Precision Multi-site Cellular Dosing using a Membrane-Based Laminar-Flow Device

使用膜层流装置进行精密多位点细胞给药

• 批准号: 7611665
• 负责人: Robyn Goforth
• 金额: $ 35万
• 依托单位: MINOTAUR TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611665
• 关键词: Ablation; Architecture; Caliber; Cell Adhesion; Cell Culture Techniques; Cell physiology; Cells; Cellular biology; Cessation of life; Characteristics; Chemicals; Chemotaxis; Computer software; Cytoskeleton; Development; Devices; Diagnosis; Differentiation and Growth; Dose; Electrophysiology (science); Environment; Equipment; Exhibits; Glioma; Goals; Hippocampus (Brain); Hybrids; Individual; Label; Lasers; Lead; Letters; Life; Maintenance; Manufacturer Name; Mediating; Medicine; Membrane; Metabolic; Methods; Microscope; Mitochondria; Modeling; Molecular; Mus; Names; Neuroblastoma; Neurons; Neurosciences; Organism; Pharmaceutical Preparations; Phase; Phenotype; Physiologic pulse; Physiological; Primary Cell Cultures; Rattus; Resolution; Sales; Scientific Advances and Accomplishments; Signal Pathway; Signal Transduction; Site; Small Business Innovation Research Grant; Staining method; Stains; Stimulus; Stream; Supporting Cell; Surface; System; Technology; Testing; Time; Width; Work; base; cell growth; cost; design; improved; in vitro testing; instrument; pressure; prototype; public health relevance; response; stem cell differentiation; submicron

DESCRIPTION (provided by applicant): The proposed Phase I SBIR project is to show the feasibility of developing an affordable commercial instrument that provides laminar-flow fluidic interfaces to cell cultures at multiple coordinates in real time. The instrument will satisfy a growing, unmet need for a method that allows superior spatio-temporal control over the interactions between chemical dosants and cells using inexpensive materials and equipment. Spatio-temporal control is critical to examining interactions between chemical dosants and cells, especially in studies focused on polarized responses within individual cells such as directional chemotaxis. Minotaur Technologies' approach is based on the rapid laser-mediated creation of apertures within a membrane that serves as a support for cell growth and also separates two flow chambers - one of which is a cell medium chamber, and the other, a dosing chamber. This use of laser-induced dielectric breakdown as a means to machine surface pores allows for a precisely-directed laminar flow stream from the higher pressure dosing chamber into the cell environment such that only certain selected cells or cell regions are dosed with the desired chemical species. In the Phase I project Minotaur will demonstrate the feasibility of dosing cells with a dosant region resolution down to 2 micrometers and show the benefits of the technology for important neuroscience applications. Although we understand much of what goes on inside cells at a molecular level, understanding of how cells function as a whole lags far behind. Frequently, the study of living cells is hampered by lack of appropriate technologies. Scientific advances depend not only on new ideas, but also on technological advances that make conceptual shifts possible. Chemical dosing of live cells with agents that selectively alter cellular function in a controlled fashion provides a vital means to study cellular differentiation, growth, and death. The instrument developed will be applicable to a broad range of cell biology problems in neuroscience and beyond, including chemotaxis, stem-cell differentiation and in vitro testing of cellular response to emerging treatments. Public Health Relevance: A fundamental component of cellular organisms is the ability of cells to sense and respond to their environment. Elucidating the mechanisms of cellular responses to external stimuli and how cell-to-cell signaling pathways coordinate cellular activities is key to understanding how cells work. The improved understanding of cellular responses in both healthy and diseased states that may be gained from use of the proposed instrument could lead to development of more effective medicines and methods of diagnosis.

描述（由申请人提供）：拟定的I期SBIR项目旨在证明开发经济实惠的商业仪器的可行性，该仪器可在多个坐标处真实的时间向细胞培养物提供层流流体界面。该仪器将满足日益增长的，未满足的需要的方法，允许上级时空控制之间的相互作用的化学dosants和细胞使用廉价的材料和设备。时空控制对于研究化学剂量和细胞之间的相互作用至关重要，特别是在专注于单个细胞内的极化反应（如定向趋化性）的研究中。Minotaur Technologies的方法是基于在膜内快速激光介导的孔的创建，该膜用作细胞生长的支撑，并且还分隔两个流动室-其中一个是细胞培养基室，另一个是剂量室。激光诱导介电击穿作为加工表面孔的手段的这种使用允许从高压计量室到电池环境中的精确定向的层流流，使得仅某些选定的电池或电池区域被计量有所需的化学物质。在第一阶段项目中，Minotaur将展示剂量区域分辨率低至2微米的细胞给药的可行性，并展示该技术对重要神经科学应用的好处。虽然我们在分子水平上了解了细胞内发生的许多事情，但对细胞整体功能的理解远远落后。对活细胞的研究常常因缺乏适当的技术而受到阻碍。科学的进步不仅取决于新的想法，也取决于使观念转变成为可能的技术进步。以可控方式选择性改变细胞功能的试剂对活细胞进行化学给药，为研究细胞分化、生长和死亡提供了重要手段。开发的仪器将适用于神经科学及其他领域的广泛细胞生物学问题，包括趋化性，干细胞分化和对新兴治疗的细胞反应的体外测试。公共卫生相关性：细胞生物体的一个基本组成部分是细胞感知和响应环境的能力。阐明细胞对外部刺激的反应机制以及细胞间信号通路如何协调细胞活动是理解细胞如何工作的关键。通过使用所提出的仪器，可以更好地了解健康和疾病状态下的细胞反应，从而开发出更有效的药物和诊断方法。