Fabrice O. Morin

Opportunities at the skin interface for continuous patient monitoring: a reverse iontophoresis model tested on lactate and glucose

Skin has the potential to provide an important noninvasive route for diagnostic monitoring of human subjects for a wide range of applications. Dimensions of surface features in skin suggest that nanodevices and microdevices could be utilized to monitor molecules and ions extracted from the skin. Methods of enhancing extraction from the skin for diagnostics are being developed including reverse iontophoresis, electroporation and sonophoresis. A model system for the simulation of in vivo extraction of molecules and ions by reverse iontophoresis is described here that displays similar behavior to skin both in terms of molecular flux levels and electrical impedance characteristics. The device has potential for use in the development of complete reverse iontophoresis/sensor systems, allowing sensor and extraction systems to be studied and optimized before being tested in the complex in vivo environment. The system has been tested using glucose and lactate and the results are reported and discussed.

Multifunctional bioactive glass scaffolds coated with layers of poly(d,l-lactide-co-glycolide) and poly(n-isopropylacrylamide-co-acrylic acid) microgels loaded with vancomycin

A new family of multifunctional scaffolds, incorporating selected biopolymer coatings on basic Bioglass® derived foams has been developed. The polymer coatings were investigated as carrier of vancomycin which is a suitable drug to impart antibiotic function to the scaffolds. It has been proved that coating with PLGA (poly(lactic-co-glycolic acid)) with dispersed vancomycin-loaded microgels provides a rapid delivery of drug to give antibacterial effects at the wound site and a further sustained release to aid mid to long-term healing. Furthermore, the microgels also improved the bioactivity of the scaffolds by acting as nucleation sites for the formation of HA crystals in simulated body fluid.

Specific Transport of Target Molecules by Motor Proteins in Microfluidic Channels

Direct transport powered by motor proteins can alleviate the challenges presented by miniaturization of microfluidic systems. There have been several recent attempts to build motor-protein-driven transport systems based on simple capturing or transport mechanisms. However, to achieve a multifunctional device for practical applications, a more complex sorting/transport system should be realized. Herein, the proof of concept of a sorting device employing selective capture of distinct target molecules and transport of the sorted molecules to different predefined directions is presented. By combining the bottom-up functionality of biological systems with the top-down handling capabilities of micro-electromechanical systems technology, highly selective molecular recognition and motor-protein-based transport is integrated in a microfluidic channel network.

Sorting and direct transportation of target molecules by bio-molecular selectivity and motor function

A bio-hybrid microsystem for sorting and carrying target molecules by bio-functional molecules is presented. Different target molecules, biotin-4-fluorescein and Rabbit anti-mouse IgG labeled with Alexa Fluor 568, were selectively attached on different beads (Streptavidin-coated and protein A-coated beads). Target molecules were separately transported by a motor protein system (kinesin on beads / microtubules on chip) without any liquid manipulation proving the feasibility of multiple target molecules on multiple beads sorter.

Fabrication and characterization of macroporous poly(ethylene glycol) hydrogels generated by several types of porogens

Polymer scaffolds play an important role in tissue engineering applications. Poly(ethylene glycol) based hydrogels have received a lot of attention in this field because of their high biocompatibility and ease of processing. However, in many cases they do not exhibit proper tissue invasion and nutrient transport because of their dense structure. In the present work, several approaches were developed and compared to each other to produce interconnected macroporous poly(ethylene glycol) hydrogels by including different types of porogens in the photocrosslinking reaction. The swelling capacity of the resulting hydrogels was analyzed and compared to non-porous hydrogel samples. Moreover, the obtained materials were characterized by means of mechanical properties and porosity using rheometry, scanning electron microscopy, and mercury intrusion porosimetry. Results showed that interconnected and uniform pores were obtained when a porogen template was used during hydrogel fabrication by photocrosslinking. On the other side, when the porogen particles were dispersed into the macromer solution before matrix photocrosslinking the interconnexion was negligible. The templates must be dissolved before the hydrogels cell-seeding in vitro, while the dispersed porogen can be used in situ in the in vitro seeding tests.

Carrying Target Molecules on Beads by Bio Molecular Motors

A motor protein system, kinesin/microtubule, transported target molecules specifically attached on bead surfaces. The target molecule, biotin-4-fluorescein, was specifically immobilized on streptavidin-coated beads, on which kinesin molecules were also attached. The target molecules were successfully transported along microtubules immobilized on a glass surface. The activity of kinesin was not disturbed by co-existing target molecules. The result has significant implication to sort out any target molecule selectively from a sample solution by a nano-scale transport system driven by the kinesin/microtubule system.

Controlling Cell Development by Microfluidic Techniques: A Step Towards Whole-Cell Biosensors with Defined Biological Features

Several microfluidic systems were designed to accommodate cell cultures and control some aspects of cell development. In particular, the development of neuronal networks was guided over microelectrode arrays, and electrical activity of the cells was recorded over more than four weeks. Further work is currently being carried out to control some topological features of P19 cell populations during their differentiation into either neuron-like cells or cardiac myocytes.

Comparative study of dexamethasone and vancomycin release behavior from stimuli-sensitive microgel aqueous dispersions

Stimuli-sensitive microgels of poly(N-isopropylacrylamide-co-acrylic acid) (designated as P(NIPAAm-co-AA)) were prepared through precipitation polymerization. Their capacity to load and release different drugs under different conditions, including physiological, in a controlled manner was analyzed. Two drugs were assayed and compared: dexamethasone and vancomycin. The prepared microgel particles show good thermosensitivity. In addition, the amount of cross-linker used in the preparation of the microgels does not greatly influence the drug-release capability of P(NIPAAm-co-AA)), but the amount of drug used to load the microgels did result in bigger amounts of drug released afterwards. These results imply potential application of prepared stimuli-sensitive microgel dispersions as drug-delivery systems and tissue engineering materials.

Combing and self-assembly phenomena in dry films of Taxol-stabilized microtubules.

Microtubules are filamentous proteins that act as a substrate for the translocation of motor proteins. As such, they may be envisioned as a scaffold for the self-assembly of functional materials and devices. Physisorption, self-assembly and combing are here investigated as a potential prelude to microtubule-templated self-assembly. Dense films of self-assembled microtubules were successfully produced, as well as patterns of both dendritic and non-dendritic bundles of microtubules. They are presented in the present paper and the mechanism of their formation is discussed.

Modeling the mechanisms driving ac electro-osmotic flow on planar microelectrodes

The authors introduce an electrical model of the electrode-electrolyte interface and use it to discuss the mechanisms responsible for the generation of ac electro-osmotic flows at the surface of planar electrodes. They propose that such flows are generated by two distinct mechanisms: nonuniform diffusion of ionic species from the bulk to the electrode surface and inhomogeneous electrochemical transfer across the electrode surface. They then proceed to explain experimental observations in two situations where one mechanism dominates over the other, in each case validating the inclusion of specific components in their model.