Dec 7 2009
Researchers at A*STAR's Institute of Microelectronics (or IME) have developed a rapid and sensitive integrated system to test for specific cardiac biomarkers in blood. Compared to the conventional testing platform known as ELISA (Enzyme-linked Immunosorbent Assay), the new integrated system significantly cuts sample preparation and analysis time which typically requires 6 hours to just 45 minutes.
The new system has demonstrated promising multiplexing capability, meaning that the new system can measure several cardiac biomarkers simultaneously; thereby contributing to the detail and certainty of diagnosis. It is also less invasive since it uses just a finger prick amount of blood. In the event of a suspected heart attack, these new features could save precious minutes in helping doctors arrive at the right diagnosis for timely medical intervention, which would make a world of difference between life and death.
The potential healthcare implications of the promising research outcome has attracted the interest of Singapore National Heart Centre who, in working with IME, proposed the clinical problems and the 'chokepoints' for rapid point-of-care (POC) test for diagnosis of heart attacks.
On the future outlook for the IME-developed silicon-based integrated system, Dr Philip Wong, Senior Consultant of Singapore National Heart Centre said, "The key to saving lives in heart attack scenarios is time and the quicker and more accurate the diagnosis can be made, the faster proper care and treatment can be instituted. The test kits can be rapidly deployed, and tests to confirm clinical diagnosis can be completed within short time frames. As the kits are deployed on-site as opposed to a central laboratory, confirmation of condition is rapid without the need to transport patients' specimens."
Silicon-based Integrated System: What is it and how does it work?
The IME-developed silicon-based integrated system is a label-free technology that uses semiconducting silicon nanowires (SiNWs) as biosensors. The working principle behind the nanowire biosensors is the field-effect transistor, which is responsible for generating a measurable electrical response when specific antibody-antigen interactions occur on the nanowire surface.
Cardiac protein biomarkers are substances that are released into the blood when the heart is injured. Specific antibodies that are immobilized onto the nanowire surface will elicit antibody-antigen interactions when allowed to come into contact with the variety of charged cardiac biomarkers. Such parallel detection of several biomarkers is made possible by the new microsystem that integrates the following elements into one single system:
- In-built filtration system to extract almost instantaneously the test serum from the whole blood sample
- An array of SiNW chips coated with different antibodies for simultaneous detection of several biomarkers
- A recording microchip for concurrent and immediate signal-readout from multiple SiNW sensors
The first demonstration of the full system capability revealed impressive sensitivity and speed as the system is able to attain a low detection limit of 1 pg/ml for cardiac biomarkers, troponin-T and creatinine kinases, from 2 µl blood in just under 45 minutes. Commercially available test kits require more than 1 ng/ml of cardiac biomarkers in order for them to be detected, which is 1000 times less sensitive than the IME-developed system. The technology and processes used for the fabrication of this integrated device have also yielded two patents to date.
"IME's proprietary nanotechnology behind the new silicon-based integrated system can be extended to other protein-based diagnostics from blood and saliva samples to provide fast, sensitive, accurate and portable solutions for protein-based disease screening," said Professor Kwong Dim-Lee, Executive Director of IME. Significance of Cardiac Biomarkers
Cardiac biomarkers, such as troponin-T and creatinine kinases are proteins used for heart attack diagnosis. Troponin and creatinine are constituents of the cardiac muscle cells that are released into the blood when the cells and tissues are injured after a heart attack. Hence elevated levels of troponin-T or creatinine kinases in the blood alert the doctors that a heart attack has taken place.
Troponin-T is established as a sensitive marker of myocardial injury in the general population. The troponin-T level in the blood increases within 4 to 6 hours after the onset of a heart attack and peaks at about 24 hours. This increase lasts for 10 to 14 days.