Biosensors for bioengineering

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. 

• 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)

• 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, England, FET-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.