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IN THE MICRO LAB:
Plumbing the width of a human hair // channels only microns deep // testing a single drop of saliva // With speed, efficiency and portability, and that’s only the beginning.

Studies in Miniature

By Logan Ward // Fall 2008
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Microfluidics

Courtesy Folch Lab

It may look like a painting by Morris Louis, but this magnified photograph shows the many-channeled plumbing of a “lab on a chip‚” created by University of Washington bioengineer Albert Folch to study cells’ reactions to chemicals. Fluids—in this case, dye and water—are pumped through pipes just 500 microns wide, en route to chambers where they will merge to form 16 combinations.

A single drop of saliva contains almost every substance present in human blood—including 1,166 proteins and unknown numbers of hormones, carbohydrates, electrolytes and mineral ions—but at concentrations 10 to 100 times lower. Last spring, researchers from three California institutions catalogued the complete set of saliva proteins, in part to identify many that are disease indicators, or biomarkers. Above-normal C-reactive protein, for example, indicates acute inflammation that has been linked to rheumatoid arthritis, lupus and even heart disease, whereas HIV antibodies (also proteins) can signal the presence of the condition. So—in theory, at least—a simple spit test might tell as much about a person’s health as a full-scale blood profile, but without the painful stick or the need for a phlebotomist to draw blood.

The problem is that current spit tests in most instances aren’t practical. The analytical equipment is too expensive, the specialized labor too costly and the wait time for results too prolonged. But now that may change, as the field of microfluidics, also known as lab-on-a-chip technology, comes into its own. Sandia National Laboratories in Livermore, Calif., has designed a palm-size device that can measure how far certain biomarkers in saliva travel through a gel the length of a fingernail—and by doing so, can spot periodontal disease even before the onset of symptoms and can potentially detect illegal drugs. What’s more, the results are available in a matter of minutes, rather than the hours or days required for a typical laboratory test performed on saliva or blood. In addition, Micronics, a company located in Redmond, Wash., has created a microfluidics device the size of a credit card that can diagnose malaria and dengue fever from a fingerprick drop of blood within minutes. Micronics expects to add more diseases to its capabilities soon.

When chemical analyses and biological assays are done on such a tiny scale, they yield quicker results that are also less expensive because the equipment can be mass produced, or is even disposable and requires just microliters of samples and testing compounds. Even more remarkable, thanks to the peculiar laws of fluid dynamics, liquids in very small spaces operate more smoothly and predictably, enabling researchers to scrutinize microscopic developments, such as the growth of nerve cells in muscle tissue, and to grow perfect protein crystals—a delicate process, essential in the search for effective drug compounds, that had been relegated to the zero-gravity environment of NASA space missions. Microfluidics, in short, is opening avenues that, on our unwieldy human scale, were never possible, let alone affordable.

Microfluidics was born when the worlds of chemistry and silicon chips collided, says Harvard University professor and chemist George Whitesides, “developing as a cooperation between people who like to make small things and people who need small things.” In the 1980s, as analytical chemists and molecular biologists delved ever deeper into the molecular structure of compounds, they yearned for a technology that would do for their lab experiments in genetic sequencing and protein analysis what computers had done for their data calculations. Because their work revolved around analyzing substances, that meant creating a way for fluids to move on a microscale.

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Diagnosis in the Fast Lane

With two microscope slides, one computer chip and nine volts of electricity, a new saliva analyzer can return results in just eight minutes.

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hed-dossier

1. “The Origins and the Future of Microfluidics,” by George M. Whitesides, Nature, July 27, 2006. A pioneer muses on the field’s successes and growing pains.

2. “Isolation of Rare Circulating Tumour Cells in Cancer Patients by Microchip Technology,” by Sunitha Nagrath et al., Nature, Dec. 20, 2007. A detailed account of the first clinical study involving Mehmet Toner’s circulating-tumor-cell chip, with findings that MIT cancer researcher and Nobel laureate Phillip Sharp calls “stunning.”

3. “Microfluidic Immunoassays as Rapid Saliva-based Clinical Diagnostics,” by Amy E. Herr et al., Proceedings of the National Academy of Science, March 27, 2007. A detailed description of a new point-of-care diagnostic device that microfluidics made possible.

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