Caterina Merla

UMR 8203 CNRS, Gustave Roussy, Univ. Paris- Sud, Université Paris-Saclay, and ENEA · Laboratory of Vectorology and Anticancer Therapy

Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the path...

Electropulsation has become a powerful technological platform for electromanipulation of cells and tissues for various medical and biotechnological applications, but the molecular changes that underlay the very first initiation step of this process have not been experimentally observed. Here, we endowed a wide-field Coherent anti-Stokes Raman Scatt...

Glioblastoma multiforme (GBM) is the most common brain cancer in adults. GBM starts from a small fraction of poorly differentiated and aggressive cancer stem cells (CSCs) responsible for aberrant proliferation and invasion. Due to extreme tumor heterogeneity, actual therapies provide poor positive outcomes, and cancers usually recur. Therefore, alt...

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting...

Background Despite the numerous literature results about biological effects of electromagnetic field exposure, the interaction mechanisms of these fields with organisms are still a matter of debate. Extremely low frequency magnetic fields can modulate redox homeostasis and we showed that 24 hours exposure to 50 Hz-1 mT has a pro-oxidant effect and...

One harmful long-term effect of ionizing radiation is cataract development. Recent studies have been focused on elucidating the mechanistic pathways involved in this pathogenesis. Since accumulating evidence has established a role of microRNAs in ocular diseases, including cataract, the goal of this work was to determine the microRNA signature of t...

We here characterize the response to the extremely low-frequency (ELF) magnetic field (MF, 50 Hz, 1 mT) of SH-SY5Y human neuroblastoma cells, cultured in a three-dimensional (3D) Alvetex® scaffold compared to conventional two-dimensional (2D) monolayers.We proved that the growing phenotype of proliferating SH-SY5Y cells is not affected by the cultu...

Purpose Cancer stem cells constitute an endless reserve for the maintenance and progression of tumors, and they could be the reason for conventional therapy failure. New therapeutic strategies are necessary to specifically target them. In this context, microsecond pulsed electric fields have been selected to expose D283Med cells, a human medullobla...

In the last years, microdosimetric numerical models of cells including intracellular compartments have been proposed, aiming to investigate the poration induced by the application of nanosecond pulsed electric fields (nsPEFs). A limitation of such models was the extremely approximate cell and organelle shapes, leading to an incorrect estimation of...

Photonic crystal fibers (PCFs) have gained popularity thanks to the use of their broad and efficient supercontinuum (SC) emission as Stokes source in ultrafast multiplex coherent anti‐Stokes Raman scattering microscopy. Here, the infrared portion of the SC emitted by a widely used PCF is studied in a basic CARS experiment with a single laser oscill...

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains significant and the long-term adverse effects in survivors are substantial. The fraction of cancer stem-like cells (CSCs) because of their self-renewal ability and multi-lineage differ...

The increasing interest towards biocompatible nanotechnologies in medicine, combined with electric fields stimulation, is leading to the development of electro-sensitive smart systems for drug delivery applications. Common examples of electro-sensitive materials include phospholipids that can be used to design nano-sized vesicles suitable for exter...

When investigating the biophysical effects induced by the interaction between electromagnetic fields and biological cells, it is crucial to estimate the electromagnetic field intensity at the microscopic scale (microdosimetry). This information allows to find a connection between the external applied field and the observed biological event required...

Background: Molecular mechanisms of interaction between cells and extremely low frequency magnetic fields (ELF-MFs) still represent a matter of scientific debate. In this paper, to identify the possible primary source of oxidative stress induced by ELF-MF in SH-SY5Y human neuroblastoma cells, we estimated the induced electric field and current den...

A power MOSFET-based push–pull configuration nanosecond-pulse generator has been designed, constructed, and characterized to permeabilize cells for biological and medical applications. The generator can deliver pulses with durations ranging from 80 ns up to 1 µ s and pulse amplitudes up to 1.4 kV. The unit has been tested for in vitro experiments o...

Coherent anti‐Stokes Raman scattering (CARS) is a versatile technique for vibrational imaging that can be realized by a simple setup using a single femtosecond laser oscillator. For such a layout, supercontinuum generation in a photonic crystal fiber (PCF) is commonly used to produce a broadband Stokes beam in the so‐called multiplex CARS spectrosc...

Exposure to extremely low frequency magnetic fields (ELF‐MFs) has been associated with an increased risk of neurodegenerative disorders. The underlying mechanisms, however, are still debated. Since epigenetics play a key role in the neurodegenerative process, we investigated whether exposure to ELF‐MF (50 Hz, 1 mT) might affect global DNA methylati...

Purpose: we characterized the response to the extremely low frequency magnetic field (ELF-MF) in an in vitro model of familial Amyotrophic Lateral Sclerosis (fALS), carrying two mutant variants of the superoxide dismutase 1 (SOD1) gene. Materials and methods: SH-SY5Y human neuroblastoma cells, stably over-expressing the wild type, the G93A or the H...

The exposure to extremely low-frequency magnetic fields (ELF-MFs) has been associated to increased risk of neurodegenerative diseases, although the underlying molecular mechanisms are still undefined. Since epigenetic modulation has been recently encountered among the key events leading to neuronal degeneration, we here aimed at assessing if the co...

The analytical and numerical design, implementation, and experimental validation of a new grounded closed coplanar waveguide for wide-band electromagnetic exposures of cells and their optical detection in real-time is reported. The realized device fulfills high-quality requirements for novel bioelectromagnetic experiments, involving elevated tempor...

The permeabilization of biological membranes by electric fields, known as electroporation, has been traditionally performed with square electric pulses. These signals distribute the energy applied to cells in a wide frequency band. This paper investigates the use of sine waves, which are narrow band signals, to provoke electropermeabilization and t...

Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non-coding RNAs expression, have been recently included among the key determinants contributing to Parkinson's Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigen...

This study reports a comprehensive analysis of the effect of 100 µs electric pulses on the biochemical composition of live cells using a label-free approach, confocal Raman microspectroscopy. We investigated different regions of interest around the nucleus of the cells and the dose-effect relationship related to different electric pulse parameters....

Purpose: The exposure of operators moving in the static field of magnetic resonance (MR) facilities was assessed through measurements of the magnetic flux density, which is experienced as variable in time because of the movement. Collected data were processed to allow the comparison with most recent and authoritative safety standards. Methods: M...

In this paper a simple prediction method for the bipolar pulse cancellation effect is proposed, based on the frequency analysis of the TMP spectra of a single cell and the computed relative global spectral content up to a defined frequency threshold. We present a spectral analysis of pulses applied in experiments, and we extract the induced TMP fro...

The emergence of nanosecond pulsed electric fields (nsPEFs) for intracellular manipulation experiments requires the use of specific miniaturized applicators. We propose the design of a versatile nsPEFs applicator, based on microwave propagating systems, suitable for in vitro exposure to undistorted 1–3 ns pulses in single and multi-cell experiments...

This paper presents a versatile low-cost procedure for complex permittivity measurements of liquids from 400 MHz to 5 GHz. Our procedure uses handheld instrumentation and custom software for data acquisition and postprocessing. The purpose is to replace the benchtop vector network analyzer (VNA) generally used in such applications with a portable a...

The scientific debate about possible effects due to exposures to electromagnetic fields is always getting attention, due to the widespread diffusion of the related sources of emission. Based mainly on epidemiological studies, potential health risk cannot still be ruled out, even if the mechanistic, animal, and in vitro toxicology literature fail to...

Over the past decades, the effects of ultrashort-pulsed electric fields have been used to investigate their action in many medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). Promising aspects of these pulses has led to several in vitro and in vivo experiments to clarify their action. Since the basic mechanisms o...

In the last decades, the advances in the micro and nano fabrication techniques have led to the development of microdevices that improved the possibility of analysis at cell level. These devices can be used in different applications (e.g., cell detection and identification, manipulation, cell treatments). The requisites, that are necessary to achiev...

In the last decades, the effects of ultrashort pulsed electric fields have been investigated demonstrating their capability to be involved in a great number of medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). In particular, experiments in literature demonstrate that internal structures can be involved when pul...

To explore the promising therapeutic applications of short nanosecond electric pulses, in vitro and in vivo experiments are highly required. In this paper, an exposure system based on monopole patch antenna is reported to perform in vivo experiments on newborn mice with both monopolar and bipolar nanosecond signals. Analytical design and numerical...

This study investigates effects of gradient magnetic fields (GMFs) emitted by magnetic resonance imaging (MRI) devices on hematopoietic stem cells. Field measurements were performed to assess exposure to GMFs of staff working at 1.5 T and 3 T MRI units. Then an exposure system reproducing measured signals was realized to expose in vitro CD34+ cells...

In this work, the inclusion of magnetic nanoparticles (MNPs) within phospholipid vesicles has been investigated as novel strategy for improving stability and reactivity of these nanoparticles and extending their potential use in the environmental field. Two phospholipids able to form liposomes characterized by different rigidity and stiffness, were...

This paper proposes the design of a new in vivo applicator of nsPEFs suitable for whole body exposure of several newborn mice. The system is based on a UWB patch antenna and exhibits a wide operating band (300-1100 MHz). To improve the system efficiency, a dielectric box, with permittivity similar to that of the mouse has been used as sample holder...

Three high-intensity static magnetic field (SMF) exposure devices have been designed and realized for application to in vitro experimental research on hairy root cultures, supposed to grow in extreme environments- as those of space aircrafts- for producing biopharmaceutical molecules. The devices allow the exposure at two different levels of induct...

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, with an etiopathogenesis involving both genetic and environmental factors. The occupational/residential exposure to the electromagnetic fields has been recently associated with an increased risk of neurodegenerative diseases; it has been thus propose...

The magnetic wireless power transfer (WPT) technology represents a promising application in contactless electric vehicle battery charging systems. In this framework, a bench prototype of resonant type, delivering a power of 560 W at 85 kHz, suitable for charging the batteries of a city car, was designed and realized. Identical transmitting and rece...

the aim of this paper is to propose a new method for better assessment of cytoplasm conductivity, which is critical to the development of electroporation protocols as well as insight into fundamental mechanisms underlying electroporation. Methods: for this goal, we propose to use nanosecond electrical pulses to bypass the complication of membrane p...

An in vitro exposure setup developed to expose suspended cells in Petri dishes on a large frequency band up to a few GHz was studied. This system was based on far field exposure with a horn antenna in an anechoic chamber. A specific incubator was designed with a water-cooling system for constant temperature inside the setup. Four exposed Petri dish...

To resolve the dilemma of cell clogging or solution parasitics encountered by Coulter counters and to evolve a general-purpose electrical detection technique, we used broadband microwave measurements to overcome electrode polarization, ac dielectrophoresis to precisely place cells between narrowly spaced electrodes, and relatively wide microfluidic...

A broadband coplanar stripline was used in conjunction with a microfluidic channel for microwave sensing of live and dead biological cells with single-cell sensitivity and reproducibility. To facilitate sensing, AC dielectrophoresis was used to trap the cells between the stripline electrodes without electrode polarization. The measured dispersion o...

Recently, the use of liposomes loaded with magnetic nanoparticles (magnetoliposomes, (MLs)) has been intensely growing as a new drug delivery system. With the use of alternating magnetic fields, it is possible to remotely control the delivery of a drug or any other macromolecule loaded inside the MLs. In this experiment, the release of a fluorescen...

Detection of identity, quantity and viability of cells at the point-of-need is critically needed for diagnostic, surveillance and monitoring purposes. In this work, we present a broadband electrical sensor combined with a microfluidic device to detect mammalian cells and bacteria. It is found that the device can detect down to single mammalian cell...

Using a novel broadband microchamber, electrical detection of live and dead single cells was demonstrated. Tests on Jurkat cells showed that live cells had lower resistance but higher capacitance than that of dead cells. The test results were compared with the limited literature on broadband electrical detection of single cells and the discrepancie...

1) UT BIORAD, ENEA, Roma, (2) IFAC-CNR, Sesto Fiorentino (Firenze), (3) INAIL, Monte Porzio Catone (Roma). Introduzione Gli ultimi anni hanno visto un uso crescente degli apparecchi di risonanza magnetica (RM) nella pratica medica; contemporaneamente è aumentata l'attenzione verso l'esposizione occupazionale dei lavoratori (medici, tecnici di radio...

A novel broadband microchamber for electrical detection of live and dead biological cells was designed, fabricated and tested. The microchamber was formed between a gold coplanar waveguide fabricated on a quartz slide and the microfluidic channels fabricated in a polydimethylsiloxane cover. The coplanar waveguide allowed broadband impedance matchin...

A novel broadband microchamber for electrical detection of live and dead biological cells was designed, fabricated and tested. The microchamber was formed between a gold coplanar waveguide fabricated on a quartz slide and the microfluidic channels fabricated in a polydimethylsiloxane cover. The coplanar waveguide allowed broadband impedance matchin...

Recently, the promising effects induced by pulsed electric fields with high intensity and short duration have been highlighted. At the nanosecond time scale, electric pulse targets become both the plasmatic membrane and the sub-cellular structures (possibility of intracellular manipulation). In this paper, a circuit cell model with nucleus is prese...

This paper provides a systematic review and classification of in vivo microwave exposure systems used from 1999 for bioelectromagnetic investigations. The main features of each system's typology are presented and discussed for different types of experiments. From our critical analysis, some key issues have been identified and addressed concerning t...

The understanding of possible nonthermal bio-effects has been an open question during the last five decades. In this paper, the authors present a critical literature review of the models of the interaction mechanisms, together with an overview of all the publications finding positive results for in vitro and in vivo studies. The systematic approach...

Recently, scientific interest in electric pulses, always more intense and shorter and able to induce biological effects on both plasma and nuclear membranes, has greatly increased. Hence, microdosimetric models that include internal organelles like the nucleus have assumed increasing importance. In this work, a circuit model of the cell including t...