This application claims priority and benefit from Swedish patent application No. 0300454-6, filed Feb. 19, 2003, the entire teachings of which are incorporated herein by reference.
The present invention relates to nozzles for ejecting a liquid, in particular for electrospray ionization, to chips carrying nozzles and to methods of manufacturing nozzles and nozzle chips.
Mass spectrometry is one of the most powerful methods used for analyzing liquid phases, see e.g. Andrew J. de Mello: “Chip-MS: Coupling the large with the small”, Lab on a Chip, 2002, Vol. 1, 7N-12N. An important advance in liquid sampling method for mass spectrometry analysis includes the development of the electrospray technique. In electrospray ionization a flowing analyte stream is forced through a capillary biased to high potential in relation to the analyzer. The high electric field produced causes the liquid when exiting the capillary to form a “Taylor cone” which is enriched with positive ions at the exit, i.e. at the tip of the cone. Positively charged droplets are formed and expelled from the tip of the Taylor cone by the electric field to form a mist of small droplets. The droplets move in the electric field and a pressure gradient towards the analyzer. During this migration of the droplets “Coulomb explosion” and evaporation act to reduce the size of the droplets, ultimately resulting in fully desolvated ions.
The nozzle used at the exit opening for the liquid to be analyzed should allow the creation of a stable Taylor cone having its tip located at a well-defined place. A finer electrospray nozzle gives a more stable and more efficient electrospray process. In particular the very outlet opening of the nozzle should be well defined having smooth surfaces without cutting burrs and having a well defined geometric position in relation to the analyzer. In the case where the liquid is water or a similar liquid the outer surfaces at the outlet opening can be given a hydrophobic coating. It can prevent the liquid from spreading along the outer surfaces of the outlet opening, thereby allowing efficient formation of droplets and electrospray.
Nozzles for electrospray ionization based on small microfluidic chips have also been described in e.g. Jun Kameoka, Harold G. Craighead, Hongwei Zhang and Jack Henion: “A polymeric microfluidic chip for CE/MS determination of small molecules”, Anal. Chem. Vol. 73, May 1, 2001, pp. 1935-1941, Jun Kameoka, Reid Orth, Bojan Ilic, David Czapiewski, Tim Wachs and H. G. Craighead: “An electrospray ionization source of integration with microfluidics”, Anal. Chem., 2002, pages EST: 5 A-E, Véronique Gobry, Jan van Oostrum, Marco Martinelli, Tatiana C. Rohner, Frédéric Reymond, Joël S. Rossier and Hubert H. Girault: “Microfabricated polymer injector for direct mass spectrometry coupling”, Proteonics 2002, Vol. 2, pp. 405-412, and Jenny Wen, Yuehe Lin, Fan xiang, Dean W. Matson, Herold R. Udseth and Richard D. Smith: “Microfabricated isoelectric focusing device for direct electrospray ionization-mass spectrometry”, Electrophoresis 2000, Vol. 21, pp. 191-197.
In published International patent application No. WO 00/30167 a polymer based electrospray nozzle structure for mass spectrometry is disclosed, in which patterned polymer layers are applied to a silicon substrate to produce an outlet channel forming the nozzle between the applied polymer layers. In published International patent application No. WO 02/05590 a soft lithography process is used for producing microfabricated emitters for electrospray ionization mass spectrometry. In U.S. Pat. No. 6,245,227 an integrated monolithic microfabricated electrospray device is disclosed comprising a basically rotationally symmetric nozzle made in silicon.
It is an object of the invention to provide nozzles for ejecting a liquid, in particular for electrospray ionization, and methods for production thereof allowing the nozzles to be produced in large volumes and at low costs.
It is another object of the invention to provide nozzles for ejecting a liquid, in particular for electrospray ionization, that can be manufactured by mainly replication, moulding and/or laminating methods applied to polymer materials.
Generally, in manufacturing nozzles and chips carrying nozzles for electrospray ionization a substrate or carrier is produced using a replication or moulding method. The substrate has channels on one of its surfaces. The channels are closed by applying a lid that can comprise a flexible, relatively thin polymer sheet to said surface. In particular an exit channel ends at an exit opening that is not closed by the lid. At the exit opening either a nozzle has already been formed in the moulding of the substrate or a separate nozzle part is attached after applying the polymer sheet. The substrate can be provided with alignment means, such as recesses or projections at its edges and/or on said surface, the alignment means having accurately defined positions in relation to the exit opening and/or the outlet opening in the nozzle.
Also, in manufacturing the nozzles, a multitude of chips can be produced from a large substrate plate to which a large polymer sheet or plate, e.g. a flexible, thin polymer film or laminate, is applied. The obtained structure is then split to form the individual chips, this simultaneous production of a multitude of chips reducing the manufacturing cost per obtained chip. In the splitting operation alignment recesses can be made available from the edges of the chips and also the structure at the nozzles can be modified, such as to produce a spout having three walls projecting in a recess formed in the moulding of the substrate plate.
A metal tip at the nozzle of a chip can be provided and may be obtained by applying a patterned metal layer to the thin polymer sheet before applying it to the substrate or by applying a separate metal foil part. The metal tip can have an outermost triangular part having a free point and concave sides connected at the free point. The concave sides can give sufficiently small angles at critical places allowing that no liquid will pass along a wall from which the free tip extends and that all liquid will be dispensed from a well defined point. The metal material can also be connected to a potential necessary for the electrospray process.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the methods, processes, instrumentalities and combinations particularly pointed out in the appended claims.
While the novel features of the invention are set forth with particularly in the appended claims, a complete understanding of the invention, both as to organization and content, and of the above and other features thereof may be gained from and the invention will be better appreciated from a consideration of the following detailed description of non-limiting embodiments presented hereinbelow with reference to the accompanying drawings, in which:
a is a view similar to that of
b is a fragmentary perspective view of a finished chip of an edge emitting device having a polymer lid recessed at the nozzle,
a-20c are fragmentary sectional views illustrating steps in manufacturing individual polymer nozzles for surface emitting devices, and
a and 21b are fragmentary sectional views illustrating steps in manufacturing individual
metal nozzles for surface emitting devices.
Now different structures of and devices for nozzle chips for ejecting a liquid, such as for electrospray ionization, will be described and methods of manufacturing them. The nozzle chips basically comprise three parts, a substrate chip, a lid applied to a top surface of the substrate chip, and a nozzle. The nozzle can be a separate part or integrated with the substrate chip. The individual substrate chips can be produced from a larger substrate plate. The individual nozzle chips can be produced from a composite larger plate comprising a substrate plate and a lid.
Substrate
In
The plate 1 is divided, e.g. by sawing, milling or punching, at splitting lines 11 to produce the separate substrate chips. The dividing of the plate can also be accomplished by providing it, in the shaping or moulding operation, with separation grooves along which the plate can be easily broken. Also, the plate can be produced on some base plate, not shown, so that the individual chips are produced in the shaping or moulding operation. In that case, in the shaping or moulding operation the plate is provided with delimiting separation channels extending from the surface of the plate down to the base plate. After finishing the production of the chip structures, the individual chips are finally separated from the base plate.
At the splitting lines 11 other recesses 13, 15 are made which act as alignment devices and will be used for mounting the separated chips in accurate positions. Such recesses can be made to have a square shape, a diagonal line of the square located along a splitting line 11. After splitting into separate chips the recesses will then have a triangular shape as seen from above. As seen from the edges of the separate substrate chips they have a short V-groove shape.
The substrate chips generally have a rectangular shape. The outlet opening 9 can be located at a short side of the rectangular shape and then the alignment recesses can located so that one recess 13 is placed on each long side, at a position displaced some distance from the center of the respective sides towards the short side at the exit opening. The other, opposite short side can carry one alignment recess 15 that is located centrally on the side.
Due to the fact that the alignment recesses and the outlet opening are formed in the same shaping or moulding step, they can be given accurate relative positions so that the finished nozzle chip can be mounted in a reproducible way in a mass spectrometer.
For an edge emitting nozzle chip the outlet opening 9 is formed in another recess 17 at the respective side of the area that will form a chip. This recess is given such a width in a direction from the respective splitting line 11 that the outermost portions of or the surfaces at the outlet opening are not affected when splitting the original large moulded plate 1 into separate chips, see
For a surface emitting nozzle chip, see
The mould used for the producing the large plate 1 can be produced by first producing a model of the desired structure made from silicon processed using the common methods of silicon processing as used for manufacturing microelectronic circuits and other microdevices. Then, in a second step the model is coated such as by electroplating to produce a metal mould. Finally the silicon is removed such as by some etching method.
After the large plate 1 has been shaped or moulded the recesses forming channels in the surface of the plate are closed, see
The lid 25 can have through-holes 24, 26 made at appropriate places to expose the alignment means such as the recesses 13, 15 and the recesses 17 at the outlet openings 9 in the substrate plate illustrated in
It is obvious that the substrate chips formed from the areas 3 of plate 1 also can be produced individually, by only shaping or moulding one or a few substrate chips at a time.
It is also obvious that each of the nozzle chips can comprise a plurality of channel systems and associated outlet channels and outlet openings including the nozzles, the outlet channels e.g. extending in parallel to each other and the outlet openings located at a common edge of the chip.
Edge Emitting Chip
Now an edge emitting nozzle chip having a polymer opening or tip will be described. In the recesses 17, see
In a first case, the outlet channel can end or mouth directly in the inner, flat sidewall 21 of the recess as seen in
In a second case, the outlet channel has one or more parts projecting from the inner flat sidewall 21 of the recess 17. These parts can form three walls 27, 29 of a spout, that can extend perpendicularly to said sidewall or be tapering, as seen in
Also, as seen in
The lower projecting part 29, 33 can generally rest at, i.e. be connected to, the bottom 31 of the recess 17 when shaping or moulding the substrate plate 1. This design can have drawbacks due to the fact that liquid can adhere to the front or vertical surfaces of the projecting parts and flow therealong. However, the lower projecting part can be made to be freely extending, having a free bottom surface to form a nozzle having the shape of a spout formed by three walls. This can be achieved in an extra milling or sawing step, removing material of the substrate below the lower projecting part, see
The edge emitting chips can also have metal tips acting as electrodes and in particular as means for guiding the liquid to be analyzed to the outermost point of the tip where it is released to form the desired drops of the Taylor cone. The substrate plate 1 has then the general shape illustrated in
The metal strip is placed so that the outermost portion 47 of the tip is located outside the outlet opening 9. The outermost portion has then a free surface also having an isosceles triangle shape, preferably having base angles and a top angle smaller than 45° due to the concave shape of the equal sides. Such a shape have advantages by the fact that liquid flowing in the channel out through the outlet opening will follow the metal because of its hydrophilic properties and then when exiting the outlet opening will be directed to the acute point 49 of the tip 47 and not leaking towards the sides or laterally along the inner side wall 21 of the recess 17 and past the regions of the triangle shape at the angles at the base of the free triangular shape, due to the small base angles.
In a first embodiment the metal strip 41 is produced by a lithographic process by first applying a metal layer or film to a surface of the polymer lid 25 and then patterning the metal to form all the metal areas required for the plate 1 to produce a multitude of individual nozzle chips. The polymer lid is then, at its surface where the metal is located, thermally or adhesively bonded to the relevant surface of the substrate. After splitting the composite plate into individual chips, compare
In a second embodiment, see
Alternatively, metal strips can be individually produced before laminating, e.g. by splitting the patterned metal foil as seen in
The structure illustrated in
Surface Emitting Chip
First a carrier or substrate plate 1 is produced as described above with reference to
The polymer lid 25 also has cut-outs or windows 65, 67 for the alignment recesses 13 adapted for alignment of the substrate of each chip and for the mesas 23 for mounting the separate nozzle parts, in the case where they have been produced in the substrate.
The nozzle 69 is a separate part that has a central through-hole 71 forming the actual outlet opening. Around the central hole a concentric recess 73 is provided that is at its inner edge bounded by a protruding substantially cylindrical portion 75 forming a spout at the outlet opening and that at its outer edge is bounded by an outer circular ridge 77.
The nozzles 69 can be produced in a UV-lithography process using e.g. a thick epoxy resist such as SU8, in two steps which are necessary for making the recessed structure. Such a process is illustrated in
The nozzles 69 can then be surface mounted using an adhesive to firmly attach them to the surface of the combined structure including the areas of the substrate 1 as a bottom layer and the polymer layer 25 on top of thereof.
The separate nozzles can also be made from metal using an electroforming or electroplating method, see
It should be understood herein and in the claims hereof that such terms as “top”, “bottom”, “upwardly”, “downwordly”, “front”, “rear” and the like have been used for illustration purposes only, in order to provide a clear and understandable description and claiming of the invention. Such terms are not in any way to be construed as limiting, because the devices of invention are omni-directional in use as can be understood by their various uses in different application fields.
While specific embodiments of the invention have been illustrated and described herein, it is realized that numerous additional advantages, modifications and changes will readily occur to those skilled in the art. Therefore, the invention in its broader aspects is not limited to the specific details, representative devices and illustrated examples shown and described herein. Accordingly, various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents. It is therefore to be understood that the appended claims are intended to cover all such modifications and changes as fall within a true spirit and scope of the invention.
Number | Date | Country | Kind |
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0300454-6 | Feb 2003 | SE | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/SE04/00229 | 2/19/2004 | WO | 10/25/2006 |