# Enhancing the Accuracy of Measuring DEP Force Applied on Cells by Considering the Friction Effect

^{1}

^{2}

^{3}

^{*}

## Abstract

**:**

## 1. Introduction

## 2. Materials and Methods

#### 2.1. Theory and Modeling

#### 2.2. The Geometry of the Electrodes and the Microchannel

#### 2.3. Simulation

#### 2.4. Cell and Device Preparation

Properties | WBC Buffer | Sperm Buffer | WBC | Sperm | Reference |
---|---|---|---|---|---|

Working frequency (MHz) | - | - | 0.8 | 1 | - |

Radius * (µm) | - | - | 3.8 | 2.5 | [45,46] |

Membrane thickness (nm) | - | - | 7 | NK ** | [47] |

Permittivity | 78 | 78 | 104 | NK ** | [46] |

Membrane permittivity | - | - | 12 | NK ** | [48] |

Conductivity (µS/cm) | 800 | 140 | 650 | NK ** | [46] |

Membrane conductivity (nS/cm) | - | - | 10 | NK ** | [46] |

Density (kg/m^{3}) | - | - | 1019 | 1100 | [49,50] |

Viscosity (mPa.s) | 1.2 | 1.2 | - | - | [51] |

#### 2.5. Fabricating of the Electrodes and the Microchannel

#### 2.6. Laboratory Setup

## 3. Results and Discussion

#### 3.1. Simulation Results

#### 3.2. Experimental DEP Force Measurement

#### 3.3. Validation

## 4. Conclusions

## Supplementary Materials

## Author Contributions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Conflicts of Interest

## References

- Brugo-Olmedo, S.; Chillik, C.; Kopelman, S. Definition and causes of infertility. Reprod. Biomed. Online
**2001**, 2, 41–53. [Google Scholar] [CrossRef] [PubMed] - Zini, A.; Finelli, A.; Phang, D.; Jarvi, K. Influence of semen processing technique on human sperm DNA integrity. Urology
**2000**, 56, 1081–1084. [Google Scholar] [CrossRef] [PubMed] - Sarbandi, I.R.; Lesani, A.; Zand, M.M.; Nosrati, R. Rheotaxis-based sperm separation using a biomimicry microfluidic device. Sci. Rep.
**2021**, 11, 18327. [Google Scholar] [CrossRef] [PubMed] - Whitesides, G.M. The origins and the future of microfluidics. Nature
**2006**, 442, 368–373. [Google Scholar] [CrossRef] - Reyes, D.R.; Iossifidis, D.; Auroux, P.-A.; Manz, A. Micro Total Analysis Systems. Introduction, Theory, and Technology. Anal. Chem.
**2002**, 74, 2623–2636. [Google Scholar] [CrossRef] - Xie, L.; Ma, R.; Han, C.; Su, K.; Zhang, Q.; Qiu, T.; Wang, L.; Huang, G.; Qiao, J.; Wang, J.; et al. Integration of Sperm Motility and Chemotaxis Screening with a Microchannel-Based Device. Clin. Chem.
**2010**, 56, 1270–1278. [Google Scholar] [CrossRef] - Pérez-Cerezales, S.; Laguna-Barraza, R.; De Castro, A.C.; Sánchez-Calabuig, M.-J.; Cano-Oliva, E.; De Castro-Pita, F.J.; Montoro-Buils, L.; Pericuesta, E.; Fernández-González, R.; Gutiérrez-Adán, A. Sperm selection by thermotaxis improves ICSI outcome in mice. Sci. Rep.
**2018**, 8, 2902. [Google Scholar] [CrossRef] - Ainsworth, C.J.; Nixon, B.; Aitken, R.J. The electrophoretic separation of spermatozoa: An analysis of genotype, surface carbohydrate composition and potential for capacitation. Int. J. Androl.
**2011**, 34, e422–e434. [Google Scholar] [CrossRef] - Simon, L.; Murphy, K.; Aston, K.I.; Emery, B.R.; Hotaling, J.M.; Carrell, D.T. Micro-electrophoresis: A noninvasive method of sperm selection based on membrane charge. Fertil. Steril.
**2015**, 103, 361–366.e3. [Google Scholar] [CrossRef] - Esfahani, M.H.N.; Deemeh, M.R.; Tavalaee, M.; Sekhavati, M.H.; Gourabi, H. Zeta Sperm Selection Improves Pregnancy Rate and Alters Sex Ratio in Male Factor Infertility Patients: A Double-Blind, Randomized Clinical Trial. Int. J. Fertil. Steril.
**2016**, 10, 253–260. [Google Scholar] [CrossRef] - De Wagenaar, B.; Dekker, S.; de Boer, H.L.; Bomer, J.G.; Olthuis, W.; Berg, A.V.D.; Segerink, L.I. Towards microfluidic sperm refinement: Impedance-based analysis and sorting of sperm cells. Lab Chip
**2016**, 16, 1514–1522. [Google Scholar] [CrossRef] [PubMed] - Zaman, M.A.; Padhy, P.; Wu, M.; Ren, W.; Jensen, M.A.; Davis, R.W.; Hesselink, L. Controlled Transport of Individual Microparticles Using Dielectrophoresis. Langmuir
**2023**, 39, 101–110. [Google Scholar] [CrossRef] [PubMed] - Riccardi, M.; Martin, O.J.F. Electromagnetic Forces and Torques: From Dielectrophoresis to Optical Tweezers. Chem. Rev.
**2022**, 123, 1680–1711. [Google Scholar] [CrossRef] [PubMed] - Gascoyne, P.R.C.; Noshari, J.; Anderson, T.J.; Becker, F.F. Isolation of rare cells from cell mixtures by dielectrophoresis. Electrophoresis
**2009**, 30, 1388–1398. [Google Scholar] [CrossRef] - Sadeghian, H.; Hojjat, Y.; Soleimani, M. Interdigitated electrode design and optimization for dielectrophoresis cell separation actuators. J. Electrost.
**2017**, 86, 41–49. [Google Scholar] [CrossRef] - Li, D.; Yu, W.; Zhou, T.; Li, M.; Song, Y.; Li, D. Conductivity-difference-enhanced DC dielectrophoretic particle separation in a microfluidic chip. Analyst
**2022**, 147, 1106–1116. [Google Scholar] [CrossRef] - Coll De Peña, A.; Mohd Redzuan, N.H.; Abajorga, M.K.; Hill, N.; Thomas, J.A.; Lapizco-Encinas, B.H. Analysis of Bacteriophages with Insulator-Based Dielectrophoresis. Micromachines
**2019**, 10, 450. [Google Scholar] [CrossRef] - Khoshmanesh, K.; Nahavandi, S.; Baratchi, S.; Mitchell, A.; Kalantar-Zadeh, K. Dielectrophoretic platforms for bio-microfluidic systems. Biosens. Bioelectron.
**2011**, 26, 1800–1814. [Google Scholar] [CrossRef] - Fuhr, G.; Muller, T.; Baukloh, V.; Lucas, K. High-frequency electric field trapping of individual human spermatozoa. Hum. Reprod.
**1998**, 13, 136–141. [Google Scholar] [CrossRef] - Garcia, M.M.; Ohta, A.T.; Walsh, T.J.; Vittinghof, E.; Lin, G.; Wu, M.C.; Lue, T.F. A Noninvasive, Motility Independent, Sperm Sorting Method and Technology to Identify and Retrieve Individual Viable Nonmotile Sperm for Intracytoplasmic Sperm Injection. J. Urol.
**2010**, 184, 2466–2472. [Google Scholar] [CrossRef] - Rosales-Cruzaley, E.; Cota-Elizondo, P.A.; Sanchez, D.; Lapizco-Encinas, B.H. Sperm cells manipulation employing dielectrophoresis. Bioprocess Biosyst. Eng.
**2012**, 36, 1353–1362. [Google Scholar] [CrossRef] - Huang, H.-Y.; Kao, W.-L.; Wang, Y.-W.; Yao, D.-J. Using a Dielectrophoretic Microfluidic Biochip Enhanced Fertilization of Mouse Embryo in Vitro. Micromachines
**2020**, 11, 714. [Google Scholar] [CrossRef] - Koh, J.B.Y. Marcos Effect of dielectrophoresis on spermatozoa. Microfluid. Nanofluidics
**2014**, 17, 613–622. [Google Scholar] [CrossRef] - Wongtawan, T.; Dararatana, N.; Thongkittidilok, C.; Kornmatitsuk, S.; Oonkhanond, B. Enrichment of bovine X-sperm using microfluidic dielectrophoretic chip: A proof-of- concept study. Heliyon
**2020**, 6, e05483. [Google Scholar] [CrossRef] [PubMed] - Hughes, M.; Morgan, H. Measurement of Bacterial Flagellar Thrust by Negative Dielectrophoresis. Biotechnol. Prog.
**1999**, 15, 245–249. [Google Scholar] [CrossRef] [PubMed] - Li, W.; Du, H.; Chen, D.; Shu, C. Analysis of dielectrophoretic electrode arrays for nanoparticle manipulation. Comput. Mater. Sci.
**2004**, 30, 320–325. [Google Scholar] [CrossRef] - Tathireddy, P.; Choi, Y.-H.; Skliar, M. Particle AC electrokinetics in planar interdigitated microelectrode geometry. J. Electrost.
**2008**, 66, 609–619. [Google Scholar] [CrossRef] - Morgan, H.; Izquierdo, A.G.; Bakewell, D.; Green, N.G.; Ramos, A. The dielectrophoretic and travelling wave forces generated by interdigitated electrode arrays: Analytical solution using Fourier series. J. Phys. D Appl. Phys.
**2001**, 34, 1553. [Google Scholar] [CrossRef] - Hong, S.; Kim, C.; Song, H.; An, S.; Yoon, H.; Jhe, W. Measuring Dielectrophoresis Force for Metallic and Non-metallic Particle Manipulations via a Quartz Tuning Fork Atomic Force Microscope. J. Korean Phys. Soc.
**2019**, 75, 1021–1027. [Google Scholar] [CrossRef] - Jeon, H.-J.; Lee, H.; Yoon, D.S.; Kim, B.-M. Dielectrophoretic force measurement of red blood cells exposed to oxidative stress using optical tweezers and a microfluidic chip. Biomed. Eng. Lett.
**2017**, 7, 317–323. [Google Scholar] [CrossRef] - Imasato, H.; Yamakawa, T. Measurement of dielectrophoretic force by employing controllable gravitational force. J. Electrophor.
**2008**, 52, 1–8. [Google Scholar] [CrossRef] - Voldman, J.; Braff, R.A.; Toner, M.; Gray, M.L.; Schmidt, M.A. Holding Forces of Single-Particle Dielectrophoretic Traps. Biophys. J.
**2001**, 80, 531–542. [Google Scholar] [CrossRef] [PubMed] - Jones, T.B. Electromechanics of Particles; Cambridge University Press: New York, NY, USA, 1995; ISBN 9780521431965. [Google Scholar]
- Abd Rahman, N.; Ibrahim, F.; Yafouz, B. Dielectrophoresis for Biomedical Sciences Applications: A Review. Sensors
**2017**, 17, 449. [Google Scholar] [CrossRef] [PubMed] - Acheson, D.J. Elementary Fluid Dynamics. J. Acoust. Soc. Am.
**1991**, 89, 3020. [Google Scholar] [CrossRef] - Bruus, H. Lecture Notes Theoretical Microfluidics. Physics
**2008**, 18, 363. [Google Scholar] - Nascimento, J.M.; Shi, L.Z.; Meyers, S.; Gagneux, P.; Loskutoff, N.M.; Botvinick, E.L.; Berns, M. The use of optical tweezers to study sperm competition and motility in primates. J. R. Soc. Interface
**2008**, 5, 297–302. [Google Scholar] [CrossRef] - Nosrati, R.; Vollmer, M.; Eamer, L.; Gabriel, M.C.S.; Zeidan, K.; Zini, A.; Sinton, D. Rapid selection of sperm with high DNA integrity. Lab Chip
**2014**, 14, 1142–1150. [Google Scholar] [CrossRef] - Shuchat, S.; Park, S.; Kol, S.; Yossifon, G. Distinct and independent dielectrophoretic behavior of the head and tail of sperm and its potential for the safe sorting and isolation of rare spermatozoa. Electrophoresis
**2019**, 40, 1606–1614. [Google Scholar] [CrossRef] - Liu, C.; Xue, C.; Sun, J.; Hu, G. A generalized formula for inertial lift on a sphere in microchannels. Lab Chip
**2016**, 16, 884–892. [Google Scholar] [CrossRef] - Farajpour, D. A review on the mechanics of inertial microfluidics. J. Comput. Appl. Mech.
**2021**, 52, 168–192. [Google Scholar] [CrossRef] - Green, N.G.; Ramos, A.; González, A.; Morgan, H.; Castellanos, A. Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. III. Observation of streamlines and numerical simulation. Phys. Rev. E
**2002**, 66, 026305. [Google Scholar] [CrossRef] [PubMed] - Tada, S.; Seki, Y. Analysis of Temperature Field in the Dielectrophoresis-Based Microfluidic Cell Separation Device. Fluids
**2022**, 7, 263. [Google Scholar] [CrossRef] - Younglai, E.; Holt, D.; Brown, P.; Jurisicova, A.; Casper, R. Sperm swim-up techniques and DNA fragmentation. Hum. Reprod.
**2001**, 16, 1950–1953. [Google Scholar] [CrossRef] [PubMed] - Maree, L.; Du Plessis, S.; Menkveld, R.; Van Der Horst, G. Morphometric dimensions of the human sperm head depend on the staining method used. Hum. Reprod.
**2010**, 25, 1369–1382. [Google Scholar] [CrossRef] - Yang, J.; Huang, Y.; Wang, X.; Wang, X.-B.; Becker, F.F.; Gascoyne, P.R. Dielectric Properties of Human Leukocyte Subpopulations Determined by Electrorotation as a Cell Separation Criterion. Biophys. J.
**1999**, 76, 3307–3314. [Google Scholar] [CrossRef] - Siani, O.Z.; Sojoodi, M.; Targhi, M.Z.; Movahedin, M. Blood Particle Separation Using Dielectrophoresis in A Novel Microchannel: A Numerical Study. Cell J.
**2019**, 22, 218–226. [Google Scholar] [CrossRef] - Huang, Y.; Wang, X.-B.; Gascoyne, P.R.; Becker, F.F. Membrane dielectric responses of human T-lymphocytes following mitogenic stimulation. Biochim. et Biophys. Acta (BBA) Biomembr.
**1999**, 1417, 51–62. [Google Scholar] [CrossRef] - Barnkob, R.; Augustsson, P.; Magnusson, C.; Lilja, H.; Laurell, T.; Bruus, H. Measuring Density and Compressibility of White Blood Cells and Prostate Cancer Cells by Microchannel Acoustophoresis. 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011. MicroTAS
**2011**, 1, 127–129. [Google Scholar] - Malvezzi, H.; Sharma, R.; Agarwal, A.; Abuzenadah, A.M.; Abu-Elmagd, M. Sperm quality after density gradient centrifugation with three commercially available media: A controlled trial. Reprod. Biol. Endocrinol.
**2014**, 12, 121. [Google Scholar] [CrossRef] - Swindells, J.F.; Snyder, C.F.; Hardy, R.C.; Golden, P.E. Viscosities of Sucrose Solutions at Various Temperatures: Tables of Recalculated Values. Suppl. Natl. Bur. Stand. Circ.
**1958**, 440, 1–7. [Google Scholar] - Ghomian, T.; Hihath, J. Review of Dielectrophoretic Manipulation of Micro and Nanomaterials: Fundamentals, Recent Developments, and Challenges. IEEE Trans. Biomed. Eng.
**2023**, 70, 27–41. [Google Scholar] [CrossRef] [PubMed] - Huang, H.-Y.; Huang, Y.-H.; Kao, W.-L.; Yao, D.-J. Embryo formation from low sperm concentration by using dielectrophoretic force. Biomicrofluidics
**2015**, 9, 022404. [Google Scholar] [CrossRef] [PubMed]

**Figure 1.**Imposed forces on sperm in fluid flow and positive DEP. (

**A**) Fluid flow and electrodes in a perpendicular arrangement. (

**B**) Fluid flow and electrodes in the same direction.

**Figure 4.**Trapping the sperm (1 MHz) and WBC (800 kHz) under the effect of positive DEP. (

**A**) The applied voltage is high enough to prevent the trapped sperm from being washed by fluid flow. (

**B**) The applied voltage is lower than the capture voltage, so the fluid flow removes the trapped sperm. (

**C**) The applied voltage is high enough to prevent WBC from being washed by fluid flow. (

**D**) The applied voltage is lower than the capture voltage, so the fluid flow removes the trapped WBC.

**Figure 5.**(

**A**) Capture voltage of sperm at different flow rates. (

**B**) Experimental measured DEP force imposed on sperm at different voltages.

**Figure 6.**(

**A**) Capture voltage of WBC in different flow rates. (

**B**) Experimental and simulation results of DEP force imposed on WBC at different voltages.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

## Share and Cite

**MDPI and ACS Style**

Khouzestani, A.; Hojjat, Y.; Tavalaee, M.; Sadeghian, H.; Nasr-Esfahani, M.H.
Enhancing the Accuracy of Measuring DEP Force Applied on Cells by Considering the Friction Effect. *Biosensors* **2023**, *13*, 540.
https://doi.org/10.3390/bios13050540

**AMA Style**

Khouzestani A, Hojjat Y, Tavalaee M, Sadeghian H, Nasr-Esfahani MH.
Enhancing the Accuracy of Measuring DEP Force Applied on Cells by Considering the Friction Effect. *Biosensors*. 2023; 13(5):540.
https://doi.org/10.3390/bios13050540

**Chicago/Turabian Style**

Khouzestani, Alireza, Yousef Hojjat, Marziyeh Tavalaee, Hesam Sadeghian, and Mohammad Hossein Nasr-Esfahani.
2023. "Enhancing the Accuracy of Measuring DEP Force Applied on Cells by Considering the Friction Effect" *Biosensors* 13, no. 5: 540.
https://doi.org/10.3390/bios13050540