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In-Vitro Elektropermabilizasyon İçin Elektrik Alanın Sonlu Elemanlar Analizi

Year 2017, Issue: 3 - -Vol14, No 3; (Supll:1) IONCC 2017 Special edition, 14 - 22, 30.12.2017

Abstract

Amaç: Farklı elektrik puls değerliklerinde hücre
solüsyonundaki elektrik alan değişimlerinin
incelenmesi amaçlanmıştır.
Materyal ve Metod: Meme kanseri hücreleri, paralel
alüminyum plak elektrotlu 4 milimetre (mm) boşluklu
elektroporasyon küvetlerine yerleştirildi. Küvetler,
elektroporasyon cihazına bağlanan elektroporasyon
odasına alındı. Hücrelere, 0-800 V aralığında genlik ile
8 karesel titreşim (tekrarlama frekansı 1 Hz'lik)
uygulanmıştır. Her bir elektrik darbesinin süresi 100 μs idi. Elektroporasyon işlemi elektrostatik özellikler
içerdiğinden dolayı Ansys Maxwell 3D Elektrostatik
ve Elektrostatik transient modülü kullanılarak analiz
işlemleri gerçekleştirilmiştir. Bu özelliğiyle literatürde
yeralan diğer çalışmalardan farklıdır. İlk olarak, küvet
içinde bulunan elektrotlar paralel plakalı kondansatör
yaklaşımı ile kapasitans değeri analitik olarak
hesaplanmıştır. İkinci olarak, yazılım ile kapasitans
değeri nümerik olarak hesaplatılmıştır. Analitik ve
nümerik analiz ile modelin doğruluğu test edilmiştir.
Üçüncü olarak, hücre solüsyonundaki elektrik alan
değişimi incelenmiştir.
Bulgular: Kapasitans (C) formül kullanılarak;
0.5461125 pF olarak hesaplanmıştır. Nümerik analizi
neticesinde kapasitans değeri 0.54387 pF olarak
bulunmuştur. Elektrik alan değişimi 1998.7-2001,3
V/cm aralığında görülmüştür. Eğer elektrik alan şiddeti
çok düşükse, hücrelerde por için gerekli potansiyel
değerine (0.7-1V) ulaşılamaz. Solüsyonun köşe
kısımlarında elektrik alan değerinin artması beklenen
bir sonuçtur. Çünkü yükler köşe noktlarında birikir.
400V uygulandığında, solüsyondaki E değeri
4 4
5.66 10  8.13 10
V/m civarındadır. Böylece
membran potansiyeli 0.56-0.81 V'tur. 800V
uygulandığında ise, E değeri
5 5
1.035 10 1.82 10
V/m civarındadır. Böylece membran potansiyeli 1.03-
1.82 V'tur.
Sonuç: Analitik ve nümerik analiz arasındaki
kapasitans değeri hata oranı %0.047 olarak
görülmüştür. Benzetim çalışmasındaki model ile
uygulamadaki gerçek model uyuşması
beklenmektedir. Solüsyon miktarı arttıça kapasitans
doğrusal olarak değişmektedir. 400V uygulandığında
yada 1000 V/cm elektrik alan değerlerinde
solüsyondaki hücrelerin geçirgenliği azdır. Ancak
gerilim 800V değerine yükseltildiğinde hücrelerin
geçirgenliğinde önemli bir artış beklenmektedir.

References

  • 1.Ongaro A, Campana LG, De Mattei M, Dughiero F, Forzan M, Pellati A, Rossi CR, Sieni E. Evaluation of the Electroporation Efficiency of a Grid Electrode for Electrochemotherapy From Numerical Model to In Vitro Tests. Technology in cancer research &treatment 2015;15(2):296-307. 2.Cukjati D, Batiuskaite D, Slivnik T, Mir LM, Miklavčič D. Sequential finite element model of tissue electropermeabilization. IEEE Transactions on Biomedical Engineering 2005;52(5):816-827. 3.Dev SB, Rabussay DP, Widera G, Hofmann GA. Medical applications of electroporation. IEEE Transactions on Plasma Science 2000;28(1):206-23. 4.Rols MP, Golzio M, Gabriel B, Teissié J. Factors controlling electropermeabilisation of cell membranes. Technology in cancer research & treatment 2002;1(5):319- 27. 5.Castiello M, Dughiero F, Scandola F, Sieni E, Campana LG, Rossi CR, De Mattei M, Pellati A, Ongaro A. A new grid electrode for electrochemotherapy treatment of large skin tumors.IEEE Transactions on Dielectrics and Electrical Insulation 2014;21(3):1424-32. 6.Hong Z, Hao Z, Wei H, Zishu W, Qin G, Hong L.An exploration for optimal parameters of electromagnetic impulse on electrochemotherapy (ECT) of tumor.CEEM Proceedings2003;118-121 7.Esmekaya, M. A., Kayhan, H., Coskun, A., &Canseven, A. G.Effects of Cisplatin Electrochemotherapy on Human Neuroblastoma Cells. The Journal of membrane biology 2016;249(5):601-610. 8.Esmekaya, M. A., Kayhan, H., Yagci, M., Coskun, A., &Canseven, A. G. Effects of Electroporation on Tamoxifen Delivery in Estrogen Receptor Positive (ER+) Human Breast Carcinoma Cells. Cell biochemistry and biophysics 2017;75(1):103-109 9.Sree G, Velvizhi VK, Sundararajan R. Electric field distribution of malignant breast tissue under needle electrode configuration. InElectrical Insulation and Dielectric Phenomena (CEIDP) 2012:267-270 10.Campana, L. G., Dughiero, F., Forzan, M., Rossi, C. R., &Sieni, E. A prototype of a flexible grid electrode to treat widespread superficial tumors by meansof Electrochemotherapy. Radiology and oncology 2016; 50(1): 49-57. 11.Bommakanti S, Agoramurthy P, Campana L, Sundararajan R. A simulation analysis of large multielectrode needle arrays for efficient electrochemotherapy of cancer tissues.InElectrical Insulation and Dielectric Phenomena (CEIDP) 2011: 187-190 12.Miklavčič, D., Šemrov, D., Mekid, H., & Mir, L. M. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. BiochimicaetBiophysicaActa(BBA)- General Subjects 2000; 1523(1): 73-83. 13.Ansys Maxwell v16 Training Manual Lectures 4,5,6. 14.Ansys Maxwell v16 Help File. 15.Jaroszeski J. M., Heller R., Gilbert R. Electrochemptherapy, Electrogenetherapy and Transdermal Drug Delivery, Methods in Molecular Medicine, Humana Press, 2000:1-488

Finite Element Analysis Of Electric Field For In-Vitro Electropermeabilization

Year 2017, Issue: 3 - -Vol14, No 3; (Supll:1) IONCC 2017 Special edition, 14 - 22, 30.12.2017

Abstract

Background: The aim of this study was to investigate
the electric field distribution inside the cell solution for
different electric pulse amplitudes.
Materials and Methods: Breast cancer cells were
loaded into a BTX 640 model cuvette with parallel
aluminum plate electrodes and the cuvette were placed
in the electroporation chamber which was connected to
electroporator. Eight square pulses of duration
100μs (having repetition frequency of 1Hz) with 400V
and 800V were applied to the electrodes. Since
electroporation involves electrostatic properties, its
analysis is performed using Ansys-Maxwell 3D
Electrostatic transient module. In this direction, it is
different from other studies in the literature. Firstly, the
capacitance of the cuvette is calculated analytically by
the parallel plate capacitor approach. Secondly; the
capacitance value is calculated numerically by the
software. The accuracy of the model is tested with
analytical and numerical analysis. Thirdly, the electric
field (E) distribution inside the cell solution was
examined.
Results: The capacitance (C) was calculated as
0.5461125pF by using the Formula. C value in the
numerical analysis was found to be 0.54387pF. The
electric field distribution was found around 1998.7-
2001,3V/cm. If E is too low, the potential value for
electroporation can not be reached. Increasing E at the
corners of the cell solution is an expected result.
Because electrical charges accumulate at corner points.
While the applied voltage is 400V, E value on the
solution is around
4 4
5.66 10  8.13 10
V/m. Thus,
the membrane potential is calculated at about 0.56-
0.81V. While the applied voltage is 800V, E is around
5 5
1.035 10 1.82 10
V/m on the solution. Thus,
the membrane potential is calculated at about 1.03 -
1.82 V.
Conclusion: The capacitance value error ratio between
analytical and numerical analysis was 0.047%. It is
expected that the actual model will be compatible with
the model in the simulation. As the amount of the cell
solution increased, a linear increase in the capacitance
value was observed. For this reason, the charging time
for electroporation of the cells is affected. In analyzes
performed with solution, when 400V is applied, the
permeability of the cells in the electric field values
(1000 V/cm) is low. However, increasing the voltage
value from 400V to 800V could significantly increase
the permeability of the cells. 

References

  • 1.Ongaro A, Campana LG, De Mattei M, Dughiero F, Forzan M, Pellati A, Rossi CR, Sieni E. Evaluation of the Electroporation Efficiency of a Grid Electrode for Electrochemotherapy From Numerical Model to In Vitro Tests. Technology in cancer research &treatment 2015;15(2):296-307. 2.Cukjati D, Batiuskaite D, Slivnik T, Mir LM, Miklavčič D. Sequential finite element model of tissue electropermeabilization. IEEE Transactions on Biomedical Engineering 2005;52(5):816-827. 3.Dev SB, Rabussay DP, Widera G, Hofmann GA. Medical applications of electroporation. IEEE Transactions on Plasma Science 2000;28(1):206-23. 4.Rols MP, Golzio M, Gabriel B, Teissié J. Factors controlling electropermeabilisation of cell membranes. Technology in cancer research & treatment 2002;1(5):319- 27. 5.Castiello M, Dughiero F, Scandola F, Sieni E, Campana LG, Rossi CR, De Mattei M, Pellati A, Ongaro A. A new grid electrode for electrochemotherapy treatment of large skin tumors.IEEE Transactions on Dielectrics and Electrical Insulation 2014;21(3):1424-32. 6.Hong Z, Hao Z, Wei H, Zishu W, Qin G, Hong L.An exploration for optimal parameters of electromagnetic impulse on electrochemotherapy (ECT) of tumor.CEEM Proceedings2003;118-121 7.Esmekaya, M. A., Kayhan, H., Coskun, A., &Canseven, A. G.Effects of Cisplatin Electrochemotherapy on Human Neuroblastoma Cells. The Journal of membrane biology 2016;249(5):601-610. 8.Esmekaya, M. A., Kayhan, H., Yagci, M., Coskun, A., &Canseven, A. G. Effects of Electroporation on Tamoxifen Delivery in Estrogen Receptor Positive (ER+) Human Breast Carcinoma Cells. Cell biochemistry and biophysics 2017;75(1):103-109 9.Sree G, Velvizhi VK, Sundararajan R. Electric field distribution of malignant breast tissue under needle electrode configuration. InElectrical Insulation and Dielectric Phenomena (CEIDP) 2012:267-270 10.Campana, L. G., Dughiero, F., Forzan, M., Rossi, C. R., &Sieni, E. A prototype of a flexible grid electrode to treat widespread superficial tumors by meansof Electrochemotherapy. Radiology and oncology 2016; 50(1): 49-57. 11.Bommakanti S, Agoramurthy P, Campana L, Sundararajan R. A simulation analysis of large multielectrode needle arrays for efficient electrochemotherapy of cancer tissues.InElectrical Insulation and Dielectric Phenomena (CEIDP) 2011: 187-190 12.Miklavčič, D., Šemrov, D., Mekid, H., & Mir, L. M. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. BiochimicaetBiophysicaActa(BBA)- General Subjects 2000; 1523(1): 73-83. 13.Ansys Maxwell v16 Training Manual Lectures 4,5,6. 14.Ansys Maxwell v16 Help File. 15.Jaroszeski J. M., Heller R., Gilbert R. Electrochemptherapy, Electrogenetherapy and Transdermal Drug Delivery, Methods in Molecular Medicine, Humana Press, 2000:1-488
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Details

Primary Language English
Journal Section Research Article
Authors

Serdal Arslan

Meriç Arda Esmekaya

Ayşe Gülnihal Canseven

Publication Date December 30, 2017
Submission Date September 29, 2017
Acceptance Date November 22, 2017
Published in Issue Year 2017 Issue: 3 - -Vol14, No 3; (Supll:1) IONCC 2017 Special edition

Cite

Vancouver Arslan S, Esmekaya MA, Canseven AG. Finite Element Analysis Of Electric Field For In-Vitro Electropermeabilization. Harran Üniversitesi Tıp Fakültesi Dergisi. 2017;14(3):14-22.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty