News U8

Non-invasive glucose sensing in tears

Currently numerous medical diagnoses or follow-ups of many diseases are carried out by conventional methods such as clinical tests in laboratories and hospitals, being these invasive, slow and expensive.

Thanks to advances in technology, Point-of-Care (PoC) devices allow testing and monitoring of a multitude of biomedical markers or parameters in order to: (i) reduce costs, save time and reduce the complexity of the analysis; (ii) allow analysis in medical centers, primary care centers or even at home and (iii) real-time results allow to accelerate the decision-making on a patient. Thus, PoC devices respond to a demand from medical doctors as is the efficient health service thanks to the rapid availability of the laboratory analysis results.

In this context, a team of scientists from Barcelona have collaboratively developed a non-enzymatic sensor for glucose sensing in a non-invasive manner in tears. The work, cover of the magazine Applied Materials Today, demonstrates the proof of concept of the functionality of this electrochemical sensor.

Ana Moya, researcher of the CIBER-BBN and member of the research group of the Institute of Microelectronics of Barcelona CSIC, responsible for the sensors manufacture explains how these devices are fabricated by the innovative technology of Printed Electronics. Specifically, electrochemical glucose sensors have been manufactured by printing microelectrodes using Inkjet Printing Technology (IJP) on a flexible substrate of polyethylene terephthalate (PET) with silver and gold inks. The IJP dispenses small drops of the material to be printed under a graphic environment. This direct writing approach without the need of masks drastically reduces the total manufacturing time and cost of the sensors, and facilitates iterative design changes during sensor development.

Gemma Gabriel, Scientific Coordinator of NANBIOSIS U8. Micro–Nano Technology Unit and researcher of the CIBER-BBN in the Institute of Microelectronics of Barcelona CSIC, explains how the IJP is a promising and low-cost alternative to conventional microelectronic manufacturing technology, which will allow the creation of a multitude of highly specific sensor platforms and sensitive with analytical application in the medical area. In line with the research group, the advance in novel functional materials with these technologies is of paramount importance for the development of new generations of disposable sensor platforms to solve a wide range of applications in the medical field.

Agostino Romeo, member of the Smart nano-bio-devices Group at the Institut de Bioingenieria de Catalunya (IBEC) led by Samuel Sánchez, highlights how the use of copper oxide microparticles (CuO) has allowed the successful modification of the electrodes, leading to a sensitive, stable and cost-effective platform for the non-enzymatic detection of glucose. The selectivity, reproducibility and life time provided by this functionalization with CuO has shown that these sensors are reliable tools to perform a personalized diagnosis of the health of an individual.

The good sensitivity and selectivity of the electrochemical sensor presented here has made it particularly suitable for the non-invasive sensing of glucose in tears. This has been demonstrated in this study in which the glucose level in human samples has been measured and correlated with commercial devices.

All this allows us to foresee that the use of this type of sensors for the diagnosis of eye diseases such as diabetes, where it is possible to achieve a painless and non-invasive monitoring, has a great opportunity in a disease as widespread in the world as it is this one. Thus, versatility, short manufacturing time and low cost makes IJP a valuable technology alternative to traditional sensor manufacturing techniques. Thus, the technology here presented can be adapted for the detection of many other substances of interest in other fluids such as saliva or urine.

Article of Reference:

Romeo A, Moya A, Leung TS, Gabriel G, Villa R, Sánchez S. “Inkjet printed flexible non-enzymatic glucose sensor for tear fluid analysis“. Applied Materials Today 10 (2018) 133-141

(DOI)

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NANBIOSIS ICTS invites groups and companies to discuss Smart Biomaterials and devices for Drug Delivery

On February 22nd, the National School of Health of the Carlos III Health Institute hosted the forum on Smart Biomaterials and biomedical devices for applications in drug delivery and regenerative medicine, organized by the ICTS Nanbiosis, an infrastructure shared by the CIBER-BBN and the Center of Minimally Invasive Surgery Jesus Usón (CCMIJU). This is the first groups/companies meeting organized by Nanbiosis, in which about 70 B2B meetings were held.

The meeting brought together about 40 participants from 14 research groups (from the CIBER-BBN and the CCMIJU) and 10 companies, which discussed the latest advances in the research lines developed by the groups and platforms of Nanbiosis and on the needs and demands of the industry in smart biomaterials and devices for targeted drug delivery and regenerative medicine.

Jesus Izco, Coordinator of Nanbiosis, presented the new “Cutting-Edge Biomedical Solutions“, soon available on the ICTS website. These are integrated solutions to advanced challenges in nanomedicine, biomaterials, medical device, and diagnostic that can be developed by several units under a one-stop shop model, optimized with the experience and scientific and technical knowledge of the research groups of excellence that manage the involved units. Some of the Cutting-edge biomedical solutions presented in the meeting were preclinical validation of biomaterials, mechanical and surface characterization, biocompatibility and studies of biofilm formation and infections.

The CIBER-BBN prsentations were: “Instructive materials for regenerative medicine” by Miguel Ángel Mateos (NANBIOSIS U5 IP: Elisabeth Engel); “Molecular biomaterials for drug delivery and biomedical applications” byNathaly Veronica Segovia (NANBIOSIS U6 / IP Jaume Veciana and Nora Ventosa); “Advances with micro-nano technologies for in vitro devices and point of care” by Rosa Villa (NANBIOSIS U8 ); “Development of new dosage forms for advanced therapies based on new biomaterials” by José Luis Pedraz (NANBIOSIS U10); “Contact lenses functionalized for the prevention of corneal infections” by Jordi Esquena (NANBIOSIS U12 / IP Carlos Rodríguez); “Combined in-silico and in-vitro models of the cell microenvironment and drug delivery effects in cancer and tissue engineering applications” by Fany Peña (NANBIOSIS U13 / IP Miguel Á. Martínez); “Surface of the biomaterial: the first contact with our body” by Marisa González (NANBIOSIS U16 ); “Use of biomaterials for the repair of soft tissue defects” by Bárbara Pérez Khöler (NANBIOSIS U17 / IP J M. Bellón and Gemma Pascual); “Controlled release systems based on mesoporous materials with molecular doors for applications in therapy and diagnosis” by Ramón Martínez Máñez (NANBIOSIS U26); “New intelligent devices and biomaterials for the treatment of pathologies of the retina and the nervous system” (Eduardo Fernández); and “Near-infrared responsive scaffolds for biomedical applications” (Nuria Vilaboa).

On the part of the CCMJU, the presentations were the following: “Application of Mesenchymal Stem Cells in preclinical models for surgical and cardiovascular research” by Javier García Casado (NANBIOSIS U14); “Regenerative medicine in animal models of cutaneous healing and diabetic models” by Beatriz Moreno (NANBIOSIS U19); “Preclinical studies of biomaterials” by Idoia Díaz-Güemes (NANBIOSIS U21 /IP: FM Sánchez Margallo); “Porcine model of myocardial infarction as a translational research platform in regenerative medicine” by Verónica Crisóstomo (NANBIOSIS U24).

In the turn of the companies, they presented some collaboration opportunities AJL, i-Vascular, Praxis Pharmaceutical, Technical Proteins Nanobiotechnology and REGEMAT 3D; and they also participated in the Rovi, Viscofan, Biomag and Biogelx Laboratories forum.

These meetings, where links are established between research groups and companies, address issues of business and scientific interest, allowing direct contacts between researchers and business managers.

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Microfluidic device that reproduces the blood-retinal barrier

The use of In vitro testing with living cells as an alternative to animal research has limitations like the difficulty to reproduce the interaction of cells. To overcome it, scientists are working on the development of systems that simulate and reproduce functions of tissues and organs in conditions very similar to reality. They are called organ-on-a-chip, which include microenvironments and microarchitectures that simulate the state of tissues and living organs.

Scientists of NANBIOSIS Unit 8 have published in an article, cover of the magazine “Lab on a Chip”, the “proof of concept” of a microfluidic device that reproduces the blood-retinal barrier, that is, a microchip that allows us to reproduce what happens ” in vivo ‘in the retina. This device can be an essential tool that revolutionizes experimentation ‘in vitro’.

José Yeste, researcher of the CIBER-BBN, explains that the micro device consists of several parallel compartments, in which different types of cells have been cultivated to emulate the structure of cellular layers of the retina. They are endothelial cells, that is, they form the internal part of the barrier, in contact with the blood capillaries, through which oxygen and nutrients reach the retina. In addition, it is also composed of neuronal cells (which form the neuroretina), and pigment epithelial cells, which constitute the outer layer. The compartments are interconnected in their lower part by a network of micro-grooves, so as to allow an intercellular communication through the exchange of signalling molecules between cells. Thus, cells can send their signals to others and interact, much like they would in a living organism. In addition, the micro device allows the endothelial cells to be subjected to the mechanical stimulus induced by the flow to emulate a more physiological microenvironment.

“Within the body, the endothelial cells that line the inside of blood vessels are subject to the mechanical stimulation of blood circulation. In cell cultures that do not reproduce this flow, the cells are as ‘lethargic’, and do not respond in the same way they would in real conditions, “explains Rosa Villa, Scientific Director of NANBIOSIS Unit 8 and leader of the group of Biomedical Applications of the Microelectronics Institute of Barcelona of the CSIC.

Scientists have evaluated the correct formation of the blood-retinal barrier by performing permeability, electrical resistance tests, as well as protein expression of tight junctions between cells. These tests were intended to verify that the barrier is well formed, that it has closed but maintains the natural permeability, sufficient to allow the passage of nutrients and oxygen, and that the cells are in contact and interact with each other.

This work has been developed in the ICTS NANBIOSIS, more specifically in Unit 8 of Micro-Nano Technology located in the IMB-CNM. It is also part of the results of the CIBER intramural project called Micro BRB: Microfluidic model of retinal neurovascular unit to identify new therapeutic targets in diabetic retinopathy (2016-2017) in wich also participates Unit 3 of NANBIOSIS

Source: http://noticiasdelaciencia.com/not/27155/un-microchip-microfluidico-reproduce-la-barrera-de-la-retina-humana/

Article of reference:

A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood–retinal barrier. Jose Yeste, Marta arcía-Ramírez, Xavi Illa, Anton Guimerà, Cristina Hernández, Rafael Simó and Rosa Villa. DOI: 10.1039/C7LC00795GLab Chip, 2018, 18, 95-105

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Graphene transistors as eficient transducers for electrocorticography

Researchers of Micro-Nano Technologies Unit (U8) of NANBIOSIS, are co-authors of a new paper published in Advanced Functional Materials. Neuroelectronic interfaces bridge the central nervous system to the outside world and hold great potential for functional restoration in persons with paralysis, other forms of motor dysfunction, or limb loss. Neuroscientists and neurosurgeons are thus looking for technologies that could ideally record the whole brain with a high spatial and temporal resolution. Electrocorticography (ECoG), the practice of placing arrays of large-diameter electrodes (few millimeters) directly on the cortex is the current clinical solution to obtaining brain recordings with high temporal resolution.

Recent research from the CIBER-BBN and IMB-CNM Biomedical Applications group (IP Rosa Villa) coordinator of NANBIOSIS Unit 8, in collaboration with ICN2 (IP JA Garrido) , IDIBAPS (IP MV Sanchez Vives) and INSERM (IP B Yvert) groups, has focused on the development of graphene technology for electrocorticography. Specifically, flexible graphene transistor arrays have been fabricated and applied to the in vivo measurement of local field potentials.

Graphene is one of the most promising material candidates for neural interfacing thanks to its biocompatibility, low dimensionality and mechanical properties. Additionally, graphene exhibits extraordinary electrical properties such as high carrier mobility and chemical stability, features that only few materials can offer therefore helping to create a very intimate interface between the tissue and the transducing system.

However, previous in vivo studies using single layer CVD graphene have used an electrode configuration. Instead, here they propose the use of a transistor configuration. The main reason for this choice is certainly the local preamplification inherent to a transistor. As a consequence, less environmental noise is picked by the device.

Their work presents a complete description of the fabrication technology, the operation of graphene solution-gated field-effect transistors (SGFET) in saline solution and of the custom characterization electronic system. The devices are finally used in in vivo experiments in which the transconductance and noise are first characterized during slow-wave activity followed by the recording of visual and auditory evoked activity as well as of synchronous activity in a rat model of epilepsy. An in-depth comparison of the signal-to-noise ratio of graphene SGFETs with that of platinum black electrodes confirms that graphene SGFET technology is approaching the performance of state-of-the art neural technologies.

Full details of the fabrication, characterization and in vivo performance of the flexible graphene transistor probes can be found in the paper below.

Hébert, C., et al., Flexible Graphene Solution‐Gated Field‐Effect Transistors: Efficient Transducers for Micro‐Electrocorticography. Advanced Functional Materials, 2017.

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Inkjet-Printed Sulfide-Selective Electrode

Gemma Gabriel, Scientific Coordinator of Unit 8 of NANBIOSIS is coauthor of the article “Inkjet-Printed Sulfide-Selective Electrode” recently publish by ACS Publications in Analitical Chemistry. Anal. Chem., 2017, 89 (22), pp 12231–12236

DOI: 10.1021/acs.analchem.7b03041

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Posters presentation by NANBIOSIS Units in CIBER-BBN ANNUAL CONFERENCE 2017

Last 13 and 14 of November, CIBER-BBN has celebrated its 11th Annual Conference in Hotel Santemar in Santander. In this conference there was a poster session with the participation of the following Units of NANBIOSIS. Special mention deserves Unit 1 with Neus Ferrer as Director and Paolo Saccardo as Coordinator (in the picture):

Posters:

U1. Protein Production Platform (PPP):

Engineering protein complexes as nano- or micro-structured vehicles or drugs for human and veterinary medicine. Ugutz Unzueta, Naroa Serna, Laura Sánchez-García, José Vicente Carratalá, Olivia Cano-Garrido, Mercedes Márquez, Paolo Saccardo, Rosa Mendoza, Raquel Díaz, Héctor, López-Laguna, Julieta Sánchez, Anna Obando, Amanda Muñoz, Andrés Cisneros, Eric Voltà, Aida Carreño, José Luis Corchero, Neus Ferrer-Miralles, Esther Vázquez, Antonio Villaverde.

Units U1. Protein Production Platform (PPP) and U18. Nanotoxicology Unit:

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles. Mireia Pesarrodona, Eva Crosa, Rafael Cubarsi, Alejandro Sanchez-Chardi, Paolo Saccardo, Ugutz Unzueta, Fabian Rueda, Laura Sanchez-Garcia, Naroa Serna, Ramón Mangues, Neus Ferrer Miralles, Esther Vázquez, Antonio Villaverde.

Units U3. Synthesis of Peptides Unit, U6. Biomaterial Processing and Nanostructuring Unit, and **U20. In Vivo Experimental Platform**:

Synthesis of different length monodisperse COL-PEG-PEPTIDE to increase biodisponibility of multifunctional nanovesicles for Fabry’s desease. Edgar Cristóbal-Lecina; Daniel Pulido; Solène Passemard; Elizabet González-Mira; Jaume Veciana; Nora Ventosa; Simó Schwartz; Ibane Abasolo; Fernando Albericio and Miriam Royo.

Units U13. Tissue & Scaffold Characterization Unit and U17. Confocal Microscopy Service::

Preclinical behavior of medium-chain cyanoacrylate glue with two different surgical application forms for mesh fixation in abdominal wall repair. Gemma Pascual, Bárbara Pérez-Köhler, Marta Rodríguez, Claudia Mesa-Ciller, Ángel Ortillés, Estefanía Peña, Begoña Calvo, Juan M. Bellón.

Units U27. High Performance Computing and U8. Micro – Nano Technology Unit:

Inspiration and Expiration Dynamics in Acute Emotional Stress Assessment. Javier Milagro, Eduardo Gil, Jorge M. Garzón-Rey, Jordi Aguiló, Raquel Bailón.

U5. Rapid Prototyping Unit:

Poly-DL-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells. Ana de la Mata, Miguel Ángel Mateos-Timoneda, Teresa Nieto-Miguel, Sara Galindo, Marina López-Paniagua, Xavier Puñet, Elisabeth Engel, Margarita Calonge.

U6. Biomaterial Processing and Nanostructuring Unit:

Strategy for engineering myoglobin nano-traps for biomedical sensing technology. E. Laukhina, O. V. Sinitsyna, N. K. Davydova, V. N. Sergeev, A. Gomez, I. Ratera, C. Blázquez Bondia, J. Paradowska, X. Rodriguez, J. Guasch, Jaume Veciana.

Structure and nanomechanics of quatsome membranes. B. Gumí-Audenis, L. PasquinaLemonche, J.A. Durán, N. Grimaldi, F. Sanz, J. Veciana, I. Ratera, N. Ventosa and M.I. Giannotti

U7. Nanotechnology Unit:

Bioreceptors nanostructuration study for early detection of Alzheimer. José Marrugo, Dr. Samuel Dulay, Dr. Mònica Mir, Prof. Josep Samitier.

RGD dendrimer-based nanopatterns promote chondrogenesis and intercellular communication for cartilage regeneration. Ignasi Casanellas, Anna Lagunas, Iro Tsintzou, Yolanda Vida, Daniel Collado, Ezequiel Pérez-Inestrosa, Cristina Rodríguez, Joana Magalhães, José A. Andrades, José Becerra, Josep Samitier.

Long-range electron transfer between redox partner proteins. Anna Lagunas, Alejandra GuerraCastellano, Alba Nin-Hill, Irene Díaz-Moreno, Miguel A. De la Rosa, Josep Samitier, Carme Rovira, Pau Gorostiza.

U8. Micro – Nano Technology Unit:

Miniaturized multi-sensing platform for pH and Dissolved Oxygen monitoring in Organ-On-aChip systems. M. Zea, A. Moya, I. Gimenez, R. Villa, G. Gabriel.

Electrochemical characterization of SWCNTs based microelectrodes fabricated by inkjet printing. M. Mass, A. Moya, G. Longinotti, M. Zea, M. Muñoz, E. Ramon, L. Fraigi, R. Villa, G. Ybarra, G. Gabriel.

U9. Synthesis of Nanoparticles Unit:

In vivo imaging and local persistance of polymeric micro- and nanomaterials labelled with the near infrared dye IR820. Isabel Ortiz de Solórzano, Gracia Mendoza, Inmaculada Pintre, Sara García-Salinas, Víctor Sebastián, Vanesa Andreu, Marina Gimeno, Manuel Arruebo.

U10. Drug Formulation:

Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids. Santiago Grijalvo, Adele Alagia, Gustavo Puras, Jon Zárate, Judith Mayr, José Luis Pedraz, Ramon Eritja

U12. Nanostructured liquid characterization unit:

Perfluorocarbon-loaded Nanocapsules from Nano-emulsion Templates as Microbubble Precursors for Biomedical Applications. G. Calderó, A. González, M. Monge, C. Rodríguez-Abreu, M.J.García-Celma, C. Solans.

Biodistribution study of polymeric drug-loaded nanoparticles in murine model. Marta Monge, Aurora Dols, Stephane Fourcade, Aurora Pujol, Carlos Rodríguez-Abreu, Conxita Solans.

U16. Surface Characterization and Calorimetry Unit:

Behavior and a comparative study between tantalum and titanium alloy implant surfaces against bacterial adhesion. M.A. Pacha-Olivenza, M.L. González-Martín.

Bacterial adhesion on calcium ion-modified titanium implant surfaces. M.A. Pacha Olivenza, R. Tejero, M. Delgado-Rastrollo, M.L. González-Martín.

Bioactive coatings to promote tissue regeneration and ingrowth into 3D custom-made porous titanium endoimplants (COATREG-3D). Santos-Ruiz L; Granados JF; Ruiz F; Yáñez JI; González A; Cabeza N; Vida Y; Pérez-Inestrosa E; Izquierdo-Barba I; Vallet-Regí M; Rubio J; Orgaz F; Rubio N; González ML; Peris JL; Monopoli D; Becerra J.

U17. Confocal Microscopy Service:

Subcutaneous implantation of a biodegradable apatite/agarose scaffold: biocompatibility and osteogenesis characterization in a rat model. Natalio García-Honduvilla, Gemma Pascual, Miguel A. Ortega, Alejandro Coca, Cynthia Trejo, Jesús Román, Juan Peña, María V. Cabañas, Julia Buján, and María Vallet-Regí.

U25. NMR: Biomedical Applications I:

Dual T1/T2 NCP-based novel contrast agents for brain tumor MRI: a preclinical study. Suarez, S; Arias-Ramos, N; Candiota, AP; Lorenzo, J; Ruiz-Molina, D; Arús, C; Novio, F.

Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide. Ferrer-Font, L; Arias-Ramos, N; Lope-Piedrafita, S; Julià- Sapé, M; Pumarola, M; Arús, C; Candiota, AP.

U26. NMR: Biomedical Applications II:

Gated nanodevices for innovative medical therapies. Maria Alfonso, Irene Galiana, Beatriz Lozano, Borja Diaz de Greñu, Cristina de la Torre, Andrea Bernardos, Sameh El Sayed, Daniel MuñozEspin, Miguel Rovira, José Ramón Murguía, Manuel Serrano, Ramón Martínez-Máñez.

NANOPROBE: Gated sensing materials and devices for the detection of infectious diseases and urological cancer. Ángela Ribes, Luís Pla, Sara Santiago-Felipe, Alba Loras-Monfort, M.Carmen Martínez-Bisbal, Elena Aznar, Guillermo Quintás-Soriano, José Luis Ruiz-Cerdá, María Angeles.

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Non-invasive glucose sensing in tears

NANBIOSIS ICTS invites groups and companies to discuss Smart Biomaterials and devices for Drug Delivery

Microfluidic device that reproduces the blood-retinal barrier

Graphene transistors as eficient transducers for electrocorticography

Inkjet-Printed Sulfide-Selective Electrode