A simple and sensitive method for detecting small forces applied to an optically trapped microsphere utilizes the transmitted beam of the trapping laser to monitor microsphere deflections within the potential well of the trap. The rms dynamic displacement detection sensitivity measured in the frequency range from 1 Hz to 10 kHz is ∼1 nm in the radial direction and ∼10 nm along the z (optic) axis. Radiation trapping force constants were calibrated against viscous drag on microspheres in the range between the Rayleigh (r<0.2λ) and Mie (r≫λ) size regimes. For a 1-μm-diam polystyrene sphere trapped with a 60 mW beam the rms spontaneous thermal motion limits the force sensitivity to better than 10−12 N and lateral spatial resolution to ∼10 nm in a frequency range from 1 Hz to the viscous rolloff frequency ∼1 kHz. The measured maximum trapping efficiencies are compared with the theoretical predictions of the ray-optics approximation.

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Mass spectrometry (MS) has many advantages as a quantitative detection technology for applications within drug discovery. However, current methods of liquid sample introduction to a detector are slow and limit the use of mass spectrometry for kinetic and high-throughput applications. We present the development of an acoustic mist ionization (AMI) interface capable of contactless nanoliter-scale "infusion" of up to three individual samples per second into the mass detector. Installing simple plate handling automation allowed us to reach a throughput of 100 000 samples per day on a single mass spectrometer. We applied AMI-MS to identify inhibitors of a human histone deacetylase from AstraZeneca's collection of 2 million small molecules and measured their half-maximal inhibitory concentration. The speed, sensitivity, simplicity, robustness, and consumption of nanoliter volumes of sample suggest that this technology will have a major impact across many areas of basic and applied research.

We report a study of a gallium phosphide, hemispherical, solid immersion lens through the imaging of 40-nm-diam fluorescent dye balls. A spatial resolution as small as 139 nm has been achieved at a wavelength of 560 nm, which is equivalent to a diffraction-limited system of numerical aperture 2.0. This resolution is a 33% improvement over conventional oil immersion objectives and previously reported solid immersion lenses, which typically have a numerical aperture around 1.5.

We describe a mass spectrometry (MS) analytical platform resulting from the novel integration of acoustic droplet ejection (ADE) technology, an open-port interface (OPI), and electrospray ionization (ESI) MS that creates a transformative system enabling high-speed sampling and label-free analysis. The ADE technology delivers nanoliter droplets in a touchless 20 manner with high speed, precision and accuracy; subsequent sample dilution within the OPI, in concert with the capabilities of modern ESI-MS, eliminates the laborious sample preparation and method development required in current approaches. This platform is applied to a variety of experiments, including high-throughput (HT) pharmacology screening, label-free in situ enzyme kinetics, in vitro and in vivo adsorption, distribution, metabolism, elimination, pharmacokinetic 25 (PK) and biomarker analysis, and HT parallel medicinal chemistry.One Sentence Summary: ADE-OPI-MS is a transformational analytical platform that increases mass spectrometry utility via sub-second speed and non-contact sampling.Mass is a fundamental molecular characteristic, and the advent of mass spectrometry (MS) to 30