Detection of superparamagnetic nanoparticles for immunoassays

International audienceWe develop a completely integrated Lab-on-Chip (LoC) for easy, rapid and cost-effective immunoassays. The pathogen sensing system is composed of a microfluidic channel surrounded by planar microcoils which are responsible for the emission and the detection of magnetic fields. The system allows the detection and quantification of superparamagnetic beads used for immunoassays in a “sandwich” antigen-antibody configuration. We successfully tested this device with different concentrations of nanoparticles and determine the limit of detection of the prototype. These results are promising and are a step toward the creation of a portable pathogen sensing device

A platform for stop-flow gradient generation to investigate chemotaxis

The ability of artificial microswimmers to respond to external stimuli and the mechanistical details of their origins belong to the most disputed challenges in interdisciplinary science. Therein, the creation of chemical gradients is technically challenging, because they quickly level out due to diffusion. Inspired by pivotal stopped flow experiments in chemical kinetics, we show that microfluidics gradient generation combined with a pressure feedback loop for precisely controlling the stop of the flows, can enable us to study mechanistical details of chemotaxis of artificial Janus micromotors, based on a catalytic reaction. We find that these copper Janus particles display a chemotactic motion along the concentration gradient in both, positive and negative direction and we demonstrate the mechanical reaction of the particles to unbalanced drag forces, explaining this behaviour

A Generative Programming Approach to Developing Pervasive Computing Systems

International audienceDeveloping pervasive computing applications is a difficult task because it requires to deal with a wide range of issues: heterogeneous devices, entity distribution, entity coordination, low-level hardware knowledge... Besides requiring various areas of expertise, programming such applications involves writing a lot of administrative code to glue technologies together and to interface with both hardware and software components. This paper proposes a generative programming approach to providing programming, execution and simulation support dedicated to the pervasive computing domain. This approach relies on a domain-specific language, named DiaSpec, dedicated to the description of pervasive computing systems. Our generative approach factors out features of distributed systems technologies, making DiaSpec-specified software systems portable. The DiaSpec compiler is implemented and has been used to generate dedicated programming frameworks for a variety of pervasive computing applications, including detailed ones to manage the building of an engineering school

Contributions à un microsystème électromagnétique et microfluidique pour la détection immunologique utilisant des nanoparticules magnétiques

L’augmentation continue de la circulation des populations et des biens ces dernières décennies accentue les risques de pandémie due à un mauvais confinement des antigènes dangereux à leur région d’apparition. Il est donc crucial de développer une technique rapide de détection de pathogène pour prévenir ces risques. Un projet multidisciplinaire a donc était mis en place entre Sorbonne Université à Paris et RWTH University à Jülich pour le développement d’un dispositif laboratoire-sur-puce intégré pour effectuer des tests immunologiques rapides, faciles et abordables. Ce dispositif de détection de pathogène est composé d’un canal microfluidique entouré de microbobines planaires en circuit imprimé responsables de l’émission et de la détection de champs magnétiques. Ainsi des nanoparticules magnétiques peuvent être détectées et quantifiées puis être corrélées à la présence du pathogène, en tant que marqueurs du test immunologique. Habituellement, l’étape de détection de la présence du pathogène dans un échantillon se fait grâce à un signal fluorescent ou électrochimique qui sont des techniques longues et avec une sensibilité limitée. En conséquence, les tests immunologiques magnétiques semblent être une alternative intéressante. L’utilisation de canaux microfluidiques permet de n’utiliser qu’une très petite quantité d’échantillon pour effectuer un test. Pendant ce doctorat, l’objectif principal a été d’améliorer le prototype du dispositif et la fonctionnalisation de surface du canal microfluidique avec des anticorps.The ever-increasing exchange of people and goods these last decades creates pandemic risks that should be prevented by containing the hazardous antigens in the region of the outbreak. Therefore, the rapid detection of a biological entity is critical to tackle this issue and others like environment contamination and bioterrorism.Consequently, a multidisciplinary project between Sorbonne Université in Paris and RWTH University in Aachen has been conducted to create a completely integrated lab-on-a-chip (LOC) for easy, rapid and cost-effective immunoassays.The pathogen sensing system is composed of a microfluidic channel surrounded by planar PCB microcoils, which are responsible for the emission and the detection of magnetic fields. This system allows the detection of magnetic nanoparticles (MNP) used for immunoassays in a “sandwich” antigen-antibody configuration. Using microfluidics allows us to test very small volume samples quickly. We successfully tested this device with different concentrations of nanoparticles, different microfluidic channel layouts, different types of nanoparticles and different materials for the microfluidic channel. Using the frequency mixing magnetic detection technique, a LOD of 15 ng/µL for 20 nm core sized MNP has been achieved with a sample volume of 14 µL corresponding to a drop of blood. Antibody coating was also achieved on a Poly(methyl methacrylate) (PMMA) surface which is a more suitable material than the classically used polydimethylsiloxane (PDMS) for our application. In this thesis, emphasis is put on the improvement of the device prototype and the surface functionalization of the microfluidic channel with antibodies

Contributions to an electromagnetic and microfluidic microsystem for immunological detection using magnetic nanoparticles

The ever-increasing exchange of people and goods these last decades creates pandemic risks that should be prevented by containing the hazardous antigens in the region of the outbreak. Therefore, the rapid detection of a biological entity is critical to tackle this issue and others like environment contamination and bioterrorism.Consequently, a multidisciplinary project between Sorbonne Université in Paris and RWTH University in Aachen has been conducted to create a completely integrated lab-on-a-chip (LOC) for easy, rapid and cost-effective immunoassays.The pathogen sensing system is composed of a microfluidic channel surrounded by planar PCB microcoils, which are responsible for the emission and the detection of magnetic fields. This system allows the detection of magnetic nanoparticles (MNP) used for immunoassays in a “sandwich” antigen-antibody configuration. Using microfluidics allows us to test very small volume samples quickly. We successfully tested this device with different concentrations of nanoparticles, different microfluidic channel layouts, different types of nanoparticles and different materials for the microfluidic channel. Using the frequency mixing magnetic detection technique, a LOD of 15 ng/µL for 20 nm core sized MNP has been achieved with a sample volume of 14 µL corresponding to a drop of blood. Antibody coating was also achieved on a Poly(methyl methacrylate) (PMMA) surface which is a more suitable material than the classically used polydimethylsiloxane (PDMS) for our application. In this thesis, emphasis is put on the improvement of the device prototype and the surface functionalization of the microfluidic channel with antibodies.L’augmentation continue de la circulation des populations et des biens ces dernières décennies accentue les risques de pandémie due à un mauvais confinement des antigènes dangereux à leur région d’apparition. Il est donc crucial de développer une technique rapide de détection de pathogène pour prévenir ces risques. Un projet multidisciplinaire a donc était mis en place entre Sorbonne Université à Paris et RWTH University à Jülich pour le développement d’un dispositif laboratoire-sur-puce intégré pour effectuer des tests immunologiques rapides, faciles et abordables. Ce dispositif de détection de pathogène est composé d’un canal microfluidique entouré de microbobines planaires en circuit imprimé responsables de l’émission et de la détection de champs magnétiques. Ainsi des nanoparticules magnétiques peuvent être détectées et quantifiées puis être corrélées à la présence du pathogène, en tant que marqueurs du test immunologique. Habituellement, l’étape de détection de la présence du pathogène dans un échantillon se fait grâce à un signal fluorescent ou électrochimique qui sont des techniques longues et avec une sensibilité limitée. En conséquence, les tests immunologiques magnétiques semblent être une alternative intéressante. L’utilisation de canaux microfluidiques permet de n’utiliser qu’une très petite quantité d’échantillon pour effectuer un test. Pendant ce doctorat, l’objectif principal a été d’améliorer le prototype du dispositif et la fonctionnalisation de surface du canal microfluidique avec des anticorps

A Platform for Stop-Flow Gradient Generation to Investigate Chemotaxis

The ability of artificial microswimmers to respond to external stimuli and the mechanistical details of their origins belong to the most disputed challenges in interdisciplinary science. Therein, the creation of chemical gradients is technically challenging, because they quickly level out due to diffusion. Inspired by pivotal stopped flow experiments in chemical kinetics, we show that microfluidics gradient generation combined with a pressure feedback loop for precisely controlling the stop of the flows, can enable us to study mechanistical details of chemotaxis of artificial Janus micromotors, based on a catalytic reaction. We find that these copper Janus particles display a chemotactic motion along the concentration gradient in both, positive and negative direction and we demonstrate the mechanical reaction of the particles to unbalanced drag forces, explaining this behaviour

A platform for stop flow gradient generation to investigate chemotaxis

The ability of artificial microswimmers to respond to external stimuli and the mechanistical details of their origins belong to the most disputed challenges in interdisciplinary science. Therein, the creation of chemical gradients is technically challenging, because they quickly level out due to diffusion. Inspired by pivotal stopped flow experiments in chemical kinetics, we show that microfluidics gradient generation combined with a pressure feedback loop for precisely controlling the stop of the flows, can enable us to study mechanistical details of chemotaxis of artificial Janus micromotors, based on a catalytic reaction. We find that these copper Janus particles display a chemotactic motion along the concentration gradient in both, positive and negative direction and we demonstrate the mechanical reaction of the particles to small forces deviations, explaining this behaviour

Entwicklung einer Plattform zur Generierung von Stop-Flow- Gradienten zur Untersuchung von Chemotaxis

Die Fähigkeit künstlicher Mikroschwimmer, auf äußere Reize zu reagieren und deren mechanistische Ursprünge, gehören zu den umstrittensten Fragen der interdisziplinären Wissenschaft. Die Erzeugung chemischer Gradienten ist dabei eine technische Herausforderung, da sie aufgrund von Diffusion schnell abflachen. Inspiriert von ‘Stop-flow’ Experimenten aus der chemischen Kinetik zeigen wir, dass die Erzeugung eines mikrofluidischen Gradienten durch Kombination mit einer Druckrückkopplungsschleife zur präzisen Kontrolle des Stoppens erfolgen kann. Das ermöglicht es uns, die mechanistischen Details der Chemotaxis von künstlichen katalytischen Janus-Mikromotoren zu untersuchen. Wir stellen fest, dass diese Kupfer-Janus-Partikel eine chemotaktische Bewegung entlang des Konzentrationsgradienten sowohl in positiver als auch in negativer Richtung zeigen, und wir demonstrieren die mechanische Reaktion der Partikel auf unausgewogene Widerstandskräfte, die dieses Verhalten erklären

Magnetic Detection Structure for LOC Immunoassays, Multiphysics Simulations and Experimental Results

The aim of this work is to develop a completely integrated Lab-On-Chip (LOC) for easy, rapid and cost-effective immunoassays. The pathogen sensing system is composed of a microfluidic channel surrounded by planar microcoils which are responsible for the emission and the detection of magnetic fields. The system allows the detection and quantification of superparamagnetic beads used for immunoassays in a “sandwich” antigen-antibody configuration. Multiphysics simulations have been achieved and preliminary experimental results have allowed to validate the structure

Magnetic Detection Structure for Lab-on-Chip Applications Based on the Frequency Mixing Technique

A magnetic frequency mixing technique with a set of miniaturized planar coils was investigated for use with a completely integrated Lab-on-Chip (LoC) pathogen sensing system. The system allows the detection and quantification of superparamagnetic beads. Additionally, in terms of magnetic nanoparticle characterization ability, the system can be used for immunoassays using the beads as markers. Analytical calculations and simulations for both excitation and pick-up coils are presented; the goal was to investigate the miniaturization of simple and cost-effective planar spiral coils. Following these calculations, a Printed Circuit Board (PCB) prototype was designed, manufactured, and tested for limit of detection, linear response, and validation of theoretical concepts. Using the magnetic frequency mixing technique, a limit of detection of 15 µg/mL of 20 nm core-sized nanoparticles was achieved without any shielding