Antifouling biosensor technology for bioanalytical detection in precision medicine

精准医学是该领域的一项相对较新的活动，专注于特定患者所经历的疾病。由于遗传和环境因素，患者的病情各不相同。这一医学领域的一个关键组成部分是对特定疾病的进展进行分析，包括及早发现的可能性。这涉及到当疾病的生物标记物出现离子血液、尿液和组织样本时对其进行定量测定。例如，生物标记物是由肿瘤释放的物种，表明存在特定的疾病，如癌症，无论是传染性类型的基因。这项建议描述了使用生物传感器技术测定人血清中此类部分的研究。后者涉及将目标生物标记物结合在电子换能器的表面。在拟议的工作中，这样的设备将基于超高频声物理。这种类型的检测的一个特殊组件是能够在预计会受到蛋白质大规模干扰的液体中操作，如血清。这项提议包括一项防止这种有害影响的战略。*描述了这项技术的两个总体应用-一个是通过两个已知的生物标志物，溶血磷脂(LPA)和热休克蛋白10(HSP-10)对卵巢癌的早期检测。第二个是在乳腺癌发生的背景下，与转移过程相关的生物标志物的类似检测。对于LPA，探头将是附着在防污声波传感器表面的蛋白质明胶。这将反过来受到纳米金颗粒与肌动蛋白的附着。然后，传感器将通过替换标记的肌动蛋白直接检测人血清中的LPA。对于HSP-10，探测器将是汤普森实验室为此目的开发的适体。第一阶段到第四阶段的患者样本可以通过官方协议从多伦多玛格丽特公主医院获得。生物传感器检测LPA的值将与LC-MS的值进行比较*转移产物甲状旁腺激素相关肽(PTHrP)的生物传感器检测将涉及夹心法。在这种情况下，探针是荷尔蒙的抗体片段。这将从血清中捕获目标，并随后与金颗粒标记的抗体相互作用。这种方法在酶联免疫吸附试验技术中非常常见。同样，经官方同意，圣迈克尔医院也提供了乳腺癌患者的样本。

Precision medicine is a relatively new activity in the field that concentrates on the disease experienced by a particular patient. Conditions vary from patient to patient because of genetic and environmental factors. A key component of this area of medicine is the assay of progression of a specific disease including the possibility for early detection. This involves the quantitative determination of biomarkers for the disease as they appear ion blood, urine and tissue samples. Biomarkers are species , for example, that are released by tumors that signal the presence of particular disease such as cancer, whether of a genetic of infectious type. This proposal describes research towards the assay of such moieties in human serum using biosensor technology. The latter involves the binding of the target biomarker at the surface of an electronic transducer. In the proposed work, such a device will be based on ultra-high frequency acoustic physics. A special component of this type of detection is the capability for operation in fluids such serum where large scale interference from proteins is anticipated. This proposal includes a strategy to prevent this deleterious effect. ***Two overall applications of the technology are described - one is the early stage detection of ovarian cancer via the 2 known biomarkers, lysophosphatidic (LPA) and heat shock protein 10 (HSP-10). The second is the analogous detection of a biomarker connected to the process of metastasis in the context of the inception of breast cancer. With respect to LPA the probe will be the protein gelsolin which will be attached to an antifouling acoustic wave sensor surface. This will in turn will be subjected to nano-gold particle attachment with actin. The sensor will then detect LPA directly in human serum via replacement of the labeled actin. For HSP-10 the probe will be aptamers developed for this purpose in the Thompson lab. Stage 1 through 4 patient samples are available from Princess Margaret Hospital in Toronto through an official agreement. Values from biosensor detection for LPA will be compared with those from LC-MS.***The biosensor assay for the metastasis product, parathyroid hormone related peptide (PTHrP), will involve a sandwich assay. The probe in this case is an antibody fragment for the hormone. This will trap the target from serum and for subsequent interaction with gold particlee labeled antibody. This approach is very common in ELISA technology. Again, sample from breast cancer patients are available from St. Michael's Hospital by official agreement.