High-Throughput Analysis from Complex Matrices: Acoustic Ejection Mass Spectrometry from Phase-Separated Fluid Samples.

Acoustic ejection mass spectrometry is a novel high-throughput analytical technology that delivers high reproducibility without carryover observed. It eliminates the chromatography step used to separate analytes from matrix components. Fully-automated liquid-liquid extraction is widely used for sample cleanup, especially in high-throughput applications.

Acoustic Ejection Mass Spectrometry for High-Throughput Analysis.

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 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.

Direct Analysis from Phase-Separated Liquid Samples using ADE-OPI-MS: Applicability to High-Throughput Screening for Inhibitors of Diacylglycerol Acyltransferase 2.

The primary goal of high-throughput screening (HTS) is to rapidly survey a broad collection of compounds, numbering from tens of thousands to millions of members, and identify those that modulate the activity of a therapeutic target of interest. For nearly two decades, mass spectrometry has been used as a label-free, direct-detection method for HTS and is widely acknowledged as being less susceptible to interferences than traditional optical techniques. Despite these advantages, the throughput of conventional MS-based platforms like RapidFire or parallel LC-MS, which typically acquire data at speeds of 6-30 s/sample, can still be limiting for large HTS campaigns.

High-Throughput Mass Spectrometry for Hit Identification: Current Landscape and Future Perspectives.

For nearly two decades mass spectrometry has been used as a label-free, direct-detection method for both functional and affinity-based screening of a wide range of therapeutically relevant target classes. Here, we present an overview of several established and emerging mass spectrometry platforms and summarize the unique strengths and performance characteristics of each as they apply to high-throughput screening. Multiple examples from the recent literature are highlighted in order to illustrate the power of each individual technique, with special emphasis given to cases where the use of mass spectrometry was found to be differentiating when compared with other detection formats.

Encrusted Urinary Tract Infections Due to Corynebacteria Species.

Introduction: Encrusted pyelitis and cystitis are peculiar disorders characterized by the calcification of the vesical, the pyelic, and/or the ureteral walls. These calcifications are composed of struvite and calcium carbonate‒apatite due to the presence of .

Methods: We have identified the clinical features and outcomes of 17 patients with encrusted pyelitis (n = 15) or encrusted cystitis (n = 2).

Acoustic Mist Ionization-Mass Spectrometry: A Comparison to Conventional High-Throughput Screening and Compound Profiling Platforms.

Drug discovery usually begins with a high-throughput screen (HTS) of thousands to millions of molecules to identify starting points for medicinal chemistry. Conventional HTS platforms require expensive reagents and typically have complex assay formats. HTS platforms based on radioactivity are expensive, both in terms of reagent cost and disposal.

Mechanisms of kidney disease in Sneddon's syndrome: Case report and literature review .

Sneddon's syndrome is a rare, noninflammatory thrombotic vasculopathy characterized by the combination of livedo racemosa, recurrent stroke, and histopathological skin lesions of endarteritis obliterans. Although multiorgan involvement suggests its systemic nature, detailed pathological description of affected organs - including the kidney - is exceptional. We report a case of Sneddon's syndrome with chronic kidney disease, associated with features of endarteritis obliterans in the skin and the kidney.

Acoustic Mist Ionization Platform for Direct and Contactless Ultrahigh-Throughput Mass Spectrometry Analysis of Liquid Samples.

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.

Acoustic Injectors for Drop-On-Demand Serial Femtosecond Crystallography.

X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected.

Novel Acoustic Loading of a Mass Spectrometer: Toward Next-Generation High-Throughput MS Screening.

High-throughput, direct measurement of substrate-to-product conversion by label-free detection, without the need for engineered substrates or secondary assays, could be considered the "holy grail" of drug discovery screening. Mass spectrometry (MS) has the potential to be part of this ultimate screening solution, but is constrained by the limitations of existing MS sample introduction modes that cannot meet the throughput requirements of high-throughput screening (HTS). Here we report data from a prototype system (Echo-MS) that uses acoustic droplet ejection (ADE) to transfer femtoliter-scale droplets in a rapid, precise, and accurate fashion directly into the MS.

Septic arthritis of the pubic symphysis: an atypical abdominal pain.

Septic arthritis of the pubic symphysis is a rare infection mostly caused by Staphylococcus aureus, and is traditionally associated with risk factors (sports, female incontinence surgery). Typical features of pubic symphysis infection include abdominal, pelvic, or groin pain that increases upon standing and walking, causing limping to occur. Acute onset of fever is often associated.

Ultrafast nonlinear sub-wavelength solid immersion spectroscopy at T = 8 K: an alternative to nonlinear scanning near-field optical microscopy.

Pump-probe measurements were performed with a subwavelength spatial resolution of 355 nm and a temporal resolution of 130 fs in a multiple quantum well sample at T= 8 K. A solid immersion lens was used to increase the spatial resolution to 0.41 lambda, demonstrating that the limit of conventional microscopy was surpassed.