Isothermal Amplification of Nucleic Acids: The Race for the Next “Gold Standard”

Abstract

Nucleic acid amplification technologies (NAATs) have become fundamental tools in molecular diagnostics, due to their ability to detect small amounts of target molecules. Since its development, Polymerase Chain Reaction (PCR) has been the most exploited method, being stablished as the “gold standard” technique for DNA amplification. However, the requirement for different working temperatures leads to the need of a thermocycler machine or complex thermal apparatus, which have been preventing its application in novel integrated devices for single workflow and high throughput analysis. Conversely, isothermal amplification methods have been gaining attention, especially for point-of-care diagnosis and applications. These non-PCR based methods have been developed by mimicking the in vivo amplification mechanisms, while performing the amplification with high sensitivity, selectivity and allowing for high-throughput analysis. These favorable capabilities have pushed forward the implementation and commercialization of several platforms that exploit isothermal amplification methods, mostly against virus, bacteria and other pathogens in water, food, environmental and clinical samples. Nevertheless, the future of isothermal amplification methods is still dependent on achieving technical maturity and broader commercialization of enzymes and reagents.

Introduction

Innovations in biotechnology and molecular biology have push forward novel nucleic acid amplification technologies (NAATs) to meet the demands for more efficient, sensitive, specific protocols capable to be integrated into portable systems and for high-throughput analyses. Polymerase Chain Reaction (PCR), introduced by Mullis in 1985 (Mullis et al., 1986) has become the leading method for DNA amplification with application in all types of molecular detection strategies, such as recognition and identification of infectious pathogens, characterization of genetic disorders, identification of disease biomarkers, gene expression studies, sample preparation for downstream applications and techniques (e.g., sequencing, labelling, etc.), among many others (Klein 2002). In fact, PCR is considered the “gold standard” in molecular analysis of nucleic acids, owing to its capability to amplify from as few as 1 to 10 molecules of target, ultimately leading to an increase to the sensitivity of molecular assays. As a result of the hype regarding PCR, many variants have been developed to address the ever-growing need for additional features, such as multiplex (Edwards and Gibbs 1994), nested (Porter-Jordan et al., 1990), quantitative (Porter-Jordan et al., 1990), reverse (Porter-Jordan et al., 1990) and digital forms (Kopp et al., 1998), which will be further addressed. This is indeed the technique against all others compare.

Still, inherent features to PCR require dedicated instrumentation capable of thermal cycling with appropriate temperature control, which is usually found in laboratory settings. This small but critical bottleneck has spurred the development of non-PCR based techniques, preferably suitable to be performed at a constant temperature—isothermal amplification (IA) methods, which aim at simplifying protocols for point-of-care (PoC) use, allowing to move the molecular diagnosis from centralized labs.

This review shall focus on the most representative and applied isothermal amplification methods, such as Nucleic Acid Sequence-based Amplification (NASBA), Loop-mediated Isothermal Amplification (LAMP), Strand Displacement Amplification (SDA), Recombinase Polymerase Amplification (RPA) and Rolling Circle Amplification (RCA), as well as their characteristics, applications and prospects to become the next gold standard amplification technique (Figure 1).

FIGURE 1

Despite the plethora of different IA concepts, they converge in the need to remove temperature cycling requirements for specific amplification (Li and Macdonald, 2015). While PCR requires the lowering and rising of two or three working temperatures, to allow annealing and denaturation of DNA strands and primers, and to facilitate strand displacement, IA methods proceed at a single working temperature, which removes the need for a thermocycler. Some of these isothermal amplification mechanisms also allow direct amplification from non-DNA targets, such as RNA (without the need for an additional retro transcription step) or protein-nucleic acids conjugates. Another interesting feature of these IA reactions is that they show increased tolerance to (bio-)chemical inhibitors often present in clinical samples (Bachmann et al., 2009; Craw and Balachandran 2012; Kaneko et al., 2007; Mori and Notomi 2009; Vincent et al., 2004). A summary of the main IA mechanisms proposed in the literature are presented in Table 1, together with key advantages and disadvantages.

Despite the exciting advantages of the IA schemes, these approaches also face some challenges, such as complex primer design, unspecific amplification, high background signal, confuse reaction mechanisms and the requirement for more enzymes and denaturing agents (Karami et al., 2011), These methods differ from each other in terms of primers, enzymes, reaction conditions, attainable sensitivity, specificity and ideal target molecules (miRNA, long DNA fragments, circular DNA and RNA targets) (Chang et al., 2012). Overall, isothermal amplification processes produce longer amplicons, have greater amplification efficiency, produce higher amplification yields and require less sample preparation steps than PCR (Klein 2002). In fact, it has been reported that non-PCR based clinical tests often outmatch the PCR results in clinical diagnosis (Aryan et al., 2010; Bachmann et al., 2009). From these, a risen trend concerning IA systems has been observable, over the last decades (Figure 2).

FIGURE 2

In fact, scientific literature has been reporting the application of isothermal amplification systems in a wide number of fields, among them: pathogen detection in clinical, environmental and food samples (Fang et al., 2010; Chow et al., 2008; Zhao et al., 2012; Mahmoudian et al., 2008a; Krõlov et al., 2014), diagnosis of various infectious diseases (Schopf et al., 2011; Hellyer and Nadeau 2004; B. A. Rohrman and Richards-Kortum 2012; Torres-Chavolla and Alocilja 2011; S. Y. Lee et al., 2007) and Single-Nucleotide Polymorphisms (SNP) detection (Li et al., 2010). Furthermore, some clinical trials based on IA systems for diagnosis and detection of infectious diseases have been performed: LAMP—(ClinicalTrials.gov Identifier:NCT02371395 2018a; ClinicalTrials.gov Identifier: NCT04579549, 2021; ClinicalTrials.gov Identifier:NCT03829735, 2020a; NASBA—ClinicalTrials.gov Identifier: NCT01838902 2018a; HDA—ClinicalTrials.gov Identifier: NCT01838902 2018b; RPA—ClinicalTrials.gov Identifier: NCT04500873 2020b). Among the publications concerning these amplification techniques, most are focused on the analysis of water and food, with LAMP covering 67 and 59% of the publications, respectively. Then RPA covers for circa 20%, and the remainders, RPA, RCA, HDA and NASBA add up to 5%.

Despite the continuous efforts to make IA strategies more robust, there are still some hurdles before these approaches might eventually counteract current PCR limitations. Some constraints relate to complex primer design, different kinetics for template denaturation, the high proficiency of the amplification might indivertibly lead to unspecific amplification, and the need for multiple enzymes that are still not in the mainstream production (Karami et al., 2011). Other bottlenecks are shared between PCR and IA, such as requirements for apparatus towards test portability. Still, some IA schemes have been endorsed for particular applications, some already being approved by Regulatory Agencies, such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), and even the World Health Organization (WHO) through the Foundation for Innovative New Diagnostics (FIND), for molecular diagnostics of critical pathogens (Guichón et al., 2004; Eiken 2021; Lucigen 2021; New England BioLabs, 2021), which has attracted further attention by diagnostics-oriented biotech companies (Karami et al., 2011). Some of these advances are depicted in Table 2.

Mature Isothermal Amplification Systems—How Close to Become the Next “Gold Standard”

Nucleic Acid Sequence-Based Amplification

Nucleic acid sequence-based amplification (NASBA) is an isothermal transcription-based technique, that mimics the retroviral RNA replication (Compton 1991). NASBA mechanism entails two phases: 1) non-cycling, where the target RNA is converted to dsDNA by reverse transcription; and 2) cycling, where the dsDNA molecules are actively transcribed into RNA products, leading to a yield of 10–100 copies of RNA from each template molecule (Hønsvall and Robertson 2017) (Figure 3A).

FIGURE 3

Even though this mechanism requires three enzymes - Reverse transcriptase, RNase H and T7 RNA polymerase, there are some advantages when compared to Reverse-transcription-PCR (RT-PCR), such as isothermal working temperature (41°C), which allows amplification on a simple heating block, shorter reaction time and less prone to inhibitory components in clinical and environmental samples (Dyer et al., 1996; Rutjes et al., 2006). In addition, NASBA uses RNA as the main target molecule, removing the need to previously prepare cDNA, thus saving time, labor and reducing the risk of contamination (Hønsvall and Robertson 2017). Also, contamination with DNA does not interfere with the reaction, because the temperature is kept bellow the DNA melting temperature, so strand displacement does not occur (Simpkins et al., 2000) (Table 3).

Nevertheless, there are limitations concerning NASBA implementation, such as the challenge to optimize three different enzymes that leads to higher costs, and the susceptibility to false positives that require additional probe-specific detection methods, which are generally more expensive than non-specific dyes (Cordray and Richards-Kortum 2012). Once amplification has been achieved, there are several ways to detect and monitor products, such as: molecular beacons, which is the most commonly used (Leone et al., 1998), fluorescence markers that bind and/or intercalate into the produced amplicons (Hønsvall and Robertson 2017) and gel electrophoresis for end-point detection (Morabito et al., 2013). Additionally, other colorimetric methods have been proposed that rely on nanoparticles, e.g., gold nanorods (Niazi et al., 2013) and spherical gold nanoparticles functionalized with specific probes (Mollasalehi and Yazdanparast, 2012).

Despite its promising performance, NASBA has yet to be widely acknowledge by users in mainstream labs and thus it remains in the “shadow” of other amplification techniques. NASBA has already shown it usefulness for the detection of common waterborne pathogens, such as Escherichia coli (Heijnen and Medema, 2009), Pseudo-nitschia multiseries (Delaney et al., 2011), norovirus (Rutjes et al., 2006) and notoriously it has been adopted by international space agencies for monitorization of recycled water in the International Space Station (Bechy-Loizeau et al., 2015). Another example suitable for the standard user is the NucliSENS EasyQ, an automatized commercially available NASBA system directed at the real-time amplification detection by fluorescence (Yao et al., 2005), (Biomerieux, 2021).

Depending on the detection method used for monitorization of the isothermal amplification profile, there is the possibility of NASBA integration into Lab-on-chip (LOC) devices, suitable for point-of-need, low-cost and portable platforms. In fact, there are some examples of LOC devices using NASBA for the assessment of environmental pathogens (Table 4), among which the first integrated chip for RNA isolation, NASBA amplification and real-time detection proposed (Dimov et al., 2008).

In summary, NASBA has been reported as more sensitive and less prone to inhibitory substances than PCR, which in combination with the isothermal profile makes it a useful point-of-need (PoN) tool. Still, the high cost of the reaction kits, the need to optimize multiple enzymes and the lack of specificity are crucial factors that prevent its widespread uptake by the general community.

Strand Displacement Amplification

In 1992, Walker et al. proposed to use the strand displacement capability of primers and enzymes for amplification of a given target (Walker et al., 1992). The strand displacement amplification (SDA) combines the action of an endonuclease, an exonuclease deficient DNA polymerase and two sets of primers, one with single-stranded restriction site overhangs, and a second set called “bumper primers” to support the displacement of the amplification product from the first set of primers. Briefly, dsDNA is initially heat denatured, allowing for the hybridization of the first set of primers with 5′ overhangs with specific recognition site for HincII restriction enzyme. Because of thiol-modified dATP, only the original primer is cleaved by HincII but not the newly synthetized strand, resulting in 3’ overhangs, which are extended by the exonuclease deficient klenow (exo-klenow) polymerase and further displace the downstream DNA strand, at temperatures ranging from 30—50°C. The exponential amplification is achieved though the coupling of sense and antisense reactions, in which the displaced sense strand serve as template for the antisense reaction and vice versa—(Deng and Gao 2015) for deeper insights into the molecular mechanism (Figure 3B).

Despite the advantages of isothermal reaction, the low temperature (between 30 and 55°C) makes it prone to unspecific primer-binding that might cause unspecific amplifications (Karami et al., 2011), similarly to what happens with NASBA. This is a critical aspect that prevent expansive implementation for diagnostics, since DNA/RNA retrieved from clinical samples usually contains several potential similar target sequences (e.g., gene families, homologous loci, etc.) that might miss-prime in relation to the desired target (de Pazet al., 2014). Generally, SDA presents high amplification efficiency for short target sequences that require initial template denaturation.

The high amplification efficiency of SDA associated to the capability to amplify small fragments (ranging from 50 to 120 bp) has highlighted its potential for miRNA expression profiling (Ye et al., 2019; Deng and Gao 2015). Still, SDA takes a long-time to detection (2.5 h), which makes SDA inadequate for on-site amplifications and detection. As such, SDA has been mainly applied to clinical diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae and herpes simplex virus from urogenital samples, on a high throughput platform commercialized since 1999 (Little et al., 1999; Akduman et al., 2002). This semiautomated system offers several advantages over the traditional methods for STDs detection, such as the exploit of an alternative NAAT while maintaining high sensibility and specificity, offers high-throughput and removes the need for separate work areas or unidirectional workflow. Additionally, offers medium-free transport for swabs and room temperature storage and the total time of the assays ranges from 3 to 4 h (Van Der Pol et al., 2001). Another example refers SDA inclusion into an automated device that combines sample preparation from whole cells and detection (J. M. Yang et al., 2002).

Loop-Mediated Isothermal Amplification

Loop-Mediated Isothermal Amplification (LAMP) (Notomi et al., 2000) has been the most widely used IA method, referenced in approximately 3,700 scientific publications, 8 clinical trials (ClinicalTrials.gov, 2021) and approved by WHO as an alternative molecular diagnostics method for pulmonary tuberculosis (World Health Organization 2016) and SARS-CoV-2 (Kashir and Ahmed, 2020).

LAMP relies on the strand-displacement activity of a DNA polymerase combined with a set of four unique primers, that may be extended to six for additional acceleration of amplification (Notomi et al., 2000; Mori and Notomi 2009). Compared to other NAATs, LAMP is 10 to 100-fold more sensitive than PCR (X. Wang X et al., 2014), with a detection limit as low as 1 copy per µL of template (H. Zhang et al., 2019), showing a higher specificity (Fujino et al., 2005) with an amplification time usually less than 1 h at 60–65°C, yielding 10⁹ copies (Notomi et al., 2000). Additional advantages include not requiring an initial template denaturation step at 95°C and being less prone to inhibitory substances often present in biological samples (Enomoto et al., 2005; Kaneko et al., 2007). Perhaps one of the most interesting benefits is that LAMP output may be visualized by the naked eye (e.g., turbidimetry), making it ideal for poor resource settings and PoC applications (Besuschio et al., 2017).

In brief, LAMP takes advantage of a polymerase with strand displacement activity and four pairs of primers, that recognize a total of six distinct sequences on the target DNA. The forward inner primer (FIP) can hybridize on the dsDNA target an initiate LAMP. The DNA synthesis is initiated by the DNA polymerase upon the annealing of the outer primer (F3) to its complementary region and its subsequent extension causes strand displacement, releasing a ssDNA molecule. This molecule serves as template for the annealing on the other end of the second inner (BIP) and outer (B3) primers, producing a stem-loop DNA structure. After this step, LAMP enters in the cycling phase in which one inner primer hybridizes to the stem-loop and initiates displacement DNA synthesis, yielding the original stem–loop molecule and a new stem–loop DNA with a stem twice as long. The cycling reaction continues leading to an accumulation of around 10⁹ copies of target under the form of concatemers in less than 1 h (Notomi et al., 2000) (Figure 3C).

The main features of LAMP, and in particular its outstanding specificity and ability to amplify without highly sophisticated equipment, makes it a valuable alternative to PCR (H. Zhang et al., 2019). In fact, LAMP has been used for detection of pathogens, e.g., detection of RNA from severe acute respiratory syndrome virus (M. M. Parida et al., 2008), identification of Methicillin Resistant Staphylococcus aureus (MRSA) (C. H. Wang et al., 2011a), tuberculosis (M. F. Lee et al., 2009), influenza A (Jung et al., 2015), Zika (J. Song et al., 2016), nervous necrosis (C. H. Wang et al., 2011b), biomarkers of disease such as Adenoviral keratoconjunctivitis (Wakabayashi et al., 2004), Varicella-zoster virus (Okamoto et al., 2004) and SNP genotyping (Iwasaki et al., 2003) and cancer diagnostics like detecting metastasis of gastric cancer (Horibe et al., 2007), KRas gene mutation (Itonaga et al., 2016) and screening of other cancer-related mutations (Srividya et al., 2019). More recently, LAMP as also been applied to the molecular detection of SARS-CoV-2 (Srividya et al., 2019), due to the rapidness and specificity of its amplification mechanisms, being exploited by many biotech-oriented companies.

Additionally, LAMP has also played an important role in quality control of food and dietary products, such as rapid detection of Salmonella (Q. Yang et al., 2018), Staphylococcus aureus (H. Yang et al., 2011), E. coli O157 (Zhao et al., 2010), Vibrio parahaemolyticus (Oh et al., 2016) and food allergens (Yuan et al., 2018).

Continuous evolution of LAMP led to improvements to reaction conditions and accuracy, which spun it into a mature and reliable assay, suitable for stand-alone molecular diagnostics (Eiken 2021; Meridian Bioscience, 2021) (Table 5). Some of the available commercially and certified detections assays take between 15 and 30 min to result. Additionally, for real-time monitorization of LAMP reaction, low complexity apparatus are also available, such as Instrument Genie II from Optigene (Horsham, United Kingdom) for fluorescence-based measurements and Ilumipro-10 from Meridian Bioscience that detects amplification products based on turbidimetry (de Paz et al., 2014).

Due to its robust and fast isothermal amplification profile, LAMP has become a suitable solution for on field molecular assays (M. Parida et al., 2004), especially for integration in lab-on-chip platforms based on microfluidics. Since the development of the first microfluidic device for the detection of hepatitis B virus, that accomplished a sensitivity of about 50 copies per reaction within 60 min (S. Y. Lee et al., 2008), other PoC devices based on LAMP have been developed targeting relevant biomarkers in infectious diseases and food quality control (Table 4).

Over the years, several modifications have been made to LAMP, such as digital LAMP where reactions occur in individualized “reactors” (micelles) yielding a 0/1 output, ideal for applications requiring quantification of target (Rane et al., 2015; Gansen et al., 2012), reverse transcription LAMP for assessing gene expression (C. H. Wang et al., 2011a), multiplex LAMP for simultaneous detection of pathogens using dedicated platforms (Abe et al., 2011) and LAMP-on-a-chip (Xuzhi Zhang et al., 2014). These developments allow for high throughput, up to 1,200 samples simultaneously, while remaining extremely sensitive (less than 10 fg of target DNA) in small sample volumes (∼10 pL) (Q. Zhu et al., 2012; C. H. Wang et al., 2011b; Rane et al., 2015). However, the complex primer design and the susceptibility to false positives still need to be addressed before LAMP is routinely applied globally (Tanner et al., 2012).

Perhaps one of the most relevant acknowledgements to LAMP has been its recognition by the WHO to fulfil all the criteria for an ideal NAAT for diagnostics (Wong et al., 2018). In fact, considering the continuous evolution of LAMP will allow expansion to other targets of relevance, which in turn will push costs of reagents down and make them more accessible, it is expected that LAMP will become a universal tool (H. Zhang et al., 2019).

Recombinase Polymerase Amplification

Recombinase Polymerase Amplification (RPA) is an isothermal amplification mechanism that operates at low temperature, usually between 37°C and 42°C, which exploits the activity of two different enzymes: a recombinase and a DNA polymerase and single stranded DNA-binding proteins. (SSBs)to ensure ssDNA stabilization (Piepenburg et al., 2006). RPA allows amplification to occur in 20—40 min, exhibiting a detection limit of 1 copy of target, being considered as one of the fastest NAATs available (de Paz et al., 2014). Briefly, RPA amplification begins with the binding of a recombinase protein (RecA from E. coli or as usually used uvsX from T4-like bacteriophages) to primers in the presence of ATP and a crowding agent (high molecular weight PEG or Carbowax20M), leading to the formation of a recombinase-primer complex. Then the complex scans the dsDNA target seeking for a homologous sequence, once homology is found the complex promotes strand displacement, forming a D-loop structure, which is stabilized by SSBs and further promotes primer-target hybridization. Finally, recombinase disassembly allows for a DNA polymerase with strand displacement activity (Bacillus subtilis Pol 1 or Sau Recombinase polymerase) to bind to the 3’ end of the primer and elongate it in the presence of dNTPs. An exponential amplification is achieved by cyclic repetition of this process (Lobato et al., 2018) (Figure 3D).

Besides the established RPA reaction setup, several improvements have been made allowing RPA to evolve to different formats, such as RT-RPA (Magro et al., 2017), digital RPA (Yeh et al., 2017) and multiplex RPA, an example is the study conducted by Kersting et al. for multiplex detection of Neisseria gonorrhoeae, Salmonella enterica and Staphylococcus aureus (Kersting et al., 2014a). Additionally, several proof of concepts on RPA incorporation with varied detection technologies have been described for improved sensitivity, reduced manual handling, improved cost effectiveness and are suitable for rapid molecular diagnosis (James and MacDonald 2015) (Table 6).

These RPA-based assays attain comparable sensitivities to those obtained with PCR, but with a significant reduction in the reaction time—time to full reaction between 10 and 20 min (Kunze et al., 2016). Moreover, RPA assays show a detection limit around 10–20 copies of target, reduced sample and reagent volumes, and the capability to amplify under high concentrations of known PCR inhibitors (Polymerase and Rpa 2017; Kersting et al., 2014b; Crannell et al., 2014a). Also, RPA does not require an initial template denaturation step and complex thermal instrumentation (Deng and Gao 2015).

RPA has been mainly applied to the detection of pathogens (Shen et al., 2011; Crannell et al., 2014b; B. Rohrman and Richards-Kortum, 2015). For example, Rohrman and Richards-Kortum accomplished the detection of 10 copies of HIV DNA in under 15 min through RPA incorporated with a lateral flow assay allowing to perform HIV diagnostics compatible with resource poor settings (B. A. Rohrman and Richards-Kortum, 2012). Additionally, an RPA assay was also developed for the detection of Tuberculosis under 20 min with a limit of detection in the femtograms of template (Boyle et al., 2014). RPA has long been translated to the commercial and laboratory stetting - TwistDX (Cambridge, United Kingdom) for both end-point detection (TwistAmp^TM LF probe) and real-time monitorization (TwistAmp^TM exo probe) (TwistDx 2021).

Apart from the traditional detection methods usually applied for PCR, a unique FRET-based fluorescence probe and a lateral-flow strip system have also been employed in RPA detection of SARS-CoV-2 N gene, which decrease background noise and enable an instrumentation-free readout (Xia and Chen 2020). In fact, the RPA’s low temperature reaction profile coupled to the high efficiency and specificity have been supporting the growing application of RPA in LOC devices for the amplification and detection of targets relevant in infectious diseases and antibiotic resistance (Table 4).

These examples demonstrate the advantages of RPA, especially as the quest for decentralized NAATs for diagnostics at PoC (Lobato et al., 2018; Daher et al., 2016). Additional reports show the possibility to use RPA for biomedical applications in surveillance of disease biomarkers (Euler et al., 2012), in the food industry (T. H. Kim et al., 2014) and in the agriculture sector (Mekuria et al., 2014). Although, no RPA assays have been approved by FDA or CE market thus far, it is anticipated that its operational advantages will prompt for the uptake of this technology for the detection of human pathogens in low resource settings, which would have a tremendous impact in reducing the high burden of infectious diseases and associated morbidity.

Rolling Circle Amplification

Rolling Circle Amplification (RCA) is an isothermal amplification protocol that operates at low temperature (23°C—60°C), which has been adapted from the in vivo RCA mechanism (Fire and Xu, 1995). This system requires a DNA polymerase with strand displacement activity (such as Phi29 DNA polymerase), that in presence of a circular template (e.g., plasmid, bacteriophages, DNA/RNA from virus or bacteria, etc.) and a specific primer generates a long DNA molecule with tandem repeats (D. Liu et al., 1996) (Figure 3E). The RCA mechanism has circular DNA as the predominant type of template, but in presence of linear DNA, a surrogate circular intermediate template is formed, that is then used for the subsequent amplification step. The RCA architecture offers two main benefits: 1) the low temperature isothermal scheme, with incubation temperatures as low as 23°C; and 2) the simplicity of its mechanism requirements (single primer and a productive DNA polymerase) (Li and Macdonald 2015), which yields high amplification efficiencies (∼10³ copies in under 1 h), that could be enhanced though the addition of ssDNA-binding proteins (Y. Zhao et al., 2015).

Interestingly, the early RCA mechanism results in a linear amplification profile over time. In order to overcome this hurdle, several techniques have been developed to allow for an exponential mechanism, such as ramification amplification (RAM) (D. Y. Zhang et al., 2001), hyper-branched RCA (HRCA) (Lizardi et al., 1998), cascade RCA (Thomas et al., 1999) and multiply primed RCA (Dean et al., 2001).

One key feature of RCA, i.e., the capability to produce long fragments has been proven of great value to produce material for whole genome amplification, especially in the analysis of viral DNA genomes (Rector et al., 2004; Inoue-Nagata et al., 2004). RCA can also be performed on a solid support or complex biological matrixes (e.g., inside the cell or on cell surfaces) allowing for molecular level detection (Konry et al., 2011).

These advantageous characteristics have spurred the development of highly sensitive RCA-based detection methods (Yue et al., 2021) (Table 7).

The low temperature isothermal profile of RCA also makes it an attractive candidate for integration in point-of-care devices (Giuffrida and Giuseppe Spoto, 2017), for example for the detection of bacteria and virus (Sato et al., 2010; Schopf et al., 2008). Other schemes have evolved from the original RCA, such as C2CA, digital RCA, microbead-based RCA, particle-based RCA, performed in a great diversity of device formats, e.g., centrifugal valve-less (Heo et al., 2016) and droplet-based devices (Giuffrida and Giuseppe Spoto, 2017), DMF chips and paper-strips (Ali et al., 2009).

Despite RCA use has been evolving over 2 decades, no RCA-based diagnostic kits have yet reached the market (de Paz et al., 2014). So far, there are only RCA research-type kits being commercialized, such as the Illustra TempliPhi DNA amplification kit from GE HealthCare (Buckinghamshire, United Kingdom) (Reagin et al., 2003).

Presently, the large number of RCA developments have focused on biotechnology applications and molecular detection schemes, several innovative concepts have been merging RCA and nanotechnology that promise extension of RCA potential to new a totally different scale and scope.

Blooming Contenders to the “Gold Standard” Title

Despite the great number of isothermal amplification systems already showing technological maturity and consolidated applications, such as the reviewed before, the quest for improved systems and specific application still encourages the development of more isothermal amplification methods. The ones with most expression have been the Multiple Displacement Amplification (MDA) (Spits et al., 2006), Exponential Amplification Reaction (EXPAR) and Nicking and Extension Amplification Reaction (NEAR) (Van Ness et al., 2003), Helicase Dependent Amplification (HDA) (Vincent et al., 2004) and Hybridization Chain Reaction (HCR) (Evanko 2004; Dirks and Pierce 2004) (Figure 4). Next, these methods are briefly overviewed.

FIGURE 4

Multiple Displacement Amplification (2002)

MDA is an alternative DNA amplification based on random hexamer primers and the activity of a high-fidelity enzyme, such as Phi29 DNA polymerase (Spits et al., 2006). Compared with PCR and other amplification techniques, MDA do not require sequence specific primers, once its mechanism exploits the random hybridization to generate large sized DNA fragments. Beside the isothermal profile (30°C), Phi 29 polymerase has proofreading activity, consequently MDA products contain less errors and higher sizes than the ones obtain via Taq amplification for the same time interval (2–3 h) (Blanco et al., 1989; Paez et al., 2004; Esteban, Salas, and Blanco 1993).

These beneficial features have spurred the application of MDA for Single Cell Genome Sequencing (Dean et al., 2002; Yoon et al., 2011; Rinke et al., 2013). Since it yields roughly 1–2 µg of DNA (enough for sequencing studies) with a genome coverage around 99% (Paez et al., 2004; Hellani et al., 2005), which allowed for the screening of genetic health condition in early-staged embryos before implantation (Hellani et al., 2005). MDA is also valuable for SPN allele detection (Ling et al., 2012) and for identifying the size of allelic polymorphic repeats (Ballantyne et al., 2006).

Exponential Amplification Reaction and Nicking and Extension Amplification Reaction (2003)

EXPAR is the exponential version of NEAR system, both simulate the SDA mechanism, where the difference in the melting temperature is exploited for target release and regeneration (Van Ness et al., 2003). A target template comprising a nicking site is designed to hybridize with the desire target. The polymerase replicates the template target, which is then nicked, producing a short fragment (8–16 bp) that is released by duplex instability, rather than by strand displacement activity (Van Ness et al., 2003). Conversely, the exponential version of NEAR uses a target template with two target complementary regions, instead of one, which after being nicked, releases a synthetized target, that can also pair up with the template target, creating a cycle of target regeneration and empowering NEAR to the desired exponential scale (Jia et al., 2010).

NEAR has a linear amplification profile, nevertheless it allows the amplification of any small targets by adding restriction sequences in the flanking regions (Maples et al., 2007). On the other hand, EXPAR is strongly limited by the requirement of targets natively flanked by restriction sites (Jia et al., 2010). Both NEAR and EXPAR (Tan et al., 2005) are particularly well suited for the detection of small fragments (8–16 bp) with high analytical sensitivity. Applications of NEAR include the detection of DNA (Zhou et al., 2014; Y. Song et al., 2014), proteins (A. X. Zheng et al., 2012; L. Xue, Zhou, and Xing 2010; Y. Huang et al., 2013; L. Xue, Zhou, and Xing 2012) and enzymes (Y. Zhao et al., 2013; X. Liu et al., 2014). Additionally, NEAR’s ability to amplify at room temperature, without initial template denaturation and higher tolerance to reaction inhibitors are two beneficial criteria for POC integration. In this regard, Wang et al., (L. Wang et al., 2017) reported on a highly specific detection assay for transgenic soya based on NEAR that is promising for PoC analysis. NEAR system is also being commercialized under kit formats. DNAble® by EnviroLogix (Portland, United States) test kit detects Salmonella and Clavibacter michiganesis (a plant pathogen) in 15 min with a sensitivity of 10³ cfu per reaction (Envirologix, 2021). Alere-i POC allows the detection of influenza A and B virus in 15 min (Alere, Waltham, United States) (Nie et al., 2014; Alere^TM now Abbott, 2021). Even though, not much is known about NEAR and EXPAR technology, their simplicity, specificity, and high adaptability are attractive features pushing for wider application.

Helicase Dependent Amplification (2004)

HDA is regarded as one of the simplest isothermal amplification schemes since it is based on the in vivo human DNA replication process (Vincent, Xu, and Kong 2004). HDA retains most of the PCR advantages, while improving the efficiency and selectivity, reducing the reaction and analysis complexity and requires less sample preparation steps, denoting the potential for integration in decentralized settings (An et al., 2005).

In the same fashion as PCR, HDA is compatible with different detection mechanisms such as gel electrophoresis for end-point measurement, fluorescent detection [with fluorescent DNA intercalator (Barbieri et al., 2014) and specific probes (Tong et al., 2008)] and electrochemical detection [with electroactive intercalator (Kivlehan et al., 2011)]], for real-time monitorization. However, HDA can also be monitored though Lateral Flow Devices (LFDs), which are much more suitable for low-cost and point-of-need scenario, than real-time assays (Du et al., 2017; Mahalanabis et al., 2010; Kolm et al., 2019; Tomlinson, Dickinson, and Boonham 2010).

Regarding HDA applications, the majority are devoted to the detection of infectious diseases. In fact, HDA has found a market niche in point-of-need testing (Craw et al., 2015), driven forward the development of commercial test kits (Gaydos et al., 2017) for pathogens such as, Herpes simplex [approved by FDA in 2011 (Lemieux et al., 2012); H. J. Kim et al., 2011)], Bordetella pertussis, Clostridium difficile Toxin A and Streptococcus from vaginal/rectal swabs (Faron et al., 2015). Quidel (proprietary for HDA technology) commercializes the AmpliVue and Solana test kits (Quidel 2021), based on HDA-Lateral Flow Devices, allowing the DNA amplification to occur in a CLIA-waiver, meaning without any sample preparation step (Weber et al., 2016). Additionally, BioHelix developed qualitative amplification detection kits (New England BioLabs, 2021) that recently receive FDA 501 (k) approval (Craw and Balachandran 2012).

Despite the usefulness of HDA in pathogen detection, it can be easily misinterpreted, since HDA presents issues often posed by the isothermal profile, such as the high risk of primer-dimer artifacts and off-target effects, ultimately leading to false positive phenomena, high background signal, inability to multiplex, low sensibility and selectivity (Barreda-García et al., 2018). Together, single-propriety commercialization, the false positive phenomena and the lack of validated assays have been hampered HDA widespread. However, if developers pushed forward the integration with LOC systems, HDA will likely show a significant increase in point-of-need pathogen detection, ultimately fueling the development of more isothermal amplification schemes.

Hybridization Chain Reaction (HCR) (2004)

HCR Evanko (2004), Dirks and Pierce (2004) differs from all the previously reported methods, since isothermal amplification is achieved via signal amplification, without requiring the generation of DNA or RNA products. Comparing to the polymerase-based methods, the signal amplification schemes are not subject to product or enzyme inhibition. Depending on the strategy for signal amplification mechanism, there are three categories: nuclease-assisted, DNAzyme-assisted and enzyme-free reactions. Regarding the last type, HCR was the first being proposed in 2004 (Dirks and Pierce, 2004) being based in the differential hybridization of two partially complementary probes (hairpin form), that can only attain the energy required for conformational change (at room temperature) when in the presence of target ssDNA or RNA, generating a long-nicked copolymer. Trough the introduction of a fluorescent label on a specific hairpin moiety, real-time tracking of HCR can be achieved (Chemeris, Nikonorov, and Vakhitov 2008). This method pioneered the development of nanostructures from DNA self-assembly (Xuan and Hsing 2014; G. Zhu et al., 2013; Ding et al., 2015; J. Zheng et al., 2013; Xuan, Fan, and Hsing 2015) and introduced DNA as an amplifying transducer for biosensing (J. Huang et al., 2011; Y. Chen et al., 2012; L. Yang et al., 2012; B. Zhang et al., 2012; P. Liu et al., 2013) and bioimaging (Choi et al., 2010; Choi, Beck, and Pierce 2014; G. Zhu et al., 2013). HCR have shown applicability in in situ analysis (Choi et al., 2010; Choi, Beck, and Pierce 2014), miRNA (L. Zhou et al., 2019) and mRNA (Choi et al., 2010) detection. Additionally, the combination of HCR with other methods such as Catalyze Hairpin Assembly for detection single nucleotide polymorphisms (Li B et al., 2012), immuno-HCR (B. Zhang et al., 2012; J. Zhou et al., 2012) and AuNPs-supporting HCR (W. J. Wang et al., 2015) as electrochemical immunoassays and RCA incorporating HCR (Bi et al., 2013).

HCR’s attractive features such as enzyme-free, isothermal profile and excellent efficiency, have contributed for its rapid gain of popularity (Deng and Gao 2015). Despite all the hype around non-enzymatic methods, they have been put aside due to leakage problems (Bi, Yue, and Zhang 2017).

Other Isothermal Amplification Schemes

Beside the up-mentioned methods, some other “niche” methods have also been developed, among them are SMART, SPIA, ICAN, SMAP 2 and BAD AMP (Figure 5).

FIGURE 5

These new isothermal amplification schemes cover broad applications, from nucleic acids detection (DNA, RNA, long RNA, SNPs, miRNA, DNA methylation) to the detection of proteins, enzymes, cancer cells, pathogens, small molecules and metal-ions (Y. Zhao et al., 2015; S. Kumar J. et al., 2018). Despite their range of applications, not all of these “blooming” amplification schemes have been applied much beyond their initial “proof-of-concept” purpose, since many of these methods still lack technical maturity (e.g., PHAMP, EIC, SPIA, ICAN and BAD AMP). Conversely, others have been endorsed over the years (e.g., MDA, SMART, HDA, EXPAR and HCR), nevertheless the strictness of conditions and reagents and the lack of accessible amplification kits and literature has been preventing wider use, forcing them to set as “niche” application schemes. As so, all schemes must undergo through improvements before they can emerge as competitors to the previously stablished methods (Li and Macdonald 2015).

Conclusions and Future Perspectives

PCR is the most widespread method and the current standard for nucleic acids amplification, its inherent features, such as the requirement for a thermocycler and the strict reaction conditions, increase the complexity of device integration and operating settings, overall rising the cost of PCR-based devices and assays. Conversely, isothermal schemes have constant and low temperature profiles, ability to use different types of molecules as starting material, low sensibility to inhibitors and offer a wide range of detection methods, which are crucial features rendering for a significantly easier LOC integration, ultimately pushing forward their implementation and rising consideration. Furthermore, the integration under chip formats contributes to enhance the sensibility, reproducibility, rapidness, cost-effectiveness and achieve more accurate results, reducing the amplification bias. All together, these features are true “game changers”, defying PCR technique for the “gold standard” title.

Generally, isothermal amplification methods offer a great potential for lower-cost, higher speed, smaller consumption of sample and reagents and the opportunity to automation of all processes from sample preparation to signal detection under lab-on-chip formats. In this regard, the isothermal amplification schemes were grouped in two main categories: the mature and consolidated ones, such as SDA, NASBA, LAMP, RPA and RCA; and the blooming schemes, that despite their promising features, still lack technical maturity and widespread application or commercialization under kit formats. This last group comprises SMART, MDA, EXPAR, HDA, HCR, SPIA and others.

Besides the nucleic acid detection purposes, isothermal amplification schemes have also been applied much further than this initial concept, such as: whole genome sequencing, single cell sequencing, electrochemical immunoassays, single-nucleotide polymorphism detection, virus and bacterial detection from biological swabs, environmental point-of-need niche applications, amplification of non-DNA templates and amplification of long, short and micro-RNA fragments. Nevertheless, the ultimate success of the isothermal schemes is still dependent on wider demonstration of specificity and cost-effectiveness. In fact, most of these methods show unspecific products formation and high background noise, due to the low amplification temperature, issues that need to be addressed before translation to the clinical scenario. Additionally, many of the schemes discussed are still protected by patents or licensed by a single proprietary company, which may be limiting the access to the necessary enzymes and reagents, ultimately leading to high market prices, thus preventing broader application. Once these rights have expired, IA-based methods should meet the requirements to become a reference to nucleic acid diagnosis and POC applications, with a profitable commercialization worldwide.

References

• 1

  AbeT.SegawaY.WatanabeH.YotoriyamaT.KaiS.YasudaA.et al (2011). Point-of-Care Testing System Enabling 30 Min Detection of Influenza Genes. Lab. Chip11 (6), 1166–1167. 10.1039/c0lc00519c

  • CrossRef
  • Google Scholar

• 2

  AkdumanD.EhretJ. M.MessinaK.RagsdaleS.JudsonF. N. (2002). Evaluation of a Strand Displacement Amplification Assay (BD ProbeTec-SDA) for Detection of Neisseria Gonorrhoeae in Urine Specimens. J. Clin. Microbiol.40 (1), 281–283. 10.1128/JCM.40.1.281-283.2002

  • CrossRef
  • Google Scholar

• 3

  Alere^TM now Abbott. 2021. “ID NOW^TM INFLUENZA A & B 2.” 2021. Available at: https://www.globalpointofcare.abbott/en/product-details/id-now-influenza-ab-2.html.

  • Google Scholar

• 4

  AliM. M.AguirreS. D.XuY.FilipeC. D. M.PeltonR.LiY. (2009). Detection of DNA Using Bioactive Paper Strips. Chem. Commun.43, 6640–6642. 10.1039/b911559e

  • CrossRef
  • Google Scholar

• 5

  AnL.TangW.RanalliT. A.KimH.-J.WytiazJ.KongH. (2005). Characterization of a Thermostable UvrD Helicase and its Participation in Helicase-dependent Amplification. J. Biol. Chem.280 (32), 28952–28958. 10.1074/jbc.M503096200

  • CrossRef
  • Google Scholar

• 6

  ArakiT.ShimizuK.NakamuraK.NakamuraT.MitaniY.ObayashiK.et al (2010). Usefulness of Peptide Nucleic Acid (PNA)-Clamp Smart Amplification Process Version 2 (SmartAmp2) for Clinical Diagnosis of KRAS Codon12 Mutations in Lung Adenocarcinoma. J. Mol. Diagn.12 (1), 118–124. 10.2353/jmoldx.2010.090081

  • CrossRef
  • Google Scholar

• 7

  AryanE.MakvandiM.FarajzadehA.HuygenK.BifaniP.MousaviS.-L.et al (2010). A Novel and More Sensitive Loop-Mediated Isothermal Amplification Assay Targeting IS6110 for Detection of Mycobacterium Tuberculosis Complex. Microbiol. Res.165 (3), 211–220. 10.1016/j.micres.2009.05.001

  • CrossRef
  • Google Scholar

• 8

  Biomerieux. 2021. “NUCLISENS EASYQ®.” 2021. Available at: https://www.biomerieux-diagnostics.com/nuclisens-easyqr.

  • Google Scholar

• 9

  BachmannL. H.JohnsonR. E.ChengH. John. R. Papp.MarkowitzL. E.IIIPappJ. R.HookE. W. (2009). Nucleic Acid Amplification Tests for Diagnosis of Neisseria Gonorrhoeae Oropharyngeal Infections. J. Clin. Microbiol.47 (4), 902–907. 10.1128/JCM.01581-08

  • CrossRef
  • Google Scholar

• 10

  BallantyneK. N.van OorschotR. A. H.John MitchellR.KoukoulasI. (2006). Molecular Crowding Increases the Amplification Success of Multiple Displacement Amplification and Short Tandem Repeat Genotyping. Anal. Biochem.355 (2), 298–303. 10.1016/j.ab.2006.04.039

  • CrossRef
  • Google Scholar

• 11

  BarbieriD.VenturoliS.RöslF.Rincon-OrozcoB. (2014). Detection of High-Risk Human Papillomavirus Type 16 and 18 Using Isothermal Helicase-dependent Amplification. Diagn. Microbiol. Infect. Dis.79 (2), 178–182. 10.1016/j.diagmicrobio.2014.02.012

  • CrossRef
  • Google Scholar

• 12

  Barreda-GarcíaS.Miranda-CastroMiranda-CastroR.de-los-Santos-ÁlvarezN.Miranda-OrdieresA. J.Lobo-CastañónM. J. (2018). Helicase-Dependent Isothermal Amplification: A Novel Tool in the Development of Molecular-Based Analytical Systems for Rapid Pathogen Detection. Anal. Bioanal. Chem.410 (3), 679–693. 10.1007/s00216-017-0620-3

  • CrossRef
  • Google Scholar

• 13

  Bechy-LoizeauA.-L.FlandroisJ.-P.AbaibouH.AbaibouHafid. (2015). Assessment of Polycarbonate Filter in a Molecular Analytical System for the Microbiological Quality Monitoring of Recycled Waters Onboard ISS. Life Sci. Space Res.6, 29–35. 10.1016/j.lssr.2015.06.002

  • CrossRef
  • Google Scholar

• 14

  BesuschioS. A.Llano MurciaM.BenatarA. F.MonneratS.CruzI.Picadode PuigA.et al (2017). Analytical Sensitivity and Specificity of a Loop-Mediated Isothermal Amplification (LAMP) Kit Prototype for Detection of Trypanosoma Cruzi DNA in Human Blood Samples. Plos Negl. Trop. Dis.11 (7), e0005779–18. 10.1371/journal.pntd.0005779

  • CrossRef
  • Google Scholar

• 15

  BiS.YueS.ZhangS. (2017). Hybridization Chain Reaction: A Versatile Molecular Tool for Biosensing, Bioimaging, and Biomedicine. Chem. Soc. Rev.46 (14), 4281–4298. 10.1039/c7cs00055c

  • CrossRef
  • Google Scholar

• 16

  BiS.ZhaoT.LuoB.ZhuJ.-J. (2013). Hybridization Chain Reaction-Based Branched Rolling Circle Amplification for Chemiluminescence Detection of DNA Methylation. Chem. Commun.49 (61), 6906–6908. 10.1039/C3CC43353F

  • CrossRef
  • Google Scholar

• 17

  BlancoL.BernadA.LázaroJ. M.MartínG.GarmendiaC.SalasM. (1989). Highly Efficient DNA Synthesis by the Phage ϕ 29 DNA Polymerase. J. Biol. Chem.264 (15), 8935–8940. 10.1016/s0021-9258(18)81883-x

  • CrossRef
  • Google Scholar

• 18

  BoyleD. S.McNerneyR.Teng LowH.LeaderB. T.MeyerA. C.MeyerJ. C.et al (2014). Rapid Detection of Mycobacterium Tuberculosis by Recombinase Polymerase Amplification. PLoS ONE9 (8), e103091–9. 10.1371/journal.pone.0103091

  • CrossRef
  • Google Scholar

• 19

  CaoA.ZhangC.-y. (2012). Sensitive and Label-free DNA Methylation Detection by Ligation-Mediated Hyperbranched Rolling Circle Amplification. Anal. Chem.84 (14), 6199–6205. 10.1021/ac301186j

  • CrossRef
  • Google Scholar

• 20

  ChangC.-C.ChenC.-C.LuS.-C. H.-H.HuiY.-H.LiangC.-W.LinC. W. (2012). Diagnostic Devices for Isothermal Nucleic Acid Amplification. Sensors12 (6), 8319–8337. 10.3390/s120608319

  • CrossRef
  • Google Scholar

• 21

  ChemerisD. A.NikonorovY. M.VakhitovV. A. (2008). Real-Time Hybridization Chain Reaction. Dokl Biochem. Biophys.419, 53–55. 10.1134/s1607672908020014

  • CrossRef
  • Google Scholar

• 22

  ChenJ.ZhouX.MaY.LinX.DaiZ.ZouX. (2016). Asymmetric Exponential Amplification Reaction on a Toehold/Biotin Featured Template: An Ultrasensitive and Specific Strategy for Isothermal MicroRNAs Analysis. Nucleic Acids Res.44 (15), gkw504. 10.1093/nar/gkw504

  • CrossRef
  • Google Scholar

• 23

  ChenY.XuJ.SuJ.XiangY.YuanR.ChaiY. (2012). In Situ Hybridization Chain Reaction Amplification for Universal and Highly Sensitive Electrochemiluminescent Detection of DNA. Anal. Chem.84 (18), 7750–7755. 10.1021/ac3012285

  • CrossRef
  • Google Scholar

• 24

  ChengY.ZhangX.LiZ.JiaoX.WangY.ZhangY. (2009). Highly Sensitive Determination of Microrna Using Target-Primed and Branched Rolling-Circle Amplification. Angew. Chem. Int. Ed.48 (18), 3268–3272. 10.1002/anie.200805665

  • CrossRef
  • Google Scholar

• 25

  ChoiH. M. T.BeckV. A.PierceN. A. (2014). Next-Generation In Situ Hybridization Chain Reaction: Higher Gain, Lower Cost, Greater Durability. ACS Nano8 (5), 4284–4294. 10.1021/nn405717p

  • CrossRef
  • Google Scholar

• 26

  ChoiH. M. T.ChangJ. Y.PadillaJ. E.FraserS. E.PierceN. A. (2010). Programmable In Situ Amplification for Multiplexed Imaging of MRNA Expression. Nat. Biotechnol.28 (11), 1208–1212. 10.1038/nbt.1692

  • CrossRef
  • Google Scholar

• 27

  ChowW. H. A.McCloskeyC.TongY.HuL.YouQ.KellyC. P.et al (2008). Application of Isothermal Helicase-dependent Amplification with a Disposable Detection Device in a Simple Sensitive Stool Test for Toxigenic Clostridium Difficile. J. Mol. Diagn.10 (5), 452–458. 10.2353/jmoldx.2008.080008

  • CrossRef
  • Google Scholar

• 28

  ChristianA. T.PatteeM. S.AttixC. M.ReedB. E.SorensenK. J.TuckerJ. D. (2001). Detection of DNA Point Mutations and MRNA Expression Levels by Rolling Circle Amplification in Individual Cells. Proc. Natl. Acad. Sci.98 (25), 14238–14243. 10.1073/pnas.251383598

  • CrossRef
  • Google Scholar

• 29

  ChuY.DengA.-P.WangW.ZhuJ.-J. (2019). Concatenated Catalytic Hairpin Assembly/Hyperbranched Hybridization Chain Reaction Based Enzyme-free Signal Amplification for the Sensitive Photoelectrochemical Detection of Human Telomerase RNA. Anal. Chem.91 (5), 3619–3627. 10.1021/acs.analchem.8b05610

  • CrossRef
  • Google Scholar

• 30

  ChungS. H.BaekC.CongV. T. J.MinJ. (2015). The Microfluidic Chip Module for the Detection of Murine Norovirus in Oysters Using Charge Switchable Micro-bead Beating. Biosens. Bioelectron.67, 625–633. 10.1016/j.bios.2014.09.083

  • CrossRef
  • Google Scholar

• 31

  ClinicalTrials.gov2021Clinical Trials with LAMP Assay. Available at: https://www.clinicaltrials.gov/ct2/results?cond=&term=Loop+mediated+isothermal+amplification&cntry=&state=&city=&dist= (Accessed July 27, 2021).

  • Google Scholar

• 32

  ClinicalTrials.gov Identifier: NCT04500873. 2020a. “Performance of RPA-LF for Cutaneous Leishmaniasis (RPA-LF).” 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04500873?term=recombinase+polymerase+amplification&draw=2&rank=1.

  • Google Scholar

• 33

  ClinicalTrials.gov Identifier: NCT04579549. 2021. “Repeat Testing for SARS-CoV-2.” 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04579549?term=Loop+mediated+isothermal+amplification&draw=2&rank=5.

  • Google Scholar

• 34

  ClinicalTrials.gov Identifier:NCT02371395. 2018b. “Validation of RealAmp Method for the Diagnosis of Malaria in Endemic Areas of Brazil.” 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02371395.

  • Google Scholar

• 35

  ClinicalTrials.gov Identifier: NCT01838902 (2018a). “Primaquine’s Gametocytocidal Efficacy in Malaria Asymptomatic Carriers (PRINOGAM).” 2018.

  • Google Scholar

• 36

  ClinicalTrials.gov Identifier:NCT03829735 (2020b). “Neonatal Vaccination against Hepatitis B in Africa - Sero-Survey in Senegal (NeoVac2S).” 2020.

  • Google Scholar

• 37

  ComptonJ. (1991). Nucleic Acid Sequence-Based Amplification. Nature350 (6313), 91–92. 10.1038/350091a0

  • CrossRef
  • Google Scholar

• 38

  ConnollyA. R.TrauM. (2010). Isothermal Detection of DNA by Beacon-Assisted Detection Amplification. Angew. Chem. Int. Edition49 (15), 2720–2723. 10.1002/anie.200906992

  • CrossRef
  • Google Scholar

• 39

  ConnollyA. R.TrauM. (2011). Rapid DNA Detection by Beacon-Assisted Detection Amplification. Nat. Protoc.6 (6), 772–778. 10.1038/nprot.2011.326

  • CrossRef
  • Google Scholar

• 40

  CordrayM. S.Richards-KortumR. R. (2012). Emerging Nucleic Acid-Based Tests for Point-of-Care Detection of Malaria. Am. J. Trop. Med. Hyg.87 (2), 223–230. 10.4269/ajtmh.2012.11-0685

  • CrossRef
  • Google Scholar

• 41

  CrannellZ. A.RohrmanB.Richards-KortumR. (2014b). Equipment-Free Incubation of Recombinase Polymerase Amplification Reactions Using Body Heat. PLoS ONE9 (11), e112146–7. 10.1371/journal.pone.0112146

  • CrossRef
  • Google Scholar

• 42

  CrannellZ. A.RohrmanB.Richards-kortumR. (2014a). Quantification of HIV-1 DNA Using Real-Time Recombinase Polymerase Amplification. Anal. Chem.86 (12), 5615–5619. 10.1021/ac5011298

  • CrossRef
  • Google Scholar

• 43

  CrawP.BalachandranW. (2012). Isothermal Nucleic Acid Amplification Technologies for Point-of-Care Diagnostics: A Critical Review. Lab. Chip12 (14), 2469–2486. 10.1039/c2lc40100b

  • CrossRef
  • Google Scholar

• 44

  CrawP.MackayR.NaveenathayalanA.HudsonC.BranavanM.SadiqS.et al (2015). A Simple, Low-Cost Platform for Real-Time Isothermal Nucleic Acid Amplification. Sensors15 (9), 23418–23430. 10.3390/s150923418

  • CrossRef
  • Google Scholar

• 45

  CuadrosJ.Martin RamírezA.GonzálezI. J.DingX. C.Perez TanoiraR.Rojo-MarcosG.et al (2017). LAMP Kit for Diagnosis of Non-falciparum Malaria in Plasmodium Ovale Infected Patients. Malar. J.16 (1), 1–5. 10.1186/s12936-016-1669-8

  • CrossRef
  • Google Scholar

• 46

  DaherR. K.StewartG.BoissinotM.BergeronM. G. (2016). Gale Stewart, Maurice Boissinot, and Michel G. Bergeron.Recombinase Polymerase Amplification for Diagnostic Applications. Clin. Chem.62 (7), 947–958. 10.1373/clinchem.2015.245829

  • CrossRef
  • Google Scholar

• 47

  de PazH. D.BrotonsP.Muñoz-AlmagroC. (2014). Molecular Isothermal Techniques for Combating Infectious Diseases: Towards Low-Cost Point-of-Care Diagnostics. Expert Rev. Mol. Diagn.14 (7), 827–843. 10.1586/14737159.2014.940319

  • CrossRef
  • Google Scholar

• 48

  DeanF. B.HosonoS.FangL.WuX.FaruqiA. F.Bray-WardP.et al (2002). Comprehensive Human Genome Amplification Using Multiple Displacement Amplification. Proc. Natl. Acad. Sci.99 (8), 5261–5266. 10.1073/pnas.082089499

  • CrossRef
  • Google Scholar

• 49

  DeanF. B.NelsonJ. R.GieslerT. L.LaskenR. S. (2001). Rapid Amplification of Plasmid and Phage DNA Using Phi29 DNA Polymerase and Multiply-Primed Rolling Circle Amplification. Genome Res.11 (6), 1095–1099. 10.1101/gr.180501

  • CrossRef
  • Google Scholar

• 50

  DelaneyJ. A.UlrichR. M.PaulJ. H. (2011). Detection of the Toxic Marine Diatom Pseudo-nitzschia Multiseries Using the RuBisCO Small Subunit (RbcS) Gene in Two Real-Time RNA Amplification Formats. Harmful Algae11, 54–64. 10.1016/j.hal.2011.07.005

  • CrossRef
  • Google Scholar

• 51

  DengH.GaoZ. (2015). Bioanalytical Applications of Isothermal Nucleic Acid Amplification Techniques. Analytica Chim. Acta853 (1), 30–45. 10.1016/j.aca.2014.09.037

  • CrossRef
  • Google Scholar

• 52

  DimovI. K.Garcia-CorderoJ. L.O'GradyJ.PoulsenC. R.ViguierC.KentL.et al (2008). Integrated Microfluidic TmRNA Purification and Real-Time NASBA Device for Molecular Diagnostics. Lab. Chip8 (12), 2071–2078. 10.1039/b812515e

  • CrossRef
  • Google Scholar

• 53

  DingJ.GuY.LiF.ZhangH.QinW. (2015). DNA Nanostructure-Based Magnetic Beads for Potentiometric Aptasensing. Anal. Chem.87 (13), 6465–6469. 10.1021/acs.analchem.5b01576

  • CrossRef
  • Google Scholar

• 54

  DirksR. M.PierceN. A. (2004). From the Cover: Triggered Amplification by Hybridization Chain Reaction. Proc. Natl. Acad. Sci.101 (43), 15275–15278. 10.1073/pnas.0407024101

  • CrossRef
  • Google Scholar

• 55

  DuX.-j.ZhouT.-j.LiP.WangS. (2017). A Rapid Salmonella Detection Method Involving Thermophilic Helicase-dependent Amplification and a Lateral Flow Assay. Mol. Cell Probes34, 37–44. 10.1016/j.mcp.2017.05.004

  • CrossRef
  • Google Scholar

• 56

  DyerJ. R.GilliamB. L.GilliamJ. J.GrossoL.CohenM. S.FiscusS. A. (1996). Quantitation of Human Immunodeficiency Virus Type 1 RNA in Cell Free Seminal Plasma: Comparison of NASBA with Amplicor Reverse Transcription-PCR Amplification and Correlation with Quantitative Culture. J. Virol. Methods60 (2), 161–170. 10.1016/0166-0934(96)02063-0

  • CrossRef
  • Google Scholar

• 57

  EdwardsM. C.GibbsR. A. (1994). Multiplex PCR: Advantages, Development, and Applications. Genome Res.3 (4), S65–S75. 10.1101/gr.3.4.S65

  • CrossRef
  • Google Scholar

• 58

  Eiken. 2021. “Products, Eiken Chemical Co., LTD.,” 2021. Available at: http://www.eiken.co.jp/en/product/index.html.

  • Google Scholar

• 59

  EnomotoY.YoshikawaT.IhiraM.AkimotoS.MiyakeF.UsuiC.et al (2005). Rapid Diagnosis of Herpes Simplex Virus Infection by a Loop-Mediated Isothermal Amplification Method. J. Clin. Microbiol.43 (2), 951–955. 10.1128/JCM.43.2.951-955.2005

  • CrossRef
  • Google Scholar

• 60

  Envirologix. 2021DNAble. Available at: https://www.envirologix.com/technology/molecular-detection/ (Accessed July 27, 2021).

  • Google Scholar

• 61

  EscadafalC.FayeO.SallA. A.FayeO.WeidmannM.StrohmeierO.et al (2014). Rapid Molecular Assays for the Detection of Yellow Fever Virus in Low-Resource Settings. Plos Negl. Trop. Dis.8 (3), e2730. 10.1371/journal.pntd.0002730

  • CrossRef
  • Google Scholar

• 62

  EstebanJ. A.SalasM.BlancoL. (1993). Fidelity of Phi 29 DNA Polymerase. Comparison between Protein-Primed Initiation and DNA Polymerization. J. Biol. Chem.268 (4), 2719–2726. 10.1016/s0021-9258(18)53833-3

  • CrossRef
  • Google Scholar

• 63

  EulerM.WangY.OttoP.TomasoH.EscuderoR.AndaP.et al (2012). Recombinase Polymerase Amplification Assay for Rapid Detection of Francisella Tularensis. J. Clin. Microbiol.50 (7), 2234–2238. 10.1128/JCM.06504-11

  • CrossRef
  • Google Scholar

• 64

  EvankoD. (2004). Hybridization Chain Reaction. Nat. Methods1 (3), 186. 10.1038/nmeth1204-186a

  • CrossRef
  • Google Scholar

• 65

  FangX.LiuY.KongJ.JiangX. (2010). Loop-Mediated Isothermal Amplification Integrated on Microfluidic Chips for Point-of-Care Quantitative Detection of Pathogens. Anal. Chem.82 (7), 3002–3006. 10.1021/ac1000652

  • CrossRef
  • Google Scholar

• 66

  FaronM. L.LedeboerN. A.GranatoP.DalyJ. A.PierceK.PancholiP.et al (2015). Detection of Group A Streptococcus in Pharyngeal Swab Specimens by Use of the AmpliVue Gas Isothermal Helicase-dependent Amplification Assay. J. Clin. Microbiol.53 (7), 2365–2367. 10.1128/JCM.01085-15

  • CrossRef
  • Google Scholar

• 67

  FireA.XuS. Q. (1995). Rolling Replication of Short DNA Circles. Proc. Natl. Acad. Sci.92 (10), 4641–4645. 10.1073/pnas.92.10.4641

  • CrossRef
  • Google Scholar

• 68

  FujinoM.YoshidaN.YamaguchiS.HosakaN.OtaY.NotomiT.et al (2005). A Simple Method for the Detection of Measles Virus Genome by Loop-Mediated Isothermal Amplification (LAMP). J. Med. Virol.76 (3), 406–413. 10.1002/jmv.20371

  • CrossRef
  • Google Scholar

• 69

  GansenA.HerrickA. M.DimovI. K.LeeL. P.ChiuD. T. (2012). Digital LAMP in a Sample Self-Digitization (SD) Chip. Lab. Chip12 (12), 2247–2254. 10.1039/c2lc21247a

  • CrossRef
  • Google Scholar

• 70

  García-FernándezS.MorosiniM.-I.MarcoF.GijonD.VergaraA.VilaJ.et al (2014). Evaluation of the Eazyplex(R) SuperBug CRE System for Rapid Detection of Carbapenemases and ESBLs in Clinical Enterobacteriaceae Isolates Recovered at Two Spanish Hospitals. J. Antimicrob. Chemother.70 (4), 1047–1050. 10.1093/jac/dku476

  • CrossRef
  • Google Scholar

• 71

  Garrido-MaestuA.AzinheiroS.CarvalhoJ.Abalde-CelaS.Carbó-ArgibayE.DiéguezL.et al (2017). Combination of Microfluidic Loop-Mediated Isothermal Amplification with Gold Nanoparticles for Rapid Detection of Salmonella Spp. In Food Samples. Front. Microbiol.8, 2159. 10.3389/fmicb.2017.02159

  • CrossRef
  • Google Scholar

• 72

  GaydosC.SchwebkeJ.DombrowskiJ.MarrazzoJ.ColemanJ.SilverB.et al (2017). Clinical Performance of the Solana Point-of-Care Trichomonas Assay from Clinician-Collected Vaginal Swabs and Urine Specimens from Symptomatic and Asymptomatic Women. Expert Rev. Mol. Diagn.17 (3), 303–306. 10.1080/14737159.2017.1282823

  • CrossRef
  • Google Scholar

• 73

  GiuffridaM. C.SpotoG. (2017). Integration of Isothermal Amplification Methods in Microfluidic Devices: Recent Advances. Biosens. Bioelectron.90, 174–186. 10.1016/j.bios.2016.11.045

  • CrossRef
  • Google Scholar

• 74

  GoldmeyerJ.LiH.McCormacM.CookS.StrattonC.LemieuxB.et al (2008). Identification of Staphylococcus Aureus and Determination of Methicillin Resistance Directly from Positive Blood Cultures by Isothermal Amplification and a Disposable Detection Device. J. Clin. Microbiol.46 (4), 1534–1536. 10.1128/JCM.02234-07

  • CrossRef
  • Google Scholar

• 75

  Gómez de la TorreT. Z.KeR.MezgerA.SvedlindhP.StrømmeM.NilssonM.et al (2012). Sensitive Detection of Spores Using Volume-Amplified Magnetic Nanobeads. Small8 (14), 2174–2177. 10.1002/smll.201102632

  • CrossRef
  • Google Scholar

• 76

  GuichónA.ChiparelliH.MartínezA.RodríguezC.TrentoA.RussiJ. C.et al (2004). Evaluation of a New NASBA Assay for the Qualitative Detection of Hepatitis C Virus Based on the NucliSens Basic Kit Reagents. J. Clin. Virol.29 (2), 84–91. 10.1016/S1386-6532(03)00091-X

  • CrossRef
  • Google Scholar

• 77

  HeijnenL.MedemaG. (2009). Method for Rapid Detection of Viable Escherichia Coli in Water Using Real-Time NASBA. Water Res.43 (12), 3124–3132. 10.1016/j.watres.2009.04.025

  • CrossRef
  • Google Scholar

• 78

  HellaniA.CoskunS.TbakhiA.Al-HassanS. (2005). Clinical Application of Multiple Displacement Amplification in Preimplantation Genetic Diagnosis. Reprod. BioMedicine Online10 (3), 376–380. 10.1016/S1472-6483(10)61799-3

  • CrossRef
  • Google Scholar

• 79

  HellyerT. J.NadeauJ. G. (2004). Strand Displacement Amplification: A Versatile Tool for Molecular Diagnostics. Expert Rev. Mol. Diagn.4 (2), 251–261. 10.1586/14737159.4.2.251

  • CrossRef
  • Google Scholar

• 80

  HeoH. Y.ChungS.KimY. T.KimD. H.SeoT. S. (2016). A Valveless Rotary Microfluidic Device for Multiplex Point Mutation Identification Based on Ligation-Rolling Circle Amplification. Biosens. Bioelectron.78, 140–146. 10.1016/j.bios.2015.11.039

  • CrossRef
  • Google Scholar

• 81

  HønsvallB. K.Robertson.L. J. (2017). From Research Lab to Standard Environmental Analysis Tool: Will NASBA Make the Leap. Water Res.109, 389–397. 10.1016/j.watres.2016.11.052

  • CrossRef
  • Google Scholar

• 82

  HoribeD.OchiaiT.ShimadaH.TomonagaT.NomuraF.GunM.et al (2007). Rapid Detection of Metastasis of Gastric Cancer Using Reverse Transcription Loop-Mediated Isothermal Amplification. Int. J. Cancer120 (5), 1063–1069. 10.1002/ijc.22397

  • CrossRef
  • Google Scholar

• 83

  HuC.KalsiS.ZeimpekisI.SunK.AshburnP.TurnerC.et al (2017). Ultra-Fast Electronic Detection of Antimicrobial Resistance Genes Using Isothermal Amplification and Thin Film Transistor Sensors. Biosens. Bioelectron.96 (January), 281–287. 10.1016/j.bios.2017.05.016

  • CrossRef
  • Google Scholar

• 84

  HuangJ.WuY.ChenY.ZhuZ.YangX.YangC. J.et al (2011). Pyrene-Excimer Probes Based on the Hybridization Chain Reaction for the Detection of Nucleic Acids in Complex Biological Fluids. Angew. Chem. Int. Ed.50 (2), 401–404. 10.1002/anie.201005375

  • CrossRef
  • Google Scholar

• 85

  HuangY.ChenJ.ZhaoS.ShiM.ChenZ.-F.LiangH. (2013). Label-Free Colorimetric Aptasensor Based on Nicking Enzyme Assisted Signal Amplification and DNAzyme Amplification for Highly Sensitive Detection of Protein. Anal. Chem.85 (9), 4423–4430. 10.1021/ac3037443

  • CrossRef
  • Google Scholar

• 86

  Ibarra-MenesesA. V.CruzI.ChicharroC.SánchezC.BiélerS.BrogerT.et al (2018). Evaluation of Fluorimetry and Direct Visualization to Interpret Results of a Loop-Mediated Isothermal Amplification Kit to Detect Leishmania DNA. Parasites Vectors11 (1), 1–9. 10.1186/s13071-018-2836-2

  • CrossRef
  • Google Scholar

• 87

  Inoue-NagataA. K.AlbuquerqueL. C.RochaW. B.NagataN. (2004). A Simple Method for Cloning the Complete Begomovirus Genome Using the Bacteriophage φ29 DNA Polymerase. J. Virol. Methods116 (2), 209–211. 10.1016/j.jviromet.2003.11.015

  • CrossRef
  • Google Scholar

• 88

  ItonagaM.MatsuzakiI.WarigayaK.TamuraT.ShimizuY.FujimotoM.et al (2016). Novel Methodology for Rapid Detection of KRAS Mutation Using PNA-LNA Mediated Loop-Mediated Isothermal Amplification. PLoS ONE11 (3), e0151654–12. 10.1371/journal.pone.0151654

  • CrossRef
  • Google Scholar

• 89

  IwasakiM.YonekawaT.OtsukaK.SuzukiW.NagamineK.HaseT.et al2003. “Validation of the Loop-Mediated Isothermal Amplification Method for Single Nucleotide Polymorphism Genotyping with Whole Blood.” Genome Lett.2 (8): 119–126. 10.1166/gl.2003.028

  • CrossRef
  • Google Scholar

• 90

  JamesA.MacDonaldJ. (2015). Recombinase Polymerase Amplification: Emergence as a Critical Molecular Technology for Rapid, Low-Resource Diagnostics. Expert Rev. Mol. Diagn.15 (11), 1475–1489. 10.1586/14737159.2015.1090877

  • CrossRef
  • Google Scholar

• 91

  JayanathN. Y.NguyenL. T.VuT. T.TranL. D. (2018). Development of a Portable Electrochemical Loop Mediated Isothermal Amplification (LAMP) Device for Detection of Hepatitis B Virus. RSC Adv.8 (61), 34954–34959. 10.1039/c8ra07235c

  • CrossRef
  • Google Scholar

• 92

  JiaH.LiZ.LiuC.ChengY. (2010). Ultrasensitive Detection of MicroRNAs by Exponential Isothermal Amplification. Angew. Chem. Int. Edition49 (32), 5498–5501. 10.1002/anie.201001375

  • CrossRef
  • Google Scholar

• 93

  JiaH.WangZ.WangC.ChangL.LiZ. (2014). Real-Time Fluorescence Detection of Hg2+ Ions with High Sensitivity by Exponentially Isothermal Oligonucleotide Amplification. RSC Adv.4 (19), 9439–9444. 10.1039/c3ra45986a

  • CrossRef
  • Google Scholar

• 94

  JonstrupS. P.KochJ.KjemsJ. (2006). A MicroRNA Detection System Based on Padlock Probes and Rolling Circle Amplification. Rna12 (9), 1747–1752. 10.1261/rna.110706

  • CrossRef
  • Google Scholar

• 95

  JungJ. H.ParkB. H.OhS. J.ChoiG.SeoT. S. (2015). Integration of Reverse Transcriptase Loop-Mediated Isothermal Amplification with an Immunochromatographic Strip on a Centrifugal Microdevice for Influenza A Virus Identification. Lab. Chip15 (3), 718–725. 10.1039/c4lc01033g

  • CrossRef
  • Google Scholar

• 96

  KanekoH.KawanaT.FukushimaE.SuzutaniT. (2007). Tolerance of Loop-Mediated Isothermal Amplification to a Culture Medium and Biological Substances. J. Biochem. Biophysical Methods70 (3), 499–501. 10.1016/j.jbbm.2006.08.008

  • CrossRef
  • Google Scholar

• 97

  KashirJ.YaqinuddinA. (2020). Loop Mediated Isothermal Amplification (LAMP) Assays as a Rapid Diagnostic for COVID-19. Med. Hypotheses141 (March), 109786. 10.1016/j.mehy.2020.109786

  • CrossRef
  • Google Scholar

• 98

  KeR.MignardiM.PacureanuA.SvedlundJ.BotlingJ.WählbyC.et al (2013). In Situ Sequencing for RNA Analysis in Preserved Tissue and Cells. Nat. Methods10 (9), 857–860. 10.1038/nmeth.2563

  • CrossRef
  • Google Scholar

• 99

  KerstingS.RauschV.BierF. F.von Nickisch-RosenegkM. (2014a). Multiplex Isothermal Solid-phase Recombinase Polymerase Amplification for the Specific and Fast DNA-Based Detection of Three Bacterial Pathogens. Microchim Acta181 (13–14), 1715–1723. 10.1007/s00604-014-1198-5

  • CrossRef
  • Google Scholar

• 100

  KerstingS.RauschV.BierF. F.Von Nickisch-RosenegkM. (2014b). Rapid Detection of Plasmodium Falciparum with Isothermal Recombinase Polymerase Amplification and Lateral Flow Analysis. Malar. J.13 (1): 1–9. 10.1186/1475-2875-13-99

  • CrossRef
  • Google Scholar

• 101

  KimH.-J.TongY.TangW.QuimsonL.CopeV. A.PanX.et al (2011). A Rapid and Simple Isothermal Nucleic Acid Amplification Test for Detection of Herpes Simplex Virus Types 1 and 2. J. Clin. Virol.50 (1), 26–30. 10.1016/j.jcv.2010.09.006

  • CrossRef
  • Google Scholar

• 102

  KimT.-H.ParkJ.KimC.-J.ChoY.-K. (2014). Fully Integrated Lab-On-A-Disc for Nucleic Acid Analysis of Food-Borne Pathogens. Anal. Chem.86 (8), 3841–3848. 10.1021/ac403971h

  • CrossRef
  • Google Scholar

• 103

  KivlehanF.MavréF.TaliniL.LimogesB.MarchalD. (2011). Real-Time Electrochemical Monitoring of Isothermal Helicase-dependent Amplification of Nucleic Acids. Analyst136 (18), 3635–3642. 10.1039/c1an15289k

  • CrossRef
  • Google Scholar

• 104

  KleinD. (2002). Quantification Using Real-Time PCR Technology: Applications and Limitations. Trends Mol. Med.8 (6), 257–260. 10.1016/S1471-4914(02)02355-9

  • CrossRef
  • Google Scholar

• 105

  KolmC.MartzyR.FührerM.MachR. L.KrskaR.BaumgartnerS.et al (2019). Mach, Rudolf Krska, Sabine Baumgartner, Andreas H. Farnleitner, and Georg H. Reischer. Detection of a Microbial Source Tracking Marker by Isothermal Helicase-dependent Amplification and a Nucleic Acid Lateral-Flow Strip Test. Sci. Rep.9 (1), 1–9. 10.1038/s41598-018-36749-7

  • CrossRef
  • Google Scholar

• 106

  KonryT.SmolinaI.YarmushJ. M.IrimiaD.YarmushM. L. (2011). Ultrasensitive Detection of Low-Abundance Surface-Marker Protein Using Isothermal Rolling Circle Amplification in a Microfluidic Nanoliter Platform. Small7 (3), 395–400. 10.1002/smll.201001620

  • CrossRef
  • Google Scholar

• 107

  KoppM. U.De MelloA. J.ManzA. (1998). Continuous-Flow PCR on a Chip Concept of a Chemical Amplifier for DNA. Rep. 1046 Sci.280 (May), 1046–1048. 10.1126/science.280.5366.1046

  • CrossRef
  • Google Scholar

• 108

  KrõlovK.FrolovaJ.TudoranO.SuhorutsenkoJ.LehtoT.SibulH.et al (2014). Sensitive and Rapid Detection of Chlamydia Trachomatis by Recombinase Polymerase Amplification Directly from Urine Samples. J. Mol. Diagn.16 (1), 127–135. 10.1016/j.jmoldx.2013.08.003

  • CrossRef
  • Google Scholar

• 109

  KumarJ.SaxenaD.ParidaM.RathinamS. (2018a). Evaluation of Real-Time Reverse-Transcription Loop-Mediated Isothermal Amplification Assay for Clinical Diagnosis of West Nile Virus in Patients. Indian J. Med. Res.147 (March), 293–298. 10.4103/0971-5916.234607

  • CrossRef
  • Google Scholar

• 110

  KumarS.AmitK.VenkatesanG. (2018b). Isothermal Nucleic Acid Amplification System: An Update on Methods and Applications. J. Genet. Genomens2 (1), 1–5. 10.1128/9781555819156.ch12https://www.omicsonline.org/open-access/isothermal-nucleic-acid-amplification-system-an-update-on-methods-andapplications.pdf

  • CrossRef
  • Google Scholar

• 111

  KunzeA.DilcherM.Abd El WahedA.HufertF.NiessnerR.SeidelM. (2016). On-Chip Isothermal Nucleic Acid Amplification on Flow-Based Chemiluminescence Microarray Analysis Platform for the Detection of Viruses and Bacteria. Anal. Chem.88 (1), 898–905. 10.1021/acs.analchem.5b03540

  • CrossRef
  • Google Scholar

• 112

  LeeM.-F.ChenY.-H.PengC.-F. (2009). Evaluation of Reverse Transcription Loop-Mediated Isothermal Amplification in Conjunction with ELISA-Hybridization Assay for Molecular Detection of Mycobacterium tuberculosis. J. Microbiol. Methods76 (2), 174–180. 10.1016/j.mimet.2008.10.005

  • CrossRef
  • Google Scholar

• 113

  LeeS.-Y.HuangJ.-G.ChuangT.-L.SheuJ.-C.ChuangY.-K.HollM.et al (2008). Compact Optical Diagnostic Device for Isothermal Nucleic Acids Amplification. Sensors Actuators B: Chem.133 (2), 493–501. 10.1016/j.snb.2008.03.008

  • CrossRef
  • Google Scholar

• 114

  LeeS.-Y.LeeC.-N.MarkH.MeldrumD. R.LinC.-W. (2007). Efficient, Specific, Compact Hepatitis B Diagnostic Device: Optical Detection of the Hepatitis B Virus by Isothermal Amplification. Sensors Actuators B: Chem.127 (2), 598–605. 10.1016/j.snb.2007.05.015

  • CrossRef
  • Google Scholar

• 115

  LemieuxB.LiY.KongH.TangY.-W. (2012). Near Instrument-free, Simple Molecular Device for Rapid Detection of Herpes Simplex Viruses. Expert Rev. Mol. Diagn.12 (5), 437–443. 10.1586/erm.12.34

  • CrossRef
  • Google Scholar

• 116

  LeoneG.Van SchijndelH.Van GemenB.KramerF. R.SchoenC. D. (1998). Molecular Beacon Probes Combined with Amplification by NASBA Enable Homogeneous, Real-Time Detection of RNA. Nucleic Acids Res.26 (9), 2150–2155. 10.1093/nar/26.9.2150

  • CrossRef
  • Google Scholar

• 117

  LiB.JiangY.ChenX.EllingtonA. D. (2012). Probing Spatial Organization of DNA Strands Using Enzyme-free Hairpin Assembly Circuits. J. Am. Chem. Soc.134 (34), 13918–13921. 10.1021/ja300984b

  • CrossRef
  • Google Scholar

• 118

  LiJ.DengT.ChuX.YangR.JiangJ.ShenG.et al (2010). Rolling Circle Amplification Combined with Gold Nanoparticle Aggregates for Highly Sensitive Identification of Single-Nucleotide Polymorphisms. Anal. Chem.82 (7), 2811–2816. 10.1021/ac100336n

  • CrossRef
  • Google Scholar

• 119

  LiJ.MacdonaldJ. (2015). Advances in Isothermal Amplification: Novel Strategies Inspired by Biological Processes. Biosens. Bioelectron.64, 196–211. 10.1016/j.bios.2014.08.069

  • CrossRef
  • Google Scholar

• 120

  LiR.-D.YinB.-C.YeB.-C. (2016). Ultrasensitive, Colorimetric Detection of MicroRNAs Based on Isothermal Exponential Amplification Reaction-Assisted Gold Nanoparticle Amplification. Biosens. Bioelectron.86, 1011–1016. 10.1016/j.bios.2016.07.042

  • CrossRef
  • Google Scholar

• 121

  LiY.ZengY.JiX.LiX.RenR. (2012). Cascade Signal Amplification for Sensitive Detection of Cancer Cell Based on Self-Assembly of DNA Scaffold and Rolling Circle Amplification. Sensors Actuators B: Chem.171-172, 361–366. 10.1016/j.snb.2012.04.060

  • CrossRef
  • Google Scholar

• 122

  LingJ.DengY.LongX.LiuJ.DuH.CaoB.et al (2012). Single-Nucleotide Polymorphism Array Coupled with Multiple Displacement Amplification: Accuracy and Spatial Resolution for Analysis of Chromosome Copy Numbers in Few Cells. Biotechnol. Appl. Biochem.59 (1), 35–44. 10.1002/bab.64

  • CrossRef
  • Google Scholar

• 123

  LittleM. C.AndrewsJ.MooreR.BustosS.JonesL.EmbresC.et al (1999). Strand Displacement Amplification and Homogeneous Real-Time Detection Incorporated in a Second-Generation DNA Probe System, BDProbeTecET. Clin. Chem.45 (6 I), 777–784. 10.1093/clinchem/45.6.777

  • CrossRef
  • Google Scholar

• 124

  LiuD.DaubendiekS. L.ZillmanM. A.RyanK.KoolE. T. (1996). Rolling Circle DNA Synthesis: Small Circular Oligonucleotides as Efficient Templates for DNA Polymerases. J. Am. Chem. Soc.118 (7), 1587–1594. 10.1021/ja952786k

  • CrossRef
  • Google Scholar

• 125

  LiuH.TianT.ZhangY.DingL.YuJ.YanM. (2017). Sensitive and Rapid Detection of MicroRNAs Using Hairpin Probes-Mediated Exponential Isothermal Amplification. Biosens. Bioelectron.89 (November 2016), 710–714. 10.1016/j.bios.2016.10.099

  • CrossRef
  • Google Scholar

• 126

  LiuP.YangX.SunS.WangQ.WangK.HuangJ.et al (2013). Enzyme-Free Colorimetric Detection of DNA by Using Gold Nanoparticles and Hybridization Chain Reaction Amplification. Anal. Chem.85 (16), 7689–7695. 10.1021/ac4001157

  • CrossRef
  • Google Scholar

• 127

  LiuX.ChenM.HouT.WangX.LiuS.LiF. (2014). Label-Free Colorimetric Assay for Base Excision Repair Enzyme Activity Based on Nicking Enzyme Assisted Signal Amplification. Biosens. Bioelectron.54: 598–602. 10.1016/j.bios.2013.11.062

  • CrossRef
  • Google Scholar

• 128

  LizardiP. M. (1997). Multiple Displacement Amplification (US6280949B1). US6280949B1, Issued 1997.

  • Google Scholar

• 129

  LizardiP. M.HuangX.ZhuZ.Bray-WardP.ThomasD. C.WardD. C. (1998). Mutation Detection and Single-Molecule Counting Using Isothermal Rolling-Circle Amplification. Nat. Genet.19 (3), 225–232. 10.1038/898

  • CrossRef
  • Google Scholar

• 130

  LobatoI. M.O'SullivanC. K.CiaraK.O’Sullivan (2018). Recombinase Polymerase Amplification: Basics, Applications and Recent Advances. Trac Trends Anal. Chem.98, 19–35. 10.1016/j.trac.2017.10.015

  • CrossRef
  • Google Scholar

• 131

  Lucigen. 2021. “LavaLAMP^TM DNA Master Mix for Amplification.” 2021. Available at: https://www.lucigen.com/LavaLAMP-DNA-Master-Mix-loop-mediated-isothermal-amplification/.

  • Google Scholar

• 132

  LutzS.WeberP.FockeM.FaltinB.HoffmannJ.MüllerC.et al (2010). Microfluidic Lab-On-A-Foil for Nucleic Acid Analysis Based on Isothermal Recombinase Polymerase Amplification (RPA). Lab. Chip10 (7), 887–893. 10.1039/b921140c

  • CrossRef
  • Google Scholar

• 133

  MaC.LiuS.ShiC. (2014). Ultrasensitive Detection of MicroRNAs Based on Hairpin Fluorescence Probe Assisted Isothermal Amplification. Biosens. Bioelectron.58, 57–60. 10.1016/j.bios.2014.02.034

  • CrossRef
  • Google Scholar

• 134

  MaC.WangW.YangQ.ShiC.CaoL. (2011). Cocaine Detection via Rolling Circle Amplification of Short DNA Strand Separated by Magnetic Beads. Biosens. Bioelectron.26 (7), 3309–3312. 10.1016/j.bios.2011.01.003

  • CrossRef
  • Google Scholar

• 135

  MagroL.JacquelinB.EscadafalC.GarneretP.KwasiborskiA.ManuguerraJ.-C.et al (2017). Paper-Based RNA Detection and Multiplexed Analysis for Ebola Virus Diagnostics. Sci. Rep.7 (1), 1–9. 10.1038/s41598-017-00758-9

  • CrossRef
  • Google Scholar

• 136

  MahalanabisM.DoJ.AlmuayadH.ZhangJ. Y.KlapperichC. M. (2010). An Integrated Disposable Device for DNA Extraction and Helicase Dependent Amplification. Biomed. Microdevices12 (2), 353–359. 10.1007/s10544-009-9391-8

  • CrossRef
  • Google Scholar

• 137

  MahmoudianL.KajiN.TokeshiM.NilssonM.BabaY. (2008a). Rolling Circle Amplification and Circle-to-Circle Amplification of a Specific Gene Integrated with Electrophoretic Analysis on a Single Chip. Anal. Chem.80 (7), 2483–2490. 10.1021/ac702289j

  • CrossRef
  • Google Scholar

• 138

  MahmoudianL.MelinJ.MohamadiM. R.YamadaK.OhtaM.KajiN.et al (2008b). Microchip Electrophoresis for Specific Gene Detection of the Pathogenic Bacteria V. Cholerae by Circle-to-Circle Amplification. Anal. Sci.24 (3), 327–332. 10.2116/analsci.24.327

  • CrossRef
  • Google Scholar

• 139

  MaplesK.BrianHolmbergR. C.MillerA. P.ProvinsJ.RothR. B. (2007). Nicking and Extension Amplification Reaction for the Exponential Amplification of Nucleic Acids. US20090081670A1.

  • Google Scholar

• 140

  MaraghS.JakupciakJ. P.WagnerP. D.RomW. N.SidranskyD.SrivastavaS.et al2008. “Multiple Strand Displacement Amplification of Mitochondrial DNA from Clinical Samples.” BMC Med. Genet.9: 1–9. 10.1186/1471-2350-9-7

  • CrossRef
  • Google Scholar

• 141

  MekuriaT. A.ZhangS.EastwellK. C. (2014). Rapid and Sensitive Detection of Little Cherry Virus 2 Using Isothermal Reverse Transcription-Recombinase Polymerase Amplification. J. Virol. Methods205, 24–30. 10.1016/j.jviromet.2014.04.015

  • CrossRef
  • Google Scholar

• 142

  Meridian Bioscience. 2021. Alethia® Molecular Platform. Available at: https://www.meridianbioscience.com/platform/molecular/alethia/. (Accessed July 29, 2021).

  • Google Scholar

• 143

  MollasalehiH.YazdanparastR. (2012). Non-Crosslinking Gold Nanoprobes for Detection of Nucleic Acid Sequence-Based Amplification Products. Anal. Biochem.425 (2), 91–95. 10.1016/j.ab.2012.03.008

  • CrossRef
  • Google Scholar

• 144

  MorabitoK.WiskeC.TripathiA. (2013). Engineering Insights for Multiplexed Real-Time Nucleic Acid Sequence-Based Amplification (NASBA): Implications for Design of Point-of-Care Diagnostics. Mol. Diagn. Ther.17 (3), 185–192. 10.1007/s40291-013-0029-4

  • CrossRef
  • Google Scholar

• 145

  MoriY.NotomiT. (2009). Loop-Mediated Isothermal Amplification (LAMP): A Rapid, Accurate, and Cost-Effective Diagnostic Method for Infectious Diseases. J. Infect. Chemother.15 (2), 62–69. 10.1007/s10156-009-0669-9

  • CrossRef
  • Google Scholar

• 146

  MotamediM. K.SaghafiniaM.KaramiA.GillP. (2011). A Review of the Current Isothermal Amplification Techniques: Applications, Advantages and Disadvantages. J. Glob. Infect Dis3 (3), 293–302. 10.4103/0974-777X.83538

  • CrossRef
  • Google Scholar

• 147

  MukaiH.UemoriT.TakedaO.KobayashiE.YamamotoJ.NishiwakiK.et al (2007). Highly Efficient Isothermal DNA Amplification System Using Three Elements of 5′-DNA-RNA-3′ Chimeric Primers, RNaseH and Strand-Displacing DNA Polymerase. J. Biochem.142 (2), 273–281. 10.1093/jb/mvm138

  • CrossRef
  • Google Scholar

• 148

  MullisK.FaloonaF.ScharfS.SaikiR.HornG.ErlichH. (1986). Specific Enzymatic Amplification of DNA In Vitro: The Polymerase Chain Reaction. Cold Spring Harbor Symposia Quantitative Biol.51 (0): 263–273. 10.1101/sqb.1986.051.01.032

  • CrossRef
  • Google Scholar

• 149

  MyrmelM.OmaV.KhatriM.HansenH. H.StokstadM.BergM.et al (2017). Single Primer Isothermal Amplification (SPIA) Combined with Next Generation Sequencing Provides Complete Bovine Coronavirus Genome Coverage and Higher Sequence Depth Compared to Sequence-independent Single Primer Amplification (SISPA). PLoS ONE12 (11), e0187780–9. 10.1371/journal.pone.0187780

  • CrossRef
  • Google Scholar

• 150

  New England BioLabs2021. IsoAmp® II Universal THDA Kit. Available at: https://international.neb.com/products/h0110-isoamp-ii-universal-thda-kit#Product Information (Accessed June 26, 2021).

  • Google Scholar

• 151

  NguyenV. A. T.NguyenH. V.DinhT. V.DuH. H.DoC. N.MarksG. B.et al (2018). Evaluation of LoopampMTBC Detection Kit for Diagnosis of Pulmonary Tuberculosis at a Peripheral Laboratory in a High burden Setting. Diagn. Microbiol. Infect. Dis.90 (3), 190–195. 10.1016/j.diagmicrobio.2017.11.009

  • CrossRef
  • Google Scholar

• 152

  NiaziA.JorjaniO.-N.NikbakhtH.GillP. (2013). A Nanodiagnostic Colorimetric Assay for 18S RRNA of Leishmania Pathogens Using Nucleic Acid Sequence-Based Amplification and Gold Nanorods. Mol. Diagn. Ther.17 (6), 363–370. 10.1007/s40291-013-0044-5

  • CrossRef
  • Google Scholar

• 153

  NieS.RothR. B.StilesJ.MikhlinaA.LuX.TangY.-W.et al (2014). Evaluation of Alere I Influenza A&B for Rapid Detection of Influenza Viruses A and B. J. Clin. Microbiol.52 (9), 3339–3344. 10.1128/JCM.01132-14

  • CrossRef
  • Google Scholar

• 154

  NilssonM.KrejciK.KochJ.KwiatkowskiM.GustavssonP.LandegrenU. (1997). Padlock Probes Reveal Single-Nucleotide Differences, Parent of Origin and In Situ Distribution of Centromeric Sequences in Human Chromosomes 13 and 21. Nat. Genet.16 (3), 252–255. 10.1038/ng0797-252

  • CrossRef
  • Google Scholar

• 155

  NotomiT.OkayamaH.MasubuchiH.YonekawaT.WatanabeK.AminoN.et al2000. “Loop-Mediated Isothermal Amplification of DNA.” Nucleic Acids Res.28 (12): 63e – 63. 10.1093/nar/28.12.e63

  • CrossRef
  • Google Scholar

• 156

  OhS. J.JungJ. H.ChoiG.LeeD. C.KimD. H.SeoT. S. (2016). Centrifugal Loop-Mediated Isothermal Amplification Microdevice for Rapid, Multiplex and Colorimetric Foodborne Pathogen Detection. Biosens. Bioelectron.75, 293–300. 10.1016/j.bios.2015.08.052

  • CrossRef
  • Google Scholar

• 157

  OkamotoS.YoshikawaT.IhiraM.SuzukiK.ShimokataK.NishiyamaY.et al (2004). Rapid Detection of Varicella-Zoster Virus Infection by a Loop-Mediated Isothermal Amplification Method. J. Med. Virol.74 (4), 677–682. 10.1002/jmv.20223

  • CrossRef
  • Google Scholar

• 158

  OyolaS. O.OttoT. D.GuY.MaslenG.ManskeM.CampinoS.et al (2012). Optimizing Illumina Next-Generation Sequencing Library Preparation for Extremely At-Biased Genomes. BMC Genomics13 (1), 1–12. 10.1186/1471-2164-13-1

  • CrossRef
  • Google Scholar

• 159

  PaezJ. G.LinM.BeroukhimR.LeeJ. C.ZhaoX.RichterD. J.et al (2004). Genome Coverage and Sequence Fidelity of 29 Polymerase-Based Multiple Strand Displacement Whole Genome Amplification. Nucleic Acids Res.32 (9), e71. 10.1093/nar/gnh069

  • CrossRef
  • Google Scholar

• 160

  PancholiP.KellyC. M.RaczkowskiM.Balada-LlasatJ. M. (2012). Detection of Toxigenic Clostridium Difficile: Comparison of the Cell Culture Neutralization, Xpert C. Difficile, Xpert C. Difficile/Epi, and Illumigene C. Difficile Assays. J. Clin. Microbiol.50 (4), 1331–1335. 10.1128/JCM.06597-11

  • CrossRef
  • Google Scholar

• 161

  PandoriM. W.BransonB. M. (2010). 2010 HIV Diagnostics Conference. Expert Rev. Anti-Infective Ther.8 (6), 631–633. 10.1586/eri.10.48

  • CrossRef
  • Google Scholar

• 162

  ParidaM.PosadasG.InoueS.HasebeF.MoritaK. (2004). Real-Time Reverse Transcription Loop-Mediated Isothermal Amplification for Rapid Detection of West Nile Virus. J. Clin. Microbiol.42 (1), 257–263. 10.1128/JCM.42.1.257-263.2004

  • CrossRef
  • Google Scholar

• 163

  ParidaM.SannarangaiahS.DashRaoP. K.RaoP. V. L.MoritaK. (2008). Loop Mediated Isothermal Amplification (LAMP): A New Generation of Innovative Gene Amplification Technique; Perspectives in Clinical Diagnosis of Infectious Diseases. Rev. Med. Virol.18 (6), 407–421. 10.1002/rmv.593

  • CrossRef
  • Google Scholar

• 164

  PengY.LiD.YuanR.XiangY. (2018). A Catalytic and Dual Recycling Amplification ATP Sensor Based on Target-Driven Allosteric Structure Switching of Aptamer Beacons. Biosens. Bioelectron.105 (October), 1–5. 10.1016/j.bios.2018.01.017

  • CrossRef
  • Google Scholar

• 165

  PiepenburgO.WilliamsC. H.StempleD. L.ArmesN. A. (2006). DNA Detection Using Recombination Proteins. Plos Biol.4 (7), e204–21. 10.1371/journal.pbio.0040204

  • CrossRef
  • Google Scholar

• 166

  PolymeraseR.RpaA. (2017). Recombinase Polymerase Amplification (RPA) an Isothermal Technique Suitable for a Range of Applications- Evaluation of RPA Volume Tolerance. BioTechniques62 (6), 295. 10.2144/000114561

  • CrossRef
  • Google Scholar

• 167

  Porter-JordanK.KeiserJ. F.AllanM.GrossA. M.NasimS.GarrettC. T. (1990). Nested Polymerase Chain Reaction Assay for the Detection of Cytomegalovirus Overcomes False Positives Caused by Contamination with Fragmented DNA. J. Med. Virol.30 (2): 85–91. 10.1002/jmv.1890300202

  • CrossRef
  • Google Scholar

• 168

  Quidel (2021). AmpliVue - Helicase Dependent Amplification Assays, 2021.

  • Google Scholar

• 169

  RaneT. D.ChenL. H.ZecH. C.WangT.-H. (2015). Microfluidic Continuous Flow Digital Loop-Mediated Isothermal Amplification (LAMP). Lab. Chip15 (3), 776–782. 10.1039/c4lc01158a

  • CrossRef
  • Google Scholar

• 170

  RatliffA. E.DuffyL. B.WaitesK. B. (2014). Comparison of the Illumigene Mycoplasma DNA Amplification Assay and Culture for Detection of Mycoplasma Pneumoniae. J. Clin. Microbiol.52 (4), 1060–1063. 10.1128/JCM.02913-13

  • CrossRef
  • Google Scholar

• 171

  ReaginM. J.GieslerGieslerAlia L. MerlaT. L.MerlaA. L.Resetar-GerkeJ. M.KapolkaK. M.MamoneJ. A. (2003). Templiphi: A Sequencing Template Preparation Procedure that Eliminates Overnight Cultures and DNA Purification. J. Biomol. Tech.14 (2), 143–148. 10.1080/02713680490905817

  • CrossRef
  • Google Scholar

• 172

  RectorA.TachezyR.Van RanstM. (2004). A Sequence-independent Strategy for Detection and Cloning of Circular DNA Virus Genomes by Using Multiply Primed Rolling-Circle Amplification. J. Virol.78 (10), 4993–4998. 10.1128/jvi.78.10.4993-4998.2004

  • CrossRef
  • Google Scholar

• 173

  ReinholtS. J.BehrentA.GreeneC.KalfeA.BaeumnerA. J. (2014). Isolation and Amplification of MRNA within a Simple Microfluidic Lab on a Chip. Anal. Chem.86 (1), 849–856. 10.1021/ac403417z

  • CrossRef
  • Google Scholar

• 174

  RinkeC.SchwientekP.SczyrbaA.IvanovaN. N.AndersonI. J.ChengJ.-F.et al (2013). Insights into the Phylogeny and Coding Potential of Microbial Dark Matter. Nature499 (7459), 431–437. 10.1038/nature12352

  • CrossRef
  • Google Scholar

• 175

  RohrmanB. A.Richards-KortumR. R. (2012). A Paper and Plastic Device for Performing Recombinase Polymerase Amplification of HIV DNA. Lab. Chip12 (17), 3082–3088. 10.1039/c2lc40423k

  • CrossRef
  • Google Scholar

• 176

  RohrmanB.Richards-KortumR. (2015). Inhibition of Recombinase Polymerase Amplification by Background Dna: A Lateral Flow-Based Method for Enriching Target DNA. Anal. Chem.87 (3), 1963–1967. 10.1021/ac504365v

  • CrossRef
  • Google Scholar

• 177

  RutjesS. A.van den BergVan Den BergH. H. J. L.LodderW. J.de Roda HusmanA. M. (2006). Real-Time Detection of Noroviruses in Surface Water by Use of a Broadly Reactive Nucleic Acid Sequence-Based Amplification Assay. Appl. Environ. Microbiol.72 (8), 5349–5358. 10.1128/AEM.00751-06

  • CrossRef
  • Google Scholar

• 178

  Sabaté del RíoJ.SteylaertsT.HenryO. Y. F.BienstmanP.StakenborgT.Van RoyW.et al (2015). Real-Time and Label-free Ring-Resonator Monitoring of Solid-phase Recombinase Polymerase Amplification. Biosens. Bioelectron.73, 130–137. 10.1016/j.bios.2015.05.063

  • CrossRef
  • Google Scholar

• 179

  Santiago-FelipeS.Tortajada-GenaroL. A.PuchadesR.MaquieiraA. (2014). Recombinase Polymerase and Enzyme-Linked Immunosorbent Assay as a DNA Amplification-Detection Strategy for Food Analysis. Analytica Chim. Acta811, 81–87. 10.1016/j.aca.2013.12.017

  • CrossRef
  • Google Scholar

• 180

  SatoK.TachiharaA.RenbergB.MawatariK.SatoK.TanakaY.et al (2010). Microbead-Based Rolling Circle Amplification in a Microchip for Sensitive DNA Detection. Lab. Chip10 (10), 1262–1266. 10.1039/b927460j

  • CrossRef
  • Google Scholar

• 181

  SchopfE.FischerN. O.ChenY.TokJ. B.-H. (2008). Sensitive and Selective Viral DNA Detection Assay via Microbead-Based Rolling Circle Amplification. Bioorg. Med. Chem. Lett.18 (22), 5871–5874. 10.1016/j.bmcl.2008.07.064

  • CrossRef
  • Google Scholar

• 182

  SchopfE.LiuY.DengJ. C.YangS.ChengG.ChenY. (2011). Mycobacterium Tuberculosis Detection via Rolling Circle Amplification. Anal. Methods3 (2), 267–273. 10.1039/c0ay00529k

  • CrossRef
  • Google Scholar

• 183

  SchweitzerB.RobertsS.GrimwadeB.ShaoW.WangM.FuQ.et al (2002). Multiplexed Protein Profiling on Microarrays by Rolling-Circle Amplification. Nat. Biotechnol.20 (4), 359–365. 10.1038/nbt0402-359

  • CrossRef
  • Google Scholar

• 184

  ShaL.ZhangX.WangG. (2016). A Label-free and Enzyme-free Ultra-sensitive Transcription Factors Biosensor Using DNA-Templated Copper Nanoparticles as Fluorescent Indicator and Hairpin DNA Cascade Reaction as Signal Amplifier. Biosens. Bioelectron.82, 85–92. 10.1016/j.bios.2016.03.066

  • CrossRef
  • Google Scholar

• 185

  ShenF.DavydovaE. K.DuW.KreutzJ. E.PiepenburgO.IsmagilovR. F. (2011). Digital Isothermal Quantification of Nucleic Acids via Simultaneous Chemical Initiation of Recombinase Polymerase Amplification Reactions on SlipChip. Anal. Chem.83 (9), 3533–3540. 10.1021/ac200247e

  • CrossRef
  • Google Scholar

• 186

  ShengQ.ChengN.BaiW.ZhengJ. (2015). Ultrasensitive Electrochemical Detection of Breast Cancer Cells Based on DNA-Rolling-Circle-Amplification-Directed Enzyme-Catalyzed Polymerization. Chem. Commun.51 (11), 2114–2117. 10.1039/c4cc08954e

  • CrossRef
  • Google Scholar

• 187

  ShimadaM.HinoF.SagawaH.MukaiH.AsadaK.KatoI. (2002). Development of the Detection System for Mycobacterium tuberculosis DNA by Using the Isothermal DNA Amplification Method ICAN. Rinsho Byori50 (5), 528–532.

  • Google Scholar

• 188

  SimpkinsS. A.ChanA. B.HaysJ.oppingB. P.CookN. (2000). An RNA Transcription-Based Amplification Technique (NASBA) for the Detection of Viable Salmonella Enterica. Lett. Appl. Microbiol.30 (1), 75–79. 10.1046/j.1472-765x.2000.00670.x

  • CrossRef
  • Google Scholar

• 189

  SmirnovD. A.BurdickJ. T.MorleyM.CheungV. G. (2004). Method for Manufacturing Whole-Genome Microarrays by Rolling Circle Amplification. Genes Chromosom. Cancer40 (1), 72–77. 10.1002/gcc.20015

  • CrossRef
  • Google Scholar

• 190

  SmolinaI. V.DemidovV. V.CantorC. R.BroudeN. E. (2004). Real-Time Monitoring of Branched Rolling-Circle DNA Amplification with Peptide Nucleic Acid Beacon. Anal. Biochem.335 (2), 326–329. 10.1016/j.ab.2004.07.022

  • CrossRef
  • Google Scholar

• 191

  SongJ.MaukM. G.HackettB. A.CherryS.BauH. H.LiuC. (2016). Instrument-Free Point-of-Care Molecular Detection of Zika Virus. Anal. Chem.88 (14), 7289–7294. 10.1021/acs.analchem.6b01632

  • CrossRef
  • Google Scholar

• 192

  SongY.LiW.DuanY.LiZ.DengL. (2014). Nicking Enzyme-Assisted Biosensor for Salmonella Enteritidis Detection Based on Fluorescence Resonance Energy Transfer. Biosens. Bioelectron.55, 400–404. 10.1016/j.bios.2013.12.053

  • CrossRef
  • Google Scholar

• 193

  SpitsC.Le CaignecC.De RyckeM.Van HauteL.Van SteirteghemA.LiebaersI.et al (2006). Whole-Genome Multiple Displacement Amplification from Single Cells. Nat. Protoc.1 (4), 1965–1970. 10.1038/nprot.2006.326

  • CrossRef
  • Google Scholar

• 194

  SrividyaA.MaitiB.ChakrabortyA.ChakrabortyG. (2019). Loop Mediated Isothermal Amplification: A Promising Tool for Screening Genetic Mutations. Mol. Diagn. Ther.23 (6), 723–733. 10.1007/s40291-019-00422-0

  • CrossRef
  • Google Scholar

• 195

  SunY.-Q.MonsteinH.-J.RybergA.BorchK. (2007). Multiple Strand Displacement Amplification of DNA Isolated from Human Archival Plasma/Serum: Identification of Cytokine Polymorphism by Pyrosequencing Analysis. Clinica Chim. Acta377 (1–2), 108–113. 10.1016/j.cca.2006.09.003

  • CrossRef
  • Google Scholar

• 196

  SunY.QuyenT. L.HungT. Q.ChinW. H.WolffA.BangD. D. (2015). A Lab-On-A-Chip System with Integrated Sample Preparation and Loop-Mediated Isothermal Amplification for Rapid and Quantitative Detection of Salmonella Spp. In Food Samples. Lab. Chip15 (8), 1898–1904. 10.1039/c4lc01459f

  • CrossRef
  • Google Scholar

• 197

  TanE.WongJ.NguyenD.ZhangY.ErwinB.Van NessL. K.et al (2005). Isothermal DNA Amplification Coupled with DNA Nanosphere-Based Colorimetric Detection. Anal. Chem.77 (24), 7984–7992. 10.1021/ac051364i

  • CrossRef
  • Google Scholar

• 198

  TangW.ChowW. H. A.LiY.KongH.TangY. W.LemieuxB. (2010). Nucleic Acid Assay System for Tier II Laboratories and Moderately Complex Clinics to Detect HIV in Low‐Resource Settings. J. Infect. Dis.201 (Suppl. 1), S46–S51. 10.1086/650388

  • CrossRef
  • Google Scholar

• 199

  TannerN. A.ZhangY.EvansT. C. (2012). Simultaneous Multiple Target Detection in Real-Time Loop-Mediated Isothermal Amplification. BioTechniques53 (2), 81–89. 10.2144/0000113902

  • CrossRef
  • Google Scholar

• 200

  TatsumiK.MitaniY.WatanabeJ.TakakuraH.HoshiK.KawaiY.et al (2008). Rapid Screening Assay for KRAS Mutations by the Modified Smart Amplification Process. J. Mol. Diagn.10 (6), 520–526. 10.2353/jmoldx.2008.080024

  • CrossRef
  • Google Scholar

• 201

  ThomasD. C.NardoneG. A.RandallS. K. (1999). Amplification of Padlock Probes for DNA Diagnostics by Cascade Rolling Circle Amplification or the Polymerase Chain Reaction.Arch. Pathol. Lab. Med.123 (12), 1170–1176. 10.1043/1543-2165-123.20.1170

  • CrossRef
  • Google Scholar

• 202

  TomlinsonJ. A.DickinsonM. J.BoonhamN. (2010). Rapid Detection of Phytophthora Ramorum and P. Kernoviae by Two-Minute DNA Extraction Followed by Isothermal Amplification and Amplicon Detection by Generic Lateral Flow Device. Phytopathology100 (2), 143–149. 10.1094/PHYTO-100-2-0143

  • CrossRef
  • Google Scholar

• 203

  TongY.TangW.KimH.-J.PanX.RanalliT. A.KongH. (2008). Development of Isothermal TaqMan Assays for Detection of Biothreat Organisms. BioTechniques45 (5), 543–557. 10.2144/000112959

  • CrossRef
  • Google Scholar

• 204

  Torres-ChavollaE.AlociljaE. C. (2011). Nanoparticle Based DNA Biosensor for Tuberculosis Detection Using Thermophilic Helicase-dependent Isothermal Amplification. Biosens. Bioelectron.26 (11), 4614–4618. 10.1016/j.bios.2011.04.055

  • CrossRef
  • Google Scholar

• 205

  TsaloglouM.-N.LaouenanF.LoukasC.-M.MonsalveL. G.ThannerC.MorganH.et al (2013). Real-Time Isothermal RNA Amplification of Toxic Marine Microalgae Using Preserved Reagents on an Integrated Microfluidic Platform. Analyst138 (2), 593–602. 10.1039/c2an36464f

  • CrossRef
  • Google Scholar

• 206

  TuP.-A.ShiuJ.-S.LeeS.-H.PangV. F.WangD.-C.WangP.-H.et al (2017). Development of a Recombinase Polymerase Amplification Lateral Flow Dipstick (RPA-LFD) for the Field Diagnosis of Caprine Arthritis-Encephalitis Virus (CAEV) Infection. J. Virol. Methods243: 98–104. 10.1016/j.jviromet.2017.01.023

  • CrossRef
  • Google Scholar

• 207

  TwistDx. 2021. “TwistAmp® Liquid Exo.” 2021. Available at: https://www.twistdx.co.uk/en/products/product/twistamp-liquid-exo.

  • Google Scholar

• 208

  UddinS.IbrahimF.SayadA.ThihaA.PeiK.MohktarM.et al (2015). A Portable Automatic Endpoint Detection System for Amplicons of Loop Mediated Isothermal Amplification on Microfluidic Compact Disk Platform. Sensors15 (3), 5376–5389. 10.3390/s150305376

  • CrossRef
  • Google Scholar

• 209

  Van Der PolB.FerreroD. V.Buck-BarringtonL.HookE.LendermanC.QuinnT.et al (2001). Multicenter Evaluation of the BDProbeTec ET System for Detection of Chlamydia Trachomatis and Neisseria Gonorrhoeae in Urine Specimens, Female Endocervical Swabs, and Male Urethral Swabs. J. Clin. Microbiol.39 (3), 1008–1016. 10.1128/JCM.39.3.1008-1016.2001

  • CrossRef
  • Google Scholar

• 210

  Van NessJ.Van NessL. K.GalasD. J.GalasDavid. J. (2003). Isothermal Reactions for the Amplification of Oligonucleotides. Proc. Natl. Acad. Sci.100 (8), 4504–4509. 10.1073/pnas.0730811100

  • CrossRef
  • Google Scholar

• 211

  VincentM.XuY.KongH. (2004). Helicase‐dependent Isothermal DNA Amplification. EMBO Rep.5 (8), 795–800. 10.1038/sj.embor.7400200

  • CrossRef
  • Google Scholar

• 212

  WakabayashiT.YamashitaR.KakitaT.KakitaM.OshikaT. (2004). Rapid and Sensitive Diagnosis of Adenoviral Keratoconjunctivitis by Loop-Mediated Isothermal Amplification (LAMP) Method. Curr. Eye Res.28 (6), 445–450. 10.1080/0271368049090581710.1080/02713680490503796

  • CrossRef
  • Google Scholar

• 213

  WalkerG. T.LittleM. C.NadeauJ. G.ShankD. D. (1992). Isothermal In Vitro Amplification of DNA by a Restriction Enzyme/DNA Polymerase System. Proc. Natl. Acad. Sci.89 (1), 392–396. 10.1073/pnas.89.1.392

  • CrossRef
  • Google Scholar

• 214

  WangC.-H.LienK.-Y.WangT.-Y.ChenT.-Y.LeeG.-B. (2011a). An Integrated Microfluidic Loop-Mediated-Isothermal-Amplification System for Rapid Sample Pre-treatment and Detection of Viruses. Biosens. Bioelectron.26 (5), 2045–2052. 10.1016/j.bios.2010.08.083

  • CrossRef
  • Google Scholar

• 215

  WangC.-H.LienK.-Y.WuJ.-J.LeeG.-B. (2011b). A Magnetic Bead-Based Assay for the Rapid Detection of Methicillin-Resistant Staphylococcus aureus by Using a Microfluidic System with Integrated Loop-Mediated Isothermal Amplification. Lab. Chip11 (8), 1521–1531. 10.1039/c0lc00430h

  • CrossRef
  • Google Scholar

• 216

  WangK.ZhangK.LvZ.ZhuX.ZhuL.ZhouF. (2014). Ultrasensitive Detection of MicroRNA with Isothermal Amplification and a Time-Resolved Fluorescence Sensor. Biosens. Bioelectron.57, 91–95. 10.1016/j.bios.2014.01.058

  • CrossRef
  • Google Scholar

• 217

  WangL.QianC.QianW.WangR.WuJ.YingY.et al (2017). A Highly Specific Strategy for in Suit Detection of DNA with Nicking Enzyme Assisted Amplification and Lateral Flow. Sensors Actuators B: Chem.253: 258–265. 10.1016/j.snb.2017.06.124

  • CrossRef
  • Google Scholar

• 218

  WangW.-J.LiJ.-J.RuiK.GaiP.-P.ZhangJ.-R.ZhuJ.-J. (2015). Sensitive Electrochemical Detection of Telomerase Activity Using Spherical Nucleic Acids Gold Nanoparticles Triggered Mimic-Hybridization Chain Reaction Enzyme-free Dual Signal Amplification. Anal. Chem.87 (5), 3019–3026. 10.1021/ac504652e

  • CrossRef
  • Google Scholar

• 219

  WangX.SeoD. J.LeeM. H.ChoiC.OnderdonkA. B. (2014). Comparison of Conventional PCR, Multiplex PCR, and Loop-Mediated Isothermal Amplification Assays for Rapid Detection of Arcobacter Species. J. Clin. Microbiol.52 (2), 557–563. 10.1128/JCM.02883-13

  • CrossRef
  • Google Scholar

• 220

  WatanabeJ.MitaniY.KawaiY.KikuchiT.KogoY.Oguchi-KatayamaA.et al (2007). Use of a Competitive Probe in Assay Design for Genotyping of the UGT1A1*28 Microsatellite Polymorphism by the Smart Amplification Process. BioTechniques43 (4), 479–484. 10.2144/000112563

  • CrossRef
  • Google Scholar

• 221

  WeberN. C.KlepserM. E.AkersJ. M.KlepserD. G.AdamsA. J. (2016). Use of CLIA-Waived Point-of-Care Tests for Infectious Diseases in Community Pharmacies in the United States. Expert Rev. Mol. Diagn.16 (2), 253–264. 10.1586/14737159.2015.1116388

  • CrossRef
  • Google Scholar

• 222

  WharamS. D.Peter MarshJ. S.McPheeJ. E.WestonA.DonaldL.CardyN. (2001). Specific Detection of DNA and RNA Targets Using a Novel Isothermal Nucleic Acid Amplification Assay Based on the Formation of a Three-Way Junction Structure. Nucleic Acids Res.29 (11), 54e–54. 10.1093/nar/29.11.e54

  • CrossRef
  • Google Scholar

• 223

  WongY.-P.OthmanS.LauY.-L.RaduS.CheeH.-Y. (2018). Loop-Mediated Isothermal Amplification (LAMP): A Versatile Technique for Detection of Micro-organisms. J. Appl. Microbiol.124 (3), 626–643. 10.1111/jam.13647

  • CrossRef
  • Google Scholar

• 224

  World Health Organization (2016). The Use of Loop-Mediated Isothermal Amplification (TB-LAMP) for the Diagnosis of Pulmonary Tuberculosis: Policy Guidance. Geneva, Switzerland: WHO Library Cataloguing-in-Publication Data.

  • Google Scholar

• 225

  WuC.CansizS.ZhangL.TengI.-T.QiuL.LiJ.et al (2015). A Nonenzymatic Hairpin DNA Cascade Reaction Provides High Signal Gain of MRNA Imaging inside Live Cells. J. Am. Chem. Soc.137 (15), 4900–4903. 10.1021/jacs.5b00542

  • CrossRef
  • Google Scholar

• 226

  XiaS.ChenX. (2020). Single-copy Sensitive, Field-Deployable, and Simultaneous Dual-Gene Detection of SARS-CoV-2 RNA via Modified RT-RPA. Cell Discov.6 (1), 4–7. 10.1038/s41421-020-0175-x

  • CrossRef
  • Google Scholar

• 227

  XuanF.FanT. W.HsingI.-M. (2015). Electrochemical Interrogation of Kinetically-Controlled Dendritic DNA/PNA Assembly for Immobilization-free and Enzyme-free Nucleic Acids Sensing. ACS Nano9 (5), 5027–5033. 10.1021/nn507282f

  • CrossRef
  • Google Scholar

• 228

  XuanF.HsingI.-M. (2014). Triggering Hairpin-free Chain-Branching Growth of Fluorescent DNA Dendrimers for Nonlinear Hybridization Chain Reaction. J. Am. Chem. Soc.136 (28), 9810–9813. 10.1021/ja502904s

  • CrossRef
  • Google Scholar

• 229

  XueL.ZhouX.XingD. (2010). Highly Sensitive Protein Detection Based on Aptamer Probe and Isothermal Nicking Enzyme Assisted Fluorescence Signal Amplification. Chem. Commun.46 (39), 7373–7375. 10.1039/C0CC02038A

  • CrossRef
  • Google Scholar

• 230

  XueQ.LvY.XuS.ZhangY.WangL.LiR.et al (2015). Highly Sensitive Fluorescence Assay of DNA Methyltransferase Activity by Methylation-Sensitive Cleavage-Based Primer Generation Exponential Isothermal Amplification-Induced G-Quadruplex Formation. Biosens. Bioelectron.66, 547–553. 10.1016/j.bios.2014.12.017

  • CrossRef
  • Google Scholar

• 231

  XueQ.LvY.ZhangY.XuS.LiR.YueQ.et al (2014). Ultrasensitive Fluorescence Detection of Nucleic Acids Using Exonuclease III-Induced Cascade Two-Stage Isothermal Amplification-Mediated Zinc (II)-Protoporphyrin IX/G-Quadruplex Supramolecular Fluorescent Nanotags. Biosens. Bioelectron.61, 351–356. 10.1016/j.bios.2014.05.047

  • CrossRef
  • Google Scholar

• 232

  XueL.ZhouX.Xing.D. (2012). Sensitive and Homogeneous Protein Detection Based on Target-Triggered Aptamer Hairpin Switch and Nicking Enzyme Assisted Fluorescence Signal Amplification. Anal. Chem.84 (8), 3507–3513. 10.1021/ac2026783

  • CrossRef
  • Google Scholar

• 233

  YanY.QiaoZ.HaiX.SongW.BiS. (2021). Versatile Electrochemical Biosensor Based on Bi-enzyme Cascade Biocatalysis Spatially Regulated by DNA Architecture. Biosens. Bioelectron.174: 112827. 10.1016/j.bios.2020.112827

  • CrossRef
  • Google Scholar

• 234

  YangH.MaX.ZhangX.WangY.ZhangW. (2011). Development and Evaluation of a Loop-Mediated Isothermal Amplification Assay for the Rapid Detection of Staphylococcus Aureus in Food. Eur. Food Res. Technol.232 (5), 769–776. 10.1007/s00217-011-1442-8

  • CrossRef
  • Google Scholar

• 235

  YangJ. M.BellJ.HuangY.TiradoM.ThomasD.ForsterA. H.et al (2002). An Integrated, Stacked Microlaboratory for Biological Agent Detection with DNA and Immunoassays. Biosens. Bioelectron.17 (6–7), 605–618. 10.1016/S0956-5663(02)00023-4

  • CrossRef
  • Google Scholar

• 236

  YangL.LiuC.RenW.LiZ. (2012). Graphene Surface-Anchored Fluorescence Sensor for Sensitive Detection of MicroRNA Coupled with Enzyme-free Signal Amplification of Hybridization Chain Reaction. ACS Appl. Mater. Inter.4 (12), 6450–6453. 10.1021/am302268t

  • CrossRef
  • Google Scholar

• 237

  YangQ.DomesleK. J.GeB. (2018). Loop-Mediated Isothermal Amplification forSalmonellaDetection in Food and Feed: Current Applications and Future Directions. Foodborne Pathog. Dis.15 (6), 309–331. 10.1089/fpd.2018.2445

  • CrossRef
  • Google Scholar

• 238

  YaoJ.LiuZ.KoL.-S.PanG.JiangY. (2005). Quantitative Detection of HIV-1 RNA Using NucliSens EasyQ HIV-1 Assay. J. Virol. Methods129 (1), 40–46. 10.1016/j.jviromet.2005.04.017

  • CrossRef
  • Google Scholar

• 239

  YeJ.XuM.TianX.CaiS.ZengS. (2019). Research Advances in the Detection of MiRNA. J. Pharm. Anal.9 (4), 217–226. 10.1016/j.jpha.2019.05.004

  • CrossRef
  • Google Scholar

• 240

  YehE.-C.FuC.-C.HuL.ThakurR.FengJ.LeeL. P. (2017). Self-powered Integrated Microfluidic point-of-care Low-Cost Enabling (SIMPLE) Chip. Sci. Adv.3, e1501645–12. 10.1126/sciadv.1501645

  • CrossRef
  • Google Scholar

• 241

  YiJ.ZhangW.ZhangD. Y. (2006). Molecular Zipper: A Fluorescent Probe for Real-Time Isothermal DNA Amplification. Nucleic Acids Res.34 (11), e81. 10.1093/nar/gkl261

  • CrossRef
  • Google Scholar

• 242

  YoonH. S.PriceD. C.StepanauskasR.RajahV. D.SierackiM. E.WilsonW. H.et al (2011). Single-Cell Genomics Reveals Organismal Interactions in Uncultivated Marine Protists. Science332 (6030), 714–717. 10.1126/science.1203163

  • CrossRef
  • Google Scholar

• 243

  YoshinoM.WatariH.KojimaT.IkedoM.KuritaJ. (2009). Rapid, Sensitive and Simple Detection Method Forkoi Herpesvirususing Loop-Mediated Isothermal Amplification. Microbiol. Immunol.53 (7), 375–383. 10.1111/j.1348-0421.2009.00145.x

  • CrossRef
  • Google Scholar

• 244

  YuanD.KongJ.LiX.FangX.ChenQ. (2018). Colorimetric LAMP Microfluidic Chip for Detecting Three Allergens: Peanut, Sesame and Soybean. Sci. Rep.8 (1), 1–8. 10.1038/s41598-018-26982-5

  • CrossRef
  • Google Scholar

• 245

  YueS.LiY.QiaoZ.SongW.BiS. (2021). Rolling Circle Replication for Biosensing, Bioimaging, and Biomedicine. Trends Biotechnol.S0167-7799 (21), 00039–41. 10.1016/j.tibtech.2021.02.007

  • CrossRef
  • Google Scholar

• 246

  ZengY.-p.HuJ.LongY.ZhangC.-y. (2013). Sensitive Detection of DNA Methyltransferase Using Hairpin Probe-Based Primer Generation Rolling Circle Amplification-Induced Chemiluminescence. Anal. Chem.85 (12), 6143–6150. 10.1021/ac4011292

  • CrossRef
  • Google Scholar

• 247

  ZhangB.LiuB.TangD.NiessnerR.ChenG.KnoppD. (2012). DNA-based Hybridization Chain Reaction for Amplified Bioelectronic Signal and Ultrasensitive Detection of Proteins. Anal. Chem.84 (12), 5392–5399. 10.1021/ac3009065

  • CrossRef
  • Google Scholar

• 248

  ZhangD. Y.BrandweinM.HsuihT.LiH. B. (2001). Ramification Amplification: A Novel Isothermal DNA Amplification Method. Mol. Diagn.6 (2), 141–150. 10.1054/modi.2001.2532310.2165/00066982-200106020-00010

  • CrossRef
  • Google Scholar

• 249

  ZhangH.XuY.FohlerovaZ.ChangH.IliescuC.NeuzilP. (2019). LAMP-on-a-Chip: Revising Microfluidic Platforms for Loop-Mediated DNA Amplification. Trac Trends Anal. Chem.113, 44–53. 10.1016/j.trac.2019.01.015

  • CrossRef
  • Google Scholar

• 250

  ZhangX.LiuC.SunL.DuanX.LiZ. (2015). Lab on a Single Microbead: An Ultrasensitive Detection Strategy Enabling MicroRNA Analysis at the Single-Molecule Level. Chem. Sci.6 (11), 6213–6218. 10.1039/c5sc02641e

  • CrossRef
  • Google Scholar

• 251

  ZhangX.LoweS. B.GoodingJ. J. (2014). Brief Review of Monitoring Methods for Loop-Mediated Isothermal Amplification (LAMP). Biosens. Bioelectron.61, 491–499. 10.1016/j.bios.2014.05.039

  • CrossRef
  • Google Scholar

• 252

  ZhaoX.DongT.YangZ.PiresN.HøivikN. (2012). Compatible Immuno-NASBA LOC Device for Quantitative Detection of Waterborne Pathogens: Design and Validation. Lab. Chip12 (3), 602–612. 10.1039/c1lc20836e

  • CrossRef
  • Google Scholar

• 253

  ZhaoX.LiY.WangL.YouL.XuZ.LiL.et al (2010). Development and Application of a Loop-Mediated Isothermal Amplification Method on Rapid Detection Escherichia Coli O157 Strains from Food Samples. Mol. Biol. Rep.37 (5), 2183–2188. 10.1007/s11033-009-9700-6

  • CrossRef
  • Google Scholar

• 254

  ZhaoY.ChenF.LiQ.WangL.FanC. (2015). Isothermal Amplification of Nucleic Acids. Chem. Rev.115 (22), 12491–12545. 10.1021/acs.chemrev.5b00428

  • CrossRef
  • Google Scholar

• 255

  ZhaoY.ChenF.WuY.DongY.FanC. (2013). Highly Sensitive Fluorescence Assay of DNA Methyltransferase Activity via Methylation-Sensitive Cleavage Coupled with Nicking Enzyme-Assisted Signalamplification. Biosens. Bioelectron.42. 56–61. 10.1016/j.bios.2012.10.022

  • CrossRef
  • Google Scholar

• 256

  ZhengA.-X.WangJ.-R.LiJ.SongX.-R.ChenG.-N.YangH.-H. (2012). Nicking Enzyme Based Homogeneous Aptasensors for Amplification Detection of Protein. Chem. Commun.48 (3), 374–376. 10.1039/c1cc15853h

  • CrossRef
  • Google Scholar

• 257

  ZhengJ.ZhuG.LiY.LiC.YouM.ChenT.et al (2013). A Spherical Nucleic Acid Platform Based on Self-Assembled DNA Biopolymer for High-Performance Cancer Therapy. ACS Nano7 (8), 6545–6554. 10.1021/nn402344v

  • CrossRef
  • Google Scholar

• 258

  ZhouJ.XuM.TangD.GaoZ.TangJ.ChenG. (2012). Nanogold-Based Bio-Bar Codes for Label-free Immunosensing of Proteins Coupling with an In Situ DNA-Based Hybridization Chain Reaction. Chem. Commun.48 (100), 12207–12209. 10.1039/c2cc36820j

  • CrossRef
  • Google Scholar

• 259

  ZhouL.WangY.YangC.XuH.LuoJ.ZhangW.et al (2019). A Label-free Electrochemical Biosensor for MicroRNAs Detection Based on DNA Nanomaterial by Coupling with Y-Shaped DNA Structure and Non-linear Hybridization Chain Reaction. Biosens. Bioelectron.126 (February), 657–663. 10.1016/j.bios.2018.11.028

  • CrossRef
  • Google Scholar

• 260

  ZhouW.HuL.YingL.ZhaoZ.PaulC.YuX.-F.et al (2018). A CRISPR-Cas9-Triggered Strand Displacement Amplification Method for Ultrasensitive DNA Detection. Nat. Commun.9 (1), 5012. 10.1038/s41467-018-07324-5

  • CrossRef
  • Google Scholar

• 261

  ZhouW.SuJ.ChaiY.YuanR.XiangY. (2014). Naked Eye Detection of Trace Cancer Biomarkers Based on Biobarcode and Enzyme-Assisted DNA Recycling Hybrid Amplifications. Biosens. Bioelectron.53, 494–498. 10.1016/j.bios.2013.10.020

  • CrossRef
  • Google Scholar

• 262

  ZhuG.ZhangS.SongE.ZhengJ.HuR.FangX.et al (2013). Building Fluorescent DNA Nanodevices on Target Living Cell Surfaces. Angew. Chem. Int. Ed.52 (21), 5490–5496. 10.1002/anie.201301439

  • CrossRef
  • Google Scholar

• 263

  ZhuQ.GaoY.YuB.RenH.QiuL.HanS.et al (2012). Self-priming Compartmentalization Digital LAMP for point-of-care. Lab. Chip12 (22), 4755–4763. 10.1039/c2lc40774d

  • CrossRef
  • Google Scholar