Phi29 motor nanopore for single molecule sensing

用于单分子传感的 Phi29 马达纳米孔

• 批准号: 9106837
• 负责人: PEIXUAN GUO
• 金额: $ 35.88万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9106837
• 关键词: Affinity; Antigens; Binding; Biological; Biological Markers; Biopolymers; Biopsy; Body Fluids; Breast; Breast Cancer Detection; Breast Cancer Early Detection; Breast Cancer Patient; Cancer Detection; Cancerous; Cancerous breast; Cell Line; Cells; Clinical; Complement; Detection; Devices; Diagnosis; Diagnostic; Disease; Duct (organ) structure; Ductal; Early treatment; Electrophysiology (science); Engineering; Epithelial Cells; Equipment; Exhibits; Fingerprint; Galectin 3; Goals; Individual; Label; Lesion; Ligand Binding; Lipid Bilayers; Liquid substance; Lobular; Malignant Neoplasms; Mammary Gland Parenchyma; Mammography; Membrane; Methodology; Methods; MicroRNAs; Monitor; Motor; Nanotechnology; Nature; Nipples; Nucleotides; Oncologist; Patients; Peptides; Phage Display; Physicians; Plasminogen Activator; Premalignant; Procedures; Process; Property; Proteins; Sampling; Seeds; Sensitivity and Specificity; Serum; Shapes; Signal Transduction; Source; Staging; System; Time; Translating; Translations; Untranslated RNA; Urokinase; Woman; base; breast cancer diagnosis; breast lesion; cancer biomarkers; chemical fingerprinting; circulating microRNA; disease diagnosis; inhibitor/antagonist; large scale production; locked nucleic acid; malignant breast neoplasm; microRNA biomarkers; nano; nanopore; nipple aspirate fluid; outcome forecast; public health relevance; rapid detection; response; routine practice; screening; single molecule; tool; tumor microenvironment; young woman

 DESCRIPTION (provided by applicant): Breast cancer is generally asymptomatic at early stages of the disease. Current state of the art screening tools such as mammography and breast examination miss early breast cancers due to the absence of mass lesions, are ineffective in detecting cancer in young women, and require invasive biopsy. New methods are needed to complement current methods for the detection and prognosis of precancerous and cancerous breast lesions while they are small and more easily treated. The analysis of the secreted glycoantigens, protein antigens and non-coding microRNAs (miRNA) in nipple aspirate fluid represents a very promising approach able to detect cancer-related biomarkers directly in body fluids mirroring the breast tissue-specific tumor microenvironment. Our long term goal is to develop a simple, sensitive and robust detection platform for diagnosing diseases at an asymptomatic early stage. Our diagnostic platform is based on the elegant and elaborate protein channel of a biological motor. We have inserted the motor channel into a lipid bilayer and the resulting system exhibits robust properties and generates extremely sensitive, stable and reproducible conductance signatures when analytes interact with the channel. We further demonstrated its utility as a highly sensitive device for detection of cancer-associated proteins i presence of many contaminants at single molecule level. The short-term goal of this proposal is to develop this motor channel as a nanopore for high-throughput single molecule detection of glyco-antigen, protein antigen and miRNA biomarkers extracted from breast cancer patient nipple aspirate fluid. The platform consists of: a membrane-embedded motor channel serving as a highly sensitive nanopore; programmable probes for capturing breast cancer associated antigens; and ultra-sensitive electrophysiological setup for multiplexed high-throughput single molecule detection. Incorporating our device into routine practice will enable physicians to monitor cellular changes within breast ducts earlier, before they develop into larger, potentially cancerous lesions.

 描述（由适用提供）：乳腺癌在疾病的早期阶段通常是不对称的。由于缺乏肿块病变，乳房X线摄影和乳房检查等最新筛查工具的现状缺失了早期的乳腺癌，无法检测年轻女性的癌症，需要侵入性活检。需要新的方法来完成当前方法，以便在小且更容易治疗的同时检测和预后。对分泌的甘氨酸，蛋白质抗原和非编码microRNA（miRNA）的分析是一种非常有前途的方法，能够直接在体液中检测到癌症相关的生物标志物，直接反映了乳房组织特异性肿瘤微环境。我们的长期目标是在不对称的早期阶段开发一个简单，敏感和健壮的检测平台，以供诊断疾病。我们的诊断平台基于生物电机的优雅蛋白质通道。我们已经将电动机通道插入脂质双层中，当分析与通道相互作用时，所得系统表现出强大的特性，并产生极其敏感，稳定和可再现的电导特征。我们进一步证明了它是一种高度敏感的装置，用于检测与癌症相关的蛋白I在单分子水平上存在许多污染物。该提案的短期目标是将这种运动通道作为纳米孔开发，用于从乳腺癌患者乳头抽吸液中提取的高通量单分子检测糖 - 抗原，蛋白质抗原和miRNA生物标志物。该平台由：一个膜上的运动通道，可作为高度敏感的纳米孔；可编程探针，用于捕获乳腺癌相关的抗原；用于多重高通量单分子检测的超敏感电生理设置。将我们的设备纳入常规实践将使医生能够在乳房管道内的细胞变化中，然后才能发展成更大的，可能取消的病变。