Exploring DNA Computers: Advances in Storage, Cryptography and Logic Circuits.

Over the last four decades, research on DNA as a functional material has primarily  focused on its predictable conformation and programmable interaction. However, its low energy consumption, high responsiveness and sensitivity also make it ideal for designing specific signaling pathways, and enabling the development of molecular computers. This review mainly discusses recent advancements  in the utilization of DNA nanotechnology for molecular computer, encompassing applications in storage, cryptography and logic circuits. It elucidates the challenges encountered in the application process and presents solutions exemplified by representative works. Lastly, it delineates the challenges and opportunities within this filed.

Multibarrier Collaborative Modulation Devices with Ultra-High Logic Operation Density.

The demands for highly miniaturized and multifunctional electronics are rapidly increasing. As scaling-down processes of transistors are restricted by physical limits, reconfigurable electronics with switchable operation functions for different tasks are developed for higher function integration based on split- or vertical-dual-gate structures. To promote the present reconfigurable electronics and exceed the function integration limit, the critical issue is to integrate complex operations into simple circuit forms by establishing more control dimensions. This work proposes a multibarrier collaborative (MBC) modulation architecture to increase the control dimension by multiple forms of potential barriers and achieves combinational and reconfigurable logic operations by a single MBC device. The MBC architecture exhibits ultrahigh logic operation density, including 58.8% area reduction for multiplexer operations and 71.4% area reduction for 4-logic reconfigurable operations. Besides, a hardware security module composed of 4 MBC devices implementing 8 types of logic operations is demonstrated. This work reveals an effective design of function integration for next-generation electronics.

DNA nanotechnology for cell-free DNA marker for tumor detection: a comprehensive overview.

Advancements in DNA nanotechnology have led to new exciting ways to detect cell-free tumor biomarkers, revolutionizing cancer diagnostics. This article comprehensively reviews recent developments in this field, discussing the significance of liquid biopsies and DNA nanomachines in early cancer detection. The accuracy of cancer diagnosis at its early stages is expected to be significantly improved by identifying biomarkers. Liquid biopsies, offering minimally-invasive testing, hold the potential for capturing tumor-specific components like circulating tumor cells, cell-free DNA, and exosomes. DNA nanomachines are advanced molecular devices that exploit the programmability of DNA sequences for the ultrasensitive and specific detection of these markers. DNA nanomachines, nanostructures made of DNA that can be designable and switchable nanostructures, have a wide range of advantages for detecting tumor biomarkers, including non-invasiveness, affordability, high sensitivity, and specificity. Scientists also work on dealing with challenges like low marker concentrations and interference, which are addressed through microfluidic integration, nanomaterial amplification, and indirect signal detection. Despite advances, multiplex detection remains a challenge. In conclusion, DNA nanomachines bear immense promise for cancer diagnostics, advocating personalized treatment and improving patient outcomes. Continued research could redefine how we find and treat tumors, leading to better patient outcomes.

A DNA Molecular Logic Circuit for Precise Tumor Identification.

Tumor-associated antigens (TAAs) are not exclusively expressed in cancer cells, inevitably causing the "on target, off tumor" effect of molecular recognition tools. To achieve precise recognition of cancer cells, by using protein tyrosine kinase 7 (PTK7) as a model TAA, a DNA molecular logic circuit Aisgc8 was rationally developed by arranging H+-binding i-motif, ATP-binding aptamer, and PTK7-targeting aptamer Sgc8c in a DNA sequence. Aisgc8 output the conformation of Sgc8c to recognize PTK7 on cells in a simulated tumor microenvironment characterized by weak acidity and abundant ATP, but not in a simulated physiological environment. Through in vitro and in vivo results, Aisgc8 demonstrated its ability to precisely recognize cancer cells and, as a result, displayed excellent performance in tumor imaging. Thus, our studies produced a simple and efficient strategy to construct DNA logic circuits, opening new possibilities to develop convenient and intelligent precision diagnostics by using DNA logic circuits.

Reconfigurable Vertical Phototransistor with MoTe2 Homojunction for High-Speed Rectifier and Multivalued Logical Circuits.

The most reported two-dimensional (2D) reconfigurable multivalued logic (RMVL) devices primarily involve a planar configuration and carrier transport, which limits the high-density circuit integration and high-speed logic operation. In this work, the vertical transistors with reconfigurable MoTe2 homojunction are developed for low-power, high-speed, multivalued logic circuits. Through top/bottom dual-gate modulation, the transistors can be configured into four modes: P-i-N, N-i-P, P-i-P, and N-i-N. The reconfigurable rectifying and photovoltaic behaviors are observed in P-i-N and N-i-P configurations, exhibiting ideal diode characteristics with a current rectification ratio over 105 and sign-reversible photovoltaic response with a photoswitching ratio up to 7.44 × 105. Taking advantage of the seamless homogeneous integration and short vertical channel architecture, the transistor can operate as an electrical switch with an ultrafast speed of 680 ns, surpassing the conventional p-n diode. The MoTe2 half-wave rectifier is then applied in high-frequency integrated circuits using both square wave and sinusoidal waveforms. By applying an electrical pulse with a 1/4 phase difference between two input signals, the RMVL circuit has been achieved. This work proposes a universal and reconfigurable vertical transistor, enabled by dual-gate electrostatic doping on top/bottom sides of MoTe2 homojunction, suggesting a high integration device scheme for high-speed RMVL circuits and systems.

2D Reconfigurable van der Waals Heterojunction for Logic Gate Circuits and Wide-Spectrum Photodetectors via Sulfur Substitution and Band Matching.

The attractive physical properties of two-dimensional (2D) semiconductors in group IVA-VIA have been fully revealed in recent years. Combining them with 2D ambipolar materials to construct van der Waals heterojunctions (vdWHs) can offer tremendous opportunities for designing multifunctional electronic and optoelectronic devices, such as logic switching circuits, half-wave rectifiers, and broad-spectrum photodetectors. Here, an optimized SnSe0.75S0.25 is grown to design a SnSe0.75S0.25/MoTe2 vdWH for logic operation and wide-spectrum photodetection. Benefiting from the excellent gate modulation under the appropriate sulfur substitution and type-II band alignment, the device exhibits reconfigurable antiambipolar and ambipolar transfer behaviors at positive and negative source-drain voltage (Vds), enabling stable XNOR logic operation. It also features a gate-modulated positive and negative rectifying behavior with rectification ratios of 265:1 and 1:196, confirming its potential as half-wave logic rectifiers. Besides, the device can respond from visible to infrared wavelength up to 1400 nm. Under 635 nm illumination, the maximum responsivity of 1.16 A/W and response time of 657/500 µs are achieved at the Vds of -2 V. Furthermore, due to the strong in-plane anisotropic structure of SnSe0.75S0.25-alloyed nanosheet and narrow bandgap of 2H-MoTe2, it shows a broadband polarization-sensitive function with impressive photocurrent anisotropic ratios of 15.6 (635 nm), 7.0 (808 nm), and 3.7 (1310 nm). The direction along the maximum photocurrent can be reconfigurable depending on the wavelengths. These results indicate that our designed alloyed SnSe0.75S0.25/MoTe2 vdWH has reconfigurable logic operation and broadband photodetection capabilities in 2D multifunctional integrated circuits.

Nitrogen-Doped 3D-Graphene Advances Near-Infrared Photodetector for Logic Circuits and Image Sensors Overcoming 2D Limitations.

The limitations of two-dimensional (2D) graphene in broadband photodetector are overcome by integrating nitrogen (N) doping into three-dimensional (3D) structures within silicon (Si) via plasma-assisted chemical vapor deposition (PACVD) technology. This contributes to the construction of vertical Schottky heterojunction broad-spectrum photodetectors and applications in logic devices and image sensors. The natural nanoscale resonant cavity structure of 3D-graphene enhances photon capture efficiency, thereby increasing photocarrier generation. N-doping can fine-tune the electronic structure, advancing the Schottky barrier height and reducing dark current. The as-fabricated photodetector exhibits exceptional self-driven photoresponse, especially at 1550 nm, with an excellent photoresponsivity (79.6 A/W), specific detectivity (1013 Jones), and rapid response of 130 µs. Moreover, it enables logic circuits, high-resolution pattern image recognition, and broadband spectra recording across the visible to near-infrared range (400-1550 nm). This research will provide new views and technical support for the development and widespread application of high-performance semiconductor-based graphene broadband detectors.

Erasable and Field Programmable DNA Circuits Based on Configurable Logic Blocks.

DNA is commonly employed as a substrate for the building of artificial logic networks due to its excellent biocompatibility and programmability. Till now, DNA logic circuits are rapidly evolving to accomplish advanced operations. Nonetheless, nowadays, most DNA circuits remain to be disposable and lack of field programmability and thereby limits their practicability. Herein, inspired by the Configurable Logic Block (CLB), the CLB-based erasable field-programmable DNA circuit that uses clip strands as its operation-controlling signals is presented. It enables users to realize diverse functions with limited hardware. CLB-based basic logic gates (OR and AND) are first constructed and demonstrated their erasability and field programmability. Furthermore, by adding the appropriate operation-controlling strands, multiple rounds of programming are achieved among five different logic operations on a two-layer circuit. Subsequently, a circuit is successfully built to implement two fundamental binary calculators: half-adder and half-subtractor, proving that the design can imitate silicon-based binary circuits. Finally, a comprehensive CLB-based circuit is built that enables multiple rounds of switch among seven different logic operations including half-adding and half-subtracting. Overall, the CLB-based erasable field-programmable circuit immensely enhances their practicability. It is believed that design can be widely used in DNA logic networks due to its efficiency and convenience.

Ultrastable N-Type Semiconducting Fiber Organic Electrochemical Transistors for Highly Sensitive Biosensors.

Organic electrochemical transistors (OECTs) have attracted increasing attention due to their merits of high transconductance, low operating voltage, and good biocompatibility, ideal for biosensors. However, further advances in their practical applications face challenges of low n-type performance and poor stability. Here, it is demonstrated that wet-spinning the commercially available n-type conjugated polymer poly(benzimidazobenzophenanthroline) (BBL) into highly aligned and crystalline fibers enhances both OECT performance and stability. Although BBL is only soluble in high-boiling-point strong acids, it can be wet-spun into high-quality fibers with adjustable diameters. The BBL fiber OECTs exhibit a record-high area-normalized transconductance (gm,A) of 2.40 µS µm-2 and over 10 times higher figure-of-merit (µC*) than its thin-film counterparts. More importantly, these fiber OECTs exhibit remarkable stability with no noticeable performance attenuation after 1500 cycles over 4 h operation, outperforming all previously reported n-type OECTs. The superior performance and stability can be attributed to shorter π-π stacking distance and ordered molecular arrangement in the fibers, endowing the BBL fiber OECT-based biosensors with outstanding sensitivity while keeping a miniaturized form factor. This work demonstrates that, beyond new material development, developing new fabrication technology is also crucial for addressing the performance and stability issues in n-type OECTs.

DNA Logic Gates Integrated on DNA Substrates in Molecular Computing.

Due to nucleic acid's programmability, it is possible to realize DNA structures with computing functions, and thus a new generation of molecular computers is evolving to solve biological and medical problems. Pioneered by Milan Stojanovic, Boolean DNA logic gates created the foundation for the development of DNA computers. Similar to electronic computers, the field is evolving towards integrating DNA logic gates and circuits by positioning them on substrates to increase circuit density and minimize gate distance and undesired crosstalk. In this minireview, we summarize recent developments in the integration of DNA logic gates into circuits localized on DNA substrates. This approach of all-DNA integrated circuits (DNA ICs) offers the advantages of biocompatibility, increased circuit response, increased circuit density, reduced unit concentration, facilitated circuit isolation, and facilitated cell uptake. DNA ICs can face similar challenges as their equivalent circuits operating in bulk solution (bulk circuits), and new physical challenges inherent in spatial localization. We discuss possible avenues to overcome these obstacles.

Multicolor Fluorescent Inks Based on Lanthanide Hybrid Organogels for Anticounterfeiting and Logic Circuit Design.

With the rapid development of information technology, the encrypted storage of information is becoming increasingly important for human life. The luminescent materials with a color-changed response under physical or chemical stimuli are crucial for information coding and anticounterfeiting. However, traditional fluorescent materials usually face problems such as a lack of tunable fluorescence, insufficient surface-adaptive adhesion, and strict synthesis conditions, hindering their practical applications. Herein, a series of luminescent lanthanide hybrid organogels (Ln-MOGs) were rapidly synthesized using a simple method at room temperature through the coordination between lanthanide ions and 2,6-pyridinedicarboxylic acid and 5-aminoisophthalic acid. And the multicolor fluorescent inks were also prepared based on the Ln-MOG and hyaluronic acid, with the advantages of being easy to write, color-adjustable, and water-responsive discoloration, which has been applied to paper-based anticounterfeiting technology. Inspired by the responsiveness of the fluorescent inks to water, we designed a logic system that can realize single-input logic operations (NOT and PASS1) and double-input logic operations (NAND, AND, OR, NOR, XOR). The encryption of a binary code can be actualized utilizing different luminescent response modes based on the logic circuit system. By adjusting the energy sensitization and luminescence mechanism of lanthanide ions in the gel structure, the information reading and writing ability of the fluorescent inks were verified, which has great potential in the field of multicolor pattern anticounterfeiting and information encryption.

Well-Balanced Ambipolar Charge Transport of Diketopyrrolepyrrole-Based Copolymers: Organic Field-Effect Transistors and High-Voltage Logic Applications.

A poly (3,6-bis(thiophen-2-yl)-2,5-bis(2-decyltetradecyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione-co-(2,3-bis(phenyl)acrylonitrile)) (PDPADPP) copolymer, composed of diketopyrrolopyrrole (DPP) and a cyano (nitrile) group with a vinylene spacer linking two benzene rings, is synthesized via a palladium-catalyzed Suzuki coupling reaction. The electrical performance of PDPADPP in organic field-effect transistors (OFETs) and circuits is investigated. The OFETs based on PDPADPP exhibit typical ambipolar transport characteristics, with the as-cast OFETs demonstrating low field-effect hole and electron mobility values of 0.016 and 0.004 cm2  V-1  s-1 , respectively. However, after thermal annealing at 240 °C, the OFETs exhibit improved transport characteristics with highly balanced ambipolar transport, showing average hole and electron mobility values of 0.065 and 0.116 cm2  V-1  s-1 , respectively. To verify the application of the PDPADPP OFETs in high-voltage logic circuits, compact modeling using the industry-standard small-signal Berkeley short-channel IGFET model (BSIM) is performed, and the logic application characteristics are evaluated. The circuit simulation results demonstrate excellent logic application performance of the PDPADPP-based ambipolar transistor and illustrate that the device annealed at 240 °C exhibits ideal circuit characteristics.

Approaching Theoretical Limits in the Performance of Printed P-Type CuI Transistors via Room Temperature Vacancy Engineering.

Development of a novel high performing inorganic p-type thin film transistor could pave the way for new transparent electronic devices. This complements the widely commercialized n-type counterparts, indium-gallium-zinc-oxide (IGZO). Of the few potential candidates, copper monoiodide (CuI) stands out. It boasts visible light transparency and high intrinsic hole mobility (>40 cm2 V-1 s-1 ), and is suitable for various low-temperature processes. However, the performance of reported CuI transistors is still below expected mobility, mainly due to the uncontrolled excess charge- and defect-scattering from thermodynamically favored formation of copper and iodine vacancies. Here, a solution-processed CuI transistor with a significantly improved mobility is reported. This enhancement is achieved through a room-temperature vacancy-engineering processing strategy on high-k dielectrics, sodium-embedded alumina. A thorough set of chemical, structural, optical, and electrical analyses elucidates the processing-dependent vacancy-modulation and its corresponding transport mechanism in CuI. This encompasses defect- and phonon-scattering, as well as the delocalization of charges in crystalline domains. As a result, the optimized CuI thin film transistors exhibit exceptionally high hole mobility of 21.6 ± 4.5 cm2 V-1 s-1 . Further, the successful operation of IGZO-CuI complementary logic gates confirms the applicability of the device.

Integrated Logic Circuits Based on Wafer-Scale 2D-MoS2 FETs Using Buried-Gate Structures.

Two-dimensional (2D) transition-metal dichalcogenides (TMDs) materials, such as molybdenum disulfide (MoS2), stand out due to their atomically thin layered structure and exceptional electrical properties. Consequently, they could potentially become one of the main materials for future integrated high-performance logic circuits. However, the local back-gate-based MoS2 transistors on a silicon substrate can lead to the degradation of electrical characteristics. This degradation is caused by the abnormal effect of gate sidewalls, leading to non-uniform field controllability. Therefore, the buried-gate-based MoS2 transistors where the gate electrodes are embedded into the silicon substrate are fabricated. The several device parameters such as field-effect mobility, on/off current ratio, and breakdown voltage of gate dielectric are dramatically enhanced by field-effect mobility (from 0.166 to 1.08 cm2/V·s), on/off current ratio (from 4.90 × 105 to 1.52 × 107), and breakdown voltage (from 15.73 to 27.48 V) compared with a local back-gate-based MoS2 transistor, respectively. Integrated logic circuits, including inverters, NAND, NOR, AND, and OR gates, were successfully fabricated by 2-inch wafer-scale through the integration of a buried-gate MoS2 transistor array.

Anti-Ambipolar Heterojunctions: Materials, Devices, and Circuits.

Anti-ambipolar heterojunctions are vital in constructing high-frequency oscillators, fast switches, and multivalued logic (MVL) devices, which hold promising potential for next-generation integrated circuit chips and telecommunication technologies. Thanks to the strategic material design and device integration, anti-ambipolar heterojunctions have demonstrated unparalleled device and circuit performance that surpasses other semiconducting material systems. This review aims to provide a comprehensive summary of the achievements in the field of anti-ambipolar heterojunctions. First, the fundamental operating mechanisms of anti-ambipolar devices are discussed. After that, potential materials used in anti-ambipolar devices are discussed with particular attention to 2D-based, 1D-based, and organic-based heterojunctions. Next, the primary device applications employing anti-ambipolar heterojunctions, including anti-ambipolar transistors (AATs), photodetectors, frequency doublers, and synaptic devices, are summarized. Furthermore, alongside the advancements in individual devices, the practical integration of these devices at the circuit level, including topics such as MVL circuits, complex logic gates, and spiking neuron circuits, is also discussed. Lastly, the present key challenges and future research directions concerning anti-ambipolar heterojunctions and their applications are also emphasized.

Self-Powered UV Photodetector of TiO2 with BaTiO3 Surface Modification and Light-Controlled Logic Circuits Application.

One-dimensional (1D) metal oxides with excellent carrier transport and light absorption properties can be applied to photodetectors (PDs), facilitating device miniaturization, portability, and integration. Surface modification of 1D semiconductors can reduce carrier recombination in PDs as a way to increase photocurrent and decrease dark current of PDs. Herein, ultrathin BaTiO3 (BTO) shell layers are grown on the surface of TiO2 nanorod arrays (NRs) by in situ conversion using hydrothermal reaction, and the self-powered TiO2-BTO NRs PDs are constructed. The effect of the thickness of BTO shell layers on the photoresponse characteristics of self-powered TiO2-BTO NRs PDs is investigated by controlling the Ba2+ conversion concentration. The results show that the BTO shell layer reduces the dark current of the PDs because of the decreased interfacial transfer resistance and improved transfer of photogenerated carriers for building a "bridge" of carrier transport between BTO and TiO2 due to the formation of Ti-O-Ti bonds. Moreover, the presence of the spontaneous polarization electric field in BTO enhances the photocurrent and response speed of PDs. The self-powered TiO2-BTO NRs PDs are integrated in series and parallel to realize the functions of "and" and "or" gates of light-controlled logic gates. The ability to convert light signals into electrical signals for the self-powered PDs in real time demonstrates its great potential for optoelectronic interconnection circuits, which has important application prospects in the field of optical communication.

A versatile MOF-derived theranostic for dual-miRNA controlled accurate cancer cell recognition and photodynamic therapy.

Precise detection and monitoring of microRNAs (miRNAs) in living tumor cells is significant for the prompt diagnosis of cancer and provides important information for treatment of cancer. A significant challenge is developing methods for imaging different miRNAs simultaneously to further enhance diagnostic and treatment accuracy. In this work, a versatile MOF-derived theranostic system (DAPM) was constructed using photosensitive metal-organic frameworks (PMOF, PM) and a DNA AND logic gate (DA). The DAPM exhibited excellent biostability and enabled sensitive detection of miR-21 and miR-155, achieving a low limit of detection (LOD) for miR-21 (89.10 pM) and miR-155 (54.02 pM). The DAPM probe generated a fluorescence signal in tumor cells where miR-21 and miR-155 co-existed, demonstrating the enhanced ability of tumor cell recognition. Additionally, the DAPM achieved efficient ROS generation and concentration-dependent cytotoxicity under light irradiation, providing effective photodynamic therapy for anti-tumors. The proposed DAPM theranostic system enables accurate cancer diagnosis, and provides spatial and temporal information for PDT.

Assembly of Reusable DNA Blocks for Data Storage Using the Principle of Movable Type Printing.

Due to its high coding density and longevity, DNA is a compelling data storage alternative. However, current DNA data storage systems rely on the de novo synthesis of enormous DNA molecules, resulting in low data editability, high synthesis costs, and restrictions on further applications. Here, we demonstrate the programmable assembly of reusable DNA blocks for versatile data storage using the ancient movable type printing principle. Digital data are first encoded into nucleotide sequences in DNA hairpins, which are then synthesized and immobilized on solid beads as modular DNA blocks. Using DNA polymerase-catalyzed primer exchange reaction, data can be continuously replicated from hairpins on DNA blocks and attached to a primer in tandem to produce new information. The assembly of DNA blocks is highly programmable, producing various data by reusing a finite number of DNA blocks and reducing synthesis costs (∼1718 versus 3000 to 30,000 US$ per megabyte using conventional methods). We demonstrate the flexible assembly of texts, images, and random numbers using DNA blocks and the integration with DNA logic circuits to manipulate data synthesis. This work suggests a flexible paradigm by recombining already synthesized DNA to build cost-effective and intelligent DNA data storage systems.

Robustness and reproducibility of simple and complex synthetic logic circuit designs using a DBTL loop.

Computational tools addressing various components of design-build-test-learn (DBTL) loops for the construction of synthetic genetic networks exist but do not generally cover the entire DBTL loop. This manuscript introduces an end-to-end sequence of tools that together form a DBTL loop called Design Assemble Round Trip (DART). DART provides rational selection and refinement of genetic parts to construct and test a circuit. Computational support for experimental process, metadata management, standardized data collection and reproducible data analysis is provided via the previously published Round Trip (RT) test-learn loop. The primary focus of this work is on the Design Assemble (DA) part of the tool chain, which improves on previous techniques by screening up to thousands of network topologies for robust performance using a novel robustness score derived from dynamical behavior based on circuit topology only. In addition, novel experimental support software is introduced for the assembly of genetic circuits. A complete design-through-analysis sequence is presented using several OR and NOR circuit designs, with and without structural redundancy, that are implemented in budding yeast. The execution of DART tested the predictions of the design tools, specifically with regard to robust and reproducible performance under different experimental conditions. The data analysis depended on a novel application of machine learning techniques to segment bimodal flow cytometry distributions. Evidence is presented that, in some cases, a more complex build may impart more robustness and reproducibility across experimental conditions. Graphical Abstract.

Mapping Temporally Ordered Inputs to Binary Message Outputs with a DNA Temporal Logic Circuit.

Molecular circuits and devices with temporal signal processing capability are of great significance for the analysis of complex biological processes. Mapping temporal inputs to binary messages is a process of history-dependent signal responses, which can help understand the signal-processing behavior of organisms. Here, we propose a DNA temporal logic circuit based on DNA strand displacement reactions, which can map temporally ordered inputs to corresponding binary message outputs. The presence or absence of the output signal is determined by the type of substrate reaction with the input so that different orders of inputs correspond to different binary outputs. We demonstrate that a circuit can be generalized to more complex temporal logic circuits by increasing or decreasing the number of substrates or inputs. We also show that our circuit had excellent responsiveness to temporally ordered inputs, flexibility, and expansibility in the case of symmetrically encrypted communications. We envision that our scheme can provide some new ideas for future molecular encryption, information processing, and neural networks.