scholarly journals DNA breathing initiated strand displacement circuits for mimicking ant foraging with nanopore readout

2021 ◽  
Author(s):  
Jinbo Zhu ◽  
Jinglin Kong ◽  
Ulrich Keyser ◽  
Erkang Wang
Keyword(s):  
Single Molecule ◽  
Dna Nanotechnology ◽  
Path Selection ◽  
Strand Displacement ◽  
Initiation Mechanism ◽  
Single Molecule Level ◽  
Sensing Platform ◽  
Dna Strand Displacement ◽  
Dna Strand Exchange ◽  
Dna Strand

Abstract DNA strand displacement reaction is essential for the development of molecular computing based on DNA nanotechnology. Additional DNA strand exchange strategies with high selectivity for input will enable novel complex systems including biosensing applications. Most approaches use bulk readout methods based on fluorescent probes that complicate the monitoring of parallel computations. Herein we propose an autocatalytic strand displacement (ACSD) circuit, which is initiated by DNA breathing and accelerated by seesaw catalytic reaction. The special initiation mechanism of the ACSD circuit enables detection of single base mutations at multiple sites in the input strand with much higher sensitivity than classic toehold-mediated strand displacement. A swarm intelligence model is constructed using the ACSD circuit to mimic foraging behaviour of ants. We introduce a multiplexed nanopore sensing platform to report the output results of a parallel path selection system on the single-molecule level. The ACSD strategy and nanopore multiplexed readout method enhance the toolbox for the future development of DNA computing.

scholarly journals Single molecule based SNP detection using designed DNA carriers and solid-state nanopores

2017 ◽  
Vol 53 (2) ◽  
pp. 436-439 ◽  
Author(s):  
Jinglin Kong ◽  
Jinbo Zhu ◽  
Ulrich F. Keyser
Keyword(s):  
Solid State ◽  
Single Molecule ◽  
Strand Displacement ◽  
Snp Detection ◽  
Single Molecule Level ◽  
Dna Strand Displacement ◽  
Dna Strand ◽  
Dna Carriers

A novel nanopore-DNA carrier method is demonstrated for SNP detection and following DNA strand displacement kinetics at the single molecule level.

scholarly journals Programming colloidal bonding using DNA strand-displacement circuitry

2020 ◽  
Vol 117 (11) ◽  
pp. 5617-5623 ◽  
Author(s):  
Xiang Zhou ◽  
Dongbao Yao ◽  
Wenqiang Hua ◽  
Ningdong Huang ◽  
Xiaowei Chen ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Thermal Annealing ◽  
Constant Temperature ◽  
Room Temperature ◽  
Dna Nanotechnology ◽  
Structural Transformations ◽  
Temperature Sensitive ◽  
Strand Displacement ◽  
Dna Strand Displacement ◽  
Dna Strand

As a strategy for regulating entropy, thermal annealing is a commonly adopted approach for controlling dynamic pathways in colloid assembly. By coupling DNA strand-displacement circuits with DNA-functionalized colloid assembly, we developed an enthalpy-mediated strategy for achieving the same goal while working at a constant temperature. Using this tractable approach allows colloidal bonding to be programmed for synchronization with colloid assembly, thereby realizing the optimal programmability of DNA-functionalized colloids. We applied this strategy to conditionally activate colloid assembly and dynamically switch colloid identities by reconfiguring DNA molecular architectures, thereby achieving orderly structural transformations; leveraging the advantage of room-temperature assembly, we used this method to prepare a lattice of temperature-sensitive proteins and gold nanoparticles. This approach bridges two subfields: dynamic DNA nanotechnology and DNA-functionalized colloid programming.

scholarly journals A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures

2020 ◽  
Vol 17 (167) ◽  
pp. 20190866 ◽  
Author(s):  
Stefan Badelt ◽  
Casey Grun ◽  
Karthik V. Sarma ◽  
Brian Wolfe ◽  
Seung Woo Shin ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Biophysical Model ◽  
Kinetic Properties ◽  
Strand Displacement ◽  
Natural Connection ◽  
Dna Strand Displacement ◽  
Wide Range ◽  
Dna Strand ◽  
High Level ◽  
Domain Level

Information technologies enable programmers and engineers to design and synthesize systems of startling complexity that nonetheless behave as intended. This mastery of complexity is made possible by a hierarchy of formal abstractions that span from high-level programming languages down to low-level implementation specifications, with rigorous connections between the levels. DNA nanotechnology presents us with a new molecular information technology whose potential has not yet been fully unlocked in this way. Developing an effective hierarchy of abstractions may be critical for increasing the complexity of programmable DNA systems. Here, we build on prior practice to provide a new formalization of ‘domain-level’ representations of DNA strand displacement systems that has a natural connection to nucleic acid biophysics while still being suitable for formal analysis. Enumeration of unimolecular and bimolecular reactions provides a semantics for programmable molecular interactions, with kinetics given by an approximate biophysical model. Reaction condensation provides a tractable simplification of the detailed reactions that respects overall kinetic properties. The applicability and accuracy of the model is evaluated across a wide range of engineered DNA strand displacement systems. Thus, our work can serve as an interface between lower-level DNA models that operate at the nucleotide sequence level, and high-level chemical reaction network models that operate at the level of interactions between abstract species.

scholarly journals Cross-Inhibitor: a time-sensitive molecular circuit based on DNA strand displacement

2020 ◽  
Vol 48 (19) ◽  
pp. 10691-10701
Author(s):  
Chanjuan Liu ◽  
Yuan Liu ◽  
Enqiang Zhu ◽  
Qiang Zhang ◽  
Xiaopeng Wei ◽  
...  
Keyword(s):  
Input Signal ◽  
Dna Nanotechnology ◽  
Strand Displacement ◽  
Important Goal ◽  
Molecular Systems ◽  
Molecular Programming ◽  
Dna Strand Displacement ◽  
Input Signals ◽  
Biochemical Systems ◽  
Dna Strand

Abstract Designing biochemical systems that can be effectively used in diverse fields, including diagnostics, molecular computing and nanomachines, has long been recognized as an important goal of molecular programming and DNA nanotechnology. A key issue in the development of such practical devices on the nanoscale lies in the development of biochemical components with information-processing capacity. In this article, we propose a molecular device that utilizes DNA strand displacement networks and allows interactive inhibition between two input signals; thus, it is termed a cross-inhibitor. More specifically, the device supplies each input signal with a processor such that the processing of one input signal will interdict the signal of the other. Biochemical experiments are conducted to analyze the interdiction performance with regard to effectiveness, stability and controllability. To illustrate its feasibility, a biochemical framework grounded in this mechanism is presented to determine the winner of a tic-tac-toe game. Our results highlight the potential for DNA strand displacement cascades to act as signal controllers and event triggers to endow molecular systems with the capability of controlling and detecting events and signals.

scholarly journals First passage time study of DNA strand displacement

2020 ◽  
Author(s):  
D. W. Bo Broadwater ◽  
Alexander W. Cook ◽  
Harold D. Kim
Keyword(s):  
Single Molecule ◽  
First Passage Time ◽  
Resonance Energy ◽  
Passage Time ◽  
Single Step ◽  
Strand Displacement ◽  
First Passage ◽  
Dna Strand Displacement ◽  
Dna Strand ◽  
Kinetics Of

AbstractDNA strand displacement, where a single-stranded nucleic acid invades a DNA duplex, is pervasive in genomic processes and DNA engineering applications. The kinetics of strand displacement have been studied in bulk; however, the kinetics of the underlying strand exchange were obfuscated by a slow bimolecular association step. Here, we use a novel single-molecule Fluorescence Resonance Energy Transfer (smFRET) approach termed the “fission” assay to obtain the full distribution of first passage times of unimolecular strand displacement. At a frame time of 4.4 ms, the first passage time distribution for a 14-nt displacement domain exhibited a nearly monotonic decay with little delay. Among the eight different sequences we tested, the mean displacement time was on average 35 ms and varied by up to a factor of 13. The measured displacement kinetics also varied between complementary invaders and between RNA and DNA invaders of the same base sequence except for T→U substitution. However, displacement times were largely insensitive to the monovalent salt concentration in the range of 0.25 M to 1 M. Using a one-dimensional random walk model, we infer that the single-step displacement time is in the range of ∼30 µs to ∼300 µs depending on the base identity. The framework presented here is broadly applicable to the kinetic analysis of multistep processes investigated at the single-molecule level.

scholarly journals A nanopore interface for high bandwidth DNA computing

2021 ◽  
Author(s):  
Karen Zhang ◽  
Yuan-Jyue Chen ◽  
Kathryn Doroschak ◽  
Karin Strauss ◽  
Luis Ceze ◽  
...  
Keyword(s):  
Fluorescence Spectroscopy ◽  
Single Molecule ◽  
Dna Computing ◽  
Direct Detection ◽  
New Paradigm ◽  
Single Molecule Level ◽  
Oxford Nanopore ◽  
Dna Strand Displacement ◽  
Order Of Magnitude ◽  
Dna Strand

DNA has emerged as a powerful substrate for programming information processing machines at the nanoscale. Among the DNA computing primitives used today, DNA strand displacement (DSD) is arguably the most popular, with DSD-based circuit applications ranging from disease diagnostics to molecular artificial neural networks. The outputs of DSD circuits are generally read using fluorescence spectroscopy. However, due to the spectral overlap of typical small-molecule fluorescent reporters, the number of unique outputs that can be detected in parallel is limited, requiring complex optical setups or spatial isolation of reactions to make output bandwidths scalable. Here, we present a multiplexable sequencing-free readout method that enables real-time, kinetic measurement of DSD circuit activity through highly parallel, direct detection of barcoded output strands using nanopore sensor array technology (Oxford Nanopore Technologies' MinION device). We show that engineered reporter probes can be detected and classified with high accuracy at the single-molecule level directly from raw nanopore signals using deep learning. We then demonstrate this method's utility in multiplexed detection of clinically relevant microRNA sequences. These results increase DSD output bandwidth by an order of magnitude over what is possible with fluorescence spectroscopy, laying the foundations for a new paradigm in DNA circuit readout and programmable multiplexed molecular diagnostics using portable nanopore devices.

scholarly journals Programming Cell-Free Biosensors with DNA Strand Displacement Circuits

2021 ◽  
Author(s):  
Jaeyoung K. Jung ◽  
Khalid K. Alam ◽  
Julius B. Lucks
Keyword(s):  
Response Times ◽  
Dna Nanotechnology ◽  
Fine Tuning ◽  
Digital Converter ◽  
Strand Displacement ◽  
Design Rules ◽  
Analog To Digital ◽  
Dna Strand Displacement ◽  
Dna Strand ◽  
Molecular Computations

ABSTRACTCell-free biosensors are emerging as powerful platforms for monitoring human and environmental health. Here, we expand the capabilities of biosensors by interfacing their outputs with toehold-mediated strand displacement circuits, a dynamic DNA nanotechnology that enables molecular computation through programmable interactions between nucleic acid strands. We develop design rules for interfacing biosensors with strand displacement circuits, show that these circuits allow fine-tuning of reaction kinetics and faster response times, and demonstrate a circuit that acts like an analog-to-digital converter to create a series of binary outputs that encode the concentration range of the target molecule being detected. We believe this work establishes a pathway to create “smart” diagnostics that use molecular computations to enhance the speed, robustness and utility of biosensors.

scholarly journals DNA nanotechnology assisted nanopore-based analysis

2020 ◽  
Vol 48 (6) ◽  
pp. 2791-2806 ◽  
Author(s):  
Taoli Ding ◽  
Jing Yang ◽  
Victor Pan ◽  
Nan Zhao ◽  
Zuhong Lu ◽  
...  
Keyword(s):  
Single Molecule ◽  
Dna Nanotechnology ◽  
Clinical Diagnostics ◽  
Dna Assembly ◽  
Label Free ◽  
One Pot ◽  
Dna Strand Displacement ◽  
Label Free Detection ◽  
Target Molecules ◽  
Dna Strand

Abstract Nanopore technology is a promising label-free detection method. However, challenges exist for its further application in sequencing, clinical diagnostics and ultra-sensitive single molecule detection. The development of DNA nanotechnology nonetheless provides possible solutions to current obstacles hindering nanopore sensing technologies. In this review, we summarize recent relevant research contributing to efforts for developing nanopore methods associated with DNA nanotechnology. For example, DNA carriers can capture specific targets at pre-designed sites and escort them from nanopores at suitable speeds, thereby greatly enhancing capability and resolution for the detection of specific target molecules. In addition, DNA origami structures can be constructed to fulfill various design specifications and one-pot assembly reactions, thus serving as functional nanopores. Moreover, based on DNA strand displacement, nanopores can also be utilized to characterize the outputs of DNA computing and to develop programmable smart diagnostic nanodevices. In summary, DNA assembly-based nanopore research can pave the way for the realization of impactful biological detection and diagnostic platforms via single-biomolecule analysis.

Sign in / Sign up

Export Citation Format

Share Document