SBIR Phase I: Electrophysiology and fluidic delivery with a nano patch-clamp probe

这个小型企业创新研究 (SBIR) 第一阶段项目旨在开发一种微机械膜片钳探针，通过控制 pN 水平的施加力，实现纳米级的亚细胞成像、电生理学和流体输送。探针可以像力感应手指一样操作来感应接触和膜破裂，不再损坏细胞。小孔径允许对离子通道进行显微注射和询问。可以获得成像、离子通道定位/映射和弹性成像等附加信息。该探针将为细胞的运作提供新的见解。该项目更广泛的影响/商业潜力是满足对研究单个活细胞结构和功能的工具日益增长的需求。膜片钳和微注射器是研究细胞活动不可或缺的工具。然而，这些工具存在许多问题，例如损坏细胞和缺乏分辨率，而最近的创新未能解决这些问题。所提出的纳米膜片钳解决了这些问题，并使单细胞分析（SCA）能够用于基础或临床研究以及药物发现。微机械膜片钳可以成为 SCA 的多功能工具，对诊断、了解疾病和新药的发现具有直接影响。由于临床试验的成本高达数十亿美元，SCA 为研究人员提供了一种廉价的方法，可以在对动物或人类进行测试之前，在细胞上快速、无害地测试和筛选候选药物。与此同时，在患者自身细胞上测试的新的个性化治疗方法，而不是一刀切的治疗方法，很有可能在未来有效治疗疾病。

This Small Business Innovation Research (SBIR) Phase I project aims to develop a micromachined patch-clamp probe that enables sub-cellular imaging, electrophysiology, and fluidic delivery at the nanoscale with control of applied force at pN levels. The probe can operate like a force sensing finger to sense contact & membrane rupture, no longer damaging cells. The small aperture allows for micro-injections and interrogation of ion channels. Additional information such as imaging, ion channel localization/mapping, and elastography can be obtained. The probe will provide new insights in the workings of cells. The broader impact/commercial potential of this project is to address the increasing need for tools to study the structure and function of single living cells. Patch clamps and micro-injectors are indispensible tools for studying cellular activity. However, these tools are plagued with numerous problems, such as damaging cells and lack of resolution, which recent innovations fail to address. The proposed nano-patch clamp addresses these problems and enables single cell analysis (SCA) for basic or clinical studies and drug discovery. The micro-machined patch clamp can become a versatile tool for SCA, which has direct implications in diagnostics, understanding disorders, and the discovery of new drugs. With the costs of clinical trials in the billion dollar range, SCA offers researchers an inexpensive way to quickly and harmlessly test and screen drug candidates on cells before testing on animals or humans. At the same time, new personalized treatments tested on the patient?s own cells, rather than one-size-fits-all treatments, have an excellent likelihood of effectively treating diseases in the future.