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July 3, 2017

Lab-on-a-chip as early warning system for preterm birth

Preterm birth is the leading cause of neonatal morbidity and mortality. Though there are many underlying causes of pregnancy-associated complications, infection and inflammation are highly significant risk factors. In the near future a new microfluidic chip system may be used as an early warning system.

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Researchers funded by the National Institute of Biomedical Imaging Bioengineering have developed a system to capture and identify a scarce blood peptide (a fragment of an inflammatory protein) called P1, that can predict increased risk of preterm birth. Early detection offers the opportunity to begin medical interventions to delay birth or increase foetus viability to save lives and reduce lifelong disabilities.

Premature birth complications

Worldwide, some 15 million babies are born prematurely every year. Almost 1 million of them die each year due to the associated complications. In the U.S. about 12 percent of babies are born prematurely. Those that survive, often face a lifetime of learning disabilities and problems with vision and hearing, according to WHO.

A range of interventions for pregnant woman are available already to reduce the risk of preterm birth – if identified early – including steroid injections that strengthen the lungs of the foetus. Other preventive measures for the mother are optimizing nutrition and other lifestyle changes.

Early warning system

Now, a research team at Brigham Young University, led by Professor Adam T. Woolley, Ph.D. Professor, Department of Chemistry, has developed an early warning system: a microfluidic chip, also called a lab-on-a chip, which performs multiple steps to capture and accurately identify the P1 peptide that predicts preterm birth. The work was published in the March online issue of Electrophoresis.

Tiffani Lash, Ph.D., director of the NIBIB program in Microfluidic Bioanalytical Systems, says it’s  exciting to see the continued growth of microfluidic technologies being used as miniaturized diagnostic platforms, particularly in the case for reducing the incidence of preterm labour and delivery. “This tiny yet sophisticated technology has great potential to be of tremendous significance on the personal, public health, and even economic levels both in the U.S. and worldwide.” 

Indicating presence of disease

The chip, a miniature laboratory of about 1 x 2 inches, is known as an “integrated” chip because it performs multiple processing steps on a single chip. This is achieved by moving the sample through different areas or reservoirs on the chip in which the sample is further processed to eventually isolate and confirm the presence of the substance of interest — indicating the presence of disease.

The Brigham Young University team uses solid phase extraction and microchip electrophoresis. The solid phase extraction is the first step, which uses the special chemical properties of the preterm birth P1 peptide to concentrate and separate it from most of the other substances in a blood sample. The next step, microfluidic electrophoresis, uses an electrical current to move and further separate the P1 molecules from any other remaining components. Finally, the enriched P1 peptide is detected as it migrates to a specific position in the microfluidic channel. 

Yes or no answer

The ultimate goal is to place a single drop of blood on the chip, and after processing, receive a “yes” or “no” answer to whether the peptide which indicates increased risk of preterm birth, is present. The chip used in these experiments is a prototype, which will need refinement and optimization before it is ready to be commercialized and used in various health care settings. But, the current results are extremely encouraging.

“Demonstrating the ability to detect minute amounts of the P1 peptide is the really tough part,” team leader Woolley says. “We are quickly moving toward a chip that is inexpensive, small, fast and requires only a single drop of blood. Our team is working towards a final product that is easily used by individuals in a range of settings including hospitals and clinics in the U.S., as well as in rural and underserved communities around the world.”

Many diseases including cancer, degenerative conditions, and infections release substances into the blood that can give an early indication of disease. Typically, such biomarkers are at very low concentrations that cannot be routinely captured and analysed. Therefore, Woolley says, the isolation and concentration strategy developed here has the potential to be adapted for identifying a range of diseases before any symptoms are observed. Early identification of patients with risk factors for a number of disorders would allow for early treatment that could potentially stop the development of disease in its earliest stages.

Watch this video about fluorescent P1 enrichment indicating increased preterm birth risk.

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