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Electrical Field Analysis of Pentagonal Needle Array Electrode for Electrochemotherapy Applications Sadasivam Pachamuthu 1 , Vishveswaran Jothi 1 , Mohamed I Neamathulla 1 , Samu Safwan P.S.S. 1 , Arun Kuppan 1 , Rajaprabu Ramachandran 1 , Raji Sundararajan 2 , and Kavitha Sankaranarayanan 3 1 B.S. Abdur Rahman University, Chennai, India 2 Purdue University, West Lafayette, IN 47907, USA 3 AU-KBC Research Centre, Anna University, Chennai, India [email protected] Abstract - Electrochemotherapy is an effective palliative way of treating inoperable chemo-resistant cancers. It is a therapeutic technique for treating tumors with nonpermeant drugs using electroporation of cells. The cells are electroporated to form temporary hydrophilic pores. The various parameters which affect the electroporation efficacy are, the voltage (electric field intensity), pulse length, number of pulses, pulse interval and the electrode. The electrode provides a contact between the high voltage pulse generator and the patient, and as such it plays a vital role in the treatment outcome. In general, needle array electrodes are used in many cases, including treating of deep seated tumors. The electric field distribution varies according to the electrode design. This paper explores the effectiveness of a pentagonal array electrode with a centre electrode for obtaining uniform electric field distribution in the treated area. This model is symmetrical in which surrounding electrodes are displaced by 4mm from the centre electrode. The diameter of the needle is 1mm. The electric field simulations were implemented in 2D in ANSYS 13.0. The electric field considered for the analysis is 1200 V/cm, same as what is currently used in the clinics. The results indicate that the electric field distribution is uniform at a value of 1200V/cm. I. INTRODUCTION Electrochemotherapy is a palliative technique which is a combination of nonpermeant chemo drugs along with electroporation, which is applied to the tumour cells to reduce their proliferation and to cause cell death [1-3]. Electroporation is a technique which applies high voltage short duration pulses at either high frequency such as 5 kHz or at low frequency such as 1 Hz [1]. Electroporation creates temporary hydrophilic pores by varying the trans-membrane potential which leads to the formation of pores which helps the non permeant drugs to pass through the cell membrane and to react with the cells [4, 5]. This technique when combined with chemo drugs such as bleomycin (and cisplatin) increases the effectiveness of the non permeant drugs up to 1000x [1]. The high intensity, short pulses are generated by the electroporator, which are applied to the cells or tissues using metal contacts, known as electrodes. The electrodes are designed to ensure uniform electric field throughout the tumour, and could be moved around to cover the entire tumor. The electrodes used in electrochemotherapy are surface and needle electrodes [1]. The needle array electrodes are more suitable to treat deep-seated tumors. Various electrode configurations are in use, such as parallel array needle electrode, hexagonal array needle electrode, and orthogonal array electrodes (Fig. 1 [6]). In this research, a pentagonal array needle electrode is proposed with a central electrode. Its electric field distribution is studied using ANSYS 13.0. Fig. 1. Needle Electrodes used in electrochemotherapy A) 8 needle electrode, B)Hexagonal array electrode, C)& D) orthogonal electrodes [6]. II. MATERIALS AND METHODS A. Pentagonal Array Electrode Used Fig. 2a shows the pentagonal electrode designed and developed. It has a centre electrode surrounded by five electrodes (Fig. 2). The electrodes are 72 0 apart for symmetry from each other as shown in Fig. 3. The centre electrode is the high voltage or the live electrode and the surrounding electrodes are at ground potential. Each needle electrode is of 1mm diameter and is placed equidistant - 5mm (centre to centre), from the centre needle electrode, with a 4mm gap between the centre and each electrode. Each ground electrode with the centre live electrode forms the conducting path, thus obtained five conducting paths. The structure thus formed is a modified honey comb structure, as honey comb is a hexagonal symmetrically displaced structure with angular displacement of 60 0 [7]. B. About ANSYS The pentagonal concentric type needle array electrode is designed using MATLAB. The designed electrode is analysed in ANSYS 13.0 [8]. It is a commercial software, which has its usage in many fields of engineering such as structural, mechanical, civil, electrical, thermal and biotechnological science. In biomedical application, blood stream velocity can be estimated from analysis using ANSYS. The ANSYS version 263 978-1-4673-1252-3/12/$31.00 ©2012 IEEE

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Page 1: [IEEE 2012 IEEE Conference on Electrical Insulation and Dielectric Phenomena - (CEIDP 2012) - Montreal, QC, Canada (2012.10.14-2012.10.17)] 2012 Annual Report Conference on Electrical

Electrical Field Analysis of Pentagonal Needle Array Electrode for Electrochemotherapy Applications

Sadasivam Pachamuthu1, Vishveswaran Jothi1, Mohamed I Neamathulla1, Samu Safwan P.S.S.1, Arun Kuppan1, Rajaprabu

Ramachandran1, Raji Sundararajan2, and Kavitha Sankaranarayanan3

1 B.S. Abdur Rahman University, Chennai, India 2 Purdue University, West Lafayette, IN 47907, USA

3 AU-KBC Research Centre, Anna University, Chennai, India [email protected]

Abstract - Electrochemotherapy is an effective palliative way of treating inoperable chemo-resistant cancers. It is a therapeutic technique for treating tumors with nonpermeant drugs using electroporation of cells. The cells are electroporated to form temporary hydrophilic pores. The various parameters which affect the electroporation efficacy are, the voltage (electric field intensity), pulse length, number of pulses, pulse interval and the electrode. The electrode provides a contact between the high voltage pulse generator and the patient, and as such it plays a vital role in the treatment outcome. In general, needle array electrodes are used in many cases, including treating of deep seated tumors. The electric field distribution varies according to the electrode design. This paper explores the effectiveness of a pentagonal array electrode with a centre electrode for obtaining uniform electric field distribution in the treated area. This model is symmetrical in which surrounding electrodes are displaced by 4mm from the centre electrode. The diameter of the needle is 1mm. The electric field simulations were implemented in 2D in ANSYS 13.0. The electric field considered for the analysis is 1200 V/cm, same as what is currently used in the clinics. The results indicate that the electric field distribution is uniform at a value of 1200V/cm.

I. INTRODUCTION

Electrochemotherapy is a palliative technique which is a combination of nonpermeant chemo drugs along with electroporation, which is applied to the tumour cells to reduce their proliferation and to cause cell death [1-3]. Electroporation is a technique which applies high voltage short duration pulses at either high frequency such as 5 kHz or at low frequency such as 1 Hz [1]. Electroporation creates temporary hydrophilic pores by varying the trans-membrane potential which leads to the formation of pores which helps the non permeant drugs to pass through the cell membrane and to react with the cells [4, 5]. This technique when combined with chemo drugs such as bleomycin (and cisplatin) increases the effectiveness of the non permeant drugs up to 1000x [1]. The high intensity, short pulses are generated by the electroporator, which are applied to the cells or tissues using metal contacts, known as electrodes. The electrodes are designed to ensure uniform electric field throughout the tumour, and could be moved around to cover the entire tumor.

The electrodes used in electrochemotherapy are surface and needle electrodes [1]. The needle array electrodes are more suitable to treat deep-seated tumors. Various electrode configurations are in use, such as parallel array needle

electrode, hexagonal array needle electrode, and orthogonal array electrodes (Fig. 1 [6]).

In this research, a pentagonal array needle electrode is proposed with a central electrode. Its electric field distribution is studied using ANSYS 13.0.

Fig. 1. Needle Electrodes used in electrochemotherapy A) 8 needle

electrode, B)Hexagonal array electrode, C)& D) orthogonal electrodes [6].

II. MATERIALS AND METHODS

A. Pentagonal Array Electrode Used Fig. 2a shows the pentagonal electrode designed and

developed. It has a centre electrode surrounded by five electrodes (Fig. 2). The electrodes are 720 apart for symmetry from each other as shown in Fig. 3. The centre electrode is the high voltage or the live electrode and the surrounding electrodes are at ground potential. Each needle electrode is of 1mm diameter and is placed equidistant - 5mm (centre to centre), from the centre needle electrode, with a 4mm gap between the centre and each electrode. Each ground electrode with the centre live electrode forms the conducting path, thus obtained five conducting paths. The structure thus formed is a modified honey comb structure, as honey comb is a hexagonal symmetrically displaced structure with angular displacement of 600 [7].

B. About ANSYS

The pentagonal concentric type needle array electrode is designed using MATLAB. The designed electrode is analysed in ANSYS 13.0 [8]. It is a commercial software, which has its usage in many fields of engineering such as structural, mechanical, civil, electrical, thermal and biotechnological science. In biomedical application, blood stream velocity can be estimated from analysis using ANSYS. The ANSYS version

263978-1-4673-1252-3/12/$31.00 ©2012 IEEE

Page 2: [IEEE 2012 IEEE Conference on Electrical Insulation and Dielectric Phenomena - (CEIDP 2012) - Montreal, QC, Canada (2012.10.14-2012.10.17)] 2012 Annual Report Conference on Electrical

13.0 is used to analyse the designed electrode and to obtain electric field distribution, voltage distribution, flux distribution, current distribution, vectors of energy distribution and pontying vector plots.

Fig. 2. Pentagonal array Needle electrode designed and developed.

Fig. 3. Design of Pentagonal array electrode designed without tumour.

C. Properties of Materials Used The materials used for the electrode analysis in the

simulation are platinum and surgical steel. The electrical properties considered for the materials are its resistivity and its relative permittivity. The resistivity and relative permittivity of the platinum used is 105nΩ-m (20oC) and 1 respectively [9]. The properties of the surgical steel used in the analysis are 740nΩ-m (20oC) and 14 up to 1 GHz of frequency [10, 11]. The surgical steel consists of stainless steel alloyed with nickel, chromium, molybdenum. It is easy to sterilize and have many applications in medical field. This material is used for bone repair and is implanted inside the human body, as it does not react with human body [12]. The surgical steel is also known as 316L if it contains austenitic steel [13]. D. Properties of Skin and Tissues

The electric field distribution is obtained in two scenarios, first the uniform distribution in tissue, followed by tumour of larger size than electrodes and finally tumour smaller than electrode configuration. The tissue’s resistivity and relative permittivity are given by 0.4545Ωm and 52, respectively (Table I, [14].

TABLE I Electrical Properties of Tissue Used

Sl.No Parameter Value 1. Conductivity of tissue 2.2 S/m 2. Relative permittivity of tissue 52

III. RESULTS & DISCUSSION

A. Designing of Electrodes The electrode to be analysed was modelled using ANSYS.

The design procedure is similar to that of designing in AutoCAD. The points which are first obtained, are known as key points, followed by lines that are formed by joining key

points, which are connected to form areas; the areas form the 2D analysis structure of the electrodes as shown in Fig. 4. If a 3D analysis is needed, then the 3D structure parameter is added for further processing and analysis in 3D. The overlapping cannot be formed here so the electrodes which are modelled inside the skin or tissues are first subtracted from the tissues then are added. After the model is obtained, the material properties of each material are applied and meshed then loads are given in appropriate areas/nodes as shown in Fig. 5. All the simulations were run for a desired electric field intensity of 1200V/cm, same as the magnitude used in clinical electrochemotherapy [14]. The result is obtained on thus solving the model and viewed in the desired form as lists, Contour plots etc. The contour plot of the voltage is shown in Fig. 6. The list is given in supplement document as it shows all the nodes in the mesh and its electric field intensity. The electrode with tumour is designed as shown in Fig. 7.

Fig. 4. Design of Pentagonal array electrode in ANSYS 13.0 without tumour.

Fig. 5. Meshed pentagonal array electrode without tumour in ANSYS 13.0.

The Contour plot of the pentagonal array electrode with a tumour less than the size of the electrode boundary is shown in Fig. 8. The tumour size considered is of 3mm diameter. The material used as electrode is surgical steel. The maximum electric field sum shown in red is 310499 V/m (3105V/cm). The minimum electric field sum shown as blue is 68999.8 V/m (690V/cm).

The pentagonal array electrode has uniform distribution of electric field intensity. The voltage distribution is compared between two extreme materials; they are surgical steel and platinum. As the conductivity of platinum is higher than surgical steel and the relative permittivity is unity, the platinum has more advantage over surgical steel but the cost of the former is much greater than the later. The maximum electric

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field is found around the junction of the tumour and tissue as there is sudden change in the properties at the junction due to the tumour as every cell in the tumour has properties different than normal tissues.

Fig. 6. Contour plot of Voltage stress distribution of pentagonal array electrode

made of surgical steel.

Fig. 7. Design of pentagonal array electrode with tumour in ANSYS 13.0.

Fig. 8. Contour plot of Electric field pentagonal array electrode with tumour.

The voltage distribution of platinum electrode is shown in

Fig. 9. The red colour shows maximum field of 480V, while blue colour is for minimum field of 53.333V or even zero as given in the legend. The various colours represent the electric field in-between maximum and minimum. The maximum voltage stress is found near the live electrode and it gradually decreases to zero as it moves away from the live electrode and attains zero at the ground electrodes.

But in case of surgical steel the voltage leaks out in certain areas beyond the ground electrodes as shown in Fig. 10. This

could affect the tissues surrounding the tumour cells resulting in a burning effect on the normal healthy tissues. However, this effect is restricted to just outside the boundary of the electrodes only and it is minimum as the voltage is 106.567V to 53.333V. The maximum voltage is applied 480V and the minimum is 0V as it reaches the ground electrodes. The pentagonal array electrode made of platinum can be used for treating tumour near nerve centres, thus it will confine the electric field and voltage within its boundary electrodes and will efficiently electroporate the tumour cells.

Fig. 9. Pentagonal array electrode made of platinum with tumour.

Fig. 10. Contour plot of Voltage stress in Pentagonal array electrode made up

of surgical steel with tumour.

Fig. 11 shows a comparison of the electric field with and

without the tumor in electrode made of surgical steel. There are intermediate variations in electric field distribution, as the permittivity and resistivity of the tumour is less than healthy tissues so the potential difference gradually decreases in without tumour while uneven changes are found due to change in properties at the junctions between the tumour and the tissues, and the tissue and the electrode.

Fig. 12 shows the plot of electric field along the distance from the center electrode for the platinum and the surgical steel materials. The platinum has a lower slope and rate of fall in electric field compared to the surgical steel. This could be as its conductivity is greater than the surgical steel and the differences in their permittivity. The voltage stress in platinum and surgical steel electrodes are similar but there are leakages that are found in the gap between the adjacent electrodes in the outer surface of the surgical steel and hence there is increase of

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electric field and voltage beyond the electrodes as seen in Fig. 10. The peak at a distance 5.4998cm shows there is leakage and it becomes to zero at 5.998 cm as shown in Fig. 12. Hence we can conclude that pentagonal surgical steel electrode can replace the platinum electrode by reducing the cost per electrode even though there is small leakage to a distance of 2mm.

Fig. 11. Graph plotted between distance and Electric field of pentagonal array Surgical steel electrode with and without tumour.

Fig. 12. Graph of Electric field sum Vs Distance between platinum and surgical

steel electrodes.

The analysis is also made for tumour size is greater than the electrode; the corresponding contour plot is shown in Fig. 13. Due to the variation in the permittivity and conductivity surrounding the electrodes by tumour cells, electrodes get short circuited and large current flows and voltage is minimum nearly zero as seen in Fig. 13. It is found that always the electrode boundary must be greater than the tumour size, appropriate size of electrode configuration must be chosen to avoid this condition.

Fig. 13. Contour plot of voltage stress in Pentagonal array electrode made of platinum with tumour bigger than the electrode.

IV. CONCLUSION

A Pentagonal array electrode configuration is designed and analysed in ANSYS. It shows uniform distribution of electric field and voltage stress. The aim of this research is to design an electrode which is more economical than existing electrode configurations as number of needles used is reduced. The designed electrode produces an electric field of 1200 V/cm and reaches zero at 4mm away from the centre electrode. Comparison of platinum and surgical steel material gives an idea to make an alloy of platinum and surgical steel in right proportion, which will acquire the advantages of both the electrodes and provide an improvised treatment for the patient and reduces the cost per sitting; since the electrodes are of use and throw type or the platinum can be replaced by surgical steel itself. Practical testing of the proposed electrode will be helpful in deciding the choice of electrode for the treatment of tumour in particular place, thus increasing the efficiency of the electrochemotherapy treatment.

REFERENCES

[1] M.G. Moller, A. Salwa, D.M. Soden, and G.C. O’Sullivan,

“Electrochemotherapy as an adjunct or alternative to other treatments for unresectable or in-transit melanoma”, Expert Rev. Anticancer Ther., Vol. 9, No. 11, pp. 1611-1630, 2009.

[2] J. Gehl and P.F. Geertsen, “Efficient palliation of haemorrhaging malignant melanoma skin metastases by electrochemotherapy”, Melanoma Research, Vol. 10, pp. 585-589, December 2000.

[3] L. G. Campana, S. Mocellin, M. Basso, O. Puccetti, G. L. De Salvo, V. Chiarion-Sileni, A. Vecchiato, L. Corti, C. R. Rossi, and D. Nitti, “Bleomycin-based electrochemotherapy: clinical outcome from a single Institution’s experience with 52 patients”, Annals of Surgical Oncology, Vol. 16, pp. 191-199, 2009.

[4] J. C. Weaver, "Electroporation of Cells and Tissues," IEEE Transl. Plasma Science, Vol. 28, pp. 24-33, February 2000.

[5] Ralf W. Glaser , Sergei L. Leikin , Leonid V. Chernomordik , Vasili F. Pastushenko and Artjom I. sokirko, “Reversible electrical breakdown of lipid layers: Formation and evolution of pores,” Biochimica et Biophysica Acta 950, November 1987, pp 275-287.

[6] Cliniporator Technical Sheet, IGEA, 2010. [7] Sukhendu B. Dev, Deepak Dhar, and Wanda Krassowska, “Electric

Field of a Six-Needle Array Electrode Used in Drug and DNA Delivery In Vivo: Analytical Versus Numerical Solution,” IEEE Transl. on Biomed. Eng., Vol. 50, No. 11, pp 1296-1300, November 2003.

[8] ANSYS Mechanical APDL Tutorials. Release 13.0. ANSYS, Inc. Southpointe, Canonsburg, November 2010.

[9] http://en.wikipedia.org/wiki/Platinum. [10] http://www.lenntech.com/stainless-steel-316l.html. [11] http://www.springerimages.com/Images/Physics/1-0.1007_s10762-

007-9299-4-4. [12] P. Thomas, A. Schuh, J. Ring, M. Thomsen, "Orthopaedic surgical

implants and allergies," Der Orthopäde, Vol. 37, 2007, pp. 75–88. [13] http://en.wikipedia.org/wiki/Surgical_stainless_steel. [14] W. Mitchell and R. Sundararajan “Electric Field Distribution in

Biological Tissues for Various Electrode Configurations-A FEMLAB Study,” in Proceedings of the COMSOL Multiphysics User's Conference, Boston, 2005.

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