Ultrasensitive Single Extracellular Vesicle Detection Using High Throughput Droplet Digital Enzyme-Linked Immunosorbent Assay

Description:
Extracellular vesicles (EVs) have attracted enormous attention for their diagnostic and therapeutic potential. However, it has proven challenging to achieve the sensitivity to detect individual nanoscale EVs, the specificity to distinguish EV subpopulations, and a sufficient throughput to study EVs among an enormous background. To address this fundamental challenge, we developed a droplet-based optofluidic platform to quantify specific individual EV subpopulations at high throughput. The key innovation of our platform is parallelization of droplet generation, processing, and analysis to achieve a throughput (∼20 million droplets/min) more than 100× greater than typical microfluidics. We demonstrate that the improvement in throughput enables EV quantification at a limit of detection = 9EVs/μL, a >100× improvement over gold standard methods. Additionally, we demonstrate the clinical potential of this system by detecting human EVs in complex media. Building on this work, we expect this technology will allow accurate quantification of rare EV subpopulations for broad biomedical applications. I will also highlight how the platforms developed in this approach are now being leveraged for high throughput screening and sub-cellular analysis.

Speaker: David Issadore - University of Pennsylvania
My research program studies new ways that the approaches that have revolutionized electronics can be leveraged to transform healthcare. My lab develops new platform technologies that combine microelectronics, microfluidics, nanomaterials, and machine learning algorithms to tackle specific, high impact problems in healthcare. We have focused our attention on developing technologies for the diagnosis of diseases that do not have conventional biomarkers, developing micro-scale manufacturing technologies that allow precision micro- and nano-material based therapeutics to be manufactured at a commercial scale, and we have explored and innovated in an assortment of other areas- including magnetically triggered delivery of therapeutics to deep tissue and the development of structured micro-materials for environmental remediation. The platforms that our lab develops are typically based on a fundamental physical insight that we use to address previously intractable problems in a new way.