Electrosonic Ejector Microarray for Development of Cancer Therapies

用于开发癌症疗法的电声喷射器微阵列

• 批准号: 7611743
• 负责人: John Mark Meacham
• 金额: $ 12.06万
• 依托单位: OPENCELL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2010-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611743
• 关键词: Address; Applied Research; Biological; Biological Assay; Brain Neoplasms; Cell Nucleus; Cell membrane; Cell physiology; Cells; Cellular biology; Chemicals; Communities; DNA; DNA delivery; Development; Device or Instrument Development; Devices; Diagnostic; Electrodes; Electroporation; Equipment; Foundations; Frequencies; Future; Gene Delivery; Genes; Glioblastoma; Health; Image; Investigation; Laboratories; Life; Manuals; Manufacturer Name; Marketing; Measures; Mechanics; Mediating; Methods; Microinjections; Microscopic; Monitor; Nanotechnology; Nucleic Acids; Operative Surgical Procedures; Performance; Pharmaceutical Preparations; Phase; Population; Positioning Attribute; Preparation; Process; RNA Interference; Recombinant Proteins; Research; Sample Size; Sampling; Small Business Innovation Research Grant; Small Interfering RNA; Suspension substance; Suspensions; System; Techniques; Technology; Therapeutic Uses; Transfection; Ultrasonics; Variant; Work; base; biomaterial compatibility; cancer cell; cancer therapy; cell type; clinical application; commercialization; conventional therapy; design; drug discovery; gene therapy; human disease; improved; interest; nanomaterials; novel; novel therapeutics; particle; public health relevance; research and development; research study; single molecule; sonoporation; success; symposium; therapy development; uptake; Address; Applied Research; Biological; Biological Assay; Brain Neoplasms; Cell Nucleus; Cell membrane; Cell physiology; Cells; Cellular biology; Chemicals; Communities; DNA; DNA delivery; Development; Device or Instrument Development; Devices; Diagnostic; Electrodes; Electroporation; Equipment; Foundations; Frequencies; Future; Gene Delivery; Genes; Glioblastoma; Health; Image; Investigation; Laboratories; Life; Manuals; Manufacturer Name; Marketing; Measures; Mechanics; Mediating; Methods; Microinjections; Microscopic; Monitor; Nanotechnology; Nucleic Acids; Operative Surgical Procedures; Performance; Pharmaceutical Preparations; Phase; Population; Positioning Attribute; Preparation; Process; RNA Interference; Recombinant Proteins; Research; Sample Size; Sampling; Small Business Innovation Research Grant; Small Interfering RNA; Suspension substance; Suspensions; System; Techniques; Technology; Therapeutic Uses; Transfection; Ultrasonics; Variant; Work; base; biomaterial compatibility; cancer cell; cancer therapy; cell type; clinical application; commercialization; conventional therapy; design; drug discovery; gene therapy; human disease; improved; interest; nanomaterials; novel; novel therapeutics; particle; public health relevance; research and development; research study; single molecule; sonoporation; success; symposium; therapy development; uptake

DESCRIPTION (provided by applicant): Despite decades of research focused mainly on gene transfection, effective intracellular delivery of biologically relevant material remains a difficult task, inhibiting research in a variety of biological and biomedical fields. This proposed work describes a commercially viable intracellular nanomaterial delivery device, the Electrosonic Ejector Microarray (EEM), that is optimized for drug and / or gene / nucleic acid and / or imaging agent delivery into cells via precise control of biophysical action (i.e., concurrent application of sono / mechanoporation, electroporation and thermoporation). The EEM is a novel microelectromechanical systems (MEMS)-enabled device that ejects a sample containing biological cells through microscopic nozzles with incorporated electroporation electrodes, thereby opening pores in the cell membrane via combined mechano / electroporation for uptake of nanomaterials.1 The high ultrasonic frequency of operation and a parallel (array) format enable fast processing of large cell populations at rates between 1 and 100 million cells per second; however, the device can potentially accommodate a wide range of sample sizes, from ~100 nL to arbitrarily large volumes when operated in continuous-flow mode. In addition, the device can be made disposable to eliminate cross-contamination and provides uniform (i.e., identical across an entire cell population) treatment on a single-cell level, which are critical capabilities for sample preparation in clinical applications of cell biology and gene therapy. The EEM is well-suited to basic / applied research, as well as diagnostic and therapeutic uses. Initial investigations will focus on cancer therapies combining mature recombinant protein therapies with emerging RNA interference (RNAi) technologies. The improved understanding of the relationship between the EEM operating parameters and realized bioeffects that will be gained through this proposed work is directly transferable to other application spaces. The primary objective of the proposed work is to develop a commercially viable EEM that demonstrates quantitative performance improvement over currently available nanomaterial delivery technologies. To achieve this objective, (1) an EEM platform that is optimized for cell treatment will be developed, (2) safe treatment of a variety of cell types and characterization of nanomaterial localization will be demonstrated, and (3) the transfection capabilities of the EEM will be optimized and its advantages over traditional transfection technologies quantified. PUBLIC HEALTH RELEVANCE: Development of the Electrosonic Ejector Microarray (EEM) will address the deficiencies of current intracellular drug / gene delivery techniques, which are inhibiting research in a variety of biological and biomedical fields. In particular, successful use of the EEM in development of therapies to treat glioblastomas, which are the most common and lethal brain tumors, will prove its feasibility in a wide range of drug discovery and gene therapy applications.

描述（由申请人提供）：尽管数十年的研究主要集中在基因转染上，但有效的生物学相关材料的细胞内递送仍然是一项艰巨的任务，抑制了各种生物学和生物医学领域的研究。这项提出的工作描述了一种商业上可行的细胞内纳米材料递送装置，电源弹出器微阵列（EEM），该设备可针对药物和 /或基因 /或成像剂通过精确控制生物物理作用（即，同时应用声音 /机械形成和热型，电子构造和电子构造，电动层构造），对药物和 /或基因 /或成像剂的递送进行了优化。 EEM是一种新型的微电机械系统（MEM）的设备，它通过与电动电极掺入的微型喷嘴弹出包含生物细胞的样品，从而在细胞膜中通过合并的机械 /电穿孔打开毛孔，以摄取纳米材料的高度频率和100个频率的频率（ENANANOMETIAL）。每秒百万个细胞；但是，该设备可以潜在地容纳各种样本量，从〜100 nl到任意大量的量，在连续流量模式下操作。此外，可以使该设备在消除交叉污染的情况下进行一次性，并在单细胞水平上提供均匀（即在整个细胞种群中相同）的均匀处理，这是在细胞生物学和基因治疗的临床应用中样本制备的关键能力。 EEM非常适合基础 /应用研究，以及诊断和治疗用途。初步研究将重点放在结合成熟重组蛋白疗法与新兴RNA干扰（RNAI）技术的癌症疗法上。对EEM操作参数与实现的生物效应之间将通过此拟议的工作获得的生物效应之间的关系的了解可以直接转移到其他应用程序空间。拟议工作的主要目的是开发一种商业上可行的EEM，该EEM证明了与当前可用的纳米材料递送技术相比的定量性能提高。为了实现这一目标，（1）将开发出优化用于细胞处理的EEM平台，（2）将证明对各种细胞类型的安全处理和纳米材料定位的表征，并且（3）EEM的转染能力将得到优化，并且其优势比传统的转型技术量化了。 公共卫生相关性：电源喷射器微阵列（EEM）的开发将解决当前细胞内药物 /基因递送技术的缺陷，这些技术抑制了各种生物学和生物医学领域的研究。特别是，成功地使用EEM在疗法开发治疗胶质母细胞瘤（最常见和致命的脑肿瘤）中将证明其在广泛的药物发现和基因治疗应用中的可行性。