03 April 2019

A hundred times faster

Laser technology helps researchers scrutinize cancer cells

"Scientific Russia"

The method of photoacoustic microscopy will help in identifying and determining the characteristics of cancer cells, writes Caltech (Laser Technology Helps Researchers Scrutinize Cancer Cells).

To develop an effective treatment, scientists need to know certain signs of the cancer that the patient is suffering from. But one of the biggest difficulties in the treatment of oncology is that cancer cells are not the same. Even within the same tumor, cancer cells may differ in their genetics, behavior, and susceptibility to chemotherapeutic drugs.

Cancer cells are usually much more metabolically active than healthy ones, and some information about the behavior of cancer cells can be gleaned by analyzing their metabolic activity. But getting an accurate estimate of these characteristics has proved difficult for researchers. Several methods have been used, including emission tomography (or PET) scanning, fluorescent dyes, and contrasts, but each has drawbacks that limit their usefulness and effectiveness.

Lihong Wang of the California Institute of Technology believes he can do better with photoacoustic microscopy, a technique in which laser light causes ultrasonic vibrations in a sample. These vibrations can be used to image cells, blood vessels and tissues.

Wang, a professor of medical engineering and electrical engineering, in collaboration with Rong Zu from Texas A&M University, uses photoacoustic microscopy to improve existing technology for measuring oxygen consumption rates. As part of this technology, many cancer cells are placed in separate microcells filled with blood. Cells with a higher metabolism will consume more oxygen and lower its level in the blood – this process is controlled by a tiny oxygen sensor placed inside each cell.

This method, as previously mentioned, has disadvantages. It would take thousands of sensors to get a significant sample of metabolic data. In addition, the presence of sensors inside cells can change the metabolic rate of cells, which will lead to the fact that the collected data will be inaccurate.

Wang's improved version eliminates oxygen sensors and instead uses photoacoustic microscopy to measure oxygen levels in each cell. He does this with the help of laser light tuned to the wavelength that the hemoglobin in the blood absorbs and converts into vibrational energy – sound. When a hemoglobin molecule becomes oxygenated, its ability to absorb light at this wavelength changes. Thus, Wang can determine how oxygenated a blood sample is by "listening" to the sound it emits when illuminated by a laser. He calls it single-cell metabolic photoacoustic microscopy (SCM-PAM).

In an article published in the journal Nature Biomedical Engineering (Hai et al., High-throughput, label-free, single-cell photoacoustic microscopy of intratumoral metabolic heterogeneity) Wang and his co-authors show that SCM-PAM represents a huge improvement in the ability to assess the rate of oxygen consumption in cancer cells. Using separate oxygen sensors to measure the rate of oxygen uptake allowed the researchers to analyze approximately 30 cancer cells every 15 minutes. Wang's SCM-PAM improves this indicator by several orders of magnitude and allows researchers to analyze about 3,000 cells in 15 minutes.

"We have methods to increase throughput by several orders of magnitude, and we hope that this new technology will soon help doctors make informed decisions on cancer prognosis and treatment," says Wang.

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