MIT scientists have developed a prototype device that allows chemotherapy patients to test their white blood cell levels without pricking a finger or taking a blood sample.
MIT scientists have developed a prototype device that allows chemotherapy patients to test their white blood cell levels without pricking a finger or taking a blood sample. Patients could use the information to take preventive action to avoid infection when white blood cell levels fall dangerously low.
Dr. Carlos Castro-Gonzalez, an MIT postdoc researcher in the Research Laboratory of Electronics (RLE) who led the research team, came up with the idea four years ago when MIT sponsored a visit by a team of postdocs to the oncology department of a Madrid hospital.
"We saw that patients are required to travel to draw blood and that limits how often they can be monitored," Castro-Gonzalez says.
Chemotherapy patients, he explains, usually receive a dose every 21 days. After each dose, their white blood cell levels fall and then gradually climb again. Yet doctors usually test blood just prior to giving a new dose. During the testing interval, however, white blood cell counts might fall, leaving patients prone to serious infections.
"If we could measure those levels more frequently at home, we could identify patients at high-risk sooner and they could receive preventive treatment before they develop the infection," Castro-Gonzalez says.
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The device consists of a wide-field microscope that tracks blood flow in the slender capillaries of the skin at the base of finger nail. Capillaries are located very close to the skin's surface in this area and some are no larger than the diameter of a white blood cell, which pass through one at time.
The patient places a finger in the device, and the microscope emits blue light. It penetrates 50 to 150 microns below the skin and is reflected back to a camera that records one minute of video per patient. For the study, three human assistants watched the videos and counted whenever a white blood cell passed through a capillary.
Rather than invent an optical device to measure blood cells, Castro-Gonzalez's team looked around for useable technologies. They discovered a simple, affordable optical system used to study capillary morphology. It does this by relying on the light-absorption properties of hemoglobin in red blood cells. The white blood cells - the ones the MIT team wanted to identify - show up as white gaps in hemoglobin.
"We had to revamp this equipment, developing a custom-made system to visualize not only the morphology but also the dynamics of what's happening inside the capillaries," Castro-Gonzalez says. "We want to look for absences or gaps in the flow of red blood cells where white blood cells can be seen passing through."
But the scientists faced some confounding factors. Gaps in the flow of hemoglobin could also indicate pockets of plasma and not white blood cells. "We studied the literature and learned about certain features in gaps and capillaries that allowed us to identify white blood cells more accurately," he says.
The researchers tested their prototype device with 11 patients at Massachusetts General Hospital and University Hospital La Paz in Madrid at various points during their chemotherapy treatment.
The device does not provide a precise white blood cell count. Instead it helps to identify whether levels are above or below a threshold considered dangerous - defined as 500 neutrophils (the most common type of white blood cell) per microliter of blood.
The technique proved 95 percent accurate. It does not replace blood testing but instead provides an early alarm system. The team published a proof-of-concept paper in Scientific Reports, an open access journal from the publishers of Nature.
Since submitting their paper, the researchers have been developing a computer algorithm to count white blood cells automatically. Preliminary results indicate that the algorithm is about as accurate as the human counters.
The paper's first author is Aurelian Bourquard, an RLE postdoc. Other team members who developed the new technology include RLE research engineer Ian Butterworth, former MIT postdoc Alvaro Sanchez-Ferro, and Technical University of Madrid graduate student Alberto Pablo Trinidad.
The research team has applied for patents on the technology, and has launched a company called Leuko. The team has received commercialization help from the MIT Innovation Initiative, the MIT Deshpande Center for Technological Innovation, the MIT Sandbox Innovation Fund, the Martin Trust Center for Entrepreneurship, the MIT Translational Fellows Program, and the MIT Venture Mentoring Service.
The researchers plan to adapt the system to generate more precise white blood cell counts, allowing clinicians to monitor bone marrow transplant recipients and people with certain infectious diseases.
"In this paper, we proved the principle that one can simply and non-invasively detect patients with dangerously low white cells," Castro-Gonzalez says. "We wanted make a product that can offer actionable information for physicians to improve their patients' outcomes."
John H. Tibbetts is an independent technical writer.
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