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

这个小企业创新研究（SBIR）第一阶段项目提出开发高通量无标记电场电位标记的干细胞表征的技术可行性。这项正在申请专利的空间域刺激响应（SDSR）技术记录来自空间电极阵列的单个细胞的刺激响应，并重建时域信号。所提出的使用SDSR的干细胞的高通量表征将解决衍生患者特异性重编程体细胞以用于研究疾病发展、创建疾病或病症的疗法以及开发在疾病中受损的人类系统细胞的完美模型的未满足的需求。这将有助于实现再生医学中分选干细胞的目标，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。该项目将成为从阻碍移植物性能的细胞中分离分化细胞的基础，而无需外源性标记或遗传修饰用于临床应用。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进行比较和关联，以评估表征。如果成功，这个项目更广泛的影响/商业潜力将是开发一种功能强大，自动化，快速，成本效益高的无标记细胞分选仪，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供应的活细胞，具有改进的控制、便携性和降低的临床应用成本。 这可能对改善人类健康和控制人类疾病产生重大影响。例如，所述系统可以是用于在神经退行性疾病（例如肌萎缩性侧索硬化症、帕金森病、阿尔茨海默病、亨廷顿病、中风、创伤性损伤（例如脊髓损伤））中替换丢失的后代、髓鞘再生和支持处于危险中的相邻细胞的潜在工具，以及用于研究这些疾病的发展和进展。从2009年到2018年，用于这些疾病的组织工程和细胞治疗产品的全球市场将增长四倍以上。具体而言，干细胞研究产品的市场估计为8.72亿美元，每年以两位数的增长率扩大，这代表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.