Flow cytometry is a technique for counting and examining microscopic particles such as cells and bacteria. Traditionally, the microscopic particles are focused to a narrow stream of fluid, by a surrounding stream, called the sheath fluid, such that focused light gives uniform signals as the particles pass by an electronic detection apparatus.
Flow cytometers allow for simultaneous analysis of the physical and/or chemical characteristics of up to 50,000 cells or particles per second and are routinely used in the diagnosis of health disorders, blood cancers and for evaluating HIV or AIDS disease progression.
However statistically accurate identification of a variety of rare cells that can also be present in blood is currently not possible in a reasonable amount of time using standard flow cytometry.
“In blood, the most common cells are red blood cells. There are one thousand times more red blood cells than white blood cells, which provide doctors with useful diagnostic information. But then there are actually one thousand times more white blood cells than other even more rare cells that can provide other critical information,” said Dino Di Carlo, an assistant professor of bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science.
“Let’s say you had late stage breast cancer or colon cancer,cells from the primary tumor can also be found in blood but in much smaller quantities. Finding these rare cells among red blood cells is like finding a needle in a haystack, except you often don’t have access to a trick like a magnet, but have to look at each one individually. That is why higher throughputs could have a very important impact for diagnosis, understanding disease and for follow-up patient treatment.”
Increases in health care costs are often a concern with new diagnostic technology. Despite the success of current flow cytometers, there also continues to be great interest in decreasing the cost of operating the equipment and of course the equipment itself. Traditional flow cytometers are bulky, requiring large bench-top equipment and are expensive, costing more than $30,000 to produce. The complexity of the equipment also requires trained personnel to operate, analyze and maintain the system. These factors make current flow cytometers less than ideal for point-of-care or resource limited settings, and lead to an increased economic burden of healthcare in general.
But all this may change in the near future as Di Carlo and his research group have developed a miniature flow cytometer that can analyze up to one million blood cells per second. The new device, unveiled in a recent paper published in the journal, Lab on a Chip, is microfluidic based and needs only a single pump and one camera.
Traditional flow cytometers have only one channel such that analysis cannot be performed in parallel, Di Carlo’s cytometer has 256 channels through which cells can flow and be analyzed in parallel. Di Carlo has also rid his microfluidic device of the sheath fluid. The miniature version allows the fluids own momentum to position cells for analysis within the channels, eliminating the need for any extra fluid. Removing the fluid also reduces operating costs and allows the equipment to be much more portable for use in much needed point-of-care and resource-poor settings.
“It’s the method of ordering the cells so you can see them without overlap and how we use inertia to focus the cells… that’s the great innovation of the work. This technique will enable many more, high throughput, rare cell applications and will allow for other types of detection. We’re working with some outside companies and other academic researchers who work on detection to further this technology along,” said Di Carlo.
Di Carlo’s team, including graduate students Claire Hur and Henry Tse next plan to combine their microflow cytometer with wide field imaging and electrical detection techniques.