Biosensors based on field-effect transistors (FETs) have attracted much attention, as they offer rapid, inexpensive, and label-free detection. While the low sensitivity of FET biosensors based on bulk 3D structures has been overcome by using 1D structures (nanotubes/nanowires), the latter face severe fabrication challenges, impairing their practical applications. In this paper, we introduce and demonstrate FET biosensors based on molybdenum disulfide (MoS2), which provides extremely high sensitivity and at the same time offers easy patternability and device fabrication, due to its 2D atomically layered structure. A MoS2-based pH sensor achieving sensitivity as high as 713 for a pH change by 1 unit along with efficient operation over a wide pH range (3-9) is demonstrated. Ultrasensitive and specific protein sensing is also achieved with a sensitivity of 196 even at 100 femtomolar concentration. While graphene is also a 2D material, we show here that it cannot compete with a MoS2-based FET biosensor, which surpasses the sensitivity of that based on graphene by more than 74-fold. Moreover, we establish through theoretical analysis that MoS2 is greatly advantageous for biosensor device scaling without compromising its sensitivity, which is beneficial for single molecular detection. Furthermore, MoS2, with its highly flexible and transparent nature, can offer new opportunities in advanced diagnostics and medical prostheses. This unique fusion of desirable properties makes MoS2 a highly potential candidate for next-generation low-cost biosensors.

The fast growth of information technology has been sustained by continuous scaling down of the silicon-based metal-oxide field-effect transistor. However, such technology faces two major challenges to further scaling. First, the device electrostatics (the ability of the transistor's gate electrode to control its channel potential) are degraded when the channel length is decreased, using conventional bulk materials such as silicon as the channel. Recently, two-dimensional semiconducting materials have emerged as promising candidates to replace silicon, as they can maintain excellent device electrostatics even at much reduced channel lengths. The second, more severe, challenge is that the supply voltage can no longer be scaled down by the same factor as the transistor dimensions because of the fundamental thermionic limitation of the steepness of turn-on characteristics, or subthreshold swing. To enable scaling to continue without a power penalty, a different transistor mechanism is required to obtain subthermionic subthreshold swing, such as band-to-band tunnelling. Here we demonstrate band-to-band tunnel field-effect transistors (tunnel-FETs), based on a two-dimensional semiconductor, that exhibit steep turn-on; subthreshold swing is a minimum of 3.9 millivolts per decade and an average of 31.1 millivolts per decade for four decades of drain current at room temperature. By using highly doped germanium as the source and atomically thin molybdenum disulfide as the channel, a vertical heterostructure is built with excellent electrostatics, a strain-free heterointerface, a low tunnelling barrier, and a large tunnelling area. Our atomically thin and layered semiconducting-channel tunnel-FET (ATLAS-TFET) is the only planar architecture tunnel-FET to achieve subthermionic subthreshold swing over four decades of drain current, as recommended in ref. 17, and is also the only tunnel-FET (in any architecture) to achieve this at a low power-supply voltage of 0.1 volts. Our device is at present the thinnest-channel subthermionic transistor, and has the potential to open up new avenues for ultra-dense and low-power integrated circuits, as well as for ultra-sensitive biosensors and gas sensors.

We present near-field Raman spectroscopy and imaging of single isolated single-walled carbon nanotubes with a spatial resolution of 25 nm. The near-field origin of the image contrast is confirmed by the measured dependence of the Raman scattering signal on tip-sample distance and the unique polarization properties. The method is used to study local variations in the Raman spectrum along a single single-walled carbon nanotube. DOI: 10.1103/PhysRevLett.90.095503 PACS numbers: 61.46.+w, 07.79.-v, 78.30.Na, 78.67.Ch Recent rapid advances in nanotechnology and nanoscience are largely due to our newly acquired ability to measure and manipulate individual structures on the nanoscale. Among the new methods are scanning probe techniques, optical tweezers, and high-resolution electron microscopes. Recently, a near-field optical technique has been demonstrated which allows spectroscopic measurements with 20 nm spatial resolution [1]. The method makes use of the strongly enhanced electric field close to a sharp metal tip under laser illumination and relies on the detection of two-photon excited fluorescence. However, fluorescence imaging requires a high fluorescence quantum yield of the system studied or artificial labeling with fluorophores. Furthermore, fluorescence quenching by the metal tip competes with the local field enhancement effect and therefore limits the general applicability. On the other hand, Raman scattering probes the unique vibrational spectrum of the sample and directly reflects its chemical composition and molecular structure. A main drawback of Raman scattering is the extremely low scattering cross section which is typically 14 orders of magnitude smaller than the cross section of fluorescence. Surface enhanced Raman scattering (SERS), induced by nanometer-sized metal structures, has been shown to provide enormous enhancement factors of up to 10 15 allowing for Raman spectroscopy even on the single molecule level [2,3]. Controlling SERS with a sharp metal tip which is raster scanned over a sample surface has been proposed [1,4], and near-field Raman enhancement has been experimentally demonstrated [5][6][7][8][9]. Here, we show the chemical specificity of this near-field technique and demonstrate an unprecedented spatial resolution.Single-walled carbon nanotubes (SWNTs) have been the focus of intense interest due to a large variety of potential nanotechnological applications. The unique properties of SWNTs arise from their particular onedimensional structure which is directly linked to the characteristic Raman bands. Raman scattering on SWNTs has been studied intensively in the literature (see, e.g., Refs. [10 -13]) and Raman enhancements of up to 10 12 have been reported for tubes in contact with fractal silver colloidal clusters [14]. In this Letter, nearfield Raman imaging of SWNTs is demonstrated using a sharp silver tip as a probe. We show, for the first time, that single isolated SWNTs can be detected optically with a spatial resolution better than 30 nm. This high-resolution capability is ap...

Animal cells divide into two daughter cells by the formation of an actomyosin-based contractile ring through a process called cytokinesis. Although many of the structural elements of cytokinesis have been identified, little is known about the signaling pathways and molecular mechanisms underlying this process. Here we show that the human ECT2 is involved in the regulation of cytokinesis. ECT2 catalyzes guanine nucleotide exchange on the small GTPases, RhoA, Rac1, and Cdc42. ECT2 is phosphorylated during G2 and M phases, and phosphorylation is required for its exchange activity. Unlike other known guanine nucleotide exchange factors for Rho GTPases, ECT2 exhibits nuclear localization in interphase, spreads throughout the cytoplasm in prometaphase, and is condensed in the midbody during cytokinesis. Expression of an ECT2 derivative, containing the NH2-terminal domain required for the midbody localization but lacking the COOH-terminal catalytic domain, strongly inhibits cytokinesis. Moreover, microinjection of affinity-purified anti-ECT2 antibody into interphase cells also inhibits cytokinesis. These results suggest that ECT2 is an important link between the cell cycle machinery and Rho signaling pathways involved in the regulation of cell division.

Highly-reducing iterative polyketide synthases are large multifunctional enzymes that make important metabolites in fungi, such as lovastatin, a cholesterol-lowering drug from Aspergillus terreus. We report efficient expression of LovB (the Lovastatin Nonaketide Synthase) from an engineered strain of Saccharomyces cerevisiae, and complete reconstitution of its catalytic function in the presence and absence of cofactors (NADPH, SAM) and its partner enzyme, the enoyl reductase LovC. The results demonstrate that LovB retains correct intermediates until completion of synthesis of dihydromonacolin L, but off-loads incorrectly processed compounds as pyrones or hydrolytic products. Experiments replacing LovC with analogous MlcG from compactin biosynthesis demonstrate a gate-keeping function for this partner enzyme. This study represents a key step in the understanding the functions and structures of this family of enzymes.Nature uses an amazing array of enzymes to make natural products (1). Among these metabolites, polyketides represent a class of over 7000 known structures of which more than 20 are commercial drugs (2). Among the most interesting but least understood enzymes making these compounds are the highly-reducing iterative polyketide synthases (HR-IPKSs) found in filamentous fungi (3). In contrast to the well-studied bacterial type I PKSs that operate in an assembly-line fashion (4), HR-IPKSs are megasynthases that function iteratively by using a set of catalytic domains repeatedly in different combinations to produce structurally diverse fungal metabolites (5). One such metabolite is lovastatin, a cholesterol-lowering drug from Aspergillus terreus (6). This compound is a precursor to simvastatin (Zocor™), a semisynthetic drug that had annual sales of over $4.3 billion prior to loss of patent protection in 2006 (7).Biosynthesis of lovastatin proceeds via dihydromonacolin L (acid form 1; lactone form 2), a product made by the HR-IPKS, LovB (Lovastatin Nonaketide Synthase), with assistance of a separate enoyl reductase, LovC (8) (Fig. 1). LovB is a 335 kDa protein that contains single copies of ketosynthase (KS), malonyl-CoA:ACP acyltransferase (MAT), dehydratase (DH), § To whom correspondence should be addressed. yitang@ucla.edu (Y.T.); john.vederas@ualberta.ca (J.C.V.).Reconstitution of catalytic function provides insight into how multifunctional enzymes synthesize important natural products. This enzyme also catalyzes a biological Diels Alder reaction during the assembly process to form the decalin ring system (10). In vitro studies of LovB (11) have been hampered by inability to obtain sufficient amounts of the functional purified megasynthase from either A. terreus or heterologous Aspergillus hosts. As a result, the programming that governs metabolite assembly by LovB or other HR-IPKSs is not understood. Key aspects that remain to be elucidated include: 1) the catalytic and structural roles of each domain in the megasynthase; 2) substrate specificities of the catalytic domains and their tolerance to...