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September 28, 2009

U of T researchers create microchip that can detect type and severity of cancer


University of Toronto researchers, Shana Kelley and Ted Sargent, have made a cancer diagnostic breakthrough. Kelley said a five-year time frame would be a "conservative estimate" to get the device on the market.

U of T researchers have used nanomaterials to develop an inexpensive microchip sensitive enough to quickly determine the type and severity of a patient's cancer so that the disease can be detected earlier for more effective treatment.

The researchers' new device can easily sense the signature biomarkers that indicate the presence of cancer at the cellular level, even though these biomolecules - genes that indicate aggressive or benign forms of the disease and differentiate subtypes of the cancer - are generally present only at low levels in biological samples. Analysis can be completed in 30 minutes, a vast improvement over the existing diagnostic procedures that generally take days.

"Today, it takes a room filled with computers to evaluate a clinically relevant sample of cancer biomarkers and the results aren't quickly available," said Shana Kelley, a professor in the Leslie Dan Faculty of Pharmacy and the Faculty of Medicine, who was a lead investigator on the project and a co-author on the publication.

"Our team was able to measure biomolecules on an electronic chip the size of your fingertip and analyse the sample within half an hour. The instrumentation required for this analysis can be contained within a unit the size of a BlackBerry."

Kelley, along with engineering professor Ted Sargent - a fellow lead investigator and U of T's Canada Research Chair in Nanotechnology - and an interdisciplinary team from Princess Margaret Hospital and Queen's University, found that conventional, flat metal electrical sensors were inadequate to sense cancer's particular biomarkers. Instead, they designed and fabricated a chip and decorated it with nanometre-sized wires and molecular "bait."


Abstract Nature Nanotechnology: Programming the detection limits of biosensors through controlled nanostructuring

Advances in materials chemistry offer a range of nanostructured shapes and textures for building new biosensors. Previous reports have implied that controlling the properties of sensor substrates can improve detection sensitivities, but the evidence remains indirect. Here we show that by nanostructuring the sensing electrodes, it is possible to create nucleic acid sensors that have a broad range of sensitivities and that are capable of rapid analysis. Only highly branched electrodes with fine structuring attained attomolar sensitivity. Nucleic acid probes immobilized on finely nanostructured electrodes appear more accessible and therefore complex more rapidly with target molecules in solution. By forming arrays of microelectrodes with different degrees of nanostructuring, we expanded the dynamic range of a sensor system from two to six orders of magnitude. The demonstration of an intimate link between nanoscale sensor structure and biodetection sensitivity will aid the development of high performance diagnostic tools for biology and medicine.


2 page pdf with supplemental information

Shana Kelly Lab webpage at the University of Toronto



"Uniting DNA - the molecule of life - with speedy, miniaturized electronic chips is an example of cross-disciplinary convergence," said Sargent. "By working with outstanding researchers in nanomaterials, pharmaceutical sciences, and electrical engineering, we were able to demonstrate that controlled integration of nanomaterials provides a major advantage in disease detection and analysis."

The speed and accuracy provided by their device is welcome news to cancer researchers.

The team's microchip platform has been tested on prostate cancer, as described in a paper published in ACS Nano, and head and neck cancer models. It could potentially be used to diagnose and assess other cancers, as well as infectious diseases such as HIV, MRSA and H1N1 flu.

"The system developed by the Kelley/Sargent team is a revolutionary technology that could allow us to track biomarkers that might have significant relevance to cancer, with a combination of speed, sensitivity, and accuracy not available with any current technology," said Dr. Fei-Fei Liu, a radiation oncologist at Princess Margaret Hospital and Head of Applied Molecular Oncology Division, Ontario Cancer Institute. "This type of approach could have a profound impact on the future management for our cancer patients."




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