LASER CELL PROCESSING FOR BASIC AND CLINICAL RESEARCH

用于基础和临床研究的激光细胞处理

• 批准号: 6619751
• 负责人: MANFRED R KOLLER
• 金额: $ 177.54万
• 依托单位: CYNTELLECT, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6619751
• 关键词: bioengineering /biomedical engineering; bioimaging /biomedical imaging; biomedical equipment development; cell sorting; cytodiagnosis; image processing; lasers; optics; tissue /cell preparation

Photosis is a technology platform that incorporates high-speed optical scanning of biological samples, image analysis, and computer-controlled laser-irradiation of specific targets within the sample for the purpose of inducing a biological response. Specific cells to be treated within a mixed population are identified by parameters such as size, shape, fluorescence, or other distinguishing features. Once identified, individual cells are targeted with a laser to induce a desired response, such as cell death, optoporation (for gene transfer), or even inactivation of a specific mRNA transcript within the cell. The current beta1-prototyle system can process hundreds of millions of cells in an hour under sterile conditions, making it useful for several research and clinical applications. In fact, this prototype has several advantages over other methods of cell processing such as flow cytometry, and this conclusion is supported by preliminary data shown within. Photosis has many potential uses, and this proposal brings together a number of institutions and researchers to investigate and define the possible applications of this novel technology. In its current configuration, the instrument uses a single color for cell detection and a laser to induce necrosis in every targeted cell. These capabilities enable the first application, which is tumor cell purging from autologous NHL stem cell transplants, because such contaminating tumor cells are known to contribute to disease relapse. Additional applications will be developed, some of which will require modifications to the system design and building of new prototypes. The prototypes will be placed at four partnership sites where the basic and clinical applications research will be carried out, including: 1) in vivo study of purified stem cell subpopulations in the xenogeneic fetal sheep transplant model; 2) human clinical trials to assess NHL purging in autologous stem cell transplantation; 3) purification of genetically- modified stem cells and T-cells expressing a selectable transgene, as well as selective transduction of specific cells in a mixture via optoporation; and 4) accurate mRNA expression profiling from purified primary human prostate cancer cell populations. PROPOSED COMMERCIAL APPLICATION: The proposed work will result in several types of novel bioengineering instrumentation for advancing the state-of-the-art in cell processing. These instruments will be used in this program to advance basic and clinical research in stem cell biology, cancer, immunology, and genomics. Once developed, the resulting technology will be useful in other areas as well, some of which are described within.

Photosis是一个技术平台， 生物样品的光学扫描、图像分析和计算机控制 对样品内的特定目标进行激光照射， 引发生物反应在混合细胞内处理的特定细胞 种群通过诸如大小、形状、荧光或 其他区别特征。一旦被识别，单个细胞被靶向 用激光诱导所需的反应，如细胞死亡，光致发光， (for基因转移），或甚至使细胞内的特定mRNA转录物失活。 牢房目前的beta1-prototyle系统可以处理数亿个 细胞在无菌条件下一个小时，使其适用于几个 研究和临床应用。事实上，这个原型有几个 优于其他细胞处理方法如流式细胞术的优点，以及 这一结论得到了所列初步数据的支持。光合作用具有 许多潜在的用途，这一建议汇集了一些机构 和研究人员来调查和定义这种可能的应用 新技术在其当前配置中，仪器使用单个 用于细胞检测的颜色和用于在每个靶细胞中诱导坏死的激光。 这些功能使第一个应用程序，这是肿瘤细胞清除 来自自体NHL干细胞移植，因为这种污染性肿瘤 已知细胞有助于疾病复发。其他应用程序将 其中一些将需要修改系统设计， 建立新的原型。原型将被放置在四个伙伴关系 将开展基础和临床应用研究的地点， 包括：1）在体内研究纯化的干细胞亚群， 异种胎羊移植模型; 2）评估NHL的人类临床试验 自体干细胞移植中的净化; 3）遗传- 修饰的干细胞和表达可选择转基因的T细胞，以及 通过光穿孔选择性转导混合物中的特定细胞;以及 4)从纯化的原代人前列腺中获得精确的mRNA表达谱 癌细胞群。 拟定商业应用： 拟议的工作将导致几种类型的新型生物工程仪器 来推动细胞处理的发展。这些仪器将被使用 该项目旨在推进干细胞生物学、癌症 免疫学和基因组学一旦开发出来，由此产生的技术将是 在其他领域也很有用，其中一些在中描述。

项目成果

Scanning cytometry with a LEAP: laser-enabled analysis and processing of live cells in situ.

使用 LEAP 扫描细胞术：利用激光对活细胞进行原位分析和处理。

• DOI: 10.1002/cyto.a.20291
• 发表时间: 2006
• 期刊: Cytometry. Part A : the journal of the International Society for Analytical Cytology
• 作者: Szaniszlo,Peter;Rose,WilliamA;Wang,Nan;Reece,LisaM;Tsulaia,TamaraV;Hanania,ElieG;Elferink,CornelisJ;Leary,JamesF
• 通讯作者: Leary,JamesF