A team from Boston University, the University of Philadelphia, Rice University (Texas) and GlaxoSmithKline (UK) designed, manufactured and tested a ultra-small nerve cuff or ‘nanoclip’ that uses electrical stimulation of nerves as an alternative to systemic pharmaceutical treatment – potentially opening the door to new therapeutics for a huge range of chronic conditions.
The team’s results are published today in the Journal of Neural Engineering.
Senior author, Dr Timothy Gardner from Boston University, said: “The goal of the project was to produce a first generation high resolution nerve interface fabricated by direct laser writing. The scale and design features of the resulting 'nanoclip' affords access to some of the smallest autonomic nerves, creating new opportunities for basic research in autonomic biology and bioelectronic medicine.
“The vision for bioelectronic medicine is to treat disease by modulating the signalling of visceral nerves near various end organs. In small animal disease models, the nerves of interest can have very small diameters and limited surgical access. To overcome this, our nanoclip has a manufacturing resolution of 200nm, and is capable of interfacing with nerves as small as 50μm in diameter.
The resolution of the printing process allowed for the incorporation of design innovations such as trapdoors to secure the device to the nerve, and quick-release mounts that facilitate keyhole surgery, removing the need for large incisions to accommodate bulky surgical instruments.
The researchers conducted tests in the tracheosyringeal (ie, hypoglossal) nerve of zebra finches, both for the safety of the nanoclip and for its effectiveness in recording and stimulating nerve activity.
By analysing the birds’ song structure and finding it returned to baseline after bilateral implants of dummy clips on the nerve, the team were able to demonstrate the safety of the device for nerve function.
Dr Gardner said: “Our ‘nanoclip’ electrode is easy to implant and can perform recording and stimulation on small diameter nerves. In doing so, it addresses key challenges in interfacing with nerves in the peripheral nervous system, and could, we believe, help to pave the way for use in the treatment of disease.
“This initial work demonstrated the successful use of our nanoclip in the stimulation and monitoring of nerve activity in the TS nerve of the zebra finch in an anesthetized preparation. Our future efforts will aim to refine this early design for recording and stimulating in chronic preparations while increasing the manufacturability of the device for a variety of nerve targets – a critical step in the development of bioelectronic therapies.
“Looking beyond these first results, we hope that eventually a broad range of diseases such as diabetes, polycystic ovarian syndrome, asthma, and cancer may be treatable through modulation of the autonomic nervous system, either by electrically blocking or stimulating the nerve to modify organs directly, or to modify the brain’s reflex control of the organs indirectly.”