New Biosensor Microchip Could Speed Up Drug Development
A team of investigators from Stanford University has developed a new biosensor microchip that could significantly speed up the process of drug development. The microchips, packed with highly sensitive magnetic nanosensors, analyze how proteins bind to one another, a critical step for evaluating the effectiveness and possible side effects of a potential medication. A single centimeter-sized array of the nanosensors can simultaneously and continuously monitor thousands of times more protein-binding events than any existing sensor. The new sensor is also able to detect interactions with greater sensitivity and deliver the results significantly faster than the present "gold standard" method.
"You can fit thousands, even tens of thousands, of different proteins of interest on the same chip and run the protein-binding experiments in one shot," said Shan Wang, the co-principal investigator of the Center of Cancer Nanotechnology Excellence, who led the research effort. Dr. Wang and his collaborators published the results of their work with the nanosensor chip in the journal Nature Nanotechnology. In theory, the chip could measure a drug's affinity for every protein in the human body.
The power of the nanosensor array lies in two advances. First, the use of magnetic nanotags attached to the protein being studied – such as a medication – greatly increases the sensitivity of the monitoring. Second, an analytical model the researchers developed enables them to accurately predict the final outcome of an interaction based on only a few minutes of monitoring data. Current techniques typically monitor no more than four simultaneous interactions and the process can take hours.
Members of Dr. Wang's research group developed the magnetic nanosensor technology several years ago and demonstrated its sensitivity in experiments in which they showed that it could detect a cancer-associated protein biomarker in mouse blood at a thousandth of the concentration that commercially available techniques could detect. That research was described in a 2009 paper in Nature Medicine (click here to see an earlier Nano News story).
The researchers tailor the nanotags to attach to the particular protein being studied. When a nanotag-equipped protein binds with another protein that is attached to a nanosensor, the magnetic nanotag alters the ambient magnetic field around the nanosensor in a small but distinct way that is sensed by the detector. That binding could be to the targeted protein, or to other proteins in the body that would be considered "off target" and could produce an undesired side effect.
The increased sensitivity to detection that comes with the magnetic nanotags enables the Stanford team to determine not only when a bond forms, but its strength as well. The rate at which a protein binds and releases reveals the strength of the bond between the drug and a protein. The nanosensors, which are based on the same type of sensor used in computer hard drives, can detect as few as 10 to 1000 molecules.
"Because our chip is completely based on existing microelectronics technology and procedures, the number of sensors per area is highly scalable with very little cost," explained Dr. Wang. And although the chips used in the work described in the Nature Nanotechnology paper had a little more than 1,000 sensors per square centimeter, Dr. Wang said it should be no problem to put tens of thousands of sensors on the same footprint. "It can be scaled to over 100,000 sensors per centimeter, without even pushing the technology limits in microelectronics industry."
This work, which is detailed in a paper titled, "Quantification of protein interactions and solution transport using high-density GMR sensor arrays," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's Web site.