Microfluidic Chip for Genome Analysis

用于基因组分析的微流控芯片

• 批准号: 8401300
• 负责人: Heinz-Ulrich Guenter Weier
• 金额: $ 23.5万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-07 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8401300
• 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; Genome; 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; granulosa cell; innovation; malignant breast neoplasm; meetings; multidisciplinary; neoplastic cell; novel; point of care; prototype; technology development; tool; tumor

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. PUBLIC HEALTH RELEVANCE: For accurate diagnosis, many situations require the assessment of not just one, but a combination of several different types of disease biomarkers. This multidisciplinary bioengineering project seeks to develop an inexpensive, versatile technology platform to detect and quantitate multiple biomarkers such as a combination of chromosomal alterations and aberrant gene expression in clinical samples.

描述(申请人提供)：疾病的生物标志物以各种形式存在，例如数字或结构染色体异常、表观遗传因素或基因表达改变、血液成分异常水平或翻译后修饰。对治疗反应的准确诊断和预测往往不能依靠单一的生物标记物，而是几种可能非常不同类型的标记物的组合。这一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)。为了支持在辅助人类生殖和癌症研究和治疗方面的诊断努力，这个经验丰富的研究团队试图开发一种DMFC，能够将单个细胞固定在指定的位置(目标1)，询问多个遗传位点以灵敏地检测临床样本中的数目和结构染色体异常(目标2-3)，以及对基因转录本或肿瘤特异性microRNAs进行半定量分析(目标4)。虽然这个R21项目将研究在少数甲状腺和乳腺癌细胞中测量多个潜在疾病生物标记物的可行性，包括易位、基因扩增和最多三个肿瘤特异性microRNA的表达，但芯片设计可以很容易地进行修改，以适应不同的应用，例如在辅助人类生殖(ART)中的非侵入性基因表达谱分析，以预测卵母细胞的能力和胚胎存活。因此，这项可行性研究的成功完成将使我们拥有一个通用的DMFC原型，以便在后续的研究中开发出更多面向临床的方案。 与公共卫生相关：为了准确诊断，许多情况需要评估几种不同类型的疾病生物标志物，而不是单一的一种。这个多学科的生物工程项目寻求开发一个廉价、通用的技术平台来检测和定量多个生物标记物，如临床样本中的染色体改变和异常基因表达的组合。