Picoliter-volume inkjet printing into planar microdevice reservoirs for low-waste, high-capacity drug loading.

Oral delivery of therapeutics is the preferred route for systemic drug administration due to ease of access and improved patient compliance. However, many therapeutics suffer from low oral bioavailability due to low pH and enzymatic conditions, poor cellular permeability, and low residence time. Microfabrication techniques have been used to create planar, asymmetric microdevices for oral drug delivery to address these limitations. The geometry of these microdevices facilitates prolonged drug exposure with unidirectional release of drug toward gastrointestinal epithelium. While these devices have significantly enhanced drug permeability in vitro and in vivo, loading drug into the micron-scale reservoirs of the devices in a low-waste, high-capacity manner remains challenging. Here, we use picoliter-volume inkjet printing to load topotecan and insulin into planar microdevices efficiently. Following a simple surface functionalization step, drug solution can be spotted into the microdevice reservoir. We show that relatively high capacities of both topotecan and insulin can be loaded into microdevices in a rapid, automated process with little to no drug waste

Design of an innovative polymerase chain reaction device based on buoyancy driven flow

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Polymerase Chain Reaction (PCR) plays a central role in the field of molecular biology. The miniaturization of PCR systems is promising as it potentially minimizes costly reagent consumption and time required for analysis. In PCR microdevices a sample solution is usually handled by external pumps. An alternative solution relies on temperature-induced density difference in the presence of a body force to induce buoyancy driven flow. This alternative method is easy to be used and does not require expensive setup, but, to date, the thermo-fluid-dynamic field in the micro-channels still needs to be optimized. The present study focuses on the design of micro-channels, having innovative and optimized shapes to obtain proper fluid actuation and DNA sample amplification within buoyancy driven flow PCR devices. A parametric study is carried out by means of computational thermal fluid dynamic modeling: several channel geometry configurations were compared in terms of time required for analysis, temperature distribution and priming volume. The advantages and disadvantages of such configurations are discussed

Evaluation of cell culture in microfluidic chips for application in monoclonal antibody production

Microfluidic chips are useful devices for cell culture that allow cell growth under highly controlled conditions, as is required for production of therapeutic recombinant proteins. To understand the optimal conditions for growth of cells amenable of recombinant protein expression in these devices,we culturedHEK-293T cells under different microfluidic experimental conditions. The cells were cultured in polymethyl methacrylate (PMMA) and polydi-methylsiloxane (PDMS)microdevices, in the absence or presence of the cell adhesion agent poly-D-lysine. Different microchannel geometries and thicknesses, as well as the influence of the flow rate have also been tested, showing their great influence in cell adhesion and growth. Results show that the presence of poly-D-lysine improves the adhesion and viability of the cells in continuous or discontinuous flow. Moreover, the optimal adhesion of cells was observed in the corners of themicrochannels, as well as in wide channels possibly due to the decrease in the flow rate in these areas. These studies provide insight into the optimal architecture of microchannels for long-term culture of adherent cells in order to use microfluidics devices as bioreactors for monoclonal antibodies production.Fil: Peñaherrera Pazmiño, Ana Belén. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sierra Rodero, Marina. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vega, M.. Universidad Tecnológica Nacional; ArgentinaFil: Rosero, G.. Universidad Tecnológica Nacional; Argentina. Universidad de Buenos Aires; ArgentinaFil: Lerner, Betiana. Universidad Tecnológica Nacional; Argentina. Universidad de Buenos Aires; ArgentinaFil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pérez, M. S.. Universidad Tecnológica Nacional; Argentina. Universidad de Buenos Aires; Argentin

Characterization of fluid flow in a microchannel with a flow disturbing step

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The flow around a flow-disturbing step in a rectangular microchannel is studied by measuring the wall shear rate along the channel, using the electrodiffusion technique and by determining the velocity field using the -PIV method. A parametric study based on the Design of Experiments (DOE) and the Response Surface Methodology (RSM) was then performed, and the effect of key design parameters on the flow characteristics was numerically investigated using CFD simulations. The computational results are in excellent agreement with the corresponding experimental ones. The CFD simulations cover both the laminar and the turbulent flow regime. It was revealed that in both flow regimes the step height has a major influence on the recirculation length. However, the Reynolds number (Re) value affects the recirculation length only in the laminar region, while the step length seems to have no significant effect compared to the Re and the step height. Finally, new correlations are proposed predicting the length of the bottom recirculation zone with reasonable accuracy and can be used as rough guidelines for the design of microdevices

Separation of suspended particles by arrays of obstacles in microfluidic devices

The stochastic transport of suspended particles through a periodic pattern of obstacles in microfluidic devices is investigated by means of the Fokker-Planck equation. Asymmetric arrays of obstacles have been shown to induce the continuous separation of DNA molecules of different length. The analysis presented here of the asymptotic distribution of particles in a unit cell of these systems shows that separation is only possible in the presence of a driving force with a non-vanishing normal component at the surface of the solid obstacles. In addition, vector separation, in which different species move, in average, in different directions within the device, is driven by differences on the force acting on the various particles and not by differences in the diffusion coefficient. Monte-Carlo simulations performed for different particles and force fields agree with the numerical solutions of the Fokker-Planck equation in the periodic system

Flow dynamics control the effect of sphingosine-1-phosphate on endothelial permeability in a microfluidic vessel bifurcation model

Blood vessels are lined by endothelial cells that form a semipermeable barrier to restrict fluid flow across the vessel wall. The endothelial barrier is known to respond to various molecular mechanisms, but the effects of mechanical signals that arise due to blood flow remain poorly understood. Here, we report a microfluidic model that mimics the flow conditions and endothelial/extracellular matrix (ECM) architecture of a vessel bifurcation to enable systematic investigation of how flow dynamics that arise within bifurcating vessels guides the endothelial response to biochemical signals. Applying the strengths of our system, we further investigate the endothelial response to sphingosine-1-phosphate, a bioactive lipid that has demonstrated flow-dependent regulation of vascular permeability. We demonstrate that bifurcated fluid flow (BFF) that arises at the base of vessel bifurcations and laminar shear stress (LSS) that arises along downstream vessel walls induce a decrease in endothelial permeability. Furthermore, we identify that flow-dynamics and chaperone proteins regulate the endothelial response to S1P. Through pharmacological inhibition of S1P receptors 1 and 2, we report ligand-independent mechanical activation of S1P receptors 1 and 2, providing support for the role of G protein-coupled receptors as mechanosensors. These findings introduce BFF as an important regulator of vascular permeability, and establish flow dynamics as a determinant of the endothelial response to S1P.Pelotonia Fellowship ProgramBarry M. Goldwater Excellence in Education FoundationThe Ohio State University College of EngineeringA one-year embargo was granted for this item.Academic Major: Biomedical Engineerin

A Micromechanical Parylene Spiral-Tube Sensor and Its Applications of Unpowered Environmental Pressure/Temperature Sensing

A multi-function micromechanical pressure/temperature sensor incorporating a microfabricated parylene spiral tube is presented. Its visible responses in expression of in situ rotational tube deformation enable unpowered sensing directly from optical device observation without electrical or any powered signal transduction. Sensor characterizations show promising pressure (14.46°/kPa sensitivity, 0.11 kPa resolution) and temperature (6.28°/°C sensitivity, 0.24 °C resolution) responses. Depending on different application requests, this sensor can be individually utilized to measure pressure/temperature of systems having one property varying while the other stabilized, such as intraocular or other in vivo pressure sensing of certain apparatus inside human bodies or other biological targets. A straightforward sensor-pair configuration has also been implemented to retrieve the decoupled pressure and temperature readouts, hence ultimately realizes a convenient environmental pressure and temperature sensing in various systems