DISCRETE SENSOR DEVICES FOR DETERMINING CANCER TARGETS

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Technologies for real time sensing of multiple tumor targets, metabolites and chemotherapeutic drugs or degradation products will have far-reaching impact in cancer research and clinical care. Sensing technologies, as that described in this proposal, will be relevant to high risk ovarian cancer patients to detect the disease in a potentially curable early stage; for more accurate staging during initial diagnostic laparotomy of patients with possible micro-metastatic disease; and for the detection during second-look laparotomy or laparoscopy of minimally residual disease after treatment in more advanced cases This project will combine the sensing capabilities of nanoscale magnetic relaxation switches (MRSW) and implantable microfabricated structures to create powerful implantable and fully biodegradable multiplexed sensors for in vivo sensing. These implanted magnetic sensing systems (IMSS) may overcome current shortcomings of in vivo imaging and ex vivo testing. The MRSW are based on magnetic nanoparticles that change relaxation state upon analyte presence and can therefore be used to detect a large variety of analytes by magnetic means down to attomolar sensitivity. Importantly, the nanoparticles are packaged into microfabricated devices to semi-isolate them from the in vivo environment through semipermeable membranes with specific molecular weight cut-offs. Thus, the analytes (e.g. secreted peptides and proteins, metabolites, chemotherapeutic agents) are free to access the sensor but the MRSW are protected from macrophage phagocytosis, immunogenicity or any changes in sensor concentration. We have developed a number of different MRSW in prior research to sense telomerase, CA-125, small molecules, peptides and glucose among others. In parallel, we have developed biodegradable and non-biodegradable, microfabricated MEMS type devices that have served as drug delivery devices. These small devices with microfabricated reservoirs are an ideal platform for integration of nanosensors since many of the important structural elements are similar. The current project will bring together the expertise of the Weissleder/Josephson team in MRSW technology and the Cima/Langerteam in developing, microfabrication and testing the novel sensors. Together with the input of clinical oncologists (Seiden) and the mouse model core (Housman, Jacks) we will apply the novel sensors to common problems in ovarian cancer.