Millifluidic valves and pumps made of tape and plastic.

There is growing interest in producing micro- and milli-fluidic technologies made of thermoplastic with integrated fluidic control elements that are easy to assemble and suitable for mass production. Here, we developed millifluidic valves and pumps made of acrylic layers bonded with double-sided tape that are simple and fast to assemble. We demonstrate that a layer of pressure-sensitive adhesive (PSA) is flexible enough to be deformed at relatively low pressures. A chemical treatment deposited on specific regions of the PSA prevents it from sticking to the thermoplastic, which enabled us to create three different types of valves in normally open or closed configurations. We characterized different aspects of their performance, their operating pressures, the cut-off pressure values to open or close the valves (for different configurations and sizes), and the flow rate and volume pumped by seven different micropumps. As an application, we implemented a glucose assay with integrated pumps and valves, automatically generating glucose dilutions and reagent mixing. The ability to create polymeric microfluidic control units made with tape paves the way for their mass manufacturing.

Computer Numerical Control Micromilling of a Microfluidic Acrylic Device with a Staggered Restriction for Magnetic Nanoparticle-based Immunoassays.

Microfluidic systems have greatly improved immunoassay techniques. However, many microfabrication techniques require specialized, expensive, or complicated equipment, making fabrication costly and incompatible with mass production, which is one of the most important preconditions for point-of-care tests (POCT) to be adopted in low-resource settings. This work describes the fabrication process of an acrylic (polymethylmethacrylate, PMMA) device for nanoparticle-conjugated enzymatic immunoassay testing using the computer numerical control (CNC) micromilling technique. The functioning of the microfluidic device is shown by performing an immunoassay to detect a commercial antibody using lysozyme as a model antigen conjugated to 100 nm magnetic nanoparticles. This device integrates a physical staggered restriction of only 5 µm in height, used to capture magnetic microparticles that make up a magnetic trap by placing an external magnet. In this way, the magnetic force on the immunosupport of conjugated nanoparticles is enough to capture them and resist flow drag. This microfluidic device is particularly suitable for low-cost mass production without the loss of precision for immunoassay performance.

An affordable 3D-printed positioner fixture improves the resolution of conventional milling for easy prototyping of acrylic microfluidic devices.

We present a simple and low-cost positioner fixture to improve the fabrication resolution of acrylic microchannels using conventional milling machines. The positioner fixture is a mechatronic platform that consists of three piezoelectric actuators assembled in a housing made of 3D printer parts. The upper part of the housing is raised by the simultaneous actuation of the piezoelectric elements and by the deformation of 3D-printed hinge-shaped supports. The vertical positioning (Z-axis) can be controlled with a resolution of 500 nm and an accuracy of ±1.5 µm; in contrast, conventional milling machines can achieve resolutions of 10 to 35 µm. Through simulations, we found that 3D-printed hinges can deform to reach heights up to 27 µm without suffering any mechanical or structural damage. To demonstrate the capabilities of our fixture, we fabricated microfluidic devices with three weir filters that selectively capture microbeads of 3, 6 and 10 µm. We used a similar weir filter design to implement a bead-based immunoassay. Our positioner fixture increases the resolution of conventional milling machines, thus enabling the fast and easy fabrication of thermoplastic fluidic devices that require finer microstructures in their design.

Functional Activity and Endothelial-Lining Integrity of Ex Vivo Arteries Exposed to Ultrasound-Mediated Microbubble Destruction.

Ultrasound-mediated microbubble destruction (UMMD) is a promising strategy to improve local drug delivery in specific tissues. However, acoustic cavitation can lead to harmful bioeffects in endothelial cells. We investigated the side effects of UMMD treatment on vascular function (contraction and relaxation) and endothelium integrity of ex vivo Wistar rat arteries. We used an isolated organ system to evaluate vascular responses and confocal microscopy to quantify the integrity and viability of endothelial cells. The arteries were exposed for 1-3 min to ultrasound at a 100 Hz pulse-repetition frequency, 0.5 MPa acoustic pressure, 50% duty cycle and 1%-5% v/v microbubbles. The vascular contractile response was not affected. The acetylcholine-dependent maximal relaxation response was reduced from 78% (control) to 60% after 3 min of ultrasound exposure. In arteries treated simultaneously with 1 min of ultrasound exposure and 1%, 2%, 3% or 5% microbubble concentration, vascular relaxation was reduced by 19%, 58%, 80% or 93%, respectively, compared with the control arteries. Fluorescent labeling revealed that apoptotic death, detachment of endothelial cells and reduced nitric oxide synthase phosphorylation are involved in relaxation impairment. We demonstrated that UMMD can be a safe technology if the correct ultrasound and microbubble parameters are applied. Furthermore, we found that tissue-function evaluation combined with cellular analysis can be useful to study ultrasound-microbubble-tissue interactions in the optimization of targeted endothelial drug delivery.

Micro-nanoparticles magnetic trap: Toward high sensitivity and rapid microfluidic continuous flow enzyme immunoassay.

In this work, we developed a microfluidic system for immunoassays where we combined the use of magnetic nanoparticles as immunosupport, a microfluidic magnetic trap, and a fluorogenic substrate in continuous flow for detection which, together with the optimization of the functionalization of surfaces to minimize nonspecific interactions, resulted in a detection limit in the order of femtomolar and a total assay time of 40 min for antibiotin antibody detection. A magnetic trap made of carbonyl-iron microparticles packaged inside a 200 µ m square microchannel was used to immobilize and concentrate nanoparticles. We functionalized the surface of the iron microparticles with a silica-polyethylene glycol (PEG) shell to avoid corrosion and unspecific protein binding. A new one-step method was developed to coat acrylic microchannels with an organofunctional silane functionalized with PEG to minimize unspecific binding. A model immunoassay was performed using nanoparticles decorated with biotin to capture antibiotin rabbit Immunoglobulin G (IgG) as target primary antibody. The detection was made using antirabbit IgG labeled with the enzyme alkaline phosphatase as a secondary antibody, and we measured fluorescence with a fluorescence microscope. All steps of the immunoassay were performed inside the chip. A calibration curve was obtained in which a detection limit of 8 pg/ml of antibiotin antibody was quantified. The simplicity of the device and the fact that it is made of acrylic, which is compatible with mass production, make it ideal for Point-Of-Care applications.

Pressure-actuated monolithic acrylic microfluidic valves and pumps.

In this article, we describe a microfluidic device with embedded valves and pumps made exclusively of layers of acrylic glass. Flat acrylic sheets are carved out with a micromilling machine and bonded together by solvent bonding. The working principle of the valves is based on a thin flexible membrane (≈100 µm) machined on one acrylic sheet and actuated with pneumatic pressure. A completely closed valve resists a pressure difference of ≈17 kPa (≈2.5 psi), and when open, it can sustain flow rates of up to 100 µL s-1. Pumping is achieved by combining two valves and a pumping chamber in series, which is also based on the bending of a thin acrylic membrane. The maximum flow rate obtained with this pumping mechanism is 20 µL min-1. Acrylic is a popular rigid thermoplastic because it is inexpensive, making it ideal for mass production of disposable devices, and also because it has demonstrated compatibility with different biochemical assays. The physical and optical properties it shares with other thermoplastics could lead to this material being implemented for similar valves and pumps. As a proof-of-concept of our technology, we implemented a controlled cell-staining assay in two parallel incubation chambers integrating four valves and one pump into one device. Our monolithic acrylic valves can enable the mass production of disposable microfluidic devices that require fluid control with pressure-actuated valves and aid in the automation of biochemical assays.

Repayment policy for multiple loans.

The Repayment Policy for Multiple Loans is about a given set of loans and a monthly incoming cash flow: what is the best way to allocate the monthly income to repay such loans? In this article, we close the almost 20-year-old open question about how to model the repayment policy for multiple loans problem together with its computational complexity. Thus, we propose a mixed integer linear programming model that establishes an optimal repayment schedule by minimizing the total amount of cash required to repay the loans. We prove that the most employed repayment strategies, such as the highest interest debt and the debt snowball methods, are not optimal. Experimental results on simulated cases based on real data show that our methodology obtains on average more than 4% of savings, that is, the debtor pays approximately 4% less to the bank or loaner, which is a considerable amount in finances. In certain cases, the debtor can save up to 40%.

Effect of finite container size on granular jet formation.

When an object is dropped into a bed of fine, loosely packed sand, a surprisingly energetic jet shoots out of the bed. In this work we study the effect that boundaries have on the granular jet formation. We did this by (i) decreasing the depth of the sand bed and (ii) reducing the container diameter to only a few ball diameters. These confinements change the behavior of the ball inside the bed, the void collapse, and the resulting jet height and shape. We map the parameter space of impact with Froude number, ambient pressure, and container dimensions as parameters. From these results we propose an explanation for the thick-thin structure of the jet reported by several groups ([J. R. Royer, Nat. Phys. 1, 164 (2005)], [G. Caballero, Phys. Rev. Lett. 99, 018001 (2007)], and [J. O. Marston, Phys. Fluids 20, 023301 (2008)]).

Coarsening of Faraday heaps: experiment, simulation, and theory.

When a layer of granular material is vertically shaken, the surface spontaneously breaks up in a landscape of small Faraday heaps that merge into larger ones on an ever increasing time scale. This coarsening process is studied in a linear setup, for which the average life span of the transient state with N Faraday heaps is shown to scale as N-3. We describe this process by a set of differential equations for the peak positions; the calculated evolution of the landscape is in excellent agreement with both the experiments and simulations. The same model explains the observational fact that the number of heaps towards the end of the process decreases approximately as N(t) proportional, variant t-1/2.

Superheating in granular matter.

Some materials remain solids even if they are heated beyond the temperature of their melting points. In condensed matter physics, this rare phenomenon is called superheating. Here we report the analogous phenomenon in granular matter: a strongly vibrated monolayer that instead of being a gas persists as a crystal for some time. Eventually, it spontaneously evaporates. We found that the system has thermodynamiclike features like coexistence and metastability. We show how the observed metastable phase is linked to energy dissipation.

Conferencia de consenso. Tratamiento de la hipertensión arterial y prevención de sus complicaciones (I parte)

En la medida en que se ha logrado mejorar las condiciones generales de salud en la población, se ha observado un aumento en la expectativa de vida de las personas. La pirámide poblacional, incluso en los países en vías de desarrollo, viene estrechando su base y ampliando su vértice, mostrando un aumento importante de la proporción de adultos y viejos. Este cambio en la composición de la población se refleja en un incremento de la prevalencia de enfermedades relacionadas con el envejecimiento y el deterioro. El cáncer, las enfermedades degenerativas y las enfermedades cardiovasculares forman parte de aquellas patologías que afectan una proporción de habitantes cada vez mayor. De hecho, las enfermedades cardiovasculares contribuyen en forma significativa a la morbimortalidad en Colombia, especialmente en los grupos de mayor edad. Se sabe que en Colombia, alrededor de 15 a 20 porciento de los adultos son hipertensos y muchos de ellos o no reciben tratamiento o simplemente no se conocen como hipertensos. La elevación de la presión arterial es el común denominador de una gran diversidad de trastornos como la enfermedad cerebrovascular, la nefropatía, la enfermedad cardiovascular, la enfermedad vascular periférica o la toxemia del embarazo. Todas ellas, miradas en conjunto, dan cuenta de una enorme carga de morbimortalidad relacionada, en última instancia, con la enfermedad hipertensiva. En los últimos años han surgido tratamientos capaces de reducir la presión arterial, los cuales paracen constituir, asimismo, una herramienta útil en la prevención de las complicaciones de la enfermedad. El médico deberá estar en capacidad de instruir y educar a sus pacientes acerca de la importancia de la prevención mediante modificaciones en el estillo de vida, y en la introducción de otras medidas no farmacológicas. Además, deberá conocer la eficacia de los diferentes tratamientos antihipertensivos disponibles hoy en día. Es su obligación saber seleccionar adecuadamente los que es bueno y apropiado para cada tipo de paciente en cada circunstancia particular. No de otro modo le será posible intervenir efectivamente en la prevención de las secuelas de la enfermedad vascular hipertensiva. El Ministerio de salud, a través de la Dirección de Recursos Humanos, lleva a cabo las Conferencias de Consenso que pretenden unificar criterios en torno a las enfermedades de mayor prevalencia e impacto sobre la población colombiana. Resumen truncado a 2500 caracteres.