Frequency domain detection of biomolecules using silicon nanowire biosensors.

We demonstrate a new protein detection methodology based upon frequency domain electrical measurement using silicon nanowire field-effect transistor (SiNW FET) biosensors. The power spectral density of voltage from a current-biased SiNW FET shows 1/f-dependence in frequency domain for measurements of antibody functionalized SiNW devices in buffer solution or in the presence of protein not specific to the antibody receptor. In the presence of protein (antigen) recognized specifically by the antibody-functionalized SiNW FET, the frequency spectrum exhibits a Lorentzian shape with a characteristic frequency of several kHz. Frequency and conventional time domain measurements carried out with the same device as a function of antigen concentration show more than 10-fold increase in detection sensitivity in the frequency domain data. These concentration dependent results together with studies of antibody receptor density effect further address possible origins of the Lorentzian frequency spectrum. Our results show that frequency domain measurements can be used as a complementary approach to conventional time domain measurements for ultra-sensitive electrical detection of proteins and other biomolecules using nanoscale FETs.

我们展示了一种基于频域电学测量的新型蛋白质检测方法，该方法使用硅纳米线场效应晶体管（SiNW FET）生物传感器。对于在缓冲溶液中或存在与抗体受体非特异性结合的蛋白质时对抗体功能化的SiNW器件进行的测量，来自电流偏置的SiNW FET的电压功率谱密度在频域呈现1/f依赖性。在存在被抗体功能化的SiNW FET特异性识别的蛋白质（抗原）时，频谱呈现出具有几千赫兹特征频率的洛伦兹形状。使用同一器件作为抗原浓度的函数进行的频域和常规时域测量表明，频域数据中的检测灵敏度提高了10倍以上。这些与浓度相关的结果以及对抗体受体密度效应的研究进一步探讨了洛伦兹频谱的可能来源。我们的结果表明，对于使用纳米级FET对蛋白质和其他生物分子进行超灵敏电学检测，频域测量可作为常规时域测量的一种补充方法。