Bioelectronic medicine, which uses electrical signals to control the nervous system, is a promising form of therapy for the treatment of chronic conditions. Researchers at the imec research centre have taken important steps to make this technology more precise, reliable and energy efficient. Thanks to innovations including a new stimulation protocol, innovative implant casings and smart, closed-loop systems, targeted nerve stimulation with minimal side effects is becoming a reality.
Bioelectronic medicine uses small electrical impulses that stimulate nerves directly via implants. This technique can suppress symptoms or enhance desired responses without affecting the entire body, as is often the case with traditional medication. This offers a solution for conditions such as rheumatoid arthritis, chronic pain, epilepsy or even depression.
The peripheral nervous system (PNS), which transmits signals between the brain and organs, is a promising target structure in this regard. Disorders in this system often arise because nerves are damaged and signals are not transmitted properly, which can lead to motor and sensory problems. By selectively stimulating nerve fibres, treatments become more accurate and effective and better tailored to the patient.
Technological challenge
Precise stimulation of peripheral nerve fibres offers important therapeutic advantages, but also poses high technical demands. It often involves deeper nerves, which makes surgery, packaging, communication and energy transfer more complex. One of the biggest challenges is selectivity: how do you activate only the nerve fibres that have the desired effect, without unintentionally affecting other functions? After all, unintended activation can lead to side effects, such as voice changes or heart palpitations. Imec scientists have tackled this challenge with a new form of targeted stimulation.
In addition, imec is developing nanotechnology for energy-efficient implants with innovative casings that can function safely in the body for long periods of time. These implants are not only small and flexible, but also smart: thanks to integrated sensors and circuits, they can register signals and respond to them. This creates closed-loop systems that only become active when necessary.
Targeted stimulation with i²CS
One of imec's most notable innovations, in collaboration with the Feinstein Institute for Medical Research, is the new stimulation protocol i²CS (intermittent interferential current stimulation). This method uses two electrical signals with different frequencies that cross each other in the body. At the intersection, an interference area is created where very localised and targeted stimulation takes place.
The vagus nerve, a bundle of nerves that controls vital organs such as the heart, lungs and intestines, is one of the most important applications for i²CS. This nerve is already a proven target for the treatment of epilepsy and therapy-resistant depression. Because this nerve consists of multiple branched fibres, it has been difficult until now to stimulate only the target fibres. Initial results show that i²CS can selectively activate the nerves to the lungs without affecting the larynx or heart.
An additional advantage is that the stimulation is pulsed, which reduces energy consumption while leaving room to measure signals. This makes the system suitable for automated, responsive therapies that intervene based on real-time information, such as an impending epileptic seizure.
Biocompatibility without compromise
In addition to the stimulation technique itself, the implant's casing is also vitally important. An implant must be resistant to body fluids, but at the same time soft enough not to cause damage or irritation to the surrounding tissues. Traditional hard metal casings, such as titanium, are too rigid for this purpose – especially for micrometre-sized implants.
That is why CMST, an imec lab at Ghent University, developed an innovative casing consisting of layers of polyimide and ultra-thin moisture-repellent coatings of metal oxides, applied using thin-film electronics techniques such as atomic layer deposition (ALD). This combination offers a unique mix of flexibility and excellent barrier properties. The associated manufacturing process is also compatible with existing thin-film production techniques, making it suitable for large-scale and cost-efficient production. This allows the creation of reliable implants that continue to function in the body for a long time, without degradation of the casing or leakage.
Smart stimulation
The future of bioelectronic medicine lies in closed-loop systems: implants that continuously register signals and only stimulate when necessary. This makes treatments not only more targeted, but also more energy-efficient. However, most existing systems still work like an on-off switch. A good example of this is the implant developed by imec in collaboration with Neurogyn, which calms an overactive bladder by specifically stimulating the pelvic nerve.
A new Horizon Europe project takes a step further towards closed-loop stimulation, in which an implant in the stump of an amputated hand picks up signals from the arm nerves and translates them into movements of a prosthesis. Feedback from the artificial hand – for example, about grip strength or position – is then fed back to the user's arm nerve, allowing them to “feel” what the prosthesis is doing, as it were.
To make such advanced systems possible, energy policy needs to be rethought. Because the implant has to be close to the nerve, remain small for wearing comfort and often does not contain a battery, energy consumption must be drastically reduced to well below 100 µW. At the same time, the system must be able to register and stimulate signals. Imec has therefore developed circuits that only become active when there are changes in the nerve signal. This significantly reduces energy consumption and makes wireless power supply feasible.
Towards a new standard in neurotherapy
By combining all these innovations – from precise stimulation via i²CS to smart implants with advanced casings and energy management – imec is contributing to the development of a new generation of bioelectronic therapies. These are not only more effective and more personalised, but also more suitable for long-term use in the body.
The technology offers particular promise for patients with chronic conditions for which medication has limited effect. By modulating the nervous system in a targeted manner instead of exposing the entire body to systemic medication, side effects are reduced and adjustments can be made more quickly. What began as a theoretical concept is slowly but surely becoming reality: electricity as a precision medicine.
