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.

精准医学是该领域相对较新的活动，专注于特定患者所经历的疾病。由于遗传和环境因素，每个患者的病情都有所不同。 该医学领域的一个关键组成部分是对特定疾病进展的分析，包括早期检测的可能性。这涉及到血液、尿液和组织样本中出现的疾病生物标志物的定量测定。例如，生物标志物是由肿瘤释放的物种，它们发出信号表明特定疾病（例如癌症）的存在，无论是遗传性还是传染性类型。 该提案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。后者涉及目标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声学物理学。此类检测的一个特殊组成部分是能够在血清等液体中进行操作，预计会受到蛋白质的大规模干扰。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 - 一是通过 2 种已知的生物标志物溶血磷脂 (LPA) 和热休克蛋白 10 (HSP-10) 进行卵巢癌的早期检测。第二个是在乳腺癌发生的背景下对与转移过程相关的生物标志物进行类似检测。 对于 LPA，探针将是附着在防污声波传感器表面的蛋白质凝溶胶。这将依次与肌动蛋白进行纳米金颗粒附着。然后，传感器将通过替换标记的肌动蛋白来直接检测人血清中的 LPA。对于 HSP-10，探针将是 Thompson 实验室为此目的开发的适体。根据官方协议，可从多伦多玛格丽特公主医院获得第一至第四阶段的患者样本。 LPA 生物传感器检测值将与 LC-MS 检测值进行比较。 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检测。本例中的探针是激素的抗体片段。这将从血清中捕获靶标，并随后与金颗粒标记的抗体相互作用。这种方法在 ELISA 技术中非常常见。同样，根据官方协议，可以从圣迈克尔医院获得乳腺癌患者的样本。