Chapter Two - Advances in DNA/RNA detection using nanotechnology

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Abstract

Specific nucleic acid detection in vitro or in vivo has become increasingly important in the discovery of genetic diseases, diagnosing pathogen infection and monitoring disease treatment. One challenge, however, is that the amount of target nucleic acid in specimens is limited. Furthermore, direct sensing methods are also unable to provide sufficient sensitivity and specificity. Fortunately, due to advances in nanotechnology and nanomaterials, nanotechnology-based bioassays have emerged as powerful and promising approaches providing ultra-high sensitivity and specificity in nucleic acid detection. This chapter presents an overview of strategies used in the development and integration of nanotechnology for nucleic acid detection, including optical and electrical detection methods, and nucleic acid assistant recycling amplification strategies. Recent 5 years representative examples are reviewed to demonstrate the proof-of-concept with promising applications for DNA/RNA detection and the underlying mechanism for detection of DNA/RNA with the higher sensitivity and selectivity. Furthermore, a brief discussion of common unresolved issues and future trends in this field is provided both from fundamental and practical point of view.

Introduction

Nucleic acid, including DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are polymeric biologic molecules composed of nucleotide monomers. Each nucleotide consists of three-components: a phosphate group, a nitrogenous base and a five-carbon sugar (deoxyribose for DNA and ribose for RNA). Nucleic acids are critical biomolecules in life due to their capacity to encode genetic information and regulate the synthesis of protein. Thus, genetic variation resulting from some minor nucleic acid sequence change has significant biomedical and biologic implications, i.e., cancer [1]. RNA also plays a key role in cancer development and further detection of diseases. In addition, expression of microRNA or messenger RNA appears related to cancer growth and development [2]. Therefore, sensitive, accurate and selective detection of nucleic acid is highly important and fundamental to biomedical research, clinical diagnosis and efficient treatment.

In support thereof, various DNA/RNA detection technologies have been developed in recent years [3], [4]. Despite this continuing evolution, many of these approaches are remain challenged by acceptable practicality, sufficient sensitivity and resistance to interferents in biologic material, i.e., serum, saliva, urine and cell extracts. To improve the limitations inherent to traditional DNA/RNA detection methods, nanomaterials have received particular attention due to their unique chemical and physical properties as signal amplification carriers and as direct signal generating biosensor elements. Moreover, nanomaterials provide unlimited opportunity for novel combinations of various materials or molecules of different composition, size, shape and dimension. When coupled with different biomolecules, these nanocomposites can provide unique probes having the desired properties for signal transfer and biosensing [5], [6]. Advances in nanotechnology include the use of noble metal nanoparticles [7], magnetic nanoparticles (MNPs) [8], quantum dots (QDs) [9], two dimensional (2D) nanomaterials [10], metal-organic frameworks (MOFs) [11] and up-conversion phosphors (UCPs) [12]. These technologic breakthroughs have significantly enabled the development of electro/optical biosensors possessing exceptional ability to detect DNA/RNA. The use of nanomaterials also enhances signal amplification because of their large specific surface area which could then be loaded with more signal tags, as well as other unique photo/electric properties for direct signal transfer and collection. In addition, the flexibility and designability during the construction of the nanobiosensing interfaces provide a promising research tool for ultrasensitive detection of DNA/RNA.

In this chapter, we review current developments in smart nanobiosensing strategies, including electrochemical, electrochemiluminescence (ECL), photoelectrochemistry (PEC), fluorescence, surface-enhanced Raman scattering (SERS) assays, as well as colorimetric and other plasmonic-based sensors. Their use in DNA/RNA detection and signal-enhancing ability and mechanism of action will be discussed. The advantages and shortcomings of specific nanomaterials such as noble metal nanoparticles, MNPs, QDs, 2D nanomaterials, MOFs and UCPs will be highlighted. Finally, we discuss unresolved challenges and future trends for nucleic acid detection from both a fundamental and practical point of view.

Section snippets

Metallic nanoparticle strategies

Because of their unique optical, chemical, electrical and catalytic properties, gold (Au) and silver (Ag) nanoparticles have been extensively studied and used for DNA/RNA detection in combination with electrochemistry, electrochemiluminescence (ECL), photoelectrochemistry (PEC), fluorescence, SERS, colorimetric assays and surface plasmon resonance (SPR) sensing approaches.

Magnetic nanoparticle strategies

Magnetic nanoparticles possessing excellent separation ability have been widely used in biosensors for DNA/RNA detection. In addition, magnetic nanoparticles could be functionalized with active groups such as hydroxyl, amine, carboxyl, aldehyde, and epoxy moieties improve target DNA binding via a stable covalent link. To date, a large number of magnetic nanoparticle based nucleic acid sensing approaches have been reported. These include SERS [143], fluorescence [144], CL [145], ECL [146], PEC

Quantum dot (QD) strategies

In recent years, quantum dot (QD) semiconductor nanocrystals have been reported to have many unique and promising optical/electronic properties superior to those of large particles, making them attractive nanomaterials for optical biosensing [168]. QD-based Förster resonance energy transfer (FRET) biosensors have attracted significant interest for the direct detection of target analytes in solution. This property effectively mitigates typical biosensing problems such as long preparation time

Two-dimensional layered nanomaterial strategies

Since the discovery of mechanically exfoliated graphene in 2004 [188], numerous studies have been conducted on graphene and other two-dimensional (2D) layered nanomaterials for use in material science, biochemistry and nanotechnology [10]. Graphene, as one of most common used 2D materials, has showed promise in nucleic acid detection due to its unique low-dimensional physical properties, excellent electrochemical performance and high fluorescence quenching efficiency [189]. Further studies

Other nanoparticle strategies

In addition to common nanoparticles listed above, others have been developed including metal-organic frameworks (MOFs), silica nanoparticles, polydopamine nanomaterials, UCNPs, DNA-tagged liposomes and carbon dots. All have been successfully employed in the construction of bioanalytical methods for sensitive DNA/RNA detection.

MOFs are an emerging class of hybrid porous materials self-assembled from metal-containing nodes and organic linkers that have attracted tremendous attention over the past

DNA/RNA detection based on nucleic acid nanotechnology

Strict Watson-Crick base-pairing rules for DNA strand hybridization make the use of DNA to be a powerful approach in the construction of nanotechnology strategies [261]. For example, employing sequence programmability and highly specific molecular recognition from DNA molecules, a large amount of DNA-based nanomaterials or frameworks have been designed and successfully applied in sensing [262]. To date, the rapid growth of technology has enabled the design and construction of elaborate DNA

Point-of-care-testing (POCT) of nucleic acid

Interestingly, point-of-care-testing (POCT) systems have become one of the most rapidly growing tools in the field of nucleic acid detection and identification. Compared to conventional biologic/biochemical approaches, POCT of nucleic acid can facilitate the detection of infectious agents [311]. As such, much research has been performed to miniaturize devices and develop portable microchips. These novel POCT devices include paper chips, microfluidic chips and capillary devices.

The paper chip

Summary and future perspectives

The accurate and sensitive detection of nucleic acid is an important diagnostic tool. As described above, the use nanotechnology including nanomaterial-based signal transfer and amplification strategies have shown great promise for DNA/RNA detection in vitro and in vivo. The unique physical, chemical, optical, electrical, and catalytic properties of these devices are synergistic in accelerating signal transduction at much lower detection limits than traditional approaches. Nanomaterials

Acknowledgments

Financial support was provided by the National Natural Science Foundation of China (Grant No. 21327902, 21505065, 21535002, 21535003, 21675074, 21775063), the “Innovation Team Development Plan” of the Ministry of Education Rolling Support (IRT_15R31).

Conflicts of interest

The authors declare no competing financial interest.

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