Heart Attack diagnosis can involve multiple tests using expensive equipment. However, access to such techniques is simply unavailable in many parts of the world — even in some rural areas of North America, and especially in remote or low-income areas and in developing countries.
Now, Korean scientists Sangmin Jeon and colleagues of the SMART Materials and Sensors Laboratory at POSTECH — Pohang University of Science and Technology in Pohang, Kyungbuk, Korea — have developed a simple, thermometer-like device designed to help doctors diagnose heart attacks wi
th minimal equipment, materials and cost. A report on research and development of the device has been published in the ACS journal Analytical Chemistry in a paper entitled: “Facile Detection of Troponin I Using Dendritic Platinum Nanoparticles and Capillary Tube Indicators“ (Analytical Chemistry, 2015; 87 (9): 5004 DOI: 10.1021/acs.analchem.5b00921), coauthored by Sanghee Lee, Donghoon Kwon, Changyong Yim, and Sangmin Jeon — a professor in the Department of Chemical Engineering at POSTECH.
The coauthors note that liquid-in-glass thermometers, such as alcohol and mercury thermometers, are frequently encountered in our daily lives at home, in hospitals, and in school laboratories. In these devices, the volume of the enclosed substance changes with temperature, and the resulting volume is easily converted to temperature using a metric scale inscribed on the capillary tube.
While state-of-the-art electronic temperature measuring devices such as remote infrared detectors are available at reasonable prices, traditional thermometers are still widely used owing to their many advantages, such as low cost, no need for external power, high reliability, and ease of use. The elegance of an old-school thermometer lies mainly in its structure, consisting of a relatively large glass bulb containing red-colored alcohol or “silver” colored mercury and a narrow capillary tube connected to the glass bulb. This structure amplifies small changes the volume inside a glass bulb, translating it to a large change in the level inside the capillary tube. This simple method for signal amplification can also be employed to measure biomarkers such as Troponin.
Troponin, a complex of three subtype proteins: troponin I (TnI), troponin C, and troponin T, is considered a specific marker for myocardial damage because the protein’s concentration in blood rises when the cardiac muscles are damaged.
A number of immunoassays have been developed for measuring Troponin concentrations using microresonators, surface plasmon resonance (SPR), surface acoustic wave (SAW) sensors, and electrochemical sensors, but these methods are impractical for most applications because they require requires bulky, expensive instruments that are often not practical for point-of-care use or in low-income areas. Yet three-quarters of deaths related to cardiovascular disease occur in low- and middle-income countries, and early diagnosis could help curb these numbers, so Dr. Jeon’s team set out to devise a sensitive, more accessible, cheaper, diagnostic test.
They note that lateral flow immunoassay (LFA) does not require any read-out instrumentation, and has been used as a point-of-care platform; albeit with the critical disadvantage of low sensitivity (1 ng/mL). LFA sensitivity could be improved by labeling with fluorescent or luminescent dyes, but that would require yet more bulky and expensive detection systems.
However, inspired by the simplicity of alcohol and mercury thermometers, Dr. Jeon and his team have demonstrated an alternative, facile and sensitive method for measuring TnI concentrations using a similarly straightforward alcohol thermometer-like glass vial and dendritic platinum nanoparticles as a way to detect troponin. When human serum with troponin even at a minute concentration is mixed with the nanoparticles and put in the vial, the ink climbs a protruding tube and can be read with the naked eye, just like a thermometer.
Using this method, TnI in human serum was captured by the antibody-functionalized dendritic platinum nanoparticles, then conjugated to the inner surface of a glass vial functionalized with TnI antibodies. After addition of a hydrogen peroxide (H2O2) solution, the vial was sealed with a capillary tube containing a drop of ink. The pressure increase inside the glass vial caused by the catalytic dissociation of H2O2 to H2O and O2 increased the ink level in the capillary tube. This increase, detected by the eye, was used to determine the TnI concentration. The detection limit of the assay was found to be 0.1 ng/mL of TnI in human serum after a 5 min dissociation reaction.
Photo Caption – A simple, thermometer-like device could make diagnosing heart attacks easier in remote or low-income locations. Image Credit: American Chemical Society
The Korean scientists summarize that they have developed a simple, low-tech, and facile method for detecting TnI in human serum using antibody-functionalized dendritic platinum nanoparticles and a capillary tube containing a drop of ink. The pressure increase caused by the catalytic dissociation of H2O2 by platinum nanoparticles induces an increase in ink level — easily identified with the naked eye. The detection limit of the assay was 0.1 ng/mL TnI in human serum after a 5 min catalytic reaction. Because the ink level increases further with reaction time, the limit of detection could be improved by increasing the reaction time.
The coauthors observe that this simple and cost-effective diagnostic technique may be especially beneficial for people in underdeveloped countries.
This research was supported by a National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2014R1A2A2A0100702)
Founded in 1986 as the first research-oriented university in Korea, POSTECH is a young university with only 27 years of history. However, thanks to wholehearted support from POSCO and the POSTECH Foundation and the efforts of students, staff, researchers, and faculty, POSTECH has risen in a short time to become a leading Korean and Asian university, adding its name to the list of top universities in the world despite its comparative youthfulness
Since its establishment, POSTECH has stayed true to its role in Korean higher education as a pioneer in science and technology research. Located in the city of Pohang, the 400-acre, park-like campus is home to the Pohang Accelerator Laboratory and minutes away from POSCO, the fourth-largest steelmaking company in the world. POSTECH has come a long way in its short history to become globally recognized as one of Asia’s premier universities and among the most selective, highly ranked research universities in Korea.
Sources:
American Chemical Society
Analytical Chemistry
POSTECH — Pohang University of Science and Technology
Image Credits:
POSTECH — Pohang University of Science and Technology
American Chemical Society
