SBIR Phase I: High Throughput Characterization of Stem Cells using Spatial Domain Stimulus Response

这一小型企业创新研究(SBIR)第一阶段项目建议开发一种基于干细胞高通量无标记电场电位标记物的技术可行性。这项正在申请专利的空间域刺激响应(SDSR)技术记录了来自空间电极阵列的单个细胞的刺激响应，并重建了时域信号。这项使用SDSR高通量鉴定干细胞的提议将解决尚未满足的需求，即衍生患者特定的重新编程的体细胞，用于研究疾病的发展，创造疾病或障碍的治疗方法，并为在疾病中受到损害的人体系统细胞开发完美的模型。这将有助于在再生医学中实现干细胞分选的目标，以避免由于畸胎瘤形成、异常重编程和转基因的存在而造成的障碍。这项拟议的项目将为从阻碍移植性能的细胞中分离分化细胞奠定基础，而不需要进行外源标记或基因修改，用于临床应用。在这个项目中，分化细胞的电场电位记录将与基因表达标记物进行比较和关联，以评估其特征。如果该项目成功，该项目的更广泛的影响/商业潜力将是开发一种强大的、自动化的、快速的、成本效益高的无标记细胞分类器，并克服阻碍干细胞生物学成功转化为临床治疗的障碍。这种细胞分选可以产生无限的活细胞供应，改善了控制性、便携性，并降低了临床应用的成本。这可能会对改善人类健康和控制人类疾病产生重大影响。例如，该系统可能是一种潜在的工具，用于替换丢失的后代、重新髓鞘形成和支持神经退行性疾病(如肌萎缩侧索硬化症、帕金森氏病、阿尔茨海默病、亨廷顿病、中风、脊髓损伤等创伤性损伤)中面临风险的相邻细胞，并用于研究此类疾病的发展和进展。从2009年到2018年，这些疾病的组织工程和细胞治疗产品的全球市场将翻两番以上。具体地说，干细胞研究产品的市场估计为8.72亿美元，并以每年两位数的增长速度扩大，这意味着一个重要的财务机会。

This Small Business Innovation Research (SBIR) Phase I project proposes to develop the technical feasibility of a high throughput label-free electrical field potential marker-based characterization of stem cells. This patent-pending technology of Spatial Domain Stimulus Response (SDSR) records stimulus response from individual cells from an array of spatial electrodes and reconstruct time domain signals. This proposed high throughput characterization of stem cells using SDSR will address the unmet need of derivation of patient-specific reprogrammed somatic cells for use in studying disease development, creating therapies for diseases or disorders and developing perfect models for the cells of the human system that are harmed in the diseases. This will contribute to the goals in regenerative medicine in sorting stem cells in order to avoid the obstacles due to teratoma formation, aberrant reprogramming, and the presence of transgenes. This proposed project will be the basis for the isolation of differentiated cells from the cells that hinder graft performance without exogenous labeling or genetic modification for clinical applications. In this project, the electrical field potential recordings of differentiated cells will be compared and correlated with gene expression markers to assess the characterization.The broader impact/commercial potential of this project, if successful, will be the development of a powerful, automated, rapid, cost-effective label-free cell sorter, and overcome the barriers that prevent successful translation of stem cell biology into clinical therapy. This cell sorting can produce an unlimited supply of viable cells with improved control, portability, and reduced cost for clinical applications. This may have a significant impact for the improvement of human health and control of human diseases. For example, the system may be a potential tool for the replacement of lost progenies, remyelination and support of adjacent cells at risk in neurodegenerative disorders such as amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's diseases, Huntington's disease, stroke, traumatic lesions such as spinal cord injury, and for studying development and progression of such diseases. The global market for tissue engineering and cell therapy products for these diseases is set to more than quadruple from 2009 to 2018. Specifically, the market for stem cell research products is estimated to be $872M, and expanding through double digit growth each year, representing a significant financial opportunity.