A Rapid Capillary-Pressure Driven Micro-Channel to Demonstrate Newtonian Fluid Behavior of Zebrafish Blood at High Shear Rates

Blood viscosity provides the rheological basis to elucidate shear stress underlying developmental cardiac mechanics and physiology. Zebrafish is a high throughput model for developmental biology, forward-genetics, and drug discovery. The micro-scale posed an experimental challenge to measure blood viscosity. To address this challenge, a microfluidic viscometer driven by surface tension was developed to reduce the sample volume required (3μL) for rapid (500 s^(−1)), at which the power law exponent (n) of zebrafish blood was nearly 1 behaving as a Newtonian fluid. The measured values of whole blood from the micro-channel (4.17cP) and the vacuum method (4.22cP) at 500 s^(−1) were closely correlated at 27 °C. A calibration curve was established for viscosity as a function of hematocrits to predict a rise and fall in viscosity during embryonic development. Thus, our rapid capillary pressure-driven micro-channel revealed the Newtonian fluid behavior of zebrafish blood at high shear rates and the dynamic viscosity during development

A review of hemorheology : measuring technologies and recent advances

Significant progress has been made over the years on the topic of hemorheology, not only in terms of the development of more accurate and sophisticated techniques, but also in terms of understanding the phenomena associated with blood components, their interactions and impact upon blood properties. The rheological properties of blood are strongly dependent on the interactions and mechanical properties of red blood cells, and a variation of these properties can bring further insight into the human health state and can be an important parameter in clinical diagnosis. In this article, we provide both a reference for hemorheological research and a resource regarding the fundamental concepts in hemorheology. This review is aimed at those starting in the field of hemodynamics, where blood rheology plays a significant role, but also at those in search of the most up-to-date findings (both qualitative and quantitative) in hemorheological measurements and novel techniques used in this context, including technical advances under more extreme conditions such as in large amplitude oscillatory shear flow or under extensional flow, which impose large deformations comparable to those found in the microcirculatory system and in diseased vessels. Given the impressive rate of increase in the available knowledge on blood flow, this review is also intended to identify areas where current knowledge is still incomplete, and which have the potential for new, exciting and useful research. We also discuss the most important parameters that can lead to an alteration of blood rheology, and which as a consequence can have a significant impact on the normal physiological behavior of blood

Numerical study of bio-fluids and mass transfer processes through membranes

La reologia de la sang (hemoreología) exerceix un ppel important en la perforació de teixits i l'alteració de les seves condicions fisiològiques és gairebé sempre la principal causa de patologies cardiovasculars. Per tant, l'estudi dels perfils de velocitat i l'esforç de tall de la sang al llarg de micro-venes és important en la investigació de malalties cardiovasculars. Recents avenços en organs-on-a-chip remarquen la possibilitat d'usar lung-on-a-xips el qual ha estat desenvolupat per reemplaçar les funcions respiratòries de l'home en assajos farmaceuticos. S'ha avançat en l'estudi de processos de micro-separació a través de membranes micro-poroses desenvolupant una eina numèrica per modelar el comportaments dels micro-dispositius usant la geometria dels lung-on-a-chip en dues i tres dimensions, on una membrana artificial separa dos canals amb dos diferents fluids i així dos diferents règims de flux. A causa de que és un problema de múltiples escales, el nou codi consisteix d'un model híbrid LBM-FD (Lattice Boltzmann - diferències finites) sobre una malla no uniforme que modela processos de transferència de massa en fluxos no newtonians. El model híbrid LBM-FD va ser usat per estudiar el transport de massa a través d'una membrana hidrofòbica i microporosa ocalizada entre un flux co-corrent passant a través de canals rectangulars, similar als microdispositius usats en el projecte lung-on-a- xip. Estecódigo ha estat usat per fer un estudi paramètric en la recerca de la correlació entre el nombre de Peclet al canal permeat i els processos de transferència de massa a través de la membrana (Sherwood number mitjana ). Les correlacions al microdispositiu bidimensional reprodueix correctament la relació lineal de amb el nombre de porus. Les correlacions mostren un valor de l'exponencial en la llei de potències de 1/3 (el que caracteritza el problema de Graetz-Leveque) de pel que fa a Pe. S'han trobat les correlacions en dues i tres dimensions. En el cas tridimensional es comparen els resultats obtinguts usant el flux del model de la llei de pontencias truncat amb un grau de pseudo-plasticitat de n = 0.7 pel que fa als resultats obtinguts per flux newtonià n = 1. El cas no-newtonià mostra un increment del 5% en la transferència de massa () respecte al cas newtonià.La reología de la sangre (hemoreología) desempeña un papel importante en la perforación de tejidos y la alteración de sus condiciones fisiológicas es casi siempre la principal causa de patologías cardiovasculares. Por lo tanto, el estudio de los perfiles de velocidad y el esfuerzo de corte de la sangre a lo largo de micro-venas es importante en la investigación de enfermedades cardiovasculares. Recientes avances remarcan la posibilidad de usar micro-dispositivos como lung-on-a-chip, el cual ha sido desarrollado para reemplazar las funciones respiratorias del hombre en ensayos farmaceuticos. Se ha avanzado en el estudio de procesos de micro-separación a través de membranas micro-porosas desarrollando una herramienta numérica para modelar el comportamientos de los micro-dispositivos usando la geometría de los lung-on-a-chip en dos y tres dimensiones. Debido a que es un problema de múltiples escalas, el nuevo código consiste de un modelo híbrido LBM-FD (Lattice Boltzmann - Diferencias finitas) sobre una malla no uniforme que modela procesos de transferencia de masa en flujos no Newtonianos. El modelo híbrido LBM-FD fue usado para estudiar el transporte de masa a través de una membrana hidrofóbica y microporosa localizada entre un flujo co-corriente pasando a través de canales rectangulares, similar a los microdispositivos usados en el proyecto lung-on-a-chip. Con este código, un estudio paramétrico en la busqueda de la correlación entre el Peclet en el canal permeado y el Sherwood promedio ha sido realizado. Las correlaciones en el microdispositivo bi-dimensional reproduce correctamente la relación lineal de con el número de poros. Las correlaciones muestran un valor del exponencial en la ley de potencias de 1/3 ( lo que caracteriza el problema de Graetz-Leveque) de con respecto a Pe. Se han hallado las correlaciones en dos y tres dimensiones. En el caso tri-dimensional se comparan los resultados obtenidos usando el flujo del modelo del modelo de la ley de pontencias truncado con un grado de pseudo-plasticidad de n=0.7 con respecto a los resultados obtenidos para flujo Newtoniano n=1. El caso no-Newtoniano muestra un incremento del 5% en la transferencia de masa () con respecto al caso Newtoniano.Blood rheology (haemorheology) plays a key role in tissue perfusion and its alteration from physiological conditions is often the main cause of cardiovascular pathologies. Therefore, the study of blood velocity profiles and wall shear stress distribution along micro-vessels is important in the field of cardiovascular diseases research. Recent advances in organ-on-a-chip highlighted the possibility of using artificial lung-on-chips which have been developed to replace the respiratory functions of the human lungs in pharmaceutical tests. We have expanded the study of micro-separation processes through micro-porous membranes by developing a numerical tool able to model the behavior of lung-on-a-chip micro-devices in both two and three dimensional geometries. As this is a multiscale problem, the new code consists in a hybrid LBM-FD (Lattice Boltzmann - finite difference) model on a non-uniform material grid, that models mass transfer processes in non-Newtonian flows. A part from the validation of the code, results obtained include the correlations of the non-dimensional numbers involved in mass transfer processes and the dependence on porosity, and the study of concentration profiles under steady (pipe flow) and the beginning of the study in non-steady (Womersley flow) conditions. The LBM-FD hybrid model was used to study the mass transport through a hydrophobic micro-porous membrane located in-between a co-current flow passing through rectangular channels, which is similar to the micro-device used in Lung-On-a-Chip research. This code has been used to perform a parametric study to find the empirical correlation between Peclet number in the permeate channel and the mass transfer processes across the membrane which is quantified by mean of Sherwood number. The correlations in the two-dimensional micro-device reproduce correctly the linear scaling law of with the number of pores. The correlations give a power value equal to 1/3 (which characteristic of the Graetz-Leveque problem) for the scaling exponent of the average Sherwood number with Pe. This has been done in 2D and 3D models. In the three-dimensional case, we compared the results obtained using the power-law flow with a shear-thinning degree of n=0.7 against the results obtained using the Newtonian hypothesis (n=1). The non-Newtonian case

Microgravity Science and Applications. Program Tasks and Bibliography for FY 1993

An annual report published by the Microgravity Science and Applications Division (MSAD) of NASA is presented. It represents a compilation of the Division's currently-funded ground, flight and Advanced Technology Development tasks. An overview and progress report for these tasks, including progress reports by principal investigators selected from the academic, industry and government communities, are provided. The document includes a listing of new bibliographic data provided by the principal investigators to reflect the dissemination of research data during FY 1993 via publications and presentations. The document also includes division research metrics and an index of the funded investigators. The document contains three sections and three appendices: Section 1 includes an introduction and metrics data, Section 2 is a compilation of the task reports in an order representative of its ground, flight or ATD status and the science discipline it represents, and Section 3 is the bibliography. The three appendices, in the order of presentation, are: Appendix A - a microgravity science acronym list, Appendix B - a list of guest investigators associated with a biotechnology task, and Appendix C - an index of the currently funded principal investigators

Laboratory Development of Third/Fourth Generation Sulphlex Binders

Study No. 7208This report presents the findings of a 2-year, multitask study to provide a new generation of Sulphlex binders with enhanced low-temperature fracture resistance. The initial phases of the program dealt with the preparation and base-line characterization of Sulphlex 233 and 198, First and Second Generation Sulphlex, respectively, considered the more promising of a broad series of formulations developed under earlier Federal Highway Administration programs. These binders were prepared individually and blended at ratios of 50/50 and 75/25 (198/233) and designated as Third Generation Sulphlex. The former was prepared by directly blending the two binders as well as by a one-pot synthesis. These binders were subjected to a series of screening tests including (a) Penetration @ 25 deg C, (b) Viscosity @ 135 deg C, (c) Specific Gravity, (d) Solubility in CHCl3, (e) Storage Stability, and (f) Glass Transition temperature. A "new and improved" Sulphlex binder designated as Fourth Generation was formulated utilizing the rationale derived from the earlier systems. Sulphlex mixtures along with a control using an AC-20 asphalt were prepared using a crushed limestone aggregate and tested in accordance with Asphalt Aggregate Mixture Analysis System (AAMAS), American Association of State Highway and Transportation Officials (AASHTO), Strategic Highway Research Program (SHRP or Superpave), and Viscoelastic Systems (VESYS) procedures including (a) Indirect Tension, (b) Diametral Resilient Modulus, (c) IDT Creep, (d) Compressive Creep, (e) Unconfined Compression, (f) Repeated Load Permanent Deformation, and (g) Aging using Resilient Modulus. A set of generic manufacturing plans and procedures were generated for the production of Sulphlex in sufficient quantity to satisfy the requirements of an hypothetical test road section

Fluidic Dielectrophoresis: Electrokinetic Polarization and Manipulation of Electrical Liquid Interfaces for Biological and Sensing Applications

Development of rapid, sensitive and portable detection systems are important for effective detection of diseases in developing countries, biowarfare/anti-terrorism applications, environmental monitoring, and for basic biological research. One of the most specific and popular sensing platform is the enzyme-linked immunosorbent assay (ELISA) platform, which identifies the presence of a substance, specifically an antigen, in a liquid sample. Biosensing assays, like ELISA, offer sensitivity and selectivity, however, its assay time is long due to immobilization and detection through a secondary antibody. The assay also requires periodic rinsing steps to avoid non-specific binding and to remove excess proteins. Finally, the fluorescent detection instrumentation is required, and is still too bulky and costly for widespread daily laboratory, clinical and point-of-care use. The main challenge for producing low cost, portable, and easy to operate biosensing systems is then to miniaturize the sensing platform without any sophisticated instrumentation and complicated reagent protocols. In this work, we first explore a well-known electrokinetic phenomenon called dielectrophoresis (DEP), which traditionally has been studied in cells and particles, but here at a liquid-liquid interface, which we call fluidic dielectrophoresis (fDEP). The liquid-liquid interface with disparaging electrical properties - conductivity and permittivity - is shown to move when subjected to an alternating current (ac) electric field and the direction and magnitude is studied at varying applied frequencies and voltages. We found that when a biomolecular reaction occurs at the liquid-liquid interface it alters the electrical properties, which is transduced by interfacial displacement; we call this novel transduction method interfacial electrokinetic transduction (IET). We began with a model biomolecular reaction between biotin and avidin to validate our detection scheme. We then performed detection of hCG in human serum. Finally, we implemented impedance spectroscopy to non-optical monitor the position of the interface. Coupled with IET, the system non-optically monitored the position of the electrical interface in the presence of a biomolecular reaction. Collectively, we successfully developed the first, in solution, label-free non-optical biosensor. This novel biosensor was shown to detect biomarkers down to femtomolar concentration in human serum within minutes

Measurement of viscosity of unadulterated human whole blood using a capillary pressure-driven viscometer

This paper presents the experimental work on the measurement of unadulterated human whole blood viscosity using a capillary-based microfluidic viscometer. The viscosity was measured by monitoring the time-varying length and mean advancing velocity of the blood column inside the viscometer. A high-aspect-ratio microfluidic channel is preferred for the device geometrical configuration. Theoretical modeling and numerical algorithms were applied to obtain the blood viscosity over a wide range of shear rates. Power law and Carreau-Yasuda models were used to model the non-Newtonian behavior of the human whole blood. The proposed approach is uniquely applicable for small sample volume (<2µL), and short measurement time (<2 min). A wide range of shear rates (varying from of 71.4s^(−1) to 5492.1s^(−1)) is produced in a single test

Development, manufacture and assessment of Clobetasol 17-propionate cream formulations

Eczema or dermatitis is the most common dermatological condition accounting for one-third of all diagnoses in the total population surveyed in South Africa. The prevalence of seborrhoeic dermatitis, extreme photodermatitis and severe psoriasis has increased markedly over the last decade and this increase may be ascribed to the HIV epidemic, first diagnosed in South Africa in 1982. Potent innovator corticosteroids, such as clobetasol 17-propionate (CP) that are used to treat skin disorders, are expensive and there is therefore a need for the production of generic topical corticosteroid products. Formulation and manufacturing processes can be challenging aspects for formulation scientists to produce a robust product that will elicit an appropriate and desirable pharmacokinetic-pharmacodynamic profile. Laboratory scale CP creams were manufactured using different concentrations of Gelot® 64 and propylene glycol in order to establish a composition that would produce a formulation, with similar physical and chemical characteristics and in vitro release profile as an innovator product, Dermovate®. These formulations were assessed in terms of their viscosity, spreadability, pH, content uniformity and in vitro release characteristics using a Franz diffusion cell apparatus. A formulation containing 3% w/w Gelot® 64 and 46% v/v propylene glycol (CPLS-02) was found to exhibit similar viscosity and spreadability characteristics and released CP in a manner similar to Dermovate®. The mechanism of drug release was evaluated using mathematical models such as zero order, first order and Higuchi models. In addition, the in vitro release profiles were characterised by use of difference (f1) and similarity (f2 and Sd) factors. A scale-up formulation with the same % w/w composition as the laboratory scale was also investigated following manufacture using a Wintech® cream/ointment mixer. A Central Composite Design approach was used to investigate the effect of process variables on the performance of the scale-up cream formulations. The homogenisation speed, anchor speed, homogenisation time and cooling time were the process variables investigated. Thirty scale-up batches were manufactured and analysed in terms of their viscosity, spreadability, pH, % drug content and cumulative % drug released per unit area over 72 hours. Model fitting using Design-Expert® software was undertaken and revealed that a correlation between the process variables and the cream responses was most suitably described by quadratic polynomial relationships. The homogenisation speed had the most significant effect on the quality of the scale-up formulations, whereas the anchor speed had a secondary effect on the measured responses, for the formulations investigated. The qualitative interpretation and statistical analysis of the in vitro release data from the scale-up formulations using ANOVA and the f1, f2 and Sd factors revealed that one scale-up batch (CPSU-04), for which the process variables were a homogenisation speed of 1900 rpm, an anchor speed of 35 rpm, a homogenisation time of 100 minutes and a cooling time of 100 minutes, released CP at a similar rate and extent to Dermovate®. A diffusion-controlled mechanism appeared to be predominant in these formulations. A human skin blanching study, using both visual and chromameter assessments, was performed to establish whether batch CPSU-04 was bioequivalent to Dermovate®. The bioequivalence of the selected scale-up formulation to Dermovate® was confirmed, following the calculation of a 90% CI

Espectrometría de masa y rigidez basada en resonadores nanomecánicos

Este trabajo de tesis doctoral está centrado en el uso de los resonadores nanomecánicos como Este trabajo de tesis doctoral está centrado en el uso de los resonadores nanomecánicos como sensores biológicos. Se han estudiado diferentes tipos de resonadores nanomecánicos, tanto desde un punto de vista teórico como experimental, incluyendo el estudio de nanohilos de silicio cónicos y microcapilares de sílice fundido, así como de micropalancas. El objetivo central ha sido el desarrollo de un espectrómetro de masa y rigidez basado en resonadores nanomecánicos para la detección biológica. Se ha utilizado la técnica de ionización mediante electrospray para depositar las partículas biológicas sobre la superficie de una micropalanca. Mediante la medida del cambio en la frecuencia de resonancia de la micropalanca, y un algoritmo matemático, se obtiene la masa y rigidez del adsorbato. Este sistema se ha utilizado para calcular la masa y rigidez de nanopartículas y bacterias, siendo esta la primera vez que se mide la rigidez en tiempo real mediante espectrometría nanomecánica