Preterm birth (PTB) is the most common complication of pregnancy, with over 500,000 early births annually in the United States. PTB is responsible for the majority of neonatal deaths and newborn illnesses. Unfortunately, the ability to assess PTB risk prior to contractions is not available clinically;this capability would enable therapeutic interventions that prevent or forestall delivery, potentially decreasing PTBs and/or the severity of neonatal complications. This renewal proposal focuses on the development of an integrated microfluidic platform for rapid, sensitive and inexpensive quantitation of serum PTB risk biomarkers (newly discovered peptides and known proteins), weeks before contractions occur. This proposal thus offers a major human health impact, potentially decreasing the prevalence of PTBs and their associated complications. This proposal tests the hypothesis that further development of microfluidic systems, which combine sample preparation, separation and quantitation in a single platform, will enable the direct measurement of PTB biomarkers in serum, allowing risk assessment and preventative measures to occur well before contractions begin. The proposed automated microfluidic platform has three main components: (1) a multiplexed immunoaffinity extraction module to selectively capture unlabeled PTB biomarkers;(2) a purification/labeling module to enrich PTB biomarkers and then allow fluorescence labeling with removal of unreacted tag;and (3) a microchip electrophoresis module to separate the labeled PTB biomarkers, enabling their quantitation. This approach improves significantly over present instrument- and personnel-intensive methods to determine PTB biomarkers, and should offer specificity comparable to sandwich immunoassays that would be problematic to develop for small peptide targets. The goal of this renewal proposal is to further develop integrated microfluidic systems for convenient, inexpensive, rapid and quantitative analysis of serum biomarkers with PTB risk correlation. This objective will be accomplished via three specific aims.
In Aim 1 electrokinetically operated microchips to quantify PTB biomarkers will be created and tested, integrating immunoaffinity extraction, solid-phase enrichment, fluorescence labeling, electrophoretic separation and biomarker quantitation.
Aim 2 will involve developing PTB biomarker analysis microdevices that use pressure actuation of on-chip valves and pumps to carry out integrated sample preparation operations. Performance of the devices from Aims 1 and 2 will then be compared.
In Aim 3 these microfluidic platforms will be used to measure PTB biomarkers in blood samples to establish the feasibility of microchip methods in predicting PTB risk weeks before contractions occur. Importantly, this work addresses the urgent need to diagnose PTB risk when therapeutic intervention is still feasible;however, the general nature of the approach should be applicable well beyond biomarkers for PTB, further exemplifying the large and important health impact of these studies.

Public Health Relevance

We will develop and evaluate inexpensive and miniature devices that can determine risk for a preterm birth using a finger-stick blood sample from a pregnant woman, several weeks before contractions might occur. After diagnosis, treatment could be initiated, and preterm birth numbers and associated complications would be reduced drastically.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01EB006124-09
Application #
8701291
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Lash, Tiffani Bailey
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham Young University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Provo
State
UT
Country
United States
Zip Code
84602
Kumar, Suresh; Sahore, Vishal; Rogers, Chad I et al. (2016) Development of an integrated microfluidic solid-phase extraction and electrophoresis device. Analyst 141:1660-8
Sahore, V; Kumar, S; Rogers, C I et al. (2016) Pressure-actuated microfluidic devices for electrophoretic separation of pre-term birth biomarkers. Anal Bioanal Chem 408:599-607
Gong, Hua; Woolley, Adam T; Nordin, Gregory P (2016) High density 3D printed microfluidic valves, pumps, and multiplexers. Lab Chip 16:2450-8
Knob, Radim; Sahore, Vishal; Sonker, Mukul et al. (2016) Advances in monoliths and related porous materials for microfluidics. Biomicrofluidics 10:032901
Yang, Rui; Pagaduan, Jayson V; Yu, Ming et al. (2015) On chip preconcentration and fluorescence labeling of model proteins by use of monolithic columns: device fabrication, optimization, and automation. Anal Bioanal Chem 407:737-47
Rogers, Chad I; Qaderi, Kamran; Woolley, Adam T et al. (2015) 3D printed microfluidic devices with integrated valves. Biomicrofluidics 9:016501
Pagaduan, Jayson V; Ramsden, Madison; O'Neill, Kim et al. (2015) Microchip immunoaffinity electrophoresis of antibody-thymidine kinase 1 complex. Electrophoresis 36:813-7
Pagaduan, Jayson V; Sahore, Vishal; Woolley, Adam T (2015) Applications of microfluidics and microchip electrophoresis for potential clinical biomarker analysis. Anal Bioanal Chem 407:6911-22
Gong, Hua; Beauchamp, Michael; Perry, Steven et al. (2015) Optical Approach to Resin Formulation for 3D Printed Microfluidics. RSC Adv 5:106621-106632
Chatterjee, Debolina; Mansfield, Danielle S; Woolley, Adam T (2014) MICROFLUIDIC DEVICES FOR LABEL-FREE AND NON-INSTRUMENTED QUANTITATION OF UNAMPLIFIED NUCLEIC ACIDS BY FLOW DISTANCE MEASUREMENT. Anal Methods 6:8173-8179

Showing the most recent 10 out of 33 publications