What is tandem mass spectrometry?
Tandem mass spectrometry (MS/MS) is perhaps the most significant advance in newborn screening in the past 30 years. A tandem mass spectrometer is a specialized instrument that detects molecules by measuring their weight (mass). Mass spectrometers measure weight electronically and display results in the form of a mass spectrum. A mass spectrum is a graph that shows each specific molecule by weight (mass) and how much of each molecule is present.
A simple newborn blood specimen contains thousands of molecules ranging from small molecules such as salt to large proteins such as hemoglobin. When alcohol is added to the dried blood spot, several hundred molecules are pulled out and can be studied. If this entire mixture is studied directly, a complex graph is produced and it is difficult to tell biochemically important molecules from other less important molecules that have the same weight.
To make the graph easier to understand, the biochemically important molecules must be separated from all other molecules. Before MS/MS technology, these molecules could only be separated by physical methods (gas and liquid chromatography) that take between 10 to 30 minutes each. A tandem mass spectrometer can accomplish this task accurately in approximately two minutes.
How does a mass spectrometer work?
A mass spectrometer works similar to how a person might sort a pocketful of change. Each coin has a unique weight and size (quarters weigh more and are larger in size than dimes). After sorting by weight and size, the quantity of each type of coin can be counted quickly. Tandem mass spectrometers can take the sorting even further. For example, consider the new quarters that feature specific state designs on the back. Each state quarter has a similar weight and size but has a slightly different structure. A tandem mass spectrometer can quickly sort biochemically important molecules of similar weight in the same manner that you can sort how many of the newer Pennsylvania, Massachusetts, or Georgia quarters you have.
Why is MS/MS the best method for newborn screening?
Tandem mass spectrometry measures many different molecules in a single test. Older testing methods require the use of several tests to look at different types of molecules making them time-consuming and expensive. With tandem mass spectrometry, the results are available quickly and are also more accurate. For example, MS/MS testing for PKU studies the levels of two chemicals: phenylalanine (phe) and tyrosine. While most babies with PKU will have an elevated level of phe, virtually all babies with this disorder will have a high level of phe compared to tyrosine. This is important because older testing methods look only at phe and may miss some babies with PKU. MS/MS testing is also more accurate than the study of phe alone because there are several reasons other than PKU that a child may have an elevated blood level of phe. These include prematurity, special diets, liver disease, and differences in blood collection. The phenylalanine to tyrosine comparison is generally not high in these instances so MS/MS testing reduces the number of falsely "abnormal" PKU results.
Tandem mass spectrometry is also superior to other testing methods because the study of multiple chemicals at a time allows us to accurately pinpoint which specific disorder a child may have. This technology is particularly helpful in the identification of specific disorders that share common chemical elevations. For example, MCAD deficiency and MADD both present with high levels of a chemical called octanoylcarnitine (C8). If we look at C8 alone and it is high, we cannot tell which of the two disorders a child might have. But, if we look at C8 in combination with other chemicals the picture becomes clearer. For example, individuals with MADD also show an unusual level of decanoylcarnitine relative to C8 and higher levels of long and short chain acylcarnitines. These findings are not seen in MCAD deficiency and distinguishes the two conditions.
Finally, there is an obvious cost benefit to running both amino acids and acylcarnitines in a single profile. Currently, PerkinElmer Genetics monitors more than 60 chemical and chemical relationships in a single test. These markers provide indicators for disease, quality assurance, and potential contaminants that may interfere with other studies. The markers also provide information regarding hyperalimentation, method of collection, and drug treatment. Tandem Mass Spectrometry measures these indicators or markers in a typical two-minute run.
The analyses conducted by PerkinElmer Genetics produce results that can be used by qualified physicians in the diagnosis of certain disorders. While evidence of such conditions will be detected in the vast majority of affected individuals, due to genetic variability, it may not be detected in all.