Tandem mass spectrometry, also known as MS/MS or MS², is a technique in instrumental analysis where two or more mass analyzers are coupled together using an additional reaction step to increase their abilities to analyse chemical samples. A common use of tandem-MS is the analysis of biomolecules, such as proteins and peptides. The molecules of a given sample are ionized and the first spectrometer separates these ions by their mass-to-charge ratio (often given as m/z or m/Q). Ions of a particular m/z-ratio coming from MS1 are selected and then made to split into smaller fragment ions, e.g. by collision-induced dissociation, ion-molecule reaction, or photodissociation. These fragments are then introduced into the second mass spectrometer , which in turn separates the fragments by their m/z-ratio and detects them. The fragmentation step makes it possible to identify and separate ions that have very similar m/z-ratios in regular mass spectrometers..

STRUCTURE

Tandem mass spectrometry includes triple quadrupole mass spectrometer (qqq), quad time of flight (Q-tof), and hybrid mass spectrometer

Triple quadrupole mass spectrometer (QQQ)

Tandem mass spectrometry that the first and third quadrupole work as a mass filter. When analytes pass the second quadrupole, the fragmentation proceeds through collision with gas. Usually used for the pharmaceutical industry.

Quadrupole time of flight (Q-tof)

Q-tof mass spectrometer combines TOF and quadrupole instruments, which cause high mass accuracy for product ions, accurate quantitation capability, and fragmentation experiment applicability. This is a method of mass spectrometry that ion fragmentation (m/z) ratio determined through a time of flight measurement.

Hybrid mass spectrometer

hybrid mass spectrometer consists of more than two mass analyzers.

APPLICATIONS

PEPTIDES

Tandem mass spectrometry can be used for protein sequencing.When intact proteins are introduced to a mass analyzer, this is called "top-down proteomics" and when proteins are digested into smaller peptides and subsequently introduced into the mass spectrometer, this is called "bottom-up proteomics". Shotgun proteomics is a variant of bottom up proteomics in which proteins in a mixture are digested prior to separation and tandem mass spectrometry. Tandem mass spectrometry can produce a peptide sequence tag that can be used to identify a peptide in a protein database.

Oligosaccharides

Oligosaccharides may be sequenced using tandem mass spectrometry in a similar manner to peptide sequencing. Fragmentation generally occurs on either side of the glycosidic bond (b, c, y and z ions) but also under more energetic conditions through the sugar ring structure in a cross-ring cleavage (x ions). Again trailing subscripts are used to indicate position of the cleavage along the chain. For cross ring cleavage ions the nature of the cross ring cleavage is indicated by preceding superscripts.

Oligonucleotides

Tandem mass spectrometry has been applied to DNA and RNA sequencing. A notation for gas-phase fragmentation of oligonucleotide ions has been proposed.

Newborn screening

Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases. The development of tandem mass spectrometry screening in the early 1990s led to a large expansion of potentially detectable congenital metabolic diseases that affect blood levels of organic acids.