Organic bioelectronics

How electrically conductive polymers help to combine electronics and living tissues

Mikhail Petrov, "Biomolecule"

Scientists have long dreamed of turning animals and plants into cyborgs controlled by electrical signals, and are trying to do it in a variety of ways. So, about 10 years ago, a new scientific field appeared – organic bioelectronics, in which electrically conductive polymers act as intermediaries between living beings and computers. Remote control of the color of rose leaves, an artificial neuron and spot pain treatment – the first results of this triple alliance are already impressive.

All living organisms are a bit robots or computers. Only instead of the usual electricity – electrons running through wires to the outlet and back - we are controlled by nerve impulses, streams of charged molecules called ions. And the "buttons" in live electrical circuits are pressed not by fingers, but by special substances – neurotransmitters. When their concentration exceeds a certain limit, a chain of biochemical reactions begins in the cell membranes of neurons, which ends with the excitation of a nerve impulse.

Now scientists are trying to "marry" computers inside us with the usual silicon chips: brain-computer interfaces are already able to recognize the activity of nerve cells and convert them into meaningful commands for electronics [1]. So, using the power of thought, you can play simple games, move a robotic prosthetic arm or even control a quadcopter. However, all these devices still sin with errors and inaccuracies – it is not easy to cross electronic and ion currents in one device.

"Translators" from the language of life to the language of microcircuits can be electrically conductive polymers that conduct both types of current simultaneously (Fig. 1). Discovered in the 70s of the last century, these materials were actively studied by many scientists: transistors, solar panels, organic light-emitting diodes (OLED) and other devices were made on their basis organic electronics.

Figure 1. Schematic representation of organic (right) and inorganic (left) semiconductors in contact with an electrolyte. The sizes of charged ions are much larger than the distances between atoms in inorganic semiconductors, and therefore ionic conductivity in these materials is impossible. At the same time, the characteristic sizes of voids between the chains of macromolecules of conjugated polymers are comparable to the sizes of hydrated ions, and therefore ionic conductivity is possible in this class of compounds. Figure from [15].

Now the advantages of electrically conductive polymers – flexibility, simplicity and variability of synthesis, as well as biocompatibility and ionic conductivity – are being tried by organic bioelectronics, a very young field of materials science, which already has something to boast about [2].

Diagnostics from the inside

The work of many brain-computer interfaces is tied to the removal of EEG: a cap with electrodes is fixed on a person's head, in which, under the action of ion currents flowing in the brain, their own electronic currents arise. In a 2013 paper, scientists from France proposed using organic electrochemical transistors for the same purposes [3].

Conventional semiconductor transistors are the main components of all electrical logic circuits, a kind of electronic buttons with three contacts. A relatively large current flowing in them from one contact to another can be controlled using a small signal (significantly less current or voltage in the case of a field-effect transistor), which is supplied to the third contact. By assembling many transistors in one circuit, it is possible to amplify, attenuate and transform any electrical signals or, in other words, process information.

Organic transistors work in a similar way, with the help of which researchers recorded epileptic activity in live laboratory mice. The third control contact in this transistor was made of a conductive polymer and injected directly into the brains of rodents. The polymer changed its structure (and, as a consequence, conductivity) along with fluctuations in the electrical activity of nerve cells, and as a result, even small characteristic changes in ion currents in the brain of the "cyborg" led to noticeable differences in the current flowing from the input contact of the transistor to the output (Fig. 2).

Figure 2. In vivo recording of brain electrical activity using organic transistors. The pink color shows the dependence removed with the help of an organic electrochemical transistor, blue – a plastic electrode, black – a metal electrode. Please note that the last two electrodes register an electrical signal by potential jumps, and the transistor – by current jumps in an electrically conductive channel. Figure from [3].

In their experiment, the French showed that organic transistors make it possible to record the electrical activity of the brain much more accurately than their modern inorganic counterparts. In experiments of other scientific groups, organic transistors are successfully used to remove ECG [4] or, for example, to determine the concentration of lactic acid [5], glucose [6] and other biomolecules.

Plastic neurons

Today, neurological and psychiatric diseases are treated mainly with the help of medications, but it can be very difficult to choose their dosage, deliver the drug to certain cells point-by-point and at the same time take into account its side effect on a variety of processes in the body. A large team of Swedish scientists from several institutes proposed to solve these problems with the help of the same electrically conductive polymers, or rather, with the help of another organic bioelectronics device – an organic electronic ion pump capable of pumping ions from one medium to another [7].

In their work, the researchers studied laboratory rats in which they first caused neuropathic pain (its cause is not an external stimulus, but the impaired functioning of the neurons themselves), and then treated it with the help of a point injection of the neurotransmitter GABA (gamma–aminobutyric acid), which reduces irritation of the central nervous system [8]. A miniature organic pump (about 12 cm in length and 6 mm in diameter) was injected into the spinal cord of rats, and its reservoir was filled with GABA (Fig. 3).

Figure 3. Implantable organic electrochemical pump. A is a photo of the device, B is a schematic representation of the device, on the left is an electrical contact, in the center is a reservoir with GABA, on the right are output channels. The total length of the device is 120 mm, the diameter of the tank is 6 mm. C – four organic electrochemical outputs are located at the points where the branches of the sciatic nerve enter the spinal cord. Figure from [7].

Video 1. Organoelectronic ion pump

As a result, the pain disappeared in the rats (this was checked using a tactile test: elastic threads of various stiffness were brought to the paws of the rats and watched, starting with what pressure the animal would pull back the paw), and no side effects were observed. Using all other methods of treating neuropathic pain with GABA, the drug is injected into the spinal cord in a large dose, which is distributed throughout the nervous system and, in addition to suppressing pain, leads to walking disorders, lethargy and other side effects.

In parallel with this work, the same group of researchers made the first artificial neuron based on polymers [9]. In it, the ion pump was combined with biosensors sensitive to glutamic acid (the most common excitatory neurotransmitter [10]) and acetylcholine (a neurotransmitter that transmits a signal from neurons to muscle tissue [11]). For example, in one of the experiments, a "plastic" neuron monitored the level of glutamate in a Petri dish, and when a certain threshold was exceeded, a current was excited in it, which opened the reservoir of an ion pump releasing acetylcholine into the environment.

The work of an artificial neuron is very similar to how real ones function: a nerve impulse is excited in one of them and runs through the entire cell to the point of contact with another neuron, glutamic acid is released there, which, as it were, presses a button and excites the next neuron (Fig. 4). So, along the chain of neurons, the impulse reaches a muscle cell that is already excited not by glutamic acid, but by acetylcholine. The plastic neuron created by the Swedes may well repeat these actions and transmit signals to other cells. In the experiment, these were SH-SY5Y neuroblastoma cells, the activation of which was monitored by characteristic increases in ion concentration during binding of acetylcholine receptors.

Figure 4. The scheme of converting a chemical signal into an electrical signal and back in an artificial polymer neuron is identical to the scheme of operation of a living neuron. The biosensor (represented in green) reacts to an increase in the concentration of one neurotransmitter (orange dots), which generates a flow of electrons that excites an organic electrochemical pump (represented in blue) that releases another neurotransmitter (blue dots). Figure from [9].

From electronic roses to the greenest energy

Studies on mice, rats and other laboratory animals need to be coordinated with ethics commissions, and therefore the most daring experiments in organic bioelectronics are easier to put on plants. So, at the end of 2015, the same Swedish group made the first cyborg rose [12]. However, she does not know how to do anything spectacular yet – neither to open at the touch of a button on the control panel, nor to change her color depending on the humidity of the environment, nor to capture the world, but the researchers still managed to do something interesting.

In the first experiment, a cut rose was placed in water with a dissolved electrically conductive polymer, which rose up the stem and formed a conductive channel in the rose. Then the scientists brought electrical contacts to the ends of the channel and inserted a control electrode into the stem – a gold wire coated with a conductive polymer. So a kind of organic transistor was assembled inside the rose. At the same time, several control electrodes could be connected to one channel at once and a simple logic circuit could be made, according to which current flows only when certain control voltages are applied to both gold wires.

In the second experiment, an aqueous solution of another electrically conductive polymer was pumped into the rose leaves using a syringe, which can change color when an external voltage is applied. Electrodes were brought to the leaf, the current was turned on and – voila: the veins of the leaf took on a bluish-green hue. This polymer injected into them turned from colorless to blue (video 2). At the same time, when the tension was removed, the leaf again became a healthy green color.

Video 2. Changing the color of the "electronic" rose leaf. Video from [12].

So scientists have shown that with the help of simple techniques inside plants, simple electronic circuits can be created. In the future, this will allow to control their physiology and, for example, to achieve higher yields without gene modifications or even to make tiny power plants using photosynthesis energy. Of course, while it sounds too expensive, but someday organic bioelectronics technologies will allow you to control each plant point-by-point, and not the entire population at once.

Bioelectronic future

The first experiments showed that organic bioelectronics devices can receive, transmit and process bioelectric signals. What's next? Now polymer materials have learned to make biocompatible and biodegradable, and therefore any living organism can be literally stuffed with chips based on them [13]. All that remains is to teach them the wireless transmission of information, and inside the human body it will be possible to create a local network of sensors that constantly monitor various medical indicators like glucose levels, heart rate and electrical activity of selected neurons, and then transmit their signals to implanted medical robots based on the same ion pumps so that they begin to fight the problem.

If you don't like the idea of becoming such a cyborg at all, you can just swallow a pill with a built–in flexible microcircuit - by acidity, temperature and concentration of different substances, it will accurately calculate where to release the medicine, and, having done a good deed, it will simply be digested inside us like some kind of sugar cube.

The text was first published on the portal "Attic" [14].

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Portal "Eternal youth" http://vechnayamolodost.ru 07.11.2016