We all know about electrodes. An electrode is primarily a conductor that contacts a nonmetallic part of a circuit. Commonly used in electrochemical cells, electrodes are commonly of two types: cathode and anode, depending on the type of chemical reaction that occurs.
But what are bioelectrodes? And why are they looked at with so much scientific and technological anticipation these days? That’s precisely what we will discuss in this article.
What are Bioelectrodes?
The scientific community defines bioelectrodes as devices that can ‘produce or measure electrical activity in the body for electrophysiological stimulation or monitoring.’ Because of their capability to convert the biochemical energy of living organisms into electrical signals, they find a wide range of applications in medicine, environmental monitoring, and biotechnology.
The most common and crucial application of bioelectrodes that we see around us is in the processes of Electrocardiography (ECG) and Electroencephalography (EEG), aimed at monitoring the electrical activity of the heart and brain, respectively. Implantable devices like pacemakers have them as components that can regulate heart rhythms.
Among other use cases, bioelectrodes help detect pollutants and monitor water quality, study cellular processes and develop biosensors.
Altogether, bioelectrodes have a variety of applications and – essentially – it is the reason that the scientific community, especially those involved in health-tech, are keen to explore it more.
In the following segment, we will look into breakthrough research that might lead to the development of a bioelectrode material that is stretchable, permeable to humidity and conforms closely to the skin.
A New Bioelectrode Material With Enhanced Stretchability and Improved Permeability
The research was carried out by a team led by Assistant Professor Tatsuhiro Horii and Associate Professor Toshinori Fujie from the Tokyo Institute of Technology (Tokyo Tech). Their purpose was to empower the burgeoning wearable healthcare and fitness market with bioelectrode materials that would not suffer from the usual problem of lacking flexibility. These materials can stretch the skin without breaking and have low humidity-permeability, leading to sweat buildup and discomfort.
They observed that materials currently used for bioelectrodes, such as metals, conductive polymers, and hydrogels, suffer from this problem. Resultantly, they’re not capable of accurately recording biosignals over extended periods.
What Material Does the New Solution Use?
In devising the solution, the researchers invented a new type of material that comprised layers of conductive fibrous networks consisting of single-wall carbon nanotubes (SWCNTs) on a stretchable poly(styrene-b-butadiene-b-styrene) (SBS) nanosheet. The nanosheets conform tightly to the skin, resulting in more accurate biosignal measurements. The carbon nanotube fibers help maintain stretchability and keep the device humidity-permeable.
While speaking about the need for developing a new and improved bioelectrode, Assistant Professor Tatsuhiro Horii said the following:
“Self-supporting electrodes that are stretchable, permeable to humidity, and conformable to skin surface bumps are required to allow for the natural deformation of skin without restricting body movements.”
Apart from its stretchability and permeability property enhancements, the bioelectrode also proved durable and resilient for extended use. In one of the durability tests, the researchers even subjected the material to repeated bending, measuring the change in resistance. They found the resistance increasing negligibly, by only 1.1 times in sweat and by 1.3 times over 300 cycles of bending.
Summarizing the overall achievements of the research, Associate Professor Toshinori Fujie said:
“We obtained skin-conformable bioelectrodes with high water vapor permeabilities, which showed comparable performance in sEMG measurements to those of conventional electrodes.”
While the above research focuses on wearable healthcare and the role of sophisticated bioelectrodes in it, researchers are also looking into ways that could make implantable bioelectrodes better. In the following segment, we briefly look into one such research.
Implantable Polymer Bioelectrode for Enhanced Tissue Responses and in Vivo Performance
While implantable bioelectrodes are valuable in building accurate instruments that help treat and diagnose by directly transmitting electrical signals in the living tissues, these bioelectrodes often suffer performatively due to adverse tissue reactions, primarily induced by high oxidative stress and subsequent inflammatory activation of macrophages.
A team of researchers tested the possibility of a novel solution in this regard. They introduced reactive oxygen species (ROS)-scavenging capabilities to the bioelectrodes. To be more specific, the researchers fabricated a polypyrrole (PPy) electrode doped with hemin-conjugated heparin (HepH) to enable the system to have robust enzyme-like antioxidant properties.
According to research results, these HepH-doped PPy electrodes exhibited a catalase-mimicking activity, as evidenced by hydrogen peroxide scavenging and oxygen gas generation in the presence of hydrogen peroxide.
These electrodes also helped reduce intracellular ROS levels and directed macrophage polarization toward an anti-inflammatory phenotype, mitigating collagenous scar tissue formation around the implanted electrodes. A real-time ECG monitoring for 20 days showed that the extended in vivo signal sensitivity of the HepH-doped PPy electrodes was as reliable as implantable bioelectrodes.
Research like this is conducted by many institutions and organizations across the world. Moreover, some companies are investing in R&D funds and resources as well. In the coming segments, we will look into a couple of such companies.
#1. Elephantech
One of the companies to do innovative work in this field is Tokyo-based Elephantech. The company manufactures Ag/AgCl bioelectrodes with P-Flex. The P-Flex implies a method wherein metal ink is printed directly, followed up by copper plating.
The manufacturing method – known as the Pure Additive method – involves converting metal into a nanoparticle ink state, which is then printed on a substrate using an inkjet printer. Electroless copper plating then helps the metal grow to form a circuit.
One of the most valuable advantages of this method is that it requires fewer manufacturing processes compared to conventional methods, resulting in significant reductions in environmental impact and improved cost performance.
Elephantech manufactures the Ag/AgCl bioelectrode using this P-Flex method. The result is in the form of an overwhelmingly low resistance to electrodes due to its copper wiring. Moreover, it is also beneficial as mounting is possible in parts.
As the manufacturing process follows inkjet printing, it is done at a reasonable price in a short period because the mold is only for Ag/AgCl paste application. It is possible to manufacture in medium and small batches, and the manufacturer is free to choose between PET film or polyimide film substrates. Making the process more flexible, agile, and adaptable, the process is conducive to material ratio adjustment of Ag/AgCl paste and prototyping for iontophoresis.
While explaining the importance of having Ag/AgCl bioelectrodes for ECG, Yoji Ishiyama wrote in his research paper, The performance required for the sensor for biomedical signal measurements:
“Generally, nickel silver or silver electrodes are used for electrode derivation of ECG or EEG though, it is recommended for monitoring to use Ag/AgCl electrodes used stably over a long time, and having low polarizing potential between the skin and the electrodes.”
The Elephantech process helps achieve sophisticated Ag/AgCl bioelectrodes and can be used widely to measure EMG, ECG, and EEG.
According to the latest information available, Elephantech raised ¥3,000,000,000 / Series E from Nomura Holdings by the end of March 2024.
#2. Imedex
Imedex is another company with over 25 years of experience in manufacturing medical bioelectrodes. The company caters to a wide base of users, including hospitals and university research institutes.
One of the standout features Imedex has achieved in its bioelectrodes is remarkable noise reduction. The company claims to have come up with optimized electrode structures called “fully shield.” Successful reduction in noise waves helps doctors to have more accurate diagnoses.
Imedex bioelectrodes are agile enough to be used in various fields. They are compatible with evolving sensor technologies. Bioelectrodes can also prove useful in the areas of wellness, fitness, and sports, not only in healthcare and diagnostics.
At a more functional level, the use of Imedex bioelectrodes can be seen in Holter monitors, strip electrodes and 16-pole electrodes. It also fits the needs of portable biosensors, inducing single induction and NASA induction types.
The company was established in 1992 with a founding capital of 12,500,000 yen. It has offices in Japan and France.
Bioelectrode Trends for the Future
The way bioelectrode research has made progress in the past years, it is evident that it will only get more and more versatile and sophisticatedly accurate in the days to come. While we have already discussed two breakthrough research that happened in recent times in this space and looked into companies that are investing resources in this field, there are many more left to be discussed. We will look into some of them in the coming segments.
In 2022, a group of researchers from the University of Grenoble, France, tested a new concept of hollow electrodes based on the assembly of two buckypapers, creating a microcavity that contains a biocatalyst. The researchers fabricated hollow bioelectrodes containing 0.16–4 mg bilirubin oxidase in a microcavity and applied it to the electro-enzymatic reduction of O2 in aqueous solution.
For hemin-modified buckypaper, the bioelectrode shows a direct electron transfer between multi-walled carbon nanotubes and bilirubin oxidase with an onset potential of 0.77 V vs. RHE. The researchers inferred that the storage stability shown by the hollow bioelectrodes was good, with an electro-enzymatic activity of 30 and 11% of its initial activity after 3 and 6 months, respectively.
The bioelectrodes were found to be satisfactorily well-built as they were permeable to water but did not allow enzyme permeation. They exhibited efficient electroenzymatic reduction of O2 by direct electron transfer with BOx molecules in solution.
The process improved due to the use of hemin and ABTS for orientation and electrical wiring of BOx, respectively. Altogether, not only do the hollow electrodes stand out for their long-term operation and storage stability, but they also helped develop a new generation of enzyme electrodes as biosensors or biofuel cells.
Another study, carried out by a team comprising researchers from Spain and the United States, looked into the effects of nanostructuration on the electrochemical performance of metallic bioelectrodes. The study was a crucial one since the use of metallic nanostructures in the fabrication of bioelectrodes (e.g., neural implants) was gaining attention.
The researchers believed that nanostructures could provide increased surface area that might benefit the performance of bioelectrodes. However, the researchers of the study we’re discussing shifted the focus and looked into the electrochemical performance of nanostructured surfaces in physiological and relevant working conditions.
Innovatively enough, the researchers introduced a versatile, scalable fabrication method based on magnetron sputtering to develop analogous metallic nano-columnar structures (NCs) and thin films (TFs) from Ti, Au, and Pt to eventually show that NCs contributed significantly towards the reduction of the impedance of metallic surfaces.
In 2023, the researchers aimed to solve the risk of in-stent restenosis after implantation by combining conventional vascular stents with liquid metal-based electrodes with impedance detection, irreversible electroporation, and blood pressure detection.
Compared to the conventional rigid electrodes, these liquid metal-based electrodes exhibited a mix of improved conductivity and stretchability. They were also more compliant with the implantation process of vascular stents and remained in the vasculature for a long period.
Even before all these developments, we could see, back in 2019, a team of researchers utilizing graphene-based bioinks in manufacturing three-dimensional bioelectrodes. They immobilized the “bioink” of glucose oxidase (GOD) in a matrix of reduced graphene oxides (RGOs), polyethylenimine (PEI), and ferrocene carboxylic acid (FcCOOH) on carbon paper (CP). The result was versatile enough with the potential for application for other enzymatic bioelectrodes.
In one of our previous articles, we discussed the innovative development in wearable technology introduced by researchers at the University of Washington. This unique device, called the Thermal Earring, was designed to monitor body temperature via the earlobe. Its strategic placement near the head ensured a direct correlation with core body temperature, distinguishing it from other wearables like smartwatches.
The Thermal Earring was impressively compact, akin to the size and weight of a small paperclip, making it not only functional but also fashionable. It incorporated a dual-sensor system that could differentiate between body and environmental temperatures, offering a reliable reading within a remarkably narrow margin of error.
Moreover, its efficient power consumption supported an impressive 28-day battery life. As wearable technologies continued to evolve, the Thermal Earring stood out for its potential applications in health monitoring, demonstrating a promising future in the integration of fashion and medical technology.
Another development we reported on involved transforming smartphones into glucometers. Researchers at the National Institute of Standards and Technology in Boulder, USA, described in their paper “Quantitative, high-sensitivity measurement of liquid analytes using a smartphone compass” how the magnetic compass in smartphones can be repurposed.
By embedding tiny magnetic particles in a custom-designed hydrogel, Mark Ferris and Gary Zabow demonstrated that changes in glucose concentration or pH cause the hydrogel to expand or contract. This movement alters the distance of the magnetic particles from the smartphone’s compass, allowing the device to measure these changes accurately.
With high sensitivity capable of detecting minute changes, this method promises a simple and accessible way to monitor health metrics like glucose levels using just a smartphone and a special app.
Concluding Thoughts
Altogether, efforts to make bioelectrodes more versatile are robustly ongoing, with more utility and accuracy to emerge in the days to come. This persistent innovation signals a future where wearable and implantable bioelectrodes become even more integral to healthcare and diagnostics, improving lives with their advanced capabilities and applications.
