Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine.NA sequencing has opened new windows of opportunities for diagnosis of genetic disease (1), biological informatics (2), forensics (3), and environmental monitoring (4). Discrimination of a single mismatch in a long DNA strand is of significant importance and is essential to detect single nucleotide polymorphism (SNP). SNP is a single-nucleotide mutation in a gene sequence and varies among paired chromosomes, between individuals, and across biological species. SNP mutations can have dramatic influence on the health. They are markers for variety of diseases, including various forms of cancer, genetic disorders (5-7), and are of critical importance for successful practical implementation of the concept of personalized medicine (8). Thus, the development of biosensors detecting SNP mutations with high sensitivity and specificity is essential for effective personalized medicine approaches.Current DNA sequencing, including SNP detection, is achieved primarily by enzyme-based methods, using DNA ligase (9), DNA polymerase (9), and nucleases (10). These methods generate highly accurate genotyping. However, the methods are expensive and time-consuming. One of the common enzyme-free methods to detect SNPs uses hybridization of the target DNA to a probe on a microarray and detects their binding events with fluorescence microscopy/spectroscopy. Hybridization-based methods for SNP detection have several disadvantages, including cross-hybridization between allele-specific probes (11). This limits the detection of a single mismatch in long probe-target hybridization as the longer probes have more frequent cross hybridization. For example, a single mismatch in the center o...

Amyloid-β (Aβ) peptides are thought to be involved in neurodegenerative diseases such as Alzheimer's disease and Down's syndrome. They form a large number of polymorphic structures, including heterogeneous ionic pores in membranes as well as different types of fibrillar and globular structures on surfaces and in solution. Understanding the origin of these structures and the factors that influence their occurrence is of great biomedical interest because of the possible relationship between structure and pathogenicity. Here, we use atomic force microscopy (AFM) and molecular dynamics (MD) simulations to demonstrate that at room temperature a truncated Aβ peptide which is generated in vivo and shown to be toxic in vitro forms fibrillar structures on hydrophobic graphite surfaces, but not on hydrophilic mica or lipid bilayers. Our results suggest that the toxic pores and fibrillar polymorphic organizations can be explained in terms of the U-shaped β-strand-turn-β-strand structural motif observed for full length Aβ and other amyloids, as well as the physicochemical properties at the interfaces. The interactions of the hydrophobic, truncated Aβ with its environment illustrate that the universal amyloid motif can provide a link between the pore and fibrillar structures and indicate that surfaces with different physicochemical properties can shift the polymorphic landscape toward other conformational states.

Hollow/porous nanoparticles, including nanocarriers, nanoshells, and mesoporous materials have applications in catalysis, photonics, biosensing, and delivery of theranostic agents. Using a hierarchical template synthesis scheme, we have synthesized a nanocarrier mimicking a golf ball, consisting of (i) solid silica core with a pitted gold surface and (ii) a hollow/porous gold shell without silica. The template consisted of 100 nm polystyrene beads attached to a larger silica core. Selective gold plating of the core followed by removal of the polystyrene beads produced a golf ball-like nanostructure with 100 nm pits. Dissolution of the silica core produced a hollow/porous golf ball-like nanostructure.

Composite colloidal structures with multi-functional properties have wide applications in targeted delivery of therapeutics and imaging contrast molecules and high-throughput molecular bio-sensing. We have constructed a multifunctional composite magnetic nanobowl using bottom-up approach on an asymmetric silica/polystyrene Janus template consisting of a silica shell around a partially exposed polystyrene core. The nanobowl consists of a silica bowl and a gold exterior shell with iron oxide magnetic nanoparticles sandwiched between the silica and gold shells. Nanobowls were characterized by electron microscopy, atomic force microscopy, magnetometry, vis-NIR and FTIR spectroscopy. Magnetically vectored transport of these nanobowls was ascertained by time-lapsed imaging of their flow in fluid through a porous hydrogel under a defined magnetic field. These magnetically-responsive nanobowls show distinct surface enhanced Raman spectroscopy (SERS) imaging capability. PEGylated magnetically-responsive nanobowls show size-dependent cellular uptake in-vitro.

Colloidal particles with two or more different surface properties (Janus particles) are of interest in catalysis, biological imaging, and drug delivery. Eccentric nanoparticles are a type of Janus particle consisting of a shell that envelops the majority of a core particle, leaving a portion of the core surface exposed. Previous work to synthesize eccentric nanoparticles from silica and polystyrene have only used microemulsion techniques. In contrast we report the solgel synthesis of eccentric Janus nanoparticles composed of a silica shell around a carboxylate-modified polystyrene core (Janus templates). In addition, we have synthesized nano-bowl-like structures after the removal of the polystyrene core by organic solvent. These Janus templates and nanobowls can be used as a versatile platform for site-specific functionalization or controlled theranostic delivery.

Here we report the design and development of DNA zippers and tweezers. Essentially a zipper system consists of a normal strand (N), a weak strand (W), and an opening strand (O). N strand is made up of normal DNA bases, while W is engineered to have inosine substituting for guanine. By altering the number and order of inosine, W is engineered to provide less than natural bonding affinities to N in forming the [N:W] helix. When O is introduced (a natural complement of N), it competitively displaces W from [N:W] and forms [N:O]. This principle is incorporated in the development of a molecular device that can perform the functions of tweezers (sense, hold, and release). Tweezers were constructed by holding N and W together using a hinge at one end. Thus, when the tweezers open, N and W remain in the same vicinity. This allows the tweezers to cycle among open and close positions by their opening and closing strands. Control over their opening and closing kinetics is demonstrated. In contrast to the previously reported DNA tweezers, the zipper mechanism makes it possible to operate them with opening strands that do not contain single-stranded DNA overhangs. Our approach yields a robust, compact, and regenerative tweezer system that could potentially be integrated into complex nanomachines.

Nanodiamonds when carboxylated (cNDs) act as reducing agents and hence could limit oxidative damage in biological systems. Gamma (γ)-irradiation of whole blood or its components is required in immunocompetent patients to prevent transfusion-associated graft versus host disease (TA-GVHD). However, γ-irradiation of blood also deoxygenates red blood cells (RBCs) and induces oxidative damage, including abnormalities in cellular membranes and hemolysis. Using atomic force microscopy (AFM) and Raman spectroscopy, we examined the effect of cNDs on γ-irradiation mediated deoxygenation and morphological damage of RBCs. γ-Radiation induced several morphological phenotypes, including stomatocytes, codocytes and echinocytes. While stomatocytes and codocytes are reversibly damaged RBCs, echinocytes are irreversibly damaged. AFM images show significantly fewer echinocytes among cND-treated γ-irradiated RBCs. The Raman spectra of γ-irradiated RBCs had more oxygenated hemoglobin patterns when cND-treated, resembling those of normal, non-irradiated RBCs, compared to the non-cND-treated RBCs. cND inhibited hemoglobin deoxygenation and morphological damage, possibly by neutralizing the free radicals generated during γ-irradiation. Thus cNDs have the therapeutic potential to preserve the quality of stored blood following γ-irradiation.

Enhanced Bragg reflections from size-matched heterostructure photonic crystal thin films prepared by the Langmuir-Blodgett method Appl. Phys. Lett. 89, 093116 (2006); 10.1063/1.2339031 Metallic photonic crystals with strong broadband absorption at optical frequencies over wide angular range J. Appl. Phys. 97, 093104 (2005); 10.1063/1.1889248 Fabrication of three-dimensional photonic crystal with alignment based on electron beam lithography Appl. Phys. Lett. 85, 5037 (2004); 10.1063/1.1825623Low-loss one-dimensional metallodielectric photonic crystals fabricated by metallic insertions in a multilayer dielectric structure