A largely unmet challenge in single-cell study is to deliver accurate molecular doses and release them with prescribed rates to a designated single living cell in the midst of many, or to a specific sub-cellular location. The overcoming of this challenge will have profound impact on single-cell bioscience and targeted medical interventions, particularly for many important brain diseases. In this work, an innovative platform based on intelligent and controllable nanoparticle robots is proposed to deliver desired dose of biosubstances at programmable release rates at desired single/sub-cellular locations. Such device will allow unprecedented levels of manipulation in both cell culture and tissue setting. Particularly, the platform will be employed to deliver drug molecules to blood-brain barrier, a vital component in the brain structures that protect the neurons from circulating insults of toxins, antibodies, immune cells. If successful, the understanding of blood-brain barrier regulation on the single/subcellular level will be unveiled, which will add new knowledges critical for finding solutions for many neurologic diseases. The project will also provide undergraduate and graduate students rarely available opportunities in the interdisciplinary field of nanorobotics, nanoelectromechanical systems, and nanosensing. An educational website will be launched to timely highlight the recent achievements and to intrigue the awareness and interest of the public in cutting-edge scientific advances. A professional symposium will be organized to bring researchers to this emerging field and to foster collaborations.
The innovative nanoparticle based robotic platform for smart biosubstance delivery and sensing will utilize strategically designed plasmonic-active nanostructures to precisely transport and programmably release biosubstances to a single live cell amidst many with sub-cellular resolution, and simultaneously monitor the molecule release process by optical spectroscopy. To realize such a system, the proposed research will address challenges on the material, device, and system levels and demonstrate the applications of the platform in manipulating and understanding localized blood-brain barrier drug permeability and delivery. It is expected to make a giant leap towards understanding and resolving the long-standing mystery of blood-brain barrier breakdown and its drug stimulated dynamics, a hallmark of many critical neurologic diseases, such as Alzheimer's disease. Not limited to the proposed blood-brain barrier study, the nanorobtic platform will provide a transformative tool with unprecedented spatial resolution, temporal precision, and molecule release controllability to facilitate other single-cell research disciplines, including cell-cell communications, signal pathways, stem cells, and biosubstance delivery. It is expected to significantly impact multiple fields, including nanorobotics, nanosensing, nanoelectromechanical systems, single-cell research, and drug delivery.
