TRANSDUCERS 2009 - 2009 International Solid-State Sensors, Actuators and Microsystems Conference, 2009
This paper presents a novel type of remotely actuated, chemical or bio-sensor based on a MEMS res... more This paper presents a novel type of remotely actuated, chemical or bio-sensor based on a MEMS resonator actuated by a multilayered (TbCo/FeCo) x25 nanostructured magnetostrictive film in liquid environment. The active film is polarized in order to induce spin reorientation transition, yielding giant sensitivity to a dynamical actuation magnetic field. Moreover, the resonator is placed at the air/liquid interface in order to increase its quality factor. Sensing results in different viscosity solutions are presented. The possibility to use such a device for the fast determination of cellular density is also demonstrated.
Le but de ce travail a ete de montrer que SDF-1 ne se lie pas seulement a son recepteur actuellem... more Le but de ce travail a ete de montrer que SDF-1 ne se lie pas seulement a son recepteur actuellement identifie, CXRA, mais egalement a d'autres ligands membranaires. Nos experiences nous ont permis de montrer, dans un premier temps, l'existence de deux classes de sites de liaison de SDF-1/CXCL12 a la surface de macrophages et de lymphocytes en culture primaire, et de cellule HeLa en lignee. Nous avons ensuite observe que SDF-1/CXCL12 se lie, non seulement a son recepteur couple a une proteine G, CXCRA, mais egalement, a un proteoglycanne : le syndecane-4. Cette liaison, GAG-dependante, faciliterait la fixation de SDF-1 a CXCRA exprime a la surface des macrophages. Nous avons egalement montre que le syndecane-4 est co-associe, en l'absence de SDF-1, a CXCRA. De plus, la liaison de SDF-1 au syndecane-4 induit une transduction de signal ainsi qu'une homo- ou hetero-oligomerisation du syndecane-4 et de CXCR4.
As more and more cell and gene therapies are being developed and with the increasing number of re... more As more and more cell and gene therapies are being developed and with the increasing number of regulatory approvals being obtained, there is an emerging and pressing need for industrial translation. Process efficiency, associated cost drivers and regulatory requirements are issues that need to be addressed before industrialisation of cell and gene therapies can be established. Automation has the potential to address these issues and pave the way towards commercialisation and mass production as it has been the case for 'classical' production industries. This review provides an insight into how automation can help address the manufacturing issues arising from the development of large-scale manufacturing processes for modern cell and gene therapy. The existing automated technologies with applicability in cell and gene therapy manufacturing are summarized and evaluated here.
Most kidney cells are continuously exposed to fluid shear stress (FSS) from either blood flow or ... more Most kidney cells are continuously exposed to fluid shear stress (FSS) from either blood flow or urine flow. Recent studies suggest that changes in FSS could contribute to the function and injury of these kidney cells. However, it is unclear whether FSS influences kidney development when urinary flow starts in the embryonic kidneys. In this study, we evaluated the influence of FSS on cultured ureteric bud (UB) cells by using a pumpless microfluidic device, which offers the convenience of conducting parallel cell culture experiments while also eliminating the need for cumbersome electronic driven equipment and intricate techniques. We first validated the function of the device by both mathematical model and experimental measurements. UB cells dissected from E15.5 mouse embryonic kidneys were cultured in the pumpless microfluidic device and subjected to FSS in the range of 0.4-0.6 dyn mm for 48 h (dynamic). Control UB cells were similarly cultured in the device and maintained under a ...
Biochemical and biophysical research communications, Jul 2, 2018
Kidney organoid is an emerging topic of importance for research in kidney development and regener... more Kidney organoid is an emerging topic of importance for research in kidney development and regeneration. Conventional culture systems for kidney organoids reported thus far use culture media containing serum, which may compromise our understanding and the potential clinical applicability of the organoid system. In our present study, we tested two serum-free culture conditions and compared their suitability for the maintenance and growth of kidney organoids in culture. One of the serum-free culture conditions was the combination of keratinocytes serum free medium (KSFM) with knockout serum replacement (KSR) (KSFM + KSR), and the other was the combination of knockout DMEM/F12 (KD/F12) and KSR (KD/F12 + KSR). With cell aggregates derived from E12.5 mouse embryonic kidneys, we found that KD/F12 + KSR was superior to KSFM + KSR in promoting the growth of the aggregate with expansion of Six2 nephron progenitor cells (NPC) and elaborated ureteric branching morphogenesis. With KD/F12 + KSR, ...
h i g h l i g h t s CdS nanoparticles with narrow size distribution are synthesized in picoliter ... more h i g h l i g h t s CdS nanoparticles with narrow size distribution are synthesized in picoliter droplets. A stabilizing agent, 3-Mercaptopropionic acid (MPA), is used to control CdS nanoparticle size. CdS nanoparticle size increases as the precursor concentration increases. The molar ratio of S 2À :Cd 2+ affects CdS nanoparticle size.
Current existing assay systems for evaluating antimicrobial activity suffer from several limitati... more Current existing assay systems for evaluating antimicrobial activity suffer from several limitations including excess reagent consumption and inaccurate concentration gradient preparation. Recently, microfluidic systems have been developed to provide miniaturized platforms for antimicrobial susceptibility assays. However, some of current microfluidic based assays require continuous flows of reagents or elaborate preparation steps during concentration preparation. In this study, we introduce a novel microfluidic chip based phenotype assay that automatically generates a logarithmic concentration gradient and allows observing the growth of pathogenic bacteria under different concentrations of antibiotics in nanoliter batch culture reactors. We chose pathogen bacterium Pseudomonas aeruginosa as a model strain and evaluated the inhibitory effects of gentamicin and ciprofloxacin. We determined the EC50 values and confirmed the validity of the present system by comparing the EC50 values ob...
Methods in molecular biology (Clifton, N.J.), 2012
In this chapter, from the engineering point of view, we introduce the results from our group and ... more In this chapter, from the engineering point of view, we introduce the results from our group and related research on three typical configurations of engineered liver tissues; cell sheet-based tissues, sheet-like macroporous scaffold-based tissues, and tissues based on special scaffolds that comprise a flow channel network. The former two do not necessitate in vitro prevascularization and are thus promising in actual human clinical trials for liver diseases that can be recovered by relatively smaller tissue mass. The third approach can implant a much larger mass but is still not yet feasible. In all cases, oxygen supply is the key engineering factor. For the first configuration, direct oxygen supply using an oxygen-permeable polydimethylsiloxane membrane enables various liver cells to exhibit distinct behaviors, complete double layers of mature hepatocytes and fibroblasts, spontaneous thick tissue formation of hepatocarcinoma cells and fetal hepatocytes. Actual oxygen concentration a...
Implantation of sheet-like liver tissues is a promising method in hepatocyte-based therapies, bec... more Implantation of sheet-like liver tissues is a promising method in hepatocyte-based therapies, because angiogenesis is expected to occur upon implantation from the surrounding tissues. In this context, we introduce here a new methodology for the formation of a functional thick hepatic tissue usable for cell sheet technology. First, we report the formation of composite tissue elements in suspension culture. Composite elements were composed of human hepatoma Hep G2 cells and mouse NIH/3T3 fibroblasts which are important modulators for thick-tissue formation. To overcome the very low attachment and organization capability between different cells in suspension, we synthesized a new cell-to-cell binding molecule based on the avidin-biotin binding system that we previously applied to attach hepatocytes on artificial substrata. This newly synthesized biotin-conjugated biocompatible anchoring molecule was inserted in the plasma membrane of both cell types. NIH/3T3 cells were further conjugat...
ABSTRACT Microfluidic technology is one of the latest platforms for detection of chemical and bio... more ABSTRACT Microfluidic technology is one of the latest platforms for detection of chemical and biological hazards. This technology may provide a higher sensitivity couple with the best specificity provided by targeting DNA molecules. This chapter introduces existing microfluidic systems and reviews some ongoing researches relevant to food safety. Microfluidic devices provide high throughput and large-scale analysis by multiplexing and parallelization of analyses on a single device.
ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
Recently, the number of potential drug targets has dramatically increased because of the recent c... more Recently, the number of potential drug targets has dramatically increased because of the recent completion of the human genome sequencing and the progress in genomics and proteomics. In parallel, the number of new drugs for those targets has also been increased due to the use of combinatorial synthesis and the increased access to natural molecules [1]. However, this has not increased consequently the number of approved new drugs delivered to patients [2]. Indeed the drug discovery process is still limited by numbers of challenges; among them the need to analyze in more rapid and accurate manner precious sample of drug candidates.
Hb25_Springer Handbook of Marine Biotechnology, 2015
During the past decade, rapid progress in physics, electronics, and material sciences has facilit... more During the past decade, rapid progress in physics, electronics, and material sciences has facilitated the development of miniaturized microfluidic systems, also known as Lab-on-a-Chip (LOC ), that represent the next generation of analytical laboratories, miniaturized to be held in one’s hand. Microfluidics has appeared as a concrete alternative than can address problems and overcome limitation in various biological and chemical domains, including stem cell research, drug discovery, and food sciences just to name a few, and has proven to be more than state-of-the-art techniques. Microfluidic techniques provide accurate and fast results with small amounts of reagents and can bring various analytical tools for in situ studies. In this chapter, we describe some of the systems developed to overcome the limitations of conventional marine biotechnology processes.
TRANSDUCERS 2009 - 2009 International Solid-State Sensors, Actuators and Microsystems Conference, 2009
This paper presents a novel type of remotely actuated, chemical or bio-sensor based on a MEMS res... more This paper presents a novel type of remotely actuated, chemical or bio-sensor based on a MEMS resonator actuated by a multilayered (TbCo/FeCo) x25 nanostructured magnetostrictive film in liquid environment. The active film is polarized in order to induce spin reorientation transition, yielding giant sensitivity to a dynamical actuation magnetic field. Moreover, the resonator is placed at the air/liquid interface in order to increase its quality factor. Sensing results in different viscosity solutions are presented. The possibility to use such a device for the fast determination of cellular density is also demonstrated.
Le but de ce travail a ete de montrer que SDF-1 ne se lie pas seulement a son recepteur actuellem... more Le but de ce travail a ete de montrer que SDF-1 ne se lie pas seulement a son recepteur actuellement identifie, CXRA, mais egalement a d'autres ligands membranaires. Nos experiences nous ont permis de montrer, dans un premier temps, l'existence de deux classes de sites de liaison de SDF-1/CXCL12 a la surface de macrophages et de lymphocytes en culture primaire, et de cellule HeLa en lignee. Nous avons ensuite observe que SDF-1/CXCL12 se lie, non seulement a son recepteur couple a une proteine G, CXCRA, mais egalement, a un proteoglycanne : le syndecane-4. Cette liaison, GAG-dependante, faciliterait la fixation de SDF-1 a CXCRA exprime a la surface des macrophages. Nous avons egalement montre que le syndecane-4 est co-associe, en l'absence de SDF-1, a CXCRA. De plus, la liaison de SDF-1 au syndecane-4 induit une transduction de signal ainsi qu'une homo- ou hetero-oligomerisation du syndecane-4 et de CXCR4.
As more and more cell and gene therapies are being developed and with the increasing number of re... more As more and more cell and gene therapies are being developed and with the increasing number of regulatory approvals being obtained, there is an emerging and pressing need for industrial translation. Process efficiency, associated cost drivers and regulatory requirements are issues that need to be addressed before industrialisation of cell and gene therapies can be established. Automation has the potential to address these issues and pave the way towards commercialisation and mass production as it has been the case for 'classical' production industries. This review provides an insight into how automation can help address the manufacturing issues arising from the development of large-scale manufacturing processes for modern cell and gene therapy. The existing automated technologies with applicability in cell and gene therapy manufacturing are summarized and evaluated here.
Most kidney cells are continuously exposed to fluid shear stress (FSS) from either blood flow or ... more Most kidney cells are continuously exposed to fluid shear stress (FSS) from either blood flow or urine flow. Recent studies suggest that changes in FSS could contribute to the function and injury of these kidney cells. However, it is unclear whether FSS influences kidney development when urinary flow starts in the embryonic kidneys. In this study, we evaluated the influence of FSS on cultured ureteric bud (UB) cells by using a pumpless microfluidic device, which offers the convenience of conducting parallel cell culture experiments while also eliminating the need for cumbersome electronic driven equipment and intricate techniques. We first validated the function of the device by both mathematical model and experimental measurements. UB cells dissected from E15.5 mouse embryonic kidneys were cultured in the pumpless microfluidic device and subjected to FSS in the range of 0.4-0.6 dyn mm for 48 h (dynamic). Control UB cells were similarly cultured in the device and maintained under a ...
Biochemical and biophysical research communications, Jul 2, 2018
Kidney organoid is an emerging topic of importance for research in kidney development and regener... more Kidney organoid is an emerging topic of importance for research in kidney development and regeneration. Conventional culture systems for kidney organoids reported thus far use culture media containing serum, which may compromise our understanding and the potential clinical applicability of the organoid system. In our present study, we tested two serum-free culture conditions and compared their suitability for the maintenance and growth of kidney organoids in culture. One of the serum-free culture conditions was the combination of keratinocytes serum free medium (KSFM) with knockout serum replacement (KSR) (KSFM + KSR), and the other was the combination of knockout DMEM/F12 (KD/F12) and KSR (KD/F12 + KSR). With cell aggregates derived from E12.5 mouse embryonic kidneys, we found that KD/F12 + KSR was superior to KSFM + KSR in promoting the growth of the aggregate with expansion of Six2 nephron progenitor cells (NPC) and elaborated ureteric branching morphogenesis. With KD/F12 + KSR, ...
h i g h l i g h t s CdS nanoparticles with narrow size distribution are synthesized in picoliter ... more h i g h l i g h t s CdS nanoparticles with narrow size distribution are synthesized in picoliter droplets. A stabilizing agent, 3-Mercaptopropionic acid (MPA), is used to control CdS nanoparticle size. CdS nanoparticle size increases as the precursor concentration increases. The molar ratio of S 2À :Cd 2+ affects CdS nanoparticle size.
Current existing assay systems for evaluating antimicrobial activity suffer from several limitati... more Current existing assay systems for evaluating antimicrobial activity suffer from several limitations including excess reagent consumption and inaccurate concentration gradient preparation. Recently, microfluidic systems have been developed to provide miniaturized platforms for antimicrobial susceptibility assays. However, some of current microfluidic based assays require continuous flows of reagents or elaborate preparation steps during concentration preparation. In this study, we introduce a novel microfluidic chip based phenotype assay that automatically generates a logarithmic concentration gradient and allows observing the growth of pathogenic bacteria under different concentrations of antibiotics in nanoliter batch culture reactors. We chose pathogen bacterium Pseudomonas aeruginosa as a model strain and evaluated the inhibitory effects of gentamicin and ciprofloxacin. We determined the EC50 values and confirmed the validity of the present system by comparing the EC50 values ob...
Methods in molecular biology (Clifton, N.J.), 2012
In this chapter, from the engineering point of view, we introduce the results from our group and ... more In this chapter, from the engineering point of view, we introduce the results from our group and related research on three typical configurations of engineered liver tissues; cell sheet-based tissues, sheet-like macroporous scaffold-based tissues, and tissues based on special scaffolds that comprise a flow channel network. The former two do not necessitate in vitro prevascularization and are thus promising in actual human clinical trials for liver diseases that can be recovered by relatively smaller tissue mass. The third approach can implant a much larger mass but is still not yet feasible. In all cases, oxygen supply is the key engineering factor. For the first configuration, direct oxygen supply using an oxygen-permeable polydimethylsiloxane membrane enables various liver cells to exhibit distinct behaviors, complete double layers of mature hepatocytes and fibroblasts, spontaneous thick tissue formation of hepatocarcinoma cells and fetal hepatocytes. Actual oxygen concentration a...
Implantation of sheet-like liver tissues is a promising method in hepatocyte-based therapies, bec... more Implantation of sheet-like liver tissues is a promising method in hepatocyte-based therapies, because angiogenesis is expected to occur upon implantation from the surrounding tissues. In this context, we introduce here a new methodology for the formation of a functional thick hepatic tissue usable for cell sheet technology. First, we report the formation of composite tissue elements in suspension culture. Composite elements were composed of human hepatoma Hep G2 cells and mouse NIH/3T3 fibroblasts which are important modulators for thick-tissue formation. To overcome the very low attachment and organization capability between different cells in suspension, we synthesized a new cell-to-cell binding molecule based on the avidin-biotin binding system that we previously applied to attach hepatocytes on artificial substrata. This newly synthesized biotin-conjugated biocompatible anchoring molecule was inserted in the plasma membrane of both cell types. NIH/3T3 cells were further conjugat...
ABSTRACT Microfluidic technology is one of the latest platforms for detection of chemical and bio... more ABSTRACT Microfluidic technology is one of the latest platforms for detection of chemical and biological hazards. This technology may provide a higher sensitivity couple with the best specificity provided by targeting DNA molecules. This chapter introduces existing microfluidic systems and reviews some ongoing researches relevant to food safety. Microfluidic devices provide high throughput and large-scale analysis by multiplexing and parallelization of analyses on a single device.
ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
Recently, the number of potential drug targets has dramatically increased because of the recent c... more Recently, the number of potential drug targets has dramatically increased because of the recent completion of the human genome sequencing and the progress in genomics and proteomics. In parallel, the number of new drugs for those targets has also been increased due to the use of combinatorial synthesis and the increased access to natural molecules [1]. However, this has not increased consequently the number of approved new drugs delivered to patients [2]. Indeed the drug discovery process is still limited by numbers of challenges; among them the need to analyze in more rapid and accurate manner precious sample of drug candidates.
Hb25_Springer Handbook of Marine Biotechnology, 2015
During the past decade, rapid progress in physics, electronics, and material sciences has facilit... more During the past decade, rapid progress in physics, electronics, and material sciences has facilitated the development of miniaturized microfluidic systems, also known as Lab-on-a-Chip (LOC ), that represent the next generation of analytical laboratories, miniaturized to be held in one’s hand. Microfluidics has appeared as a concrete alternative than can address problems and overcome limitation in various biological and chemical domains, including stem cell research, drug discovery, and food sciences just to name a few, and has proven to be more than state-of-the-art techniques. Microfluidic techniques provide accurate and fast results with small amounts of reagents and can bring various analytical tools for in situ studies. In this chapter, we describe some of the systems developed to overcome the limitations of conventional marine biotechnology processes.
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Papers by Morgan Hamon