Bone marrow aspirate Photo by Chad McNeeley
Engineers say they have devised a microfluidic technique to capture and count circulating plasma cells from small samples of blood.
They believe the technique, described in Scientific Reports, may allow patients with multiple myeloma (MM) to avoid bone marrow biopsies in favor of conventional blood draws.
“Procedures of the traditional tissue biopsy are painful, associated with complications such as potential infections, and often available only in central hospitals, which require patients to travel long distances,” said Mohammad Qasaimeh, PhD, of New York University Abu Dhabi in United Arab Emirates.
“Capturing plasma cells from blood samples can serve as a liquid biopsy, which can be performed in clinics as often as required, and serve as a diagnostic and prognostic test during and after chemotherapy treatment. Moreover, captured cells can be used for drug testing and, thus, serve as a tool for personalized medicine.”
About the technique
The current microfluidic technique builds on a design that was developed by George Whitesides, PhD, of Harvard University in Cambridge, Massachusetts.
Dr Whitesides and his colleagues fabricated a 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.
Researchers have since reproduced this microfluidic design, coating the microchip’s floor with certain molecules to attract cells of interest.
Qasaimeh and colleagues used the microfluidic herringbone design to capture circulating plasma cells. They coated the channels of a microchip with CD138, an antibody expressed on the membranes of plasma cells.
The team then flowed 1 mL samples of blood through the device. The herringbone grooves circulated the blood in the microfluidic channels, where the antibodies grabbed onto any passing plasma cells and let 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 as determine the kinds of antibodies each cell secretes.
Capturing cells
The researchers tested the device using blood samples from healthy donors as well as MM patients.
The team observed very low numbers of circulating plasma cells in healthy samples—2 to 5 cells per mL of blood—and substantially higher counts in MM patients—45 to 184 cells per mL.
The researchers noted that MM patients in remission also exhibited higher counts of circulating plasma cells—20 to 24 cells per mL—than healthy donors.
Rahit Karnik, PhD, of Massachusetts Institute of Technology in Cambridge, said this device may reveal more subtle information about a patient’s state, even in remission.
“When patients go into remission, their antibody levels can look normal,” Dr Karnik said. “But we detect a level of circulating plasma cells that is above the baseline. It’s hard to tell whether these cells are cancerous, but at least this technique is giving us more information. With the ease of a blood draw, this may enable us to track cancer in a much better way.”
Analyzing antibodies
The researchers also looked at antibodies produced by the plasma cells captured in the device.
The team determined the ratio of plasma cells producing kappa- and lambda-type antibodies and compared them to conventional blood tests for the same antibodies, for both healthy subjects and MM patients.
Both sets of results matched, which validates the microfluidic device’s accuracy.
Next steps
Dr Karnik said, in the future, researchers may use this design to perform genetic tests on the captured cells or look for mutations in the cells that may further characterize MM.
“We can capture and stain these cells in the device, which opens the possibility of studying whether there are new mutations in the cells,” Dr Karnik said.
“With cancers like multiple myeloma, even for patients in remission, cancer can recur. Detecting the level or mutation of plasma cells in blood might provide an early detection method for these patients.”
