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'Lab on a chip' may reduce preterm births

In the United States, one half million babies are born preterm. Worldwide, the number is estimated at 15 million. Complications associated with preterm birth are the number one cause of death for children under 5. Survivors often face a range of continuing health problems.


Help may come from a palm-sized plastic rectangle dotted with a few pinholes. The small chip — an integrated microfluidic device — is designed to predict with up to 90 percent accuracy, a woman's risk for a future preterm birth. With it, Brigham Young University (BYU) researchers hope to minimize the problems of premature delivery.

"It's like we're shrinking a whole laboratory and fitting it into one small microchip," explains Mukul Sonker, post doctoral chemistry student and lead author. The work recently published in Electrophoresis, is funded in part by the National Institutes of Health.


The goal was to take a finger-prick of blood and measure a panel of nine identified preterm birth biomarkers — essentially flags that indicate disease or other conditions. No current biomarker-based diagnostics exist for preterm births. Doctors can only observe mothers for potential risk factors.

"The symptom of preterm labor is going into labor — at that point you are managing the outcome instead of trying to prepare."

Adam Woolley PhD, Professor, Department of Chemistry, Brigham Young University, Provo, Utah, USA, study co-author.


With their oldest child, Woolley's wife began having contractions early in her third trimester. Only with hospital intervention did contractions stop, allowing her to carry their son to full term. Wolley: "Ours was only a glimpse into the potential problems of a preterm birth, but it is still really satisfying to know that the research my students and I are doing now could help others in some way with this important medical issue."

For the study, Sonker and Woolley with postdoctural candidates Radim Knob and Vishal Sahore, created a chip with an integrated system that pre-concentrates then separates nine maternal biomarkers. Sonker: "... if you preconcentrate proteins and peptides on the chip, you can get enough of a signal for prediction."


Once fully developed, adds Woolley, "it will help make detecting biomarkers a simple, automated task. Among its benefits, the chip is cheap, small and fast."


The annual costs associated with preterm birth in the United States alone is close to $30 billion. A preterm labor screening chip would allow medical facilities the economic advantage of intervention before mother and newborn need the significant costs of preterm delivery with post partum folow-up.


"There are a lot of preterm babies who don't survive. If we could get them to survive and thrive, it would be a huge gain to society."

Adam Woolley PhD


Abstract
Integration in microfluidics is important for achieving automation. Sample preconcentration integrated with separation in a microfluidic setup can have a substantial impact on rapid analysis of low-abundance disease biomarkers. Here, we have developed a microfluidic device that uses pH-mediated solid phase extraction (SPE) for the enrichment and elution of preterm birth (PTB) biomarkers. Furthermore, this SPE module was integrated with microchip electrophoresis for combined enrichment and separation of multiple analytes, including a PTB peptide biomarker (P1). A reversed-phase octyl methacrylate monolith was polymerized as the SPE medium in polyethylene glycol diacrylate modified cyclic olefin copolymer microfluidic channels. Eluent for pH-mediated SPE of PTB biomarkers on the monolith was optimized using different pH values and ionic concentrations. Nearly 50-fold enrichment was observed in single channel SPE devices for a low nanomolar solution of P1, with great elution time reproducibility (<7% RSD). The monolith binding capacity was determined to be 400 pg (0.2 pmol). A mixture of a model peptide (FA) and a PTB biomarker (P1) was extracted, eluted, injected, and then separated by microchip electrophoresis in our integrated device with ~15-fold enrichment. This device shows important progress towards an integrated electrokinetically operated platform for preconcentration and separation of biomarkers.

Keyword search
Integrated microfluidics; Microchip electrophoresis; Monoliths; Solid phase extraction

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Apr 18, 2017   Fetal Timeline   Maternal Timeline   News   News Archive   



Mukul Sonker (left) and Adam Woolley work with the chip they've designed
to eventually help predict a woman's risk of preterm birth.
Image Credit: Nate Edwards/BYU

 


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