Combining lasers with a principle discovered by Alexander Graham Bell over 100 years ago, researchers have developed a new way to collect high-resolution information about the shape of red blood cells. Because diseases like malaria can alter the shape of the body's cells, the device may provide a way to accurately diagnose various blood disorders.
The study relies on a physical principle, known as "the photoacoustic effect," originally discovered by Bell in 1880. The famed inventor observed that when a material absorbs light from a pulsing light source, it produces sound waves. Since then, scientists have learned that the effect occurs because the object heats up as it absorbs light; the heat causes the object to expand, and this physical change leads to the emission of sound waves.
Today, researchers can induce the photoacoustic effect by using lasers. The most advanced lasers can pulse in the nanosecond range (once every 100 of nanoseconds), generating sound waves from cells and tissues that are at very high frequencies. The higher the frequency, the more information scientists are able to glean about the shape of the object.
Michael Kolios, a photoacoustics scientist at Ryerson University in Toronto, wondered whether he could use the photoacoustic effect to determine the shape of red blood cells. His team developed a laser that pulses every 760 nanoseconds to induce red blood cells to emit sound waves with frequencies of more than 100MHz, one of the highest frequencies ever achieved. Testing the laser on blood samples collected from a group of human volunteers, Kolios and colleagues showed that the high-frequency sound waves emitted by red blood cells in the blood samples revealed the tiniest details about the cells' shapes. The approach could accurately distinguish samples from a person with malaria, which is characterized by the swelling of red blood cells, from samples from a person with sickle cell anemia, in which the red blood cells distort into a serrated crescent shape, the team reports today in the Biophysical Journal.
The method requires as few as 21 red blood cells. Standard blood tests, in contrast, need more than one drop of blood, and red blood cells need to be analyzed manually by pathologists with a microscope, a task that is slow and prone to human error. The faster diagnosis with Kolios's technology allows doctors to quickly determine whether the donor's blood is disease-free immediately prior to blood transfusion. The speed of the approach outperforms standard blood tests by hours, a key advantage for life-saving blood transfusions where every second counts.
Kolios hopes to bring this new device into the clinic. But Nicholas Au, a hematopathologist at the Women's and Children's Hospital of British Columbia in Vancouver, says the new technique cannot replace the standard blood test, which reveals more information about the shape of white blood cells and platelets. The shape change in these cells is indicative of diseases like cancer or clotting disorders. Kolios' team's method works best with red blood cells because of their biconcave shape, which gives them the unique ability to absorb light better than platelets and white blood cells.
Still, Kolios' technology holds enormous promise, says Li Hong Wang, a photoacoustics scientist of Washington University in St. Louis. "What's exciting is the potential application of this method in identifying not only abnormal red blood cells, but also circulating tumor cells," he says. The latter could be done, he notes, with a pulsing ultraviolet laser, which could accurately measure the amount of a light-absorbing pigment (known as melanin) inside cells using sound waves, allowing scientists to identify circulating tumor cells based on their abnormally high melanin content. While Kolios's device could be costly, with a price tag of $100,000 for just the laser, Wang is optimistic that the price would go down in light of the growing biomedical demand.