At the Heart of Things

Dozens of laboratory directors, cardiologists, internal medicine physicians, clinical chemists, and biomedical engineers visited Bar-Ilan University in late September for a three-day symposium on innovative high-sensitivity cardiac troponin and other cardiac biomarkers testing. The symposium was held under the auspice of the International Federation of Clinical Chemistry and The European Federation of Clinical Chemistry and Laboratory Medicine, and sponsored by the major manufacturing companies in this field

"Troponin is a protein that is secreted to the bloodstream following a heart attack," explains Dr. Amos Danielli, head of the optical imaging and biosensing laboratory at the Alexander Kofkin Faculty of Engineering and BINA at Bar-Ilan University as well as symposium organizer. "Only eight percent of ER visits involving chest pain are actually heart attacks. More than 90 percent of the patients presenting with chest pain do not have a heart attack and most of them can and should be discharged. Unfortunately, the devices currently at our disposal can't detect low levels of cardiac troponin, so everyone ends up being hospitalized for at least 6-9 hours. Only then, if cardiac troponin levels are still low and undetected, they are discharged." 

Emergency rooms are short on space and high on action. Suspicion of a heart attack is the second most common reason for ER visits. If we had a way to rapidly rule-out heart attack by detecting low levels of cardiac troponin in the blood, it would be extremely beneficial to both patients' wellbeing and ER efficiency.   

"If we want emergency medicine to use these innovative solutions, we must create collaborations between the emergency medicine system and minds behind these technologies. This symposium was a great platform for establishing these connections," notes Dr. Danielli, who implements such cooperation in his lab, and whose many partners attended the symposium as guests and speakers.  

Dr. Danielli began researching and developing this optical-based highly sensitive detection of proteins, viruses, and DNA sequences during his doctoral studies at Tel Aviv University and post-doctoral research at Washington University. For the past five years, he and his students have been continuing the study at Bar-Ilan University. "We have been able to identify protein molecules in blood for a while now, by linking them with fluorescent molecules that emit light when lit. However, in low concentrations, the signal is relatively weak and often goes undetected. Imagine the blood tube is the size of a room," says Dr. Danielli, "and the size of the laser beam is the size of a fist. Inside this fist there may be as little as 2-3 fluorescent molecules." At that stage, Dr. Danielli added to the solution magnetic particles that attach to the target protein molecules. The result: protein molecules with fluorescent molecule on one side and a magnetic particle on the other. Other scientists make such sandwiches, too, and use the magnetic quality to draw all target molecules to one side of the test tube. Now they can pump the rest of the liquid out of the tube and replace it with distilled water. This is an extremely complicated process, and it does not guarantee that all the target protein molecules indeed group where they should and that the rest of the solution is fully removed.

"At this point, I set a goal, to simplify the process and hone its accuracy. My innovation relies on the use of two electro-magnets, magnates activated by electric current. When positioned just so, they generate a strong magnetic field that draws all of the target molecules to the narrow area of the laser beam. This significantly increased the signal of the target molecules. Now, to obviate the pumping stage, we alternate between the electro-magnets, going from one to the other. The molecules shift from side to side through the laser beam and outside of it: inside the beam, they shine; outside they do not. We’ve generated a unique flickering effect that differs from the fixed noise of the solution. This enables us to easily determine the exact percentage of targeted protein in the solution."   

This high-sensitive innovative technology is already being used in a collaborative research with four other labs at Bar-Ilan University, and its simplicity is expected to assist in the development of small point-of-care devices, the size of machine coffeemaker. Based on Dr. Danielli's technology, the first device is already in place at Tel Hashomer Haim Sheba Medical Center, used for detecting Zika virus in blood samples. Such an advance could not have taken place was it not for Dr. Danielli's research collaboration with Prof. Eli Schwartz, Israel’s leading expert on tropical diseases and travel medicine, and Dr. Yaniv Lustig from the Central Virology Laboratory in Tel Hashomer, a former doctoral student of Prof. Shulamit Michaeli, Vice President of Research at Bar-Ilan University.

Thanks to a generous grant by the US-Israel Binational Science Foundation, Dr. Danielli is able to carry out this research on West Nile Fever together with esteemed clinical chemist and world expert, Dr. Michael Diamond of Washington University.  

"With the dedication of my staff and the help of my notable partners," says Dr. Danielli "I'm continuing my work with the hope that it will soon be used to test low levels of cardiac troponin in blood, benefitting patients and emergency medicine systems around the world."