Study On Molecular Boolean Logic And Fuzzy Logic And Its Applications In Graphene-based Intelligent Biochemical Sensing

Molecular Boolean Logic and Computing (MBLC) is becoming increasingly popular, because a chemist’s bottom-up approach toward for information processing might be an attractive alternative, which is potential to overcome the development bottleneck of information technology:the chip size, cross-talk, and heat dissipation. And, construction of digital, intelligent,"sensing and acting" biochemical sensors based on MBLC will be helpful in development of nanoscience, biochemical sensing, biomedical engineering, environmental monitoring, etc. However, MBLC is suffering from several well-identified problems:1) lack of multi-functionality, for example, most previous logic gates usually perform only simple operations;2) poor gate connectivity and scale integration;3) buildups of inputs and waste products which will complicate logic operations;4) ignoring dynamic characteristics of MBLC operation;5) difficulty in distinguishing logical0and1. Moreover, Design and applications of logic-based sensing systems are still at a very early stage, and face lots of challenges, such as unideal digital responses, difficulty of differentiating and utilizing fuzzy signals, and lack of input-output codes, etc. Thus, it is very important for solving above problems and achieving practical applications of logic-based sensor to develop novel models of MBLC, provide new theory on MBLC, and combine new materials with new systems. In this dissertation, valuable explorations have been carried out on how to construct molecular logic gates, conncet logic systems, design artificial molecular neuron, solve and utilize fuzzy signals, and construct graphene-based intelligent logic analysis systems for detection of Hg2+, G-quadruplex (G4) DNA, Fe2+, hydroxyl radical (HO·).1. A Reversible Fluorescence Nanoswitch Based on Bifunctional Reduced Graphene Oxide:Use for Detection of Hg2+and Molecular Logic Gate OperationThe marriage of nanomaterials (including graphene, carbon nanotubes, and gold nanoparticles, et al.) with inexpensive, label-free, common, and stable organic dyes to develop novel sensors with versatile features possesses more great potential. Herein, an organic dye-reduced graphene oxide (rGO) nanoswitch, which is constructed by simply mixing the diluted aqueous solutions of both components, is successfully and efficiently utilized for the label-free, simple, sensitive, and selective determination of Hg2+. Our approach uses the highly selective Hg2+adsorption capacity and effective fluorescence quenching capacity of bifunctional rGO. Moreover, Based on the fact that the addition of cysteine (Cys) into the Hg2+-restored fluorescence system can lead to the release of Hg2+from rGO platform, resulting in the reformation of organic dye-rGO and requenching of dye fluorescence, a reversible on-off INHIBIT rGO logic gate based on the Cys-Hg2+system has also been designed. Molecular logic-gate operation which exhibits intrinsic attractive properties can expand the application of graphene. This proposed nanoswitch design using carbon nanomaterials-common organic dye complex provides a general design strategy, which may expand application potential of various nanomaterials with fluorescence resonance energy transfer (FRET) in label-free optical bionanotechnology, molecular-level chemical sensing, and environmental health science.2. A Simple and Facile Strategy Based on Fenton-Induced DNA Cleavage for Fluorescent Turn-On Detection of Hydroxyl Radicals and Fe2+Recently many graphene-based FRET optical sensors are well-known for external competition sensing approaches. However, the directly switching off FRET based on the probe cleavage remains rarely reported. Herein, a novel DNA-GO-Fenton hybrid system was constructed for sensitive and selective determination of Fe2+and HO·. This strategy is based on exceptional fluorescence quenching ability of GO towards the proximate dye and the switching off of FRET through the highly selective HO-induced cleavage of DNA strands. Due to the π-stacking interactions, a mixture of dye-labeled single-stranded DNA and GO forms a self-assembly of two components which almost completes fluorescence quenching of the dye and needs neither specific design of the probe DNA structure nor additional modification of the DNA termini. In comparison with traditional covalent assembly to fabricate sensing probe, the proposed approach reduces background signal and simplifies procedures for the preparation of functional probe. The GO as efficient nanoquencher modules incorporate in fluorescent probes for DNA damage caused by HO·-generating Fenton reagent. Therefore, switching off FRET depends on the amounts of Fe2+and HO·. In vitro assays with Fe2+and HO· demonstrated increases in fluorescence intensity with a linear range from10nM to1μM and a detection limit as low as2.4nM. The approach based on Fenton-DNA cleavage switch expands Fenton reaction for discriminating various chemical species of an element (such as Fe2+and Fe3+). Besides, the general strategy can be shown potential applications in sensing radical scavengers and investigating new Fenton-like reactions. Our proposed general strategy with its simplicity, sensitivity, and specificity will hold great promise in applications such as probing and bioimaging ROS in vivo, monitoring activity of cleavage enzymes and environmental contaminations, and open new opportunities for the development and design of other extended nanomaterials-DNA systems for oxidative DNA damage study, molecular engineering and sensing applications in the future.3. Fuzzy Logic Sensing of G-quadruplex DNA and Its Cleavage Reagents Based on Reduced Graphene OxideThe specific detection of G4formation can be a great help in studying the dynamic nature of G4structures and designing biosensor and molecular switches based on configurational change. The probing of G4formation also facilitates the discovery of G4DNA cleavage agents which can be used DNA cleaving anti-cancer agents. However, the existing methods for identifying G4structures are not only time-consuming, laborious and comparatively expensive but also require specialized equipment. Herein, by combining the merits of nanotechnology and fuzzy logic theory, we develop a simple, label-free, and general strategy based on an organic dye-graphene hybrid system for fluorescence intelligent sensing of G4formation, HO·, and Fe2+in vitro. By exploiting AO dyes-graphene as a nanofilter and nanoswitch and the ability of graphene to interact with DNA with different structures, our approach can efficiently distinguish, quantitatively detect target analytes. In vitro assays with G4DNA demonstrated increases in fluorescence intensity of the AO-rGO system with a linear range of16-338nM and a detection limit as low as2.0nM. The requenched fluorescence of the G4TBA-AO-rGO system has a non-linear response to Fenton reagent. But this requenching reduces the fluorescence intensity in a manner proportional to the logarithm to the base10of the concentration of Fenton reagent in the range of0.1-100μM and100-2000μM, respectively. Furthermore, we develop a novel and intelligent sensing method based on fuzzy logic which mimics human reasoning, solves complex and non-linear problems, and transforms the numerical output into the language description output for potential application in biochemical systems, environmental monitoring systems, and molecular-level fuzzy logic computing system.4. Boolean Logic Tree of Graphene-Based Chemical System for Molecular Computation and Intelligent Molecular Search QueryThere is a great deal of interest and excitement recently in building and designing of novel artificial computational devices using biochemical molecular events or engineered biological units as building blocks. The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analysing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. Based on the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable’words’and chemical interactions as’syntax’ logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in bio-sensing, nanotechnology, and drug delivery. 5. Molecular Neuron:From Sensing to Logic Computation, Information Encoding, and EncryptionThe impressive functions of brain circuits have inspired many scientists to attempt in designing neuron analogues by using artificial molecular systems or electronic devices. However, the study of molecular neuron has not produced an equal variety of models. Here, using UV-Vis absorption, fluorescence, and resonance light scattering spectroscopies for recording of the pH-dependent graded responses of common indicators—Congo red (CR) dyes, we show how CR molecules can be used to construct molecular neuron and exhibit neuron-like behavior. Our molecular neural model uses molecular groups as’dendrites’which receive the environmental stimuli inputs (pH), molecular matrix as’soma’which acts as the summation function, and the change in optical characteristics as’axon’which represents outputs. Our approach allows us to utilize simple molecules as McCulloch-Pitts neuron (the linear threshold gate) for experimental implementation of large-scale logic computation in batch mode and to use extraordinary information density inherent in molecular neuron for alphanumeric information encoding and molecular cryptography. Our results suggest that molecules could be used as universal artificial neurons with the capability of responding to the environmental stimuli, remembering patterns of molecular events, and making decisions.