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Detecting the undetectable in prostate cancer screening
Date:10/19/2009

ples from 18 post-prostatectomy patients collected over the course of a number of years.

The researchers were able to reliably and accurately quantify PSA values at less than 0.1 nanograms per milliliter, the clinical limit of detection for commercial assays. The lower limit of detection for PSA using the bio-barcode assay is approximately 300 times lower than the lower limit of detection for commercial tests. The PSA measurements were used to classify the patients as either having no evidence of disease or having a relapse of disease.

The Northwestern team is now conducting a similar retrospective study of 260 patients and eventually plans to do a large prospective study.

The ultra-sensitive technology is based on gold nanoparticle probes, decorated with DNA and antibodies that can recognize and bind to PSA when present at extremely low levels in a blood sample. A magnetic microparticle, outfitted with a second antibody for PSA, also is used in the assay. When in solution, the antibody-functionalized particles "recognize" and bind to PSA, sandwiching the protein between the two particles.

The key is that attached to each tiny gold nanoparticle (just 30 nanometers in diameter) are hundreds of identical strands of DNA. Mirkin calls this "bar-code DNA" because they have designed it as a label specific to the PSA target. After the "particle-protein-particle" sandwich is removed magnetically from solution, the DNA is removed from the sandwich and read using a Verigene ID system, a nanotechnology platform designed to detect and quantify DNA.

The amount of PSA present is calculated based on the amount of bar-code DNA. For each molecule of captured PSA, hundreds of DNA strands are released, which is one of the ways the PSA signal is amplified.

The title of the PNAS paper is "The Nanoparticle-Based Bio-Barcode Assay Re-Defines 'Undetectable' PSA and Biochemical Recurrence Following Radical Prostatectomy." In ad
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
Source:Eurekalert

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