Broadband microwave flow cytometry: comprehensive nanoparticle sensing and characterization

Clemson University, Clemson SC

Investigators

Abstract

Nanoparticles are ubiquitous and have large impacts on many aspects of everyone's daily life. Among many others, extracellular vesicles, viruses, and prion proteins are natural nanoparticles and play essential roles in biology, disease, and medicine. For instance, extracellular vesicles are key in cell communication, growth and development, and can effectively mediate drug delivery. Viruses cause severe diseases like influenza epidemic and HIV/AIDS. Prion proteins are linked to Alzheimer's. On the other hand, numerous artificial nanoparticles have been synthesized for many important applications including magnetic resonance imaging (MRI), cancer hyperthermia therapy, drug and gene delivery, flexible electronics manufacturing, solar cell development, and surface plasmon resonance sensing. Additionally, more than 1000 commercial products are developed with nanoparticles. Thus, there is a widespread and urgent need for convenient and accurate measurement of particle size, size distribution, density (particles/mL), and surface charge. These parameters are essential for any further nanoparticle exploration, such as colloidal stability, biological behavior, and toxicity. Nevertheless, measuring these basic parameters is very difficult due to small particle size (less than 100 nm in diameter), significant size variation, and diverse particle origin. They require single-particle, multi-parameter, high sensitivity and high throughput measurement, which is not available from existing techniques such as tunable resistive pulse sensing, advanced flow cytometry, nanoparticle tracking, dynamic light scattering, and transmission electron microscopy. This project proposes a novel broadband microwave flow cytometry method to address the problem. The proposed method is expected to significantly facilitate nanoparticle efforts, such as those mentioned above, and strongly impact the development and advancement of nanomaterials, biology, medicine, mesoscopic physics, chemistry, and nanoparticle products. The project also provides support and training to graduate students as well as postdoctoral scholars in the emerging area of nanoparticle instrumentation science and technology. It enables a female faculty member from a predominantly undergraduate institution to participate in cutting-edge nanoscale science research. Additionally, it offers an exciting topic to attract high school, undergraduate, and underrepresented students to experience and study advanced science, technology, engineering, and mathematics. The objective of this project is to develop and demonstrate broadband microwave flow cytometry techniques for the detection and comprehensive measurement of nanoparticles in a label-free and non-invasive manner. Automated tunable interferometers together with nano-sensing structures and nanofluidic channels will be developed to measure single nanoparticles at multiple microwave frequencies. The targeted particle size is from 20 nm to 200 nm in diameter. The minimum detectable particle volume is about 10 times smaller than that of tunable resistive pulse sensing, an existing technique considered as one of the most promising nanoparticle characterization methods. Physical and electrical models of a few nanoparticles will be established for data interpretation and parameter extraction. Algorithms will be developed to obtain the size, size distribution, density (particles/mL), surface charge (i.e. zeta potential) and frequency dependent dielectric properties of nanoparticles. Such dielectric properties are currently not available with any other technique. The targeted throughput is 1 particle/second for a comprehensive multi-parameter measurement and 10 particles/second for simple detection. The throughputs can be further improved in future development. Commonly used nanoparticles (polystyrene and magnetic iron oxide) and copolymer micelles will be used to test the proposed techniques, and the performance will be evaluated by comparing with light scattering measurement results.