@conference {232, title = {Networks of Injectable Microdevices Powered and Digitally Linked by Volume Conduction for Neuroprosthetics: a Proof-of-Concept}, booktitle = {2023 11th International IEEE/EMBS Conference on Neural Engineering (NER)}, year = {2023}, doi = {10.1109/NER52421.2023.10123743}, url = {https://ieeexplore.ieee.org/abstract/document/10123743}, author = {Laura Becerra-Fajardo and Jesus Minguillon and Albert Comerma and Antoni Ivorra} } @conference {211, title = {Injectable Temperature Sensors Based on Passive Rectification of Volume-Conducted Currents}, booktitle = {2021 IEEE Biomedical Circuits and Systems Conference (BioCAS)}, year = {2021}, publisher = {IEEE}, organization = {IEEE}, address = {Berlin, Germany}, doi = {10.1109/BioCAS49922.2021.9645006}, author = {Laura Becerra-Fajardo and Aracelys Garc{\'\i}a-Moreno and Alvarez-De-Eulate, Nerea and Antoni Ivorra} } @conference {210, title = {In Vitro Evaluation of a Protocol and an Architecture for Bidirectional Communications in Networks of Wireless Implants Powered by Volume Conduction}, booktitle = {5th International Conference on Neurorehabilitation (ICNR2020)}, volume = {28}, year = {2020}, pages = {103-108}, publisher = {Springer Nature}, organization = {Springer Nature}, edition = {Converging Clinical and Engineering Research on Neurorehabilitation IV, Biosystems \& Biorobotics}, doi = {10.1007/978-3-030-70316-5_17}, author = {Laura Becerra-Fajardo and Jesus Minguillon and Camila Rogrigues and Filipe O. Barroso and Pons, Jos{\'e} Luis and Antoni Ivorra} } @conference {173, title = {First Steps Towards an Implantable Electromyography (EMG) Sensor Powered and Controlled by Galvanic Coupling}, booktitle = {World Congress on Medical Physics and Biomedical Engineering 2018. IFMBE Proceedings}, volume = {68/3}, year = {2018}, month = {2019}, pages = {19-22}, publisher = {Springer}, organization = {Springer}, address = {Prague, Czech Republic}, abstract = {

In the past it has been proposed to use implanted electromyography (EMG) sensors for myoelectric control. In contrast to surface systems, these implanted sensors provide signals with low cross-talk. To achieve this, miniature implantable devices that acquire and transmit real-time EMG signals are necessary. We have recently in vivo demonstrated electronic implants for electrical stimulation which can be safely powered and independently addressed by means of galvanic coupling. Since these implants lack bulky components as coils and batteries, we anticipate it will be possible to accomplish very thin implants to be massively deployed in tissues. We have also shown that these devices can have bidirectional communication. The aim of this work is to demonstrate a circuit architecture for embedding EMG sensing capabilities in our galvanically powered implants. The circuit was simulated using intramuscular EMG signals obtained from an analytical infinite volume conductor model that used a similar implant configuration. The simulations showed that the proposed analog front-end is compatible with the galvanic powering scheme and does not affect the implant{\textquoteright}s ability to perform electrical stimulation. The system has a bandwidth of 958 Hz, an amplification gain of 45 dB, and an output-referred noise of 160 {\textmu}Vrms. The proposed embedded EMG sensing capabilities will boost the use of these galvanically powered implants for diagnosis, and closed-loop control.

}, doi = {10.1007/978-981-10-9023-3_4}, author = {Laura Becerra-Fajardo and Antoni Ivorra} } @conference {181, title = {Monitoring the Effect of Contact Pressure on Bioimpedance Measurements}, booktitle = {018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)}, year = {2018}, month = {2019}, pages = {4949-4952}, doi = {10.1109/EMBC.2018.8513173}, author = {A. Ruiz-Vargas and Antoni Ivorra and J. W. Arkwright} } @conference {172, title = {Powering Implants by Galvanic Coupling: A Validated Analytical Model Predicts Powers Above 1 mW in Injectable Implants}, booktitle = {World Congress on Medical Physics and Biomedical Engineering 2018. IFMBE Proceedings}, volume = {68/3}, year = {2018}, month = {2019}, pages = {23-26}, publisher = {Springer}, organization = {Springer}, address = {Prague, Czech Republic}, abstract = {

While galvanic coupling for intrabody communications has been proposed lately by different research groups, its use for powering active implantable medical devices remains almost non-existent. Here it is presented a simple analytical model able to estimate the attainable power by galvanic coupling based on the delivery of high frequency (\>1 MHz) electric fields applied as short bursts. The results obtained with the analytical model, which is in vitro validated in the present study, indicate that time-averaged powers above 1 mW can be readily obtained in very thin (diameter \< 1 mm) and short (length \< 20 mm) elongated implants when fields which comply with safety standards (SAR \< 10 W/kg) are present in the tissues where the implants are located. Remarkably, the model indicates that, for a given SAR, the attainable power is independent of the tissue conductivity and of the duration and repetition frequency of the bursts. This study reveals that galvanic coupling is a safe option to power very thin active implants, avoiding bulky components such as coils and batteries.

}, doi = {10.1007/978-981-10-9023-3_5}, author = {Marc Tudela-Pi and Laura Becerra-Fajardo and Antoni Ivorra} } @conference {175, title = {Two-Port Networks to Model Galvanic Coupling for Intrabody Communications and Power Transfer to Implants}, booktitle = {2018 IEEE Biomedical Circuits and Systems Conference (BioCAS)}, year = {2018}, month = {10/2018}, pages = {407-410}, isbn = {978-1-5386-3603-9}, doi = {10.1109/BIOCAS.2018.8584691}, author = {Laura Becerra-Fajardo and Marc Tudela-Pi and Antoni Ivorra} } @conference {156, title = {Injectable Stimulators Based on Rectification of High Frequency Current Bursts: Power Efficiency of 2~mm Thick Prototypes}, booktitle = {Converging Clinical and Engineering Research on Neurorehabilitation II: Proceedings of the 3rd International Conference on NeuroRehabilitation (ICNR2016), October 18-21, 2016, Segovia, Spain}, year = {2017}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, address = {Cham}, abstract = {

To overcome the miniaturization bottleneck imposed by existing power generation/transfer technologies for implantable stimulators, we have proposed a heterodox electrical stimulation method based on local rectification of high frequency (>=1\ MHz) current bursts delivered through superficial electrodes. We have reported 2\ mm thick addressable injectable stimulators, made of off-the-shelf components, that operate according to this principle. Since a significant amount of high frequency power is wasted by Joule heating, the method exhibits poor energy efficiency. In here we have performed a numerical case study in which the presence of the above implant prototypes is simulated in an anatomically realistic leg model. The results from this study indicate that, despite low power transfer efficiency (~0.05\ \%), the power consumed by the external high frequency current generator is low enough (\<4\ W) to grant the use of small portable batteries.

}, isbn = {978-3-319-46669-9}, doi = {10.1007/978-3-319-46669-9_110}, url = {http://dx.doi.org/10.1007/978-3-319-46669-9_110}, author = {Laura Becerra-Fajardo and Garcia-Arnau, Roser and Antoni Ivorra}, editor = {Ib{\'a}{\~n}ez, Jaime and Gonz{\'a}lez-Vargas, Jos{\'e} and Azor{\'\i}n, Jos{\'e} Mar{\'\i}a and Akay, Metin and Pons, Jos{\'e} Luis} } @conference {147, title = {3D Assessment of Irreversible Electroporation Treatments in Vegetal Models}, booktitle = {1st World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food \& Environmental Technologies}, series = {IFMBE Proceedings}, volume = {53}, year = {2016}, pages = {294-297}, publisher = {Springer Singapore}, organization = {Springer Singapore}, keywords = {In-vivo assessment, Irreversible electroporation, Potato, Three-dimensional, Vegetal model}, isbn = {978-981-287-816-8}, url = {http://dx.doi.org/10.1007/978-981-287-817-5_65}, author = {Q. Castellv{\'\i} and J. Ban{\'u}s and Antoni Ivorra}, editor = {Jarm, Tomaz and Kramar, Peter} } @conference {146, title = {Incorporation of the Blood Vessel Wall into Electroporation Simulations}, booktitle = {1st World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food \& Environmental Technologies}, series = {IFMBE Proceedings}, volume = {53}, year = {2016}, pages = {223-227}, publisher = {Springer Singapore}, organization = {Springer Singapore}, keywords = {Blood vessel, Blood vessel wall, Electric field, Electroporation, Simulation}, isbn = {978-981-287-816-8}, url = {http://dx.doi.org/10.1007/978-981-287-817-5_50}, author = {Louis Silve and Radwan Qasrawi and Antoni Ivorra}, editor = {Jarm, Tomaz and Kramar, Peter} } @conference {140, title = {Bidirectional communications in wireless microstimulators based on electronic rectification of epidermically applied currents}, booktitle = {Neural Engineering (NER), 2015 7th International IEEE/EMBS Conference on}, year = {2015}, month = {April}, doi = {10.1109/NER.2015.7146680}, author = {Laura Becerra-Fajardo and Antoni Ivorra} } @conference {132, title = {Charge Counter for Performing Active Charge-Balance in Miniaturized Electrical Stimulators}, booktitle = {6th European Conference of the International Federation for Medical and Biological Engineering SE - 64}, series = {IFMBE Proceedings}, volume = {45}, year = {2015}, month = {2015///}, pages = {256 - 259}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, keywords = {active charge-balance, dc-blocking capacitor, FES, miniaturization, rectifier}, isbn = {978-3-319-11127-8}, url = {http://dx.doi.org/10.1007/978-3-319-11128-5_64}, author = {Laura Becerra-Fajardo and Antoni Ivorra}, editor = {Lackovi{\'c}, Igor and Vasic, Darko} } @conference {139, title = {Impact of Liver Vasculature on Electric Field Distribution during Electroporation Treatments: An Anatomically Realistic Numerical Study}, booktitle = {6th European Conference of the International Federation for Medical and Biological Engineering}, series = {IFMBE Proceedings}, volume = {45}, year = {2015}, pages = {573-576}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, keywords = {blood vessels, conductivity, Electroporation, numerical modeling}, isbn = {978-3-319-11127-8}, url = {http://dx.doi.org/10.1007/978-3-319-11128-5_143}, author = {Radwan Qasrawi and Antoni Ivorra}, editor = {Lackovi{\'c}, Igor and Vasic, Darko} } @conference {133, title = {Selective Electroporation of Liver Tumor Nodules by Means of Hypersaline Infusion: A Feasibility Study}, booktitle = {6th European Conference of the International Federation for Medical and Biological Engineering}, series = {IFMBE Proceedings}, volume = {45}, year = {2015}, pages = {821-824}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, abstract = {

Spread tumors in liver are not suitable to be treated with local treatments, such as conventional surgery or radiofrequency ablation, thus entailing a poor prognosis. Electroporation-based therapies imply the delivery of pulsed high electric fields and currently are performed in a local fashion using needle or plate electrodes. Here, however, it is proposed a novel electroporation paradigm in which field delivery is not local. All the tumor nodules will be selectively treated using large plate electrodes at both sides of the liver. By infusing an hypersaline solution of high electrical conductivity through the portal vein, the electrical conductivity of healthy tissues and tumor nodules will be made significantly different so that the electric field will be focused on the undesirable tissues. Numerical simulations were used to evaluate the feasibility of the proposed technique. In addition, an in vivo procedure was carried out to assess whether it is possible and practical to significantly modify the conductivity of the liver tissue by hypersaline infusion. Both the numerical simulations and the in vivo procedure provided encouraging results.

}, keywords = {Disseminated nodules, Electroporation, Hypersaline, Liver, Spread tumors}, isbn = {978-3-319-11127-8}, doi = {10.1007/978-3-319-11128-5_204}, url = {http://dx.doi.org/10.1007/978-3-319-11128-5_204}, author = {Q. Castellv{\'\i} and Patricia S{\'a}nchez-Vel{\'a}zquez and Berjano, Enrique and Burd{\'\i}o, Fernando and Antoni Ivorra} } @conference {190, title = {Flexible Thread-like Electrical Stimulation Implants Based on Rectification of Epidermically Applied Currents which Perform Charge Balance}, booktitle = {2nd International Conference on NeuroRehabilitation (ICNR2014), Aalborg, 24-26 June, 2014}, year = {2014}, pages = {447-455}, publisher = {Springer}, organization = {Springer}, address = {Aalborg, Denmark}, isbn = {978-3-319-08072-7}, doi = {10.1007/978-3-319-08072-7_67}, author = {Antoni Ivorra and Laura Becerra-Fajardo} } @conference {131, title = {Towards addressable wireless microstimulators based on electronic rectification of epidermically applied currents}, booktitle = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society}, year = {2014}, month = {2014///}, pages = {3973 - 3976}, publisher = {IEEE}, organization = {IEEE}, address = {Chicago}, abstract = {

Electrical stimulation has been explored to restore the capabilities of the nervous system in paralysis patients. This area of research and of clinical practice, known as Functional Electrical Stimulation, would greatly benefit from further miniaturization of implantable stimulators. To that end, we recently proposed and demonstrated an innovative electrical stimulation method in which implanted microstimulators operate as rectifiers of bursts of innocuous high frequency current supplied by skin electrodes, thus generating low frequency currents capable of stimulating excitable tissues. A diode could suffice in some applications but, in order to broaden the method{\textquoteright}s clinical applicability, we envision rectifiers with advanced capabilities such as current control and addressability. We plan flexible thread-like implants (diameters \< 300 urn) containing ASICs. As an intermediate stage, we are developing macroscopic implants (diameters \~{} 2 mm) made of off-the-shelf components. Here we present a circuit which responds to commands modulated within the high frequency bursts and which is able to deliver charge-balanced currents. We show that a number of these circuits can perform independent stimulation of segments of an anesthetized earthworm following commands from a computer.

}, keywords = {Batteries, Capacitors, Electrical Stimulation, Electrodes, Implants, Microcontrollers, Rectifiers}, author = {Laura Becerra-Fajardo and Antoni Ivorra} } @conference {Gonzalez-Sosa2013, title = {{Fast flow-through non-thermal pasteurization using constant radiofrequency electric fields}}, booktitle = {Tenth International Bioelectrics Symposium (BIOELECTRICS 2013)}, year = {2013}, address = {Karlsruhe, Germany}, abstract = {

Pulsed Electric Field technologies have captured the attention of researchers on food pasteurization because of their non-thermal inactivation mechanism, which results in fresh-like products. Nevertheless, high voltage pulsing required by these technologies implies complex and costly generators. Here, as an alternative, it is proposed a method, partially inherited from research on cell electroporation for gene transfection, in which the liquid to be treated flows at high speed through a miniature chamber where the electric field is permanently applied. In particular, it is proposed that the constantly applied electric field consists of an AC signal (\> 100 kHz) so that electrochemical by-products are minimized. The method, while being compatible with batch processing, will allow use of lower voltages and will avoid the pulsation requirement.\ 

}, author = {J. Gonz{\'a}lez-Sosa and A. Ruiz-Vargas and G. Arias and Q. Castellv{\'\i} and Antoni Ivorra} } @conference {Castellvi2013, title = {{In vivo study using Tumor Treatment Fields (TTFs) and prolonged mild hyperthermia as adjuvant methods for cancer treatment}}, booktitle = {Tenth International Bioelectrics Symposium (BIOELECTRICS 2013)}, year = {2013}, address = {Karlsruhe, Germany}, abstract = {

Delivery of the so called Tumor Treatment Fields (TTFs) was proposed a few years ago as a cancer therapy and has been object of study in a recent phase III trial in which their efficacy against glioblastomas was assessed with modest results [1]. TTFs are alternating electric fields at a frequency in the order of 100 kHz and a magnitude below 300 V/m which are applied continuously for weeks. According to their proposers, TTFs inhibit tumor growth by interfering with the cell division process through electrical forces without causing significant heating in tissues. However, we estimate that TTFs are capable of producing temperature increases of about some tens of kelvin which cannot be neglected, particularly because TTFs are applied for long periods of time. Therefore, we hypothesized that the promising results reported in initial in vitro and in vivo studies on the use of TTFs could be mediated by heat rather than by electrical forces. Heat induction (i.e. hyperthermia) has been extensively used as an adjuvant in cancer treatment. Typically, cancer hyperthermia involves generating moderate temperature increases during about one hour after radiotherapy or chemotherapy sessions. Nevertheless, to the best of our knowledge, there are no in vivo studies on the use of mild hyperthermia for long periods of time, despite there are in vitro studies showing that cell survival to hyperthermia depends both on the temperature and the exposition time. In order to test our hypothesis and also to independently validate the efficacy of TTFs, we have carried out a study in which nude mice subcutaneously implanted with human exocrine pancreatic adenocarcinomas were physically treated for 7 days; either with heat from a resistor or with TTFs delivered by electrodes. The animals were paired: one was treated and the other was sham treated. Four treatment groups were created: hyperthermia (H) (n=5+5), hyperthermia + gemcitabine chemotherapy (H\&Ch) (n=6+6), TTFs (TTF) (n=5+5) and TTFs + gemcitabine therapy (TTF\&Ch) (n=7+7). Our hypothesis has not been validated: no statistically significant effects were observed in the H and H\&Ch groups. On the other hand, although the TTF group did also not produce any significant effect, the animals treated with the TTFs + chemotherapy combination show a tumor growth rate about 200\% smaller (p=0.018) than the animals treated only with chemotherapy.

}, author = {Q. Castellv{\'\i} and Mireia M. Ginest{\`a} and G. Capella and Antoni Ivorra} } @conference {Ivorra2013, title = {Wireless Microstimulators Based on Electronic Rectification of Epidermically Applied Currents: Safety and Portability Analysis}, booktitle = {18th IFESS Annual Conference}, year = {2013}, pages = {213{\textendash}216}, address = {Donostia-San Sebasti{\'a}n, Spain}, abstract = {

Miniaturization of implantable medical electronic devices is currently compromised by the available means for electrically powering them. Most common energy supply techniques for implants {\textendash} batteries and inductive couplers {\textendash} comprise bulky parts which, in most cases, are significantly larger than the circuitry they feed. For overcoming such miniaturization bottleneck in the case of implants for electrical stimulation, we recently proposed and demonstrated a method in which the implants operate as rectifiers of bursts of high frequency (HF) current supplied by remote electrodes. In this way, low frequency currents capable of performing stimulation of excitable tissues are generated locally around the implants whereas the auxiliary high frequency currents only cause innocuous heating. This approach has the potential to reduce the diameter of the implants to one-tenth the diameter of current microstimulators and, more importantly, to allow that most of the implants{\textquoteright} volume consists of flexible materials. Implants based on the proposed method may look like short pieces of flexible thread. With currently available microelectronic techniques, diameters down to 200 $μ$m are easily conceivable. The numerical study presented here, in which a hypothetical but plausible clinical scenario for paralysis is analyzed, shows that the auxiliary high frequency (1 MHz) currents will be indeed safe according to safety standards and that portable systems based on portable batteries will be feasible.

}, author = {Antoni Ivorra and Laura Becerra-Fajardo} } @conference {Ivorra2012, title = {{Injectable Rectifiers as Microdevices for Remote Electrical Stimulation: an Alternative to Inductive Coupling}}, booktitle = {World Congress 2012 on Medical Physics and Biomedical Engineering}, year = {2012}, pages = {1581{\textendash}1584}, address = {Beijing, China}, abstract = {

Miniaturization of implantable medical electronic devices is currently compromised by the available means for electrically powering them. Most common energy supply techniques for implants {\textendash} batteries and inductive couplers {\textendash} comprise bulky parts which, in most cases, are significantly larger than the circuitry they feed. For overcoming such miniaturization bottleneck in the case of implants for electrical stimulation, we recently proposed and demonstrated a method based on making the implants operate as rectifiers of bursts of high frequency current supplied by remote electrodes. In this way, low frequency current is generated locally around the implant and this low frequency current performs stimulation of excitable tissues whereas the high frequency current only causes innocuous heating. The present paper reports further progress in this technology. We first describe construction and functional test of an injectable stimulator consisting of a single miniature diode (300 m {\texttimes} 300 m {\texttimes} 600 m) and two thin electrodes which is implanted trough a 19G needle into an anesthetized earthworm. We then propose a circuit architecture for implementing smart implants based on this technology. Both accomplishments are steps towards the implementation of injectable addressable microsystems for neuroprosthetics. These systems based on the proposed technology will look like short pieces of flexible thread rather than rigid capsules, as it was the case of previous miniature electrical stimulation implants. With currently available microelectronic techniques, very thin stimulation implants (diameter \< 200 m) are easily conceivable. This technology may be foundational to a broad range of new developments in the field of implantable medical devices with applications ranging from wound healing to nerve stimulation for pain relief. In addition, other non-medical devices could also emerge such as implantable identification devices.

}, keywords = {Electrical Stimulation, Implantable Devices, Microsystems, Neuroprosthetics, Rectifiers}, author = {Antoni Ivorra and Sacrist{\'a}n, J. and Baldi, A.} } @conference {Becerra-Fajardo2012, title = {{Proof of Concept of a Stimulator Based on AC Current Rectification for Neuroprosthetics}}, booktitle = {XXX Congreso Anual de la Sociedad Espa{\~n}ola de Ingenir{\'\i}a Biom{\'e}dica}, year = {2012}, address = {San Sebasti{\'a}n, Spain}, abstract = {

For several years, researchers have developed techniques to replace and enhance the capabilities of our neural system by means of implantable electrical stimulation technologies. Even though important work has been done in this field, further progress must be accomplished in terms of miniaturization in order to ensure comfort, simpler surgical implantation procedures, and the capability of using multiple wireless smart stimulators for achieving more muscle recruitment. In the past, with the objective of accomplishing an unprecedented level of miniaturization, we have proposed the development of implantable stimulators that would act as rectifiers of AC current supplied by external electrodes. Here it is described the development and evaluation of an addressable stimulator based on discrete component technology as a proof-of-concept of the proposed method. This macroscopic version of the stimulator is capable of generating magnitude controlled bipolar pulses according to commands modulated in the AC current. Multiple evaluations were done to test the device, including DC current testing, in-vitro and in-vivo testing, concluding that the developed system is an effective proof-of-concept of the method proposed, being able to perform controlled electrical stimulation. Electrical current testing showed that anodal and cathodal currents were generated, and in-vivo testing showed the effective electrical stimulation of an anesthetized earthworm. It is concluded that the idea of developing smart rectifiers as implantable stimulators is feasible. This represents a first step towards the design of an implantable device with a miniaturization level without precedents.

}, author = {Laura Becerra-Fajardo and Antoni Ivorra} } @conference {Silve2011, title = {{Detection of permeabilisation obtained by micropulses and nanopulses by means of bioimpedance of biological tissues}}, booktitle = {5th European Conference on Antennas and Propagation (EUCAP)}, year = {2011}, pages = {3164{\textendash}3167. {\textcopyright} 2011 Institute of Electrical and Electronics Engineers, Inc.}, address = {Rome, Italy}, abstract = {

In this paper permeabilisation of potato tissue caused by either microsecond electric pulses or nanosecond electric pulses is compared. The intensity of permeabilisation is quantified by means of bio-impedance change. Thanks to this method, the impact of the repetition frequency was investigated. Data show that very low repetition frequencies can be much more efficient to permeabilise.

}, author = {Aude Silve and Antoni Ivorra and L.M. Mir} } @conference {Ivorra2010c, title = {{Introduction to tissue Irreversible Electroporation and effects of electroporation on tissue passive electrical properties}}, booktitle = {Bioelectrochemistry Gordon Research Conference}, year = {2010}, address = {Biddeford, Maine, USA}, author = {Antoni Ivorra} } @conference {Ivorra2010b, title = {{Irreversible Electroporation for Tissue Ablation}}, booktitle = {5th Course ("Medical Applications of Electromagnetic Fields: Research and Therapy") of the School of Bioelectromagnetism Alessadro Chiabreara}, year = {2010}, author = {Antoni Ivorra} }