Multiple myeloma is a cancer of the plasma cells, which are white blood cells produced in bone marrow that churn out antibodies to help fight infection. When plasma cells become cancerous, they produce abnormal proteins, and the cells can build up in bone marrow, ultimately seeping into the bloodstream.
The disease is typically diagnosed through a bone marrow biopsy, in which a needle is inserted near a patient’s hip bone to suck out a sample of bone marrow – a painful process for many patients. Clinicians can then isolate and analyse the plasma cells in the bone marrow sample to determine if they are cancerous.
There is currently no way to easily detect plasma cells that have escaped into the bloodstream. Circulating plasma cells are not normally found in healthy people, and the ability to detect these cells in blood could enable doctors to diagnose and track the progression of multiple myeloma.
Now engineers at MIT have devised a microfluidic technique to capture and count circulating plasma cells from small samples of blood. The technique, which relies on conventional blood draws, may provide patients with a less painful test for multiple myeloma.
The group’s technique builds on a microfluidic design that was previously developed by George Whitesides, a professor of chemistry at Harvard University. Whitesides and his colleagues fabricated a small microchip, the channel of which they etched with repeating, V-shaped grooves, similar to a herringbone pattern. The grooves cause any fluid flowing through the microchip to swirl about in eddies, rather passing straight through. The cells within the fluid therefore have a higher chance of making contact with the floor of the device, as first shown by Memhmet Toner at Massachusetts General Hospital.
Researchers including Karnik have since reproduced this microfluidic design, coating the microchip’s floor with certain molecules to attract cells of interest.
In its latest work, Karnik’s team used the microfluidic herringbone design to capture circulating plasma cells. They coated the channels of a microchip, about the size of a glass slide, with CD138, an antibody that is also expressed on the membranes of plasma cells. The team then flowed small, 1-milliliter samples of blood through the device. The herringbone grooves circulated the blood in the microfluidic channels, where the antibodies, acting as tiny Velcro pads, grabbed onto any passing plasma cells while letting the rest of the blood flow out of the device.
Once the cells were isolated in the microchip, the researchers could count the cells, as well determine the kinds of antibodies that each cell secretes.
‘With the ease of a blood draw’
The researchers tested the device using blood samples from healthy donors as well as patients with the disease. After counting the number of cells captured in each sample, they observed very low numbers of circulating plasma cells in healthy samples – about two to five cells per milliliter of blood – versus substantially higher counts in patients diagnosed with multiple myeloma, of about 45 to 184 cells per milliliter.