The development of high quality seals for silicon patch-clamp chips.

International audiencePlanar patch-clamp is a two-dimensional variation of traditional patch-clamp. By contrast to classical glass micropipette, the seal quality of silicon patch-clamp chips (i.e. seal resistance and seal success rate) have remained poor due to the planar geometry and the nature of the substrate and thus partially obliterate the advantages related to planar patch-clamp. The characterization of physical parameters involved in seal formation is thus of major interest. In this paper, we demonstrate that the physical characterization of surfaces by a set of techniques (Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), surface energy (polar and dispersive contributions), drop angles, impedance spectroscopy, combined with a statistical design of experiments (DOE)) allowed us discriminating chips that provide relevant performances for planar patch-clamp analysis. Analyses of seal quality demonstrate that dispersive interactions and micropore size are the most crucial physical parameters of chip surfaces, by contrast to surface roughness and dielectric membrane thickness. This multi-scale study combined with electrophysiological validation of chips on a diverse set of cell-types expressing various ion channels (IRK1, hERG and hNa(v)1.5 channels) unveiled a suitable patch-clamp chip candidate. This original approach may inspire novel strategies for selecting appropriate surface parameters dedicated to biochips

Study and conception of a 2D transparent detector to monitor the beam in real time for modulated radiotherapy treatments

La Radiothérapie Conformationnelle avec Modulation d'Intensité (RCMI), aussi dénommée IMRT, est une technique avancée de radiothérapie de haute précision qui repose sur l'utilisation d'un collimateur multi-lames, placé en sortie de l'accélérateur, dont les lames vont se déplacer pendant la séance d'irradiation afin de produire un faisceau d'intensité modulée, adaptée à la forme des structures anatomiques du patient. Un tel dispositif permet d'obtenir une répartition de dose homogène dans le volume cible et d'épargner au mieux les tissus sains environnants1, ouvrant la voie à l'escalade de dose et donc à l'amélioration des résultats thérapeutiques. Néanmoins, la mise en œuvre d'une telle technique nécessite la réalisation d'un contrôle du système de délivrance de la dose de manière à s'assurer que la fluence délivrée par l'appareil de traitement est bien conforme à la fluence attendue.Intensity Modulated Radiotherapy (IMRT) is a high-precision radiotherapy technique based on the use of a multi-leaf collimator, placed at the output of the accelerator. The modulation is adapted to the patient's anatomical structures and obtained by leaves movement during the beam administration. To ensure that the delivered fluence is consistent with the expected one, a control is necessary. In clinical routine, this control isn't achieved on the patient, but on a phantom, before the beginning of the treatment New emerging solutions make possible an online control, done during the treatment of the patient. They can be divided into three classes: those which use data acquired by the accelerator, those which exploit the portal imager and those which use a dedicated detector placed at the exit of the head of the accelerator, upstream of the patient. The thesis work presented here relate to the development of a detector of this third class, Tradera (Transparent Detector for Radiotherapy). The choice was made to use a segmented plane ionization chamber.The first phase of the project was to design the detector thanks to studies made by Monte Carlo simulations. For this it was necessary to model the photon beam. The choice of a point source of photons, quick to set up, has been retained. The characteristics of the particles at the detector input obtained with our model were compared with those obtained with a more complex model: a phase space obtained from the database of the IAEA. Once the model validated, Geant4 code was used to size the various elements of our detector. A innovative geometry has been proposed. It consists in introducing material in the sensitive volume of the detector to limit the lateral travel of the electrons from the interaction of photons, and thus improve the spatial resolution of the detector. In practice, a checkerboard with plastic pads is introduced in the sensitive volume. The benefit of this solution has been shown by simulations.The second phase was to assess a prototype in a clinical beam with radiation equipment and test the performance of various associated acquisition electronics. For a long time, reading was made at the output of a single channel at a time. First, a picoammeter was used to measure the average output current. Then the ionization current has been studied at the time scale of a pulse of the beam, allowing the development of a charge preamplifier dedicated to our application. This charge preamplifier permit to know, for a single beam pulse, the electrical charge measured by one channel of the prototype with a uncertainty of 5%, and thus makes it possible to study the evolution of the charge pulse as a function of irradiation time. Once the choice of this readout electronics was validated, the charge preamplifier was realized in small series : the acquisition in multi-channels on an area of ​​3 cm square was possible. The first beam images could then be obtained for static and dynamic beam

Etude et conception d’un détecteur 2D transparent permettant le suivi en temps réel de l'administration des traitements rcmi

Intensity Modulated Radiotherapy (IMRT) is a high-precision radiotherapy technique based on the use of a multi-leaf collimator, placed at the output of the accelerator. The modulation is adapted to the patient's anatomical structures and obtained by leaves movement during the beam administration. To ensure that the delivered fluence is consistent with the expected one, a control is necessary. In clinical routine, this control isn't achieved on the patient, but on a phantom, before the beginning of the treatment New emerging solutions make possible an online control, done during the treatment of the patient. They can be divided into three classes: those which use data acquired by the accelerator, those which exploit the portal imager and those which use a dedicated detector placed at the exit of the head of the accelerator, upstream of the patient. The thesis work presented here relate to the development of a detector of this third class, Tradera (Transparent Detector for Radiotherapy). The choice was made to use a segmented plane ionization chamber.The first phase of the project was to design the detector thanks to studies made by Monte Carlo simulations. For this it was necessary to model the photon beam. The choice of a point source of photons, quick to set up, has been retained. The characteristics of the particles at the detector input obtained with our model were compared with those obtained with a more complex model: a phase space obtained from the database of the IAEA. Once the model validated, Geant4 code was used to size the various elements of our detector. A innovative geometry has been proposed. It consists in introducing material in the sensitive volume of the detector to limit the lateral travel of the electrons from the interaction of photons, and thus improve the spatial resolution of the detector. In practice, a checkerboard with plastic pads is introduced in the sensitive volume. The benefit of this solution has been shown by simulations.The second phase was to assess a prototype in a clinical beam with radiation equipment and test the performance of various associated acquisition electronics. For a long time, reading was made at the output of a single channel at a time. First, a picoammeter was used to measure the average output current. Then the ionization current has been studied at the time scale of a pulse of the beam, allowing the development of a charge preamplifier dedicated to our application. This charge preamplifier permit to know, for a single beam pulse, the electrical charge measured by one channel of the prototype with a uncertainty of 5%, and thus makes it possible to study the evolution of the charge pulse as a function of irradiation time. Once the choice of this readout electronics was validated, the charge preamplifier was realized in small series : the acquisition in multi-channels on an area of ​​3 cm square was possible. The first beam images could then be obtained for static and dynamic beam.La Radiothérapie Conformationnelle avec Modulation d'Intensité (RCMI), aussi dénommée IMRT, est une technique avancée de radiothérapie de haute précision qui repose sur l'utilisation d'un collimateur multi-lames, placé en sortie de l'accélérateur, dont les lames vont se déplacer pendant la séance d'irradiation afin de produire un faisceau d'intensité modulée, adaptée à la forme des structures anatomiques du patient. Un tel dispositif permet d'obtenir une répartition de dose homogène dans le volume cible et d'épargner au mieux les tissus sains environnants1, ouvrant la voie à l'escalade de dose et donc à l'amélioration des résultats thérapeutiques. Néanmoins, la mise en œuvre d'une telle technique nécessite la réalisation d'un contrôle du système de délivrance de la dose de manière à s'assurer que la fluence délivrée par l'appareil de traitement est bien conforme à la fluence attendue

Etude et conception d’un détecteur 2D transparent permettant le suivi en temps réel de l'administration des traitements rcmi

Intensity Modulated Radiotherapy (IMRT) is a high-precision radiotherapy technique based on the use of a multi-leaf collimator, placed at the output of the accelerator. The modulation is adapted to the patient's anatomical structures and obtained by leaves movement during the beam administration. To ensure that the delivered fluence is consistent with the expected one, a control is necessary. In clinical routine, this control isn't achieved on the patient, but on a phantom, before the beginning of the treatment New emerging solutions make possible an online control, done during the treatment of the patient. They can be divided into three classes: those which use data acquired by the accelerator, those which exploit the portal imager and those which use a dedicated detector placed at the exit of the head of the accelerator, upstream of the patient. The thesis work presented here relate to the development of a detector of this third class, Tradera (Transparent Detector for Radiotherapy). The choice was made to use a segmented plane ionization chamber.The first phase of the project was to design the detector thanks to studies made by Monte Carlo simulations. For this it was necessary to model the photon beam. The choice of a point source of photons, quick to set up, has been retained. The characteristics of the particles at the detector input obtained with our model were compared with those obtained with a more complex model: a phase space obtained from the database of the IAEA. Once the model validated, Geant4 code was used to size the various elements of our detector. A innovative geometry has been proposed. It consists in introducing material in the sensitive volume of the detector to limit the lateral travel of the electrons from the interaction of photons, and thus improve the spatial resolution of the detector. In practice, a checkerboard with plastic pads is introduced in the sensitive volume. The benefit of this solution has been shown by simulations.The second phase was to assess a prototype in a clinical beam with radiation equipment and test the performance of various associated acquisition electronics. For a long time, reading was made at the output of a single channel at a time. First, a picoammeter was used to measure the average output current. Then the ionization current has been studied at the time scale of a pulse of the beam, allowing the development of a charge preamplifier dedicated to our application. This charge preamplifier permit to know, for a single beam pulse, the electrical charge measured by one channel of the prototype with a uncertainty of 5%, and thus makes it possible to study the evolution of the charge pulse as a function of irradiation time. Once the choice of this readout electronics was validated, the charge preamplifier was realized in small series : the acquisition in multi-channels on an area of ​​3 cm square was possible. The first beam images could then be obtained for static and dynamic beam.La Radiothérapie Conformationnelle avec Modulation d'Intensité (RCMI), aussi dénommée IMRT, est une technique avancée de radiothérapie de haute précision qui repose sur l'utilisation d'un collimateur multi-lames, placé en sortie de l'accélérateur, dont les lames vont se déplacer pendant la séance d'irradiation afin de produire un faisceau d'intensité modulée, adaptée à la forme des structures anatomiques du patient. Un tel dispositif permet d'obtenir une répartition de dose homogène dans le volume cible et d'épargner au mieux les tissus sains environnants1, ouvrant la voie à l'escalade de dose et donc à l'amélioration des résultats thérapeutiques. Néanmoins, la mise en œuvre d'une telle technique nécessite la réalisation d'un contrôle du système de délivrance de la dose de manière à s'assurer que la fluence délivrée par l'appareil de traitement est bien conforme à la fluence attendue