Dr. Moran Bercovici’s lab is developing novel lab-on-a-chip microfluidic technologies for applications ranging from medical diagnostics to defense against bioterrorism.
From monitoring our drinking water, through genetic testing, and to cancer detection, biochemical and medical diagnostics have become an essential part of our life. These diagnostic tests typically require modern labs which make use of highly sensitive equipment and specially trained personnel. As a result, such labs are expensive to operate and the need for sample transport, pooling, labeling, and reporting often results in sample-to-answer time of several days. Furthermore, in large parts of the developing world the basic infrastructure for such labs (such as running water and stable power supply) is simply nonexistent.
“Imagine if each one of us would have the power of an entire lab in their pocket, for just a fraction of the price” says Dr. Moran Bercovici, director of Technion’s Microfluidic Technologies Laboratory. “That may sounds like science fiction, but just imagine describing a smart phone to someone 20 years ago”. Dr. Bercovici’s lab is developing novel lab-on-a-chip microfluidic technologies for applications ranging from medical diagnostics to defense against bioterrorism.
Microfluidics is the science and technology of fluids at small scales. Going down to the micro and nano scale, the physics of fluids changes dramatically. For example, surface forces and electric body forces, often negligible at larger scales, begin to dominate. “If we understand these small scale processes well enough, it can enable us not only to miniaturize large scale processes to the size of a chip, but also to create new and powerful functionality which doesn’t even exist in large scale.” The field is at the interface between several disciplines, and strongly couples fluid mechanics, electricity, chemistry, and biology. “Tying everything together is challenging, but is also what makes this field so exciting” says Dr. Bercovici.
In a recent study performed by Dr. Bercovici and colleagues during his postdoc at Stanford University, the researchers demonstrated the ability to accelerate the detection of DNA sequences by more than 10,000 fold, doing what would otherwise take days in just a few seconds. To achieve this, they leverage an electrophoretic technique called isotachophoresis (ITP), which focuses charged species based on their electrophoretic mobility (velocity under an electric field). To perform ITP, researchers fill a microfluidic channel with a solution having high mobility ions called a leading electrolyte (LE) and fill a small reservoir with a mixture of the sample and low mobility ions (trailing electrolyte, TE). When an electric field is applied to the channel, sample ions electromigrate and accumulate at a narrow, order 10 µm, interface formed between the LE and TE (Movie 1). “This can increase the concentration of the sample by several orders of magnitude” explains Bercovici.
“What we showed is that if you could focus two reacting species in that same location, then what you get is essentially a virtual reaction chamber in which the local high concentrations accelerate the reaction” explains Bercovici. To demonstrate the diagnostic value of their new technique, the researchers have focused target DNA sequences together with DNA probes which fluoresce upon hybridization to the target. Consistent with their theoretical prediction, they achieved reduction in detection time from 3.5 days to 23 seconds.
“Until now we’ve only demonstrated it for DNA, but we believe this technique has a huge potential in improving the sensitivity and speed of a large number of diagnostic tests.” Says Bercovici. “We continue to work in parallel on gaining better and deeper understanding of flow at the microscale, on developing analytical and computational prediction tools, and on leveraging these to create new tools and new capabilities”.
- Bercovici, M., Kaigala, G.V., Mach, K.E., Han, C.M., Liao, J.C. & Santiago, J.G. Rapid Detection of Urinary Tract Infections Using Isotachophoresis and Molecular Beacons. Analytical Chemistry 83, 4110-4117 (2011).
- Garcia-Schwarz, G., Bercovici, M., Marshall, L.A. & Santiago, J.G. Sample dispersion in isotachophoresis. Journal of Fluid Mechanics 1, 1-21 (2011).
- Bercovici, M., Kaigala, G.V., Backhouse, C.J. & Santiago, J.G. Fluorescent Carrier Ampholytes Assay for Portable, Label-Free Detection of Chemical Toxins in Tap Water. Analytical Chemistry 82, 1858-1866 (2010).
- Bercovici, M. Open source simulation tool for electrophoretic stacking, focusing, and separation. Journal of Chromatography A 1216, 1008-1018 (2009).