Get Your Blood Scanned on a Barcode Chip

Some day when you put a pinprick’s worth of blood into a lab-on-a-chip developed at Caltech, you’ll be able to tell within 10 minutes if you’re at risk for heart disease or cancer. The device, known as the Integrated Blood-Barcode Chip, or IBBC, measures the concentrations of dozens of proteins in your blood serum at once. It was developed by a group led by James Heath, Caltech’s Gilloon Professor and professor of chemistry, along with postdoc Rong Fan and grad student Ophir Vermesh, and by Leroy Hood (BS ’60, PhD ’68), president of the Institute for Systems Biology in Seattle, Washington.

An IBBC is essentially a microscope slide coated with silicone rubber. The rubber’s underside is molded into a system of microscopic channels. As a pinprick of blood flows through the channels, the protein-rich plasma is separated out, and protein biomarkers are measured in the plasma.

Nowadays, blood tests take hours, not counting the time needed to draw a vial of blood from your arm and deliver it to the lab. There, the blood is centrifuged to separate the plasma, which is analyzed for each specific protein separately. “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. “We wanted to lower the cost of such measurements by orders of magnitude. 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.” A test kit for a single protein currently costs about $50. Says Heath, “We are optimistic that our platform, when fully developed, will reduce this cost to pennies per biomarker.”

A single chip can simultaneously test the blood from eight patients, and each test measures many proteins at once. “We’re aiming to measure 100 proteins per fingerprick within a year or so. It’s a pretty enabling technology,” Heath says.
The IBBC analyzes a blood drop by gently pumping it through a relatively wide channel. Smaller channels branching from the main one skim off some of the plasma and direct it along a “barcode”—one per channel. Each line in the barcode is 20 millionths of a meter wide and covered with an 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 each protein captured.

In the paper announcing this work in the December issue of Nature Biotechnology, the researchers measured human chorionic gonadotropin, a 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. The scientists also analyzed the blood of breast- and prostate-cancer patients for a number of biomarkers. These proteins vary in type and concentration—a woman with breast cancer, for example, will produce a different suite of biomarkers than a man with prostate cancer, and a woman with an aggressive breast cancer may produce proteins that are different from a woman with a less-deadly cancer. After the diagnosis, biomarkers may change as treatment progresses, so an IBBC could also be used much as a diabetic tests his or her blood sugar.

The barcode chip is now in human clinical trials on patients with glioblastoma, a common, aggressive brain tumor. The researchers are also using the chips to determine how diet and exercise change the composition of the proteins in the blood of healthy people.

Currently, the barcoded information is “read” with a common laboratory scanner that is also used for gene- and protein-expression studies. “But it should be very easy to design something like a supermarket UPC scanner to read the information,” making the process even more user-friendly, says postdoc Rong Fan, the first author on the paper.

The paper’s other authors are Alok Srivastava, a postdoc at the Institute for Systems Biology; Brian Yen, then a Caltech postdoc; postdoc Lidong Qin; grad students Habib Ahmad and Gabriel Kwong; and undergrads Chao Chao Liu and Julianne Gould. The work was funded by the National Cancer Institute and by the Institute for Collaborative Biotechnologies through a grant from the United States Army Research Office. —KS