Microfluidic impedance flow cytometry enabling high-throughput single-cell electrical property characterization

International Journal of Molecular Sciences

Volumn 16, Issue 5, 2015, Pages 9804-9830

  Chen, Jian ^a   Xue, Chengcheng ^a   Zhao, Yang ^a   Chen, Deyong ^a   Wu, Min Hsien ^b   Wang, Junbo ^a  

^a INSTITUTE OF ELECTRONICS   (China)

^b CHANG GUNG UNIVERSITY   (Taiwan)

Author keywords

High throughput; Impedance flow cytometry; Microfluidics; Single cell electrical property analysis

Indexed keywords

CD4 ANTIBODY;

BLOOD CELL COUNT; CELL ELONGATION; CELL LABELING; CELL MEMBRANE CONDUCTANCE; CELLULAR PARAMETERS; ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY; ESCHERICHIA COLI; FLOW CYTOMETRY; HUMAN; MICROELECTRODE; MICROFLUIDICS; OSTEOBLAST; POINT OF CARE TESTING; REVIEW; SENSITIVITY AND SPECIFICITY; SINGLE CELL ANALYSIS; SINGLE CELL ELECTRICAL PROPERTY; ANIMAL; HIGH THROUGHPUT SCREENING; IMPEDANCE; POINT OF CARE SYSTEM; PROCEDURES;

ANIMALS; ELECTRIC IMPEDANCE; FLOW CYTOMETRY; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MICROFLUIDICS; POINT-OF-CARE SYSTEMS; SINGLE-CELL ANALYSIS;

EID: 84929340112     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms16059804     Document Type: Review

References (128)

1. Morgan, H.; Sun, T.; Holmes, D.; Gawad, S.; Green, N.G. Single cell dielectric spectroscopy. J. Phys. D-Appl. Phys. 2007, 40, 61–70.
2. Valero, A.; Braschler, T.; Renaud, P. A unified approach to dielectric single cell analysis: Impedance and dielectrophoretic force spectroscopy. Lab Chip 2010, 10, 2216–2225.
3. Liang, X.; Graham, K.A.; Johannessen, A.C.; Costea, D.E.; Labeed, F.H. Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance. Integr. Biol. 2014, 6, 545–554.
4. Coley, H.M.; Labeed, F.H.; Thomas, H.; Hughes, M.P. Biophysical characterization of mdr breast cancer cell lines reveals the cytoplasm is critical in determining drug sensitivity. Biochim. Biophys. Acta 2007, 1770, 601–608.
5. Zhao, Y.; Zhao, X.T.; Chen, D.Y.; Luo, Y.N.; Jiang, M.; Wei, C.; Long, R.; Yue, W.T.; Wang, J.B.; Chen, J. Tumor cell characterization and classification based on cellular specific membrane capacitance and cytoplasm conductivity. Biosens. Bioelectron. 2014, 57, 245–253.
6. Song, H.; Wang, Y.; Rosano, J.M.; Prabhakarpandian, B.; Garson, C.; Pant, K.; Lai, E. A microfluidic impedance flow cytometer for identification of differentiation state of stem cells. Lab Chip 2013, 13, 2300–2310.
7. Watkins, N.N.; Hassan, U.; Damhorst, G.; Ni, H.; Vaid, A.; Rodriguez, W.; Bashir, R. Microfluidic CD4+ and CD8+ t lymphocyte counters for point-of-care hiv diagnostics using whole blood. Sci. Trans. Med. 2013, 5, 214ra170.
8. Han, X.; van Berkel, C.; Gwyer, J.; Capretto, L.; Morgan, H. Microfluidic lysis of human blood for leukocyte analysis using single cell impedance cytometry. Anal. Chem. 2012, 84, 1070–1075.
9. Du, E.; Ha, S.; Diez-Silva, M.; Dao, M.; Suresh, S.; Chandrakasan, A.P. Electric impedance microflow cytometry for characterization of cell disease states. Lab Chip 2013, 13, 3903–3909.
10. Holmes, D.; Pettigrew, D.; Reccius, C.H.; Gwyer, J.D.; van Berkel, C.; Holloway, J.; Davies, D.E.; Morgan, H. Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry. Lab Chip 2009, 9, 2881–2889.
11. Holmes, D.; Morgan, H. Single cell impedance cytometry for identification and counting of CD4 t-cells in human blood using impedance labels. Anal. Chem. 2010, 82, 1455–1461.
12. Zheng, Y.; Nguyen, J.; Wei, Y.; Sun, Y. Recent advances in microfluidic techniques for single-cell biophysical characterization. Lab Chip 2013, 13, 2464–2483.
13. Labeed, F.H.; Coley, H.M.; Thomas, H.; Hughes, M.P. Assessment of multidrug resistance reversal using dielectrophoresis and flow cytometry. Biophys. J. 2003, 85, 2028–2034.
14. Broche, L.M.; Labeed, F.H.; Hughes, M.P. Extraction of dielectric properties of multiple populations from dielectrophoretic collection spectrum data. Phys. Med. Biol. 2005, 50, 2267–2274.
15. Duncan, L.; Shelmerdine, H.; Hughes, M.P.; Coley, H.M.; Hubner, Y.; Labeed, F.H. Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells. Phys. Med. Biol. 2008, 53, N1–N7.
16. Vykoukal, D.M.; Gascoyne, P.R.; Vykoukal, J. Dielectric characterization of complete mononuclear and polymorphonuclear blood cell subpopulations for label-free discrimination. Integr. Biol. 2009, 1, 477–484.
17. Wu, L.; Lanry Yung, L.Y.; Lim, K.M. Dielectrophoretic capture voltage spectrum for measurement of dielectric properties and separation of cancer cells. Biomicrofluidics 2012, 6, 14113.
18. Bebarova, M. Advances in patch clamp technique: Towards higher quality and quantity. Gen. Physiol. Biophys. 2012, 31, 131–140.
19. Kornreich, B.G. The patch clamp technique: Principles and technical considerations. J. Vet. Cardiol. 2007, 9, 25–37.
20. Dale, T.J.; Townsend, C.; Hollands, E.C.; Trezise, D.J. Population patch clamp electrophysiology: A breakthrough technology for ion channel screening. Mol. Biosyst. 2007, 3, 714–722.
21. Liem, L.K.; Simard, J.M.; Song, Y.; Tewari, K. The patch clamp technique. Neurosurgery 1995, 36, 382–392.
22. Cahalan, M.; Neher, E. Patch clamp techniques: An overview. Methods Enzymol. 1992, 207, 3–14.
23. Sakmann, B.; Neher, E. Patch clamp techniques for studying ionic channels in excitable membranes. Annu. Rev. Physiol. 1984, 46, 455–472.
24. Auerbach, A.; Sachs, F. Patch clamp studies of single ionic channels. Annu. Rev. Biophys. Bioeng. 1984, 13, 269–302.
25. Rohani, A.; Varhue, W.; Su, Y.H.; Swami, N.S. Electrical tweezer for highly parallelized electrorotation measurements over a wide frequency bandwidth. Electrophoresis 2014, 35, 1795–1802.
26. Lei, U.; Sun, P.H.; Pethig, R. Refinement of the theory for extracting cell dielectric properties from dielectrophoresis and electrorotation experiments. Biomicrofluidics 2011, 5, 044109.
27. Voyer, D.; Frenea-Robin, M.; Buret, F.; Nicolas, L. Improvements in the extraction of cell electric properties from their electrorotation spectrum. Bioelectrochemistry 2010, 79, 25–30.
28. Jones, T.B. Basic theory of dielectrophoresis and electrorotation. IEEE Eng. Med. Biol. Mag. 2003, 22, 33–42.
29. Goater, A.D.; Pethig, R. Electrorotation and dielectrophoresis. Parasitology 1998, 117 (Suppl.), S177–S189.
30. Fuhr, G.; Glaser, R.; Hagedorn, R. Rotation of dielectrics in a rotating electric high-frequency field-model experiments and theoretical explanation of the rotation effect of living cells. Biophys. J. 1986, 49, 395–402.
31. Egger, M.; Donath, E.; Ziemer, S.; Glaser, R. Electrorotation--a new method for investigating membrane events during thrombocyte activation. Influence of drugs and osmotic pressure. Biochim. Biophys. Acta 1986, 861, 122–130.
32. Fuhr, G.; Hagedorn, R.; Goring, H. Separation of different cell-types by rotating electric-fields. Plant Cell Physiol. 1985, 26, 1527–1531.
33. Yobas, L. Microsystems for cell-based electrophysiology. J. Micromech. Microeng. 2013, 23, 083002.
34. Sabuncu, A.C.; Zhuang, J.; Kolb, J.F.; Beskok, A. Microfluidic impedance spectroscopy as a tool for quantitative biology and biotechnology. Biomicrofluidics 2012, 6, 34103.
35. Sun, T.; Morgan, H. Single-cell microfluidic impedance cytometry: A review. Microfluid. Nanofluid. 2010, 8, 423–443.
36. Cheung, K.C.; di Berardino, M.; Schade-Kampmann, G.; Hebeisen, M.; Pierzchalski, A.; Bocsi, J.; Mittag, A.; Tarnok, A. Microfluidic impedance-based flow cytometry. Cytom. A 2010, 77, 648–666.
37. Wootton, R.C.; Demello, A.J. Microfluidics: Exploiting elephants in the room. Nature 2010, 464, 839–840.
38. Whitesides, G.M. The origins and the future of microfluidics. Nature 2006, 442, 368–373.
39. Squires, T.M.; Quake, S.R. Microfluidics: Fluid physics at the nanoliter scale. Rev. Mod. Phys. 2005, 77, 977.
40. Sackmann, E.K.; Fulton, A.L.; Beebe, D.J. The present and future role of microfluidics in biomedical research. Nature 2014, 507, 181–189.
41. El-Ali, J.; Sorger, P.K.; Jensen, K.F. Cells on chips. Nature 2006, 442, 403–411.
42. Meyvantsson, I.; Beebe, D.J. Cell culture models in microfluidic systems. Annu. Rev. Anal. Chem. 2008, 1, 423–449.
43. Paguirigan, A.L.; Beebe, D.J. Microfluidics meet cell biology: Bridging the gap by validation and application of microscale techniques for cell biological assays. BioEssays News Rev. Mol. Cell. Dev. Biol. 2008, 30, 811–821.
44. Velve-Casquillas, G.; Le Berre, M.; Piel, M.; Tran, P.T. Microfluidic tools for cell biological research. Nano Today 2010, 5, 28–47.
45. Thompson, A.M.; Paguirigan, A.L.; Kreutz, J.E.; Radich, J.P.; Chiu, D.T. Microfluidics for single-cell genetic analysis. Lab Chip 2014, 14, 3135–3142.
46. Yin, H.; Marshall, D. Microfluidics for single cell analysis. Curr. Opin. Biotechnol. 2012, 23, 110–119.
47. Lecault, V.; White, A.K.; Singhal, A.; Hansen, C.L. Microfluidic single cell analysis: From promise to practice. Curr. Opin. Chem. Biol. 2012, 16, 381–390.
48. Ryan, D.; Ren, K.; Wu, H. Single-cell assays. Biomicrofluidics 2011, 5, 21501.
49. Zare, R.N.; Kim, S. Microfluidic platforms for single-cell analysis. Annu. Rev. Biomed. Eng. 2010, 12, 187–201.
50. Sims, C.E.; Allbritton, N.L. Analysis of single mammalian cells on-chip. Lab Chip 2007, 7, 423–440.
51. Di Carlo, D.; Lee, L.P. Dynamic single-cell analysis for quantitative biology. Anal. Chem. 2006, 78, 7918–7925.
52. Cho, Y.H.; Yamamoto, T.; Sakai, Y.; Fujii, T.; Kim, B. Development of microfluidic device for electrical/physical characterization of single cell. J. Microelectromech. Syst. 2006, 15, 287–295.
53. Jang, L.S.; Wang, M.H. Microfluidic device for cell capture and impedance measurement. Biomed. Microdevices 2007, 9, 737–743.
54. Senez, V.; Lennon, E.; Ostrovidov, S.; Yamamoto, T.; Fujita, H.; Sakai, Y.; Fujii, T. Integrated 3-d silicon electrodes for electrochemical sensing in microfluidic environments: Application to single-cell characterization. IEEE Sens. J. 2008, 8, 548–557.
55. Hua, S.Z.; Pennell, T. A microfluidic chip for real-time studies of the volume of single cells. Lab Chip 2009, 9, 251–256.
56. Wang, M.H.; Jang, L.S. A systematic investigation into the electrical properties of single hela cells via impedance measurements and comsol simulations. Biosens. Bioelectron. 2009, 24, 2830–2835.
57. Jang, L.S.; Li, H.H.; Jao, J.Y.; Chen, M.K.; Liu, C.F. Design and fabrication of microfluidic devices integrated with an open-ended mems probe for single-cell impedance measurement. Microfluid. Nanofluid. 2010, 8, 509–519.
58. Malleo, D.; Nevill, J.T.; Lee, L.P.; Morgan, H. Continuous differential impedance spectroscopy of single cells. Microfluid. Nanofluid. 2010, 9, 191–198.
59. Han, K.H.; Han, A.; Frazier, A.B. Microsystems for isolation and electrophysiological analysis of breast cancer cells from blood. Biosens. Bioelectron. 2006, 21, 1907–1914.
60. Cho, S.B.; Thielecke, H. Micro hole-based cell chip with impedance spectroscopy. Biosens. Bioelectron. 2007, 22, 1764–1768.
61. James, C.D.; Reuel, N.; Lee, E.S.; Davalos, R.V.; Mani, S.S.; Carroll-Portillo, A.; Rebeil, R.; Martino, A.; Apblett, C.A. Impedimetric and optical interrogation of single cells in a microfluidic device for real-time viability and chemical response assessment. Biosens. Bioelectron. 2008, 23, 845–851.
62. Cho, Y.; Kim, H.S.; Frazier, A.B.; Chen, Z.G.; Shin, D.M.; Han, A. Whole-cell impedance analysis for highly and poorly metastatic cancer cells. J. Microelectromech. Syst. 2009, 18, 808–817.
63. Chen, J.; Zheng, Y.; Tan, Q.; Zhang, Y.L.; Li, J.; Geddie, W.R.; Jewett, M.A.; Sun, Y. A microfluidic device for simultaneous electrical and mechanical measurements on single cells. Biomicrofluidics 2011, 5, 14113.
64. Kang, G.; Kim, Y.-J.; Moon, H.-S.; Lee, J.-W.; Yoo, T.-K.; Park, K.; Lee, J.-H. Discrimination between the human prostate normal cell and cancer cell by using a novel electrical impedance spectroscopy controlling the cross-sectional area of a microfluidic channel. Biomicrofluidics 2013, 7, 044126.
65. Tan, Q.; Ferrier, G.A.; Chen, B.K.; Wang, C.; Sun, Y. Quantification of the specific membrane capacitance of single cells using a microfluidic device and impedance spectroscopy measurement. Biomicrofluidics 2012, 6, 034112.
66. Jang, L.S.; Huang, P.H.; Lan, K.C. Single-cell trapping utilizing negative dielectrophoretic quadrupole and microwell electrodes. Biosens. Bioelectron. 2009, 24, 3637–3644.
67. Lan, K.C.; Jang, L.S. Integration of single-cell trapping and impedance measurement utilizing microwell electrodes. Biosens. Bioelectron. 2011, 26, 2025–2031.
68. Hong, J.-L.; Lan, K.-C.; Jang, L.-S. Electrical characteristics analysis of various cancer cells using a microfluidic device based on single-cell impedance measurement. Sens. Actuators B Chem. 2012, 173, 927–934.
69. Chen, N.-C.; Chen, C.-H.; Chen, M.-K.; Jang, L.-S.; Wang, M.-H. Single-cell trapping and impedance measurement utilizing dielectrophoresis in a parallel-plate microfluidic device. Sens. Actuators B Chem. 2014, 190, 570–577.
70. Thein, M.; Asphahani, F.; Cheng, A.; Buckmaster, R.; Zhang, M.Q.; Xu, J. Response characteristics of single-cell impedance sensors employed with surface-modified microelectrodes. Biosens. Bioelectron. 2010, 25, 1963–1969.
71. Asphahani, F.; Wang, K.; Thein, M.; Veiseh, O.; Yung, S.; Xu, J.A.; Zhang, M.Q. Single-cell bioelectrical impedance platform for monitoring cellular response to drug treatment. Phys. Biol. 2011, 8, 015006.
72. Asphahani, F.; Zheng, X.H.; Veiseh, O.; Thein, M.; Xu, J.; Ohuchi, F.; Zhang, M.Q. Effects of electrode surface modification with chlorotoxin on patterning single glioma cells. Phys. Chem. Chem. Phys. 2011, 13, 8953–8960.
73. Wu, Y.; Han, X.; Benson, J.D.; Almasri, M. Micromachined coulter counter for dynamic impedance study of time sensitive cells. Biomed. Microdevices 2012, 14, 739–750.
74. Wu, Y.; Benson, J.D.; Critser, J.K.; Almasri, M. Note: Microelectromechanical systems coulter counter for cell monitoring and counting. Rev. Sci. Instrum. 2010, 81, 076103.
75. Swanton, E.M.; Curby, W.A.; Lind, H.E. Experiences with the coulter counter in bacteriology. Appl. Microbiol. 1962, 10, 480–485.
76. Bryan, A.K.; Engler, A.; Gulati, A.; Manalis, S.R. Continuous and long-term volume measurements with a commercial coulter counter. PLoS ONE 2012, 7, e29866.
77. Gawad, S.; Schild, L.; Renaud, P. Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing. Lab Chip 2001, 1, 76–82.
78. Gou, H.-L.; Zhang, X.-B.; Bao, N.; Xu, J.-J.; Xia, X.-H.; Chen, H.-Y. Label-free electrical discrimination of cells at normal, apoptotic and necrotic status with a microfluidic device. J. Chromatogr. A 2011, 1218, 5725–5729.
79. Cheung, K.; Gawad, S.; Renaud, P. Impedance spectroscopy flow cytometry: On-chip label-free cell differentiation. Cytom. Part A 2005, 65A, 124–132.
80. Haandbaek, N.; Burgel, S.C.; Heer, F.; Hierlemann, A. Characterization of subcellular morphology of single yeast cells using high frequency microfluidic impedance cytometer. Lab Chip 2014, 14, 369–377.
81. Bernabini, C.; Holmes, D.; Morgan, H. Micro-impedance cytometry for detection and analysis of micron-sized particles and bacteria. Lab Chip 2011, 11, 407–412.
82. Haandbaek, N.; With, O.; Burgel, S.C.; Heer, F.; Hierlemann, A. Resonance-enhanced microfluidic impedance cytometer for detection of single bacteria. Lab Chip 2014, 14, 3313–3324.
83. Chen, J.; Zheng, Y.; Tan, Q.; Shojaei-Baghini, E.; Zhang, Y.L.; Li, J.; Prasad, P.; You, L.; Wu, X.Y.; Sun, Y. Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells. Lab Chip 2011, 11, 3174–3181.
84. Zheng, Y.; Shojaei-Baghini, E.; Azad, A.; Wang, C.; Sun, Y. High-throughput biophysical measurement of human red blood cells. Lab Chip 2012, 12, 2560–2567.
85. Zhao, Y.; Chen, D.; Li, H.; Luo, Y.; Deng, B.; Huang, S.B.; Chiu, T.K.; Wu, M.H.; Long, R.; Hu, H. et al. A microfluidic system enabling continuous characterization of specific membrane capacitance and cytoplasm conductivity of single cells in suspension. Biosens. Bioelectron. 2013, 43C, 304–307.
86. Barat, D.; Spencer, D.; Benazzi, G.; Mowlem, M.C.; Morgan, H. Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer. Lab Chip 2012, 12, 118–126.
87. Spencer, D.C.; Elliott, G.; Morgan, H. A sheath-less combined optical and impedance micro-cytometer. Lab Chip 2014, 14, 3064–3073.
88. Van Berkel, C.; Gwyer, J.D.; Deane, S.; Green, N.G.; Holloway, J.; Hollis, V.; Morgan, H. Integrated systems for rapid point of care (poc) blood cell analysis. Lab Chip 2011, 11, 1249–1255.
89. Gawad, S.; Cheung, K.; Seger, U.; Bertsch, A.; Renaud, P. Dielectric spectroscopy in a micromachined flow cytometer: Theoretical and practical considerations. Lab Chip 2004, 4, 241–251.
90. Mernier, G.; Piacentini, N.; Tornay, R.; Buffi, N.; Renaud, P. Cell viability assessment by flow cytometry using yeast as cell model. Sens. Actuators B Chem. 2011, 154, 160–163.
91. Meissner, R.; Joris, P.; Eker, B.; Bertsch, A.; Renaud, P. A microfluidic-based frequency-multiplexing impedance sensor (fmis). Lab Chip 2012, 12, 2712–2718.
92. Mernier, G.; Hasenkamp, W.; Piacentini, N.; Renaud, P. Multiple-frequency impedance measurements in continuous flow for automated evaluation of yeast cell lysis. Sens. Actuators B Chem. 2012, 170, 2–6.
93. Shaker, M.; Colella, L.; Caselli, F.; Bisegna, P.; Renaud, P. An impedance-based flow microcytometer for single cell morphology discrimination. Lab Chip 2014, 2014, 2548–2555.
94. Choi, H.; Jeon, C.S.; Hwang, I.; Ko, J.; Lee, S.; Choo, J.; Boo, J.-H.; Kim, H.C.; Chung, T.D. A flow cytometry-based submicron-sized bacterial detection system using a movable virtual wall. Lab Chip 2014, 14, 2327–2333.
95. Spencer, D.; Morgan, H. Positional dependence of particles in microfludic impedance cytometry. Lab Chip 2011, 11, 1234–1239.
96. Shelby, J.P.; White, J.; Ganesan, K.; Rathod, P.K.; Chiu, D.T. A microfluidic model for single-cell capillary obstruction by plasmodium falciparum infected erythrocytes. Proc. Natl. Acad. Sci. USA 2003, 100, 14618–14622.
97. Guo, Q.; Reiling, S.J.; Rohrbach, P.; Ma, H. Microfluidic biomechanical assay for red blood cells parasitized by plasmodium falciparum. Lab Chip 2012, 12, 1143–1150.
98. Kwan, J.M.; Guo, Q.; Kyluik-Price, D.L.; Ma, H.; Scott, M.D. Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells. Am. J. Hematol. 2013, 88, 682–689.
99. Rosenbluth, M.J.; Lam, W.A.; Fletcher, D.A. Analyzing cell mechanics in hematologic diseases with microfluidic biophysical flow cytometry. Lab Chip 2008, 8, 1062–1070.
100. Hou, H.W.; Li, Q.S.; Lee, G.Y.H.; Kumar, A.P.; Ong, C.N.; Lim, C.T. Deformability study of breast cancer cells using microfluidics. Biomed. Microdevices 2009, 11, 557–564.
101. Byun, S.; Son, S.; Amodei, D.; Cermak, N.; Shaw, J.; Kang, J.H.; Hecht, V.C.; Winslow, M.M.; Jacks, T.; Mallick, P. et al. Characterizing deformability and surface friction of cancer cells. Proc. Natl. Acad. Sci. USA 2013, 110, 7580–7585.
102. Luo, Y.N.; Chen, D.Y.; Zhao, Y.; Wei, C.; Zhao, X.T.; Yue, W.T.; Long, R.; Wang, J.B.; Chen, J. A constriction channel based microfluidic system enabling continuous characterization of cellular instantaneous young’s modulus. Sens. Actuators B Chem. 2014, 202, 1183–1189.
103. Zhao, Y.; Chen, D.; Luo, Y.; Li, H.; Deng, B.; Huang, S.-B.; Chiu, T.-K.; Wu, M.-H.; Long, R.; Hu, H. et al. A microfluidic system for cell type classification based on cellular size-independent electrical properties. Lab Chip 2013, 13, 2272–2277.
104. Huang, S.B.; Zhao, Z.; Chen, D.Y.; Lee, H.C.; Luo, Y.N.; Chiu, T.K.; Wang, J.B.; Chen, J.; Wu, M.H. A clogging-free microfluidic platform with an incorporated pneumatically-driven membrane-based active valve enabling specific membrane capacitance and cytoplasm conductivity characterization of single cells. Sens. Actuators B Chem. 2014, 190, 928–936.
105. Morgan, H.; Holmes, D.; Green, N.G. High speed simultaneous single particle impedance and fluorescence analysis on a chip. Curr. Appl. Phys. 2006, 6, 367–370.
106. Benazzi, G.; Holmes, D.; Sun, T.; Mowlem, M.C.; Morgan, H. Discrimination and analysis of phytoplankton using a microfluidic cytometer. Iet Nanobiotechnol. 2007, 1, 94–101.
107. Gawad, S.; Sun, T.; Green, N.G.; Morgan, H. Impedance spectroscopy using maximum length sequences: Application to single cell analysis. Rev. Sci. Instrum. 2007, 78, 054301.
108. Holmes, D.; She, J.K.; Roach, P.L.; Morgan, H. Bead-based immunoassays using a micro-chip flow cytometer. Lab Chip 2007, 7, 1048–1056.
109. Sun, T.; Gawad, S.; Bernabini, C.; Green, N.G.; Morgan, H. Broadband single cell impedance spectroscopy using maximum length sequences: Theoretical analysis and practical considerations. Meas. Sci. Technol. 2007, 18, 2859–2868.
110. Sun, T.; Green, N.G.; Gawad, S.; Morgan, H. Analytical electric field and sensitivity analysis for two microfluidic impedance cytometer designs. Iet Nanobiotechnol. 2007, 1, 69–79.
111. Sun, T.; Holmes, D.; Gawad, S.; Green, N.G.; Morgan, H. High speed multi-frequency impedance analysis of single particles in a microfluidic cytometer using maximum length sequences. Lab Chip 2007, 7, 1034–1040.
112. Sun, T.; van Berkel, C.; Green, N.G.; Morgan, H. Digital signal processing methods for impedance microfluidic cytometry. Microfluid. Nanofluid. 2009, 6, 179–187.
113. Barat, D.; Benazzi, G.; Mowlem, M.C.; Ruano, J.M.; Morgan, H. Design, simulation and characterisation of integrated optics for a microfabricated flow cytometer. Opt. Commun. 2010, 283, 1987–1992.
114. Gawad, S.; Holmes, D.; Benazzi, G.; Renaud, P.; Morgan, H. Impedance spectroscopy and optical analysis of single biological cells and organisms in microsystems. Methods Mol. Biol. 2010, 583, 149–182.
115. Sun, T.; Bernabini, C.; Morgan, H. Single-colloidal particle impedance spectroscopy: Complete equivalent circuit analysis of polyelectrolyte microcapsules. Langmuir 2010, 26, 3821–3828.
116. Sun, T.; Swindle, E.J.; Collins, J.E.; Holloway, J.A.; Davies, D.E.; Morgan, H. On-chip epithelial barrier function assays using electrical impedance spectroscopy. Lab Chip 2010, 10, 1611–1617.
117. Sun, T.; Tsuda, S.; Zauner, K.P.; Morgan, H. On-chip electrical impedance tomography for imaging biological cells. Biosens. Bioelectron. 2010, 25, 1109–1115.
118. Kumar, S.; Kumar, S.; Ali, M.A.; Anand, P.; Agrawal, V.V.; John, R.; Maji, S.; Malhotra, B.D. Microfluidic-integrated biosensors: Prospects for point-of-care diagnostics. Biotechnol. J. 2013, 8, 1267–1279.
119. Chin, C.D.; Linder, V.; Sia, S.K. Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip 2012, 12, 2118–2134.
120. Kiechle, F.L.; Holland, C.A. Point-of-care testing and molecular diagnostics: Miniaturization required. Clin. Lab. Med. 2009, 29, 555–560.
121. Sorger, P.K. Microfluidics closes in on point-of-care assays. Nat. Biotechnol. 2008, 26, 1345–1346.
122. Sia, S.K.; Kricka, L.J. Microfluidics and point-of-care testing. Lab Chip 2008, 8, 1982–1983.
123. Linder, V. Microfluidics at the crossroad with point-of-care diagnostics. Analyst 2007, 132, 1186–1192.
124. Yu, Z.T.; Aw Yong, K.M.; Fu, J. Microfluidic blood cell sorting: Now and beyond. Small 2014, 10, 1687–1703.
125. van der Meer, A.D.; Poot, A.A.; Duits, M.H.; Feijen, J.; Vermes, I. Microfluidic technology in vascular research. J. Biomed. Biotechnol. 2009, 2009, 823148.
126. Toner, M.; Irimia, D. Blood-on-a-chip. Annu. Rev. Biomed. Eng. 2005, 7, 77–103.
127. Hassan, U.; Bashir, R. Electrical cell counting process characterization in a microfluidic impedance cytometer. Biomed. Microdevices 2014, 16, 697–704.
128. Hassan, U.; Watkins, N.N.; Edwards, C.; Bashir, R. Flow metering characterization within an electrical cell counting microfluidic device. Lab Chip 2014, 14, 1469–1476.