Pathologists will be interested to learn that this latest version of the acoustic tweezer device requires about five hours to identify the CTCs in a sample of blood

Medical laboratory leaders and pathologists are well aware that circulating tumor cells (CTCs) released by primary tumors into the bloodstream are fragile and easily damaged. Many studies have sought to find ways to separate CTCs from surrounding cells. Such a process could then be used as an early-detection biomarker to detect cancer from a sample of blood.

One team of researchers believe it has a way to accomplish this. These researchers are using sound waves to gently detect and isolate CTCs in blood samples. In turn, this could make it possible to diagnose cancer using “liquid biopsies” as opposed to invasive conventional biopsies.

Researchers from Carnegie Mellon University (CMU) in collaboration with researchers from the Massachusetts Institute of Technology (MIT) and Pennsylvania State University (Penn State) have developed a method for using acoustic tweezers and sound waves to separate blood-borne cancer cells from white blood cells. The research team believes this new device could one day replace invasive biopsies, according to a CMU article.

Sound Waves Key to Manipulating CTCs without Damaging Them

The method devised by the researchers from CMU, MIT, and Penn State employs sound waves—similar to waves in ultrasound imaging—to separate the blood cells from the CTCs without contacting them.

“The group has developed gentle and efficient acoustic tweezers. These tweezers can move and manipulate thousands of cells without touching them, preserving their characteristics. Development of tools like this will have a significant number of applications in both the research lab and the clinic,” stated Richard Conroy, PhD, Director of Applied Science and Technology, the National Institute of Biomedical Imaging and Bioengineering, in an article posted on the NIBIB Website.

This MIT video shows cancer cells in blood being removed from surrounding white blood cells through the use of the acoustic tweezers device. (Video copyright: Massachusetts Institute of Technology.)

Research Round Two: Develop a Better, Faster Device to Detect CTCs

The CMU/MIT/Penn State researchers have studied isolating CTCs in blood for several years. Their earlier device also used sound waves to sort the tumors cells from white blood cells. However, it was too slow for clinical use because it required 30 to 60 hours to separate cells, the researchers said.

So they turned to new methodology that uses acoustic-based and “contact-free sorting” methods to more carefully isolate and sort CTCs from white blood cells. The new device is up to 20 times faster than the prior attempt (now taking five hours to process a five-milliliter sample).

“Acoustic-based methods, which are known to preserve the integrity, functionality, and viability of biological cells using label-free and contact-free sorting, have thus far not been successfully developed to isolate rare CTCs using clinical samples from cancer patients,” they wrote in a paper about the study published in the Proceedings of the National Academy of Sciences (PNAS).

“In this work, we demonstrate the development of an acoustic-based microfluidic device that is capable of high-throughput separation of CTCs from peripheral blood samples obtained from cancer patients,” they continued in the PNAS piece.

But not only are the CTCs fragile. They are also elusive and extremely rare.

“Looking for circulating tumor cells in a blood sample is like looking for a needle in a haystack. Typically, the CTCs are about one in every one billion blood cells in the sample,” noted Tony Jun Huang, PhD, Penn State Professor of Engineering Science and Mechanics. He was quoted in a Penn State article about the research.

Subra Suresh (center), President, Carnegie Mellon University posing with (left to right) Tony Huang, Ming Dao, Peng Li, and Zhangli Peng: researchers from the Massachusetts Institute of Technology and Carnegie Mellon University who developed the acoustic tweezer device. (Photo copyright: Pennsylvania State University.)

Subra Suresh (center), President, Carnegie Mellon University posing with (left to right) Tony Huang, Ming Dao, Peng Li, and Zhangli Peng: researchers from the Massachusetts Institute of Technology and Carnegie Mellon University who developed the acoustic tweezer device. (Photo copyright: Pennsylvania State University.)

How Does the Acoustic Tweezer Device Work?

The team built microfluidic devices with two acoustic transducers (A.K.A. sound-wave producers) on either side of a micro channel, MIT explained in a statement.

CMU describes the acoustic tweezers testing a blood sample as follows:

1) Researchers remove the red blood cells from the sample;
2) They introduce remaining blood products into a channel in the dime-sized chip;
3) Blood samples traveling along the channel pass through sound waves that have been angled across the channel;
4) Pressure nodes, created by the angle, push the cancer cells away from the channel’s center;
5) The cancer cells travel along a different path than the normal white blood cells;
6) The two paths collect the separated cells.

Pictured above is the acoustic tweezers that researchers say is shown separating cancer cells from blood cells. The yellow transducers supply sound to move the cells as they pass through the high throughput device. (Photo copyright: Tony Jun Huang, PhD, Pennsylvania State University.)

Pictured above is the acoustic tweezers that researchers say is shown separating cancer cells from blood cells. The yellow transducers supply sound to move the cells as they pass through the high throughput device. (Photo copyright: Tony Jun Huang, PhD, Pennsylvania State University.)

CTCs Found in Patient Blood Samples

The researchers analyzed blood samples from three breast cancer patients. In one person, they isolated one tumor cell. In another person, eight CTCs were separated, while 59 tumor cells were isolated in a third individual.

“With an integrated experimental and modeling approach, this new generation of the device has improved cell sorting throughput 10 to 20 times higher than previously achieved and made it possible for us to work with patient samples,” said Ming Dao, PhD, Principal Research Scientist in MIT’s Department of Materials Science and Engineering in a news story published in the Journal of the National Cancer Institute (JNCI).

A patent application has been filed by the organizations for their acoustic tweezers. But the researchers also plan to improve it, aiming toward a goal of 30 minutes to separate CTCs from a vial of blood.

Much Interest in Finding Ways to Detect Circulating Tumor Cells

Other research institutions also are capitalizing on CTC research. At least 30 companies are focusing on CTC technology, according to a story published in OncLive.

Among them, Janssen Diagnostics, owners of CELLSEARCH technology, is reportedly the only CTC diagnostic that has obtained Food and Drug Administration (FDA) clearance.

Biocept (NASDAQ:BIOC) has reportedly partnered with The University of Texas MD Anderson Cancer Center in its OncoCEE device to study ovarian cancer CTCs.

Other companies named in the article that have invested in CTC technology include:

Fluidgm,
Fluxion, and
Miltenyi Biotec.

Clinical laboratory executives and pathologists will want to stay abreast of key developments in the “liquid biopsy” arena. While the questions may continue to be the same about whether a person has cancer and how it is being expressed, the path to discovery may be entirely different, faster, and cheaper. Ultimately, for patients, success in CTC technology research may pay off because diagnostic testing can be done in a manner that is less invasive and not as emotionally taxing.

—Donna Marie Pocius

 

Related Information:

Device Extracts Rare Tumor Cells Using Sound

Sound Waves Gently Cull Circulating Tumor Cells from Blood Samples

Acoustic Separation of Circulating Tumor Cells

Sound Separates Cancer Cells from Blood Samples

Acoustic Device Can Rapidly Isolate Circulating Tumor Cells from Patient Blood Samples

Using Sound to Separate Circulating Tumor Cells

Many Companies Join Race to Create Novel CTC Technology