Rapid and Electronic Identification and Quantification of Age‐Specific Circulating Exosomes via Biologically Activated Graphene Transistors

Abstract

Increasing access to modern clinical practices concomitantly extends lifespan, ironically revealing new classes of degenerative and inflammatory diseases of later years. Here, an electronic graphene field‐effect transistor (gFET) is reported, termed EV‐chip, for label‐free, rapid identification and quantification of exosomes (EV) associated with aging through specific surface markers, CD63 and CD151. Studies suggest that blood‐derived exosomes carry specific biomolecules that can be used toward diagnostic applications of age and health. However, to observe improvements in patient outcomes, earlier detection at the point‐of‐care (POC) is required. Unfortunately, conventional techniques and other electronic‐based platforms for exosome sensing are burdensome and inept for the POC distinction of aged blood factors. It is shown that EV‐chip can quantitatively detect purified exosomes from plasma, with a limit of detection (LOD) of 2 × 104 particles mL−1 and a limit of quantification (LOQ) of 6 × 104 particles mL−1. The sensitivity and compact electronics of the EV‐chip improves upon previously published electronic biosensors, making it ideal for a physician's office or a simple biological laboratory. The sensitivity, selectivity, and portability of the EV‐chip demonstrate the potential of the biosensor as a powerful point‐of‐care diagnostic and prognostic tool for age‐related diseases.

Influences of age, race, and sex on extracellular vesicle characteristics

“…It should be noted that lower EV levels in older individuals have not been observed in all studies 35 , 36 . Other studies have shown no differences in EV concentration with advancing age 35 , 36 .…”

“…It should be noted that lower EV levels in older individuals have not been observed in all studies 35 , 36 . Other studies have shown no differences in EV concentration with advancing age 35 , 36 . These differences may lie in lower cohort numbers and different age ranges in these cross-sectional studies.…”

“…Apoptosis markers including p53, cleaved PARP, and cleaved Caspase-3 were decreased with age in human plasma EVs 32 . EV associated CD151 has been shown to be higher in aged individuals in multiples studies 32 , 36 . Differential EV protein cargo with age has also been implicated in the ability of EVs from older individuals to stimulate hematopoietic stem cells 36 .…”

“…EV associated CD151 has been shown to be higher in aged individuals in multiples studies 32 , 36 . Differential EV protein cargo with age has also been implicated in the ability of EVs from older individuals to stimulate hematopoietic stem cells 36 . Activation of monocytes or T cells is also affected by the age of the EV donor 32 , 39 .…”

An electro-optical bead-nanochip technology for the ultrasensitive and multi-dimensional detection of small extracellular vesicles and their markers

“…In NEXOS, the steps involving the labeling of sEVs with detection antibodies, capture of sEVs with MBs, and counterstaining with s-GNPs or poly-HRP strep, are high-throughput, occurring in a conventional microtiter well plate. Furthermore, the sandwich capture of sEVs with MBs in a liquid format and labelling with s-GNPs (E-NEXOS) or fluorescent reporters (O-NEXOS) has advantages over some of the emerging new technologies based on surface-based antibody capture of sEVs [17, 32, 33].…”