First Biocompatible, Ion-Driven Transistor Enables Real-Time Signal Sensing and Stimulation of Brain Signals

New developments in electronic systems that have the ability to acquire, process, and communicate with biological substrates have triggered a number of significant advances in medicine, particularly in neurology.

IGT-based NAND and NOR gates conform to the surface of orchid petals (left). Scale bar, 1 cm. Optical micrographs of NOR (upper right) and NAND (lower right) logic gates. Input (I1, I2) and output (O) configuration is indicated. Scale bar, 100 mm. (Image credit: Jennifer Gelinas/Columbia University Irving Medical Center)

There is a growing application of these bioelectronic systems for understanding dynamic living organisms and for treating various diseases in humans. These systems need devices that are capable of recording body signals, processing them, identifying patterns, and delivering chemical or electrical stimulation to tackle issues.

Transistors form the core of these systems. These devices switch or amplify electronic signals on circuits. Conversely, they also need to fulfill a wide range of criteria to work in a safe and efficient way in biological environments, for example, the human body. So far, scientists were not successful in developing transistors that possess all the features required for fast, safe, and consistent operation in these environments over a long period of time.

A research team has now created the first biocompatible, ion-driven transistor that is sufficiently fast to allow stimulation of brain signals and signal sensing in real time. The group was headed by Dion Khodagholy, an assistant professor of electrical engineering at Columbia Engineering, and also Jennifer N. Gelinas, from Columbia University Medical Center, Department of Neurology, and the Institute for Genomic Medicine.

The internal-ion-gated organic electrochemical transistor—or IGT in short—functions through mobile ions restricted inside a conducting polymer channel to allow shortened ionic transit time as well as volumetric capacitance (ionic interactions involving the whole bulk of the channel). The IGT is characterized by high speed and large transconductance (rate of amplification), and it can also be autonomously gated and micro-fabricated to produce integrated circuits that are both scalable and conformable.

The researchers reported the results of their study in Science Advances, showing the potential of their IGT to offer a conformable, soft, tiny interface with human skin, utilizing local amplification for recording high-quality neural signals, appropriate for sophisticated data processing.

We’ve made a transistor that can communicate using ions, the body’s charge carriers, at speeds fast enough to perform complex computations required for neurophysiology, the study of the nervous system function. Our transistor’s channel is made out of fully biocompatible materials and can interact with both ions and electrons, making communication with neural signals of the body more efficient. We’ll now be able to build safer, smaller, and smarter bioelectronic devices, such as brain-machine interfaces, wearable electronics, and responsive therapeutic stimulation devices, that can be implanted in humans over long periods of time.

Dion Khodagholy, Assistant Professor, Department of Electrical Engineering, Columbia Engineering

Earlier, bioelectronic devices were integrated with conventional silicon-based transistors, which have to be vigilantly encapsulated so as to prevent contact with body fluids—for the correct operation of the device as well as for the patient safety. Owing to this requirement, implants based on these types of transistors were stiff and bulky. Within the organic electronics field, a significant amount of work has been performed in parallel to make inherently flexible transistors from plastic, including designs like electrochemical or electrolyte-gated transistors that are capable of modulating their output according to ionic currents. Conversely, these devices do not have the ability to work sufficiently fast to carry out the computations needed for bioelectronic devices employed in neurophysiology applications.

Together with George Spyropoulos, a postdoctoral research fellow and the study’s first author, Khodagholy developed a transistor channel predicated on conducting polymers to allow the modulation of ions. Also, in order to make the device to operate quickly, the team altered the material to have its very own mobile ions. By reducing the distance required by ions to move inside the polymer structure, the duo enhanced the transistor’s speed by an order of magnitude when compared to other identically-sized ionic devices.

Importantly, we only used completely biocompatible material to create this device. Our secret ingredient is D-sorbitol, or sugar. Sugar molecules attract water molecules and not only help the transistor channel to stay hydrated, but also help the ions travel more easily and quickly within the channel.

Dion Khodagholy, Assistant Professor, Department of Electrical Engineering, Columbia Engineering

Since the IGT can considerably enhance the tolerability and ease of EEG (electroencephalography) procedures for patients, the investigators chose this platform to prove the translational capacity of their device. To demonstrate this, they used their transistor to capture human brain waves from the scalp’s surface, and eventually showed that the local amplification of IGT directly at the scalp-device interface made it possible to decrease the contact size by five orders of magnitude—that is, the whole device fits easily between hair follicles, considerably streamlining the placement. In addition, the device can be easily and manually controlled, enhancing both electrical and mechanical stability. Furthermore, no chemical adhesives were required, since the micro-EEG IGT device conforms to the scalp, which means the patient did not experience skin irritation caused by adhesives and felt more comfortable overall.

Such kinds of devices can even be applied for making implantable closed-loop devices, like those presently used for treating certain forms of medically refractory epilepsy. Devices like these not only offer more information but would also be easier and smaller to implant.

Our original inspiration was to make a conformable transistor for neural implants. While we specifically tested it for the brain, IGTs can also be used to record heart, muscle, and eye movement.

Jennifer N. Gelinas, Department of Neurology, Columbia University Medical Center and Institute for Genomic Medicine

Together, Gelinas and Khodagholy are currently studying whether there are any physical limitations to the type of mobile ions that can be integrated into the polymer. The researchers are also exploring novel materials in which mobile ions can be embedded and how they can further improve their method with regards to using transistors for developing built-in circuits for responsive stimulation devices.

We are very excited that we could substantially improve ionic transistors by adding simple ingredients,” noted Khodagholy. “With such speed and amplification, combined with their ease of microfabrication, these transistors could be applied to many different types of devices. There is great potential for the use of these devices to benefit patient care in the future.”

Internal ion-gated organic electrochemical transistor: A Building Block for Intergrated Bioelectronics (Video credit: George Spyropoulos/Columbia Engineering)

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