Discovery and design of new drugs for cancer therapy can be based on different strategies, e.g., effect of a drug on extent and duration of apoptosis, or induced cytoskelatal changes affecting motility and invasiveness. Information underlying these strategies may be gathered using techniques comprising the emerging discipline of cytomics. Foremost of these, for our purposes, is High Content Screening (HCS). We propose to develop new nanoscale sensors suitable for HCS that will have multiple applications for development of new cancer drugs: at the highest level as a basic research tool for real-time three-dimensional in vivo cell imaging for screening of new cancer drugs, and at a finer level, as a tool for real-time imaging of targeteddrug carrier interaction with cell membranes. Ultimately, we envision these sensors being incorporated into the bottom of disposable cell-culture dishes. In this configuration, acquisition of real-time, high resolution (~30nm) image data over the entire volume of the cell culture from the array surface to a height of 10-20 microns would be performed simultaneously for a variety of physical parameters affecting or affected by cell physiology: surface charge, optical emision (i.e., fluorescent optical imaging), or physical strain induced by piezo-electric crystals embedded in the cell culture nano-array (i.e., ultrasonic imaging). Development of simultaneous in vivo, multimodal nano-volume imaging will be pursued along two parallel lines: conventional PZT (Lead-Zirconium-Titanate) based ultrasonic transduction reduced in size, and the other based on a novel sensor technology, offering potential improvements in sensitivity and scalability, at reduced cost. These will be based on the recent experimental observation that hybrid thin film structures possessing an appropriately selected geometric interface (between a semiconductor and a metal) display a new phenomenon that has been labeled extraordinary magneto-resistance (EMR). We have demonstrated that EMR devices are scalable from macroscopic to nanoscopic dimensions in the range of millimeters to 20 nm.
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