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NEW EXPERIMENTAL PROCEDURE DETECTS POSSIBLE TRACES OF DISEASE IN CEREBROSPINAL FLUID
If proven successful in further clinical studies, the procedure could become the first tool for early diagnosis of Alzheimer's, and the first test to conclusively identify the disease in living patients. Chad Mirkin and William Klein of the National Science Foundation Nanoscale Science and Engineering Center for Nanopatterning and Detection Technologies at Northwestern University, and their colleagues, announce their findings the week of Jan. 31 in the online edition of the Proceedings of the National Academy of Sciences. Because of the extreme sensitivity of the BCA process that Mirkin's team developed, the researchers were able to detect within each fluid sample a miniscule amount of proteins called amyloid ß-derived diffusible ligands. The goal is to detect and validate infinitesimal amounts of the biomarkers in blood. Research by Klein and his colleagues suggests that ADDLs first appear in the earliest stages of Alzheimer's. If the BCA process can identify the markers before symptoms develop, doctors may be able to combat the illness in its nascent form when treatments may be most effective. In the first steps of the BCA process, unique microparticles latch onto the biomarker targets - in this study, the ADDLs. The particles are magnetic, a property that aids collection at the end of the procedure. Researchers then add a second ingredient that consists of a gold nanoparticle core surrounded by hundreds of identical DNA strands, which serve as hundreds of "bio-bar-codes" the researchers can detect at the end of the test. Ultimately, the gold-DNA particles and magnetic particles sandwich the biomarker targets. A magnet separates the sandwich complexes from the rest of the sample. The complexes are then heated to release the DNA bar codes, which are then measured by an extremely sensitive detector. Each DNA piece greatly increases the sensitivity of the test and its potential to tell doctors a patient carries the ADDLs. According to the researchers, BCA is about 1 million times more sensitive than the next best thing, standard enzyme-linked immunoassays. ELISAs do not have the sensitivity required to detect ADDLs in cerebrospinal fluid. BCA could eventually be configured to detect hundreds of diseases simultaneously, with a single procedure, doctors could quickly and inexpensively test a blood sample for any number of ailments. The researchers developed BCA to detect a mere few dozen molecules amongst a sample filled with billions and have already experimented with biomarkers for AIDS and prostate cancer. This research was supported by both NSF's Engineering Research Centers program and the NSF Office on International Science and Engineering.
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