GOALI: NANOTHERMITE BASED MICRO SHOCKWAVE GENERATORS AND NANOPARTICLES FOR TARGETED AND EFFICIENT DRUG DELIVERY
The objective of this research is to develop a novel digitally controlled micro shockwave generator by integrating nanothermites with microelectromechanical systems (MEMS). The approach is based on shockwaves from redox reactions of nanothermites. The shockwaves are used to deliver genes and/or drugs into cells with high transfection efficiency and cell survival. Furthermore, organosilicate nanoparticles synthesized on site will be utilized as an effective and targeted delivery vehicle via the shockwave. Intellectual Merit. The proposed miniaturized systems will cover the large impulse range necessary for permeabilization of a variety of cells and tissues with different mechanical properties and/or environments. Unlike physical gene delivery methods which rely on bulky and expensive instrumentation or chemical delivery methods that exhibit low transfection efficiency, the proposed MEMS-based shockwave generator -- alone or in combination with nanoparticles - - will produce shockwave interactions and drug delivery at the single cell level, providing unprecedented control over cell transfection processes. Broader Impacts. The proposed research is expected to transform the study and understanding of biological processes in health and disease, and enable novel diagnostics and interventions. Educational objectives include recruitment of students from regional college programs, including those with predominantly Black and Hispanic enrollment and a summer ?Nano Camp? for high school students. Undergraduate and graduate students, particularly from rural areas of Missouri will be trained to develop leadership, ownership, mentoring, career skills and entrepreneurship to prepare them for the 21st century work force.
The overall goal of this project was to develop a novel operator- friendly nanothermite reaction actuator that generates transient pressure pulses to facilitate intracellular delivery of genes and/or drugs with high transfection efficiency and minimal damage. The pressure pulses generated from this system can be tuned to a particular application by engineering the nanothermite composite with energetic additives like Nitrocellulose (NC) or Ammonium Nitrate (AN) nanoparticles or by modifying the system components. In this work, a novel nanothermite reaction actuator was developed and extensively characterized with respect to pressure generating behaviors, shockwave characteristics, and transfection efficiency both cytoplasmic and intranculear. The actuator was constructed from a micro-initiator chip integrated with nanothermite energetic charges, a transmission gel tube, and transfection vessel. The pressure-time responses generated by various nanothermite compositions were measured using a pressure transducer installed at the base of the actuator. Shockwave velocities were measured using a three transducer array installed across the gel tube of the system. The nanothermite reactor actuator demonstrated the delivery of various materials into various cells and tissue lines with versatile transfection and cell viabilities. As a specific example the intranuclear delivery of FITC-Dextran into chicken cardiomyocytes was conducted using various nanothermite compositions and tailored delivery ranging from 20% to 90% with cell viabilities ranging from 50% to 95% was confirmed. Tunable nanothermite reactions enable versatile pressure generating characteristics which extend the technology to a spectrum of biomedical molecular delivery applications. Additionally, the inherently high energy densities and low critical combustion diameters associated with nanothermite gives rise to its integration with micro-systems, enabling portable molecular delivery actuators. This work was conducted in collaboration between the University of Missouri and NEMS/MEMS Works, LLC. (private industry), which mutually authored a patent, peer reviewed publication, and worked towards commercialization of the technology during development.
