Modular integration and on-chip sensing approaches for tunable fluid control polymer microdevices

228 p.Doktore tesi honetan mikroemariak kontrolatzeko elementuak diseinatu eta garatuko dira, mikrobalbula eta mikrosentsore bat zehazki. Ondoren, gailu horiek batera integratuko dira likido emari kontrolatzaile bat sortzeko asmotan. Helburu nagusia gailuen fabrikazio arkitektura modular bat frogatzea da, non Lab-on-a-Chip prototipoak garatzeko beharrezko fase guztiak harmonizatuz, Cyclic-Olefin-Polymer termoplastikozko mikrogailu merkeak pausu gutxi batzuetan garatuko diren, hauen kalitate industriala bermatuz. Ildo horretan, mikrogailuak prototipotik produkturako trantsizio azkar, erraz, errentagarri eta arriskurik gabeen bidez lortu daitezkeenetz frogatuko da

Precise Integration of Polymeric Sensing Functional Materials within 3D Printed Microfluidic Devices

This work presents a new architecture concept for microfluidic devices, which combines the conventional 3D printing fabrication process with the stable and precise integration of polymeric functional materials in small footprints within the microchannels in well-defined locations. The approach solves the assembly errors that normally occur during the integration of functional and/or sensing materials in hybrid microfluidic devices. The method was demonstrated by embedding four pH-sensitive ionogel microstructures along the main microfluidic channel of a complex 3D printed microfluidic device. The results showed that this microfluidic architecture, comprising the internal integration of sensing microstructures of diverse chemical compositions, highly enhanced the adhesion force between the microstructures and the 3D printed microfluidic device that contains them. In addition, the performance of this novel 3D printed pH sensor device was investigated using image analysis of the pH colour variations obtained from photos taken with a conventional camera. The device presented accurate and repetitive pH responses in the 2 to 12 pH range without showing any type of device deterioration or lack of performance over time.This research was founded by the University of the Basque Country (ESPPOC 16/65 and PIF16/204), “Ministerio de Ciencia y Educación de España” grant PID2020-120313GB-I00/AIE/10.13039/501100011033, and “Gobierno Vasco” grant IT1633-22

Microtechnologies for Cell Microenvironment Control and Monitoring

A great breadth of questions remains in cellular biology. Some questions cannot be answered using traditional analytical techniques and so demand the development of new tools for research. In the near future, the development of highly integrated microfluidic analytical platforms will enable the acquisition of unknown biological data. These microfluidic systems must allow cell culture under controlled microenvironment and high throughput analysis. For this purpose, the integration of a variable number of newly developed micro- and nano-technologies, which enable control of topography and surface chemistry, soluble factors, mechanical forces and cell-cell contacts, as well as technology for monitoring cell phenotype and genotype with high spatial and temporal resolution will be necessary. These multifunctional devices must be accompanied by appropriate data analysis and management of the expected large datasets generated. The knowledge gained with these platforms has the potential to improve predictive models of the behavior of cells, impacting directly in better therapies for disease treatment. In this review, we give an overview of the microtechnology toolbox available for the design of high throughput microfluidic platforms for cell analysis. We discuss current microtechnologies for cell microenvironment control, different methodologies to create large arrays of cellular systems and finally techniques for monitoring cells in microfluidic devices.E.A.-H. acknowledges funding from the Basque Government, Department of Education, for predoctoral fellowship 2016. M.G.-H. acknowledges funding from the University of the Basque Country UPV/EHU, PIF16/204 predoctoral fellowship "call for recruitment of research personnel in training". J.E.-E. acknowledges funding from the University of the Basque Country UPV/EHU, postdoctoral fellowship ESPPOC 16/65 "Call for recruitment and specialization of Doctor Researchers 2016". M.M.D.P. and L.B.-D., acknowledge funding support from University of the Basque Country UPV/EHU, UFI11/32, and from Gobierno Vasco under Grupos Consolidados with Grant No. IT998-16. F.B.-L. acknowledges funding support from the Ramon y Cajal Programme (Ministerio de Economia y Competitividad), Spain. F.B.-L. and L.B.-D. acknowledge funding support from the European Union's Seventh Framework Programme (FP7) for Research, Technological Development and Demonstration under Grant agreement No. 604241 as well as Gobierno Vasco, Dpto. Industria, Innovacion, Comercio y Turismo under ELKARTEK 2015 with Grant No. KK-2015/0000088

Modular integration and on-chip sensing approaches for tunable fluid control polymer microdevices

228 p.Doktore tesi honetan mikroemariak kontrolatzeko elementuak diseinatu eta garatuko dira, mikrobalbula eta mikrosentsore bat zehazki. Ondoren, gailu horiek batera integratuko dira likido emari kontrolatzaile bat sortzeko asmotan. Helburu nagusia gailuen fabrikazio arkitektura modular bat frogatzea da, non Lab-on-a-Chip prototipoak garatzeko beharrezko fase guztiak harmonizatuz, Cyclic-Olefin-Polymer termoplastikozko mikrogailu merkeak pausu gutxi batzuetan garatuko diren, hauen kalitate industriala bermatuz. Ildo horretan, mikrogailuak prototipotik produkturako trantsizio azkar, erraz, errentagarri eta arriskurik gabeen bidez lortu daitezkeenetz frogatuko da

On-demand generation and removal of alginate biocompatible microvalves for flow control in microfluidics

[EN] This paper describes, for the first time, the use of alginate hydrogels as miniaturised microvalves within microfluidic devices. These biocompatible and biodegradable microvalves are generated in situ and on demand, allowing for microfluidic flow control. The microfluidic devices were fabricated using an origami inspired technique of folding several layers of cyclic olefin polymer followed by thermocompression bonding. The hydrogels can be dehydrated at mild temperatures, 37◦C, to slightly open the microvalve and chemically erased using an ethylenediaminetetraacetic acid disodium salt (EDTA) solution, to completely open the channel, ensuring the reusability of the whole device and removal of damaged or defective valves for subsequent regeneration.FBL acknowledges the Ramón y Cajal Programme (Ministerio deEconomía y Competitividad), Spain. This project has received fund-ing from the European Union´ıs Seventh Framework Programme(FP7) for Research, Technological Development and Demonstrationunder grant agreement no. 604241. FBL personally acknowledgesto Elkartek (KK-2015/00088) Grant form the Gobierno Vasco andto Marian M. De Pancorbo for letting him to use her laboratoryfacilities at UPV/EHU

Diagnosi azkarrera bideratutako gailu mikro-fluidikoen garapen eta azterketa

This work presents a new concept of a hybrid Point-of-Care (POC) device developed for the detection of cancer biomarkers in blood, circulating DNA, for early cancer diagnostics. The device is composed of both, paper and polymeric based self-powered microfluidic structures and it includes several modules with different functions: sample preparation, signal amplification and detection. This POC device will en-able in situ analysis and quick delivery of results, as well as a low cost tool for diagnostics which could impact clinical decision making and personalized medicine.; Lan honetan minbiziaren diagnosi goiztiarrerako eta tratamenduen ego-kitzapenerako kontzeptu berri bat aurkezten da, non gailu hibrido miniaturizatu batekin odoleko DNA zirkulatzailea analizatuz, kasuan kasuko mutazioaren presentziarik ote dagoen ezagutu nahi den. Egitura hibridodun gailua paperezko zein material polime-rikozko mikro-egituraz osatuta egongo da, eta laginaren prestakuntzarako, seinalearen anplifikaziorako eta detekziorako modulu ezberdinak izango ditu. Halaber, analisiak in situ egin eta emaitzak denbora gutxian eskuratzeko aukera emango digu, kostu gu-txiko analisiekin pazientearen jarraipen egokituago bat egin ahal izateko

Large Volume Self-powered Disposable Microfluidics by the Integration of Modular Polymer Micropumps with Plastic Microfluidic Cartridges

Microfluidic microsystems are often designed to analyse samples of small volume of fluid, however, some applications require the analysis of larger volumes. The ideal miniaturized microfluidic analytical device should be autonomous and capable of integrating all the required functions within a single fluidic network. While a number of self-powered microfluidic networks designs are available, the autonomous manipulation of large sample volumes in microsystems is still a challenge. We have developed a universal self-powered microfluidic architecture by combining polymeric micropumps and plastic microfluidic cartridges, which may be adapted to a large range of volume of fluid. Our polymeric micropumps were able to trigger flow rates from 0.25 to 20 L·min-1 during more than 40 minutes, moving over 800 microliters of fluid. A number of fluidic operations were demonstrated, including: mixing, aliquoting, waste storage and auto-draining of the microfluidic channels. Finally, a self-powered cartridge for the separation of plasma from whole blood was successfully validated, demonstrating that this constitutes a universal scheme to process a wide range of fluid volumes, an unprecedented fact in self-powered microfluidics.The authors would like to acknowledge the University of the Basque Country (ESPPOC 16/65), the Gobierno de España, Ministerio de Economia y Competitividad, with grant no. BIO2016-80417-P. The authors acknowledge funding support from Gobierno Vasco, Dpto. Industria, Innovación, Comercio y Turismo under ELKARTEK 2017 with grant no. KK-2017/0000088, and Gobierno Vasco Dpto. Educación for the consolidation of the research groups (IT1271-19). L.B.D. and F.B.L. personally acknowledge funds from the DNASURF (H2020-MSCA-RISE-778001) project

Type 1 Diabetes Mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets

Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft volumes that can enhance the host’s immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device. APA microcapsules demonstrated higher mechanical integrity and stability than A microcapsules, showing better pseudoislets viability and biological function. Importantly, we obtained a reduction of the graft volume of 77.5% for A microcapsules and 78.6% for APA microcapsules. After subcutaneous implantation of induced diabetic Wistar rats with magnetically purified APA microencapsulated pseudoislets, blood glucose levels were restored into normoglycemia (< 200 mg/dL) for almost 17 weeks. In conclusion, our described microfluidic magnetic sorting device represents a great alternative approach for the graft volume reduction of microencapsulated pseudoislets and its application in T1DM disease.University of the Basque Country UPV/EHU (Spain) (EHUa16/06 to L.SB, and ESPPOC 16/65), the Basque Country Government (Spain) (Grupos Consolidados with Grant N° IT907-16 to JL. P, Elkartek with Grant N°KK-2017/ 0000088 and RIS3 with Grant N°307616FKA4) and the Spanish Government (Spain) (RYC-2012-10796). Authors also wish to thank the intellectual and technical assistance from the ICTS “NANBIOSIS”, more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country UPV/EHU, Prof. Maechler from the University of Geneva Medical Center for providing the INS1E cell line, Adhesive Research for providing PSA sheets and Prof. Martínez de Pancorbo for her laboratory facilities at University of the Basque Country UPV/EHU