Devising the best treatment for a cancer patient requires doctors to know something about the traits of the particular cancer. One of the greatest difficulties in treating cancer is that cancer cells are not all the same. Even within the same tumor, cancer cells can differ in their genetics, behavior, and susceptibility to chemotherapy drugs.
Cancer cells are generally much more metabolically active than healthy cells and some insights into a cancer cell’s behavior can be gleaned by analyzing its metabolic activity. But getting an accurate assessment of these characteristics has proven difficult. Several methods, including position emission tomography (or PET) scans, fluorescent dyes, and contrasts have been used, but each has drawbacks that limit their usefulness.
Photoacoustic microscopy (PAM) is a technique in which laser light induces ultrasonic vibrations in a sample. Those vibrations can be used to image cells, blood vessels, and tissues. PAM is being used to improve on an existing technology for measuring the oxygen-consumption rate (OCR). That existing technology takes many cancer cells and places them each into individual “cubbies” filled with blood. Cells with higher metabolisms will use up more oxygen and lower the blood oxygen level, a process monitored by a tiny oxygen sensor placed inside each cubby.
This method, however, also has weaknesses. Getting a meaningful sample size of metabolic data for cancer cells would require researchers to embed thousands of sensors into a grid. Additionally, the presence of the sensors within the cubbies can alter the metabolic rates of the cells, causing the collected data to be inaccurate.
The improved version does away with the oxygen sensors and instead uses PAM to measure the oxygen level in each cubby. This is performed with laser light that is tuned to a wavelength that the hemoglobin in blood absorbs and converts into vibrational energy, or sound. As a hemoglobin molecule becomes oxygenated, its ability to absorb light at that wavelength changes, thus determining how oxygenated a sample of blood is by “listening” to the sound it makes when illuminated by the laser. This is called single-cell metabolic photoacoustic microscopy (SCM-PAM).
SCM-PAM represents a huge improvement in the ability to assess the OCR of cancer cells. Using individual oxygen sensors to measure OCR limited researchers to analyzing roughly 30 cancer cells every 15 minutes. SCM-PAM improves that by two orders of magnitude and allows researchers to analyze around 3,000 cells in about 15 minutes.