HAIFA, ISRAEL and ZURICH (August 8, 2017) – Proteins are one of the most important classes of biomarkers – biological molecules indicative of a disease or health of an individual. Protein detection is critical in a wide variety of tests that include the diagnosis of malaria, detection of a cardiovascular event, cancer screening and monitoring, and more.
Now, a team from Technion-Israel Institute of Technology in Haifa, Israel and IBM Research in Zurich has improved the sensitivity of protein detection in immunoassays by more than 1,000-fold, when compared to standard immunoassay implementation. The team’s method – which appears on the cover of the peer-reviewed journal Analytical Chemistry – is based on a simple piece of hardware: a microfluidic chip containing flow channels the width of a human hair.
High sensitivity in detection is particularly important when protein biomarkers are present in extremely small numbers, as is the case in the early stages of a disease. The team’s approach might one day enable simple devices capable of analyzing small samples (such as a drop of blood), replacing the large and sophisticated laboratory equipment that is currently required.
“We use an old focusing technique called isotachophoresis (ITP) in a new way,” says Assistant Professor Moran Bercovici, of the Technion Faculty of Mechanical Engineering. “Using a combination of electric fields and specialized chemistry, we collect proteins into a tiny volume and precisely deliver them to react with detection antibodies patterned on the surface of the microchannel.”
“We essentially cheat the detector,” says Federico Paratore, a joint PhD student between the groups, and the lead author on the work. “We present a protein concentration that is 10,000-fold higher than in the original sample to a standard detector, and get the detector to respond accordingly.”
The test is a simple one, as demonstrated by Paratore. A few drops of the sample are introduced into the microfluidic chip, and an electric field is turned on. The proteins are compressed to a volume of approximately 50 picoliters – about 1 million times smaller than the volume of a human teardrop, and the result is visible within a few minutes.
Paratore is part of a joint European Union project, Virtual Vials, and works across both sites, combining the strengths of the Technion’s team in electrokinetics and fluid mechanics with IBM-Zurich’s expertise in microtechnology and diagnostics. At the Technion, Paratore collaborated with Tal Zeidman-Kalman and Tally Rosenfeld, who are co-authors of this paper.
“The elegance of this approach is in its simplicity, and of course the immense enhancement in assay sensitivity that could be applied to a range of immunoassay,” says Dr. Govind Kaigala, scientist at IBM Research in Zurich. “We strongly believe such a technology will help to fill the gaps in existing immunoassay technology, and be applied directly to biological samples such as blood, saliva, or urine.”