Christopher B. Arena 1 Bioelectromechanical Systems Lab, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech, 330 Kelly Hall (MC0298), Stanger Street, Blacksburg, VA 24061 e-mail: carena@vt.edu Roop L. Mahajan Institute for Critical Technology and Applied Science (ICTAS), Virginia Tech Department of Mechanical Engineering, Virginia Tech Department of Engineering Science and Mechanics, Virginia Tech, 410 H Kelly Hall (MC0298), Stanger Street, Blacksburg, VA 24061 Marissa Nichole Rylander Tissue Engineering Nanotechnology and Cancer Research Lab, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech Department of Mechanical Engineering, Virginia Tech, 335 Kelly Hall (MC0298), Stanger Street, Blacksburg, VA 24061 Rafael V. Davalos Bioelectromechanical Systems Lab, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech, 329 Kelly Hall (MC0298), Stanger Street, Blacksburg, VA 24061 An Experimental and Numerical Investigation of Phase Change Electrodes for Therapeutic Irreversible Electroporation Irreversible electroporation (IRE) is a new technology for ablating aberrant tissue that utilizes pulsed electric fields (PEFs) to kill cells by destabilizing their plasma membrane. When treatments are planned correctly, the pulse parameters and location of the electro- des for delivering the pulses are selected to permit destruction of the target tissue without causing thermal damage to the surrounding structures. This allows for the treatment of surgically inoperable masses that are located near major blood vessels and nerves. In select cases of high-dose IRE, where a large ablation volume is desired without increasing the number of electrode insertions, it can become challenging to design a pulse protocol that is inherently nonthermal. To solve this problem we have developed a new electrosur- gical device that requires no external equipment or protocol modifications. The design incorporates a phase change material (PCM) into the electrode core that melts during treatment and absorbs heat out of the surrounding tissue. Here, this idea is reduced to practice by testing hollow electrodes filled with gallium on tissue phantoms and monitor- ing temperature in real time. Additionally, the experimental data generated are used to validate a numerical model of the heat transfer problem, which is then applied to investi- gate the cooling performance of other classes of PCMs. The results indicate that metallic PCMs, such as gallium, are better suited than organics or salt hydrates for thermal man- agement, because their comparatively higher thermal conductivity aids in heat dissipation. However, the melting point of the metallic PCM must be properly adjusted to ensure that the phase transition is not completed before the end of treatment. When translated clini- cally, phase change electrodes have the potential to continue to allow IRE to be performed safely near critical structures, even in high-dose cases. [DOI: 10.1115/1.4025334] Keywords: nonthermal ablation, irreversible electroporation, electrochemotherapy, phase change materials, latent heat storage, Joule heating, thermal damage, radio fre- quency ablation Introduction Reversible electroporation has been used over the past two dec- ades to facilitate the transport of molecules across cell membranes without directly compromising cell viability [1–3]. Additionally, irreversible electroporation (IRE) has emerged as an effective focal ablation technique that disrupts cell membranes beyond the point of recovery [4]. When performed clinically, these proce- dures involve placing electrodes into, or around, a target tissue and applying a series of short, but intense, pulsed electric fields (PEFs). Oftentimes, patient specific treatment plans are employed to guide procedures by merging medical imaging with algorithms for determining the electric field distribution in the tissue [5–7]. The electric field dictates treatment outcomes by increasing a cell’s transmembrane potential to levels where it becomes ener- getically favorable for the membrane to shift to a state of enhanced permeability [8]. Successful cancer treatments have been designed that combine reversible electroporation with the delivery of chemotherapeutic agents [9] or plasmid DNA [10] in the form of electrochemotherapy (ECT) and electrogenetherapy (EGT), respectively. The same is true for IRE, without the requirement for adjuvant molecules [11]. PEF protocols for tissue electroporation are designed to limit Joule heating. That is, the number of pulses, pulse duration, pulse amplitude, and pulse repetition rate are chosen in combinations that can induce electroporation without raising the tissue tempera- ture to levels capable of causing thermal damage. ECT and IRE typically involve multiple, high voltage (1000 V) pulses with durations on the order of hundreds of microseconds, whereas EGT protocols also include lower voltage (100 V) pulses with dura- tions on the order of tens of milliseconds to facilitate electropho- resis of DNA [12]. Because the mechanism of action is nonthermal, treatments can be performed in close proximity to major blood vessels without concern for heat sink effects that can protect tumors from thermally mediated therapies. Additionally, the nonthermal mode of ablation in IRE spares extracellular ma- trix components, including major nerve [13] and blood vessel [14] architecture, which promotes rapid recovery following treatment [15] and allows for the treatment of several surgically inoperable tumors [6,7]. Situations can arise in which it is challenging to design an elec- troporation protocol that simultaneously covers the targeted tissue with a sufficient electric field and avoids unwanted thermal effects. For instance, hallmarks of thermal damage have been seen adjacent to the electrodes in select cases of high-dose IRE, where the applied voltage was raised (3000 V) to ablate a large volume in a single treatment [16]. This is presumably due to the steep electric potential gradient that occurs in the vicinity of the elec- trode edges. Similarly, when treating subcutaneous lesions, there 1 Corresponding author. Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received April 10, 2013; final manuscript received July 30, 2013; accepted manuscript posted September 6, 2013; published online October 3, 2013. Assoc. Editor: Ram Devireddy. Journal of Biomechanical Engineering NOVEMBER 2013, Vol. 135 / 111009-1 Copyright V C 2013 by ASME Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 11/18/2013 Terms of Use: http://asme.org/terms