A Needle in the Haystack

I read an interesting article on protein analysis in biological fluids in the latest issue of LC/GC North America magazine. The article itself was about how to separate the wheat from the chaff during analysis. The article made me realize how difficult diagnostic tests are to develop. When trying to diagnose a protein related disease or pathophysiological condition, the issue boils down to how to detect very small amounts of a specific protein needed for diagnosis that is buried among the large number of proteins in the sample.

A specific example is the prostate specific antigen (PSA) test in human serum/plasma. Even when there is a bad prostate problem, the PSA protein that signals a problem is present in a very tiny amount. That alone makes it hard to detect. But compounding the problem is sorting out the PSA protein from many other proteins in the plasma. Albumin, responsible for managing blood volume and transporting substances in the bloodstream, accounts for over half the protein in plasma. Immunoglobulin G, a protein that helps defend the body from attacks (e.g. by toxins), accounts for roughly 15-20% of protein in serum. These two proteins alone make finding and measuring the PSA protein very hard. But how hard?

To put the problem in perspective, finding and measuring PSA in a single blood sample is about the same as trying to find a single, specific nail (the PSA protein) among all the fingers and toes of every human being (all the serum proteins) in the world. Talk about finding a needle in a haystack! And to think PSA analyses are done in several minutes, hundreds of times a day. Amazing.