Novel Mass Tags for Single Nucleotide Polymorphism Detection

Birikh, Klara R.; Korshun, Vladimir A.; Bernad, Pablo L.; Malakhov, Andrei D.; Milner, Natalie; Khan, Safraz; Southern, Edwin M.; Shchepinov, Mikhail S.

doi:10.1021/ac071291y

Cited by 15 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…25 For the sensitive identification of oligonucleotides by mass spectrometry mass tags have been recently invented as 5 0 labels. 26 But also modifiers for the 3 0 end as modified solid support have been developed and a range of fluorescent dyes, quenchers and affinity tags like biotin are commercially available. Widely used in real-time PCR and other diagnostic applications are both 5 0 and 3 0 labelled probes.…”

Section: Basic Considerationsmentioning

confidence: 99%

Novel strategies for the site-specific covalent labelling of nucleic acids

2008

View full text Add to dashboard Cite

To broaden the scope of applications in DNA nano- and biotechnology, material science, diagnostics and molecular recognition the functionalization of DNA is of utmost importance. In the last decade many new methods have been developed to achieve this goal. Apart from the direct chemical synthesis of modified DNA by automated phosphoramidite chemistry incorporation of labelled triphosphates and the post-synthetic labelling approach evolved as valuable methods. New bioorthogonal reactions as Diels-Alder, click and Staudinger ligations pushed forward the post-synthetic approach as new insights into DNA polymerase substrate specificity allowed generation and amplification of labelled DNA strands. These novel developments are summarized herein.

show abstract

Section: Basic Considerationsmentioning

confidence: 99%

Novel strategies for the site-specific covalent labelling of nucleic acids

2008

View full text Add to dashboard Cite

show abstract

“…Compared with spectroscopic-technique-based biosensors, mass spectrometry has the advantage of excellent specificity. However, its detection limit for direct detection of miRNA is generally in the nanomolar level. , One of the main reasons for the relatively low sensitivity of mass spectrometry for miRNAs is the low ionization efficiency of miRNAs. , Various methods including organic mass tags, metal element labeling, and isothermal amplification are used to increase the ionization efficiency and enhance the sensitivity for miRNA detection. − Among them, metal nanoparticles are quite promising mass tags offering high detection sensitivity because of the presence of many thousands of metal atoms in a single metal nanoparticle of a 10 nm diameter. − Although the sensitivity problem of mass spectrometry for miRNA detection is effectively solved by mass tagging techniques, its specificity is lost since the mass spectral signals come from the mass tags instead of miRNAs themselves, and the discrimination between the target miRNAs from nontarget ones with SNPs is based on the differences in their mass spectral intensities. Mass spectrometric methods possessing both high sensitivity and specificity are highly desired for the detection of miRNAs.…”

Section: Introductionmentioning

confidence: 99%

Highly Sensitive and Specific Mass Spectrometric Platform for miRNA Detection Based on the Multiple-Metal-Nanoparticle Tagging Strategy

et al. 2021

View full text Add to dashboard Cite

The multiple-metal-nanoparticle tagging strategy has generally been applied to the multiplexed detection of multiple analytes of interest such as microRNAs (miRNAs). Herein, it was used for the first time to improve both the specificity and sensitivity of a novel mass spectroscopic platform for miRNA detection. The mass spectroscopic platform was developed through the integration of the ligation reaction, hybridization chain reaction amplification, multiple-metal-nanoparticle tagging, and inductively coupled plasma mass spectrometry. The high specificity resulted from the adoption of the ligation reaction is further enhanced by the multiple-metal-nanoparticle tagging strategy. The combination of hybridization chain reaction amplification and metal nanoparticle tagging endows the proposed platform with the feature of high sensitivity. The proposed mass spectrometric platform achieved quite satisfactory quantitative results for Let-7a in real-world cell line samples with accuracy comparable to that of the real-time quantitative reverse-transcriptase polymerase chain reaction method. Its limit of detection and limit of quantification for Let-7a were experimentally determined to be about 0.5 and 10 fM, respectively. Furthermore, due to the unique way of utilizing the multiple-metal-nanoparticle tagging strategy, the proposed platform can unambiguously discriminate between the target miRNA and nontarget ones with single-nucleotide polymorphisms based on their response patterns defined by the relative mass spectral intensities among the multiple tagged metal elements and can also provide location information of the mismatched bases. Its unique advantages over conventional miRNA detection methods make the proposed platform a promising and alternative tool in the fields of clinical diagnosis and biomedical research.

show abstract

“…Most successfully the mass tags have been applied in MALDI-imaging mass spectrometry (MALDI-MSI) [1][2][3][4][5][6] , but also in single nucleotide polymorphism detection [7][8][9] , combinatorial synthesis [10,11] and as ionization enhancers [12] . Two different types of mass tag molecules have been reported in the literature, either peptide tags connected to a binder via a photocleavable linker group [3] or triphenylmethyl-(trityl) based tags [1,2,5,6,[10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Mass-Tag Enhanced Immuno-Laser Desorption/Ionization Mass Spectrometry for Sensitive Detection of Intact Protein Antigens

et al. 2015

View full text Add to dashboard Cite

A new read-out method for antibody arrays using laser desorption/ionization-mass spectrometry (LDI-MS) is presented. Small, photocleavable reporter molecules with a defined mass called "mass-tags" are used for detection of immunocaptured proteins from human plasma. Using prostate specific antigen (PSA), a biomarker for prostate cancer, as a model antigen, a high sensitivity generic detection methodology based immunocapture with a primary antibody and with a biotin labeled secondary antibody coupled to mass-tagged avidin is demonstrated. As each secondary antibody can bind several avidin molecules, each having a large number of mass-tags, signal amplification can be achieved. The developed PSA sandwich mass-tag analysis method provided a limit of detection below 200 pg/mL (6 pM) for a 10 μL plasma sample, well below the clinically relevant cutoff value of 3-4 ng/mL. This brings the limit of detection (LOD) for detection of intact antigens with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) down to levels comparable to capture by anti-peptide antibodies selected reaction monitoring (SISCAPA SRM) and enzyme linked immunosorbent assay (ELISA), as 6 pM corresponds to a maximal amount of 60 amol PSA captured on-spot. We propose the potential use of LDI (laser desorption/ionization) with mass-tag read-out implemented in a sandwich assay format for low abundant and/or early disease biomarker detection.

show abstract

Novel Mass Tags for Single Nucleotide Polymorphism Detection

Cited by 15 publications

References 11 publications

Novel strategies for the site-specific covalent labelling of nucleic acids

Novel strategies for the site-specific covalent labelling of nucleic acids

Highly Sensitive and Specific Mass Spectrometric Platform for miRNA Detection Based on the Multiple-Metal-Nanoparticle Tagging Strategy

Mass-Tag Enhanced Immuno-Laser Desorption/Ionization Mass Spectrometry for Sensitive Detection of Intact Protein Antigens

Contact Info

Product

Resources

About