@article{vrabel_fesmire_rich_kobrin_sano_zaharoff_2024, title={A novel in vitro model of clinical cryoablation to investigate the transition zone for focal tumor ablation}, volume={114}, ISSN={["1090-2392"]}, DOI={10.1016/j.cryobiol.2023.104844}, abstractNote={Cryoablation (CA) of solid tumors is highly effective at reducing tumor burden and eliminating small, early stage tumors. However, complete ablation is difficult to achieve and cancer recurrence is a significant barrier to treatment of larger tumors compared to resection. In this study, we explored the relationship between temperature, ice growth, and cell death using a novel in vitro model of clinical CA with the Visual-ICE (Boston Scientific) system, a clinically approved and widely utilized device. We found that increasing the duration of freezing from 1 to 2 min increased ice radius from 3.44 ± 0.13 mm to 5.29 ± 0.16 mm, and decreased the minimum temperature achieved from -22.8 ± 1.3 °C to -45.5 ± 7.9 °C. Furthermore, an additional minute of freezing increased the amount of cell death within a 5 mm radius from 42.5 ± 8.9% to 84.8 ± 1.1%. Freezing at 100% intensity leads to faster temperature drops and a higher level of cell death in the TRAMP-C2 mouse prostate cancer cell line, while lower intensities are useful for slow freezing, but result in less cell death. The width of transition zone between live and dead cells decreased by 0.4 ± 0.2 mm, increasing from one to two cycles of freeze/thaw cycles at 100% intensity. HMGB-1 levels significantly increased with 3 cycles of freeze/thaw compared to the standard 2 cycles. Overall, a longer freezing duration, higher freezing intensity, and more freeze thaw cycles led to higher levels of cancer cell death and smaller transition zones. These results have the potential to inform future preclinical research and to improve therapeutic combinations with CA.}, journal={CRYOBIOLOGY}, author={Vrabel, Maura R. and Fesmire, Christopher C. and Rich, Matthew J. and Kobrin, Robert L. and Sano, Michael B. and Zaharoff, David A.}, year={2024}, month={Mar} }
 @article{fesmire_williamson_petrella_kaufman_topasna_sano_2024, title={Integrated Time Nanosecond Pulse Irreversible Electroporation (INSPIRE): Assessment of Dose, Temperature, and Voltage on Experimental and Clinical Treatment Outcomes}, volume={71}, ISSN={["1558-2531"]}, DOI={10.1109/TBME.2023.3340718}, number={5}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Fesmire, Christopher C. and Williamson, Robert H. and Petrella, Ross A. and Kaufman, Jacob D. and Topasna, Nomi and Sano, Michael B.}, year={2024}, month={May}, pages={1511–1520} }
 @article{fesmire_peal_ruff_moyer_mcparland_derks_o'neil_emke_johnson_ghosh_et al._2024, title={Investigation of integrated time nanosecond pulse irreversible electroporation against spontaneous equine melanoma}, volume={11}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2024.1232650}, abstractNote={IntroductionIntegrated time nanosecond pulse irreversible electroporation (INSPIRE) is a novel tumor ablation modality that employs high voltage, alternating polarity waveforms to induce cell death in a well-defined volume while sparing the underlying tissue. This study aimed to demonstrate the in vivo efficacy of INSPIRE against spontaneous melanoma in standing, awake horses.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Fesmire, Chris C. and Peal, Bridgette and Ruff, Jennifer and Moyer, Elizabeth and McParland, Thomas J. and Derks, Kobi and O'Neil, Erin and Emke, Carrie and Johnson, Brianna and Ghosh, Shatorupa and et al.}, year={2024}, month={Jan} }
 @article{petrella_levit_fesmire_tang_sano_2022, title={Polymer Nanoparticles Enhance Irreversible Electroporation In Vitro}, volume={69}, ISSN={["1558-2531"]}, DOI={10.1109/TBME.2022.3143084}, abstractNote={Expanding the volume of an irreversible electroporation treatment typically necessitates an increase in pulse voltage, number, duration, or repetition. This study investigates the addition of polyethylenimine nanoparticles (PEI-NP) to pulsed electric field treatments, determining their combined effect on ablation size and voltages. U118 cells in an in vitro 3D cell culture model were treated with one of three pulse parameters (with and without PEI-NPs) which are representative of irreversible electroporation (IRE), high frequency irreversible electroporation (H-FIRE), or nanosecond pulsed electric fields (nsPEF). The size of the ablations were compared and mapped onto an electric field model to describe the electric field required to induce cell death. Analysis was conducted to determine the role of PEI-NPs in altering media conductivity, the potential for PEI-NP degradation following pulsed electric field treatment, and PEI-NP uptake. Results show there was a statistically significant increase in ablation diameter for IRE and H-FIRE pulses with PEI-NPs. There was no increase in ablation size for nsPEF with PEI-NPs. This all occurs with no change in cell media conductivity, no observable degradation of PEI-NPs, and moderate particle uptake. These results demonstrate the synergy of a combined cationic polymer nanoparticle and pulsed electric field treatment for the ablation of cancer cells. These results set the foundation for polymer nanoparticles engineered specifically for irreversible electroporation.}, number={7}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Petrella, Ross A. and Levit, Shani L. and Fesmire, Christopher C. and Tang, Christina and Sano, Michael B.}, year={2022}, month={Jul}, pages={2353–2362} }
 @article{sano_fesmire_petrella_2021, title={Electro-Thermal Therapy Algorithms and Active Internal Electrode Cooling Reduce Thermal Injury in High Frequency Pulsed Electric Field Cancer Therapies}, volume={49}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-020-02524-x}, abstractNote={Thermal tissue injury is an unintended consequence in current irreversible electroporation treatments due to the induction of Joule heating during the delivery of high voltage pulsed electric fields. In this study active temperature control measures including internal electrode cooling and dynamic energy delivery were investigated as a process for mitigating thermal injury during treatment. Ex vivo liver was used to examine the extent of thermal injury induced by 5000 V treatments with delivery rates up to five times faster than current clinical practice. Active internal cooling of the electrode resulted in a 36% decrease in peak temperature vs. non-cooled control treatments. A temperature based feedback algorithm (electro-thermal therapy) was demonstrated as capable of maintaining steady state tissue temperatures between 30 and 80 °C with and without internal electrode cooling. Thermal injury volumes of 2.6 cm 3  were observed for protocols with 60 °C temperature set points and electrode cooling. This volume reduced to 1.5 and 0.1 cm 3  for equivalent treatments with 50 °C and 40 °C set points. Finally, it was demonstrated that the addition of internal electrode cooling and active temperature control algorithms reduced ETT treatment times by 84% (from 343 to 54 s) vs. non-cooled temperature control strategies with equivalent thermal injury volumes.}, number={1}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Sano, Michael B. and Fesmire, Christopher C. and Petrella, Ross A.}, year={2021}, month={Jan}, pages={191–202} }
 @article{petrella_fesmire_kaufman_topasna_sano_2020, title={Algorithmically Controlled Electroporation: A Technique for Closed Loop Temperature Regulated Pulsed Electric Field Cancer Ablation}, volume={67}, ISSN={["1558-2531"]}, DOI={10.1109/TBME.2019.2956537}, abstractNote={Objective: To evaluate the effect of a closed-loop temperature based feedback algorithm on ablative outcomes for pulsed electric field treatments. Methods: A 3D tumor model of glioblastoma was used to assess the impact of 2 μs duration bipolar waveforms on viability following exposure to open and closed-loop protocols. Closed-loop treatments evaluated transient temperature increases of 5, 10, 15, or 22 °C above baseline. Results: The temperature controlled ablation diameters were conditionally different than the open-loop treatments and closed-loop treatments generally produced smaller ablations. Closed-loop control enabled the investigation of treatments with steady state 42 °C hyperthermic conditions which were not feasible without active feedback. Baseline closed-loop treatments at 20 °C resulted in ablations measuring 9.9 ± 0.3 mm in diameter while 37 °C treatments were 20% larger (p < 0.0001) measuring 11.8 ± 0.3 mm indicating that this protocol induces a thermally mediated biological response. Conclusion: A closed-loop control algorithm which modulated the delay between successive pulse waveforms to achieve stable target temperatures was demonstrated. Algorithmic control enabled the evaluation of specific treatment parameters at physiological temperatures not possible with open-loop systems due to excessive Joule heating. Significance: Irreversible electroporation is generally considered to be a non-thermal ablation modality and temperature monitoring is not part of the standard clinical practice. The results of this study indicate ablative outcomes due to exposure to pulses on the order of one microsecond may be thermally mediated and dependent on local tissue temperatures. The results of this study set the foundation for experiments in vivo utilizing temperature control algorithms.}, number={8}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Petrella, Ross Aaron and Fesmire, Christopher C. and Kaufman, Jacob D. and Topasna, Nomi and Sano, Michael B.}, year={2020}, pages={2176–2186} }
 @article{sano_petrella_kaufman_fesmire_xing_gerber_fogle_2020, title={Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms}, volume={121}, ISSN={["1879-0534"]}, DOI={10.1016/j.compbiomed.2020.103807}, abstractNote={Electro-thermal therapy (ETT) is a new cancer treatment modality which combines the use of high voltage pulsed electric fields, dynamic energy delivery rates, and closed loop thermal control algorithms to rapidly and reproducibly create focal ablations. This study examines the ablative potential and profile of pulsed electric field treatments delivered in conjunction with precise temperature control algorithms. An ex vivo perfused liver model was utilized to demonstrate the capability of 5000 V 2 μs duration bipolar electrical pulses and dynamic temperature control algorithms to produce ablations. Using a three applicator array, 4 cm ablation zones were created in under 27 min. In this configuration, the algorithms were able to rapidly achieve and maintain temperatures of 80 °C at the tissue-electrode interface. A simplified single applicator and grounding pad approach was used to correlate the measured ablation zones to electric field isocontours in order to determine lethal electric field thresholds of 708 V/cm and 867 V/cm for 45 °C and 60 °C treatments, respectively. These results establish ETT as a viable method for hepatic tumor treatment with ablation profiles equivalent to other energy based techniques. The single applicator and multi-applicator approaches demonstrated may enable the treatment of complex tumor geometries. The flexibility of ETT temperature control yields a malleable intervention which gives clinicians robust control over the ablation modality, treatment time, and safety profile.}, journal={COMPUTERS IN BIOLOGY AND MEDICINE}, author={Sano, Michael B. and Petrella, Ross A. and Kaufman, Jacob D. and Fesmire, Christopher C. and Xing, Lei and Gerber, David and Fogle, Callie A.}, year={2020}, month={Jun} }
 @article{kaufman_fesmire_petrella_fogle_xing_gerber_sano_2020, title={High-Frequency Irreversible Electroporation Using 5,000-V Waveforms to Create Reproducible 2-and 4-cm Ablation Zones - A Laboratory Investigation Using Mechanically Perfused Liver}, volume={31}, ISSN={["1535-7732"]}, DOI={10.1016/j.jvir.2019.05.009}, abstractNote={To investigate if high-frequency irreversible electroporation (H-FIRE) treatments can be delivered at higher voltages and with greater energy delivery rates than currently implemented in clinical irreversible electroporation protocols.Treatments using 3,000 V and 5,000 V were administered to mechanically perfused ex vivo porcine liver via a single applicator and grounding pad (A+GP) as well as a 4-applicator array (4AA). Integrated energized times (IET) 0.01-0.08 seconds and energy delivery rates 25-300 μs/s were investigated. Organs were preserved at 4°C for 10-15 hours before sectioning and gross analysis using a metabolic stain to identify the size and shape of ablation zones.A+GP ablations measured between 1.6 cm and 2.2 cm, which did not increase when IET was increased from 0.02 seconds to 0.08 seconds (P > .055; range, 1.9-2.1 cm). Changes in tissue color and texture consistent with thermal damage were observed for treatments with energy delivery rates 50-300 μs/s, but not for treatments delivered at 25 μs/s. Use of the 4AA with a 3-cm applicator spacing resulted in ablations measuring 4.4-4.9 cm with energy delivery times of 7-80 minutes.H-FIRE treatments can rapidly and reproducibly create 2-cm ablations using an A+GP configuration. Treatments without thermal injury were produced at the expense of extended treatment times. More rapid treatments resulted in ablations with varying degrees of thermal injury within the H-FIRE ablation zone. Production of 4-cm ablations is possible using a 4AA.}, number={1}, journal={JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY}, author={Kaufman, Jacob D. and Fesmire, Christopher C. and Petrella, Ross A. and Fogle, Callie A. and Xing, Lei and Gerber, David and Sano, Michael B.}, year={2020}, month={Jan}, pages={162–168} }
 @article{fesmire_petrella_fogle_gerber_xing_sano_2020, title={Temperature Dependence of High Frequency Irreversible Electroporation Evaluated in a 3D Tumor Model}, volume={48}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-019-02423-w}, abstractNote={Electroporation is a bioelectric phenomenon used to deliver target molecules into cells in vitro and irreversible electroporation (IRE) is an emerging cancer therapy used to treat inoperable tumors in situ. These phenomena are generally considered to be non-thermal in nature. In this study, a 3D tumor model was used to investigate the correlation between temperature and the effectiveness of standard clinical IRE and high frequency (H-FIRE) protocols. It was found for human glioblastoma cells that in the range of 2 to 37 °C the H-FIRE lethal electric field threshold value, which describes the minimum electric field to cause cell death, is highly dependent on temperature. Increasing the initial temperature from 2 to 37 °C resulted in a significant decrease in lethal electric field threshold from 1168 to 507 V/cm and a 139% increase in ablation size for H-FIRE burst treatments. Standard clinical protocol IRE treatments resulted in a decrease in lethal threshold from 485 to 453 V/cm and a 7% increase in ablation size over the same temperature range. Similar results were found for pancreatic cancer cells which indicate that tissue temperature may be a significant factor affecting H-FIRE ablation size and treatment planning in vivo while lower temperatures may be useful in maintaining cell viability for transfection applications.}, number={8}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Fesmire, Christopher C. and Petrella, Ross A. and Fogle, Callie A. and Gerber, David A. and Xing, Lei and Sano, Michael B.}, year={2020}, month={Aug}, pages={2233–2246} }
 @article{sano_dewitt_teeter_xing_2018, title={Optimization of a single insertion electrode array for the creation of clinically relevant ablations using high-frequency irreversible electroporation}, volume={95}, ISSN={0010-4825}, url={http://dx.doi.org/10.1016/J.COMPBIOMED.2018.02.009}, DOI={10.1016/J.COMPBIOMED.2018.02.009}, abstractNote={High-frequency irreversible electroporation (H-FIRE) is an emerging ablation modality, delivering rapid bursts of bipolar microsecond-duration electrical pulses to non-thermally ablate tissue including tumors. With advantages over current electroporation techniques including mitigation of muscle stimulation and reduced susceptibility to heterogeneous tissue properties, H-FIRE may produce more uniform and predictable ablations and can potentially be delivered with a single applicator device. However, the resulting ablations tend to be smaller than those provided with equivalent energy monopolar pulse protocols. Here, we develop numerical simulations that demonstrate the potential for clinically relevant ablations with H-FIRE delivered via a single insertion technique comprised of an expandable array and a distally placed grounding pad. Based on existing in vivo data and new in vitro results, delivery of H-FIRE with a clinical IRE single electrode probe (1 cm long) is predicted to produce a 2.2 cm3 ablation while an optimized eight tine array produces a 3.2 cm3 ablation when the same H-FIRE bursts are delivered (5000 V). We demonstrate that alternative pulse protocols can be used to increase ablation volumes with this optimized array and these results indicate that in vivo investigation of a single insertion array and grounding pad are warranted.}, journal={Computers in Biology and Medicine}, publisher={Elsevier BV}, author={Sano, Michael B. and DeWitt, Matthew R. and Teeter, Stephanie D. and Xing, Lei}, year={2018}, month={Apr}, pages={107–117} }
 @article{sano_fan_cheng_saenz_sonn_hwang_xing_2018, title={Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an Ex Vivo Swine Model}, volume={29}, ISSN={["1535-7732"]}, DOI={10.1016/j.jvir.2017.12.019}, abstractNote={Purpose To compare the intensity of muscle contractions in irreversible electroporation (IRE) treatments when traditional IRE and high-frequency IRE (H-FIRE) waveforms are used in combination with a single applicator and distal grounding pad (A+GP) configuration. Materials and Methods An ex vivo in situ porcine model was used to compare muscle contractions induced by traditional monopolar IRE waveforms vs high-frequency bipolar IRE waveforms. Pulses with voltages between 200 and 5,000 V were investigated, and muscle contractions were recorded by using accelerometers placed on or near the applicators. Results H-FIRE waveforms reduced the intensity of muscle contractions in comparison with traditional monopolar IRE pulses. A high-energy burst of 2-μs alternating-polarity pulses energized for 200 μs at 4,500 V produced less intense muscle contractions than traditional IRE pulses, which were 25–100 μs in duration at 3,000 V. Conclusions H-FIRE appears to be an effective technique to mitigate the muscle contractions associated with traditional IRE pulses. This may enable the use of voltages greater than 3,000 V necessary for the creation of large ablations in vivo.}, number={6}, journal={JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY}, author={Sano, Michael B. and Fan, Richard E. and Cheng, Kai and Saenz, Yamil and Sonn, Geoffrey A. and Hwang, Gloria L. and Xing, Lei}, year={2018}, month={Jun}, pages={893–898} }
 @article{cheng_sano_jenkins_zhang_vernekohl_zhao_wei_zhang_zhang_liu_et al._2018, title={Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures}, volume={12}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/ACSNANO.8B02038}, DOI={10.1021/ACSNANO.8B02038}, abstractNote={Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide (TiO2), as a radio-sensitizer for radiation therapy of triple-negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DAT uptake for a radio-sensitized radiation therapy.}, number={5}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Cheng, Kai and Sano, Michael and Jenkins, Cesare H. and Zhang, Guanglei and Vernekohl, Don and Zhao, Wei and Wei, Chenxi and Zhang, Yan and Zhang, Zhe and Liu, Yijin and et al.}, year={2018}, month={Apr}, pages={4946–4958} }
 @article{miklovic_latouche_dewitt_davalos_sano_2017, title={A Comprehensive Characterization of Parameters Affecting High-Frequency Irreversible Electroporation Lesions}, volume={45}, ISSN={0090-6964 1573-9686}, url={http://dx.doi.org/10.1007/S10439-017-1889-2}, DOI={10.1007/S10439-017-1889-2}, abstractNote={Several focal therapies are being investigated clinically to treat tumors in which surgery is contraindicated. Many of these ablation techniques, such as radiofrequency ablation and microwave ablation, rely on thermal damage mechanisms which can put critical nerves or vasculature at risk. Irreversible electroporation (IRE) is a minimally invasive, non-thermal technique to destroy tumors. A series of short electric pulses create nanoscale defects in the cell membrane, eventually leading to cell death. Typical IRE protocols deliver a series of 50-100 µs monopolar pulses. High frequency IRE (H-FIRE) aims to replace these monopolar pulses with integrated bursts of 0.25-10 µs bipolar pulses. Here, we examine ablations created using a broad array of IRE and H-FIRE protocols in a potato tissue phantom model. Our results show that H-FIRE pulses require a higher energy dose to create equivalent lesions to standard IRE treatment protocols. We show that ablations in potato do not increase when more than 40 H-FIRE bursts are delivered. These results show that H-FIRE treatment protocols can be optimized to produce clinically relevant lesions while maintaining the benefits of a non-thermal ablation technique.}, number={11}, journal={Annals of Biomedical Engineering}, publisher={Springer Nature}, author={Miklovic, Tyler and Latouche, Eduardo L. and DeWitt, Matthew R. and Davalos, Rafael V. and Sano, Michael B.}, year={2017}, month={Jul}, pages={2524–2534} }
 @article{sano_fan_xing_2017, title={Asymmetric Waveforms Decrease Lethal Thresholds in High Frequency Irreversible Electroporation Therapies}, volume={7}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/SREP40747}, DOI={10.1038/SREP40747}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Sano, Michael B. and Fan, Richard E. and Xing, Lei}, year={2017}, month={Jan} }
 @article{latouche_sano_lorenzo_davalos_martin_2017, title={Irreversible electroporation for the ablation of pancreatic malignancies: A patient‐specific methodology}, volume={115}, ISSN={0022-4790 1096-9098}, url={http://dx.doi.org/10.1002/JSO.24566}, DOI={10.1002/JSO.24566}, abstractNote={Background and ObjectivesIrreversible Electroporation (IRE) is a focal ablation technique highly attractive to surgical oncologists due to its non‐thermal nature that allows for eradication of unresectable tumors in a minimally invasive procedure. In this study, our group sought to address the challenge of predicting the ablation volume with IRE for pancreatic procedures.}, number={6}, journal={Journal of Surgical Oncology}, publisher={Wiley}, author={Latouche, Eduardo L. and Sano, Michael B. and Lorenzo, Melvin F. and Davalos, Rafael V. and Martin, Robert C. G., II}, year={2017}, month={Feb}, pages={711–717} }
 @article{sano_fan_hwang_sonn_xing_2016, title={Production of Spherical Ablations Using Nonthermal Irreversible Electroporation: A Laboratory Investigation Using a Single Electrode and Grounding Pad}, volume={27}, ISSN={1051-0443}, url={http://dx.doi.org/10.1016/J.JVIR.2016.05.032}, DOI={10.1016/J.JVIR.2016.05.032}, abstractNote={Purpose To mathematically model and test ex vivo a modified technique of irreversible electroporation (IRE) to produce large spherical ablations by using a single probe. Materials and Methods Computed simulations were performed by using varying voltages, electrode exposure lengths, and tissue types. A vegetable (potato) tissue model was then used to compare ablations created by conventional and high-frequency IRE protocols by using 2 probe configurations: a single probe with two collinear electrodes (2EP) or a single electrode configured with a grounding pad (P+GP). The new P+GP electrode configuration was evaluated in ex vivo liver tissue. Results The P+GP configuration produced more spherical ablation volumes than the 2EP configuration in computed simulations and tissue models. In prostate tissue, computed simulations predicted ablation volumes at 3,000 V of 1.6 cm3 for the P+GP configurations, compared with 0.94 cm3 for the 2EP configuration; in liver tissue, the predicted ablation volumes were 4.7 times larger than those in the prostate. Vegetable model studies verify that the P+GP configuration produces larger and more spherical ablations than those produced by the 2EP. High-frequency IRE treatment of ex vivo liver with the P+GP configuration created a 2.84 × 2.21-cm ablation zone. Conclusions Computer modeling showed that P+GP configuration for IRE procedures yields ablations that are larger than the 2EP configuration, creating substantial ablation zones with a single electrode placement. When tested in tissue models and an ex vivo liver model, the P+GP configuration created ablation zones that appear to be of clinically relevant size and shape.}, number={9}, journal={Journal of Vascular and Interventional Radiology}, publisher={Elsevier BV}, author={Sano, Michael B. and Fan, Richard E. and Hwang, Gloria L. and Sonn, Geoffrey A. and Xing, Lei}, year={2016}, month={Sep}, pages={1432–1440.e3} }
 @article{sano_arena_bittleman_dewitt_cho_szot_saur_cissell_robertson_lee_et al._2015, title={Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth}, volume={5}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/SREP14999}, DOI={10.1038/SREP14999}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Sano, Michael B. and Arena, Christopher B. and Bittleman, Katelyn R. and DeWitt, Matthew R. and Cho, Hyung J. and Szot, Christopher S. and Saur, Dieter and Cissell, James M. and Robertson, John and Lee, Yong W. and et al.}, year={2015}, month={Oct} }
 @article{ivey_latouche_sano_rossmeisl_davalos_verbridge_2015, title={Targeted cellular ablation based on the morphology of malignant cells}, volume={5}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/SREP17157}, DOI={10.1038/SREP17157}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Ivey, Jill W. and Latouche, Eduardo L. and Sano, Michael B. and Rossmeisl, John H. and Davalos, Rafael V. and Verbridge, Scott S.}, year={2015}, month={Nov} }
 @article{sano_arena_dewitt_saur_davalos_2014, title={In-vitro bipolar nano- and microsecond electro-pulse bursts for irreversible electroporation therapies}, volume={100}, ISSN={1567-5394}, url={http://dx.doi.org/10.1016/J.BIOELECHEM.2014.07.010}, DOI={10.1016/J.BIOELECHEM.2014.07.010}, abstractNote={Under the influence of external electric fields, cells experience a rapid potential buildup across the cell membrane. Above a critical threshold of electric field strength, permanent cell damage can occur, resulting in cell death. Typical investigations of electroporation effects focus on two distinct regimes. The first uses sub-microsecond duration, high field strength pulses while the second uses longer (50 μs+) duration, but lower field strength pulses. Here we investigate the effects of pulses between these two extremes. The charging behavior of the cell membrane and nuclear envelope is evaluated numerically in response to bipolar pulses between 250 ns and 50 μs. Typical irreversible electroporation protocols expose cells to 90 monopolar pulses, each 100 μs in duration with a 1 second inter-pulse delay. Here, we replace each monopolar waveform with a burst of alternating polarity pulses, while keeping the total energized time (100 μs), burst number (80), and inter-burst delay (1s) the same. We show that these bursts result in instantaneous and delayed cell death mechanisms and that there exists an inverse relationship between pulse-width and toxicity despite the delivery of equal quantities of energy. At 1500 V/cm only treatments with bursts containing 50 μs pulses (2×) resulted in viability below 10%. At 4000 V/cm, bursts with 1 μs (100×), 2 μs (50×), 5 μs (20×), 10 μs (10×), and 50 μs (2×) duration pulses reduced viability below 10% while bursts with 500 ns (200×) and 250 ns (400×) pulses resulted in viabilities of 31% and 92%, respectively.}, journal={Bioelectrochemistry}, publisher={Elsevier BV}, author={Sano, Michael B. and Arena, Christopher B. and DeWitt, Matthew R. and Saur, Dieter and Davalos, Rafael V.}, year={2014}, month={Dec}, pages={69–79} }
 @article{salmanzadeh_sano_gallo-villanueva_roberts_schmelz_davalos_2013, title={Investigating dielectric properties of different stages of syngeneic murine ovarian cancer cells}, volume={7}, ISSN={1932-1058}, url={http://dx.doi.org/10.1063/1.4788921}, DOI={10.1063/1.4788921}, abstractNote={In this study, the electrical properties of four different stages of mouse ovarian surface epithelial (MOSE) cells were investigated using contactless dielectrophoresis (cDEP). This study expands the work from our previous report describing for the first time the crossover frequency and cell specific membrane capacitance of different stages of cancer cells that are derived from the same cell line. The specific membrane capacitance increased as the stage of malignancy advanced from 15.39 ± 1.54 mF m−2 for a non-malignant benign stage to 26.42 ± 1.22 mF m−2 for the most aggressive stage. These differences could be the result of morphological variations due to changes in the cytoskeleton structure, specifically the decrease of the level of actin filaments in the cytoskeleton structure of the transformed MOSE cells. Studying the electrical properties of MOSE cells provides important information as a first step to develop cancer-treatment techniques which could partially reverse the cytoskeleton disorganization of malignant cells to a morphology more similar to that of benign cells.}, number={1}, journal={Biomicrofluidics}, publisher={AIP Publishing}, author={Salmanzadeh, Alireza and Sano, Michael B. and Gallo-Villanueva, Roberto C. and Roberts, Paul C. and Schmelz, Eva M. and Davalos, Rafael V.}, year={2013}, month={Jan}, pages={011809} }
 @article{gallo-villanueva_sano_lapizco-encinas_davalos_2013, title={Joule heating effects on particle immobilization in insulator-based dielectrophoretic devices}, volume={35}, ISSN={0173-0835}, url={http://dx.doi.org/10.1002/ELPS.201300171}, DOI={10.1002/ELPS.201300171}, abstractNote={In this work, the temperature effects due to Joule heating obtained by application of a direct current electric potential were investigated for a microchannel with cylindrical insulating posts employed for insulator‐based dielectrophoresis. The conductivity of the suspending medium, the local electric field, and the gradient of the squared electric field, which directly affect the magnitude of the dielectrophoretic force exerted on particles, were computationally simulated employing COMSOL Multiphysics. It was observed that a temperature gradient is formed along the microchannel, which redistributes the conductivity of the suspending medium leading to an increase of the dielectrophoretic force toward the inlet of the channel while decreasing toward the outlet. Experimental results are in good agreement with simulations on the particle‐trapping zones anticipated. This study demonstrates the importance of considering Joule heating effects when designing insulator‐based dielectrophoresis systems.}, number={2-3}, journal={ELECTROPHORESIS}, publisher={Wiley}, author={Gallo-Villanueva, Roberto C. and Sano, Michael B. and Lapizco-Encinas, Blanca H. and Davalos, Rafael V.}, year={2013}, month={Oct}, pages={352–361} }
 @article{sano_gallo-villanueva_lapizco-encinas_davalos_2013, title={Simultaneous electrokinetic flow and dielectrophoretic trapping using perpendicular static and dynamic electric fields}, volume={15}, ISSN={1613-4982 1613-4990}, url={http://dx.doi.org/10.1007/S10404-013-1175-Z}, DOI={10.1007/S10404-013-1175-Z}, number={5}, journal={Microfluidics and Nanofluidics}, publisher={Springer Science and Business Media LLC}, author={Sano, Michael B. and Gallo-Villanueva, Roberto C. and Lapizco-Encinas, Blanca H. and Davalos, Rafael V.}, year={2013}, month={Mar}, pages={599–609} }
 @article{salmanzadeh_kittur_sano_c. roberts_schmelz_davalos_2012, title={Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis}, volume={6}, ISSN={1932-1058}, url={http://dx.doi.org/10.1063/1.3699973}, DOI={10.1063/1.3699973}, abstractNote={Ovarian cancer is the leading cause of death from gynecological malignancies in women. The primary challenge is the detection of the cancer at an early stage, since this drastically increases the survival rate. In this study we investigated the dielectrophoretic responses of progressive stages of mouse ovarian surface epithelial (MOSE) cells, as well as mouse fibroblast and macrophage cell lines, utilizing contactless dielectrophoresis (cDEP). cDEP is a relatively new cell manipulation technique that has addressed some of the challenges of conventional dielectrophoretic methods. To evaluate our microfluidic device performance, we computationally studied the effects of altering various geometrical parameters, such as the size and arrangement of insulating structures, on dielectrophoretic and drag forces. We found that the trapping voltage of MOSE cells increases as the cells progress from a non-tumorigenic, benign cell to a tumorigenic, malignant phenotype. Additionally, all MOSE cells display unique behavior compared to fibroblasts and macrophages, representing normal and inflammatory cells found in the peritoneal fluid. Based on these findings, we predict that cDEP can be utilized for isolation of ovarian cancer cells from peritoneal fluid as an early cancer detection tool.}, number={2}, journal={Biomicrofluidics}, publisher={AIP Publishing}, author={Salmanzadeh, Alireza and Kittur, Harsha and Sano, Michael B. and C. Roberts, Paul and Schmelz, Eva M. and Davalos, Rafael V.}, year={2012}, month={Jun}, pages={024104} }
 @article{sano_salmanzadeh_davalos_2012, title={Multilayer contactless dielectrophoresis: Theoretical considerations}, volume={33}, ISSN={0173-0835}, url={http://dx.doi.org/10.1002/elps.201100677}, DOI={10.1002/elps.201100677}, abstractNote={Dielectrophoresis (DEP), the movement of dielectric particles in a nonuniform electric field, is of particular interest due to its ability to manipulate particles based on their unique electrical properties. Contactless DEP (cDEP) is an extension of traditional and insulator‐based DEP topologies. The devices consist of a sample channel and fluid electrode channels filled with a highly conductive media. A thin insulating membrane between the sample channel and the fluid electrode channels serves to isolate the sample from direct contact with metal electrodes. Here we investigate, for the first time, the properties of multilayer devices in which the sample and electrode channels occupy distinct layers. Simulations are conducted using commercially available finite element software and a less computationally demanding numerical approximation is presented and validated. We show that devices can be created that achieve a similar level of electrical performance to other cDEP devices presented in the literature while increasing fluid throughput. We conclude, based on these models, that the ultimate limiting factors in device performance resides in breakdown voltage of the barrier material and the ability to generate high‐voltage, high‐frequency signals. Finally, we demonstrate trapping of MDA‐MB‐231 breast cancer cells in a prototype device at a flow rate of 1.0 mL/h when 250 VRMS at 600 kHz is applied.}, number={13}, journal={ELECTROPHORESIS}, publisher={Wiley}, author={Sano, Michael B. and Salmanzadeh, Alireza and Davalos, Rafael V.}, year={2012}, month={Jul}, pages={1938–1946} }
 @article{sano_henslee_schmelz_davalos_2011, title={Contactless dielectrophoretic spectroscopy: Examination of the dielectric properties of cells found in blood}, volume={32}, ISSN={0173-0835}, url={http://dx.doi.org/10.1002/elps.201100351}, DOI={10.1002/elps.201100351}, abstractNote={Abstract}, number={22}, journal={ELECTROPHORESIS}, publisher={Wiley}, author={Sano, Michael B. and Henslee, Erin A. and Schmelz, Eva and Davalos, Rafael V.}, year={2011}, month={Nov}, pages={3164–3171} }
 @article{sano_caldwell_davalos_2011, title={Modeling and development of a low frequency contactless dielectrophoresis (cDEP) platform to sort cancer cells from dilute whole blood samples}, volume={30}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2011.07.048}, DOI={10.1016/j.bios.2011.07.048}, abstractNote={Contactless dielectrophoresis (cDEP) devices are a new adaptation of dielectrophoresis in which fluid electrodes, isolated from the main microfluidic channel by a thin membrane, provide the electric field gradients necessary to manipulate cells. This work presents a continuous sorting device which is the first cDEP design capable of exploiting the Clausius-Mossotti factor at frequencies where it is both positive and negative for mammalian cells. Experimental devices are fabricated using a cost effective technique which can achieve 50 μm feature sizes and does not require the use of a cleanroom or specialized equipment. An analytical model is developed to evaluate cDEP devices as a network of parallel resistor-capacitor pairs. Two theoretical devices are presented and evaluated using finite element methods to demonstrate the effect of geometry on the development of electric field gradients across a wide frequency spectrum. Finally, we present an experimental device capable of continuously sorting human leukemia cells from dilute blood samples. This is the first cDEP device designed to operate below 100 kHz resulting in successful manipulation of human leukemia cells, while in the background red blood cells are unaffected.}, number={1}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Sano, Michael B. and Caldwell, John L. and Davalos, Rafael V.}, year={2011}, month={Dec}, pages={13–20} }
 @article{henslee_sano_rojas_schmelz_davalos_2011, title={Selective concentration of human cancer cells using contactless dielectrophoresis}, volume={32}, ISSN={0173-0835}, url={http://dx.doi.org/10.1002/elps.201100081}, DOI={10.1002/elps.201100081}, abstractNote={Abstract}, number={18}, journal={ELECTROPHORESIS}, publisher={Wiley}, author={Henslee, Erin A. and Sano, Michael B. and Rojas, Andrea D. and Schmelz, Eva M. and Davalos, Rafael V.}, year={2011}, month={Aug}, pages={2523–2529} }
 @article{sano_rojas_gatenholm_davalos_2010, title={Electromagnetically Controlled Biological Assembly of Aligned Bacterial Cellulose Nanofibers}, volume={38}, ISSN={0090-6964 1573-9686}, url={http://dx.doi.org/10.1007/S10439-010-9999-0}, DOI={10.1007/S10439-010-9999-0}, abstractNote={We have developed a new biofabrication process in which the precise control of bacterial motion is used to fabricate customizable networks of cellulose nanofibrils. This article describes how the motion of Acetobacter xylinum can be controlled by electric fields while the bacteria simultaneously produce nanocellulose, resulting in networks with aligned fibers. Since the electrolysis of water due to the application of electric fields produces the oxygen in the culture media far from the liquid-air boundary, aerobic cellulose production in 3D structures is readily achievable. Five separate sets of experiments were conducted to demonstrate the assembly of nanocellulose by A. xylinum in the presence of electric fields in micro- and macro-environments. This study demonstrates a new concept of bottom up material synthesis by the control of a biological assembly process.}, number={8}, journal={Annals of Biomedical Engineering}, publisher={Springer Science and Business Media LLC}, author={Sano, Michael B. and Rojas, Andrea D. and Gatenholm, Paul and Davalos, Rafael V.}, year={2010}, month={Mar}, pages={2475–2484} }
 @article{shafiee_sano_henslee_caldwell_davalos_2010, title={Selective isolation of live/dead cells using contactless dielectrophoresis (cDEP)}, volume={10}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/b920590j}, DOI={10.1039/b920590j}, abstractNote={Contactless dielectrophoresis (cDEP) is a recently developed method of cell manipulation in which the electrodes are physically isolated from the sample. Here we present two microfluidic devices capable of selectively isolating live human leukemia cells from dead cells utilizing their electrical signatures. The effect of different voltages and frequencies on the gradient of the electric field and device performance was investigated numerically and validated experimentally. With these prototype devices we were able to achieve greater than 95% removal efficiency at 0.2-0.5 mm s(-1) with 100% selectivity between live and dead cells. In conjunction with enrichment, cDEP could be integrated with other technologies to yield fully automated lab-on-a-chip systems capable of sensing, sorting, and identifying rare cells.}, number={4}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Shafiee, Hadi and Sano, Michael B. and Henslee, Erin A. and Caldwell, John L. and Davalos, Rafael V.}, year={2010}, pages={438} }
 @article{shafiee_caldwell_sano_davalos_2009, title={Contactless dielectrophoresis: a new technique for cell manipulation}, volume={11}, ISSN={1387-2176 1572-8781}, url={http://dx.doi.org/10.1007/S10544-009-9317-5}, DOI={10.1007/S10544-009-9317-5}, abstractNote={Dielectrophoresis (DEP) has become a promising technique to separate and identify cells and microparticles suspended in a medium based on their size or electrical properties. Presented herein is a new technique to provide the non-uniform electric field required for DEP that does not require electrodes to contact the sample fluid. In our method, electrodes are capacitively-coupled to a fluidic channel through dielectric barriers; the application of a high-frequency electric field to these electrodes then induces an electric field in the channel. This technique combines the cell manipulation abilities of traditional DEP with the ease of fabrication found in insulator-based technologies. A microfluidic device was fabricated based on this principle to determine the feasibility of cell manipulations through contactless DEP (cDEP). We were able to demonstrate cell responses unique to the DEP effect in three separate cell lines. These results illustrate the potential for this technique to identify cells through their electrical properties without fear of contamination from electrodes.}, number={5}, journal={Biomedical Microdevices}, publisher={Springer Science and Business Media LLC}, author={Shafiee, Hadi and Caldwell, John L. and Sano, Michael B. and Davalos, Rafael V.}, year={2009}, month={May}, pages={997–1006} }