A new "barcode chip" developed by researchers at the California Institute of Technology (Caltech) promises to revolutionize diagnostic medical testing.
In less than 10 minutes, and using just a pinprick's worth of blood, the chip can measure the concentrations of dozens of proteins, including those that herald the presence of diseases like cancer and heart disease.
The device, known as the Integrated Blood-Barcode Chip, or IBBC, was developed by a group of Caltech researchers led by James R. Heath, the Elizabeth W. Gilloon Professor and professor of chemistry, along with postdoctoral scholar Rong Fan and graduate student Ophir Vermesh, and by Leroy Hood, president of the Institute for Systems Biology in Seattle, Washington.
An IBBC, described in a paper in the advance online edition of Nature Biotechnology , is about the size of a microscope slide and is made out of a glass substrate covered with silicone rubber. The chip's surface is molded to contain a microfluidics circuit--a system of microscopic channels through which the pinprick of blood is introduced, protein-rich blood plasma is separated from whole blood, and a panel of protein biomarkers is measured from the plasma.
The chip offers a significant improvement over the cost and speed of standard laboratory tests to analyze proteins in the blood. In traditional tests, one or more vials of blood are removed from a patient's arm and taken to a laboratory, where the blood is centrifuged to separate whole blood cells from the plasma. The plasma is then assayed for specific proteins. "The process is labor intensive, and even if the person doing the testing hurries, the tests will still take a few hours to complete," says Heath. A kit to test for a single diagnostic protein costs about $50.
"We wanted to dramatically lower the cost of such measurements, by orders of magnitude," he says. "We measure many proteins for the cost of one. Furthermore, if you reduce the time it takes for the test, the test is cheaper, since time is money. With our barcode chip, we can go from pinprick to results in less than 10 minutes."
A single chip can simultaneously test the blood from eight patients, and each test measures many proteins at once. The researchers reported on devices that could measure a dozen proteins from a fingerprick of blood, and their current assays are designed for significantly more proteins. "We are aiming to measure 100 proteins per fingerprick within a year or so. It's a pretty enabling technology," Heath says.
To perform the assay, a drop of blood is added to the IBBC's inlet, and then a slight pressure is applied, which forces the blood through a channel. As the blood flows, plasma is skimmed into narrow channels that branch off from the main channel. This part of the chip is designed as if it were a network of resistors, which optimizes plasma separation.
The plasma then flows across the "barcodes." The barcodes consist of a series of lines, each 20 micrometers across and patterned with a different antibody that allows it to capture a specific protein from the plasma passing over. When the barcode is "developed," the individual bars emit a red fluorescent glow, whose brightness depends upon the amount of protein captured.
In the Nature Biotechnology paper, the researchers used the chip to measure variations in the concentration of human chorionic gonadotropin (hCG), the hormone produced during pregnancy. "The concentration of this protein increases by about 100,000-fold as a woman goes through the pregnancy cycle, and we wanted to show that we could capture that whole concentration range through a single test," Heath says.