Going with the flow

GAME-CHANGER: Bioengineering professor Luke Lee led an international research team that has developed a revolutionary blood analysis chip that could diagnose diseases such as HIV and tuberculosis within minutes. (Photo by Peg Skorpinski.)

For someone who is ill, the wait for an accurate diagnosis can be difficult, if not downright dangerous to one’s health. Physicians often rely on blood tests to confirm their opinion, but the time it takes to learn the results can delay appropriate and important treatment.

Globally, this problem most severely impacts people living in remote areas. Limited access to clinics and laboratories that perform and process blood tests means that residents of outlying places often postpone or forgo testing that could pinpoint their illness and lead to the most effective medical care.

But this public health challenge might just be a thing of the past. A major milestone in microfluidics could soon lead to stand-alone, self-powered chips that can diagnose diseases within minutes. Working as part of an international team of researchers, Berkeley engineers have developed a device that is able to process whole blood samples without the use of external tubing and extra components.

“The dream of a true lab-on-a-chip has been around for a while, but most systems developed thus far have not been truly autonomous,” says Ivan Dimov, post-doctoral researcher in bioengineering and co-lead author of the study. “By the time you add tubing and sample prep setup components required to make previous chips function, they lose their characteristic of being small, portable and cheap. In our device, there are no external connections or tubing required, so this can truly become a point-of-care system.”

Dimov works in the lab of the study’s principal investigator, Luke Lee, bioengineering professor and co-director of the Berkeley Sensor & Actuator Center.

“This is a very important development for global healthcare diagnostics,” says Lee. “Field workers would be able to use this device to detect diseases such as HIV or tuberculosis in a matter of minutes. The fact that we reduced the complexity of the biochip and used plastic components makes it much easier to manufacture in high volume at low cost. Our goal is to address global health care needs with diagnostic devices that are functional, cheap and truly portable.”

For the new Self-powered Integrated Microfluidic Blood Analysis System (SIMBAS) biochip, the researchers took advantage of the laws of microscale physics to speed up processes that may take hours or days in a traditional lab.

POINT-OF-CARE SYSTEM: Photograph of the stand-alone 1-by-2-inch SIMBAS chip simultaneously processing five separate whole-blood samples by separating the plasma from the blood cells and detecting the presence of biotin (vitamin B7). (Photo by Ivan Dimov.)

The SIMBAS biochip uses trenches patterned underneath microfluidic channels that are about the width of a human hair. When whole blood is dropped onto the chip’s inlets, the relatively heavy red and white blood cells settle down into the trenches, separating from the clear blood plasma. The blood moves through the chip in a process called degas-driven flow.

For degas-driven flow, air molecules inside the permeable polymeric device are removed by placing the device in a vacuum-sealed package. When the seal is broken, the device is brought to atmospheric conditions, and air molecules are reabsorbed into the device material. This generates a pressure difference, which drives the blood fluid flow in the chip.

In experiments, the researchers were able to capture more than 99 percent of the blood cells in the trenches and selectively separate plasma using this method.

“This prep work of separating the blood components for analysis is done with gravity, so samples are naturally absorbed and propelled into the chip without the need for external power,” says Dimov.

The team demonstrated the proof-of-concept of SIMBAS by placing into the chip’s inlet a 5-microliter sample of whole blood that contained biotin (vitamin B7) at a concentration of about 1 part per 40 billion.

“That can be roughly thought of as finding a fine grain of sand in a 1700-gallon sand pile,” says Dimov.

The biodetectors in the SIMBAS chip provided a readout of the biotin levels in 10 minutes.

“The SIMBAS platform may create an effective molecular diagnostic biochip platform for cancer, cardiac disease, sepsis and other diseases in developed countries as well,” says Lee.

Other co-lead authors of the study are Lourdes Basabe-Desmonts, senior scientist at Dublin City University’s Biomedical Diagnostics Institute, and Jose L. Garcia-Cordero, currently post-doctoral scientist at École Polytechnique Fédérale de Lausanne (EPFL Switzerland). Antonio J. Ricco, adjunct professor at the Biomedical Diagnostics Institute at Dublin City University, and Benjamin Ross, a bioengineering graduate student who works with Lee, also co-authored the study.

Their work on SIMBAS appeared as the cover story in the March 7, 2011 edition of the peer-reviewed journal Lab on a Chip.