We present a MoS2 biosensor to electrically detect prostate specific antigen (PSA) in a highly sensitive and label-free manner. Unlike previous MoS2-FET-based biosensors, the device configuration of our biosensors does not require a dielectric layer such as HfO2 due to the hydrophobicity of MoS2. Such an oxide-free operation improves sensitivity and simplifies sensor design. For a quantitative and selective detection of PSA antigen, anti-PSA antibody was immobilized on the sensor surface. Then, introduction of PSA antigen, into the anti-PSA immobilized sensor surface resulted in a lable-free immunoassary format. Measured off-state current of the device showed a significant decrease as the applied PSA concentration was increased. The minimum detectable concentration of PSA is 1 pg/mL, which is several orders of magnitude below the clinical cut-off level of ~4 ng/mL. In addition, we also provide a systematic theoretical analysis of the sensor platform – including the charge state of protein at the specific pH level, and self-consistent channel transport. Taken together, the experimental demonstration and the theoretical framework provide a comprehensive description of the performance potential of dielectric-free MoS2-based biosensor technology.
We present a robust, sensitive, fluorescent or radio label-free self-assembled optical diffraction biosensor that utilizes rolling circle amplification (RCA) and magnetic microbeads as a signal enhancement method. An aptamer-based sandwich assay was performed on microcontact-printed streptavidin arranged in 15-μm-wide alternating lines, and could specifically capture and detect platelet-derived growth factor B-chain (PDGF-BB). An aptamer served as a template for the ligation of a padlock probe and the circularized probe could in turn be used as a template for RCA. The concatameric RCA product hybridized to biotinylated oligonuclotides which then captured streptavidin-labeled magnetic beads. In consequence, the signal from the captured PDGF-BB was amplified via the concatameric RCA product, and the diffraction gratings on the printed areas produced varying intensities of diffraction modes. The detected diffraction intensity and the density of the microbeads on the surface varied as a function of PDGF-BB concentration. Our results demonstrate a robust biosensing platform that is easy to construct and use, and devoid of fluorescence microscopy. The self-assembled bead patterns allow both a visual analysis of the molecular binding events under an ordinary bright-field microscope and serve as a diffraction grating biosensor.Detection of proteins in a sensitive and rapid manner plays an essential role in clinical applications. Numerous studies have been reported on using antibody-based immunoassay systems as recognition elements for detecting proteins. 1-3 Antibodies, however, are generally produced in vivo, which generates difficulties in engineering their properties. In contrast, aptamers, generated by an in vitro selection process, are single-stranded oligonucleotides (DNA or RNA) that can specifically bind and recognize a variety of analytes ranging from small organic molecules to proteins, even to whole cells. As a result, aptamers have been usedTo whom correspondence should be addressed. Phone: +1 (765) as recognition elements in a number of biosensing platforms. 4-7 However, even though aptamers uniquely transduce the recognition of analytes into the generation of readily observable signals, analytes in small quantities are still difficult to detect with aptamers alone, pointing to a need for novel signal enhancement schemes.Among many other biosensing platforms, the effectiveness of optical diffraction based biosensors has been demonstrated for recognizing binding events of various biomolecules, which operate based on changes in effective height or refractive index on periodically patterned gratings. [8][9][10][11][12] In many studies, in order to detect small amount of biomolecules, additional signal enhancement was necessary. 13 The enhancement was accomplished either by microfabrication of solid diffraction gratings or by in situ assembled diffraction gratings that are self-fabricated by nano or micro-size particles. Compared to the microfabrication of diffraction gratings which increases cost, tim...
Continuous monitoring of hydrogen sulfide (H2S) in human breath for early stage diagnosis of halitosis is of great significance for prevention of dental diseases. However, fabrication of a highly selective and sensitive H2S gas sensor material still remains a challenge, and direct analysis of real breath samples has not been properly attempted, to the best of our knowledge. To address the issue, herein, we introduce facile cofunctionalization of WO3 nanofibers with alkaline metal (Na) and noble metal (Pt) catalysts via the simple addition of sodium chloride (NaCl) and Pt nanoparticles (NPs), followed by electrospinning process. The Na-doping and Pt NPs decoration in WO3 grains induces the partial evolution of the Na2W4O13 phase, causing the buildup of Pt/Na2W4O13/WO3 multi-interface heterojunctions that selectively interacts with sulfur-containing species. As a result, we achieved the highest-ranked sensing performances, that is, response (R air/R gas) = 780 @ 1 ppm and selectivity (R H2S/R EtOH) = 277 against 1 ppm ethanol, among the chemiresistor-based H2S sensors, owing to the synergistic chemical and electronic sensitization effects of the Pt NP/Na compound cocatalysts. The as-prepared sensing layer was proven to be practically effective for direct, and quantitative halitosis analysis based on the correlation (accuracy = 86.3%) between the H2S concentration measured using the direct breath signals obtained by our test device (80 cases) and gas chromatography. This study offers possibilities for direct, highly reliable and rapid detection of H2S in real human breath without the need of any collection or filtering equipment.
In this report, we describe the development of a quartz crystal microbalance biosensor for detection of folate binding protein (FBP). Using a simple folate-BSA conjugate adsorbed onto a Au-coated quartz sensor, a detection limit of 30 nM was achieved. Binding of FBP to the sensor surface could be blocked at concentrations as high as 1 microM with a 100-fold excess of folic acid, indicating the specificity of the folate-FBP interaction and the absence of nonspecific binding to the functionalized surface. Moreover, capture could be achieved in the presence of blood serum, making the assay amenable to the analysis of bodily fluids. Further signal enhancement based on an anti-FBP antibody and protein-A-coated gold nanosphere sandwich assay extended the detection limit to 50 pM (approximately 3 orders-of-magnitude improvement). Given the overexpression of FBP in certain malignancies and inflammatory disorders, we expect the methodology described here to be useful to detect FBP as a possible biomarker for disease diagnosis.
Molybdenum disulfide (MoS) field-effect transistor (FET)-based biosensors have attracted significant attention as promising candidates for highly sensitive, label-free biomolecule detection devices. In this paper, toward practical applications of biosensors, we demonstrate reliable and quantitative detection of a prostate cancer biomarker using the MoS FET biosensor in a nonaqueous environment by reducing nonspecific molecular binding events and realizing uniform chemisorption of anti-PSA onto the MoS surface. A systematic and statistical study on the capability of the proposed device is presented, and the biological binding events are directly confirmed and characterized through intensive structural and electrical analysis. Our proposed biosensor can reliably detect various PSA concentrations with a limit of 100 fg/mL. Moreover, rigorous theoretical simulations provide a comprehensive understanding of the operating mechanism of the MoS FET biosensors, and further suggests the enhancement of the sensitivity through engineering device design parameters.
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