Acoustics for "liquid biopsy"
Researchers at Duke University, the Massachusetts Institute of Technology and Nanyang Technological University in Singapore have developed a gentle non-contact method for isolating circulating tumor cells from blood samples using sound waves.
Circulating tumor cells are the smallest particles of the tumor, breaking away from it and moving through the body with the blood flow. They contain a lot of information associated with the prognosis of the course of the disease and the effectiveness of certain treatment methods about the type of tumor, its physical characteristics and genetic mutations. The ability to quickly and efficiently isolate these cells from a blood sample and cultivate them in the laboratory provides an opportunity to obtain a "liquid biopsy" to establish an accurate diagnosis, predict the course and individual selection of therapy.
However, the concentration of such cells in the blood is negligible (units per billion blood cells), and their detection is an extremely difficult task. The technologies currently available are very far from perfect and often damage or kill circulating tumor cells in the process of their detection. In addition, they are ineffective, work only with certain types of cancer, or the procedure used is too long for many situations.
The approach proposed by the authors is based on the use of sound waves and makes it possible to isolate circulating tumor cells from a 7.5 ml blood tube within an hour. At the same time, the effectiveness of the procedure is at least 86%. The developers hope that additional improvements will transform this approach into a new method of analysis performed using inexpensive disposable chips.
The approach is to fix a standing sound wave at an angle to the liquid flowing through a tiny channel. A sound wave is essentially a pressure wave pushing particles suspended in a flowing liquid. This acoustic pressure has a stronger effect on large dense malignant cells than on normal blood cells, pushing them into a separate channel.
A penny-sized device extracts circulating tumor cells from biological fluids using sound waves.
The energy intensity and frequency of sound waves are comparable to the parameters of waves used in medical ultrasound studies. The risk of damage to circulating tumor cells is also minimized due to the fact that each cell is exposed to a sound wave only for a fraction of a second and does not require labeling or surface modification.
The technology was first demonstrated three years ago, after which it was improved to a state in which it is suitable for clinical use. The first modification consists in the manufacture of one of the walls of the channel from glass, reflecting from which the sound wave amplifies the pressure waves inside the channel. In addition, the channel for separating cancer cells was placed in the center of the main channel, which speeds up the sample processing process.
The resulting prototype of the device processes liquid at a rate of 7.5 ml per hour, which is 7 times higher than the original figure. At the same time, the device retained 86% efficiency and numerous other advantages over other methods.
The developers tested their method on a blood sample of patients with prostate cancer and successfully analyzed the isolated cells for a number of biomarkers, as well as growth rate characteristics. They demonstrated that the expression levels of key therapeutic targets, such as prostate-specific antigen (PSA), on circulating tumor cells of different patients vary very widely.
Currently, the authors are working on further improving the speed and efficiency of the technology, as well as exploring the possibilities of its application in clinical practice. They also plan to use it in a number of scientific projects, such as studying the mechanisms that allow circulating tumor cells to survive in the bloodstream and form metastases.
Article by Mengxi Wu et al. Circulating Tumor Cell Phenotyping via High‐Throughput Acoustic Separation is published in the journal Small.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from Duke University: Sound Waves Could Provide 'Liquid Biopsies'.