The limitations of current cancer therapies highlight the urgent need for a more effective therap... more The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy. Cancer is predicted to affect almost 17 million people worldwide by 2020 1,2. To reduce the cancer burden, various research efforts have been made to improve both diagnostic and therapeutic strategies. The most common types of cancer therapy clinically rely on radiation, chemotherapy, and surgical resection. Despite advances in the respective technologies and novel therapeutic strategies under investigation, an optimal treatment with reduced risks and side effects has yet to be discovered. Therefore, a strong incentive exists to explore alternative forms of therapy. One approach that has recently been studied is the use of electromagnetic and radiofrequency fields as a complement to current care regimes 3,4. The roots of electromagnetic cancer treatment can be traced back to the 1920s when Lakhovsky developed the " Radio-Cellular-Oscillator " to apply radio frequencies to cancer cells 5. In the 1980–1990s, The National Council on Radiation Protection and Measurements recommended a reduction in the allowable exposure intensity limits for electromagnetic radiation, reducing the level of interest in this treatment modality 6. However, because of the persistent limitations of current cancer therapies, interest in alternative forms of treatment including electromagnetic stimulation, have reemerged. The different electromagnetic stimulation methods can be distinguished by their wave frequency, voltage intensity, and duration of application as well as the mechanism by which they affect biological tissues. For instance, low frequencies (< 1 kHz) are typically used to stimulate excitable tissues (nerve, muscle, heart), whereas frequencies higher than 10 MHz, which are often used for tumor ablation 7 , cause tissue heating. Electromagnetic stimulation has recently showed promising results in gene delivery strategies for various applications ranging from wound healing to cancer treatment 8. DNA, cytokines, or drugs can be introduced into cells by transferring nanosecond pulsed electric fields to permeabilize cell membranes as an extension of
This paper makes an analytical overview of a hybrid network for off-highway vehicles where ISOBUS... more This paper makes an analytical overview of a hybrid network for off-highway vehicles where ISOBUS and FlexRay protocols co-exist. A functional analysis has been conducted and a methodology for a quantitative evaluation of the overall system (in terms of performance and reliability) ...
Cardiac cell function is substantially influenced by the nature and intensity of the mechanical l... more Cardiac cell function is substantially influenced by the nature and intensity of the mechanical loads the cells experience. Cardiac fibroblasts (CFs) are primarily involved in myocardial tissue remodeling: at the onset of specific pathological conditions, CFs activate, proliferate, differentiate, and critically alter the amount of myocardial extra-cellular matrix with important consequences for myocardial functioning. While cyclic mechanical strain has been shown to increase matrix synthesis of CFs in vitro, the role of mechanical cues in CFs proliferation is unclear. We here developed a multi-chamber cell straining microdevice for cell cultures under uniform, uniaxial cyclic strain. After careful characterization of the strain field, we extracted human heart-derived CFs and performed cyclic strain experiments. We subjected cells to 2% or 8% cyclic strain for 24 h or 72 h, using immunofluorescence to investigate markers of cell morphology, cell proliferation (Ki67, EdU, phospho-Hist...
A method (100) is described to produce a microfluidic device (50, 60, 70) from a watertight struc... more A method (100) is described to produce a microfluidic device (50, 60, 70) from a watertight structure (32, 33). The method (100) comprises a step (10) of forming, inside such a watertight structure (32, 33), a first fluidic microchannel network (51, 62, 72), that can be filled with one or more fluids, organic and inorganic, to be stimulated or controlled, and a second network of mxcrochannels (52, 61, 73), that can be filled with an electrically conductive material that can act as impedance or conductor and interacts with such one or more fluids to be stimulated or controlled. Moreover, a microfluidic device (50, 60, 70) is described, made with the aforementioned method (100).
Microfluidic devices fabricated from cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS... more Microfluidic devices fabricated from cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS) were combined with VisiSens sensor foils to enable monitoring of oxygen tensions in the devices. The oxygen consumption of rat lung microvascular endothelial cells (EC) and rat hepatocytes (Hep) was numerically simulated and experimentally validated using the VisiSens set-up. The VisiSens system enabled determining oxygen levels in the microfluidic devices and allows suggesting suitable culture device material depending on the application and cell line of interest. Furthermore, a previously characterized hypoxia microfluidic chip was evaluated and VisiSens was found to exhibit superior sensing capabilities when compared to similar products.
Progress in biophysics and molecular biology, 2014
The relatively recent development of microfluidic systems with wide-ranging capabilities for gene... more The relatively recent development of microfluidic systems with wide-ranging capabilities for generating realistic 2D or 3D systems with single or multiple cell types has given rise to an extensive collection of platform technologies useful in muscle tissue engineering. These new systems are aimed at (i) gaining fundamental understanding of muscle function, (ii) creating functional muscle constructs in vitro, and (iii) utilizing these constructs a variety of applications. Use of microfluidics to control the various stimuli that promote differentiation of multipotent cells into cardiac or skeletal muscle is first discussed. Next, systems that incorporate muscle cells to produce either 2D sheets or 3D tissues of contractile muscle are described with an emphasis on the more recent 3D platforms. These systems are useful for fundamental studies of muscle biology and can also be incorporated into drug screening assays. Applications are discussed for muscle actuators in the context of micro...
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Associat... more ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Associat... more ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
The limitations of current cancer therapies highlight the urgent need for a more effective therap... more The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy. Cancer is predicted to affect almost 17 million people worldwide by 2020 1,2. To reduce the cancer burden, various research efforts have been made to improve both diagnostic and therapeutic strategies. The most common types of cancer therapy clinically rely on radiation, chemotherapy, and surgical resection. Despite advances in the respective technologies and novel therapeutic strategies under investigation, an optimal treatment with reduced risks and side effects has yet to be discovered. Therefore, a strong incentive exists to explore alternative forms of therapy. One approach that has recently been studied is the use of electromagnetic and radiofrequency fields as a complement to current care regimes 3,4. The roots of electromagnetic cancer treatment can be traced back to the 1920s when Lakhovsky developed the " Radio-Cellular-Oscillator " to apply radio frequencies to cancer cells 5. In the 1980–1990s, The National Council on Radiation Protection and Measurements recommended a reduction in the allowable exposure intensity limits for electromagnetic radiation, reducing the level of interest in this treatment modality 6. However, because of the persistent limitations of current cancer therapies, interest in alternative forms of treatment including electromagnetic stimulation, have reemerged. The different electromagnetic stimulation methods can be distinguished by their wave frequency, voltage intensity, and duration of application as well as the mechanism by which they affect biological tissues. For instance, low frequencies (< 1 kHz) are typically used to stimulate excitable tissues (nerve, muscle, heart), whereas frequencies higher than 10 MHz, which are often used for tumor ablation 7 , cause tissue heating. Electromagnetic stimulation has recently showed promising results in gene delivery strategies for various applications ranging from wound healing to cancer treatment 8. DNA, cytokines, or drugs can be introduced into cells by transferring nanosecond pulsed electric fields to permeabilize cell membranes as an extension of
This paper makes an analytical overview of a hybrid network for off-highway vehicles where ISOBUS... more This paper makes an analytical overview of a hybrid network for off-highway vehicles where ISOBUS and FlexRay protocols co-exist. A functional analysis has been conducted and a methodology for a quantitative evaluation of the overall system (in terms of performance and reliability) ...
Cardiac cell function is substantially influenced by the nature and intensity of the mechanical l... more Cardiac cell function is substantially influenced by the nature and intensity of the mechanical loads the cells experience. Cardiac fibroblasts (CFs) are primarily involved in myocardial tissue remodeling: at the onset of specific pathological conditions, CFs activate, proliferate, differentiate, and critically alter the amount of myocardial extra-cellular matrix with important consequences for myocardial functioning. While cyclic mechanical strain has been shown to increase matrix synthesis of CFs in vitro, the role of mechanical cues in CFs proliferation is unclear. We here developed a multi-chamber cell straining microdevice for cell cultures under uniform, uniaxial cyclic strain. After careful characterization of the strain field, we extracted human heart-derived CFs and performed cyclic strain experiments. We subjected cells to 2% or 8% cyclic strain for 24 h or 72 h, using immunofluorescence to investigate markers of cell morphology, cell proliferation (Ki67, EdU, phospho-Hist...
A method (100) is described to produce a microfluidic device (50, 60, 70) from a watertight struc... more A method (100) is described to produce a microfluidic device (50, 60, 70) from a watertight structure (32, 33). The method (100) comprises a step (10) of forming, inside such a watertight structure (32, 33), a first fluidic microchannel network (51, 62, 72), that can be filled with one or more fluids, organic and inorganic, to be stimulated or controlled, and a second network of mxcrochannels (52, 61, 73), that can be filled with an electrically conductive material that can act as impedance or conductor and interacts with such one or more fluids to be stimulated or controlled. Moreover, a microfluidic device (50, 60, 70) is described, made with the aforementioned method (100).
Microfluidic devices fabricated from cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS... more Microfluidic devices fabricated from cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS) were combined with VisiSens sensor foils to enable monitoring of oxygen tensions in the devices. The oxygen consumption of rat lung microvascular endothelial cells (EC) and rat hepatocytes (Hep) was numerically simulated and experimentally validated using the VisiSens set-up. The VisiSens system enabled determining oxygen levels in the microfluidic devices and allows suggesting suitable culture device material depending on the application and cell line of interest. Furthermore, a previously characterized hypoxia microfluidic chip was evaluated and VisiSens was found to exhibit superior sensing capabilities when compared to similar products.
Progress in biophysics and molecular biology, 2014
The relatively recent development of microfluidic systems with wide-ranging capabilities for gene... more The relatively recent development of microfluidic systems with wide-ranging capabilities for generating realistic 2D or 3D systems with single or multiple cell types has given rise to an extensive collection of platform technologies useful in muscle tissue engineering. These new systems are aimed at (i) gaining fundamental understanding of muscle function, (ii) creating functional muscle constructs in vitro, and (iii) utilizing these constructs a variety of applications. Use of microfluidics to control the various stimuli that promote differentiation of multipotent cells into cardiac or skeletal muscle is first discussed. Next, systems that incorporate muscle cells to produce either 2D sheets or 3D tissues of contractile muscle are described with an emphasis on the more recent 3D platforms. These systems are useful for fundamental studies of muscle biology and can also be incorporated into drug screening assays. Applications are discussed for muscle actuators in the context of micro...
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Associat... more ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Associat... more ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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