Scientists at Imperial College London and the University of Vigo have developed an ultra-sensitive biomarker test that should enable them to detect signs of a disease in its earliest stages, even at very low concentrations.

The researchers have demonstrated that test can find a biomarker associated with prostate cancer, called Prostate Specific Antigen (PSA), but the team says that the biosensor can be easily reconfigured to test for other diseases or viruses where the related biomarker is known.

“It is vital to detect diseases at an early stage if we want people to have the best possible outcomes; diseases are usually easier to treat at this stage, and early diagnosis can give us the chance to halt a disease before symptoms worsen,” said Professor Molly Stevens, senior author of the study from the Departments of Materials and Bioengineering at Imperial College London.

In their study, the team detected PSA at 10⁻¹⁸ (0.000000000000000001) grams per milliliter. By comparison, an existing test called an Enzyme-Linked Immunosorbent Assay (ELISA) test can detect PSA at 10⁻⁹ (0.000000001) grams per milliliter, nine orders of magnitude more concentrated.

How it works

Their signal-generation mechanism redefines the limit of detection of nanoparticle sensors by inducing a signal that is larger when the target molecule is less concentrated. The key step to achieve this inverse sensitivity is to use an enzyme that controls the rate of nucleation of silver nanocrystals on plasmonic transducers.

The biosensors consist of nano-sized gold stars floating in a solution containing other blood-derived proteins. Attached to the surface of these gold stars are antibodies, which latch onto PSA when they detect it in a sample.

A secondary antibody, which has an enzyme called glucose oxidase attached to it, recognizes the PSA and creates a distinctive silver crystal coating on the gold stars, which is actually more apparent when the PSA biomarkers are in low concentrations. This silver coating acts like a signal that PSA is present, and it can then be easily detected by scientists using optical microscopes.

The team plans clinical testing to assess the efficacy of the biosensor in detecting a range of different biomarkers associated with conditions such as HIV and other infections.

Ref.: Laura Rodríguez-Lorenzo, Roberto de la Rica, Ramón A. Álvarez-Puebla, Luis M. Liz-Marzán, Molly M. Stevens, Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth, Nature Materials, 2012, DOI: 10.1038/nmat3337