Realizing flexible bioelectronic medicines for accessing the peripheral nerves - technology considerations

Abstract

Patients suffering from conditions such as paralysis, diabetes or rheumatoid arthritis could in the future be treated in a personalised manner using bioelectronic medicines (BEms) (Nat Rev Drug Discov 13:399-400, 2013, Proc Natl Acad Sci USA 113:8284-9, 2016, J Intern Med 282:37-45, 2017). To deliver this personalised therapy based on electricity, BEms need to target various sites in the human body and operate in a closed-loop manner. The specific conditions and anatomy of the targeted sites pose unique challenges in the development of BEms. With a focus on BEms based on flexible substrates for accessing small peripheral nerves, this paper discusses several system-level technology considerations related to the development of such devices. The focus is mainly on miniaturisation and long-term operation. We present an overview of common substrate and electrode materials, related processing methods, and discuss assembly, miniaturisation and long-term stability issues.

Fig. 1

Artistic impression of a flexible BEm for accessing the peripheral nerves (concept). The BEm features a compact layout, with all components required for its wireless closed-loop operation integrated on the device. Small and thin ASICs connect to electrodes and give the system its intelligence. They receive and store energy, communicate with the outside world, process the acquired signals, and deliver the personalised therapy in the form of electrical stimuli

Fig. 2

Examples of various interfaces that have been used to access the peripheral nerves. a A silicon-based penetrating electrode array, the Utah Slanted Electrode Array, reproduced from (Branner et al. 2004), b–e polymer-based FINE, TIME, LIFE, and CUFF electrode arrays, reproduced from (Schiefer et al. 2010) and (Badia et al. 2011). The scale bar for b is on the right of the picture and is in mm. c–e are all implanted in the rat sciatic nerve. a–e have been reproduced with permission