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Biosensors for bioengineering

About

The Biosensors for bioengineering group is a junior group under IBEC’s Tenure Track scheme.

Our research is focused on multi tissues organs-on-a-chip (OOC) and more specifically in the metabolic crosstalk within tissues and their relationship with metabolic diseases. Our projects are focused on four key tissues regulating glucose homeostasis, namely, the pancreas, liver, skeletal muscle, and adipose tissue. To achieve this objective, it is necessary a combined interdisciplinary approach.

Biomaterials and tissue engineering research

1) We have several lines of research related with skeletal muscle. Our first approach was with C2C12 mice cell line. We evaluated the influence of mechanical stiffness and geometrical confinement on the 3D culture of myoblast-laden chemically modified gelatin photo-cross linkable composite hydrogels in terms of in vitro myogenesis.

2) Encapsulation of beta-cells like from human skin fibroblast (collaboration with IDIBAPS). This work addresses two critical issues in the design of an efficient beta-cell replacement therapy: an accessible cell source for generation of substitute beta-cells and an adequate delivery device for transplantation. On one hand, we propose to generate transplantable functional insulin-producing beta-cells from fibroblasts through direct reprogramming strategies that bypass the pluripotent iPS stage. On a second objective, we are working in a new system of encapsulating beta-cells like in two steps, microencapsulation to protect cells from immune system and microencapsulation to mechanically protect them and manipulate them.

3) We are developing three-dimensional micro liver models using various biomaterials to recreate the in vivo-like mechanical properties and using hepatocytes and stellate cells. We are collaborating with Grifols company to test some drugs in our model.

4) We have a collaboration project with NovoNordisk to work in new approaches to encapsulate retinal cells.

Biosensing technology:

1) Integrating biosensors in an organ-on-a-chip. We are studying with in situ electrochemical biosensors the release of insulin under the effect of external stimuli, changes in glucose levels and myokines secreted by skeletal muscle (multi-OOC approach).

2) Related with this project we are implementing new biosensors systems. To fully exploit the potential of the organs-on-a-chip, there is a need to interface them to integrated sensing modules, capable to monitor in real-time their biochemical response to external stimuli, like stress or drugs.  The goal of this project is to answer this need, by developing a novel technology based on integrating localized surface plasmon resonance (LSPR) sensing module to organs-on-a-chip devices to monitor disease and evaluate drug response in organs-on-a-chip models.

3) Myotonic dystrophy type 1 (DM1) (collaboration with Hospital de la Fe and INCLIVA, Valencia, Spain). We have developed human skeletal muscle micro physiological tissues using micro molding technology and we have integrated them with amperometric biosensors to study the inflammatory process related with electrical and chemical stimuli. We have used transdifferentiated skin fibroblast human cells from DM1 patients and healthy human. Using this platform, we have started to evaluate different treatments, to screen drugs and to evaluate doses.

4) NMR integrated with OOC. The objective of this project is to develop a new technology based on magnetic resonance spectroscopy and imaging using dynamic nuclear polarisation (DNP-MR) integrated with OOC devices to monitor disease and evaluate drug response in OOC models. As a proof-of-concept, this project will fabricate a biomimetic multi OOC integrated device composed of liver spheroids and pancreatic islets and develop the necessary DNP-MR hardware and software to study metabolic diseases and for future drug screening applications. We are working in collaboration with Oxford instrument and Multiwave companies. 

Staff

Projects

NATIONAL PROJECTSFINANCERPI
Development of a “Muscle-on-a-Chip” (MoC) platform for the preclinical evaluation of potential therapies for Duchenne muscular dystrophy (2020-2022)DUCHENNE ESPAÑA, IV Convocatoria Ayudas a Proyectos de InvestigaciónJuanma Fernandez
BLAD · BioLiver Assist Device (2020-2021)AGAUR, Ajuts per a projectes innovadors amb potencial d’incorporació al sector productiu – LLAVORJavier Ramón
INNOTEC- Javier Ramon- Naturfiltr (2021-2023)TECNIOJavier Ramón
ASITOC Atomic-Sensor-Integrated Tissue-On-a-Chip: optically detected biomagnetism to understand muscular diseases (2021-2022)BIST_Barcelona Institute of Science and TechnologyJuanma Fernandez
INTERNATIONAL PROJECTSFINANCERPI
DAMOC · ‘Diabetes Approach by Multi-Organ-on-a-Chip’ (2017-2022)ERCJavier Ramón
BLOC · Benchtop NMR for Lab-on-Chip (2020-2022)European Comission FET-OpenJavier Ramón
PRIVATELY FUNDED PROJECTSFINANCERPI
Tatami · Therapeutic targeting of MBNL microRNAs as innovative treatments for myotonic dystrophy (2019-2022)Fundació bancaria “La Caixa”Javier Ramón
FINISHED PROJECTSFINANCERPI
Programa Faster Future 2020: COVID-19 (2021)FundraisingJavier Ramón
INDUCT · Fabrication of a biomimetic in vitro model of the intestinal tube muscle wall: smooth muscle-on-a-chip (2018-2020)MINECOJavier Ramón

Publications



(See full publication list in ORCID)
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Equipment


Micro and nanofabrication techniques:

  • 3D microstructures on hydrogel materials
  • Mini-bioreactor for 3D cell culture
  • Microelectrodes fabrication
  • Synthesis and chemical modification of polymers and surfaces
  • Dielectrophoretic cells and micro particles manipulation

Characterization techniques:

  • Optical Microscopes (white light/epifluorescence)
  • Electrochemical techniques (Potentiometric/Amperometric/Impedance spectroscopy)
  • Immunosensing techniques (Fluorescence ELISA/Colorimetric ELISA/magneto ELISA)

Equipment:

  • Microfluidic systems (High precision syringe pumps/Peristaltic pumps/Micro valves)
  • Biological safety cabinet (class II)
  • Epifluorescence microscope for live-cell imaging
  • Pulsar – a high-resolution, 60MHz benchtop NMR spectrometer from Oxford Instruments

Access to the Nanotechnology Platform (IBEC Core Facilities): equipment for hot embossing lithography, polymer processing and photolithography, chemical wet etching, e-beam evaporation and surface characterization (TOF-SIMS)
Access to the Scientific and Technological Centers (University of Barcelona): equipment for surface analysis (XPS, AFM, XRD), organic structures characterization (NMR) and microscopy techniques (SEM, TEM, confocal)

Collaborations

  • Prof. Josep Samitier
    IBEC
  • Dr. Elena Martinez
    IBEC
  • Dr. Anna Novials
    Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS)
  • Dr. Ramon Gomís
    Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS)
  • Dr. Eduard Montanya
    The Bellvitge Biomedical Research Institute (IDIBELL)
  • Prof. Enric Bertran
    Physics and Engineering of Amorphous Materials and Nanostructures (FEMAN), Department of Applied Physics, University of Barcelona
  • Dr. Montserrat Costa
    2020, Director Plasma Proteins Research, Bioscience Industrial Group, Grifols, Barcelona Spain
    Collaborative project 
  • Tryfon Antonakakis
    2019, Co-Founder & CEO Multiwave Technologies AG 3 Chemin du
    Pré Fleuri 1228, Geneva Switzerland
    FET-open project 
  • Robert Hardy
    2019,  Project Manager Oxford Instruments plc Abingdon, Oxfordshire, EnglandFET-open project 
  • Dr. Carlos Villaescusa
    2018, Principal Scientist/Specialist, Project Leader, Department of Stem Cell Discovery, Novo Nordisk Denmark
    Collaborative project 

Clinical collaborations

  • Project “TATAMI” funded by Fundación Bancaria “La Caixa” – CaixaHealth program. In this project, we are developing a platform to perform drug screening analysis in human engineered microtissues in close collaboration with Professor Ruben Artero from Instituto de Investigaciones Clínicas de Valencia (INCLIVA) and medical doctor Vilchez from Hospital de la Fe (Valencia) 
  • We are also collaborating with Hospital de Sant Pau (Barcelona), with the group of senior professor Isabel Illa Sendra we are developing human microtissues to study the myasthenia gravis neuromuscular rare disease. 
  • In a Smart Specialization Project (RIS3CAT, ADVANCECAT project), I am working with senior professor Eduard Montanya from Hospital de Bellvitge (Barcelona) to develop transplantable patches of human pancreatic islets. 
  • Finally, we are collaborating with Doctor Jesus Castro from Hospital de la Vall de Hebron (Barcelona) to study chronic fatigue. 

News

The Biosensors for bioengineering group led by Javier Ramón has developed a sensing platform for the in-situ detection of tissue-secreted pro-inflammatory molecules, the so-called cytokines. This new methodology opens a new door in the understanding of metabolic-disorders such those found in muscular diseases, as well as the development of drug-screening applications. Although 40% of total body mass is skeletal muscle tissue, there is no specialized clinical doctor for the treatment of muscular diseases, according to the American Medical Association. The research group of Dr. Javier Ramón at IBEC works to fill this gap between muscle disorders and ad hoc therapies.

Researchers at IBEC develop a bioengineering platform to detect pro-inflammatory molecules in muscular disorders

The Biosensors for bioengineering group led by Javier Ramón has developed a sensing platform for the in-situ detection of tissue-secreted pro-inflammatory molecules, the so-called cytokines. This new methodology opens a new door in the understanding of metabolic-disorders such those found in muscular diseases, as well as the development of drug-screening applications. Although 40% of total body mass is skeletal muscle tissue, there is no specialized clinical doctor for the treatment of muscular diseases, according to the American Medical Association. The research group of Dr. Javier Ramón at IBEC works to fill this gap between muscle disorders and ad hoc therapies.

This weekend Javier Ramon’s European Research Council-funded project, DAMOC, was one of eight highlighted in a special exhibition in Madrid to mark the ERC’s tenth anniversary. Alcobendas’ Museo Nacional de Ciencia y Tecnología (MUNCYT) displayed the most “outstanding” projects led by researchers in Spain as part of a full weekend of activities to celebrate the first decade of the prestigious funding body, which was launched in 2007 by the European Union and has funded nearly 7,000 researchers, among them six Nobel Prize winners.

IBEC researcher’s ERC project highlighted in Madrid exhibition

This weekend Javier Ramon’s European Research Council-funded project, DAMOC, was one of eight highlighted in a special exhibition in Madrid to mark the ERC’s tenth anniversary. Alcobendas’ Museo Nacional de Ciencia y Tecnología (MUNCYT) displayed the most “outstanding” projects led by researchers in Spain as part of a full weekend of activities to celebrate the first decade of the prestigious funding body, which was launched in 2007 by the European Union and has funded nearly 7,000 researchers, among them six Nobel Prize winners.

IBEC’s Dr. Javier Ramón is one of just six researchers in Catalonia to have been awarded a 2016 Starting Grant by the European Research Council (ERC). The senior researcher in the Biomimetic Systems for Cell Engineering group won funding for his project ‘Diabetes Approach by Multi-Organ-on-a-Chip’ (DAMOC) from Europe’s most prestigious funding body. With the support, which will last for up to five years, Javier will start a new line to design a innovative new tool to test drugs for diabetes. As well as improving drug testing approaches, the multi-organ-on-a-chip device will provide new therapies to prevent the loss of beta cell mass and defects in the glucose uptake in skeletal muscle associated with type 2 diabetes. “This project will give me the opportunity to have a multidisciplinary group of researchers working together from the beginning in a synchronized way, the most rewarding experience that a researcher can have,” he says.

ERC funding for new diabetes approach at IBEC

IBEC’s Dr. Javier Ramón is one of just six researchers in Catalonia to have been awarded a 2016 Starting Grant by the European Research Council (ERC). The senior researcher in the Biomimetic Systems for Cell Engineering group won funding for his project ‘Diabetes Approach by Multi-Organ-on-a-Chip’ (DAMOC) from Europe’s most prestigious funding body. With the support, which will last for up to five years, Javier will start a new line to design a innovative new tool to test drugs for diabetes. As well as improving drug testing approaches, the multi-organ-on-a-chip device will provide new therapies to prevent the loss of beta cell mass and defects in the glucose uptake in skeletal muscle associated with type 2 diabetes. “This project will give me the opportunity to have a multidisciplinary group of researchers working together from the beginning in a synchronized way, the most rewarding experience that a researcher can have,” he says.

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