GB2631767A

GB2631767A - Device and method for aerosol collection

Info

Publication number: GB2631767A
Application number: GB2310773.3A
Authority: GB
Inventors: Cramer Rainer
Original assignee: University of Reading
Current assignee: University of Reading
Priority date: 2023-07-13
Filing date: 2023-07-13
Publication date: 2025-01-15
Also published as: WO2025012662A1; GB202310773D0

Abstract

A device for collecting an aerosolised plume from a sample, the device formed of an electrically non-conductive or minimally conductive material and comprising at least one aperture configured to collect the plume and a cavity for receiving an inlet of an analytical instrument. The aerosolised plume may be ionic or non-ionic or a combination thereof and may be produced by an ablation, desorption, or evaporation technique. The at least one aperture may be cylindrical or conical and have a diameter of 1-10 mm. The material may be an electrical insulator or dielectric material such as ASA, ABS, HIPS, PEEK, polycarbonate, polypropylene, or nylon. The analytical instrument may be a mass spectrometer using at least one of time-of-flight, quadrupole, ion trap, orbitrap, or electric and/or magnetic sector mass analysers.

Description

DEVICE AND METHOD FOR AEROSOL COLLECTION

Technical Field

[1] The present invention relates to a device and method for collecting aerosols produced by ablation, desorption or evaporation techniques. Specifically, the aerosols may be collected for use in analytical instrumentation such as a mass spectrometer.

Background Art

[2] In analytical chemistry and other related fields, samples are frequently ablated or desorbal to produce aerosolised plumes that will be further analysed. For instance, in mass spectrometry "MS", there are two main soft ionisation techniques: electrospray ionisation "ESI" and matrix-assisted laser desorption/ionisation "MALDI". These two techniques have low fragmentation rates and are able to produce plumes which may he further desolvated and ionized to produce molecular ions that are suitable for mass spectrometric detection and analysis.

[3] Accordingly, efficient devices and methods for collecting such a plume are desirable, ideally suited for increasing both the efficiency of plume collection and the subsequent transfer into an analytical instrument.

[4] Various methods and apparatuses are known from the prior art which utilise setups that enclose the space around the location of plume generation and/or provide curtain gases. These are designed to guide the plume towards the inlet of an analytical instrument. However, such setups are often fairly large and complex, requiring extended designs, parts, and implementations.

[5] Stahnke H, Kittlaus S, Kempe G, Hemmerling C, Alder L -"The influence of electrospray ion source design on matrix effects" -J Mass Spectrum. 2012;47(7):875-84 concerns an investigation into the extent to which the design of electrospray ion sources influences the susceptibility to matrix effects in liquid chromatography-tandem mass spectrometry, finding no relation between source geometry and extent of signal suppression.

[6] US 9831078 B2 discloses a method of providing ions in a mass spectrometry system comprising introducing neutral analyte molecules to a first end of an ion funnel, ionising the neutral analyte molecules in the ion funnel to form analyte ions, and guiding the analyte ions to a second end of the ion funnel.

[007] Other designs include devices which are integrated into an analytical instrument. For instance, the ESI MS design disclosed in Marginean I, Page JS, Tolmachev AV, Tang KQ, Smith RD -"Achieving 50% Ionization Efficiency in Subambient Pressure Ionization with Nanoelectrospray" -Anal Chem. 2010;82(22):9344-9 requires the ion source to be under vacuum. However, this requires substantial modifications which result in a loss of the benefits of a simple ambient ionisation source set-up.

10081 US 6,455,846 B1 and Wu S, Zhang K, Kaiser NK, Bruce JE --Incorporation ()fa flared inlet capillary tube on a Fourier transform ion cyclotron resonance mass spectrometer" -J Am Soc Mass Spent. 2006;17(6):772-9 relate to improvements in plume collection by focussing on changes to the inlet capillary/tube or other inlets of the analytical instrument. However, because these are integrated with the instruments, they are typically made of the same (metal) material as the original inlet.

[9] None of the integral inlet designs are optimised for plume collection of all aerosol particles/molecules. As such, there still remains a need for plume collection of particles that will be desolvated and ionised at a later stage.

Summary of the Invention

[10] Therefore, an object of the present invention is to provide a small and inexpensive add-on device which can he easily fitted to the inlet capillary/tube or other inlet shapes such as cones, as commonly found with analytical instruments such as mass spectrometers, thus avoiding the need for larger modifications to the ion source.

[11] According to a first aspect, there is provided a device for collecting an aerosolised plume from a sample, the device formed of an electrically non-conductive or minimally conductive material and comprising at least one aperture configured to collect the plume and a cavity for receiving an inlet of an analytical instrument.

[12] Advantageously, the selection of material for their present invention allows the device to he located in close proximity to electrodes that are required to define electrical fields for ion production and guidance. Furthermore, the electrically non-conductive or minimally conductive material is selected to permit ion production and extraction from an aerosolised plume without any electrical breakthrough between the electrical field-defining electrodes. Moreover, compared to other plume collection devices, the present invention is small and can be easily and cost-effectively manufactured, for instance by three-dimensional printing.

[13] In embodiments, the aerosolised plume is at least one of ionic and non-ionic or a combination of ionic and non-ionic. In this way, both ionised particles and neutral particles which will be ionised at a later stage -may be collected.

[14] In embodiments, the aerosolised plume is produced by at least one of an ablation, desorption or evaporation technique. In this way, a variety of samples and techniques may be used for plume collection. In embodiments, these may be one of laser-induced ablation and desorption techniques such as LDI, MALDI and their derivatives, ESI and their derivatives such as DESI and paperspray, ion spray, thermospray, plasma-induced ablation and desorption/ionization techniques, plume generation by arc/spark-based discharges, and gases and plumes generated by evaporation of substances and mixtures.

[15] In embodiments, the at least one aperture is either cylindrical or conical. In this way, the aperture can efficiently collect a larger volume of aerosolised plume by ensuring less plume volume is lost during transfer.

[16] In embodiments, the at least one aperture has a diameter of between 1-10 mm.

[17] In embodiments, the material is an electrical insulator or dielectric material. In this way, effective enclosure of a sample may be achieved whilst mitigating the risk of electrical breakdown occurring between electrodes.

[18] In embodiments, the electrical insulator or dielectric material is PEEK or 3D printing material, including but not limited to ASA, ABS, HIPS, polycarbonate, polypropylene and nylon. In embodiments, the materials are at least one of heat-resistant, chemically resistant and rigid.

[19] According to a second aspect, there is provided a system comprising the device of any of the above embodiments and an analytical instrument comprising an inlet configured to receive an aerosolised plume generated from a sample.

10201 In embodiments, the analytical instrument is a mass spectrometer.

10211 In embodiments, the mass spectrometer uses at least one of time-of-flight "TOF", quadrupole "Q", ion trap "IT", orbitrap, electric and/or magnetic sector mass analysers.

[22] In embodiments, an interference fit is provided between the device and an inlet of the analytical instrument. In this way, a greater volume of aerosolised plume is delivered to the analytical instrument.

[23] In embodiments, an airtight enclosure is provided between the device and the sample.

10241 In embodiments, an electrical field or a pressure differential is provided between the inlet of the analytical instrument and the sample.

[025] In embodiments, an opening is provided to allow adequate access for a sample desorption/ablation probe to reach the sample. In embodiments, the desorption/ablation probe is a laser beam.

10261 In embodiments, an inlet to the space enclosed by the device's aperture is provided for the introduction of gases or liquids to enhance the ambient environment for best analyte collection to the analytical instrument. In embodiments, this inlet can also be used for the introduction of reagent gases to facilitate analyte reactions. In this way, the well-defined and restricted space within the device can act as a reaction chamber.

[27] According to a third aspect, there is provided a method of collecting an aerosolised plume comprising the steps of placing the device according to any of claims 1 to 7 in close proximity to a sample, generating an aerosolised plume via one of an ablation, desorption or evaporation technique, and entraining the aerosolised plume towards an inlet of an analytical instrument.

Brief Description of the Drawings

[28] Figures 1 A and 1B show cross-sectional and top views respectively of a device according to embodiments of the invention; Figures 2A and 2B show ion signal improvements for bradykinin using the device of Figure 1; Figure 3 shows protein signals when using the device of Figure 1; and Figure 4 is a cross-sectional view of the device of Figure 1, configured for use with an ESI source.

Detailed Description

[29] Figures lA and 1B show views of a device according to an embodiment of the invention. The device illustrated in claim I has an exterior shape that is approximately cylindrical. However, the exterior shape is not crucial to the working of the device and can he adjusted to fit the analytical instrument and/or facilitate its manufacture. The interior of the device comprises a cavity to receive an inlet tube of an analytical instrument. The device further comprises an aperture with an approximately conical funnel shape which opens up towards a sample located on a sample plate.

[30] For techniques employing laser-based ablation or desorption, an additional small opening can be provided. This additional opening allows a laser beam to pass through the device in order to reach and contact the sample surface. Similar openings can be made for other probe-based ablation or desorption techniques, such as plasma-based techniques, or techniques using other beams such as molecular or ionising radiation beams. For techniques where the sample is not located on a sample plate, the entrainment of the sample and thus the sample plume can he achieved by other means as shown in Figure 4.

[31] The at least one aperture of the device is constructed to provide only small openings to the surrounding area proximate to the device when entraining the sample. Theses openings are typically minimised, leading to restrictions of the air or gas flow to and from the sunounding space into the device. If an analytical instrument under vacuum is employed, the air/gas flow, resulting from these restrictions, will create a pneumatic drag of the plume into the analytical instrument This pneumatic drag acts to entrain a plume generated from aerosolising a sample towards the inlet of the analytical instrument. The aperture of the device towards which the sample is located is sized such that pneumatic drag is increased, but absolute contact with the sample delivery plate is not excluded.

[32] The device of Figure 1 is constructed from electric insulators or dielectric material. This material is chosen because it does not substantially interfere with the electric field for ion extraction. As a result, the device will not cause electric breakdowns that could interfere with the analytical integrity of the plume, even if the device is in contact with the electrodes of differential potential.

[33] In use, the device is pushed onto an inlet tube of an analytical instrument. The cavity of the device is shaped such that a tight fit, in some embodiments an interference fit, is provided between the device and the inlet tube. A sample is typically located 0-2mm from the device and is aerosolised into a plume by at least one of an ablation, desorption, or evaporation technique. The aerosolised plume contains ionic and non-ionic components.

[34] The configuration of the device acts to entrain the aerosolised plume towards the inlet of the analytical instrument. That is, a combination of the positioning of the sample, the device and instrument, together with the presence of at least one of an electrical field or a pressure differential causes substantially more of the generated plume to be delivered for further analysis than those devices of the prior art.

[35] Figures 2A and 2B display exemplary analyte ion signal improvements obtained using the device shown in Figure 1. In the present example, the device (PCD) is applied to an APMALDI source on a Q-TOF mass spectrometer and compared to the set-up without using the device (No PCD); charge states are denoted by "+" and "++". Figure 2B shows the data of Figure 2A with a zoomed in y-axis scale.

[36] Using LAP-MALDI MS, improvements for doubly protonated bradykinin (at a concentration of 1pmolluL) are found to be between 2-fold to 7-fold. These improvements are dependent on the amount of heat applied to the inlet tube, and in singly protonated bradykinin, improvements of up to 40-fold or more have been recorded.

[37] Comparing the ion signals at optimal heat settings at an inlet tube, it is seen that the improvement is approximately 3-fold for the doubly protonated bradykinin and 6-fold for the singly charged bradykinin. Interestingly, while no bradykinin ion signals arc recorded for the lower or no heating settings without the device, such signals can be recorded with the device.

[38] Figure 3 shows the effect of the device of Figure 1 when utilised for the detection of cytochrome C ions of various charge states at the low-picomole level, employing the same instrumental set-up as detailed above. As before, a comparison is made between using the device (PCD) and not using it (No PCD). For all charge states, the cytochromc C ion signal increased with the device; in most cases by a factor of 2 or more.

10391 In Figure 4, a device according to the present invention is depicted which has been optimised for an ESI source. As illustrated, the device is again tightly pushed onto the inlet of the instrument. However, due to the small dimensions of the ESI delivery tip, the cross-sectional area of the interior cavity of the device reduces in size with increased distance from the inlet of the instrument. Ideally, the sample is located within the cavity.

[40] Notably, the device shown in Figure 4 creates a circular opening at the solvent delivery tube and accordingly, similar air or gas flows to the device depicted in Figure 1 are provided. As above, if an analytical instrument under vacuum is employed with the setup shown in Figure 4, the air or gas flow resulting from this opening will create a pneumatic drag of the aerosolised plume into the analytical instrument.

[41] It will be understood that the embodiments described above show applications of the invention only for the purposes of illustration. In practice, the invention may be applied to many different configurations, the details of which are straightforward for the person skilled in the art to implement.

Claims

Claims 1. A device for collecting an aerosolised plume from a sample, the device being formed of an electrically non-conductive or minimally conductive material and comprising: at least one aperture configured to collect the plume; and a cavity for receiving an inlet of an analytical instrument.
2. The device according to claim 1, wherein the aerosolised plume is at least one of ionic and non-ionic or a combination of these.
3. The device according to any preceding claim, wherein the aerosolised plume is produced by at least one of an ablation, desorption or evaporation technique.
4. The device according to any preceding claim wherein the at least one aperture is either cylindrical or conical.
5. The device according to any preceding claim, wherein the at least one aperture has a diameter of between 1-10 mm.
6. The device according to any preceding claim, wherein the material is an electrical insulator or dielectric material.
7. The device according to claim 6, wherein the electrical insulator or dielectric material is one of ASA, ABS, HIPS, PEEK, polycarbonate, polypropylene and nylon.
8. A system comprising: the device of any preceding claim; and an analytical instrument comprising an inlet, configured to receive an aerosolised plume generated from a sample.
9. The system of claim 8, wherein the analytical instrument is a mass spectrometer.
10. The system of claim 9, wherein the mass spectrometer uses at least one of time-of-flight "TOF", quadrupole "Q", ion trap "IT", orbitrap, electric and/or magnetic sector mass analysers.
11. The system of any of claims 8 to 10, wherein an interference fit is provided between the device and an inlet of the analytical instrument.
12. The system of any of claims 8 to 11, wherein an airtight enclosure is provided between the device and the sample.
13. The system of any of claims 8 to 11, wherein the inlet is provided to the cavity of the device.
14. The system of any of claims 8 to 13, further comprising an electric field between the inlet of the analytical instrument and the sample.
15. The system of any of claims 8 to 13, further comprising a pressure differential between the inlet of the analytical instrument and the sample.
16. The system of any of claims 8 to 15, further comprising an opening for a sample desorption/ablation probe.
17. The system of any of claims 8 to 15, further comprising a further inlet to the space enclosed by the aperture of the device.
18. A method of collecting an aerosolised plume comprising the steps of: placing the device according to any of claims 1 to 7 in close proximity to a sample; generating an aerosolised plume via one of an ablation, desorption or evaporation technique; and entraining the aerosolised plume towards an inlet of an analytical instrument.
19. The method of claim 18 wherein the entraining is assisted by at least one of an electrical field or a pressure differential provided between the sample and the inlet of the analytical instrument.