Introduction

Glioblastoma multiforme (GBM) is a highly aggressive and invasive brain tumor. The World Health Organization (WHO) classifies grade IV glioma as the most severe form of central nervous system disease. The median survival rate ranges from 14.6 to 16.7 months, with a five-year survival rate of merely 5%, even with treatments such as surgery, radiation therapy, and chemotherapy [1]. Consequently, developing effective therapies for GBM remains a significant challenge. Recent studies have demonstrated the potential of electric fields in cancer treatment. Tumor Treating Fields (TTFields), utilizing high-frequency alternating current (AC) fields (100-300 kHz), have shown efficacy in tumor treatment [2-3]. In vitro studies indicate that TTFields can inhibit cell proliferation at intensities of 1-3 V/cm. TTFields are hypothesized to disrupt or delay cell division during early mitotic phases. During cytokinesis, TTFields may induce dielectrophoretic forces that displace polarizable macromolecules and ions toward the furrow, causing membrane blebbing and subsequent cell death [4-5]. TTFields have been clinically validated as an adjuvant therapy to chemotherapy in GBM treatment and have received FDA approval as a monotherapy for recurrent GBM.  The Optune system, developed by Novocure Ltd., generates TTFields for clinical administration. Clinical trials demonstrated a median overall survival of 20.5 months (16.7-25.0 months) for TTFields combined with temozolomide, significantly longer than the 15.6 months (13.3-19.1 months) observed with temozolomide alone [6]. TTFields shows a promising adjuvant therapy for GBM treatment. Effective TTFields treatment requires high-frequency AC fields (100-300 kHz) with intensities of 1-3 V/cm. However, few studies have addressed the design of TTFields delivery devices. For research experiment, the protocol that oscillator or an AC generator, connected to a high voltage amplifier is usually used to produce AC field with high frequency in the range from 100 kHz to 300 kHz. In general, Novocure Ltd. also used this protocol to generate AC field for TTFields experiment by lab researchers [7-9]. Due to the conflict of interest, they did not open the structure of clinical apparatus. Optune apparatus consists of the transducer arrays with insulated electrodes, electric field generator (set at a frequency of 200 kHz) and battery. Patients receive TTFields via four transducer arrays delivering 200 kHz electric fields to the brain. Each transducer array delivers currents ranging from 400 to 1000 mA, typically 900 mA, with head impedance values between 58.6 and 91.2 Ω. The system generates voltages exceeding 50 V and power outputs around 50 W [10-12]. The use of insulated electrodes creates predominantly capacitive impedance, resulting in displacement currents through the head. However, the output power is constrained by the limitations of high-voltage amplifiers. For instance, generating 50 V AC fields requires matching DC power supplies, with average power consumption reaching at least 36 W when delivering 1000 mA currents. These technical constraints pose challenges for developing portable clinical devices with stable high-power outputs. With advancements in power electronics, DC/AC inverters have become widely adopted in industrial applications including induction heating systems, communication networks, and uninterruptible power supplies [13-21]. A typical DC/AC inverter comprises a full-bridge inverter and a resonant tank utilizing PWM control. The full-bridge inverter generates rectangular pulses, while resonant step-up topologies (LLC/LCC/LCLC) serve dual functions: filtering to produce AC waveforms and voltage boosting through high-ratio line-frequency transformers [22-26]. For instance, Blinov et al. developed a 50 kHz DC/AC inverter converting 40 V DC to 230 V AC for telecommunications [27], while Kummari et al. demonstrated a DC/AC inverter achieving 325 V AC output [28]. High-power DC/AC inverters for UPS and battery systems typically combine low-voltage SPWM circuits with line-frequency transformers for voltage amplification [29-30]. High-frequency AC fields (100-300 kHz) constitute the operational foundation of TTFields devices. Although DC/AC inverters represent a viable topology for therapeutic high-frequency AC field generation, PWM control becomes impractical at therapeutic frequencies (>2 MHz) due to excessive switching losses. Resonant step-up converters (LLC/LCC/LCLC) offer dual advantages: extracting fundamental frequency components from rectangular pulses while providing voltage gain. Standard 3.7 V lithium batteries provide portable high-current DC sources suitable for outdoor TTFields operation, addressing the Optune system’s requirement for supplemental batteries during mobile use exceeding one hour [31]. Developing 3.7 V-powered inverters with optimized high-gain/high-frequency characteristics remains critical for portable TTFields implementation. Notably, no prior studies have reported TTFields generation using capacitive-impedance DC/AC inverters. At therapeutic frequencies, capacitive impedance may interact with resonant converters, potentially compromising voltage output. This work implements a 3.7 V-powered full-bridge inverter with resonant tank to generate 200 kHz therapeutic fields. An LCLLC topology was developed by integrating a 1:1 line transformer into the LCLC converter, achieving 17.8× voltage gain (66.0 V). Theoretical analysis guided parameter selection for the modified circuit, where transformer excitation inductance was optimized to align the operating frequency with the primary resonance. A prototype employing four parallel 3.7 V/3200 mAh batteries successfully generated 200 kHz waveforms, maintaining stable AC output for 8.7 hours suitable for extended outdoor use. This study showed an easy-implemented topology with a voltage regulation to design the TTFields apparatus.