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.
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. Additional information such as imaging, ion channel localization/mapping, and elastography can be obtained. The probe provides new insights in the workings of cells. We are pleased to report that we have successfully micromachined the device and our preliminary testing indicates that the initial feasibility questions have been answered in the affirmative. The results of Phase I demonstrate that the nano-patch clamp probe (fluidic cantilever) can be used for electrophysiological measurements and fluidic delivery. We fabricated cantilever probes demonstrating a viable fabrication process. We overcame several microfabrication challenges. We successfully micromachined polymeric probes with a fluidic channel and an opening at the tip for fluidic delivery. We managed to successfully batch fabricate an opening by uniquely integrating the opening formation in the micromachining process. In addition, these cantilevers have unprecedented compliance having one of the lowest spring constants reported. These features allow for high throughput production of highly sensitive devices for biological applications. 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.
