this article was developed to identify multiple cells and trigger alternating current (ac) bias potential for measuring the radius and crossover frequency of multiple cells. Compared to the manual method, the automated system significantly improves the efficiency of the SMC measurement.

[1]  Fang Yang,et al.  Dielectrophoretic separation of colorectal cancer cells. , 2010, Biomicrofluidics.

[2]  Huayan Pu,et al.  Micropipette Aspiration of Single Cells for Both Mechanical and Electrical Characterization , 2019, IEEE Transactions on Biomedical Engineering.

[3]  Siyuan Yu,et al.  Patterned Optoelectronic Tweezers: A New Scheme for Selecting, Moving, and Storing Dielectric Particles and Cells. , 2018, Small.

[4]  Yu Sun,et al.  Biophysical Characterization of Bladder Cancer Cells with Different Metastatic Potential , 2013, Cell Biochemistry and Biophysics.

[5]  Jonathan J. Chen,et al.  Biophysical and biomolecular determination of cellular age in humans , 2017, Nature Biomedical Engineering.

[6]  Wenfeng Liang,et al.  Extracellular-controlled breast cancer cell formation and growth using non-UV patterned hydrogels via optically-induced electrokinetics. , 2014, Lab on a chip.

[7]  R. Pethig,et al.  Use of dielectrophoretic collection spectra for characterizing differences between normal and cancerous cells , 1992, Conference Record of the 1992 IEEE Industry Applications Society Annual Meeting.

[8]  F F Becker,et al.  Electrorotation of liposomes: verification of dielectric multi-shell model for cells. , 1997, Biochimica et biophysica acta.

[9]  Wenfeng Liang,et al.  Characterization of the self-rotational motion of stored red blood cells by using optically-induced electrokinetics. , 2016, Optics letters.

[10]  Lianqing Liu,et al.  Rapidly patterning micro/nano devices by directly assembling ions and nanomaterials , 2016, Scientific Reports.

[11]  Yan Peng,et al.  SMC Difference of Normal and Cancerous Human Urothelial Cells Quantified with an Opto-Electrokinetic Device , 2018, 2018 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS).

[12]  Yu Sun,et al.  Mechanical characterization of benign and malignant urothelial cells from voided urine , 2013 .

[13]  Min-Hsien Wu,et al.  The utilization of optically-induced-dielectrophoresis (ODEP)-based virtual cell filters in a microfluidic system for continuous isolation and purification of circulating tumour cells (CTCs) based on their size characteristics , 2017 .

[14]  Ming C. Wu,et al.  Massively parallel manipulation of single cells and microparticles using optical images , 2005, Nature.

[15]  Roland T. Chin,et al.  On the Detection of Dominant Points on Digital Curves , 1989, IEEE Trans. Pattern Anal. Mach. Intell..

[16]  Wenfeng Liang,et al.  Distinctive translational and self-rotational motion of lymphoma cells in an optically induced non-rotational alternating current electric field. , 2015, Biomicrofluidics.

[17]  Keiichi Abe,et al.  Topological structural analysis of digitized binary images by border following , 1985, Comput. Vis. Graph. Image Process..

[18]  Pei-Yu Chiou,et al.  Microfluidic integrated optoelectronic tweezers for single-cell preparation and analysis. , 2013, Lab on a chip.

[19]  Lianqing Liu,et al.  Performance Investigation of Multilayer MoS2 Thin-Film Transistors Fabricated via Mask-free Optically Induced Electrodeposition. , 2017, ACS applied materials & interfaces.

[20]  Makoto Sugai,et al.  Electrorotation of non-spherical cells: Theory for ellipsoidal cells with an arbitrary number of shells , 1993 .

[21]  N. Otsu A threshold selection method from gray level histograms , 1979 .

[22]  Michael P Hughes,et al.  Differences in the biophysical properties of membrane and cytoplasm of apoptotic cells revealed using dielectrophoresis. , 2006, Biochimica et biophysica acta.

[23]  H. Morgan,et al.  Electrohydrodynamics and dielectrophoresis in microsystems: scaling laws , 2003 .

[24]  Junbo Wang,et al.  Single-Cell Electrical Phenotyping Enabling the Classification of Mouse Tumor Samples , 2016, Scientific reports.

[25]  Peter R. C. Gascoyne,et al.  Isolation of Circulating Tumor Cells by Dielectrophoresis , 2014, Cancers.

[26]  Wenfeng Liang,et al.  Determination of Cell Membrane Capacitance and Conductance via Optically Induced Electrokinetics. , 2017, Biophysical journal.

[27]  Wenfeng Liang,et al.  Simultaneous separation and concentration of micro- and nano-particles by optically induced electrokinetics , 2013 .

[28]  Dino Di Carlo,et al.  Hydrodynamic stretching of single cells for large population mechanical phenotyping , 2012, Proceedings of the National Academy of Sciences.

[29]  E Neher,et al.  Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Lianqing Liu,et al.  3-D Non-UV Digital Printing of Hydrogel Microstructures by Optically Controlled Digital Electropolymerization , 2015, Journal of Microelectromechanical Systems.

[31]  Jacob N. Israelachvili,et al.  Interactions and visualization of bio-mimetic membrane detachment at smooth and nano-rough gold electrode surfaces , 2013 .

[32]  W. Yue,et al.  Tumor cell characterization and classification based on cellular specific membrane capacitance and cytoplasm conductivity. , 2014, Biosensors & bioelectronics.

[33]  Ping-Hei Chen,et al.  Optically-induced-dielectrophoresis (ODEP)-based cell manipulation in a microfluidic system for high-purity isolation of integral circulating tumor cell (CTC) clusters based on their size characteristics , 2018 .

[34]  Tokiko Endo,et al.  Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ , 2011, Histopathology.