Mass spectrometric methods for detecting mutations in a target nucleic acid
View Patent ↗Provided herein in certain embodiments are processes that generally include the following steps: amplifying a target nucleic acid molecule; ionizing and volatilizing the amplification product and analyzing the ionized and volatilized product by mass spectrometry. In some embodiments the amplification product is a natural nucleic acid and detection of the target nucleotide sequence by mass spectrometry indicates the presence of the target nucleotide sequence in the biological sample.
1. A process for detecting one or more target nucleotide sequences in a biological sample, comprising:
a) amplifying a target nucleic acid molecule, wherein the amplification product is a natural nucleic acid;
b) ionizing and volatilizing the product of step (a); and
c) analyzing the product of step (b) by mass spectrometry, wherein detection of the target nucleotide sequence by mass spectrometry indicates the presence of the target nucleotide sequence in the biological sample.
2. The process of claim 1 , wherein the target nucleotide sequence is a mutation.
3. The process of claim 1 , wherein a plurality of nucleic acids of step (a) are arranged on a solid support in an array and each spot on the array is subject to mass spectrometric analysis.
4. The process of claim 1 , wherein the mass spectrometry format is matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.
5. The process of claim 1 , wherein the mass spectrometry format is electrospray (ES) mass spectrometry.
6. The process of claim 1 , wherein the target nucleotide sequence is a DNA fingerprint or is implicated in a disease or condition selected from the group consisting of a genetic disease, a chromosomal abnormality, a genetic predisposition, a viral infection, a fungal infection, a bacterial infection and a protist infection.
7. The process of claim 6 , whereby a genetic disease, chromosomal abnormality, genetic predisposition to a disease or condition or infection by a pathogen is detected or identity determined.
8. The process of claim 1 , which further comprises exchanging cations bound to the amplification product of step (a).
9. The process of claim 1 , wherein the amplification product of step (a) is a natural oligodeoxyribo nucleic acid.
10. The process of claim 1 , wherein the backbone of the amplification product of step (a) has a phosphodiester backbone.
11. The process of claim 1 , wherein the amplification product of step (a) is contacted with a capture oligonucleotide linked to a solid support.
12. The process of claim 1 , wherein the target nucleic acid is contacted with a capture oligonucleotide linked to a solid support.