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.

A method of newborn screening (“NBS”) is disclosed comprising directing ultrasonic energy or ultrasonic waves into a metabolite or analyte sample derived from a newborn, neonate or infant so as to cause a mist of charged sample droplets or sample ions to be ejected. The charged sample droplets or sample ions are then mass analysed and a determination is made as to whether or not one or more first metabolites or analytes indicative of a disorder or inborn error are present in the sample.

An ultrasonic transmitter (95) and detector (e.g., integrated as an ultrasound transducer) utilized in a feedback control system automatically monitors and/or detects surface profile (e.g., shape) of the liquid-air interface and adjusts the flow rate of sampling liquid to ensure that experimental conditions remain consistent at the time of sample introduction during serial samplings. The feedback control can provide for automated adjustment of the surface profile of the liquid-air interface in accordance with changes in desired set point according to an experimental workflow (e.g., automated adjustment between an interface corresponding to a vortex sampling set point and an overflow cleaning set point). Improvements in desorption efficiency and quality of mass spectrometry data by degassing of the liquid solvent utilized within the sampling interfaces, and/or utilization in a feedback control system for generating data indicative of a surface profile of the liquid-air interface within the interface's sampling port may be realized.

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to a vibrating sharp edge spray ionization (VSSI) method suitable for coupling with a mass spectrometer, a VSSI method modified with a capillary suitable for use with continuous-flow separation methods such as liquid chromatography, and a VSSI method suitable for coupling with a capillary electrophoresis (CE) device in order to introduce the CE sample flow into a mass spectrometer. Also disclosed herein are devices for carrying out these methods and methods of making the same. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

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.

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.

A method of analyzing and/or sorting selected cells or other biological components, for example for cell-based therapy, includes sampling a sample with an open end of a probe to obtain a fluid stream with the sample in it. The probe with the open end also has a fluid supply to convey fluid to the open end, and a fluid exhaust to convey the fluid stream away from the open end. The method then includes conveying the fluid stream to a flow cytometer and analyzing the fluid stream by flow cytometry; and/or separating it into at least two components. An apparatus with the probe connected to the flow cytometer may support this method. The method can provide for sampling of multiple samples efficiently, in particular to select cells for cell-based therapies.

Technologies for rapid equilibration for water isotope analysis are disclosed. In at least one illustrative embodiment, a vaporizer may include an injection block that defines a chamber and a septum positioned over an inlet of the chamber to seal the chamber. The chamber may be configured to be fluidly coupled to a pump to develop a vacuum within the chamber, and the septum may be configured to receive a needle that is inserted into the chamber. A thermally conductive wool may be positioned within the chamber and may be configured to receive a tip of the needle.

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.

A system for sampling a liquid includes a sample fluid conduit including a membrane having pores. The membrane prevents the passage of the sample liquid through the pores at a first pressure of the sample liquid in the sample fluid conduit. A surface sampling capture probe has a distal end. The capture probe includes a solvent supply conduit and a solvent exhaust conduit. A solvent composition flowing at the distal end of the capture probe establishes a liquid junction with the membrane and establishes a second pressure within the liquid junction at the membrane. The second pressure is lower than the first pressure. Sample liquid will be drawn through the pores of the membrane by the second pressure at the liquid junction. A method for sampling a liquid and for performing chemical analysis on a liquid are also disclosed.