BURLINGAME, CA, United States
BURLINGAME, CA, United States

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Nuccitelli R.,Bioelectromed Corporation | Lui K.,Bioelectromed Corporation | Kreis M.,Bioelectromed Corporation | Athos B.,Bioelectromed Corporation | Nuccitelli P.,Bioelectromed Corporation
Biochemical and Biophysical Research Communications | Year: 2013

The cellular response to 100ns pulsed electric fields (nsPEF) exposure includes the formation of transient nanopores in the plasma membrane and organelle membranes, an immediate increase in intracellular Ca2+, an increase in reactive oxygen species (ROS), DNA fragmentation and caspase activation. 100ns, 30kV/cm nsPEF stimulates an increase in ROS proportional to the pulse number. This increase is inhibited by the anti-oxidant, Trolox, as well as the presence of Ca2+ chelators in the intracellular and extracellular media. This suggests that the nsPEF-triggered Ca2+ increase is required for ROS generation. © 2013 Elsevier Inc.


Pliquett U.,Institute fur Bioproze und Analysenmetechnik e.V. | Nuccitelli R.,Bioelectromed Corporation
Bioelectrochemistry | Year: 2014

Experimental evidence shows that nanosecond pulsed electric fields (nsPEF) trigger apoptosis in skin tumors. We have postulated that the energy delivered by nsPEF is insufficient to impart significant heating to the treated tissue. Here we use both direct measurements and theoretical modeling of the Joule heating in order to validate this assumption.For the temperature measurement, thermo-sensitive liquid crystals (TLC) were used to determine the surface temperature while a micro-thermocouple (made from 30. μm wires) was used for measuring the temperature inside the tissue. The calculation of the temperature distribution used an asymptotic approach with the repeated calculation of the electric field, Joule heating and heat transfer, and the subsequent readjustment of the electrical tissue conductivity. This yields a temperature distribution both in space and time.It can be shown that for the measured increase in temperature an unexpectedly high electrical conductivity of the tissue would be required, which was indeed found by using voltage and current monitoring during the experiment. Using impedance measurements within tafter=. 50. μs after the pulse revealed a fast decline of the high conductivity state when the electric field ceases. The experimentally measured high conductance of a skin fold (mouse) between plate electrodes was about 5 times higher than those of the maximally expected conductance due to fully electroporated membrane structures (. Gmax/. Gelectroporated). ≈. 5. Fully electroporated membrane structure assumes that 100% of the membranes are conductive which is estimated from an impedance measurement at 10. MHz where membranes are capacitively shorted. Since the temperature rise in B-16 mouse melanoma tumors due to equally spaced (. δt=. 2. s) 300. ns-pulses with E=. 40. kV/cm usually does not exceed δτ=. 3. K at all parts of the skin fold between the electrodes, a hyperthermic effect on the tissue can be excluded. © 2014 Elsevier B.V.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 2.21M | Year: 2012

DESCRIPTION (provided by applicant): BioElectroMed is developing a new medical device called the EndoPulse that works in conjunction with an echoendoscope to deliver nanosecond pulsed electric field therapy to treat pancreatic carcinoma as well as lesions in the kidney and liver. The EndoPulse is designed to penetrate through the stomach wall into a pancreatic carcinoma before extending an electrode array on both sides of the tumor. We are also developing a high voltage model of the PulseCure nanosecond pulse generator that can generate 30 kV/cm between the two electrode arrays, exposing the entire tumor to this field strength. We have determined that the application of 500 pulses 100 ns long and 30 kV/cm in amplitude triggers apoptosis in all the human tumor cells between the electrodes and causes them to self-destruct within two weeks. We propose to complete the design and testing of both the EndoPulse and PulseCure prototypes and have the final versions manufactured under GMP for use in human clinical trials. These two instruments will then be used to ablate small regions of pancreas in pigs to demonstrate safety and efficacy prior to submitting the application to the FDA for an Investigational Device Exemption (IDE) required for the clinical trial. Once the IDE is granted, we will conduct a six-patient feasibility clinical trial at Stanford University Medical Center with Drs. Ann Chen and Subhas Banerjee acting as Co-Principal Investigators of this trial. These two gastroenterologists receive 3-4patients per month with non-resectable pancreatic carcinomas for which there is currently no effective therapy. If the PulseCure -EndoPulse system can reliably ablate pancreatic carcinomas, it would offer the first effective, non-surgical therapy for pancreatic cancer that could extend the lives of tens of thousands of patients each year. PUBLIC HEALTH RELEVANCE: This research will develop a breakthrough, minimally invasive approach to the treatment of pancreatic tumors for which current treatment options are poor and costly. This new medical device called the EndoPulse is readily extendable to treat other focal internal lesions especially in the liver, kidney and lymph nodes. The EndoPulse is guided to the internal tumor by ultrasound imaging inan echoendoscope and applies ultrashort electrical pulses that cause the tumor cells to self-destruct.


Patent
Bioelectromed Corporation | Date: 2010-03-17

Systems and methods for treating tumors on or within internal organs of mammals that have been imaged with endoscopic ultrasound are described. The system uses an expandable bipolar electrode assembly that can be imaged by ultrasound and can penetrate, e.g., the stomach, intestine or bowel wall, etc. and be positioned in or around the tumor on an internal organ while being guided by an operator who visualizes its position with ultrasound imaging. It utilizes an electrode assembly that extends down an internal cavity in the endoscope to allow the operator to spread the electrodes for pulse delivery of a nanosecond pulsed electric field (nsPEF) to the tumor.


Nanosecond pulsed electric field (nsPEF) parameters for destroying tumors with a single treatment are described. A nsPEF generator may be used with an electrode assembly to apply the pulses to one or more tumors where the parameters for the nsPEF are optimized for treating such tumors.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.70M | Year: 2010

DESCRIPTION (provided by applicant): BioElectroMed is developing a new medical device called the PulseCure System that utilizes nanosecond pulsed electric fields to eliminate both benign and malignant skin lesions. We have used the PulseCure to treat malignant melanoma and basal cell carcinoma in mice with very high efficacy. With a single, 6-minute treatment using 100 ns pulses, we can trigger complete remission of malignant melanomas without recurrence in nude mice. During this 6 minute treatment period the tumor is only exposed to the electric field for total of 200 5s yet this stimulates pyknosis, apoptosis, DNA fragmentation and reduces blood flow to the tumor. This results in a mean tumor size regression of 90% within two weeks and complete remission within 1 month. We have developed a new suction electrode design for use on much thicker human skin and have demonstrated the efficacy of this new design on the mouse model. We also developed a microprocessor-controlled pulse delivery system for easy use in the clinical trials of the PulseCure. Here we propose to optimize the pulse parameters using the most effective suction electrode configuration to minimize treatment time and make several improvements to the PulseCure system necessary for human trials. These improvements include reducing electromagnetic interference, implementing safety features required by the ANSI/AAMI ES60601-1 and ES60601-2 standards, fabricating an adjustable arm to facilitate electrode placement on humans, developing a computer interface to record both patient and treatment data and automation of matching resistor selection and spark gap spacing. We will then conduct a feasibility study treating human skin scheduled for removal from patients during a plastic surgery procedure as well as Basal Cell Carcinomas on volunteers with Basal Cell Nevus Syndrome. Next we will conduct a Pilot Clinical Trial treating 30 basal cell carcinomas on 10 patients with Basal Cell Nevus Syndrome. If the PulseCure can reliably eliminate malignant skin lesions, it would offer a welcome, non-surgical and perhaps scar-free alternative to surgery that could improve the quality of life for tens of thousands of dermatology patients. PUBLIC HEALTH RELEVANCE: We are developing a new medical device, the PulseCure, for treating both benign and malignant skin lesions. The PulseCure uses ultrashort electrical pulses to trigger skin tumors to self- destruct. It offers a non-surgical therapy that may be a scar-free and could improve the quality of life for tens of thousands of dermatology patients.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 472.96K | Year: 2010

DESCRIPTION (provided by applicant): BioElectroMed is developing a new medical device called the EndoPulse that will deliver nanosecond pulsed electric fields (nsPEF) to treat pancreatic carcinomas. We have extensive evidence supporting the efficacy of nsPEF in eliminating all three types of skin cancer, basal and squamous cell carcinoma and melanoma. The mechanism by which nsPEF causes tumor regression involves increasing the permeability of intracellular membranes and triggering apoptosis. This electric field-induced membrane permeability increase is not cell specific so the same pulse parameters that are effective at eliminating skin tumors should also be effective at treating pancreatic tumors. The main advantage of this nsPEF application over other tumor treatments is that it minimizes damage to healthy tissue surrounding the tumor. Only cells located within the electrode array are stimulated by nsPEF application to undergo apoptosis. The main challenge is the accurate placement of the electrodes around the tumor and this will be accomplished using endoscopic ultrasound (EUS). The EndoPulse electrodes will be inserted down the accessory channel of the endoscope and guided to the tumor using ultrasound imaging. During Phase I of this project we have three specific aims: 1) Fabricate a nanosecond pulsed electric field (nsPEF) electrode compatible with endoscopic ultrasound and capable of applying nsPEF to pancreatic tumors; 2) Determine the optimal pulse parameters to use with the EndoPulse electrode to trigger apoptosis in pancreatic tumors using a murine subcutaneous xenograft model; 3) Demonstrate safety and feasibility of EUS-guided nsPEF ablation of normal pancreatic tissue in a pig. Phase II will then launch clinical trials at Stanford Medical Center under the direction of Dr. Ann Chen. If the EndoPulse can reliably eliminate pancreatic carcinomas, it would offer a much needed breakthrough in the treatment of this deadly disease. PUBLIC HEALTH RELEVANCE: We are developing a new medical device, the EndoPulse, for treating pancreatic carcinoma for which there are currently no effective therapies. The EndoPulse exposes the tumor to ultrashort electrical pulses which permeabilize intracellular membranes and trigger apoptosis or programmed cell death. This causes pancreatic carcinomas to self-destruct. The EndoPulse is guided to the carcinoma via an accessory channel in an ultrasound imaging endoscope which will also be used to image the placement of the electrodes around the tumor. Endoscopically delivered electrical pulses to trigger tumor remission offers a much needed breakthrough in the treatment of pancreatic cancer.


Trademark
Pulse Inc, NANOBLATE Corporation and Bioelectromed Corporation | Date: 2012-08-21

Electrodes for medical use.


Trademark
Pulse Inc, NANOBLATE Corporation and Bioelectromed Corporation | Date: 2012-01-10

Medical devices, namely, a therapeutic device, namely, an electric pulsed field therapy apparatus for treating cancer.


Trademark
Pulse Inc, NANOBLATE Corporation and Bioelectromed Corporation | Date: 2012-04-03

Electrodes for applying pulsed electric fields to skin lesions.

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