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Cell Junction Proteins-Mimetic Artificial Nanochannel System: Basic Logic Gates Implemented by Nanofluidic Diodes Yuting Wang, and Jin Zhai Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b03986 • Publication Date (Web): 31 Jan 2019 Downloaded from http://pubs.acs.org on February 2, 2019
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Langmuir
Cell Junction Proteins-Mimetic Artificial Nanochannel System: Basic Logic Gates Implemented by Nanofluidic Diodes Yuting Wang, and Jin Zhai* Key Laboratory of Smart bioinspired Interfacial Science and Technology of Ministry of Education School of Chemistry Beijing Advanced Innovation Center for Biomedical Engineering Beihang University Beijing 100191, P. R. China Supporting Information Placeholder ABSTRACT: Inspired by communication modes of cell junction proteins, artificial bi-channel nanofluidic diodes system was constructed and investigated to implement basic “AND” and “OR” logic gates in different connection modes. Input conditions were set as conducting and non-conducting states of each nanofluidic diode unit. Output results were set as response current of the system at rated voltage. Besides, nanofluidic diodes with different ionic permeability were connected in multiple modes and different logic operation results were obtained. This novel logic device based on nanofluidic diodes provided a new approach to establish diverse stimuli-responsive signals processing networks, and have prospect to obtain nanofluidic diodes intelligence chips by integrating in large scale.
INTRODUCTION Nanofluidic diodes are artificial nanochannels with rectification properties1. It is an ionic transistor which was achieved by introducing an uneven distribution of the surface potential in the channel2. Just like semiconductor transistors in electronic computer3, ionic transistors can also be used to construct complex logic circuits networks to perform a variety of logical computing functions4-6. In this work, we wanted to explore a simple way to achieve basic logic gate functions by artificial nanofluidic diodes. Learn from nature, different connection modes of cell junction proteins capable of different ion transport behaviors have attracted our attention. In living organisms, a huge number of interconnected biological networks exist widely to form complex biological communication systems, which makes the cell communication possible7. A variety of ion channel proteins embedded in the cytomembranes makes up of the structural unit of these networks to transport materials and transmit signals for cellular homeostasis and the regulation of growth and division. There are direct and indirect basic intercellular communication modes commonly existed between neighboring cells. Gap junction is a significant form of direct cell communication, which was formed by punctate ‘plaques’ at the interfaces between cells8. These clustered intercellular channels “plaques” was composed of two hexameric connexons proteins (hemichannels) which allowing the diffusion of ions and small molecules between the cytoplasm of adjacent cells without being affected by the extracellular matrix. There is evidence revealed that the rates of molecules flux through gap junction connexons were 1-3 orders of magnitude higher than those predicted by diffusion, indicating a significant affinity
Figure 1. Schematic diagram of artificial bi-channel systems: The separation and stacking connection modes of artificial bi-channel devices inspired by cell junction proteins ：Separation mode imitated indirect communication between cells, which was put the two nanoporous films separated by conducting solution. Stacking mode imitated the structure of gap junction between cells, which was putting the two nanoporous films stick together. In stacking monde, current density mutated and formed a field focusing region at the connected interface. This region acted as a barrier to current conduction and produced a field focusing resistor (Rff), which makes the response current in this mode significantly lower.
between the messenger molecules and the pore wall9. In addition, there is coupling of electric fields and structures between the two hemichannels10, and substance transfer between adjacent cells is accomplished by the synergism of two hemichannels. In other cases, cells indirect communicated with channel proteins mediated by intercellular matrix. Instead of docking directly, the ion channels in the adjacent cytomembranes are separated by extracellular matrix. Therefore, the extracellular matrix involvement is required in substrates transfer, and there is no coupling effect of structure and electric field between the two channel proteins, so the substrates transfer of each channel unit is independent with each other. Inspired by the two communication structures of cell junction proteins, we attempt to design artificial bi-channel systems in two operation modes to realize basic logic
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gate functions by nanoporous films11. As shown in Figure 1, separation mode imitated indirect communication between cells, which was constructed by putting the two nanoporous films separated by conducting solution. Electric fields inside the nanochannel units had no influence with each other, and each channel unit had individual ionic transport properties. Stacking mode of the bi-channel system imitated the structure of gap junction between cells, which was putting the two nanoporous films stick together to produce electric field and structure coupling effects of the channel units. Recently, various nanofluidic diodes have been reported12, and their highest rectification ratio could be achieved over thousands13. Based on the prominent properties, artificial nanofluidic diodes could be regarded as a binary computing unit, which was represented as “1” in conducting state or “0” in nonconducting state. These channel units could be connected together in different modes to achieve basic logic operations, such as “AND” gate and “OR” gate14. “AND” gate outputs high response current only if all the channel units are in conducting states, meanwhile “OR” gate outputs high response current if one or both the channel units in conducting states. The implementation of these basic logic operations builds a foundation of constructing complex logic computing networks. In addition, multiple stimuliresponsive signals could be introduced to affect the logical calculation results in the future research, so the system can analyze external signal comprehensively15. Because of the nanometer size and high rectification ratio of the nanofluidic diodes, its information processing capability has prospect comparable with semiconductor transistors.
EXPERIMENTAL PART Nanochannel preparation: Poly (ethylene terephthalate) (PET) films was irradiated by rapid heavy ions (thickness, 23μm; ion track density, 4×109 cm-2) and treated by UV light for 12h on each side before chemical etching. Etching solution (6M NaOH) was added on the working electrode side and stopping solution (1M KCl + 1M HCOOH) was added on the other side of the film. Channel 1 and channel 2 were parallel prepared together for synchronization reaction process of 20 minutes at 50 °C. Channel 3 and channel 4 were prepared for 17 minutes and 23 minutes at 50 °C respectively. The voltage (1V) was used to monitor the etching process. Then the etching was stopped by soaking the film in stopping solution at room temperature, and finally, the film was washed in Milli-Q water (18.2 MΩ) to remove residual salts. Current-Voltage measurement: Ionic current was measured by a Keithley 6487 picoammeter (Keithley instruments, Cleveland, Ohio). The scanning voltage varied from -2 to +2 V; Ag/AgCl electrodes were applied to measure the resulting ionic current. Before the ionic current measurement, films should be wetted by Milli-Q water. In the stacking mode, the bi-channel devices were formed by stacking the nanoporous films together, and the two films were carefully placed with their flat sides on top of each other to prevent air bubbles from being trapped between the two films, and they were then mounted between the two chambers of a conductivity cell. In the separation mode, the bichannel devices were formed by separated the two films by a chamber with conductive solution. Experimental facility schematic diagram and its detailed size was performed in Figure S2. After assembly, the chambers were filled with 0.1M KCl pH 7 buffer solution, and the films are infiltration in this conductive solution at least half hours to keep stable of the nanochannels
before tested. Each measurement was repeated at least five times to obtain the average current at different voltages.
RESULTS AND DISCUSSION Herein, we designed a logic device based on bi-channel artificial nanofluidic diodes which were connected in stacking mode and separation mode. In stacking mode, unlike lipid bilayer membranes in organisms, the artificial ionic channel porous films have no fluidity and local flexibility, which make these nanopore arrays on each PET films misalignment with each other. The current density mutated and formed a field focusing region at the connected interface16. This region acted as a barrier to current conduction and produced a field focusing resistor (Rff)17, which makes the response current in this mode significantly lower. Therefore, different response current would be generated when bichannel system connected in stacking or separation modes, thus forms different logical calculation results. Based on this, different logic gates could be built by adjusting connection modes of the channel units. Poly (ethylene terephthalate) (PET) films with conical shaped nanochannel matrixes are easy to be prepared and commonly have stable rectification property, so it was adopted to assemble the structural unit of the bi-channel device18. First, a bi-channel logical device was built with two same nanofluidic diodes, which were set as channel 1 and channel 2. The selected two PET porous films were etched synchronously to ensure that they performed similar conical channel characters and I-V curves19, thus eliminate the channel connected order difference effects in bi-channel systems. Due to their asymmetric structures, channel 1 and channel 2 could be regarded as nanofluidic diodes respectively. When the direction of the applied electric field from tip side to base side, channel 1 or channel 2 performed higher current outputs, that is, the nanofluidic diode units were in conducting states. On the contrary, they performed
Figure 2. a) Four states of bi-channel system; I-V curves in four cascade states of bi-channel devices in b) stacking mode and d) separation mode; response current at +2 V bias in four cascade states of bi-channel devices in c) stacking mode and e) separation mode. (The drawn conical pores only indicated the direction of each conical nanopores in the2 porous films and did not reflected the number of the pores.)
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Langmuir lower current outputs and non-conducting states20. As shown in Figure 2a, channel 1 and channel 2 were assembled in four states in stacking mode (STA 1&2) and separation mode (SEP 1&2) respectively by adjusting the connection directions of each channel unit: state 1 was connected channel 1 tip side to channel 2 base side; state 2 was connected channel 1 tip side to channel 2 tip side; state 3 was connected channel 1 base side to channel 2 base side; state 4 was connected channel 1 base side to channel 2 tip side. I-V curves show that STA 1&2 and SEP 1&2 modes performed completely different response current properties. At STA 1&2 mode, Rff reduced the response current and eliminated the rectification properties with the system (Figure 2b). However, STA 1&2 state 3, porous films were connected by the base side of the conical channels, and the larger channel joint area reduced the mutation of the electric field. Therefore, Rff had little effects, and the system performed higher output current (Figure 2b, blue line). At SEP 1&2 mode, Rff was not existed, each channel unit exhibited their individual ion transport properties. I-V curves were shown in Figure 2d, the asymmetric structures of state 1 and 4 presented opposite rectification property, which was obtained higher output current and lower output current respectively in the opposite bias (Figure 2d, black line and pink line). Meanwhile, the symmetric structures of state 2 and 3 presented higher output current (Figure 2d, red line and blue line, almost coincide). According to the I-V curves of STA 1&2 and SEP 1&2 modes, logic gates at rated voltage were built. At +2 V bias, channel 1 and channel 2 in the bi-channel systems were set as input A and input B, and conducting states were set as “1” and non-conducting states was set as “0” (Figure 2c). The response current of the bichannel system was set as output results. Higher current was set as “1”, and lower current was set as “0”. In state 1, the directions of applied electric field of both channel 1 and channel 2 were from base side to tip side. Channel units are in non-conducting states, thus input A and input B were “0” value. In state 2, change the direction of applied electric field of channel 2 from tip side to the base side, channel 1 was still in conducting state, but channel 2 was in non-conducting state. Input A was “0” and input B was “1”. In state 3, the direction of applied electric field of channel 1 was from tip side to base side and channel 2 was from base side to tip side. Input A was “1” and Input B was “0”. In state 4, the directions of applied electric field of both channel 1 and channel 2 were from tip side to base side. Input A and Input B were “1” value. Under the four input states, STA 1&2 and SEP 1&2 modes performed different output results. STA 1&2 mode output high response current only in state 3, and exhibited similar “AND” gate property. While, SEP 1&2 mode output high response current in state 2, state 3 and state 4, and exhibited “OR” gate property (Figure 2e). Set-up diagram of each state and truth table of STA 1&2 and SEP 1&2 modes were listed in Figure 3. Therefore, bichannel device implemented the operations of basic logic gates, which could become the structure units of complex logical
networks, and different functions of logic gate could be realized by adjusting the connection modes. Next, effects of channel units with different ionic permeability on logical output results of the systems were investigated. Two nanoporous films were adopted with ionic current difference for one order of magnitudes, which were set as channel 3 (high permeability) and channel 4 (low permeability). They were etched in different conditions to obtain different aperture sizes. System was investigated in four connection modes, which were channel 3 connected channel 4 in stacking mode (STA 3&4), channel 3 connected channel 4 in separation mode (SEP 3&4), channel 4 connected channel 3 in stacking mode (STA 4&3) and channel 4 connected channel 3 in separation mode (SEP 4&3). I-V curves of four states under each mode were obtained by adjusting the connection directions of channel units. As shown in Figure 4, bichannel devices consisting of channel 3 and channel 4 still performed different response current and rectification properties in stacking and separation mode, but it was different from channel 1&2 system. In stacking mode, Rff plays a major role in response current of the system. Because channel 3 had larger tip side aperture than channel 4, Rff (depended on the size of tip side) were low at negative bias and high at positive bias in STA 3&4 state 1. So bi-channel device performed greater rectification property. I-V curve of STA 4&3 state 4 performed opposite rectification property (these two states had same connection structure and opposite testing voltage). While in STA 3&4 state 4 and STA 4&3 state 1 (these two states had same connection structure and opposite testing voltage), higher Rff at bias on both directions made their I-V curves performed low output current and no rectification property. State 2 and state 3 in stacking mode had similar properties with channel 1&2 system. At +2 V bias, input conditions were also set as conducting and non-conducting states of each channel unit. Different output results were obtained under the four states. STA 3&4 still achieved similar “AND” gate property, while STA 4&3 obtained the calculation results equal to the value of input A. In separation mode, channel 4 has relatively low permeability, which plays a major role in the response current of the system. So bi-channel system performed the volt-ampere properties of channel 4 in each state under different connection orders. At +2 V bias, four cascade states were also tested in two connection orders. Output values were equal to the input conditions of channel 4. Therefore, in bi-channel system with different permeability, connection order affected the logical operation results. In STA 3&4 mode, bi-channel device performed similar “AND” gate which was different from SEP 3&4 mode. While, in channel 4&3 connection order, both of the stacking and separation mode performed same output results which depended on the less permeable channel. These properties made it possible to design complex logic circuits with different functions by regulating connection orders of bi-channel devices.
Figure 3. The tested connection modes and logic gate of channel 1&2 systems. Channel 1 and channel 2 are two same nanochannels, which have no connection order effects. The responsive current was set as output result, which was tested at +2V bias for each states.
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Figure 4. The tested connection modes and logic gate of channel 3&4 and channel 4&3 systems. Channel 3 and channel 4 have ionic current difference for one order of magnitudes. The responsive current was set as output result, which was tested at +2V bias for each states.
CONCLUSIONS In summary, we designed an artificial bi-channel nanofluidic diode logic device, which was consisted of two conical PET porous films. Conducting and non-conducting states were set as input conditions and the response current at rated voltage was set as output results. At +2V bias, channel 1&2 system implement “AND” and “OR” logic gates in stacking and separation connection mode respectively, which was the basic unit that makes up the complex logic circuit. Channel 3&4 and channel 4&3 bi-channel system achieved different logical operation functions through controlling the connection order of the channel unit. These bi-channel nanofluidic diodes mimicked the connection modes of cell junction proteins, which provide a new idea to construct complex artificial information communication networks. Artificial nanochannels with multiple simuli-responsive
functions, such as pH, light, temperature, ions, molecules, could be introduced in this logic device to achieve intelligent processing results. In the future, these nanochannels with different functions will probably be integrated on large scale to form nanofluidic diodes chips, which open a new field to form artificial intelligence computer. It superiority is that the artificial nanofluidic diodes circuits have three-dimensional nanostructure compared with semiconductor transistor circuits, which provide more powerful information processing capability.
ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website.
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Langmuir (19) Xu, Y.; Sui, X.; Guan, S.; Zhai, J.; Gao, L., Olfactory Sensory Neuron-Mimetic CO2 Activated Nanofluidic Diode with Fast Response Rate. Adv. Mater. 2015, 27, (11), 1851-1855. (20) Yan, R.; Liang, W.; Fan, R.; Yang, P., Nanofluidic Diodes Based on Nanotube Heterojunctions. Nano Lett. 2009, 9, (11), 3820-3825.
AUTHOR INFORMATION Corresponding Author
[email protected] Notes The authors declare no competing financial interests.
ACKNOWLEDGMENT This work was supported by the National Key Research and Development Program of China (2017YFA0206902, 2017YFA0206900), the National Natural Science Foundation (21471012, 21771016), the International Science and Technology Cooperation Program of China (2014DFA52820).
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TABLE OF CONTENTS GRAPHIC
Based on the connection mode of cell junction proteins, artificial nanochannels was connected in stacking mode and separation mode respectively to realize basic logical gate functions.
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