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（由申请人提供）：乳腺癌在疾病的早期阶段通常无症状。目前最先进的筛查工具，如乳房X线摄影和乳房检查，由于没有肿块病变而错过了早期乳腺癌，在检测年轻女性的癌症方面无效，并且需要侵入性活检。需要新的方法来补充目前用于癌前和癌性乳腺病变的检测和预后的方法，同时它们是小的并且更容易治疗。对乳头抽吸液中分泌的糖抗原、蛋白抗原和非编码microRNA（miRNA）的分析代表了一种非常有前途的方法，能够直接在反映乳腺组织特异性肿瘤微环境的体液中检测癌症相关生物标志物。我们的长期目标是开发一个简单、灵敏和强大的检测平台，用于在无症状的早期阶段诊断疾病。我们的诊断平台是基于生物马达的优雅而精致的蛋白质通道。我们已经将马达通道插入到脂质双层中，并且当分析物与通道相互作用时，所得到的系统表现出稳健的特性并产生极其灵敏、稳定和可再现的电导特征。我们进一步证明了其作为在单分子水平上检测许多污染物存在下的癌症相关蛋白的高灵敏度装置的实用性。该提案的短期目标是将该运动通道开发为纳米孔，用于从乳腺癌患者乳头抽吸液中提取的糖抗原、蛋白抗原和miRNA生物标志物的高通量单分子检测。该平台包括：作为高灵敏度纳米孔的膜嵌入的马达通道;用于捕获乳腺癌相关抗原的可编程探针;以及用于多路高通量单分子检测的超灵敏电生理学设置。将我们的设备应用于常规实践将使医生能够在乳腺导管发展成更大的潜在癌性病变之前更早地监测乳腺导管内的细胞变化。