ANALYTIC NEBULISER

Abstract

The invention provides an analytic nebuliser device for delivering a sample in aerosolised form, the device comprising a nebuliser nozzle configured to receive a flow of said sample and generate a plume of aerosolised sample spray and a chamber configured to receive a flow of make-up gas and connecting with a plurality of microchannels having outlets arranged around and adjacent to said nebuliser nozzle wherein the microchannels are configured to produce a make-up gas stream with high linear velocity around said aerosolised sample spray to shape and direct said plume. The invention extends to a mass spectrometry or spectroscopy system including the above analytic nebuliser device, to provide in operation the aerosolised sample spray to an ionisation device of the system.

Claims

1. An analytic nebulizer device for delivering a sample in aerosolized form, the device comprising: a nebulizer nozzle configured to receive a flow of said sample and generate a plume of aerosolized sample spray; and a chamber configured to receive a flow of make-up gas and connecting with a plurality of microchannels having outlets arranged around and adjacent to said nebulizer nozzle; wherein the microchannels are configured to produce a make-up gas stream with high linear velocity around said aerosolized sample spray to shape and direct said plume.

2. The device of claim 1, wherein the chamber and microchannels are arranged and connected such that the make-up gas stream is controllable separately to any other gas flow applied to the device, and in particular any nebulizer gas flow.

3. The device of claim 1, wherein the nozzle has a central axis and the microchannels are configured to direct said make-up gas stream substantially parallel to said central axis.

4. The device of claim 1, wherein the microchannels are angled relative to said central axis in such a way as to increase the swirl of the make-up gas and/or to direct the make-up gas stream into the aerosol plume to increase mixing of the two.

5. The device of claim 1, wherein the outlets of the microchannels are in a plane close to that of the nebulizer nozzle outlet.

6. The device of claim 5, wherein the outlets of the microchannels are within 5 mm of the termination of the nozzle outlet.

7. The device of claim 1, including between 3 and 10 microchannels, preferably 6 microchannels.

8. The device of claim 1, wherein the nozzle has a central axis and the microchannels are evenly angularly spaced around the nebulizer nozzle and equidistant from said central axis.

9. The device of claim 8, wherein the distance of the microchannels from the central axis is in the range 2-12 mm.

10. The device of claim 1, wherein the microchannels are in the range 0.02 to 0.5 mm in diameter.

11. The device of claim 10, wherein the outlets of the microchannels are in the range 0.02 to 0.05 mm in dimension.

12. The device of claim 1, including an adaptor, wherein said chamber and said microchannels are provided in the adaptor, the device further including an inlet connectable with a source of make-up gas, the adaptor configured to attach around a nebulizer body and position the outlets of said microchannels around and adjacent to said nebulizer nozzle.

13. The device of claim 12, wherein the adaptor has an outer portion configured to support and engage with a spray chamber.

14. The device of claim 1, wherein the nebulizer nozzle forms part of a nebulizer, and said chamber and said microchannels are integrated into the nebulizer.

15. A mass spectrometry or spectroscopy system including an analytic nebulizer device according to claim 1, further configured to provide in operation the aerosolized sample spray to an ionization device of the system.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Further aspects of the present invention and further embodiments of the aspects described in the preceding paragraphs will become apparent from the following description, given by way of example and with reference to the accompanying drawings.

[0032] FIG. 1 shows a sample transferring device in accordance with an embodiment of the present invention;

[0033] FIG. 2 is a side view of a nebuliser assembly of the sample transferring device of FIG. 1;

[0034] FIG. 3 is an end view of the nebuliser assembly of FIG. 2;

[0035] FIG. 4 illustrates the effect of the separation of nebuliser assembly microchannel outlets on transport efficiency;

[0036] FIG. 5 illustrates the reproducibility of results between different samples of nebuliser assembly tested;

[0037] FIG. 6 illustrates the effect of sample flow rate on transport efficiency;

[0038] FIG. 7 is a side view of an alternative nebuliser assembly in accordance with an embodiment of the invention;

[0039] FIG. 8 is an end view of the nebuliser assembly of FIG. 7.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0040] Single cell analysis ICP-MS (SC-ICP-MS) is a rapidly growing technique used in life science research which can enhance understandings in cellular biology, oncology and drug discovery. Single-Cell ICP-MS enables the intra-cellular quantitation of metals in individual cells and is used in the study of disease aetiology and in the development of new treatments.

[0041] The present invention can be used in an SC-ICP-MS system, or in any system that involves delivery of a sample by way of a nebulised spray to an ionisation device, such as a plasma torch for analytical atomic spectroscopy.

[0042] In FIG. 1, a sample transferring assembly 10 comprises a pneumatic nebuliser assembly 12 and a shaped spray chamber 14. Spray chamber 14 provides a conduit for passing a sample spray from an inlet end 16 to an outlet end 18, and is supported by a chamber mount 22 for secure connection to a mass spectrometer, illustrated figuratively by reference 100. Spray chamber 14 includes a drain outlet 20 positioned at its lowest point, for removal of liquid droplets deposited on the inner walls of the chamber.

[0043] Nebuliser assembly 12, shown in FIG. 2 and described in further detail below, includes a nebuliser adaptor 30 that sealingly connects into spray chamber inlet end 16. The nebuliser of assembly 12 includes a liquid sample inlet 50 at its upstream end, a nebulising gas inlet with a screw type quick connector 34 and a spray nozzle 52 at its downstream end, the spray nozzle designed to produce a cone-shaped aerosol spray into spray chamber 14. The constructional details of such a nebuliser are well known, and will not be further described here.

[0044] FIG. 1 also shows a spray chamber drain line 42 comprising capillary tubing with a push connection for coupling to drain outlet 20, a nebulising gas line 36 having a quick connect screw connection for coupling to fluid inlet 34, a sample supply line 38 with a push connection for connection to sample inlet 50 and a make-up gas line 40 with an outlet screw connector 32, discussed further below.

[0045] As illustrated in FIG. 2, nebuliser adaptor 30 has a generally tubular shape and features a through bore sized to accommodate the outer tube 54 of the nebuliser, and further includes a downstream narrowed cylindrical portion 56 terminating in a transverse downstream face 57. This narrowed cylindrical portion 56 has an annular outer groove towards its downstream end carrying an O-ring 58, sized to sealingly fit within inlet end 16 of spray chamber 14. As shown, the narrowed portion 56 of adaptor 30 is concentric with nebuliser tube 54. In the upstream end of adaptor 30 a threaded bore 60 is provided, connecting with a make-up gas passage 62. Bore 60 and passage 62 are inclined to the axis of nebuliser tube 54, and the downstream end of passage 62 connects to an annular chamber 64 within narrowed portion 56 of assembly 30, close to the downstream end. Six small bores 66, parallel to the nebuliser centreline and of equal angular separation around nozzle 52, connect chamber 64 through face 57. When make-up gas line 40 is connected to adaptor 30 (by engagement of screw connector 32 with threaded bore 60) the bores 66 provide a plurality of gas microjets around nebuliser nozzle 52 by which make-up gas flow 41 exits adaptor 30.

[0046] In an embodiment tested by the inventors, bores 66 with a diameter of 300 μm were used, at a radius of 3.5 mm from the nebuliser nozzle axis. As will be understood, for different applications, different dimensions may be suitable.

[0047] As the skilled reader will appreciate, the nebuliser and the nebuliser spray chamber 14 are typically made of glass. However other materials are possible, in particular suitable polymer materials such as PEEK.

[0048] In use, nebuliser assembly 12 is connected into spray chamber 14, which is mounted to mass spectrometer 100 by way of chamber mount 22. Nebulising gas line 36 is connected to the nebuliser by way of gas inlet connector 34, sample supply line 38 is connected to nebuliser sample inlet end 50, make-up gas line 40 is connected to adaptor assembly 30 by way of connector 32 and drain line is connected to spray chamber drain outlet 20.

[0049] The make-up gas supplied by microjet bores 66 around aerosol nozzle 52 can serve a number of functions. Firstly, the make-up gas can be used to increase the gas output of the sample transfer system. Further or alternatively, the stream of gas may be provided at a higher velocity than the nebuliser plume in order to ensure that the sample aerosol effectively penetrates the outer skin of the analytical plasma.

[0050] Further or alternatively, and like the prior art device described in U.S. Pat. No. 10,147,592, the gas exiting microjet bores 66 can be used to form an annular sheath to shield the inside surfaces of spray chamber 14 to prevent or reduce deposition of sample aerosol on the inner walls, so improving transport efficiency of the system.

[0051] In particular, as noted above, the make-up gas exiting microjet bores 66 can be used to produce a high linear velocity, laminar flow gas surrounding the nebuliser aerosol plume. In accordance with the present invention, this can be used to alter the shape or to constrain the nebuliser sample plume to better suit the geometry of the chamber, injector or torch. If properly applied, this sheath of annular make-up gas can be used to fully constrain the sample aerosol all the way from the nebuliser nozzle to the ionisation device, this aerosol plume shaping potentially meaning that spray chamber 14 may not be required, allowing spraying of the aerosol directly into the plasma torch.

[0052] Further or alternatively the device of the invention can be used to rapidly and efficiently chemically modify the aerosolised sample, by using a selected reactive gas such as oxygen, chlorine or ammonia as the make-up gas.

[0053] Moreover, as noted above, the make-up gas exiting microjet bores 66 can be used to provide a high linear velocity shear gas that improves nebulisation efficiency by preventing droplet agglomeration and impacting droplets in the aerosol plume in order to produce an aerosol with a smaller droplet size distribution, which can significantly assist in improving transport efficiency of the system.

[0054] A significant advantage of the invention is that it is a relatively simple matter to machine the bores 66 with great precision, hence affording accurate positioning of the peripheral ring of microjets and hence allowing accurate control of the sheathing gas and hence shaping of the aerosol plume. The more accurate control means that a lower flow of make-up gas can be used when compared with prior solutions, thus increasing nebulisation efficiency.

[0055] From tests conducted by the inventors, and as FIG. 4 illustrates, the radial separation of the microjets from the nebuliser nozzle axis can dramatically affect the transport efficiency of the aerosol to the ionisation device. The two curves show how the sensitivity of a mid-mass element significantly decreases when the radius of the outlet of bores 66 from the nebuliser nozzle axis is increased from 3.5 mm (“Cd Microjet_7 mm”) to 5.5 mm (“Cd Microjet_11 mm”).

[0056] The 6 curves in FIG. 5 illustrate the consistency of transport efficiency for six different systems tested. The reproducibility between the results of different tests arises from the ease and precision possible with the manufacture of the device of the invention.

[0057] Similarly, the test results of FIG. 6 show the consistency of performance of the device of the invention across a range of sample uptake rates (sample flow rate in μL/min against signal intensity in counts-per-second, cps).

[0058] As noted above, the embodiment tested by the inventors used microchannel bores 66 with a diameter of 300 μm. As will be understood, for different applications, different bore dimensions may be suitable, for example in the range 0.02 to 0.5 mm.

[0059] The embodiment described and illustrated above comprises an adaptor assembly 30 used to modify a conventional nebuliser to produce the desired microjets of make-up gas. Alternatively, the invention can be realised in an integrated nebuliser construction, as illustrated in FIGS. 7 and 8. In this embodiment, an outer tubular body 154 terminating in a transverse downstream face 157 surrounds a tapering inner tubular body 151, which terminates in central nebuliser flow nozzle 152 in face 157. The space formed between bodies 151 and 154 provides a make-up gas chamber 164. Around nebuliser nozzle 152 are arranged six bores 166 through transverse face 157, to provide microchannels connecting chamber 164 with gas microjet outlets (see FIG. 8). The device works in a similar way to that described above with reference to FIGS. 1-3, with a source of pressured make-up gas connected to chamber 164.

[0060] It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention.

[0061] By way of clarification and for avoidance of doubt, as used herein and except where the context requires otherwise, the term “comprise” and variations of the term, such as “comprising”, “comprises” and “comprised”, are not intended to exclude further additions, components, integers or steps.