Selection of phage-displayed antibodies with high affinity and specificity by electrophoresis in microfluidic devices.

A method development aimed for high-throughput and automated antibody screening holds great potential for areas ranging from fundamental molecular interactions to the discovery of novel disease markers, therapeutic targets, and monoclonal antibody engineering. Surface display techniques enable efficient manipulation of large molecular libraries in small volumes. Specifically, phage display appeared as a powerful technology for selecting peptides and proteins with enhanced, target-specific binding affinities. Here, we present a phage-selection microfluidic device wherein electrophoresis was performed under two orthogonal electric fields through an agarose gel functionalized with the respective antigen. This microdevice was capable of screening and sorting in a single round high-affinity phage-displayed antibodies against virus glycoproteins, including human immunodeficiency virus-1 glycoprotein 120 or the Ebola virus glycoprotein (EBOV-GP). Phages were differentially and laterally swept depending on their antigen affinity; the high-affinity phages were recovered at channels proximal to the application site, whereas low-affinity phages migrated distal after electrophoresis. These experiments proved that the microfluidic device specifically designed for phage-selection is rapid, sensitive, and effective. Therefore, this is an efficient and cost-effective method that allowed highly controlled assay conditions for isolating and sorting high-affinity ligands displayed in phages.

Metronomic doses and drug schematic combination response tested within chambered coverslips for the treatment of breast cancer cells (JIMT-1).

Low-dose metronomic (LDM) chemotherapy is an alternative to conventional chemotherapy and is the most frequently used approach in low dose chemotherapy regimens. The selection of patients, drug dosages, and dosing intervals in LDM is empirical. In this study, we systematically examined the schedule-dependent interaction of drugs on a breast cancer cell line (BCC) cultured in chambered coverslips. The LDM studies were combined with cell staining in order to better characterize different cell states and cell death modes, including caspase-dependent apoptosis, caspase-independent cell death and autophagy-dependent cell death. Microscope images were examined using the Fiji Trainable Weka Segmentation plugin to analyse cell area in 7500 images showing different modes of cell death. Paclitaxel combined with LDM chemotherapy demonstrated a reduction in the area covered by live cells. In contrast, there was an induction of high levels of cell death due to caspase-dependent apoptosis.

Novel Reproducible Manufacturing and Reversible Sealing Method for Microfluidic Devices.

Conventional manufacturing methods for polydimethylsiloxane (PDMS)-based microdevices require multiple steps and elements that increase cost and production time. Also, these PDMS microdevices are mostly limited to single use, and it is difficult to recover the contents inside the microchannels or perform advanced microscopy visualization due to their irreversible sealing method. Herein, we developed a novel manufacturing method based on polymethylmethacrylate (PMMA) plates adjusted using a mechanical pressure-based system. One conformation of the PMMA plate assembly system allows the reproducible manufacture of PDMS replicas, reducing the cost since a precise amount of PDMS is used, and the PDMS replicas show uniform dimensions. A second form of assembling the PMMA plates permits pressure-based sealing of the PDMS layer with a glass base. By reversibly sealing the microdevice without using plasma for bonding, we achieve chip on/off configurations, which allow the user to open and close the device and reuse it in an easy-to-use way. No deformation was observed on the structures of the PDMS microchannels when a range of 10 to 18 kPa pressure was applied using the technique. Furthermore, the functionality of the proposed system was successfully validated by the generation of microdroplets with reused microdevices via three repetitions.

Single cell transfection of human-induced pluripotent stem cells using a droplet-based microfluidic system.

Microfluidic tools have recently made possible many advances in biological and biomedical research. Research in fields such as physics, engineering, chemistry and biology have combined to produce innovation in microfluidics which has positively impacted diverse areas such as nucleotide sequencing, functional genomics, single-cell studies, single molecules assays and biomedical diagnostics. Among these areas, regenerative medicine and stem cells have benefited from microfluidics since these tools have had a profound impact on their applications. In this study, we present a high-performance droplet-based system for transfecting individual human-induced pluripotent stem cells. We will demonstrate that this system has great efficiency in single cells and captured droplets, like other microfluidic methods but with lower cost. Moreover, this microfluidic approach can be associated with the PiggyBac transposase-based system to increase its transfection efficiency. Our results provide a starting point for subsequent applications in more complex transfection systems, single-cell differentiation interactions, cell subpopulations and cell therapy, among other potential applications.

Cost-effective fabrication of photopolymer molds with multi-level microstructures for PDMS microfluidic device manufacture.

This paper describes a methodology of photopolymer mold fabrication with multi-level microstructures for polydimethylsiloxane (PDMS) microfluidic device manufacture. Multi-level microstructures can be performed by varying UVA exposure time and channel width. Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and profilometry techniques have been employed to characterize the molds. Multiple molds with multi-level microstructures can be formed in a unique piece. Overall height/depth of the structures reaches up to 677 µm and a minimum of 21 µm. The method provides several advantages such as reduction of fabrication time, multiple structures with diverse topologies, a great variety of depth and height in a single mold and low cost of fabrication. The effectiveness of multi-level microstructure fabrication was evaluated by constructing PDMS microfluidic devices for cell culture and proliferation.

Hybrid microchannel-solid state micropore device for fast and optical cell detection.

This paper presents a methodology for cell detection and counting using a device that combines PDMS (polydimethylsiloxane) microfluidic multilayer channels with a single solid state micropore. Optimal conditions of solid-state micropore fabrication from crystalline silicon wafers are presented. Micropores of varying size can be obtained by directly etching using an etchant agent concentration of 50 wt% KOH, at varying temperatures (40, 60, 80 °C) and voltages (100, 500, 1000 mV). Scanning Electron Microscopy (SEM), and profilometry techniques have been used for the micropore characterization. In order to find optimal conditions for cell detection a COMSOL Multiphysics simulation was performed. Pressure drop, shear stress, fluid viscosities and flow rates parameters were evaluated. The potential viability of the device for cell detection and counting, avoiding cellular damage, is demonstrated.

Gestión de la innovación en los servicios de salud pública / Innovation management in public health services

Los términos conocimiento, tecnología e innovación cada vez más forman parte del vocabulario empresarial, al reconocerse como pilares para el éxito de cualquier organización en el siglo XXI. Especialmente en la prestación de servicios sociales como la salud pública la gestión de la innovación debe constituir una prioridad para la atención con calidad y efectividad de los acuciantes problemas de salud que afectan a la humanidad. El objetivo del artículo es analizar el desarrollo de la gestión de la innovación en los servicios de salud pública. El análisis bibliográfico realizado incluyó material de los últimos seis años en cuatro bases de datos regionales, acerca de la gestión de la innovación en servicios de salud pública. La investigación ha constituido una preocupación constante en los servicios de salud pública, lo que requiere de la gestión continua de la innovación en sus entidades, con énfasis en los aspectos que la literatura considera más relevantes, como el talento humano, la estrategia y cultura organizacional, la relación con los clientes y entidades colaboradoras, en especial, las educativas. La gestión de la innovación constituye una prioridad para las entidades de salud, en correspondencia con las políticas públicas que promueven la solución continua a los problemas poblacionales de salud(AU)

The terms knowledge, technology and innovation are increasingly part of the business vocabulary, recognizing as pillars for the success of any organization in the twenty-first century. Especially in the provision of social services such as public health, innovation management must be a priority for the quality and effectiveness of the pressing health problems that affect humanity. The objective of this article is to analyze the development of innovation management in public health services. The bibliographic analysis included material from the last six years in four regional databases on the management of innovation in public health services. Research has been a constant concern in the public health services, which requires the continuous management of innovation in its entities, with emphasis on the aspects that literature considers more relevant, such as human talent, strategy and organizational culture, the relationship with clients and collaborating entities, especially educational ones. Innovation management is a priority for health institutions, in accordance with public policies that promote a continuous solution to population health problems(AU)

Análisis crítico de la responsabilidad social en entidades de salud / Critical analysis of social responsibility in health entities

RESUMEN El estudio de la responsabilidad social, más allá de ser llamativo, resulta de por sí responsable e importante si se toma en consideración que cada vez son más las obligaciones que las organizaciones deben asumir con sus empleados, la sociedad y el medio ambiente. En el artículo se realiza un análisis crítico de la práctica de la responsabilidad social en entidades de salud. Se revisó la bibliografía publicada en los últimos cinco años en tres bases de datos regionales, sobre la responsabilidad social en el sector de la salud en Iberoamérica. Se evidenció la evolución del término de responsabilidad social, en concordancia con otros temas de la gestión organizacional con los que se relaciona dicha práctica, con regularidades en el sector de la salud dada la naturaleza de esta actividad, como es la relación con aspectos culturales de la organización, éticos y ambientales, y con potencialidades para su efectivo desarrollo a partir de un adecuado control social. El estudio de la responsabilidad social en entidades de salud permite visualizar los retos que aún quedan pendientes para el desarrollo efectivo de las relaciones entre las organizaciones y la sociedad

ABSTRACT The study of social responsibility, beyond striking, is of itself responsible and important if one takes into account that more and more obligations that organizations must assume with their employees, society and the environment. This article presents a critical analysis of the practice of social responsibility in health institutions. We reviewed the literature published in the last five years in three regional databases on social responsibility in the health sector in Latin America. It was evidenced the evolution of the term of social responsibility, in agreement with other subjects of the organizational management with which this practice is related, with regularities in the health sector given the nature of this activity, like the relation to cultural aspects of the organization, ethical and environmental, and with potential for its effective development from an adequate social control. The study of social responsibility in health institutions allows us to visualize the remaining challenges for the effective development of relations between organizations and society