Figure 1. Comparison of Various Classes of Circulating Biomarkers vis-à-vis Their Potential for Biofluid Biopsies. [Select Biosciences]
There is increasing interest in the potential of circulating biomarker classes as a means to developing minimally invasive biopsies primarily for cancer but with penetrance into many other disease classes such as CNS disorders. Several circulating biomarker classes are being studied in this context most notable of which are circulating free DNA (cfDNA), circulating RNA, circulating tumor cells (CTCs), and extracellular vesicles (EVs)—these various classes represent either the biomarkers themselves or the vectors carrying the circulating biomarkers (Figure 1).

Which Biofluid to Utilize?

One of the challenges in the development of biofluid biopsies is the “sample preparation” on the front-end from clinically relevant patient samples.

Currently, the most commonly studied biofluid samples are:

  • Whole Blood—for CTC Capture
  • Plasma—for Extracellular Vesicles (EVs) and Extracellular Nucleic Acids
  • Serum—for Extracellular Vesicles (EVs) and Extracellular Nucleic Acids
  • Urine—for Extracellular Vesicles (EVs) and Extracellular Nucleic Acids

Less common biofluid classes:

  • Cerebrospinal fluid (CSF)

Biofluid Biopsies Will Migrate Eventually to the Point-of-Care (POC) Setting

There is mounting evidence that biofluid biopsies will migrate toward the point-of-care (POC) setting for the following reasons:

  • Beyond cancer, biofluids may be harvested for other disease classes including traumatic brain injury (TBI) where biopsies of the brain are not feasible and biofluids offer an important alternative—diagnoses of TBI must necessitate movement toward the POC setting
  • If biofluids are to be deployed for routine cancer screening in otherwise clinically healthy subjects, this of course must be performed in doctor’s offices, outpatient clinics—the POC setting
  • Technology development for POC diagnostics such as smartphone-based diagnostics is proceeding at a rapid pace and we believe that these technologies will impact biofluid-based diagnostics especially in resource-limited settings and for public health

    Categorization of Potential Circulating Biomarker Classes to Illustrate Associations Amongst the Publications and Therefore the Intersections of the Various Spaces



Figure 2. The Circulating Biomarker Classes Are Interconnected.

Select Biosciences has sought to segment the various circulating biomarker classes and forge connections between these classes based on the scientific publications wherein these circulating biomarkers are mentioned. Figure 2 presents this segmentation and provides a compelling argument for the interconnectivity of these biomarker classes and the postulate that biofluid biopsy development will necessitate combinations of these various circulating biomarker classes.

Taken together, our tracking of this marketplace reveals that the various circulating biomarker classes offer opportunity for biofluid biopsy development—at this point in the trajectory of the field it appears that “each” of these circulating biomarker classes will have a role to play and the future of biofluid biopsies is most-likely a combination of several circulating biomarkers providing a real-time picture into the trajectory of the disease progression and responsiveness to the treatment regimen.

Enal Razvi, Ph.D., conducted his doctoral work on viral immunology and subsequent to receiving his Ph.D. went on to the Rockefeller University in New York to serve as Aaron Diamond Post-doctoral fellow under Professor Ralph Steinman [Nobel Prize Winner in 2011 for his discovery of dendritic cells in the early-70s with Zanvil Cohn]. Subsequently, Dr. Razvi completed his research fellowship at Harvard Medical School. For the last two decades Dr. Razvi has worked with small and large companies and consulted for more than 100 clients worldwide. He currently serves as Biotechnology Analyst and Managing Director of SelectBio U.S. He can be reached at

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