Ultrafast spectroscopy study of DNA photophysics after proflavine intercalation.

Proflavine (PF), an acridine DNA intercalating agent, has been widespread applied as an anti-microbial and topical antiseptic agent due to its ability to suppress DNA replication. On the other hand, various studies show that PF intercalation to DNA can increase photogenotoxicity and has potential chances to induce carcinomas of skin appendages. However, the effects of PF intercalation on the photophysical and photochemical properties of DNA have not been sufficiently explored. In this study, the excited state dynamics of the PF intercalated d(GC)9 • d(GC)9 and d(AT)9 • d(AT)9 DNA duplex are investigated in an aqueous buffer solution. Under 267 nm excitation, we observed ultrafast charge transfer (CT) between PF and d(GC)9 • d(GC)9 duplex, generating a CT state with an order of magnitude longer lifetime compared to that of the intrinsic excited state reported for the d(GC)9 • d(GC)9 duplex. In contrast, no excited state interaction was detected between PF and d(AT)9 • d(AT)9. Nevertheless, a localized triplet state with a lifetime over 5 µs was identified in the PF-d(AT)9 • d(AT)9 duplex.

New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies.

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.

Utility of intercalator displacement assays for screening of ligands for i-motif DNA structures.

Cytosine rich sequences can form intercalated, i-motif DNA structures stabilized by hemi-protonated cytosine:cytosine base pairing. These sequences are often located in regulatory regions of genes such as promoters. Ligands targeting i-motif structures may provide potential leads for treatments for genetic disease. The focus on ligands interacting with i-motif DNA has been increasing in recent years. Here, we describe the fluorescent intercalator displacement (FID) assay using thiazole orange binding i-motif DNA and assess the binding affinity of a ligand to the i-motif DNA by displacing thiazole orange. This provides a time and cost-effective high throughput screening of ligands against secondary DNA structures for hit identification.

Interactions between DNA and the acridine intercalator: A computational study.

Cancer is a global public health problem characterized by deviations in the mechanisms that control cell proliferation, resulting in mutations and variations in the structure of DNA. The mechanisms of action of chemotherapeutic drugs are related to their interactions and binding with DNA; consequently, the development of antineoplastic agents that target DNA has extensively focused on use of acridine, a heterocyclic molecule that binds to deoxyribonucleic acid via intercalation, a process that modifies DNA and makes replication impossible. In this context, this study aimed to computationally investigate how acridine intercalators interact with DNA by evaluating the mechanism of interactions, binding, and interaction energies using quantum mechanics calculations. Molecular electrostatic potential (MEP) analysis revealed that acridine has well- distributed negative charges in the center of the molecule, indicative of a dominant electron-rich region. Acridine exhibits well-defined π orbitals (HOMO and LUMO) on the aromatic rings, suggesting that charge transfer occurs within the molecule and may be responsible for the pharmacological activity of the compound. Structural analysis revealed that acridine interacts with DNA mainly through hydrogen bonds between HAcridine… ODNA with bond lengths ranging from 2.370 Što 3.472 Å. The Binding energy (ΔEBind) showed that acridine interacts with DNA effectively for all complexes and the electronic energy results (E+ZPE) for complexes revealed that the complexes are more stable when the DNA-centered acridine molecule. The Laplacian-analysis topological QTAIM parameter (∇2ρ(r)) and total energy (H(r)) categorized the interactions as being non-covalent in nature. The RGD peak distribution in the NCI analysis reveals the presence of van der Waals interactions, predominantly between the intercalator and DNA. Accordingly, we confirm that acridine/DNA interactions are relevant for understanding how the intercalator acts within nucleic acids.

Effective stabilization of heavy metals in solid waste and sludge pyrolysis using intercalated-exfoliated modified vermiculite: Experiment and simulation study.

Pyrolysis is effective in reducing the volume of solid waste and sludge, and produces less pollutants than incineration and landfill, but the process still suffers from heavy metal pollution. Four types of intercalated-exfoliated modified vermiculite (UIV, DIV, TIV and 3IV) were prepared using urea, dimethylsulfoxide, tributyl phosphate and 3-aminopropyltriethoxysilane as intercalators for the control of Cd, Cr, Cu, Pb and Zn in municipal sewage sludge (MSL), paper mill sludge (PML), municipal domestic waste (MWA) and aged refuse (AFE). The larger the interlayer spacing of the vermiculite, the more favorable the retention of heavy metals. 3IV was the most effective additive, with an average retention of more than 75 % of all heavy metals at 450 ℃ for the four raw materials. Cr, Cu, Pb and Zn were all at low potential ecological risk (Pr), while Cd was moderate or considerable Pr, and the addition of 3IV reduced the Pr. Distribution of intercalators between vermiculite interlayers was haphazard, and interlayer spacing results were close to those of the experiment (except for tributyl phosphate). The reactive electrons mainly flowed from the Highest Occupied Molecular Orbital (HOMO) of vermiculite flakes to the Lower Unoccupied Molecular Orbital (LUMO) of heavy metal chlorides. In contrast, the reactive electrons mostly flowed from the HOMO of heavy metal oxides to the LUMO of vermiculite flakes. Heavy metal oxides were more readily adsorbed on vermiculite flakes than heavy metal chlorides, and the adsorption capacity of Cr and Zn was stronger than that of Cd, Pb and Cu.

Target-regulated photoactivities of CdS/Ni-MOF heterojunction with [Ru(bpy)2dppz]2+ intercalator: a bisphenol A photoelectrochemical aptasensor.

Bisphenol A (BPA), an important endocrine disrupting compound, has infiltrated human daily lives through electronic devices, food containers, and children's toys. Developing of novel BPA assay methods with high sensitivity holds tremendous importance in valuing the pollution state. Here, we constructed an ultrasensitive photoelectrochemical (PEC) aptasensor for BPA determination by regulating photoactivities of CdS/Ni-based metal-organic framework (CdS/Ni-MOF) with [Ru(bpy)2dppz]2+ sensitizer. CdS/Ni-MOF spheres exhibited excellent photocatalytic performance, serving as a potential sensing platform for the construction of target recognition process. [Ru(bpy)2dppz]2+ were embedded into DNA double-stranded structure, functioning as sensitizer for modulating the signal response of the developed PEC aptasensor. The proposed PEC sensor exhibited outstanding analytical performances, including a wide linear range (0.1 to 1000.0 nM), low detection limit (0.026 nM, at 3σ/m), excellent selectivity, and high stability. This work provides a perspective for the design of ideal photosensitive materials and signal amplification strategies and extends their application in environment analysis.

Controlling Chiroptical Responses via Chemo-Mechanical Deformation of DNA Origami Structures.

DNA origami-based templates have been widely used to fabricate chiral plasmonic metamaterials due to their precise control of the placement of nanoparticles (NPs) in a desired configuration. However, achieving various chiroptical responses inevitably requires a change in the structure of DNA origami-based templates or binding sites on them, leading to the use of significantly different sets of DNA strands. Here, we propose an approach to controlling various chiroptical responses with a single DNA origami design using its chemo-mechanical deformation induced by DNA intercalators. The chiroptical response could be finely tuned by altering the concentration of intercalators only. The silver (Ag) enhancement was used to amplify the chiroptical signal by enlarging NPs and to maintain it by stiffening the template DNA structure. Furthermore, the sensitivity in the chiroptical signal change to the concentration of intercalators could be modulated by the type of intercalator, the mixture of two intercalators, and the stiffness of DNA origami structures. This approach would be useful in a variety of optical applications that require programmed spatial modification of chiroptical responses.

Discovery of novel benzimidazole acyclic C-nucleoside DNA intercalators halting breast cancer growth.

Breast cancer continues to be the most frequent cancer worldwide. In practice, successful clinical outcomes were achieved via targeting DNA. Along with the advances in introducing new DNA-targeting agents, the "sugar approach" design was employed herein to develop new intercalators bearing pharmacophoric motifs tethered to carbohydrate appendages. Accordingly, new benzimidazole acyclic C-nucleosides were rationally designed, synthesized and assayed via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay to evaluate their cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells compared to normal fibroblasts (Wi-38), compared to doxorubicin. (1S,2R,3S,4R)-2-(1,2,3,4,5-Pentahydroxy)pentyl-1H-5,6-dichlorobenzimidazole 7 and (1S,2R,3S,4R)-2-(1,2,3,4,5-pentahydroxy)pentyl-1H-naphthimidazole 13 were the most potent and selective derivatives against MCF-7 (half-maximal inhibitory concentration [IC50 ] = 0.060 and 0.080 µM, selectivity index [SI] = 9.68 and 8.27, respectively) and MDA-MB-231 cells (IC50 = 0.299 and 0.166 µM, SI = 1.94 and 3.98, respectively). Thus, they were identified as the study hits for mechanistic studies. Both derivatives induced DNA damage at 0.24 and 0.29 µM, respectively. The DNA damage kinetics were studied compared to doxorubicin, where they both induced faster damage than doxorubicin. This indicated that 7 and 13 showed a more potent DNA-damaging effect than doxorubicin. Docking simulations within the DNA double strands highlighted the role of both the heterocyclic core and the sugar side chain in exhibiting key H-bond interactions with DNA bases.

Supercoiling-dependent DNA binding: quantitative modeling and applications to bulk and single-molecule experiments.

DNA stores our genetic information and is ubiquitous in applications, where it interacts with binding partners ranging from small molecules to large macromolecular complexes. Binding is modulated by mechanical strains in the molecule and can change local DNA structure. Frequently, DNA occurs in closed topological forms where topology and supercoiling add a global constraint to the interplay of binding-induced deformations and strain-modulated binding. Here, we present a quantitative model with a straight-forward numerical implementation of how the global constraints introduced by DNA topology modulate binding. We focus on fluorescent intercalators, which unwind DNA and enable direct quantification via fluorescence detection. Our model correctly describes bulk experiments using plasmids with different starting topologies, different intercalators, and over a broad range of intercalator and DNA concentrations. We demonstrate and quantitatively model supercoiling-dependent binding in a single-molecule assay, where we directly observe the different intercalator densities going from supercoiled to nicked DNA. The single-molecule assay provides direct access to binding kinetics and DNA supercoil dynamics. Our model has broad implications for the detection and quantification of DNA, including the use of psoralen for UV-induced DNA crosslinking to quantify torsional tension in vivo, and for the modulation of DNA binding in cellular contexts.

Study of nitrogen heterocycles as DNA/HSA binder, topoisomerase inhibitors and toxicological safety.

Four new nitrogen-containing heterocyclic derivatives (acridine, quinoline, indole, pyridine) were synthesized and their biological properties were evaluated. The compounds showed affinity for DNA and HSA, with CAIC and CAAC displaying higher binding constants (Kb) of 9.54 × 104 and 1.06 × 106, respectively. The fluorescence quenching assay (Ksv) revealed suppression values ranging from 0.34 to 0.64 × 103 M-1 for ethidium bromide (EB) and 0.1 to 0.34 × 103 M-1 for acridine orange (AO). Molecular docking confirmed the competition of the derivatives with intercalation probes at the same binding site. At 10 µM concentrations, the derivatives inhibited topoisomerase IIα activity. In the antiproliferative assays, the compounds demonstrated activity against MCF-7 and T47-D tumor cells and nonhemolytic profile. Regarding toxicity, no acute effects were observed in the embryos. However, some compounds caused enzymatic and cardiac changes, particularly the CAIC, which increased SOD activity and altered heart rate compared to the control. These findings suggest potential antitumor action of the derivatives and indicate that substituting the acridine core with different cores does not interfere with their interaction and topoisomerase inhibition. Further investigations are required to assess possible toxicological effects, including reactive oxygen species generation.

Isatin-indoloquinoxaline click adducts with a potential to overcome platinum-based drug-resistance in ovarian cancer.

Herein, a series of isatin tethered indolo[2,3-b]quinoxaline hybrids was synthesized by considering the pharmacophoric features of known DNA intercalators and topoisomerase II inhibitors. The anti-proliferative properties of the synthesized compounds were evaluated against ovarian cancer cell lines (SKOV-3 and Hey A8). Four of the compounds exhibited promising anti-proliferative activities, with one of them being 10-fold more potent than cisplatin against drug-resistant Hey A8 cells. Further investigations were carried out to determine the DNA intercalating affinities of the most active compounds as potential mechanisms for their anti-proliferative activities. ADMET in silico studies were performed to assess the physicochemical, pharmacokinetics, and toxicity parameters of active compounds. This study, to the best of our knowledge, is the first report on the potential of isatin-indoloquinoxaline hybrids as structural blueprints for the development of new DNA intercalators. Additionally, it explores their potential to circumvent platinum-based resistance in ovarian cancer.

cGAS-STING Pathway Activation and Systemic Anti-Tumor Immunity Induction via Photodynamic Nanoparticles with Potent Toxic Platinum DNA Intercalator Against Uveal Melanoma.

The cGAS-STING pathway, as a vital innate immune signaling pathway, has attracted considerable attention in tumor immunotherapy research. However, STING agonists are generally incapable of targeting tumors, thus limiting their clinical applications. Here, a photodynamic polymer (P1) is designed to electrostatically couple with 56MESS-a cationic platinum (II) agent-to form NPPDT -56MESS. The accumulation of NPPDT -56MESS in the tumors increases the efficacy and decreases the systemic toxicity of the drugs. Moreover, NPPDT -56MESS generates reactive oxygen species (ROS) under the excitation with an 808 nm laser, which then results in the disintegration of NPPDT -56MESS. Indeed, the ROS and 56MESS act synergistically to damage DNA and mitochondria, leading to a surge of cytoplasmic double-stranded DNA (dsDNA). This way, the cGAS-STING pathway is activated to induce anti-tumor immune responses and ultimately enhance anti-cancer activity. Additionally, the administration of NPPDT -56MESS to mice induces an immune memory effect, thus improving the survival rate of mice. Collectively, these findings indicate that NPPDT -56MESS functions as a chemotherapeutic agent and cGAS-STING pathway agonist, representing a combination chemotherapy and immunotherapy strategy that provides novel modalities for the treatment of uveal melanoma.

Development of an Innovative Colorimetric DNA Biosensor Based on Sugar Measurement.

The development of biosensors for target detection plays a crucial role in advancing various fields of bioscience. This work presents the development of a genosensor that exploits the colorimetric phenol-sulfuric acid sugar reaction for the detection of DNA, and RNA as specific targets, and DNA intercalator molecules. The biosensor combines simplicity and reliability to create a novel bioassay for accurate and rapid analysis. A 96-well microplate based on a polystyrene polymer was used as the platform for an unmodified capture DNA immobilization via a silanization process and with (3-Aminopropyl) triethoxysilane (APTES). After that, a hybridization step was carried out to catch the target molecule, followed by adding phenol and sulfuric acid to quantify the amount of DNA or RNA sugar backbone. This reaction generated a yellow-orange color on the wells measured at 490 nm, which was proportional to the target concentration. Under the optimum conditions, a calibration curve was obtained for each target. The developed biosensor demonstrated high sensitivity, good selectivity, and linear response over a wide concentration range for DNA and RNA targets. Additionally, the biosensor was successfully employed for the detection of DNA intercalator agents that inhibited the hybridization of DNA complementary to the immobilized capture DNA. The developed biosensor offers a potential tool for sensitive and selective detection in various applications, including virus diagnosis, genetic analysis, pathogenic bacteria monitoring, and drug discovery.

DNA major versus minor groove occupancy of monomeric and dimeric crystal violet derivatives. Toward structural correlations.

Six monomeric (1a-1f) and five dimeric (2a-2e) derivatives of the triphenylmethane dye crystal violet (CV) have been prepared. Evaluation of the binding of these compounds to CT DNA by competitive fluorescent intercalator displacement (FID) assays, viscosity experiments, and UV and CD spectroscopy suggest that monomeric derivative 1a and dimeric derivative 2d likely associate with the major groove of DNA, while dimeric derivatives 2a and 2e likely associate with the minor groove of DNA. Additional evidence for the groove occupancy assignments of these derivatives was obtained from ITC experiments and from differential inhibition of DNA cleavage by the major groove binding restriction enzyme BamHI, as revealed by agarose gel electrophoresis. The data indicate that major groove ligands may be optimally constructed from dye units containing a sterically bulky 3,5-dimethyl-N,N-dimethylaniline group; furthermore, the groove-selectivity of olefin-tethered dimer 2d suggests that stereoelectronic interactions (n â†’ π*) between the ligand and DNA are also an important design consideration in the crafting of major-groove binding ligands.

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers.

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines. The inhibitory potencies of the best members against Topo I and Topo II were also assayed besides their DNA intercalation abilities. Compound 7d NPs exhibited the best inhibition against Topo I and Topo II enzymes with IC50 of 0.042 and 1.172 µM, respectively. The ability of compound 7d NPs to arrest the cell cycle and induce apoptosis was investigated. It arrested the cell cycle in the A549 cell at the S phase and prompted apoptosis by 41.02% vs. 23.81% in the control. In silico studies were then performed to study the possible binding interactions between the designed members and the target proteins.

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines.In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised.Cytotoxicity, Topo I and Topo II inhibitory assays, and DNA intercalation abilities were evaluated.Compound 7d NPs showed the best Topo I and Topo II inhibition.Cell cycle arrest, apoptosis induction, and molecular docking studies were performed.

Comparison of Salvianolic Acid A Adsorption by Phenylboronic-Acid-Functionalized Montmorillonites with Different Intercalators.

Due to its success in treating cardio-cerebrovascular illnesses, salvianolic acid A (SAA) from Salvia miltiorrhiza is of major importance for effective acquisition. For the adsorption of salvianolic acid, cationic polyelectrolytes, and amino-terminated silane intercalated with phenylboronic-acid-functionalized montmorillonites, known as phenylboronic-acid-functionalized montmorillonites with PEI (PMP) and phenylboronic-acid-functionalized montmorillonites with KH550 (PMK), respectively, were produced. In this paper, detailed comparisons of the SAA adsorption performance and morphology of two adsorbents were performed. PMP showed a higher adsorption efficiency (>88%) over a wide pH range. PMK showed less pH-dependent SAA adsorption with a faster adsorption kinetic fitting in a pseudo-second-order model. For both PMP and PMK, the SAA adsorption processes were endothermic. Additionally, it was clearer how temperature affected PMP adsorption. PMK has a higher adsorption selectivity. This study demonstrates how the type of intercalator can be seen to have an impact on adsorption behavior through various structural variations and offers an alternative suggestion for establishing a dependable method for the synthesis of functional montmorillonite from the intercalator's perspective.

Cobalt bis(dicarbollide) is a DNA-neutral pharmacophore.

Cobalt bis(dicarbollide) (COSAN) is a metallacarborane used as a versatile pharmacophore to prepare biologically active hybrid organic-inorganic compounds or to improve the pharmacological properties of nucleosides, antisense oligonucleotides, and DNA intercalators. Despite these applications, COSAN interactions with nucleic acids remain unclear, limiting further advances in metallacarborane-based drug development. Although some studies showed that COSAN intercalates into DNA, COSAN-containing intercalators do not, and while COSAN shows low cytotoxicity, intercalators are often highly toxic. The present study aimed at comprehensively characterizing interactions between COSAN and DNA using a wide range of techniques, including UV-Vis absorption, circular (CD) and linear (LD) dichroism, nuclear magnetic resonance (NMR) spectroscopy, thermal denaturation, viscosity, differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC), and equilibrium dialysis measurements. Our results showed that COSAN has no effect on DNA structure, length, stability, or hybridization, with no or only faint signs of COSAN binding to DNA. Moreover, DNA is not necessary for COSAN to induce cytotoxicity at high concentrations, as shown by in vitro experiments. These findings demonstrate that COSAN is a DNA-neutral pharmacophore, thus confirming the general safety and biocompatibility of metallacarboranes and opening up new opportunities for further developing metallacarborane-based drugs.

DNA intercalation makes possible superior-gain organic photoelectrochemical transistor detection.

DNA intercalation has increasingly been studied for various scenario implementations due to the diverse functions of DNA/intercalators. Nascent organic photoelectrochemical transistor (OPECT) biosensing taking place in organic electronics and photoelectrochemical bioanalysis represents a promising technological frontier in the arena. In this work, we first devise DNA intercalation-enabled OPECT for miRNA detection with a superior gain up to 17100. Intercalation of [Ru(bpy)2dppz]2+ within the miRNA-initiated hybrid chain reaction (HCR)-derived duplex DNA is realized for producing anodic photocurrent upon light stimulation, causing the corresponding target-dependent alternation in gate voltage (VG) and hence the modulated channel current (IDS) of poly (3,4-ethylenedioxythiophene) doped with poly (styrene sulfonate) (PEDOT:PSS) under specific drain voltage (VDS) for quantitative miRNA-21 analysis, which shows a wide linear relationship and a low detection limit of 5.5 × 10-15 mol L-1. This study features the DNA intercalation-enabled organic electronics with superior gain and is envisaged to attract more attention to explore DNA adducts for innovative bioelectronics and biosensing, given the diverse DNA binders with multiple functions.

Switching between DNA binding modes with a photo- and redox-active DNA-targeting ligand, part II: the influence of the substitution pattern.

A disulfide-functionalized photoactive DNA ligand is presented that enables the control of its DNA-binding properties by a combination of a photocycloaddition reaction and the redox reactivity of the sulfide/disulfide functionalities. In particular, the initially applied ligand binds to DNA by a combination of intercalation and groove-binding of separate benzo[b]quinolizinium units. The association to DNA is interrupted by an intramolecular [4 + 4] photocycloaddition to the non-binding head-to-head cyclomers. In turn, the subsequent cleavage of these cyclomers with dithiothreitol (DTT) regains temporarily a DNA-intercalating benzoquinolizinium ligand that is eventually converted into a non-binding benzothiophene. As a special feature, this sequence of controlled deactivation, recovery and internal shut-off of DNA-binding properties can be performed directly in the presence of DNA.

Multi intercalators FRET enhanced detection of minute amounts of DNA.

A novel approach is presented that increases sensitivity and specificity for detecting minimal traces of DNA in liquid and on solid samples. Förster Resonance Energy Transfer (FRET) from YOYO to Ethidium Bromide (EtBr) substantially increases the signal from DNA-bound EtBr highly enhancing sensitivity and specificity for DNA detection. The long fluorescence lifetime of the EtBr acceptor, when bound to DNA, allows for multi-pulse pumping with time gated (MPPTG) detection, which highly increases the detectable signal of DNA-bound EtBr. A straightforward spectra/image subtraction eliminates sample background and allows for a huge increase in the overall detection sensitivity. Using a combination of FRET and MPPTG detection an amount as small as 10 pg of DNA in a microliter sample can be detected without any additional sample purification/manipulation or use of amplification technologies. This amount of DNA is comparable to the DNA content of a one to two human cells. Such a detection method based on simple optics opens the potential for robust, highly sensitive DNA detection/imaging in the field, quick evaluation/sorting (i.e., triaging) of collected DNA samples, and can support various diagnostic assays.