Detecting cancer with silica nanoparticles

Tumor necrosis factor-alpha is a widely accepted biomarker for cancer, but the minute amounts of this protein circulating in blood makes detecting the molecule and measuring its concentration accurately a technological challenge.

Using silica nanoparticles labeled with the molecule guanine, researchers at the Pacific Northwest National Laboratory have now created a simple and inexpensive electrochemical method that detects tumor necrosis factor-alpha at clinically useful levels. Moreover, this assay is amenable to miniaturization, suggesting that it could be easily incorporated into a microfluidics-based assay system.

Reporting its work in the journal Analytical Chemistry, a research team headed by Yuehe Lin, Ph.D., loaded guanine molecules onto the surface of silica nanobeads that also contained a chemical anchor known as avidin. They also attached biotin, which binds with extraordinary strength to avidin, to an antibody that binds to the tumor necrosis factor-alpha protein. The researchers attached a second antibody, one that binds to a different part of the tumor necrosis factor-alpha protein, to a carbon electrode, which functions as the electrochemical sensor.

When tumor necrosis factor-alpha is present in a solution added to the antibody-labeled electrode, it binds to the antibody. Adding the second antibody produces a sandwich around the tumor necrosis factor-alpha molecule. At this point, the researchers then added their labeled silica nanoparticle, which binds to the antibody-tumor necrosis factor-alpha sandwich. In a final step, the investigators added a molecule that reacts with the guanines on the nanoparticle, creating an electrical current that the electrode senses. The current flowing into the electrode is proportional to the amount of tumor necrosis factor-alpha bound to the first antibody. Experiments with this system showed that the limit of detection for the device is approximately 2 picomolar, well within the range needed to detect physiological levels of tumor necrosis factor-alpha.

This work is detailed in a paper titled, “Sensitive immunoassay of a biomarker tumor necrosis factor-alpha based on poly(guanine)-functionalized silica nanoparticle label.” This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website. View abstract.