DISCRETE SENSOR DEVICES FOR DETERMINING CANCER TARGETS

用于实时检测多个肿瘤靶点、代谢物和化疗药物或 降解产物将对癌症研究和临床护理产生深远影响。感测 这项提议中描述的技术将与高危卵巢癌患者相关，以检测到 该病处于潜在可治愈的早期阶段；在最初诊断剖腹手术时，为了更准确地进行分期 对于可能有微转移疾病的患者；以及在二次剖腹手术或 腹腔镜术治疗后微小残留病变的晚期病例本项目将结合 纳米级磁弛豫开关(MRSW)和可植入微细加工的传感能力 为活体传感创造强大的可植入和完全可生物降解的复合传感器的结构。 这些植入的磁传感系统(IMSS)可以克服目前活体成像的缺点 和体外试验。磁致伸缩开关是基于磁性纳米颗粒，其改变弛豫状态 分析物的存在，因此可用于通过磁性手段检测多种分析物 大气压敏感度。重要的是，纳米颗粒被封装到微型制造的设备中，以半隔离 它们通过比分子量的半透膜从体内环境中释放 断头台。因此，分析物(例如分泌肽和蛋白质、代谢物、化疗药物)是 可以自由接触传感器，但MRSW受到保护，不受巨噬细胞吞噬、免疫原性或 传感器浓度的任何变化。在之前的研究中，我们已经开发了许多不同的MRSW 检测端粒酶、CA-125、小分子、多肽和葡萄糖等。与此同时，我们有 开发了可生物降解和不可生物降解的微型制造MEMS类型的器件，这些器件已用作 药物输送装置。这些带有微型储罐的小型设备是一个理想的平台 纳米传感器的集成，因为许多重要的结构元素都是相似的。当前项目 将汇集Weissleder/Josephson团队在MRSW技术方面的专业知识和 CIMA/LIGER团队参与了新型传感器的开发、微制造和测试。加上……的投入 临床肿瘤学家(Seiden)和小鼠模型核心(Housman，Jack)我们将把新型传感器应用于 卵巢癌的常见问题。

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.