How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”


New Technique Identifies Cancer In Urine Or Blood

A team of researchers, led by Professor Yoon-Kyoung Cho of Life Science at UNIST  (South Korea) has recently developed a new technique that effectively identifies cancer-causing substances in the urine or blood.

In the study, Professor Yoon-Kyoung Cho of Life Science, a group leader at IBS Research Center for Soft and Living Matter (CSLM) presented an integrated centrifugal microfluidic platform (Exodisc), a device that isolates extracellular vesicles (EVs) from urine.  The research team expects that this may be potentially useful in clinical settings to test urinary EV-based biomarkers for cancer diagnostics.

Extracellular vesicles (EVs) are cell-derived nanovesicles (40-1000 nm in size), present in almost all types of body fluids, which play a vital role in intercellular communication and are involved in the transport of biological signals for regulating diverse cellular functions. Despite the increasing clinical importance of EVs as potential biomarkers in the diagnosis and prognosis of various diseases, current methods of EV isolation and analysis suffer from complicated procedures with long processing times. For instance, even ultracentrifugation (UC), the most commonly used method for EV isolation, requires time-consuming steps involving centrifugation and acquisition of large sample volumes, and the results suffer from low yield and purity.

To overcome these limitations, Professor Cho presented a new lab-on-a-disc platform for rapid, size-selective, and efficient isolation and analysis of nanoscale EVs from raw biological samples, such as cell-culture supernatant (CCS) or cancer-patient urine.


The Exodisc is compoased of two independent filteration units (20nm and 600nm in size) within a disk-shaped chip to enable the processing of two different samples simulateously,” says Hyun-Kyung Woo (Combined M.S./Ph.D. student of Natural Science), the first author of the study. “Upon spinning the disc, the urine sample is transferred through two integrated nanofilters, allowing for the enrichment of unirary EVs within the size range of 20 to 600 nm.”
Using Exodisc, it is possible to isolate EVs from raw samples within 30 minutes,” says Professor Cho. “The process of passing the filter through centrifugal force is automatically carried out, effectively recovering the enriched EVs.”

On-disc ELISA using urinary EVs isolated from bladder cancer patients showed high levels of CD9 and CD81 expression, suggesting that this method may be potentially useful in clinical settings to test urinary EV-based biomarkers for cancer diagnostics,” explains Vijaya Sunkara of Life Sciences, the co-first author.
The results of the study has been published in the February issue of ACS Nano journal.