New biosensor detects inflammatory marker in muscle with high sensitivity

In a recent publication in the journal Nanophotonics, IBEC researchers present a new biosensor for the direct and sensitive detection of the protein interleukin-6 in muscle, an indicator of inflammation and potential disease, proving the high performance of the device on bioengineered 3D skeletal muscles. This new approach may result in a promising tool for measuring the efficacy of drug candidates for diseases where inflammation is present such as muscular dystrophy.

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Left: Photography of a 70 nm Au evaporated Blu-Ray disc substrate and the characteristic diffraction of light.  Right: Representative confocal microscopy images of 3D skeletal muscle microtissues.

What do diseases like cancer, rheumatoid arthritis, diabetes, covid-19, depression or muscular dystrophy have in common? Despite their profound differences, they are each linked to inflammatory processes triggered by a common culprit: interleukin-6 (IL-6). This biomolecule belongs to a broad family of proteins known as cytokines, which are involved in the immune response of the body. Since its levels are often elevated in infection, inflammation, and auto-immune diseases, it’s a reliable gauge of the severity of numerous diseases. On the other hand, reduced levels can show to what extent a treatment is working. Therefore, being able to quickly and accurately measure cytokines such as IL-6 is crucial in drug discovery and testing. Unfortunately, it’s often difficult to do so since it’s present at extremely low concentrations. 

Now, IBEC’s researchers from the Biosensors for Bioengineering Group at IBEC presents in a new study published by the journal Nanophotonics, the harnesses nanoengineering for the fast, accurate, easily reproducible and cost-effective detection of IL-6. The study was senior-authored by Group Leader Javier Ramón Azcón and first-authored by Postdoctoral Researcher Gerardo López Muñoz, with contributions from fellow group members Juanma Fernandez CostaMaria Alejandra Ortega Machuca, Jordina Balaguer-Trias and Eduard Martin-Lasierra. 

Improving sensitivity and reproducibility 

In this work, a new biosensor based on industrially produced Blu-Ray was developed to detect the protein IL-6 in bioengineered 3D skeletal muscles. Firstly, the researchers bioengineered 3D skeletal muscle tissues by using a photomold encapsulation technique that they had previously developed. Then, they induced the release of different concentrations of IL-6 in the samples, each of which they then analysed with their biosensor. The biosensor, which is based on a plasmonic nanostructure — a particle whose electron density can couple with electromagnetic radiation of wavelengths that are far larger than the particle itself — showed increased sensitivity when measuring variations in IL-6 concentrations, even when they were extremely low.  

Indeed, this technique outperformed other plasmonic and nanoplasmonic biosensing platforms by at least one order of magnitude in the detection of IL-6 in muscle tissue. Its sensitivity was similar to that of electrochemical biosensing platforms, but it offers the additional advantage of being direct and label-free. Furthermore, thanks to the use of industrial scale fabricated 1D nanocrystals present in Blu-ray, it could become a highly reproducible multichannel sensor.  

A promising tool for drug assessment 

The authors identify further opportunities to finetune their technique, including the use of other plasmonic materials such as graphene or nanoporous gold, to extend its application to a wider array of biomarkers. 

Overall, their approach offers a new, direct, label-free and real-time quantification of biomarkers that minimizes set-up complexity. It could be used to measure biomarkers in bioengineered 3D tissues or organoids with applications in the early screening of lead drug candidates for numerous diseases. Future studies will focus on real-time and multiplexed biosensing for developing monitoring platforms for cell cultures.  

Our technique outperformed other biosensing platforms of this type by at least one order of magnitude in the detection of IL-6 in muscle tissue.  

Javier Ramon, ICREA Research Professor at IBEC 

 

Reference article: 

Gerardo A Lopez-Muñoz, Juan M Fernández-Costa , Maria Alejandra Ortega, Jordina Balaguer-Trias, Eduard Martin-Lasierra and Javier Ramón-Azcón. Plasmonic nanocrystals on polycarbonate substrates for direct and label-free biodetection of Interleukin-6 in bioengineered 3D skeletal musclesNanophotonics, 2021.