Biomimetic Nanofluidics: Frontier Exploration for Future Artificial Intelligence and Brain-Computer Interfaces

  Since the advent of the world’s first electronic computer in 1946, computer technology has become the fastest-growing technology in the past 70 years and has the most disruptive impact on human production and life, especially the rapid development of artificial intelligence technology in recent years. It is far beyond people’s expectations and imagination. However, the accelerated development of artificial intelligence technology is based on the exponential growth of computing volume, which brings huge energy consumption. Therefore, there is an increasingly urgent need to develop a new generation of energy-efficient and intelligent computers. On the other hand, the human brain needs about 10 465 kJ of energy every day, of which only about 20% of the energy is used by the brain [1]. The power consumption of the human brain is only 24.22 watts, which is far less than one A desktop computer, not to mention an energy-hungry supercomputer. It can be seen that the human brain is an ultra-low energy consumption, ultra-high-performance biological intelligent system, and “brain imitation” has become an important breakthrough direction for researchers to explore new intelligent technologies.
  The development of brain science has given people a deeper understanding of the physiological process of the brain’s ultra-low energy consumption in the process of computing and memory. Nerve signals in the human brain are conducted through action potentials, and the generation of action potentials is inseparable from the regulation of ion transport within nano-confined ions by ion channels in neuron cells, and it is this regulation of ion transport that constitutes The physiological basis for moving from low-level muscle contractions to high-level thinking activities. On the other hand, nanofluidics, as a technology to study the behavior of fluids in nano-confined space, has developed rapidly in the past 15 years. The maturity of micro-nano-fabrication technology and nano-microscopic technology has gradually made it possible to control the movement of ions in nano-space.
  Biomimetic nanofluidics [2] is an emerging interdisciplinary subject born under the background of the rapid maturity of these different technologies. Inspired by the neural signal generation and storage mechanism in the brain, it designs a nano-confined space system with the help of micro-nano technology in the field of nanofluidics, so as to realize the intelligent regulation of its internal ion and other fluid transport behavior, with a view to using An artificial nanofluidic device platform reproduces neural electrical signals in the human brain. Artificial nanofluidic devices will surely have broad application prospects in the future interdisciplinary fields such as artificial intelligence, brain-computer interface and brain-like intelligence.
Signal Transmission Mechanisms in the Nervous System

  In order to successfully mimic the electrical signals in the nervous system, it is first necessary to clarify the mechanism by which the electrical signals are generated in the nervous system. In 1939, AL Hodgkin and AF Huxley of the University of Cambridge used self-made microelectrodes to insert into the neurons of squid, and first observed the transmembrane electrical signals and action potentials of neurons. It is the basic signal unit in nerve conduction, and the ion mechanism model for generating action potential (Hodgkin-Huxley model) [3] is proposed, which is of pioneering significance in the research on the mechanism of nerve signal generation and conduction. the Nobel Prize in Physiology or Medicine. Specifically, electrical signals in the nervous system are conducted through action potentials, and the generation of action potentials is closely related to two key ion channels (K+, Na+ channels) on the neuron cell membrane. Most ion channels are micro-channels with a certain configuration formed by specific protein molecules through self-assembly. When the external environmental conditions change, such as membrane potential, ion concentration, temperature, pH, etc., the configuration of protein molecules will change, thus Change the effective pore size of ion channels to achieve selective transport regulation of different ions.

  Both K+ and Na+ channels in nerve conduction are gated by voltage, that is to say, when the potential difference between the inside and outside of the cell membrane (that is, the membrane potential) reaches a certain value, the ion channel will open and close. change. The generation of action potentials in the nervous system is roughly divided into four stages: when there is no external stimulus, the neuron is in a resting state. At this time, the Na+ concentration inside the cell membrane is lower than that outside the cell membrane, and the K+ concentration inside the cell membrane is higher than that of the cell membrane. Externally, due to the difference in ion concentration inside and outside the cell membrane, the overall potential difference (membrane potential) between the inside and outside of the cell membrane is -64 mV. At this time, both ion channels are in a closed state; when the cell is stimulated by the outside world, the membrane potential begins to gradually increase, reaching the The voltage-gated threshold of the channel, the Na+ channel responds quickly and quickly opens. At this time, the K+ response is slow and remains closed. The high concentration of Na+ outside the cell quickly flows into the cell membrane, which increases the potential inside the cell membrane and forms a peak ; Then, the Na+ channel is closed and the K+ channel is opened through the configuration change of porin, and the high concentration of K+ inside the cell membrane diffuses out, resulting in a rapid drop in the internal potential of the cell membrane; when the membrane potential drops below the resting potential, the two The channel is gradually restored to the closed state, and the membrane potential is gradually restored to the initial state by ion diffusion, so that a complete action potential spike is formed. When this action potential is transmitted to the next neuron, it will become the external stimulus for the next neuron, further activating the next neuron to generate a new action potential. By analogy, external stimulation signals can be quickly conducted in the nervous system.
Biomimetic Nanofluidics

  Biomimetic nanofluidics, inspired by the signal transmission and storage mechanism of the biological nervous system, takes the function of ion channel controllable ion transport as a template, and constructs a nanofluidic device platform with similar functions through the design of nanomaterials. , including the preparation of nano-confined space, the study of material transport mechanism in confined space, the development of nano-fluidic devices for intelligent applications, etc., and the ultimate goal of building an intelligent computing system with ions as signal carriers.
  Advantages of ions as signal carriers The signal carriers that generate electrical signals in
  bionic nanofluidics are ions, which are very different from the signal carriers (electrons and holes) in most existing computers. The nanofluidic ion system brings some unique advantages: firstly, the bionic nanofluidic ion system does not have the cancellation of holes and electrons, and is more stable in the dynamic life process; secondly, the ion species and chemical properties are diverse, due to this Diversity can provide stronger coding and parallel computing capabilities in the future, providing more flexibility for design; at the same time, the mass of ions with the same charge is much larger than the mass of electrons with the same charge (>1000 times), In this way, it can better resist various external noises; it has the characteristics of low energy consumption, low heat generation, etc., which are closer to the real state of the organism. In addition, the regulation of fluid transport behavior by nanofluidic systems is not limited to ions, it can also be further extended to a wider range of biomolecular systems such as drug molecules and neurotransmitters, providing more opportunities for imitating more abundant physiological processes in the nervous system. possibility. These characteristics all bring bright prospects for the development of brain-like intelligence and brain-computer interface applications in the future.

  progress in iontronics Iontronics has generally experienced two stages: the initial development in the macroscopic system and the rapid development in the microscopic system. In 1959, the use of an ion-selective ion-exchange membrane was the first to realize a non-linear ion conduction electrical signal similar to a semiconductor PN junction in an aqueous system, that is, an IV electrical signal with a rectification effect. This achievement opened the prelude to the exploration of specific electrical signal output by controlling the motion of ions in the solution system [5]. Subsequently, ionic rectifier devices based on ion-exchange membranes in macroscopic systems have been constructed and studied one after another, and related theories have also been developed to a certain extent. However, iontronic devices in macroscopic systems do not have advantages in terms of size, energy and cost efficiency, and integration, so the development of iontronics has been relatively slow for a long time. Until around 2000, nanofluidics, as an emerging discipline to study the controllable transport behavior of fluids in nano-confined space (1-100 nanometers), has gradually become a frontier hot field concerned by the scientific community [6, 7], especially in recent years. In the past 15 years, the number of research work on nanofluidics has grown exponentially and has become one of the most active areas of scientific research. Especially in recent years, micro-nano fabrication and imaging and characterization technologies at the micro-nano scale have become more and more mature, and nanofluidic technology has entered a stage of rapid development. Various ion transport phenomena have gradually changed from imagination to reality. The gradual maturity of nanofluidic technology promotes the research of ion electronics gradually from macroscopic research to the new research field of microscopic nano-confined space.

  Initial studies on nanofluidic devices for regulating ion transport focused on one-dimensional nanofluidic device systems. For example, artificial single nanochannels are prepared by physical and chemical methods, and biomolecules, such as DNA molecules, are further used to modify and functionalize the interior of the nanochannels, and the change of the configuration of DNA molecules under specific environmental stimuli can be used to change the nanochannels. Effective pore size, so as to realize the regulation of ion transport behavior inside the channel [4]. Similar to semiconductor diodes, which have a unidirectional “rectification effect” for electron transport, the design of nanochannels can also achieve specific transport behavior of ions in different directions, which is called “nanocurrent diodes”. Further, more complex molecules or molecules with different responsiveness, such as amino acids, short peptide chains or some polymer materials, are used to construct biomimetic ion channels with more complex functions. Biomimetic symmetric/asymmetric artificial ion channels are developed to imitate the more complex ion channel structures and functions in biological systems, such as the preparation of nanocurrent diodes with various responsive synergies such as pH, temperature, ion concentration, electric field, magnetic field, and light response. system [4,7], and then integrated these nanochannels with specific transmission functions into microfluidic chips. In 2009, the first ionic logic circuit with aqueous phase as the working environment and ions as the information carrier was realized [5] . In 2019, researchers composited carbon nanotubes with flexible polymers and designed a new method to adjust ion transport in nanochannels in real time through the dynamic change of channel curvature, so as to obtain different rectification properties and endow artificial nanochannels with dynamic deformation. It is closer to the dynamic life process in the organism and is called “biomimetic dynamic nanochannel” [8].
  In recent years, with the further development of nanofluidic systems, two-dimensional materials represented by graphene, boron nitride, molybdenum disulfide, etc. have emerged rapidly, and they have a planar nano-confined structure formed between layers. , in this two-dimensional confined space, the translational degrees of freedom of ion motion are increased compared with the one-dimensional nanofluid system, which leads to an increase in the number of interactions between ions and more diverse forms of interaction, and ions will appear more diverse. Aggregated morphologies, while the hysteresis effect of ion motion brings a potential memory effect for maintaining these aggregated morphologies. For example, in 2021 [9], a two-dimensional confinement space constructed by graphene sheets, in which the monolayer electrolyte gradually agglomerates under the induction of an electric field, and reorganizes into chain-like clusters. The formation of chain-like clusters changes the system. The ionic conductance of the system endows the system with a memory effect of time-dependent ionic conductance, and obtains a “nanocurrent memristor”. Based on this nanocurrent memristor unit, the voltage spike action potential signal similar to that generated by biological neurons has been successfully reproduced. It demonstrates the great potential of nanofluidic ionic devices in mimicking the behavior of biological nervous systems. With the rapid development of iontronics in nanoscale systems, the new concept of biomimetic nanofluidics was first proposed in 2021 [2].
Application prospect of bionic nanofluidics

  Brain-computer interface (BCI) has always been a hot topic in literature such as science fiction. It is worth mentioning that in recent years, due to the rapid development of computer, brain science, bionic science, flexible electronics and material science, BCI technology has gradually moved from literature to reality, not only in the scientific community, but also in the social and corporate world. increasingly received positive attention. In 2020, the implantable brain chip released by E. Musk’s Neuralink company is expected to be used to control technical equipment such as mobile phones and computers through consciousness, once again causing extensive discussion and imagination of BCI technology from all walks of life. But at this stage, the two-way communication between the brain and the computer is far from practical. One of the main reasons is that the two systems use two different signaling media. Since bionic nanofluidics imitates the signal transmission mechanism and working environment of the brain, the signal carriers used are the same ions as in the brain, and the working environment is also the same water environment as the brain, which greatly improves the artificial The compatibility of nanofluidic devices with biological brains makes it possible to bridge the gap between brains and computers.
  At present, many top research teams around the world are conducting related research, and many of the latest research results have provided novel and rich perspectives and possible breakthroughs for the future development of this field. For example, the non-equilibrium properties of biological systems due to disturbance or dynamic deformation have attracted extensive attention in the scientific community [8]. The introduction of dynamic non-equilibrium properties will provide more dimensions for the study of complex response characteristics in organisms. Chinese researchers [10] proposed that the macroscopic quantum resonance state of biological ion channels may be used as an information carrier for signal transmission in the nervous system, and this signal transmission mechanism may be the reason for the extremely excellent energy saving of the nervous system. Since the information transmission between nanofluidic devices and biological systems uses the same “language”, it will break the information barriers between natural systems and artificial systems, making it a communication bridge between biological brains and artificial brains, which will greatly promote Development of interactive brain-computer interfaces and wearable (or implantable) devices. In addition, ionic devices work in an aqueous environment, which can also utilize the solid-liquid phase transition of aqueous solutions to study more challenging technologies, such as cryonics and hibernation in future interstellar travel.
  The ultimate goal of bionic nanofluidics research is to design an ultra-efficient and energy-saving artificial brain similar to the human brain by imitating the information generation and transmission mechanism in the human brain, and to develop artificial intelligence into a brain-like intelligence similar to the human brain. This is a huge project, which is still in the initial stage of development and faces many challenges. It needs the joint promotion of the progress of many disciplines in various fields. For example, to imitate the brain, the first theoretical basis is the development of brain science, which requires the efforts of brain science experts. When we have a better understanding of the neural network structure in the human brain and the mechanism of action such as signaling or memory, it will inspire and promote the design of brain-like structures. Advances in materials science are also required to enable sufficiently advanced micro- and nanofabrication techniques to precisely fabricate the biomimetic nanofluidic devices involved. At the same time, the development of computers and artificial intelligence is indispensable, and a set of algorithms that can adapt to this emerging nano-current component can be formed in order to finally achieve the goal.

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