A multiple electrochemical sensing fibre for long-term disease biomarkers monitoring in vivo

To fabricate a stable device-tissue interface, the bundles of carbon nanotubes fibres were twisted to form a hierarchical structure that mimic the native tissues. After modification, the sensing fibres could realize the long-term monitoring of multiple disease biomarkers in vivo.

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Learning the working principle of the central nervous system and understanding real time physiological information arouse brand-new requirements for biomedical devices. Given that 55% of human body weight is made of fluids and the body functions based on humoral regulation i.e. the on-going biochemical reactions, the implantable biochemical sensors shall provide essential yet important clue for the metabolism of human body. However, the mechanical mismatch between soft, dynamic tissue and traditional rigid devices obstacles the formation and maintenance of a stable device-tissue interfaces and the associating accurate reading. On the one hand, the implantation surgery of current electronics results in high degree of trauma. On the other hand, the unstable interface shall lead to the accumulation of inflammatory cells and scarring. Both materials and structures have thus been evolving towards advanced monitoring of physiological signals e.g. emerging nano-mesh structure, and the emerging materials of polymer, graphene and carbon nanotubes. All these attempts are designed towards a more stable device-tissue interface and improved sensing both the resolution and the fidelity. However, long-term detection of multiple biochemical signals in vivo is still far from satisfactory, which might come from the mismatch of the mechanical properties at different scales of the anisotropic and heterogeneous tissue, and the lack of multi-functional integration for the temporal-spatial resolved and multiple signals monitoring.

We put forward an idea in mimicking the structure of native tissues to match the mechanical properties of soft tissues. Carbon nanotube (CNT) fibres in resemblance to muscle fibres are prepared by hierarchical assembly of CNTs i.e. in-situ growth of CNT forest followed by dry spinning process. The hierarchical structure has rendered the fibres with matched bending stiffnesses, which ensures a dynamic stable interface with most tissues both at the macroscopic and the cellular scale.

In order to realize the detection of biochemicals, we further built a single sensing fibre (SSF) library by developing various electrochemical sensing fibres via versatile modification methodology. And multiple fibres can be further integrated to make multi-ply sensing fibers (MSF), demonstrating two different terminal geometrical structures to realize advanced monitoring including spatial analysis and real-time multiplex monitoring. With the end of the five H2O2 sensing fibres distributed along the axial direction, the spatial monitoring of H2O2 during tumor growth was revealed. With the ends of glucose, Ca2+ sensing fibres and reference fibre integrated and laid at the radical plane, the simultaneous monitoring of blood glucose and Ca2+ was achieved. And the sensing fibres worked stably over 4 weeks.

Fig.1: a, Schematic of the hierarchical structure of muscle. b, Representative transmission electron microscope image of a multi-walled CNT. Scale bar, 3 nm. c,d, Representative SEM images of a primary CNT fibre (c) and a hierarchically helical CNT fibre assembled from primary CNT fibres (d). Scale bars, 6 μm (c) and 20 μm (d). e, Schematic of the preparation process (i), schematic of the structure (ii) and a representative SEM image (iii) of an MSF with axial terminals and five evenly spaced SSFs for spatial analysis. Scale bar, 50 μm. f, Schematic of the preparation process (i), schematic of the structure (ii) and a representative SEM image (iii) of an MSF with radial terminals for multiplex monitoring, such as glucose, Ca2+, Na+, K+ and pH. Scale bar, 50 μm. The orange arrows in e and f indicate the twisting direction of the motor during preparation.

The bio-inspired devices guided fabrication of stable and friendly tissue-device interfaces for long time application. It is possible to obtain a large amount of SSFs with different functions and then to prepare the MSFs by a twisting process. In the future, we believe the MSFs could be applied in many biomedical fields to discover and understand the mechanisms of various diseases and could even be a tool for physiological information monitoring and disease prediction. 

Link of the paper: https://www.nature.com/articles/s41551-019-0462-8


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Liyuan Wang

PhD Student, Fudan University

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