"Lab-on-a-chip" Diagnostic Device to Detect Disease Biomarkers

"Lab-on-a-chip" Diagnostic Device to Detect Disease Biomarkers
NYUAD Assistant Professor of Mechanical and Biomedical Engineering Rafael Song is developing an ultra-sensitive biosensor for the detection of various disease biomarkers.

While working on developing new 3D-printing techniques for his Ph.D., Assistant Professor of Mechanical and Biomedical Engineering Rafael Song became interested in building smaller objects. "I started learning about microfabrication techniques, which allowed me to build things on a micro-scale level," said Song. "I realized there is a huge market potential to develop compact, portable, biomedical devices." When the application of microfabrication to biomedical areas became popular during his time at the Massachusetts Institute of Technology, it spearheaded Song's career toward a convergence of biology and engineering, also called bioengineering.

With his main research topic on biosensing, Song is currently developing an ultra-sensitive biosensor for the detection of various disease biomarkers. "If you can detect certain biomarkers at very early stage, then you can detect the disease and have a higher chance to treat it successfully," Song said.

A disease at a very early stage contains only a very low concentration of biomarkers, often less than a picogram per milliliter, and the current biosensors in the market are either too slow or incapable of detecting small concentration levels. This means that by the time the sensor detects biomarkers at a sufficiently higher concentration level, the disease would have progressed. "Hence, the goal is to develop a biosensor that can detect a small amount of biomarkers at a very early stage and rapidly," said Song.

Currently, commercially available biosensors are not able to detect molecules below a concentration of one picogram per milliliter. Song and his team in the Micro- and Nanoscale Bioengineering group at NYU Abu Dhabi are working to push down the threshold to below one picogram per milliliter into low femtomolar concentrations or below. While the more common techniques use nanomaterials such as nanowires and carbon nanotubes to detect smaller amounts of biomarkers in blood or fluid samples, Song came up with a different approach. He couples existing biosensors with an electrokinetic concentrator chip to concentrate the molecules at a specific site of detection.

By using an electrokinetic concentrator chip, molecules are moved to a concentrated spot (detection site) electrokinetically to increase detection sensitivity and detection speed. "So far we have been able to increase the local concentration of DNA by three orders of magnitude, or 1,000 fold, after 30 minutes," said Song. This electrokinetic concentration method can be extended to any charged biomolecules such as proteins, micro particles, or even ions.

With the molecules of interest now closer to the sensor, there is a higher chance of interaction to detect the presence of abnormal molecules. Called the Ion Concentration Polarization (ICP) method, Song uses the basic physical phenomenon of applying electrical potential difference across an ion-selective membrane. This polarization creates an ion depletion region, repelling all charged molecules from the membrane and allowing a formation of a concentrated plug when coupled with a pressure- or electroosmotically driven flow inside a microfluidic channel.

My ultimate goal is to develop a point-of-care, portable diagnostic tool for global health.

Rafael Song, NYUAD assistant professor of Mechanical and Biomedical Engineering.

As he continues to develop this research, Song will collaborate with Professor Rastislav Levicky from NYU Polytechnic School of Engineering, who has been working on morpholino-based detection for the past few years. Conventional morpholino sensors have low detection sensitivity and are slow. The coupling of Song's electrokinetic concentrator chip with Levicky's morpholino-based sensor will address both issues. This NYUAD-Polytechnic School of Engineering collaboration has been supported by NYUAD's Research Enhancement Fund for two years, and based on this work, new proposals have been submitted to various US funding agencies and a joint publication is in preparation.

Essentially creating a "lab-on-a-chip," Song is trying to shrink the size of a conventional lab by integrating the sample processing steps and a detection step all in one chip with microfabrication technology borrowed from the semiconductor industry. To enable research in lab-on-a-chip technologies at NYUAD, a state-of-the art microfabrication core facility has been established.

With no limitations on testing different disease types, this technique has a broad range of possible applications. "This chip is so flexible, it can be tailored toward detection of any cancer-related biomarker or any disease biomarker," Song said. "My ultimate goal is to develop a point-of-care, portable diagnostic tool for global health."

NYUAD's strategic location also comes into play here. With a new initiative in the Engineering division at NYUAD called Engineers for Social Impact — which emphasizes experiential learning by students through field work and developing locally sustainable engineering designs and technologies — the outcome of Song's research could potentially be integrated into its Global Health program. This initiative would also encourage students to "come up with creative solutions that will improve the lives of end users at the bottom of the socio-economic pyramid," Song said.

"We are so well positioned with our location in Abu Dhabi that we can bring students to sites and try to implement our technology where it's urgently needed."

This article originally appeared in NYUAD's 2013-14 Research Report (13MB PDF).