Straightforward Readout Research Articles

Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe and very high-frequency applications

Scanning probe microscopies (SPM) and cantilever-based sensors generally use low-frequency mechanical devices of microscale dimensions or larger. Almost universally, off-chip methods are used to sense displacement in these devices, but this approach is not suitable for nanoscale devices. Nanoscale mechanical sensors offer a greatly enhanced performance that is unattainable with microscale devices. Here we describe the fabrication and operation of self-sensing nanocantilevers with fundamental mechanical resonances up to very high frequencies (VHF). These devices use integrated electronic displacement transducers based on piezoresistive thin metal films, permitting straightforward and optimal nanodevice readout. This non-optical transduction enables applications requiring previously inaccessible sensitivity and bandwidth, such as fast SPM and VHF force sensing. Detection of 127 MHz cantilever vibrations is demonstrated with a thermomechanical-noise-limited displacement sensitivity of 39 fm Hz(-1/2). Our smallest devices, with dimensions approaching the mean free path at atmospheric pressure, maintain high resonance quality factors in ambient conditions. This enables chemisorption measurements in air at room temperature, with unprecedented mass resolution less than 1 attogram (10(-18) g).

A potent and specific morpholino antisense inhibitor of hepatitis C translation in mice

Hepatitis C virus (HCV) is an RNA virus infecting one in every 40 people worldwide. Current treatments are ineffective and HCV is the leading cause of liver failure leading to transplantation in the United States and Europe. Translational control of HCV is a prime therapeutic target. We assessed the inhibitory potential of morpholino phosphoramidate antisense oligonucleotides (morpholinos) on HCV translation by codelivering them with reporter plasmids expressing firefly luciferase under the translational control of the HCV internal ribosome entry site (IRES) into the livers of mice. Real-time imaging of HCV IRES luciferase reporter messenger RNA (mRNA) translation in living mice showed that a 20-mer complementary to nucleotides 345-365 of the IRES inhibited translation by greater than 95% for at least 6 days and showed mismatch specificity. No significant nonspecific inhibition of a cap-dependent luciferase or encephalomyocarditis virus (EMCV) IRES luciferase reporter translation was observed. Inhibition by the 20-mer morpholino was dose dependent, with 1 nmol/mouse giving the highest inhibition. In conclusion, morpholino antisense oligonucleotides are potent inhibitors of HCV IRES translation in a preclinical mouse model; morpholinos have potential as molecular therapeutics for treating HCV and other viral infections. The in vivo model described is a broadly applicable, straightforward, and rapid readout for inhibitor efficacy. As such, it will greatly facilitate the development of novel therapeutic strategies for viral hepatitis. Notably, the level of antisense inhibition observed in this in vivo model is similar to the maximal inhibition we have obtained previously with RNA interference in mice. (H epatology 2003;38:503-508.)

Dosimetry by ESR spectroscopy of alanine

Dosimetry based on electron spin resonance analysis of radiation-induced free radicals in amino acids (e.g. l -alanine) is relevant to biological dosimetry applications. Typical features are a wide dose range covering more than 5 decades (1–105 Gy), energy independent response for photons above 100 keV, long-term stability of the ESR signal, and fast straightforward readout technique. Typical dosimeter samples, consisting of small pellets of microcrystalline amino acids in paraffin, are rugged, non-toxic, and insensitive to surface contaminations. Moreover, they are prepared homogeneously and inexpensively in large batches and can be evaluated repeatedly and supply archival dosimetry data. They have proven to be highly useful in various applications of radiation processing and sterilization dosimetry, food irradiation, quality control, radiation dosimetry, radiation therapy measurements, and as a reference system for dosimetry mailing intercomparisons.