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Silicon nanowire device for inexpensive monitoring of key cardiac marker In addition to cTnT, the technique is After a heart attack, effective diagnosis and tor (known as CMOS) technology will be compatible with other target molecules for treatment decisions in the days following an important consideration for mass prowhich specific antibodies can be attached to the incident are critical to long-term surduction of the devices, Zhang notes. the nanowires. The experimental revival and recovery; but the variability sults reported in this paper demonof symptoms in patients with susstrate the device’s ability to detect the pected acute coronary syndrome target molecule in a matrix in which complicates the diagnosis of acute the total protein concentration exmyocardial infarction. Cardiologists ceeds the biomarker by 12 orders of have significantly improved their magnitude. Furthermore, the high diagnostic ability by monitoring sensitivity and rapid response of the cardiac biomarkers, such as cardiac SiNW technology could permit develtroponin-T (cTnT), a regulatory opment of arrays of wires, each tarprotein found in cardiac muscle. geted to a different biomarker. This Now, as described in AC (DOI would allow physicians to perform 10.1021/ac901157x), Guo-Jun multiple confirmatory diagnoses siZhang and colleagues from the Inmultaneously. The research team is stitute of Microelectronics (Sincurrently investigating the possibility gapore) have demonstrated a silicon of using the SiNW array for such mulnanowire (SiNW) device that ultitiplexed detection. mately could provide real-time This graph illustrates the conductance of SiNW devices, which James Heath of the California monitoring of troponin levels in have been functionalized with cTnT antibodies, in human serum Institute of Technology sees clear human blood serum. spiked with cTnT. The limit of detection is 30 fg/mL. advantages to the SiNW device comCardiac troponins appear in separed to current technologies. “The rum within 4⫺8 hours after the onAfter fabrication, the nanowire surface use of nanowires to detect the cardiac markset of cardiac symptoms and remain elwas modified chemically to allow attachers is a nice application, since troponins are evated for as long as one week. Because ment of troponin-specific antibodies. monitored at high frequency in patients folelevated levels of cTnT have been associBinding of the biomolecules to the funclowing potential cardiac arrest,” he says. ated with greater risk of death, monitoring tionalized surface changed the conductiv“One clear potential application would be of troponin is a valuable diagnostic and ity of the nanowires. The research team the continuous monitoring of the troponins, therapeutic tool. Currently, cTnT levels demonstrated a real-time response in a rather than the current stepwise procedure.” are measured with immunoassay techbuffer solution with a 3⫻ background Heath points out that desalination of serum, niques such as ELISA. signal for a 1 femtogram per milliliter (fg/ which is not part of current routine proce“Because the [new] technique is realmL) solution of cTnT. Subsequent experi- dures, could be a challenge and suggests that time detection, the analysis time is rements that used desalted human serum a platform that both desalts the serum and duced from six hours for ELISA to a few instead of a buffer solution yielded a lower continuously monitors the cardiac markers minutes,” says Zhang. “Also, the SiNW real-time detection limit of 30 fg/mL, but would be a logical next step. sensor would significantly reduce the $50 this is still 3 orders of magnitude lower The characteristics of SiNWs and the per sample cost of immunoassay measurethan ELISA-related detection methods. preliminary results reported for this device ments, particularly when you account for Zhang finds these results extremely pave the way for the development of a the possibility of mass production for senencouraging for the development of sysmedical diagnostic system to provide an tems that can perform rapid monitoring of early and accurate indication of cardiac sor fabrication.” The device consists of 36 clusters of 5 actual patient blood samples. “This techcellular necrosis. Because damage to the nique addresses SiNW biosensors for deindividually addressable nanowires each, myocardium can be directly related to the tecting biomarkers in serum,” he says. along with an integrated SiNW array bioconcentrations of the cTnT protein, such “We are currently developing an intesensor. To manufacture the SiNWs, the a device would effectively differentiate a grated microsystem [that could be] useful researchers used the standard top-down patient suffering from unstable angina as both a routine monitoring device and a fabrication processes of conventional optifrom a more serious case of heart attack; diagnostic tool.” He adds that these appli- this would be a significant addition to the cal lithography, etching, and oxidation. cations would require the integration of This approach’s compatibility with physician’s ability to treat a patient. —Steve Miller sample preparation into the system. complementary metal-oxide semiconduc10.1021/AC9014325 2009 AMERICAN CHEMICAL SOCIETY
Published on Web 07/10/2009
AUGUST 1, 2009 / ANALYTICAL CHEMISTRY
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