Microfluidic Chip for Genome Analysis

用于基因组分析的微流控芯片

基本信息

批准号：
8525360
负责人：
Heinz-Ulrich Guenter Weier
金额：
$ 18.77万
依托单位：
UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
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：
2012-08-07 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8525360
关键词：
Affect Area Benign Biological Assay Biological Markers Biomedical Engineering Blood Breast Breast Cancer Cell Cancer Patient Carcinoma Cell Count Cell Cycle Stage Cell Line Cell Nucleus Cells Chromatin Chromosome abnormality Chromosomes, Human, Pair 12 Classification Clinical Clinical Research Competence Conceptus Cytogenetic Analysis Cytogenetics Cytoplasm Cytosol DNA DNA Probes DNA Sequence Rearrangement Detection Development Devices Diagnosis Diagnostic Differential Diagnosis Disease Embryo Epigenetic Process Feasibility Studies Fertilization in Vitro Fine-needle biopsy Fluorescent in Situ Hybridization Freezing Gene Amplification Gene Deletion Gene Expression Gene Expression Profiling Gene Rearrangement Generations Genes Genetic Glass Harvest Human In Situ Individual Interphase Cell Investigation Karyotype Label Lesion Live Birth Location Longevity Malignant - descriptor Malignant neoplasm of thyroid Measures Mesenchymal Metaphase Methodology Methods MicroRNAs Microfluidics Molecular Profiling Numerical Chromosomal Abnormality Oocytes Patients Phenotype Placenta Positioning Attribute Post-Translational Protein Processing Prediction of Response to Therapy Pregnancy Premalignant Proto-Oncogenes Protocols documentation Puncture biopsy Radiation Reproduction Research Research Personnel Resolution Sampling Slide Specimen Stretching Structural Chromosomal Abnormality Supporting Cell Techniques Technology Testing Thick Thyroid Adenoma Time Tissue Sample Tissues Transcript Work anticancer research base cancer diagnosis cancer therapy clinical practice design disease diagnosis experience genome analysis granulosa cell innovation malignant breast neoplasm meetings multidisciplinary neoplastic cell novel point of care prototype technology development tool tumor

项目摘要

DESCRIPTION (provided by applicant): Biomarkers for disease exist in a variety of forms such as numerical or structural chromosome aberrations, epigenetic factors or altered gene expression, abnormal levels of blood constituents or post-translational modifications. Often accurate diagnosis and prediction of response to therapy cannot rely on a single biomarker, but a combination of several, potentially very different types of markers. This multidisciplinary bioengineering project targets the development of a versatile, inexpensive technology platform termed 'disposable microfluidic chip' (dMFC). To support diagnostic efforts in assisted human reproduction and cancer research and therapy, this team of experienced investigators seeks to develop a dMFC capable of immobilizing individual cells in defined positions (Aim 1), interrogating multiple genetic loci for sensitive detection of numerical and structural chromosome aberrations in clinical samples (Aims 2-3) as well as the semi- quantitative analysis of gene transcripts or tumor-specific microRNAs (Aim 4). While this R21 project will investigate the feasibility of measuring multiple potential disease biomarkers including translocations, gene amplifications and expression of up to three tumor-specific microRNAs in small numbers of thyroid and breast cancer cells, the chip design can easily be modified to suit different applications such as noninvasive gene expression profiling in assisted human reproduction (ART) to predict oocyte competence and embryo survival. Thus, the successful completion of this feasibility study will equip us with a versatile prototype dMFC to develop more clinically oriented protocols in subsequent studies.

描述（由申请人提供）：疾病的生物标志物以多种形式存在，例如数值或结构染色体畸变、表观遗传因素或改变的基因表达、血液成分的异常水平或翻译后修饰。通常，准确的诊断和治疗反应的预测不能依赖于单一的生物标志物，而是依赖于几种可能非常不同类型的标志物的组合。这个多学科生物工程项目的目标是开发一种多功能、廉价的技术平台，称为“一次性微流控芯片”(dMFC)。为了支持辅助人类生殖以及癌症研究和治疗方面的诊断工作，这支经验丰富的研究人员团队致力于开发一种 dMFC，能够将单个细胞固定在确定的位置（目标 1），询问多个遗传位点，以灵敏地检测染色体的数值和结构畸变临床样本（目标 2-3）以及基因转录本或肿瘤特异性 microRNA 的半定量分析（目标 4）。虽然这个 R21 项目将研究测量多种潜在疾病生物标志物的可行性，包括易位、基因扩增以及少量甲状腺和乳腺癌细胞中多达三种肿瘤特异性 microRNA 的表达，但芯片设计可以轻松修改以适应不同的应用例如人类辅助生殖 (ART) 中的非侵入性基因表达谱分析，以预测卵母细胞能力和胚胎存活率。因此，这项可行性研究的成功完成将为我们提供一个多功能的原型 dMFC，以便在后续研究中开发更多面向临床的方案。