Trends in Biotechnology
Volume 37, Issue 12, December 2019, Pages 1367-1382
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Review
Strand Displacement Strategies for Biosensor Applications

https://doi.org/10.1016/j.tibtech.2019.10.001Get rights and content

Highlights

  • SDRs directly connect a biosensing recognition event to its signaling event, producing simple, integrated platforms.

  • Combining SDRs into cascades provides inherent amplification of target signals, thus boosting the sensitivity of the biosensing system.

  • The incorporation of orthogonal strand displacement cascades allows multiplexed detection of multiple targets in one sample.

  • SDRs can be applied universally to a diverse type of targets, including nucleic acids, proteins, and small molecules.

DNA has many unique properties beyond encoding genetic information, one of which is its physicochemical stability based on Watson–Crick base pairing. Differences in sequence complementarity between multiple DNA strands can lead to the strand displacement reaction (SDR). SDRs have been regularly applied in synthetic biology, drug delivery, and, importantly, biosensing. SDR-based biosensors have high controllability, high sensitivity, and low interference, and can be used for multiplexed detection. Such biosensors have been demonstrated to detect nearly every class of biomolecule. As the field continues to mature, such platforms can be used as an integral tool for the manipulation of biomolecular reactions, bringing biosensors one step closer to the ultimate goal of point-of-care systems.

Section snippets

Dynamic Nucleic Acid Hybridization for Strand Displacement

Although nucleic acids primarily function to transfer genetic information between generations of organisms, their physiochemical properties, including stable secondary structure and the dependable encodability of the Watson–Crick base pair, provide a multitude of opportunities for applications in nanotechnology 1, 2, 3, 4. One such application is the thermodynamically driven SDR (Figure 1, Key Figure) [5]. Typically, this reaction involves three elements: a substrate strand, an initiator

Biosensing Applications of SDRs

The dynamic nature, high degree of control, and freedom of the SDR design make this a powerful tool for biomolecule detection and, therefore, for biosensors. One key element of a biosensor is a specific recognition element to preferentially bind to the target analyte. Recognition elements can be antibodies, proteins, DNA or RNA aptamers, or single-stranded nucleic acids. Binding between the recognition element and the analyte is converted to an observable signal by signal transducers. Common

Optical Sensors

Optical sensors function as homogeneous assays, directly performing target analysis in a single container containing the sample specimen. Readout from such assays is based on a change in absorbance or fluorescence due to the binding of the analyte of interest to a recognition element. Therefore, optical readout negates the need for engineering and fabrication of complex sensing devices.

Electrochemical Biosensors

Electrochemical readout is one of the best-established and most reliable technologies for point-of-care sensors, and the electrochemical glucose sensor sets the standard for such devices 59, 60. These biosensors have continued to increase in popularity over the past decade 19, 42, 54, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71. Their continued success can be attributed to the simplicity and low cost of the instrumentation required [66]. However, limitations remain for some types of

Peptide-Based SDRs

Most current SDR technologies rely on nucleic acids. However, nature has provided another class of programmable biopolymers, based on amino acids, which are more functionally diverse than nucleic acids. Developing SDRs with peptides combines the functionality of amino acids with the controllability of the SDR. To date, fairly simple coiled-coil-based peptide SDRs have been demonstrated [87]. Very recently, a biosensing motor based on a peptide displacement reaction for Tau protein detection was

Glossary

CRISPR/Cas9
clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) constitute an RNA-guided endonuclease that targets its complementary sequence through recognition of protospacer adjacent motif (PAM) by Cas protein and complementarity confirmation by guide RNA.
Circulating nucleic acids (CNAs)
DNA/RNA segments that are released from dying cells into the bloodstream.
DNA origami
folding of DNA to construct 2D or 3D shapes through computational

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