Disclosed are methods for separating target and non-target analytes in a sample. The methods can utilize an acoustic droplet ejector (ADE) and an open port interface (OPI) to achieve liquid chromatography (LC)-like separation for an analytical instrument such as, for example, a mass spectrometer.

Focused acoustic radiation, referred to as tonebursts, are applied to a volume of liquid to generate a set of droplets. The droplets generated are substantially smaller in scale than the focal spot size of the acoustic beam (e.g., the frequency at which the acoustic transducer operates). Further, the droplets have trajectories that are substantially in the direction of the acoustic beam propagation direction. In one embodiment, a first toneburst is applied to temporarily raise a protuberance on a free surface of the fluid. After the protuberance has reached a certain state, a second toneburst is applied to the protuberance to break it into very small droplets. In one embodiment, the state of the protuberance at which the second toneburst is supplied is the time period shortly after the protuberance reaches its maximum height but before the protuberance recedes back into the volume of fluid.

An ion source is disclosed comprising a nebulizer and a target. The nebulizer is arranged and adapted to emit, in use, a stream of analyte droplets which are caused to impact upon the target and to ionize analyte to form a plurality of analyte ions. The target is vibrated by a piezo-electric vibration device to reduce the size of resultant secondary droplets.

A system and method are provided for loading a sample into an analytical instrument using acoustic droplet ejection (ADE) in combination with a continuous flow sampling probe. An acoustic droplet ejector is used to eject small droplets of a fluid sample containing an analyte into the sampling tip of a continuous flow sampling probe, where the acoustically ejected droplet combines with a continuous, circulating flow stream of solvent within the flow probe. Fluid circulation within the probe transports the sample through a sample transport capillary to an outlet that directs the analyte away from the probe to an analytical instrument, e.g., a device that detects the presence, concentration quantity, and/or identity of the analyte. When the analytical instrument is a mass spectrometer or other type of device requiring the analyte to be in ionized form, the exiting droplets pass through an ionization region, e.g., an electrospray ion source, prior to entering the mass spectrometer or other analytical instrument. The method employs active flow control and enables real-time kinetic measurements.

Provided herein are systems and methods for sampling analytes into an atmospheric pressure inlet mass spectrometer using ultrasonic nebulization-assisted atmospheric pressure chemical ionization. The systems can include a mass spectrometer having an input and an ultrasonic nebulizer chip. The ultrasonic nebulizer chip can be operatively coupled to the mass spectrometer, such that when the ultrasonic nebulizer chip nebulizes the analyte to provide a nebulized analyte, at least some of the nebulized analyte enters the input of the mass spectrometer.

Disclosed are methods and systems that provide for the analysis of one or more analytes of interest in an acoustic ejection mass spectrometer (AEMS) system that incorporates an open port interface (OPI) and differentiation mass spectrometry (DMS) that allows for operation of the system in a pseudo-continuous mode to scan and determine optimal DMS settings for the one or more analytes of interest, and for operation of the system in a discontinuous mode to analyze for the presence of the one or more analytes of interest in a sample.

A method of ionizing a sample is provided, comprising providing a fluid sample, wherein the fluid sample contains an analyte, applying one or more pulses of acoustic energy to the fluid sample to cause a spray of the fluid sample to eject from the surface of the fluid sample, and applying an AC, RF or alternating voltage to the fluid sample using an electrode.

The presently claimed and described technology provides a sample processing system comprising at least one sample introduction device, wherein the at least one sample introduction device is configured to receive a sample; a mass analyzer coupled to the sample introduction device; a control system configured to at least control the at least one sample introduction device and/or the mass analyzer, wherein the mass analyzer is configured to perform a first mass analysis on the sample, wherein the first mass analysis is mass screening for an analyte of interest in the sample, and wherein if the analyte of interest is detected in the sample, the mass analyzer is configured to perform a second mass analysis, wherein the second mass analysis is a quantitative analysis, comprising: ionizing the sample; monitoring, by mass spectrometry, at least one product ion transition for the at least one analyte and at least one isotopic ion transition for the at least one analyte; determining intensity and/or abundance of the at least one product ion transition and/or the at least one isotopic ion transition; and quantifying the at least one analyte present in the sample using the intensity and/or abundance of the at least one product ion transition and/or isotopic ion transition.

Focused acoustic radiation, referred to as tonebursts, are applied to a volume of liquid to generate a set of droplets. The droplets generated are substantially smaller in scale than the focal spot size of the acoustic beam (e.g., the frequency at which the acoustic transducer operates). Further, the droplets have trajectories that are substantially in the direction of the acoustic beam propagation direction. In one embodiment, a first toneburst is applied to temporarily raise a protuberance on a free surface of the fluid. After the protuberance has reached a certain state, a second toneburst is applied to the protuberance to break it into very small droplets. In one embodiment, the state of the protuberance at which the second toneburst is supplied is the time period shortly after the protuberance reaches its maximum height but before the protuberance recedes back into the volume of fluid.

Disclosed herein is a method of preparing macromolecular structures for analysis, including placing a macromolecular sample on a surface acoustic wave (SAW) device including: a piezoelectric surface, a first transducer in contact with the piezoelectric surface, a second transducer in contact with the piezoelectric surface, and a sample region disposed between the first transducer and the second transducer and configured to receive the macromolecular sample, the sample region configured to remain electrically isolated from each of the first transducer and the second transducer; applying disruption electrical energy, having a disruption frequency and a disruption power, to each of the first transducer and the second transducer to transform the macromolecular sample into a disrupted macromolecular sample; and applying nebulization electrical energy, comprising a nebulization frequency and a nebulization power, to each of the first transducer and the second transducer, to transform the disrupted macromolecular sample into a nebulized macromolecular sample.