Novel Surfaces for Enriching Epithelial Cells: A Breastmilk Model

用于富集上皮细胞的新型表面：母乳模型

基本信息

批准号：
8242351
负责人：
MARIA M. SANTORE
金额：
$ 20.22万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8242351
关键词：
Accounting Address Adhesives Adsorption Antibodies Binding Body Fluids Breast Breast Cancer Early Detection Buffers Cancer cell line Cancerous Carcinoma Cell Adhesion Cell Fraction Cell Line Cell Separation Cell surface Cells Charge Childbirth Collecting Cell Collection DNA Detection Development Discrimination Early Diagnosis Early treatment Economic Development Elements Engineering Epithelial Epithelial Cells Exclusion Exploratory/Developmental Grant Fatty acid glycerol esters Flow Cytometry Foundations Future Harvest Human Human Milk Immunoglobulin Fragments Incidence Individual Lactation Liquid substance Literature Lymphocyte Malignant Neoplasms Malignant neoplasm of lung Measures Methods Methylation Microfluidic Microchips Microfluidics Milk Minor Modeling Modification Molecular Molecular Analysis Mucous body substance Pattern Performance Physiological Polymers Population Process Property Proteins Risk Risk Assessment Saliva Scheme Screening for cancer Screening procedure Specimen Surface Suspension substance Suspensions System Technology Testing Time Tissues Training Translating Urine Woman Work base biocompatible polymer cancer risk cancer therapy cancer type cell type combat design innovation instrumentation malignant breast neoplasm mortality nanoparticle nanoscale neuronal cell body novel programs research study scale up success

项目摘要

DESCRIPTION (provided by applicant): Harvesting and concentrating epithelial cells from body fluids is a challenging (expensive and time-consuming) but important task required for translational advances in the early-detection and treatment of cancer, since many cancer types involve epithelial cells. As an example, a highly promising and accurate risk detection method for breast cancer, based on changes in the DNA of breast epithelial cells found in human milk, requires purification and concentration of these cells, and exclusion of lymphocytes, fats, and proteins that are prevalent in milk. Because the necessary immediate epithelial enrichment process is costly in terms of labor, instrumentation, and lab supplies (antibody-coated beads), alternate methods of epithelial cell collection and concentration are needed. The proposed program will develop surfaces capable of selectively adhering epithelial cells from milk and rejecting the undesired cell fractions and molecules. The potential impact of this separation scheme comes from the innovative features of the surfaces themselves: robust and economical nano-scale adhesive elements such as polymer coils and immobilized nanoparticles are employed instead of expensive and fragile biomolecular fragments and antibodies. These sophisticated surfaces could be deployed in highly sensitive microfluidic devices or on beads, which could be used in the field by individuals who lack highly specialized training. The screening methods made possible by these innovative surfaces are expected to have wide accessibility and therefore broad positive impact for early detection of breast cancer. At the same time the surface design strategies developed in this program could, with minor modification, be applied to the creation of additional surfaces targeting cancer and pre-cancerous cell changes in other epithelial tissues, collected from urine, saliva, and mucus. PUBLIC HEALTH RELEVANCE: This proposal will develop novel surfaces that selectively adhere epithelial cells from suspensions and human breast milk, to enable their subsequent analysis for molecular indicators of breast cancer or cancer risk. The surfaces are innovative because they will achieve selective binding of targeted cells using immobilized nano-scale adhesive elements rather than biomolecular fragments or antibodies. The surfaces developed in this proposal can be refined for other body fluids besides milk, and form the foundation for scaled-up portable cell enrichment technologies that increase the accessibility of early risk assessment to a broader population of women.

描述（由申请人提供）：从体液中收获和浓缩上皮细胞是一项具有挑战性（昂贵且耗时）但对于癌症早期检测和治疗的转化进展所需的重要任务，因为许多癌症类型涉及上皮细胞。例如，一种非常有前途且准确的乳腺癌风险检测方法，基于人乳中乳腺上皮细胞 DNA 的变化，需要纯化和浓缩这些细胞，并排除淋巴细胞、脂肪和蛋白质多见于牛奶中。由于必要的立即上皮细胞富集过程在劳动力、仪器和实验室用品（抗体包被的珠子）方面成本高昂，因此需要上皮细胞收集和浓缩的替代方法。拟议的计划将开发能够选择性地粘附牛奶中的上皮细胞并拒绝不需要的细胞成分和分子的表面。这种分离方案的潜在影响来自于表面本身的创新特征：采用坚固且经济的纳米级粘合元件，例如聚合物线圈和固定纳米粒子，而不是昂贵且脆弱的生物分子片段和抗体。这些复杂的表面可以部署在高度敏感的微流体装置或珠子上，这些装置可以由缺乏高度专业化培训的个人在现场使用。这些创新表面使筛查方法成为可能，预计将具有广泛的可及性，从而对乳腺癌的早期检测产生广泛的积极影响。与此同时，该项目中开发的表面设计策略只需稍作修改，即可应用于创建针对从尿液、唾液和粘液中收集的其他上皮组织中的癌症和癌前细胞变化的额外表面。公共健康相关性：该提案将开发新型表面，选择性地粘附悬浮液和母乳中的上皮细胞，以便随后分析乳腺癌或癌症风险的分子指标。该表面具有创新性，因为它们将使用固定的纳米级粘合元件而不是生物分子片段或抗体来实现目标细胞的选择性结合。该提案中开发的表面可以针对除牛奶之外的其他体液进行改进，并构成扩大便携式细胞富集技术的基础，从而增加更广泛的女性群体早期风险评估的可及性。