Dr. Kiana Aran Develops Exosome and Extracellular Vesicles Detection Technology called EV-Chip

Keck Graduate Institute (KGI) Assistant Professor Dr. Kiana Aran and collaborators have published a paper titled “Rapid and Electronic Identification and Quantification of Age-Specific Circulating Exosomes via Biologically Activated Graphene Transistors” this month in the peer-reviewed journal Advanced Biology.

The paper reports a novel biosensor called the EV-Chip, a prototype portable, low-cost reader for detecting and quantifying exosome biomarkers of cancer and other aging-related diseases. It demonstrates the EV-Chip’s clinical potential to evaluate human liquid biopsy samples through rapid, label-free identification of known biomarkers, CD63 and CD151. The publication resulted from a collaboration between Cardea Bio, Inc., KGI, the Keck Science Department, and UC Berkeley.

In addition to her role at KGI, Aran also serves as Chief Scientific Officer at Cardea Bio, a company integrating molecular biology with semiconductor electronics via graphene-based biology-gated “Cardean Transistors.”

“Modern clinical advances have extended the bounds of the human lifespan, revealing a new class of health issues related to the aging process, such as cancer, inflammatory, and degenerative diseases,” said Aran.

“Through our EV-Chip, scientists will be able to use the EV-Chip for biomarker discovery and unlock a new source of diagnostic biomarkers and therapies to combat these diseases more effectively.”

The EV-Chip has high-specificity antibodies that bind to one or more exosome biomarkers of interest embedded into a Cardean Transistor chip. It can be functionalized to detect virtually any exosome biomarker. When a plasma-derived exosome sample is added, the one molecule-thick, biocompatible graphene transistor detects antibody binding events and sends digital feedback back to a small device that can connect easily to any computer and returns results within an hour. The whole setup is small and simple to use, making it well-suited to a physician’s office or biological lab.

The EV-Chip stands to offer a degree of precision and real-time, direct quantification of exosome biomarkers not possible with other technologies, which involve large sample sizes, lengthy incubation periods, and chemical labeling. These methods also require vast expertise to run highly technical instruments and complete complex procedures at a central lab, which has created a bottleneck in discovering biomarkers of cancer and other aging-related diseases.

Dr. Paul Grint, Chairman of the Board of Directors of Cardea, added, “Exosomes are promising biomarkers for aging-related diseases, particularly cancer. They have dynamic sets of proteins embedded in their walls that reflect cellular activities such as cell-cell communication, migration, and adhesion—activities that change due to cancer and aging. Without a way to measure exosomes at the point of care, they remain an untapped diagnostic resource.”

In the paper, the authors demonstrated the EV-Chip’s capabilities by using it to analyze two exosomal surface markers, CD63 and CD151. CD63 is a biomarker for cancer and viral infection, while CD151 is a cancer biomarker with prognostic and diagnostic value in tumor metastasis¹ and generally increases with age.² The EV-chip quantified the CD63 with remarkable sensitivity, four to five orders of magnitude greater than a commercially available ELISA kit. Similarly, when used to measure CD151 in young and old subjects, the technology detected age-related changes as reliably as standard methods. Overall, the results demonstrate the EV-Chip’s potential to usher in a new era of powerful non-invasive point-of-care diagnostics and prognostic tools to manage aging-related diseases.

“The talented scientists who contributed to this chipset development and paper have given the world a new technology with the potential to radically accelerate the discovery and use of new exosomes biomarkers,” said Michael Heltzen, CEO of Cardea Bio. “Advances enabled by the EV-chip will further our understanding of intercellular communication and cellular biology that will help us gain a new degree of insight to important areas such as cancer and other age-related diseases.”

The EV-Chip is a Cardean chipset variant that utilizes the Cardean transistor to detect live molecular signals. Others include Cardea’s CRISPR-Chip™ technology, which detects large nucleic acid insertion and deletions, and its newer product version, the SNP-Chip, which detects single nucleotide polymorphisms (SNPs).

Advanced Biology is an interdisciplinary and international academic journal that publishes original manuscripts, reviews, perspectives, and commentary of high significance to life scientists working in all areas of biology. The journal focuses on applied research and technologies that enhance and harness biological systems and showcases novel findings of wide biological relevance resulting from both basic and applied research.

References
1. R. Sadej, A. Grudowska, L. Turczyk, et al. Lab. Invest. 2014, 94, 41.
2. E. Eitan, J. Green, M. Bodogai, et al, Sci. Rep. 54 2017, 7, 1342.