Designing artificial sodium ion reservoirs to emulate biological synapses

Emulating neurons/synapses in the brain is an important step to realizing highly efficient computers. This fact makes neuromorphic devices important emerging solutions to the limitations imposed by the current computing architecture. To mimic synaptic functions in the brain, it is critical to replicate ionic movements in the nervous system. It is therefore important to note that ions move easily in liquids. In this study, we demonstrate a liquid-based neuromorphic device that is capable of mimicking the movement of ions in the nervous system by controlling Na+ movement in an aqueous solution. The concentration of Na+ in the solution can control the ionic conductivity of the device. The device shows short-term and long-term plasticity such as excitatory postsynaptic current, paired-pulse facilitation, potentiation, and depression, which are key properties for memorization and computation in the brain. This device has the potential to overcome the limitations of current von Neumann architecture-based computing systems and substantially advance the technology of neuromorphic computing. A liquid-based electronic device that acts like a human brain cell has been developed by researchers in South Korea. Electronic components that mimic information processing in the brain, so-called neuromorphic devices, could form computer architectures that are low-power and tolerant to the failure of individual elements. Dongshin Kim and Jang-Sik Lee from the Pohang University of Science and Technology demonstrated a liquid-based electronic device that works by the flow of electrically charged ions, as in the nervous system. Using disodium terephthalate as a reservoir of sodium ions, the team were able to control the ion concentration in an aqueous solution held between two electrodes. The device replicated many of the characteristics of biological synapses such as memory effects, which they achieved by adjusting the frequency and amplitude of electrical pulses applied across the electrodes. A liquid-based neuromorphic device that can mimic the movement of ions in a nervous system is demonstrated by controlling Na+ movement in an aqueous solution. The liquid-based neuromorphic device consists of disodium terephthalate, Nafion, NaCl solution, and electrodes. The top and bottom electrodes work as pre- and post synaptic neurons, respectively, and the NaCl solution/Na2TP@Nafion works as a synapse. The device shows short-term and long-term plasticity such as EPSC, PPF, STDP, potentiation, and depression.

In this study, we demonstrate a neuromorphic device in which electrical signals are transported using Na + through an aqueous solution because liquids can be practical components for neuromorphic device applications 34,35 . Disodium terephthalate (Na 2 TP) is used as a Na + reservoir to regulate the concentration of Na + ([Na + ]) in the liquid. Then, a change in [Na + ] induces synaptic functions in the device. The device exhibits characteristics of biological synapses such as potentiation, depression, excitatory postsynaptic current (EPSC), paired-pulse facilitation (PPF), and spike timing-dependent plasticity (STDP). The device also has long-term plasticity (LTP) characteristics that affect memory functions in the brain 36 . Furthermore, because a microfluidic system can be adopted to demonstrate an integrated array of liquid-based devices, the device has the potential to be integrated using microfluidic technology.

Results
A device that controlled [Na + ] was fabricated in the form of a two-terminal structure to mimic the transmission of signals between neurons and synapses (Fig. 1a). This artificial synapse consisted of Na 2 TP, Nafion, a NaCl solution, and electrodes. Na 2 TP is hydrophilic; consequently, the Na 2 TP layer can easily absorb liquids; therefore, Nafion was used to coat Na 2 TP to prevent direct contact with liquid [37][38][39][40] . Na 2 TP was mixed with the Nafion solution (Na 2 TP@Nafion) and deposited on the bottom electrode by spin coating. The microstructures of Nafion, Na 2 TP, and Na 2 TP@Nafion were investigated using scanning electron microscopy (SEM) (Fig. S1, Supplementary information). Na 2 TP has two sites that absorb Na + , and the existence of these two carbonyl groups allows for the insertion of two Na + ions ( Fig. 1b) [39][40][41] . A top-electrode/ NaCl solution/Na 2 TP@Nafion/bottom-electrode structure was used to mimic the functions of the synapse (Fig. 1c). The top and bottom electrodes acted as pre-and postsynaptic neurons, respectively, and the NaCl solution/ Na 2 TP@Nafion acted as a synapse.
The device exhibited short-term plasticity (STP) and LTP characteristics of synapses. These characteristics were achieved by adjusting the frequency and amplitude of the applied pulses. STP is an important feature of computing process in the nervous system 2,36 . The device demonstrated STP functions, such as EPSC, PPF, and excitatory postsynaptic potential (EPSP) [42][43][44][45] . The conductance of the device decreased temporarily when five positive pulses (0.5 V, 0.1 s) were applied to the device (Fig. 2a). However, when five negative pulses (−2 V, 0.1 s) were applied, the current of the device increased temporarily (Fig. 2b). In both cases, the conductance of the device returned to its initial value. The EPSC characteristics of the device were measured by applying a negative pulse (−1 V, 0.1 s) (Fig. 2c). When voltage pulses were applied to the solution, the ions migrated; however, they drifted back to their random positions after the application of voltage pulses owing to diffusion in the solution 5,34 . The device also showed EPSC characteristics with a short pulse (−3 V, 5 ms) (Fig. S2, Supplementary information). The device exhibited PPF, which is an increased postsynaptic response to the second pulse that arrives shortly after the first pulse (Fig. S3, Supplementary information). As the interval between the pulses decreased, the amplification of the second reaction response increased. The PPF ratio change in response to the time interval was expressed by a double-exponential function (Fig. 2d). The amplification of the responses was proportional to the frequencies of the applied pulses ( Fig. S4, Supplementary information). The device also showed EPSP characteristics, which are postsynaptic potentials that allow postsynaptic neurons to transport signals 46 . When a positive current pulse (0.1 mA, 0.1 s) was applied to the device, its potential increased temporarily and then gradually returned to the initial state (Fig. 2e). However, when pulses of positive current (0.1 mA, 0.1 s) were applied repeatedly, the increased potential of the device was maintained (Fig. 2f).
The LTP experienced a long-lasting change in its synaptic strength, thus suggesting the potentiation/ depression of synapses after repetitive stimulation-the result of information memorization 47 . When LTP was induced by the application of positive pulses to the top electrode, the device exhibited depression characteristics (Fig. 3a) linearly, and the device exhibited multiple different states during the depression process. To isolate the effects of ion diffusion in the solution, the conductance of the device was read 5 s after each stimulus was applied. To demonstrate the linear characteristics of potentiation and depression, nonidentical pulses were applied. When positive voltages were applied to the top electrode, Na + moved to the Na 2 TP@Nafion layer and was absorbed in the Na 2 TP. The resulting decline in [Na + ] in the solution produced depression characteristics. In contrast, when negative pulses were applied to the top electrode, Na 2 TP released Na + into the solution, thereby increasing [Na + ] as the conductance gradually increased as a result. These processes thus demonstrated the potentiation characteristics of the device (Fig. 3b). In addition, potentiation and depression characteristics were assessed with other concentrations to validate the effect of [Na + ] (Fig. S5, Supplementary information). All devices showed potentiation and depression characteristics, but the device with higher [Na + ] had a larger conductance change. The device exhibited endurance characteristics of potentiation and depression operations (Fig. S6, Supplementary information). Each pulse sequence consisted of 16 positive pulses (3 V, 0.1 s) followed by 16 negative pulses (−3 V, 0.1 s). A read pulse (0.1 V, 0.1 s) was applied to measure conductance after each stimulation pulse. The pulse sequence was repeated more than 200 times. In addition, STDP characteristics were emulated by applying pre-and postsynaptic pulses (Fig. 3c). Pre-and postsynaptic pulses (−3 V, 50 ms) were applied to the top and bottom electrodes, respectively. The synaptic weight change (%) of the device was plotted as a function of the time difference between the pre-and postsynaptic pulses. The device followed the Hebbian rule and therefore behaved similarly to biological synapses 48,49 . Strong stimuli resulted in LTP, which meant that the changed conductance values of the device were maintained with increasing amplitudes of the input pulses. Long-term potentiation characteristics were determined by applying 10 negative voltage pulses (Fig. 3d). When voltage pulses with amplitudes of −3, −4, or −5 V were applied to the device, the conductance of the device was maintained at increased values. The memory states of the device were maintained for more than 600 s (Fig. S7, Supplementary information). However, when voltage pulses with an amplitude of −1 V were applied to the device, the conductance of the device was not maintained at an increased value (Fig. S8, Supplementary information). These results imply that the device can memorize information in the long term according to the strength of the stimulus. Long-term depression characteristics were also characterized by the application of 10 positive voltage pulses (Fig. S9, Supplementary information). When voltage pulses with amplitudes of 2, 2.5, or 3 V were applied to the device, the conductance of the device was maintained at decreased values. The device showed both STP and LTP characteristics as a function of the strength of applied pulses. The emulated STP and LTP characteristics were similar to those of biological synapses, which are essential characteristics involved in the memorization and computation processes of the brain [50][51][52][53][54] . The performance of our device was compared with that of previous artificial synapses (Table S1, Supplementary information).

Discussion
The neuromorphic characteristics of the device are due to changes in the conductance of the NaCl aqueous solution. The device operation is composed of four states. In the initial state, Na + and Clare distributed randomly in the NaCl solution (Fig. 4a). The NaCl solution and Na 2 TP are separated by Nafion. When positive bias pulses are applied to the device in the initial state, Na + and Clcan be moved by bias polarity (Fig. 4b). Owing to the ion diffusion characteristics in the solution, the ionic current gradually decreases with repeated applications of stimuli. Na + cannot be absorbed in the Na 2 TP if the applied voltage is low; consequently, the [Na + ] in the solution does not change, and the conductance of the device returns to its original state. However, when sufficient voltage is applied, Na + can pass through Nafion and react with Na 2 TP. Na + is then absorbed into the Na 2 TP, causing a decrease in [Na + ] in the solution, which leads to a decrease in the conductivity of the device (Fig. 4c). When a negative voltage is applied to the device, Na + that has been absorbed in the Na 2 TP can be released from the Na 2 TP (Fig. 4d). The applied negative voltage drives an increase in the [Na + ] in the solution, causing potentiation. The number and amplitude of the bias pulses can control the [Na + ] in the solution. The reactions between Na + and Na 2 TP were analyzed by electrochemical impedance spectroscopy (EIS). The movement and concentration of the ions can be estimated based on these EIS results 55 . The diameter of the semicircles in the Nyquist plot decreased when the bias voltages applied to the device increased (Fig. S10a,  Supplementary information). It was inferred that the diameter of the semicircles changed owing to the reaction between Na 2 TP and Na + when bias voltages were applied 56,57 . These characteristics were also observed in the Bode plot of impedance (Fig. S10b, Supplementary  information). When the applied voltage increased, the impedance of the device decreased in the low-frequency range because of the concentration change in the solution 56 .
We developed a neuromorphic device that controlled [Na + ] using ion reservoirs for synaptic properties. The device, which was based on a NaCl solution and Na 2 TP, exhibited the synaptic characteristics of potentiation, depression, STP, LTP, and STDP according to the applied stimuli. The signal transmission processes of the neurons were emulated using electrochemical reactions between Na + and Na 2 TP@Nafion. The device used a change in [Na + ] in the solution to control synaptic properties. This device utilized an aqueous solution to emulate synaptic functions. This liquid-based artificial synapse has potential applications in biocompatible devices.

Device fabrication
The proposed device had a two-terminal structure. A SiO 2 /Si substrate with a size of 1.5 cm×1.5 cm was used. The substrate was sequentially cleaned by sonication in acetone, ethanol, and deionized water for 10 min each. Ti (10 nm) was deposited on the SiO 2 /Si substrate using electron-beam evaporation. Pt (100 nm) was then deposited using sputtering for the bottom electrode. Na 2 TP@-Nafion was synthesized by mixing Na 2 TP and Nafion at a weight ratio of 1:9. Na 2 TP@Nafion was spin-coated on the Pt bottom electrode at 1500 rpm for 60 s. Then, 70 μl of the NaCl solution was dropped on the Na 2 TP@Nafion layer. NaCl was dissolved in deionized water. Finally, the Au probe tip was brought in contact with the NaCl solution as the top electrode. The distance from the tip to the surface of Na 2 TP@Nafion was approximately 2 mm.

Characterization
All electrical properties were measured under ambient conditions and at room temperature. Electrical and electrochemical characteristics were obtained using a semiconductor parameter analyzer (KEITHLEY 4200A-SCS, Tektronix Inc., OR, USA) and an electrochemical impedance analyzer (Gamry-3000, Gamry Instruments, PA, USA), respectively. During electrical measurements, the bottom  Fig. 4 Schematic illustrations of the working mechanism of the device. a Initial state of the device. b Depression process of the device. Na + migrated to the Na 2 TP@Nafion layer when positive voltage pulses were applied to the top electrode. c After the depression process. Na + was absorbed in Na 2 TP, and the conductance of the device decreased. d Potentiation process of the device. When negative voltage pulses were applied to the top electrode, Na + was released from the Na 2 TP@Nafion layer, and the conductance of the device increased.
Pt electrode was grounded, and an electrical bias was applied using the probe tip. During electrochemical measurements, the Pt electrode was used as the counter electrode, while the probe tip was used as the working electrode. The microstructures of Nafion, Na 2 TP, and Na 2 TP@Nafion were investigated using field-emission SEM (JSM 7800, JEOL Ltd., Tokyo, Japan).