Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive.1-13 However, detecting these biomarkers in physiological fluid samples is difficult because of problems like biofouling and nonspecific binding, and the resulting need to use purified buffers greatly reduces the clinical relevance of these sensors. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. A microfluidic purification chip captures multiple biomarkers simultaneously from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 uL sample of whole blood in less than 20 minutes. This study marks the first use of label-free nanosensors with physiologic solutions, positioning this technology for rapid translation to clinical settings.
Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive. However, detecting these biomarkers in physiological fluid samples is difficult because of ionic screening. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. 1 A microfluidic purification chip captures multiple biomarkers simultaneously from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 uL sample of whole blood in less than 20 minutes.
Silicon nanowire field effect transistors (FETs) have emerged as ultrasensitive, label-free biodetectors that operate by sensing bound surface charge. However, the ionic strength of the environment (i.e., the Debye length of the solution) dictates the effective magnitude of the surface charge. Here, we show that control of the Debye length determines the spatial extent of sensed bound surface charge on the sensor. We apply this technique to different methods of antibody immobilization, demonstrating different effective distances of induced charge from the sensor surface.
Semiconducting nanowires are promising ultrasensitive, label-free sensors for small molecules, DNA, proteins, and cellular function. Nanowire field effect transistors (FETs) function by sensing the charge of a bound molecule; however, solutions of physiologic ionic strength compromise detection of specific binding events due to ionic (Debye) screening. We demonstrate a general solution to this limitation with the development of a hybrid nanoelectronic-enzyme linked immunosorbent assay (ne-ELISA), which combines the power of enzymatic conversion of bound substrate with electronic detection. This novel configuration produces a local enzyme-mediated Correspondence to: Mark A. Reed, mark.reed@yale.edu; Tarek M. Fahmy, tarek.fahmy@yale.edu. † These authors contributed equally to this work. § Present address: Nanoterra, Cambridge, MA 02139 Supporting Information is available on the WWW under the http://www.small-journall.com or from the authors.
NIH Public Access
Author ManuscriptSmall. Author manuscript; available in PMC 2011 January 1.
NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript pH change proportional to bound ligand concentration. We show that nanowire FETs configured as pH sensors can be used for quantitative detection of interleukin-2 (IL-2) in physiologically buffered solution at concentrations as low as 1.6 pg/mL. By successfully bypassing the Debye screening inherent in physiologic fluids, the ne-ELISA promises wide applicability for ligand detection in a range of relevant solutions.
The minority carrier lifetimes of VLS‐grown axial p–n junction silicon nanowires are characterized by the reverse recovery transients of electrically injected minority carriers. Nanowire‐diameter‐dependent lifetimes and various electrical properties indicate the enhanced surface recombination with decreasing diameters, suggesting the significance of surface passivations for effective carrier transport in photovoltaic applications.
Nanoscale Field Effect Transistors have emerged as a promising technology for ultrasensitive, unlabeled diagnostic applications. However, their use as quantitative sensors has been problematic because of the need for individual sensor calibration. In this work we demonstrate an internal calibration scheme for multiplexed nanoribbon field effect sensors by utilizing the initial current rates rather than end point detection. A linear response is observed consistent with initial binding kinetics. Moreover, we are able to show that top-down fabrication techniques yield reproducible device results with minimal fluctuations, enabling internal calibration.
We apply our self-consistent PDE model for the electrical response of field-effect sensors to the 3D simulation of nanowire PSA (prostate-specific antigen) sensors. The charge concentration in the biofunctionalized boundary layer at the semiconductor-electrolyte interface is calculated using the propka algorithm, and the screening of the biomolecules by the free ions in the liquid is modeled by a sensitivity factor. This comprehensive approach yields excellent agreement with experimental current-voltage characteristics without any fitting parameters. Having verified the numerical model in this manner, we study the sensitivity of nanowire PSA sensors by changing device parameters, making it possible to optimize the devices and revealing the attributes of the optimal field-effect sensor.
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