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January 18, 2012

Chip for Cardiac biomarker analysis from fingerprick blood with results in 45 minutes and 100 times more sensitivity

A*STAR Institute of Microelectronics have now developed a handheld blood testing device with significantly improved sensitivity.


Cardiovascular diseases are the major cause of death among adults worldwide. Electrocardiogram (ECG) is a first test when a patient suffering from chest pain sees a doctor, however, it is lack of the required sensitivity. Standard assays to detect cardiac biomarkers, like enzyme-linked immunosorbent assay (ELISA) are sensitive, but suffer from important sample and reagent consumption in large-scale studies. Moreover they are performed in central laboratories of clinics and hospitals and take a long time, which is highly incompatible with the quick decisions needed to save a heart attack patient. Herein, we describe an integrated chip allowing rapid, sensitive, and simultaneous analysis of three cardiac biomarkers in fingerprick blood. The integrated chip is composed of a filtration chip for plasma separation from blood and a silicon nanowire (SiNW) array sensor chip for protein detection. These two chips are fabricated separately and bonded to form a single unit after alignment. The integrated chip is capable of reducing the dead volume of the sample by eliminating the tubing between the two chips. After the plasma is filtrated by the filtration chip, the SiNW sensor, spotted with three different antibodies, enabled us to detect three cardiac biomarkers, troponin T (cTnT), creatine kinase MM (CK-MM) and creatine kinase MB (CK-MB), simultaneously. The integrated chip is able to attain a low detection limit of 1 pg / ml for the three cardiac biomarkers from 2 microliters of blood in 45 min.




The device has two functions — a blood plasma filter and a silicon nanowire biosensor — integrated onto one chip (see image), and it has the capability to identify protein markers in finger-prick blood samples within 45 minutes.

The integrated chip device developed by Zhang and his team is the first technology of its kind. The test chip is designed to search for three particular cardiac protein biomarkers: troponin T, creatine kinase MM, and creatine kinase MB. If the presence of any of these three biomarkers is detected, it indicates a high risk of heart attack or other heart disorder.

The filter function uses a series of ‘micropillars’ in a carefully designed sequence that acts to separate plasma from the main blood sample. Prior to detection of the biomarkers, all interfering components in the blood need to be removed. This is usually undertaken through the use of lab equipment known as a centrifuge, but Zhang has eliminated the need for this step by integrating the plasma extraction functionality on the chip.

The researchers allowed the blood plasma to flow onto the nanowire biosensor, the surface of which was marked with spots of the three different cardiac protein antibodies. These spots react with the proteins present in the plasma, causing a change in electrical resistance that the researchers could measure. This allows for the detection of biomarkers with good specificity without reducing sensitivity.

The results produced by the new integrated chip device are a marked improvement of up to two orders of magnitude better than current test kits. The researchers are optimistic about the commercial potential of their device, as it uses a simple design that is easy to manufacture. They will continue to develop this technology and undertake clinical trials of the device with industrial partners.

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