Project Description

Our Motivation

In today's fast-evolving tech landscape, human-machine interfaces are becoming more advanced, with new technologies harnessing the body's electrical signals to control devices . A prominent inspiring example that has made global headlines is the implantable brain–computer interface Neuralink, designed to allow those with quadriplegia the ability to control electronic devices with their thoughts [1]. Another inspiring example closer to home is Craig Mackinlay, current member of the UK House of Lords and former MP, also known as the “Bionic MP” [2]. Mackinlay had to undergo an amputation on all of his limbs after battling sepsis, and now uses both upper and lower bionic limbs, which are controlled by signals from the muscle (Figure 1).

Craig Mackinley, bionic MP, fitted with his prosthetic limbs
Figure 1. “Bionic MP” Craig Mackinley, who underwent a quadruple amputation after battling sepsis, and now utilises bionic technology. Photo taken by Isabella Allen, BBC News.

Our project aims to improve the interpretation of the body’s electric signals to have better control over upper limb prosthetics. Our project is geared towards individuals who have suffered traumatic limb loss, such as Craig Mackinlay, as globally the prevalence of traumatic amputation has increased from 370 million to 552 million cases between 1990 and 2019 [3].

What are Myoelectric Prosthetics?

Myoelectric prosthetics are a type of upper-limb prosthetics that are directed by the electrical signals generated from muscle contractions in the residual limb [4]. These signals are detected by skin-surface dry electrodes which are then translated into the user’s intended motion. Furthermore, they usually do not require any additional surgery to fit, making them ideal for those who do not wish or are unable to undergo any invasive procedures [5]. This advantage means they can even be fitted to children as young as 3 years [6].

What's the issue?

A direct connection with their affixed contact points is essential for the electrodes to effectively measure the electrical impulses [5]. However, myoelectric prosthetics are often heavy due to the weight of their batteries and motors, causing excessive sweating that results in the electrodes slipping from their contact points [7]. This leads to signal disruptions and imprecise motion in the prosthetics, resulting in lagging limb movement (Figure 2).

Diagram of the problem and consequences with myoelectric prosthetics outlining how the weight leads to excessive sweating, movement of the electrode and lagging limb movement
Figure 2. The issue with myoelectric prosthetics and motion artefacts

This issue is known as “motion artefacts”, which are not only a problem in myoelectric prosthetics, but in other medical equipment such as in magnetic resonance imaging (MRI) and in electromyographic (EMG) sensors [8]. As a result of motion artefacts, the patient rejection rate of myoelectric prosthetics is around 50%[9]. Consequently, there is an ongoing effort to research and implement strategies to reduce interference in myoelectric signals from noise and motion artefacts, such as skin abrasion in order to improve the electrode–skin contact surface, electrode fixing and using conductive gels [10].

Introducing: E.lectrode

One of the primary causes of motion artefacts is the lack of binding to the skin, making it easier for the electrode to move from its contact point. To solve this problem, we leverage the power of synthetic biology in our project to develop recombinant skin-specific nanowires that enhance signal accuracy and user comfort, while also being non-toxic and biocompatible. E.lectrode aims to achieve this by engineering Escherichia coli to express electrically conductive pili (E-pili) derived from Geobacter sulfurreducens. Type IV pili are multimeric protein complexes made up of pilin monomers, the primary one being the PilA monomer[11]. By combining the PilA monomer with a protein-binding peptide, we will create nanowires that specifically target and bind to proteins at the skin surface [11,12]. These engineered E-pili will be able to maintain stable signal connection despite movement of the electrode, thereby enhancing the precision of EMG signal interpretation [10] and allowing the prosthetic to continue having the same degree of flexibility without motion artefacts (Figure 3).

Application of skin-specific nanowires
Figure 3. Intended application of our skin-specific nanowires. The E-pili would coat the electrode, maintaining the electrical connection between the electrode and the skin even in the event of movement. Image adapted from X.C.Wang, Upper Limb Prosthesis for Traumatic Above Elbow Amputation for Volleyball Playing.

Overall, these E-pili will provide a novel biomaterial that can be used in minimally invasive, precision prosthetic electrodes.

The type IV E-pili from Geobacter sulfurreducens behave similarly to a nanowire, and can be modified to incorporate small protein-binding tags at its carboxyl end[12]. Previous iGEM teams have already explored nanowire applications: Tongji University in China developed a quantitative antibody detection system using e-pili from Geobacter metallireducens[13] and Links China created a density humidity power generation cell with e-pili from Geobacter sulfurreducens[14]. However, the use of E-pili for conducting human electrical signals has not been explored previously, with no previous reports from either iGEM teams or the wider scientific literature. We chose a collagen-binding tag for our proof of concept due to its well-characterised binding interaction and the abundance of collagen in the skin, thus being easier to test experimentally [15]. Ultimately, these nanowires will be engineered to bind to proteins on the skin surface such as keratin and integrin. In order to express the proteins safely, we opted to use a non-virulent expression host, E. coli NEB 5-alpha. To ensure that the native pili do not compromise the yield of the heterologous and conductive nanowires, we knocked out the fimA gene, which encodes the native pilin monomer, using CRISPR-Cas12a.

Our aims are to express and purify the engineered E-pili from the expression host, and test these for collagen binding and conductivity. The development of a successful proof of concept could open avenues towards the mitigation of motion artefacts in all EMG-powered devices using microbial skin-specific nanowires.

References