Final Report Summary - OEAN (Organic Electronic Artificial Neurons)
Disorders of the nervous system effect hundreds of millions of people worldwide and the costs of these afflictions, both in terms of life lost and healthcare expenditure, are a heavy burden on us all. While some therapies have proven successful, treatments are still lacking for some of the most prevalent and debilitating forms of neurological impairments. Development of novel treatments will depend on precise interaction with the neurological pathways responsible for the disability. However, the complex circuitry of the nervous system has proven difficult to interface. While techniques ranging from pharmaceutics to electrophysiology have yielded insight into the function and dynamics of neural circuitry, better therapies demand new technological solutions. The neuron itself is the most effective interface to other neurons. It is localized, it is highly selective, and it can transduce chemical signals into electrical signals and vice versa, without requiring liquid flow. A human-made device that could operate in such a chemical-electrical-chemical manner would enable its user one crucial addition to the biological neuron’s set of capabilities: the ability to observe neural signaling electronically by connection to control hardware. This “artificial neuron” would thus become a key to studying, and eventually augmenting, neural signaling pathways with the ease and precision of modern electronics.
Biosensing technology is mature, and electronically controlled substance delivery is developing rapidly. Indeed, we have recently demonstrated the first combination of these techniques in vitro as a functioning artificial neuron. The challenge is to merge these technologies into a single, implantable device, and develop the resulting device into a tool for the treatment of neurological disabilities in a clinical setting.
Based on these recent in vitro proofs-of-principle of the artificial neuron with a commercially available sensor, we propose to replace the sensor component with technology developed in our laboratory that has several advantages compared to commercially available sensors. These next-generation, transistor-based sensors are manufactured in a similar fashion to the controlled neurotransmitter delivery component of the system. Therefore, their integration in a single device coupling the sensing and delivery elements is facilitated. The primary material in these devices is a conducting polymer, which is a plastic material able to conduct electricity. One of the great advantages of this class of materials is that they can be processed from solution and deposited using classic printing techniques, such as inkjet printing, potentially leading to low-cost production of devices.
For this project, we chose to focus on one of the main neurotransmitters in the human body, glutamate, which is an excitatory neurotransmitter. A common way to detect this chemical is to use a method involving a modification of the electrical properties of the device. However, this molecule cannot be directly detected because it does not generate any electrical modification when in contact with the device, i.e. it is not electrochemically active. To solve this issue, one typically proceeds to an indirect detection using an oxidase enzyme, which degrades the neurotransmitter into various products including hydrogen peroxide, which is electrochemically active and consequently induces a modification in the electrical properties of the sensor. Hydrogen peroxide detection is commonly achieved using devices made of platinum, which is a metal that shows a good reactivity towards hydrogen peroxide. However, one of the objectives of this work was to develop a device that can be produced using printing techniques so the use of bulk platinum electrodes is prohibitive. We oriented our work towards the use of nanometer-scale platinum particles, which are approximately ten thousand times thinner than a human hair and can be mixed with our solution of conducting polymer. The mixture is then deposited on a substrate and cured in order to remove the water. We obtained a thin film of the conducting polymer with platinum nanoparticles embedded within the polymer matrix (Figure 1).
The first step of the project has been to develop the sensing component of our device. We developed organic electrochemical transistors, which are devices based on conducting polymers and have an inherent amplification property. This leads to stronger detection signals (as electrical current) compared to commercial biosensors (as electrical voltage) used in our previous work. The devices were used to detect glutamate (Figure 1) and the limit of detection achieved (~micromolar concentration) is consistent with the concentration of glutamate in the human body. First attempts to manufacture these devices by inkjet printing showed promising results and further optimization of the printing process is ongoing.
This combination of conducting polymer and platinum nanoparticles is an interesting platform for many applications in other fields thanks to the combined electrical (and ionic) properties of the conducting polymer and the catalytic properties of platinum nanoparticles. Furthermore, the possibility to print this composite allows for potentially low-cost production.
The second step of the project was to combine the sensing and the delivery elements. We found that the presence of platinum nanoparticles in the delivery element did not affect its properties so we could build the two individual components from the same material (the conducting polymer with the platinum nanoparticles), greatly simplifying the manufacturing process. We designed our devices so that the sensing and the delivery occur at the same location. This means that the output channel of our delivery component is right next to the sensing element. The system is configured so that when the signal of the sensor reaches a certain value, which corresponds to a defined concentration of glutamate, the delivery component is activated. The delivery element can be loaded with various chemicals depending on the application targeted. We are currently proceeding towards in vitro measurements to validate the use of our devices with living cells.
Our devices are not only interesting within the professional medical domains. The biosensor market is in constant growth. According to a recent study published by Transparency Market Research, the biosensors market was about 9.6 billion dollars in 2011 and is expected to reach almost 19 billion in 2018. A growing part of that market is wellness monitoring. For example, Apple is increasingly including health monitoring in its iPhone platform, and will be launching its iWatch shortly, which has the potential to monitor various biometrics. Our devices could easily be modified to monitor other chemicals than neurotransmitters. For instance, several chemicals can be measured from the sweat, and by changing the enzyme on our devices, we could monitor glucose, to estimate the blood sugar level, or lactate, to optimize performance during physical exertion. We could also monitor sodium to indicate early stage of dehydration. Combining these features with the potential for low cost production through printing techniques, and the possibility of adapting onto flexible, conformable substrates, we believe our technology is a promising candidate for next generation biosensing and biometric applications.
Biosensing technology is mature, and electronically controlled substance delivery is developing rapidly. Indeed, we have recently demonstrated the first combination of these techniques in vitro as a functioning artificial neuron. The challenge is to merge these technologies into a single, implantable device, and develop the resulting device into a tool for the treatment of neurological disabilities in a clinical setting.
Based on these recent in vitro proofs-of-principle of the artificial neuron with a commercially available sensor, we propose to replace the sensor component with technology developed in our laboratory that has several advantages compared to commercially available sensors. These next-generation, transistor-based sensors are manufactured in a similar fashion to the controlled neurotransmitter delivery component of the system. Therefore, their integration in a single device coupling the sensing and delivery elements is facilitated. The primary material in these devices is a conducting polymer, which is a plastic material able to conduct electricity. One of the great advantages of this class of materials is that they can be processed from solution and deposited using classic printing techniques, such as inkjet printing, potentially leading to low-cost production of devices.
For this project, we chose to focus on one of the main neurotransmitters in the human body, glutamate, which is an excitatory neurotransmitter. A common way to detect this chemical is to use a method involving a modification of the electrical properties of the device. However, this molecule cannot be directly detected because it does not generate any electrical modification when in contact with the device, i.e. it is not electrochemically active. To solve this issue, one typically proceeds to an indirect detection using an oxidase enzyme, which degrades the neurotransmitter into various products including hydrogen peroxide, which is electrochemically active and consequently induces a modification in the electrical properties of the sensor. Hydrogen peroxide detection is commonly achieved using devices made of platinum, which is a metal that shows a good reactivity towards hydrogen peroxide. However, one of the objectives of this work was to develop a device that can be produced using printing techniques so the use of bulk platinum electrodes is prohibitive. We oriented our work towards the use of nanometer-scale platinum particles, which are approximately ten thousand times thinner than a human hair and can be mixed with our solution of conducting polymer. The mixture is then deposited on a substrate and cured in order to remove the water. We obtained a thin film of the conducting polymer with platinum nanoparticles embedded within the polymer matrix (Figure 1).
The first step of the project has been to develop the sensing component of our device. We developed organic electrochemical transistors, which are devices based on conducting polymers and have an inherent amplification property. This leads to stronger detection signals (as electrical current) compared to commercial biosensors (as electrical voltage) used in our previous work. The devices were used to detect glutamate (Figure 1) and the limit of detection achieved (~micromolar concentration) is consistent with the concentration of glutamate in the human body. First attempts to manufacture these devices by inkjet printing showed promising results and further optimization of the printing process is ongoing.
This combination of conducting polymer and platinum nanoparticles is an interesting platform for many applications in other fields thanks to the combined electrical (and ionic) properties of the conducting polymer and the catalytic properties of platinum nanoparticles. Furthermore, the possibility to print this composite allows for potentially low-cost production.
The second step of the project was to combine the sensing and the delivery elements. We found that the presence of platinum nanoparticles in the delivery element did not affect its properties so we could build the two individual components from the same material (the conducting polymer with the platinum nanoparticles), greatly simplifying the manufacturing process. We designed our devices so that the sensing and the delivery occur at the same location. This means that the output channel of our delivery component is right next to the sensing element. The system is configured so that when the signal of the sensor reaches a certain value, which corresponds to a defined concentration of glutamate, the delivery component is activated. The delivery element can be loaded with various chemicals depending on the application targeted. We are currently proceeding towards in vitro measurements to validate the use of our devices with living cells.
Our devices are not only interesting within the professional medical domains. The biosensor market is in constant growth. According to a recent study published by Transparency Market Research, the biosensors market was about 9.6 billion dollars in 2011 and is expected to reach almost 19 billion in 2018. A growing part of that market is wellness monitoring. For example, Apple is increasingly including health monitoring in its iPhone platform, and will be launching its iWatch shortly, which has the potential to monitor various biometrics. Our devices could easily be modified to monitor other chemicals than neurotransmitters. For instance, several chemicals can be measured from the sweat, and by changing the enzyme on our devices, we could monitor glucose, to estimate the blood sugar level, or lactate, to optimize performance during physical exertion. We could also monitor sodium to indicate early stage of dehydration. Combining these features with the potential for low cost production through printing techniques, and the possibility of adapting onto flexible, conformable substrates, we believe our technology is a promising candidate for next generation biosensing and biometric applications.
