Semiconductor nanowire FET sensors: Label-free, ultasensitive, multiplexed biomolecule detection and biophysical studies.

摘要

One-dimensional nanomaterials such as nanowires have attracted substantial interests in the study of interplays between these nanostructures and biology. Semiconducting silicon nanowires (SiNWs) can be fabricated as high-performance field-effect transistors (FETs), and their unique features such as similar diameters to biomolecules, high surface-to-volume ratios, chemically tailorable physical properties and overall structure robustness enable their applications in sensitive biomolecule detection and bio-diagnostic assays. Moreover, their properties of direct electrical real-out during biosensing and compatibility with large-scale integrated electronics make nanowire FET sensors an ideal candidate as a general/powerful platform for label-free, real-time, multiplexed biomolecule detection as well as biophysical studies.; We first describe the successful synthesis and fabrication of high-performance n-type (phosphorus-doped) and p-type (boron-doped) SiNW FETs. One important application of these SiNW FET biosensors is the detection of proteins including cancer markers and bacterial toxins. Modified with surface receptors such as monoclonal antibodies or gangliosides, these nanowire FETs can reliably detect proteins at femtomolar range in buffer, and low picomolar range in clinical samples such as serum or urine. In addition, multiplexed detection of >10 proteins have been carried out in a single chip simultaneously, while the binding kinetics can also been measured in parallel. This study demonstrates that potential clinical applications of nanowire sensors for disease diagnosis and treatment, as well as biophysical studies.; In addition, we report the direct, real-time electrical detection of viruses. Simultaneous fluorescent microscopy and electrical measurement show that the conductance changes in SiNW FET sensor directly relate to the binding/unbinding of single virus particles on nanowire surface. This study defines ultimate sensitivity limit of detecting single biological entity by nanowire sensors.; Moreover, the sensitivity of nanowire sensors can be further optimized by various device optimization approaches, such as reducing the nanowire diameter, shrinking the transistor channel length, and operating the SiNW FET in the sub-threshold regime.; Finally, frequency domain analysis has been carried out to study the microscopic fluctuations on nanowire surface during biomolecule binding. These novel approaches can be used to push the sensitivity limit of these nanowire sensors, while at the same time addressing fundamental biophysical questions and suggesting new applications.