Acoustic-based separation method for cancer research

discovery Scientists say that acoustic-based separation method offers the potential to serve as an invaluable supplemental tool in cancer research, wr

It has been reported that the human body is composed of 37.2 trillion cells, which is 37.2 multiplied by 1000,000,000,000. Now imagine a patient suffering from cancer. A typical cancer tumour will contain millions or even billions of cells with genetic mutations, driving the cells to grow, divide and invade the local tissue in which they are embedded.

As the tumour grows and the cells proliferate, not all of them stay put together. Some of these cells peel off or disentangle themselves from the edges of the tumour and are swept away by the bloodstream into the body. These cells are called ‘circulating tumour cells’ or CTCs, and they are very small in number, but contain vital information, useful to oncologists and clinicians.

Why look for CTCs, you may ask? CTCs serve as a liquid biopsy target for cancer diagnosis, genotyping, and prognosis. Monitoring the phenotypic and genotypic changes in CTCs during the course of chemotherapy treatment may be beneficial for guiding therapeutic decisions. In addition, they could provide new insights into the mostly elusive, yet deadly, process of cancer metastasis.

To realise these potential benefits from CTCs, a better understanding of them is needed. However, CTCs are difficult targets to probe owing to their extremely low concentration in peripheral blood (usually in the range of 1‒100 cells/ml of blood). Therefore, effective cell separation methods are required to facilitate the study of CTCs.

Another important factor to consider is that currently, targeted cancer treatment for patients is carried out by the analysis of the primary tumour(s). The difficulties with this approach are that the primary tumours contain cells that cause metastasis or recurrence, and samples for analysis are obtained by needle core biopsies or surgical removal of the tumour tissue. Both are invasive procedures and prohibit the extraction of the tissue from locations inaccessible by surgery.

So, there is a need for non-invasive methods capable of detecting CTCs, independent of the epithelial cell marker. The obvious question would be how we separate these circulating tumour cells, from among the millions of healthy cells in which they hide. Not an easy task by any means.

New technique
Now a team of American scientists, from The Pennsylvania State University, Massachusetts Institute of Technology, University of Notre Dame, the Penn State Hershey Cancer Institute and the Carnegie Mellon University have succeeded in demonstrating that it is possible to separate these circulating tumour cells, using ‘acoustic tweezers’ a technique they have developed.

The resultant device, a microfluidic chip, uses the principle of tilted angle Standing Surface Acoustic Waves (taSSAW), to separate these rare circulating tumour cells from healthy white blood cells in the bloodstream.

They have published their research findings in the online early edition of the prestigious American journal, the Proceedings of the National Academy of Sciences (PNAS).

Current CTC separation methods, such as the centrifugal separation, magnetic, mechanical or fluorescence marker combinations result in cell separation, but end up either damaging the cell or altering its genetic and physical make up. There is therefore a need to separate these rare tumour cells in a gentler and more benign way so as to provide clinicians undamaged cells for further study.

The teams of scientists explain that, “Acoustic tweezers were made by manufacturing an inter-digital transducer, which creates the sound waves onto the piezoelectric chip surface. Standard photolithographic techniques were used to create micro channels in which the liquid containing the cells flow.”

Procedure
To test a blood sample using the device, the researchers remove the red blood cells from the sample, and introduce the remaining blood product into a channel in the micro miniature device. As the sample travels along the channel, it passes through sound waves that have been angled across the channel. By angling the sound waves, the researchers have created a zone of pressure nodes that push the cells away from the center of the channel.

Since cancer cells have physical properties such as different size and compressibility than normal white blood cells, they are propelled at different trajectories by the sound waves. The researchers were able to establish what path each cell type would take, and therefore created two channels along those paths to collect the separated circulating tumour cells.

The scientists say, “We performed systematic parametric studies of key factors influencing the performance of the testing platform and determined how these parameters affect the separation results. After optimising the design parameters, such as the tilt angle and the length of the interdigitated transducers (IDTs) as well as the device power, we tested and validated the performance of the device by testing cultured cell lines for different types of cancer.

As a result, the separation of rare cancer cells from WBCs was achieved with higher efficiency than previously possible. Finally the researchers say, “We applied our SSAW device for high-throughput separation of clinical samples and successfully identified CTCs from breast cancer patients in all cases studied here.”

Subra Suresh, a co-author of the study is reported to have said that “the current gold-standard for finding Cancer Tumour Cells, requires scientists to tag the cells using antibodies. Our technique has the added advantage of being label-free, without the need for any tagging that could chemically alter the cells. Our new approach would allow scientists and clinicians to gain more information on cell pathology and cancer metastasis than is currently possible.”

The researchers say that “Acoustic tweezers technology has significant advantages over existing technologies because of its versatility, miniaturisation, power consumption and technical simplicity. They expect it to become a powerful tool for many applications such as tissue engineering, cell studies, and drug screening and discovery.”

They further add that, their acoustic-based separation method thus offers the potential to serve as an invaluable supplemental tool in cancer research, diagnostics, drug efficacy assessment, and therapeutics owing to its excellent biocompatibility, simple design, and label-free automated operation while offering the capability to isolate rare CTCs in a viable state.

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