Wednesday, July 16, 2008

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Center for Cancer Nanotechnology Excellence Focused on Therapy Response
Stanford University CCNE

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Sanjiv Sam Gambhir, M.D., Ph.D.
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Project 1: Magneto Nano Protein Chip and Multiplex Sorter for Monitoring Tumor Markers

Project Investigators: Amit Kulkarni, Shan Wang, Peter Bonitatebus, Jeffrey Chalmers, Zhebo Ding, Robert Wilson

We are developing a magneto-nanosensor protein chip and a multiplex magnetic sorter based on magnetic nanoparticles that allow rapid conversion of discrete biomolecular binding events into electrical signals. These nanotechnologies can detect target molecules down to the single molecule level in less than an hour. Such sensitivity and detection speed are unavailable or impractical with current technologies. The two main components of this project, a magneto-nanosensor chip and a nanoparticle-based magnetic sorter, can operate independently or in conjunction. The magneto-nanosensor chip will recognize and quantify protein tumor markers and relevant protein profiles in mouse and human serum samples with unprecedented sensitivity and specificity. These magneto-nanosensors function by exhibiting significant resistance changes which are induced solely by external magnetic fields and are therefore insensitive to solution conditions such as buffers, pH or ionic strength. Biological sensing is accomplished by affinity labeling both the sensor surface and magnetic nanoparticles to simultaneously attach to distinct domains of specifically targeted biological molecules. The magneto-nanosensor then detects the attachment of the biomolecules through the magnetic field induced by the magnetic nanoparticles. For sufficiently small sensors and appropriate magnetic nanoparticle tags, affinity bonding due to a single, specific molecule can be detected as a simple change in the sensor electrical resistance so that expensive excitation sources or remote sensors are not required. The magnetic sorter will rapidly segregate biomolecules, based upon the tunable magnetic properties of the magnetic nanoparticles which bind them, by causing them to deflect at different speeds under a given magnetic field and gradient. In particular, we will be extending technologies to capture and characterize circulating tumor cells from mouse and human serum samples and subsequently analyze the cell lysate for monitoring cancer therapy.

Relevance to public health: The magneto-nanosensor protein chips and multiplex magnetic sorter developed in this project can ultimately be used by cancer biologists as well as clinical oncologists to rapidly follow numerous proteins in clinical samples in an automated and high-throughput fashion. By essentially applying patient serum or tissue samples to the magneto-nanosensor chip, one can readily ascertain the presence or absence of a large number of tumor markers. Additionally, the multiplex magnetic sorter can perform high-throughput enrichment of circulating tumor targets or depletion of impurities, improving complex proteomic analysis that currently suffers from poor signal-to-noise ratio.

Keywords

Early Detection; Multiplexing
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