Antifouling biosensor technology for bioanalytical detection in precision medicine

用于精准医学生物分析检测的防污生物传感器技术

• 批准号: RGPIN-2017-05916
• 负责人: Thompson, Michael
• 金额: $ 1.38万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=710554
• 关键词: Antifouling; biosensor; technology; bioanalytical; detection

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.

精密药物是该领域相对较新的活动，它集中在特定患者所经历的疾病上。由于遗传和环境因素，病人因患者而异。 该医学领域的关键组成部分是特定疾病进展的测定法，包括早期检测的可能性。这涉及对疾病的生物标志物的定量确定，因为它们出现离子血，尿液和组织样品。例如，生物标志物是由肿瘤释放的，这些肿瘤释放出来，这些肿瘤是特定疾病（例如癌症）的存在，无论是传染性的遗传。 该提案描述了使用生物传感器技术对人血清中这种部分进行分析的研究。后者涉及靶生物标志物在电子传感器表面的结合。 在拟议的工作中，这种设备将基于超高频率声学物理。这种类型检测的一个特殊组成部分是在流体中进行操作的能力，如预计蛋白质大规模干扰的血清。该提案包括防止这种有害影响的策略。 描述了该技术的两个总体应用 - 一个是通过两种已知的生物标志物，溶血磷脂（LPA）和热休克蛋白10（HSP -10）对卵巢癌的早期检测。第二个是在乳腺癌开始时与转移过程相关的生物标志物的类似检测。 关于LPA，探针将是蛋白质凝胶素，该蛋白质将附着在防染色的声波传感器表面上。反过来，这将受到肌动蛋白的纳米金颗粒附着。然后，传感器将通过更换标记的肌动蛋白直接在人血清中检测LPA。对于HSP-10，探针将是为此目的而在汤普森实验室中开发的适体。第1阶段至4个患者样本可通过正式协议从多伦多公主医院获得。 LPA的生物传感器检测值将与LC-MS的值进行比较。 转移产物的生物传感器测定，甲状旁腺相关肽（PTHRP）将涉及三明治测定。在这种情况下，探针是激素的抗体片段。这将捕获血清中的靶标，并随后与标记为抗体的金颗粒相互作用。这种方法在ELISA技术中非常普遍。同样，可以通过官方协议从圣迈克尔医院获得乳腺癌患者的样本。