@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}, abstractNote={Objective: This study sought to investigate a novel strategy using temperature-controlled delivery of nanosecond pulsed electric fields as an alternative to the 50-100 microsecond pulses used for irreversible electroporation. Methods: INSPIRE treatments were carried out at two temperatures in 3D tumor models using doses between 0.001 s and 0.1 s. The resulting treatment zones were quantified using viability staining and lethal electric field intensities were determined numerically. Computational modeling was then used to determine parameters necessary for INSPIRE treatments to achieve equivalent treatment zones to clinical electroporation treatments and evaluate the potential for these treatments to induce deleterious thermal damage. Results: Lethal thresholds between 1109 and 709 V/cm were found for nominal 0.01 s treatments with pulses between 350 ns and 2000 ns at physiological temperatures. Further increases in dose resulted in significant decreases in lethal thresholds. Given these experimental results, treatment zones comparable to clinical electroporation are possible by increasing the dose and voltage used with nanosecond duration pulses. Temperature-controlled simulations indicate minimal thermal cell death while achieving equivalent treatment volumes to clinical electroporation. Conclusion: Nanosecond electrical pulses can achieve comparable outcomes to traditional electroporation provided sufficient electrical doses or voltages are applied. The use of temperature-controlled delivery may minimize thermal damage during treatment. Significance: Intense muscle stimulation and the need for cardiac gating have limited irreversible electroporation. Nanosecond pulses can alleviate these challenges, but traditionally have produced significantly smaller treatment zones. This study suggests that larger ablation volumes may be possible with the INSPIRE approach and that future in vivo studies are warranted.}, 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.MethodsA custom applicator and a pulse generation system were utilized in a pilot study to treat horses presenting with spontaneous melanoma. INSPIRE treatments were administered to 32 tumors across 6 horses and an additional 13 tumors were followed to act as untreated controls. Tumors were tracked over a 43–85 day period following a single INSPIRE treatment. Pulse widths of 500ns and 2000ns with voltages between 1000 V and 2000 V were investigated to determine the effect of these variables on treatment outcomes.ResultsTreatments administered at the lowest voltage (1000 V) reduced tumor volumes by 11 to 15%. Higher voltage (2000 V) treatments reduced tumor volumes by 84 to 88% and eliminated 33% and 80% of tumors when 500 ns and 2000 ns pulses were administered, respectively.DiscussionPromising results were achieved without the use of chemotherapeutics, the use of general anesthesia, or the need for surgical resection in regions which are challenging to keep sterile. This novel therapeutic approach has the potential to expand the role of pulsed electric fields in veterinary patients, especially when general anesthesia is contraindicated, and warrants future studies to demonstrate the efficacy of INSPIRE as a solid tumor treatment.}, 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{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_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{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={AbstractIrreversible electroporation (IRE) is a promising non-thermal treatment for inoperable tumors which uses short (50–100 μs) high voltage monopolar pulses to disrupt the membranes of cells within a well-defined volume. Challenges with IRE include complex treatment planning and the induction of intense muscle contractions. High frequency IRE (H-FIRE) uses bursts of ultrashort (0.25–5 μs) alternating polarity pulses to produce more predictable ablations and alleviate muscle contractions associated with IRE. However, H-FIRE generally ablates smaller volumes of tissue than IRE. This study shows that asymmetric H-FIRE waveforms can be used to create ablation volumes equivalent to standard IRE treatments. Lethal thresholds (LT) of 505 V/cm and 1316 V/cm were found for brain cancer cells when 100 μs IRE and 2 μs symmetric H-FIRE waveforms were used. In contrast, LT as low as 536 V/cm were found for 2 μs asymmetric H-FIRE waveforms. Reversible electroporation thresholds were 54% lower than LTs for symmetric waveforms and 33% lower for asymmetric waveforms indicating that waveform symmetry can be used to tune the relative sizes of reversible and irreversible ablation zones. Numerical simulations predicted that asymmetric H-FIRE waveforms are capable of producing ablation volumes which were 5.8–6.3x larger than symmetric H-FIRE waveforms indicating that in vivo investigation of asymmetric waveforms is warranted.}, 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.MethodsIn compliance with HIPAA and hospital IRB approval, we established a pre‐treatment planning methodology for IRE procedures in pancreas, which optimized treatment protocols for individual cases of locally advanced pancreatic cancer (LAPC). A new method for confirming treatment plans through intraoperative monitoring of tissue resistance was also proved feasible in three patients.ResultsResults from computational models showed good correlation with experimental data available in the literature. By implementing the proposed resistance measurement system 210 ± 26.1 (mean ± standard deviation) fewer pulses were delivered per electrode‐pair.ConclusionThe proposed physics‐based pre‐treatment plan through finite element analysis and system for actively monitoring resistance changes can be paired to significantly reduce ablation times and risk of thermal effects during IRE procedures for LAPC.}, 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={To mathematically model and test ex vivo a modified technique of irreversible electroporation (IRE) to produce large spherical ablations by using a single probe.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.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 cm(3) for the P+GP configurations, compared with 0.94 cm(3) 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.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={AbstractIrreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models.}, 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={AbstractTreatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.}, 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 (1 s) 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={AbstractThe use of non‐invasive methods to detect and enrich circulating tumor cells (CTCs) independent of their genotype is critical for early diagnostic and treatment purposes. The key to using CTCs as predictive clinical biomarkers is their separation and enrichment. This work presents the use of a contactless dielectrophoresis (cDEP) device to investigate the frequency response of cells and calculate their area‐specific membrane capacitance. This is the first demonstration of a cDEP device which is capable of operating between 10 and 100 kHz. Positive and negative dielectrophoretic responses were observed in red blood cells, macrophages, breast cancer, and leukemia cells. The area‐specific membrane capacitances of MDA‐MB231, THP‐1 and PC1 cells were determined to be 0.01518 ± 0.0013, 0.01719 ± 0.0020, 0.01275 ± 0.0018 (F/m2), respectively. By first establishing the dielectrophoretic responses of cancerous cells within this cDEP device, conditions to detect and enrich tumor cells from mixtures with non‐transformed cells can be determined providing further information to develop methods to isolate these rare cells.}, 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={AbstractThis work is the first to demonstrate the ability of contactless dielectrophoresis (cDEP) to isolate target cell species from a heterogeneous sample of live cells. Since all cell types have a unique molecular composition, it is expected that their dielectrophoretic (DEP) properties are also unique. cDEP is a technique developed to improve upon traditional and insulator‐based DEP devices by replacing embedded metal electrodes with fluid electrode channels positioned alongside desired trapping locations. Through the placement of the fluid electrode channels and the removal of contact between the electrodes and the sample fluid, cDEP mitigates issues associated with sample/electrode contact. MCF10A, MCF7, and MDA‐MB‐231 human breast cells were used to represent early, intermediate, and late‐staged breast cancer, respectively. Trapping frequency responses of each cell type were distinct, with the largest difference between the cells found at 20 and 30 V. MDA‐MB‐231 cells were successfully isolated from a population containing MCF10A and MCF7 cells at 30 V and 164 kHz. The ability to selectively concentrate cells is the key to development of biological applications using DEP. The isolation of these cells could provide a workbench for clinicians to detect transformed cells at their earliest stage, screen drug therapies prior to patient treatment, increasing the probability of success, and eliminate unsuccessful treatment options.}, 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} }