Antifouling biosensor technology for bioanalytical detection in precision medicine

精准医学是该领域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，情况因人而异。这一医学领域的一个关键组成部分是分析特定疾病的进展，包括早期发现的可能性。这包括在血液、尿液和组织样本中出现疾病的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，表明存在特定的疾病，如癌症，无论是遗传性的还是感染性的。本提案描述了使用生物传感器技术测定人类血清中这些部分的研究。后者涉及目标生物标志物在电子换能器表面的结合。在提出的工作中，这种装置将基于超高频声学物理。这种类型的检测的一个特殊组成部分是在液体中操作的能力，如血清，其中预计会受到蛋白质的大规模干扰。这项建议包括一项防止这种有害影响的战略。

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.