Biomedical Engineering Core

摘要 可获取样本（血液、唾液、尿液等）中发现的循环标记物代表了一种令人兴奋的生物标志物 由于其微创性，潜在地，这些循环标记物可以使 旨在了解疾病的病理生理学并将这些发现转化为 通过匹配疾病的分子特征， 适当的治疗方案（即，精准医学）。循环标记物的吸引人的性质（即，液体 活检标记物）是在样品中发现的过多的标记物类型，例如生物细胞、无细胞的 分子（蛋白质和无细胞DNA）和细胞外囊泡（纳米组装体，如外来体）。 不幸的是，这些液体活检标记物的基础研究和临床转化一直具有挑战性， 缺乏用于分离它们有效平台，该平台也可以容纳下游分子 循环标记物货物的表征。KIPM将产生生物医学工程核心， 为COBRE研究人员提供变革性工具，包括硬件和相关的分析， 为手头的项目进行编程，并为研究者提供高质量的循环标记物， 各种分子表征分析（DNA/RNA下一代测序，蛋白质组学， 免疫测定、突变检测、液相色谱法/质谱法和许多其他方法）。的 硬件工具是芯片实验室或微流体平台，其已经被优化用于分离 循环标志物，并在各种应用领域进行临床验证。微流体工具还具有 BME核心成员开发的经过验证的检测方法和自动化工作流程。这些 工具具有值得注意的性能指标相比，市售产品直接为 分离循环标志物。微流体以高规模生产模式以低成本生产 因为它们由塑料制成并使用注塑成型形成适当的结构， 建立了生产CD、DVD和蓝光光盘的生产线。使用这些工具集， 核心将创建一个实验室，可以立即为COBRE研究人员提供精准医学服务 基于项目。由于BME核心采用的工具的独特功能，生成的数据集 由KIPM调查人员和独特的工具来获取这些数据集将提高他们的竞争力， 为他们的项目寻求联邦资金的支持。对于无法有效服务的COBRE项目， 核心的现有工具，核心将与项目PI设计新的工具，以适应他们的 该项目还将为BME核心添加新的流程功能。BME Core具有检测设计 能力和原型工具来支持这项活动。

Abstract Circulating markers found in accessible samples (blood, saliva, urine, etc.) represent an exciting biomarker class due to the minimally invasive nature of securing them. Potentially, these circulating markers can enable studies directed toward understanding the pathophysiology of a disease and translating those discoveries to the bedside for managing a host of human diseases by matching the molecular characteristics of the disease to proper treatment regimens (i.e., precision medicine). The attractive nature of circulating markers (i.e., liquid biopsy markers) is the plethora of marker types found in the sample such as biological cells, cell-free molecules (proteins and cell-free DNA) and extracellular vesicles (nanometer assemblies such as exosomes). Unfortunately, basic studies and clinical translation of these liquid biopsy markers has been challenging due to the lack of efficient platforms for their isolation that can also accommodate downstream molecular characterization of the circulating marker cargo. KIPM will generate the Biomedical Engineering Core that will provide to COBRE investigators transformative tools, including hardware and the associated assays, that can be programmed for the project at hand and provide to investigators high quality circulating markers to serve as inputs for a variety of molecular characterization assays (DNA/RNA Next Generation Sequencing, proteomics, immunoassays, mutation detection, liquid chromatography/mass spectrometry, and many others). The hardware tools are lab-on-a-chip or microfluidic platforms that have been optimized for the isolation of circulating markers and clinically validated in a variety of application areas. The microfluidic tools also have validated assays and an automated workflow that has been developed by members of the BME Core. These tools have noteworthy performance metrics compared to commercially available products directed for the isolation of circulating markers. The microfluidics are produced in a high scale production mode at low cost because they are made from plastics and formed into the appropriate structures using injection molding, an established production pipeline for producing CDs, DVDs and Blu-Ray discs. Using these tool sets, the BME Core will create a laboratory that can immediately service COBRE investigators on their precision medicine based projects. Due to the unique capabilities of the tools employed by the BME Core, the data sets generated by the KIPM investigators and the unique tools to acquire these data sets will improve their competitiveness in seeking federally-funded support of their projects. For COBRE projects that cannot be effectively serviced by the Core’s existing tools, the Core will work with the project PI to design new tools to accommodate their project that will also add new process capabilities to the BME Core. The BME Core has assay design capabilities and prototyping tools to support this activity.