Medium Scale Integration of Molecular Logic Gates in an Automaton

Macdonald, Joanne; Li, Yang; Sutovic, Marko; Lederman, Harvey; Pendri, Kiran; Lu, Wei; Andrews, Benjamin L.; Stefanović, Darko; Stojanović, Milan N.

doi:10.1021/nl0620684

Cited by 183 publications

(139 citation statements)

References 32 publications

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“…[12][13][14][15] In the decade since Adleman's invention, reports have been made of a wide and diverse range of DNA logic devices. [16][17][18][19][20][21][22] Winfree, Stojanovic, Willner, Katz and their co-workers have, for example, developed optically reported 'AND' , 'OR' and 'SET-RESET' logic gate operations. 7,[23][24][25][26][27][28][29][30][31] Although the above examples serve as promising proofs of principle (see also refs [27][28][29][30][31][32][33][34][35], it remains necessary to create complex, multicomponent devices on a single biomolecular platform to achieve increased computational complexity and develop realistic DNAbased information processing systems.…”

Section: Introductionmentioning

confidence: 99%

DNA biomolecular-electronic encoder and decoder devices constructed by multiplex biosensors

et al. 2012

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We fabricated and tested encoders and decoders based on a multiplex, DNA-based electrochemical biosensor that uses electronic (electrochemical) signals as its readout. These devices use two or more sequence-specific DNA probes, with each being modified with a distinct redox reporter. These probes, when interrogated together, serve as encoders and decoders, converting patterns that are encoded and decoded by the presence or absence of specific DNA sequences into specific electronic outputs. We demonstrated these multifunctional, bio-electrochemical devices, for example, 4-to-2 and 8-to-3 encoders and 1-to-2 and 2-to-3 decoders. Accordingly, these devices bridge the division between DNA-based devices and silicon-based electronics. NPG Asia Materials (2012) 4, e1; doi:10.1038/am.2012.1; published online 18 January 2012Keywords: biosensors; decoder; DNA-based; encoder; multiplex INTRODUCTIONIn recent decades, serious attempts have been made to implement computational approaches, models and paradigms that utilize the information transfer and processing abilities of naturally occurring and modified biomolecules. 1-11 A decade ago, for example, Adleman performed a now-classic experiment in which computations were conducted using DNA molecules, demonstrating that biology can provide new computing substrates. [12][13][14][15] In the decade since Adleman's invention, reports have been made of a wide and diverse range of DNA logic devices. [16][17][18][19][20][21][22] Winfree, Stojanovic, Willner, Katz and their co-workers have, for example, developed optically reported 'AND' , 'OR' and 'SET-RESET' logic gate operations. 7,[23][24][25][26][27][28][29][30][31] Although the above examples serve as promising proofs of principle (see also refs 27-35), it remains necessary to create complex, multicomponent devices on a single biomolecular platform to achieve increased computational complexity and develop realistic DNAbased information processing systems. In this study, we fabricated and tested encoders and decoders based on a multiplex, DNA-based electrochemical biosensor that uses electronic (electrochemical) signals as its readout. These devices uses two or more sequence-specific DNA probes that, when interrogated together, serve as encoders, converting patterns that are encoded and decoded by the presence or absence of specific DNA sequences into specific electronic outputs.

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Section: Introductionmentioning

confidence: 99%

DNA biomolecular-electronic encoder and decoder devices constructed by multiplex biosensors

et al. 2012

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“…Since Adelman's (1994) pioneering DNA-based solution to the directed Hamiltonian path problem, a vast effort has been directed at producing molecular analogs to the usual NOT, AND, XOR, and similar logic gates, and at constructing systems using them (e.g., Stojanovic et al, 2002;Macdonald et al, 2006). Here, we will examine far more subtle naturallyoccurring logic gates associated with the molecular fuzzy lockand-key.…”

Section: Introductionmentioning

confidence: 99%

A formal approach to the molecular fuzzy lock-and-key

Wallace

2013

Preprint

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The fuzzy lock-and-key (FLK) powers a vast array of sophisticated logic gates at inter-and intra-cellular levels. We invoke representations of groupoid tiling wreath products analogous to the study of nonrigid molecules -or of related fuzzy symmetry extensions -to build a Morse Function that can describe spontaneous symmetry breaking phase transitions driven by information catalysis. The Function can, however, also be used to construct an Onsager-like stochastic dynamics, linked to the phase transition approach by the rich stability criteria associated with stochastic differential equations. The two methods provide complementary ways of looking at the FLK. A limit condition emerging from the stochastic dynamics gives insight into a cellular 'generalized inflammation' requiring progressively higher commitment of metabolic free energy for maintenance of basic FLK processes. These results suggest that more systematic study may illuminate pathologies associated with the failure of the FLK, a centrally-important but enigmatic biological process.

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“…(Who is Mortal?). This biomolecular computing system compares favourably with previous approaches in terms of expressive power, performance and precision 2,4,8,9,11,12,19 . A compiler translates facts, rules and queries into their molecular representations and subsequently operates a robotic system that assembles the logical deductions and delivers the result.…”

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confidence: 96%

“…Biomolecular implementations of finite automata 8,9 and logic gates 4,[10][11][12][13] have already been developed [14][15][16][17][18] . Here, we report an autonomous programmable molecular system based on the manipulation of DNA strands that is capable of performing simple logical deductions.…”

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confidence: 99%

Molecular implementation of simple logic programs

2009

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Autonomous programmable computing devices made of biomolecules could interact with a biological environment and be used in future biological and medical applications [1][2][3][4][5][6][7] . Biomolecular implementations of finite automata 8,9 and logic gates 4,10-13 have already been developed [14][15][16][17][18] . Here, we report an autonomous programmable molecular system based on the manipulation of DNA strands that is capable of performing simple logical deductions. Using molecular representations of facts such as Man(Socrates) and rules such as Mortal(X) Man(X) (Every Man is Mortal), the system can answer molecular queries such as Mortal(Socrates)? (Is Socrates Mortal?) and Mortal(X)? (Who is Mortal?). This biomolecular computing system compares favourably with previous approaches in terms of expressive power, performance and precision 2,4,8,9,11,12,19 . A compiler translates facts, rules and queries into their molecular representations and subsequently operates a robotic system that assembles the logical deductions and delivers the result. This prototype is the first simple programming language with a molecular-scale implementation.Our logic system consists of propositions, implications and queries, represented by short DNA molecules, some single-stranded and some double-stranded, as shown in Fig. 1a. A proposition p, such as 'Socrates is a Man', is represented by a double-stranded (ds) DNA molecule with a sticky end representing p on one end and a fluorophore (a fluorescent molecule) with a matching quencher (a molecule that absorbs excitation energy from a fluorophore) at its other end. A query p?, such as 'Is Socrates a Man?', is represented by a dsDNA molecule with a sticky end complementary to the representation of p and a recognition site (marked light red) for the restriction enzyme FokI. A molecular query p? can be positively answered by the molecular proposition p, because they have complementary sticky ends, as shown in Fig. 1b. The sticky end of the query molecule q? hybridizes with that of the proposition molecule q. FokI is attracted to its recognition site on the query (before hybridization or possibly following it) and cleaves the proposition molecule q. This results in the separation of its remaining sense and antisense strands, which in turn abolishes the quenching of the green fluorophore, allowing the fluorophore to emit green light in response to light excitation. This green emission can be interpreted by an outside observer as a positive response to the query.An implication p q (for example 'Socrates is Mortal if Socrates is a Man') is represented by a hairpin single-stranded (ss) DNA with three components: a sticky end representing the proposition p, a segment complementary to the representation of q and a segment that together with an auxiliary complementary strand forms a recognition site for FokI. The implication p q can be used to reduce the query p? to the query q?, meaning that to positively answer p? it suffices to positively answer q? This query reduction is justified by the d...

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Medium Scale Integration of Molecular Logic Gates in an Automaton

Cited by 183 publications

References 32 publications

DNA biomolecular-electronic encoder and decoder devices constructed by multiplex biosensors

DNA biomolecular-electronic encoder and decoder devices constructed by multiplex biosensors

A formal approach to the molecular fuzzy lock-and-key

Molecular implementation of simple logic programs

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