Biological Dynamics advances exosome isolation technique

A study published in ACS Nano demonstrates that their proprietary “lab-on-a-chip” ExoVerita system can simplify and streamline the process for isolation and recovery of exosomes. Using exosomes to identify diagnostic biomarkers is a rapidly growing field, and the success of the ExoVerita system may help to develop minimally invasive diagnostic tests to provide faster answers to critical clinical questions in high-burden diseases, such as cancer, traumatic brain injury and infectious diseases.

Exosomes found in the circulatory system are a primary source of important cancer-related RNA and protein biomarkers that are expected to lead to early detection, liquid biopsy and point-of-care diagnostic applications. They are secreted from most cell types and released in bodily fluids such as urine, blood plasma and saliva.

Due to their stability and ability to transport information about their origin and the state of their parental cells, exosomes are believed to have great potential to power the next generation of liquid biopsies and cancer biomarkers. However, isolating exosomes is a challenging process due to their small size and low density, requiring a time-consuming, labor-intensive process yielding few diagnostic applications.

“Current exosome isolation methods are generally expensive, complex and cumbersome, which could limit large-scale diagnostic applications,” said Dr. Michael Heller, principal investigator on the paper and scientific advisory board member for Biological Dynamics. “This study describes a relatively simple, rapid and non-destructive method for the isolation of exosomes, that preserves their valuable biomarker information for direct analysis. The technology is setting the stage for rapid, seamless sample-to- answer liquid biopsy, cancer therapy monitoring and ultimately early disease detection.”

The method described in the study uses Biological Dynamics’ lab-on- a-chip technology, known as ExoVerita, employing an ACE microarray chip device to rapidly isolate and recover exosomes from undiluted human plasma samples. The ACE chip reversibly captures macromolecules in biofluids—such as whole blood, serum and plasma—providing a simplified, no-dilution, sample-to- answer workflow. It thus bypasses many fundamental limitations of current technologies, making the system a potentially robust solution for liquid biopsy, cancer patient therapy monitoring and ultimately early disease detection. The ExoVerita technology may be the first to isolate and analyze exosomal DNA, RNA and proteins at the same time, which Biological Dynamics hopes can further the field of exosome research and advance new ways of treating diseases at a rapid pace.

In the study published recently, the researchers evaluated human breast cancer patient plasma and plasma samples spiked with glioblastoma exosomes using the ExoVerita ACE system. Despite the use of a relatively small sample volume (<50 microliters), the system was able to successfully capture exosomes in 30 minutes, while preserving the integrity of RNA, transmembrane, and internal proteins. The research team also eluted the exosomes off the chip and confirmed that the extraction process provides viable mRNA for qPCR/RT-PCR analysis.

“This data supports our confidence in the potential for our platform to develop important molecular diagnostics to improve the detection and treatment of cancer,” says Dr. Raj Krishnan, CEO of Biological Dynamics. “This study, along with previous publications, demonstrates our technology can isolate and analyze exosomal DNA, RNA and proteins at the same time. By providing one platform to access the three pillars of diagnostics, we are positioned to develop a new generation of multimodal diagnostics to transform the field.”

According to Krishnan, ExoVerita is currently being used as a collaborative tool to advance the findings that exosomes offer. One example he cites is the system’s ability to measure bioabsorption in assessing drug delivery systems by analyzing a blood sample to identify drug amounts in one’s system and thus review drug dilution and efficacy. “Our goal is to build systems by finding partners within the research space to develop and discover new findings for exciting research, new ways of treating disease,” he says.

Depending on researcher’s preference, the ExoVerita system could be used with the company’s universal single-channel and three-channel chips. Most of the company’s recent research work has been done on the three-channel chips. All of Biological Dynamics’ automated systems are using an eight-channel version of the chip, according to the company.