Membrane integration in biomedical microdevices

The present work has been performed under the Erasmus Mundus Doctorate in Membrane Engineering (EUDIME) program. The home institute was the Chemical and Environmental Engineering Department at the University of Zaragoza, within the Nanostructured Films and Particles (NFP) group. The NFP is a member of the Nanoscience Institute of Aragon (INA). Two host universities were: Faculdade de Ciências e Tecnologia at the University Nova de Lisboa (Portugal) and Mesoscale Chemical Systems group at the University of Twente (The Netherlands). This research has been carried out for approximately 4 years (2013-2017) and it was part of the EUDIME (FPA 2011-0014, SGA 2012-1719), which was funded by the European Union. The target of the research presented in this thesis is a design, development and fabrication of a microfluidic device with integrated membrane in the form of a membrane contactor for various biological applications. The microfluidic devices are fabricated and tested for oxygenation of blood and separation of anaesthetic gas. In the first part of the work, the microfluidic system for blood oxygenation, so called lungon- a-chip, is introduced. In such system, one chamber is devoted to pure oxygen, and the other chamber is designed for blood and they are separated by a dense permeable membrane. Computer modelling is performed in order to design the liquid chamber with homogenous liquid flow, low pressure drop of the system and low shear stress without compensation of high oxygenation. Two different microdevice geometries are proposed: alveolar and meander type design with vertical membrane arrangement. Fabricated devices as well as integrated membranes are made of PDMS by soft-lithography and their surface is modified in order to make them more hydrophilic. The experiments of blood oxygenation are performed and the oxygen concentration is measured by an oximeter electrode and compared to the mathematically modelled values. The sensitivity analysis of the key parameters and the possible improvements of the proposed architectures based on the mathematical simulations are presented as well. The second part of the thesis, introduces the concept of an alveolar microfluidic device as gas-ionic liquid micro-contactor for removal of CO2 from anaesthesia gas, containing Xe. The working principle involves the transport of CO2 through a flat PDMS membrane followed by the capture and enzymatic bioconversion in the ionic liquid solvent. As proof of concept demonstration, simple gas permeability experiments are performed followed by the experiments with ionic liquid and ionic liquid with the enzyme. Finally, an alternative concept of a silicon/glass microfluidic device with an integrated membrane in the form of a fractal geometry with nanonozzles as pores at the vertices of the third-level octahedra for the controlled addition of gaseous species is introduced. Fractal geometry, that is a three-dimensional repetitive unit, is fabricated by a combination of anisotropic etching of silicon and corner lithography. As a proof of concept, simple gas permeation experiments are performed, and the achieved results reveal the potentialities of the chip for high temperature gas-liquid contactors

Fabrication and characterization of nanoparticles/PMMA electrospun nanofiber membranes

Currently, one of the most serious problems is to maintain the water balance in terms of quality and quantity. In recent times, membrane technology is considered to be essential as it ensures high water quality with low cost and maintenance of sustainable water resources. In this work different membranes were fabricated by electrospinning technique. PMMA (polymethyl methacrylate) was used as a base polymer material and the silver nanoparticles, silver nanowires or titanium dioxide were incorporated into the matrix. The aim was to produce polymeric membranes containing nanoparticles, fabricated by electrospinning in order to obtain the highest bactericidal effect for water treatment. The bactericidal effect was observed for three kinds of membranes however, the best results were obtained by the silver nanoparticles membrane with the in situ manufacturing method. The distribution of the nanoparticles in this membrane resulted more uniform, the size of the nanoparticles was smaller and the texture was the most mechanically resistant

Study on the recycling of zeolitic imidazolate frameworks and polymer Pebax® 1657 from their mixed matrix membranes applied to CO2 capture

Mixed matrix membranes (MMMs) consisting of fillers (e.g. metal organic frameworks (MOFs)) in polymer matrix are considered as an interesting alternative for capturing post combustion CO2 towards a sustainable development. This research is focused on the recycling of MMMs made of polymer Pebax® 1657 and MOF ZIF-94. Upon MMM preparation, characterization and testing, MMMs were dissolved to recover polymer and MOFs separately. Recovered products were characterized by SEM, EDX, FTIR, TGA, XRD, DLS, mass spectrometry and N2 adsorption to compare their size, shape and other properties with those of fresh ones. Mean particle size of fresh and recycled ZIF-94 were 148 ± 44 nm and 164 ± 32 nm, respectively. Incorporation of recycled ZIF-94 in MMMs produced defect free membranes which was confirmed by SEM and gas separation measurements. These MMMs, with a 10 wt% ZIF-94 loading, were tested for the separation of the CO2/N2 mixture with a CO2 permeability of 157 ± 6.5 Barrer (with 67 % improvement compared to fresh pure polymer membrane with 94 ± 2 Barrer) and a CO2/N2 selectivity of 27.5 ± 1.4 (5 % lower than that of the fresh MMM, 29.3 ± 1.8, but 20 % higher than the corresponding to the pure polymer membrane, 23 ± 2). Demonstrating its wide feasibility, the proposed methodology was also applicable for recycling of ZIF-8 from Pebax® 1657 based MMMs

Metal-organic framework (mof)-pebax-based mixed matrix membranes for post-combustion CO2 capture

Las membranas más interesantes para aplicaciones de separación de CO2 son las denominadas MMM (membranas de matriz mixta), compuestas por una fase polimérica continua y una fase dispersa, también llamada relleno. Por su afinidad hacia el CO2, existen varios MOF (¿metal-organic framework¿) adecuados para fabricar MMM. Sin embargo, la sostenibilidad de los materiales de la membrana presenta limitaciones en términos de síntesis de MOF y de fabricación de MMM, debido al impacto medioambiental de los desechos químicos involucrados. Como caso de estudio más representativo, el ZIF-94 obtenido del reciclado de las aguas madre de su cristalización, se incorporó a MMM aplicadas a la separación CO2/N2. Además, se estableció el reciclado de MMM para extraer sus componentes clave (MOF y polímero) y reutilizarlos en MMM. Por otro lado, se estudió el MIL-178(Fe), otro material poroso unidimensional nanoestructurado, para comprobar su adaptabilidad en MMM aplicadas a la separación CO2/N2 y CO2/CH4.<br /

Nanofiltration thin-film composite membrane on either the internal or the external surface of a polysulfone hollow fiber

The inner and outer surfaces of a porous hollow fiber polysulfone support are compared as substrates for the synthesis of polyamide thin‐film composite (TFC) membranes by interfacial polymerization. While both surfaces have pores common of microfiltration membranes, the inner surface has a larger pore diameter than the outer surface (2,700 nm compared to 950 nm). The inner TFC membrane showed higher water nanofiltration permeance than the outer (2.20 ± 0.17 compared to 0.13 ± 0.03 L m−2 hr−1 bar−1). This was due to the influence of the porosity and roughness, which were different on both support surfaces. These membranes are interesting because they were synthesized in a hollow fiber support with a high membrane area per volume unit (~6,900 m2/m3) and the substrate used was commercial, which means that the TFC membrane obtained is suitable for industrial application. A mathematical simulation of the nanofiltration run with COMSOL Multiphysics 5.3 software confirmed the experimental trends observed.Financial support from the Spanish MINECO and FEDER (MAT2016‐77290‐R), the Aragón Government (T43‐17R), and the ESF is gratefully acknowledged. C. Echaide‐Górriz thanks the Aragón Government for his PhD grant.Peer reviewe

Membrane Integration in Biomedical Microdevices

El objetivo principal de esta tesis es el desarrollo y fabricación de un dispositivo microfluídico basado en membranas integradas y el estudio de diversos “contactores de membrana” para las diversas aplicaciones biomedicas. Los dispositivos microfluídicos se fabricaron y se aplicarón en la oxigenación de la sangre y separación de la mezcla de gas anestésico. Para la oxigenación de la sangre, el modelo matemático de transferencia de oxígeno en las unidades principales de los dispositivos microfluídicos subraya la importancia de la arquitectura de bifurcación y la distribución de los distribuidores del flujo dentro de la cámara de líquido.La aplicación de un microcontactor de membrana líquida gaseosa para la eliminación en línea de CO2 demostró cuán efectivos pueden ser los dispositivos miniaturizados para los estudios fundamentales de recuperación de gas anestésico.<br /

Pre-combustion gas separation by ZIF-8-polybenzimidazole mixed matrix membranes in the form of hollow fibres—long-term experimental study

Polybenzimidazole (PBI) is a promising and suitable membrane polymer for the separation of the H2/CO2 pre-combustion gas mixture due to its high performance in terms of chemical and thermal stability and intrinsic H2/CO2 selectivity. However, there is a lack of long-term separation studies with this polymer, particularly when it is conformed as hollow fibre membrane. This work reports the continuous measurement of the H2/CO2 separation properties of PBI hollow fibres, prepared as mixed matrix membranes with metal-organic framework (MOF) ZIF-8 as filler. To enhance the scope of the experimental approach, ZIF-8 was synthesized from the transformation of ZIF-L upon up-scaling the MOF synthesis into a 1 kg batch. The effects of membrane healing with poly(dimethylsiloxane), to avoid cracks and non-selective gaps, and operation conditions (use of sweep gas or not) were also examined at 200°C during approximately 51 days. In these conditions, for all the membrane samples studied, the H2 permeance was in the 22–47 GPU range corresponding to 22–32 H2/CO2 selectivity values. Finally, this work continues our previous report on this type of application (Etxeberria-Benavides et al. 2020 Sep. Purif. Technol.237, 116347 (doi:10.1016/j.seppur.2019.116347)) with important novelties dealing with the use of ZIF-8 for the mixed matrix membrane coming from a green methodology, the long-term gas separation testing for more than 50 days and the study on the membrane operation under more realistic conditions (e.g. without the use of sweep gas)

Microfluidic preparation of thin film composite hollow fiber membrane modules for water nanofiltration: Up-scaling, reproducibility and MOF based layers

Background The commercialization of thin film composite (TFC) hollow fiber (HF) membranes remains challenging owing to issues associated with membrane manufacturing. Methods TFC membranes were synthesized by microfluidic interfacial polymerization of polyamide (PA) on polysulfone hollow fiber (HF) membrane modules. A total of 33 HF membrane modules were prepared with different number of HFs (from 1 to 25) and different lengths (from 10 to 50 cm). They were evaluated in a nanofiltration operation in terms of water permeance and rose Bengal (RB) and MgSO4 rejections. Significant findings Among the 33 modules, 73% showed RB rejections higher than 95%, while 36% of the modules reached rejections above 99%. During the membrane synthesis, different parameters, such as PA monomer concentration, residence time and reaction time, were studied. As a result, the amount of monomer was reduced by ca. 80%. The versatility of microfluidics allowed incorporating hydrophilic metal-organic framework (MOF) ZIF-93 to produce HF modules with PA/MOF bilayered membranes (a continuous layer of MOF between the support and the PA film) which led to an important enhancement of the water permeance from 1.3 (bare PA membrane) to 5.3 L·m−2·h−1·bar−1 (PA/ZIF-93 HF membrane), maintaining RB rejection above 95%

On the improvement of alveolar-like microfluidic devices for efficient blood oxygenation

In this work, we study alveolar-like microfluidic devices with a horizontal membrane arrangement that demonstrate a great potential as small-scale blood oxygenator. The design criteria for the fabricated devices were to maximize the oxygen saturation level and minimize liquid chamber volume while ensuring the physiological blood flow in order to avoid thrombus formation and channel blockage during operation. The liquid chamber architecture was iteratively modified upon analysis of the fluid dynamics by computer modelling. Accordingly, two alveolar type architectures were fabricated, Alveolar Design 1 (AD1) and Alveolar Design 2 (AD2), and evaluated for oxygenation of sheep blood. The attained O2 transfer rate at 1 mL/min of blood flow rate for both devices was rather similar: 123 mL·min-1 ·m-2 and 127 mL·min-1 ·m-2 for AD1 and AD2 microfluidic devices, respectively. Among the studied, AD2 type geometry would lead to the lowest pressure drop and shear stress value upon implementation in a scaled microfluidic artificial lung (µAL) to satisfy oxygenation requirements of a 2.0 kg neonate.Government of Aragon and the Education, Audiovisual and Culture Executive Agency (EU-EACEA) within the EUDIME – ‘Erasmus Mundus Doctorate in Membrane Engineering’ program (FPA 2011-0014, SGA 2012-1719, http://eudime.unical.it). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011 financed by the Instituto de Salud Carlos III with the assistance of the European Regional Development Fund

Understanding blood oxygenation in a microfluidic meander double side membrane contactor

Lung disease is one of the most important causes of high morbidity in preterm infants. In this work, we study a simple and easy to fabricate microfluidic device that demonstrates a great potential for blood oxygenation. A meander type architecture with double side vertical membrane arrangement has been selected as reference model to investigate the oxygenation process. The design criteria for the fabricated devices has been to maximize the oxygen saturation level while ensuring the physiological blood flow in order to avoid thrombus formation and channel blockage during operation. A mathematical model for the oxygen transfer has been developed and validated by the experimental study. The obtained results demonstrate that blood was successfully oxygenated up to approximately 98% of O-2 saturation and that the oxygen transfer rate at 1 mL/min blood flow rate was approximately 92 mL/minm(2). Finally, a sensitivity analysis of the key parameters, i.e. size of the channel, oxygen concentration in the gas phase and oxygen permeation properties of the membrane, is carried out to discuss the performance limits and to settle the guidelines for future developments.The authors would like to acknowledge the financial support from the Government of Aragón and the Education, Audiovisual and Culture Executive Agency (EU-EACEA) within the EUDIME - 'Erasmus Mundus Doctorate in Membrane Engineering' program (FPA 2011-0014, SGA 2012-1719, http://eudime.unical.it). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011 financed by the Instituto de Salud Carlos III with the assistance of the European Regional Development Fund. Authors acknowledge the LMA-INA for offering access to their instruments and expertise