scholarly journals Toward a clinical real time tissue ablation technology: combining electroporation and electrolysis (E2)

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e7985 ◽  
Author(s):  
Enric Guenther ◽  
Nina Klein ◽  
Paul Mikus ◽  
Florin Botea ◽  
Mihail Pautov ◽  
...  

Background Percutaneous image-guided tissue ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation—E2—affords tissue ablation with greater efficiency, that is, lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as tissue behavior to enable real time tissue ablation of clinically relevant volumes. Results Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.

2016 ◽  
Author(s):  
Nina Klein ◽  
Enric Guenther ◽  
Paul Mikus ◽  
Michael K Stehling ◽  
Boris Rubinsky

Background: Electrolytic ablation and electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of electroporation and electrolysis (E2). Method: A new device that delivers a controlled dose of electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW), was applied to the pig liver and the effect of various parameters on the extent of tissue ablation was examined with histology. Results: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in electroporation or electrolysis separately, cannot ablate the tissue Discussion: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible electroporation with injection of drugs) and irreversible electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and electroporation, without the need to inject drugs as in reversible electroporation or use paralyzing anesthesia as in irreversible electroporation.


Sensors ◽  
2020 ◽  
Vol 20 (11) ◽  
pp. 3158 ◽  
Author(s):  
Borja López-Alonso ◽  
Héctor Sarnago ◽  
Óscar Lucía ◽  
Pablo Briz ◽  
José Miguel Burdío

Classical application of electroporation is carried out by using fixed protocols that do not clearly assure the complete ablation of the desired tissue. Nowadays, new methods that pursue the control of the treatment by studying the change in impedance during the applied pulses as a function of the electric field are being developed. These types of control seek to carry out the treatment in the fastest way, decreasing undesired effects and treatment time while ensuring the proper tumour ablation. The objective of this research is to determine the state of the treatment by continuously monitoring the impedance by using a novel versatile high-voltage generator and sensor system. To study the impedance dynamics in real time, the use of pulses of reduced voltage, below the threshold of reversible electroporation, is tested to characterise the state-of-the-treatment without interfering with it. With this purpose, a generator that provides both low voltage for sense tissue changes and high voltage for irreversible electroporation (IRE) was developed. In conclusion, the characterisation of the effects of electroporation in vegetal tissue, combined with the real-time monitoring of the state-of-the-treatment, will enable the provision of safer and more effective treatments.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung Jeong ◽  
Hongbae Kim ◽  
Junhyung Park ◽  
Ki Woo Kim ◽  
Sung Bo Sim ◽  
...  

AbstractIrreversible electroporation (IRE) is a tissue ablation method, uses short high electric pulses and results in cell death in target tissue by irreversibly permeabilizing the cell membrane. Potato is commonly used as a tissue model for electroporation experiments. The blackened area that forms 12 h after electric pulsing is regarded as an IRE-ablated area caused by melanin accumulation. Here, the 2,3,5-triphenyltetrazolium chloride (TTC) was used as a dye to assess the IRE-ablated area 3 h after potato model ablation. Comparison between the blackened area and TTC-unstained white area in various voltage conditions showed that TTC staining well delineated the IRE-ablated area. Moreover, whether the ablated area was consistent over time and at different staining times was investigated. In addition, the presumed reversible electroporation (RE) area was formed surrounding the IRE-ablated area. Overall, TTC staining can provide a more rapid and accurate electroporated area evaluation.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3190 ◽  
Author(s):  
Nina Klein ◽  
Enric Guenther ◽  
Paul Mikus ◽  
Michael K. Stehling ◽  
Boris Rubinsky

Background Electrolytic ablation and electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study, we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of electroporation and electrolysis (E2). Method A new device that delivers a controlled dose of electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW) was applied to the pig liver, and the effect of various parameters on the extent of tissue ablation was examined with histology. Results Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in electroporation or electrolysis separately, cannot ablate the tissue. Discussion The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible electroporation with injection of drugs) and irreversible electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and electroporation, without the need to inject drugs as in reversible electroporation or use paralyzing anesthesia as in irreversible electroporation.


2016 ◽  
Author(s):  
Nina Klein ◽  
Enric Guenther ◽  
Paul Mikus ◽  
Michael K Stehling ◽  
Boris Rubinsky

Background: Electrolytic ablation and electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of electroporation and electrolysis (E2). Method: A new device that delivers a controlled dose of electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW), was applied to the pig liver and the effect of various parameters on the extent of tissue ablation was examined with histology. Results: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in electroporation or electrolysis separately, cannot ablate the tissue Discussion: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible electroporation with injection of drugs) and irreversible electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and electroporation, without the need to inject drugs as in reversible electroporation or use paralyzing anesthesia as in irreversible electroporation.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Maizels ◽  
E Heller ◽  
M Landesberg ◽  
I Huber ◽  
G Arbel ◽  
...  

Abstract Background Cardiac electroporation is a promising novel non-thermal ablation method, gaining significant interest with recent first-in-man data suggesting effective cardiac lesion generation with no collateral damage. Nevertheless, significant knowledge gaps exist regarding its electrophysiological consequences in cardiomyocytes, including; cell specificity, protocol optimization, irreversibility threshold, recovery time-constants, and the mechanistic nature of its cytolytic and anti-arrhythmic properties. Purpose Establishing an innovative in-vitro model for the study of cardiac electroporation-ablation, utilizing human induced pluripotent stem cells (hiPSCs). Methods and results Healthy-control hiPSC-derived cardiomyocytes were enzymatically dissociated and seeded as circular cell sheets (hiPSC-CCSs). Electroporation-ablation experiments were performed using a custom designed high-frequency electroporation (HF-EP) generator. Two needle-shaped electrodes were used for HF-EP delivery (Figure 1). Subsequently, detailed voltage- and Ca2+-mapping studies of the hiPSC-CCSs were conducted (Figure 2). HF-EP application resulted in the generation of electrically isolated lesions within the hiPSC-CCSs (Figure 3). Further characterization of the temporal changes and electrophysiological properties following electroporation revealed that; (1) lesions persisted over prolonged periods of time (days), indicating irreversible electroporation, (2) a temporal decrease in lesion dimensions was noted, consistent with a significant reversible electroporation component (Figures 3–5), (3) most tissue recovery had occurred within the first 15 minutes following electroporation, with little recovery beyond that time-frame, (4) increasing pulse-number augmented lesion area as well as the proportion of irreversible damage, and (5) electroporation sensitization was achieved by increasing extracellular Ca2+, indicating its crucial role in electroporation cytolysis, potentially via direct cellular toxicity and apoptosis facilitation (Figures 5–6). Finally, evaluating for HF-EP anti-arrhythmic properties, we targeted multiple rotors or focal triggered-activity generated in the hiPSC-CCSs. HF-EP application generated sustained line-blocks, isolating arrhythmogenic substrates within the hiPSC-CCSs while blocking the propagation of arrhythmic wavefronts (Figure 7). Conclusion Our results demonstrate the ability to study cardiac electroporation utilizing hiPSC-derived cardiomyocytes, provide novel insights into its temporal and electrophysiological characteristics, facilitate electroporation protocol optimization, screen for potential electroporation sensitizers, and to study its mechanistic nature and anti-arrhythmic properties. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Division of Cardiology, and Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center - Tel Hashomer, Ramat-Gan, Israel Figures 1–4 Figures 5–7


2017 ◽  
Author(s):  
Ryan Rayl ◽  
Stephen Wratten

Historically, handling insects has usually involved their being killed, but non-lethal approaches are necessary when evaluating the biology of such organisms. Anesthesia has been used as one of these non-lethal approaches. Two common anesthetics used in this way have been carbon dioxide and chilling. These have been used frequently in the literature but have sub-lethal effects on insects that may affect further experimentation. An alternative anesthetic that has potential for experimental use is triethylamine (TEA). This shows promise because of its ease of use and potency as an insect anesthetic, but evidence, if any, of the sub-lethal effects is almost non-existent in the literature. Here, longevity was use as a proxy for fitness as this is a common approach to laboratory work of this type for pests and their natural enemies. A series of experiments were carried out to find the optimal rates for these three selected anesthetics. The organism selected for this work was the fly Scaptomyza flava (Fallén), the larvae of which mine the leaves of commercial brassica crops worldwide. It is a ‘cosmetic’ pest in that damage thresholds for crop rejection are very low and prophylactic use of insecticides is the norm. One way of mitigating the negative environmental aspects of this approach is to enhance biological control. One such way of enhancing biological control is the use of flowering plants, as they can provide alternative resources to natural enemies, which can enhance their ability to control pests. To evaluate these flowering plants, handling of the insects is necessary and anesthesia is used for this purpose. For each anesthetic an optimal rate was found, then these rates were compared to each other in a subsequent experiment. These anesthetics differed markedly in their value in terms of the duration of the anesthesia and other practical considerations. TEA had the longest effect, CO2 and chilling had the shortest. All three were similar in their effects on longevity (i.e. recovery time and mortality rates).


2021 ◽  
Vol 8 (6) ◽  
pp. 1237
Author(s):  
Aditia Angga Perdana ◽  
Meinarini Catur Utami ◽  
Qurrotul Aini

<p class="infAbstract">Toyota Sales Operation atau dikenal sebagai AUTO2000 adalah bagian dari perseroan terbuka PT. Astra yang beroperasi di sektor otomotif dan sudah menjalankan beberapa servis untuk menaikkan kepuasan pelanggan. Salah satunya dengan menghadirkan AUTO2000 <em>Mobile</em>, sebagai fasilitas pemesanan servis kendaraan secara <em>online</em> yang bertujuan untuk memudahkan pengguna untuk mempercepat proses bisnis dan mengurangi bahkan menghilangkan durasi waktu mengantri. Namun dalam penerapannya masih banyak kekurangan maupun kelemahan yang dirasakan pengguna di antaranya masih ada <em>bugs</em>, tidak ada fitur <em>real-time chat</em> serta beberapa pengguna masih kesulitan menggunakan aplikasi tersebut. Capaian riset ini adalah menginvestigasi tingkat kepuasan pelanggan dan memperoleh variabel signifikan yang berdampak pada kepuasan pelanggan Aplikasi AUTO2000 <em>Mobile</em>. Metode riset ini menerapkan <em>End-User Computing Satisfaction</em> (EUCS) dengan cara kuantitatif dan diseminasi kuesioner mendapatkan informasi dari objek penelitian. Populasi dalam riset ini adalah pemakai AUTO2000 <em>Mobile</em>. Dari populasi tersebut terpilih sebanyak 252 responden dan diseminasi kuesioner dilaksanakan melalui daring dan membagikan secara langsung dengan cara <em>simple random sampling</em>. Setelah itu, data yang dikumpulkan diolah dengan program Microsoft Excel 2016 serta PLS-SEM mengoperasikan <em>tool</em> SmartPLS 3.2.7. Hasilnya, terdapat 5 jalur yang diuji, H<sub>0</sub> ditolak untuk empat variabel dan H<sub>0</sub> diterima untuk satu variabel. Terdapat empat variabel yang berpengaruh signifikan pada kepuasan pelanggan AUTO2000 <em>Mobile</em> yaitu: <em>accuracy</em>, <em>content</em>, <em>format</em> dan <em>ease of use</em>.</p><p class="infAbstract"> </p><p class="infAbstract"><em><strong>Abstract</strong></em></p><p class="Judul2"><em>Toyota Sales Operation or known as AUTO2000 is part of the public company PT. Astra </em><em>that</em><em> engaged in the automotive sector and has done several service improvements to increase customer satisfaction. One of them is by presenting AUTO2000 Mobile, which is an online vehicle service ordering facility that is implemented </em><em>to make </em><em>it easier for users</em><em>, therefore</em><em> it is </em><em>considered to</em><em> speed up business processes and reduce or even eliminate the duration of the queue. But in its implementation there are still many shortcomings and weaknesses felt by users including bugs, there is no real-time chat feature</em><em>,</em><em> and some users still have difficulty using the application, </em><em>hence</em><em> it is </em><em>prominent</em><em> to </em><em>conduct</em><em> </em><em>study dealing with</em><em> end-user satisfaction. The </em><em>aim</em><em> of this </em><em>research</em><em> is to analysis of end-user satisfaction </em><em>level </em><em>and determine the </em><em>variables</em><em> that </em><em>impact</em><em> end-user satisfaction of the AUTO2000 Mobile Application. This research method </em><em>deals with</em><em> End-User Computing Satisfaction (EUCS) with a quantitative approach and questionnaire distribution to obtain data from respondents. The </em><em>research subject</em><em> in this study </em><em>are</em><em> AUTO2000 Mobile users. </em><em>The</em><em> </em><em>population consist of</em><em> 252 respondents</em><em> and q</em><em>uestionnaires </em><em>are</em><em> distributed online and offline with simple random sampling. Furthermore, the </em><em>obtained </em><em>data were analyzed using Ms. Excel 2016 and with the PLS-SEM approach using SmartPLS 3.2.7. The result, from the 5 paths tested, H<sub>0</sub> is rejected for </em><em>four</em><em> variables and H<sub>0</sub> is accepted for </em><em>one</em><em> variable</em><em>. There are four variables that have a significant effect on customer satisfaction of AUTO2000 Mobile, namely: accuracy, content, format and ease of use.</em></p><p class="infAbstract"><em><strong><br /></strong></em></p>


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