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Microfluidics, Sound Waves Combined for Liquid Biopsies

Exosome illustration

Exosome illustration (National Cancer Institute)

19 September 2017. Biomedical engineers from several universities developed a microfluidics, or lab-on-a-chip, device that uses sound waves to quickly isolate tiny packets of cell materials for detecting diseases. The team from Massachusetts Institute of Technology, Duke University, University of Pittsburgh, and Nanyang Technological University Singapore describe the technology in yesterday’s issue of Proceedings of the National Academy of Sciences.

The researchers are seeking faster, less destructive, and more automated methods for diagnosing disease from ordinary blood samples, particularly to capture and analyze exosomes, an emerging target for a number of biomedical applications. Exosomes are tiny — 40 to 150 nanometer — lipid-membrane containers in cells that gather up and secrete cytoplasm, the gel-like material outside the cell nucleus. While originally believed to carry out waste removal and other maintenance tasks, exosomes were shown in recent years to perform useful delivery functions carrying proteins and genetic material to other cells, and drawing increased attention from a range of biological disciplines.

Exosomes offer a great deal of potential in biomedical processes, since they’re found in many biological fluids, such as blood, urine, saliva, and breast milk. Since many of these fluids can be captured with minimal or no invasiveness, they could also substitute for some tissue biopsies now used to detect solid tumor cancers. And exosomes are more abundant than circulating tumor cells, a source of biomarkers in many current liquid biopsies.

Many of today’s processes for isolating, capturing, and accumulating exosomes with high purity and quality use centrifuges, which while effective, can take hours or days to collect a sufficient quantity of exosomes for testing, as well as employ physical forces that can harm exosomes and reduce their useful yield. The authors — led by MIT’s Ming Dao and Subra Suresh (since named president-designate of Nanyang Technological University), Duke’s Tony Jun Huang, and Yoel Sadovsky, director of the Magee-Women’s Research Institute affiliated with University of Pittsburgh — say alternative methods for exosome capture are being developed, but they often run into problems with need for additional reagents, low yields, impurities, or long turnaround times.

Among the more promising methods use chip devices with microfluidics containing fine channels where small specimen samples, often no more than a drop, can be quickly analyzed to expose exosomes. In this project, the researchers start with microfluidics, but add in acoustics, where sound waves can quickly isolate exosomes from whole blood samples. Their device contains a pair of transducers, units that convert energy from one form to another, to create sound waves. The chip first separates blood cells and platelets containing exosomes, then a second module using higher frequency sound waves isolates exosomes from their supporting materials.

Tests show the chip device’s process called acoustofluidics can process blood samples quickly and with high purity. The team’s prototype chip analyzed whole blood samples of 100 microliters in about 25 minutes. The device captured 82 percent of exosomes in the samples, returning exosomes with a purity of 98 percent. “This new generation of integrated device design,” says MIT’s Dao in a joint statement, “makes it possible for centrifugation-free sorting of different blood components, which can drastically reduce the cost and processing time involved with liquid biopsy assays.”

The authors also note that acoustofluidics can be integrated more easily into single-step and automated systems. The device can analyze blood samples and return results in a single process, rather than requiring multiple steps with additional pieces of bulky lab equipment, such as centrifuges, and instruments. In addition, the single-step process is more likely safer and requires less training for operators, as well as better able to return consistent results.

The team next plans to refine the chip device into a practical tool to detect biomarkers indicating diseases. The researchers say they received funding to apply the technology to indicators of abnormal pregnancy, but believe it can be used to detect other disorders as well.

The following video from Duke University, tells more about the acoustofluidics device.

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