Abstract:
The invention provides a planar component for interfacing an atmospheric pressure ionizer to a vacuum system. The component combines electrostatic optics and skimmers with an internal chamber that can be filled with a gas at a prescribed pressure and is fabricated by lithography, etching and bonding of silicon.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to United Kingdom Patent Application No. GB0611221.3, filed Jun. 8, 2006, and United Kingdom Patent Application No. GB0620256.8, filed Oct. 12, 2006, which are expressly incorporated herein by reference and made a part hereof. 
     FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     Not applicable. 
     TECHNICAL FIELD 
     This invention relates to mass spectrometry, and in particular to the use of mass spectrometry in conjunction with liquid chromatography or capillary electrophoresis. The invention more particularly relates to a microengineered interface device for use in mass spectrometry systems. 
     BACKGROUND OF THE INVENTION 
     Electrospray is a method of coupling ions derived from a liquid source such as a liquid chromatograph or capillary electrophoresis system into a vacuum analysis system such as a mass spectrometer (Whitehouse et al. 1985; U.S. Pat. No. 4,531,056). The liquid is typically a dilute solution of analyte in a solvent. The spray is induced by the action of a strong electric field at the end of capillary containing the liquid. The electric field draws the liquid out from the capillary into a Taylor cone, which emits a high-velocity spray at a threshold field that depends on the physical properties of the liquid (such as its conductivity and surface tension) and the diameter of the capillary. Increasingly, small capillaries known as nanospray capillaries are used to reduce the threshold electric field and the volume of spray (U.S. Pat. No. 5,788,166). 
     The spray typically contains a mixture of ions and droplets, which in turn contain a considerable fraction of low-mass solvent. The problem is generally to couple the majority of the analyte as ions into the vacuum system, at thermal velocities, without contaminating the inlet or introducing an excess background of solvent ions or neutrals. The vacuum interface carries out this function. Capillaries or apertured diaphragms can restrict the overall flow into the vacuum system. Conical apertured diaphragms, often known as molecular separators or skimmers can provide momentum separation of ions from light molecules from within a gas jet emerging into an intermediate vacuum (Bruins 1987; Duffin 1992; U.S. Pat. No. 3,803,811, U.S. Pat. No. 6,703,610; U.S. Pat. No. 7,098,452). Off-axis spray (USRE35413E) and obstructions (U.S. Pat. No. 6,248,999) can reduce line-of-sight contamination by droplets, and orthogonal ion sampling (U.S. Pat. No. 6,797,946) can reduce contamination still further. Arrays of small, closely spaced apertures can improve the coupling of ions over neutrals (U.S. Pat. No. 6,818,889). Co-operating electrodes (U.S. Pat. No. 5,157,260) and quadrupole ion guides (U.S. Pat. No. 4,963,736) can apply fields to encourage the preferential transmission of ions. The use of a differentially pumped chamber containing a gas at intermediate pressure can thermalise ion velocities, while the use of heated ion channels (U.S. Pat. No. 5,304,798) can encourage droplet desolvation. The device of U.S. Pat. No. 5,304,798 is fabricated in a thermally and electrically conductive material, and is a massive device, the heated channel being of the order of 1-4 cm long. 
     Vacuum interfaces are now highly developed, and can provide extremely low-noise ion sampling with low contamination. However, the use of macroscopic components results in orifices and chambers that are unnecessary large for nanospray emitters and that require large, high capacity pumps. Furthermore, the assemblies must be constructed from precisely machined metal elements separated by insulating, vacuum-tight seals. Consequently, they are complex and expensive, and require significant cleaning and maintenance. 
     SUMMARY OF THE INVENTION 
     These problems and others are addressed by the present invention by providing key elements of an interface to a vacuum system as a miniaturised component with reduced orifice and channel sizes thereby reducing the size and pumping requirements of vacuum interfaces. The advance over prior art is achieved by using the methods of microengineering technology such as lithography, etching and bonding of silicon to fabricate suitable electrodes, skimmers, gas flow channels and chambers. In further embodiments the invention provides for a making of such components with integral insulators and vacuum seals so that they may ultimately be disposable. 
     Accordingly the invention provides an interface component according to claim  1  with advantageous embodiments provided in the dependent claims thereto. The invention also provides a system according to claim  30 . A method of fabricating an interface is also provided in claim  31 . 
     These and other features of the invention will be understood with reference to the following figures. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows in section ( 1   a ) and plan ( 1   b ) view the first two layers of a planar microengineered vacuum interface for an electrospray ionization system according to the present invention. 
         FIG. 2  shows in section ( 1   a ) and plan ( 1   b ) view a third layer of a planar microengineered vacuum interface for an electrospray ionization system according to the present invention. 
         FIG. 3  shows how a planar microengineered vacuum interface for an electrospray ionization system may be formed by a stacking arrangement. 
         FIG. 4  shows a mounting of an assembled planar microengineered vacuum interface for an electrospray ionization system on a flange according to the teachings of the present invention, with  FIG. 4   a  being prior to assembly and  FIG. 4   b  an assembled interface. 
         FIG. 5  shows a mounting arrangement for using a planar microengineered vacuum interface with a capillary electrospray source according to the present invention. 
         FIG. 6  shows a construction of a two stage planar microengineered vacuum interface for an electrospray ionization system according to another embodiment of the present invention. 
         FIG. 7  shows a modification to the arrangement of  FIG. 6  including a suspended internal electrode. 
         FIG. 8  shows how field concentrating features may be shaped to provide improved field concentration and improved momentum separation of molecules according to the teaching of the invention. 
     
    
    
     DETAILED DESCRIPTION 
     A detailed description of the invention is provided with reference to exemplary embodiments shown in  FIGS. 1 to 8 . 
     A device in accordance with the teaching of the invention is desirably fabricated or constructed as a stacked assembly of semiconducting substrates, which are desirably formed from silicon. Such techniques will be well known to the person skilled in the art of microengineering.  FIG. 1  shows the first substrate, which is constructed as a multilayer. A first layer of silicon  101  is attached to a second layer of silicon  102  by an insulating layer of silicon dioxide  103 . Such material is known as bonded silicon on insulator (BSOI) and is available commercially in wafer form. A further insulating layer  104  is provided on the outside of the second silicon layer. 
     The first silicon layer carries or defines a first central orifice  105 . The interior side walls  112  of the first layer which define the orifice, include a proud or upstanding feature  106  on the outer side of the first wafer which is provided at a higher level than the remainder of the top surface  113  of the first layer. The outer region of the first wafer and the insulating layer are both removed, so that the second wafer is exposed in these peripheral regions  107 . These peripheral regions define a step between the first and second wafer layers, and as will be described later may be used for locating external electrical connectors or the like. The second silicon layer carries an inner chamber  108 , which consists of a second central orifice  109  intercepted by a transverse lateral passage  110 , shown in the plan view of  FIG. 1B . In this way a skimmer, channel, capillary or series of orifices may be fabricated by means of micromachining, semiconductor processes or MEMS technology. 
     The features  105 ,  106 ,  107 ,  109  and  110  may all be formed by photolithography and by combinations of silicon and silicon dioxide etching process that are well known in the art. In particular, deep reactive ion etching using an inductively coupled plasma etcher is a highly anisotropic process that may be used to form high aspect ratio features (&gt;10:1) at high rates (2-4 μm/min). The etching may be carried out to full wafer thickness using silicon dioxide or photoresist as a mask, and may conveniently stop on oxide interlayers similar to the layer  103 . The minimum feature size that can be etched through a full-wafer thickness (500 μm) is typically smaller than can be obtained by mechanical drilling. 
       FIG. 2  shows the second substrate, which is constructed as a single layer. A layer of silicon  201  carries or defines a central orifice  202 , the side walls  212  of which define a proud feature  203  upstanding from the top surface  213  of the second substrate. Two additional orifices  204  and  205  are also defined in this wafer and are arranged on either side of the central orifice  202 . The features  202 ,  203 ,  204  and  205  may again be formed by photolithography and by silicon etching processes that are well known in the art. 
       FIG. 3  shows the attachment of the first substrate  301  to the second substrate  302  in a stacked assembly. The prefix numbers used in  FIGS. 1 and 2  are changed to 3, but the supplementary numbers remain the same. The two contacting surfaces  303  and  304  are desirably metallised, so that the two substrates may be aligned and attached together by compression bonding or by soldering, so that a hermetically sealed joint is formed around the periphery of the assembly. Additional features may be provided to aid alignment, or allow self-alignment. The metallisation also provides an improved electrical contact to the second substrate  302 . The two additional surfaces  305  and  306  are also desirably metallised, to provide improved electrical contact to the two silicon layers of the first substrate  301 . Bond wires  307  are then attached to all three silicon layers of the stacked assembly. The two substrates may be coupled to one another in a manner to ensure that the central orifices of each of the two substrates coincide thereby defining a central channel or cavity  310  through the two substrates. Alternative configurations may benefit from a non-alignment of the central orifices such that a non-linear channel is defined through the substrate. Such arrangements will be apparent to the person skilled in the art. 
     It will be appreciated that the stacked assembly of the three features  105 ,  109  and  202  now form a set of three cylindrical or semi-cylindrical surfaces, which can provide a three-element electrostatic lens that can act on a separately provided ion stream  308  passing through the assembly. Such a lens arrangement may be configured as an Einzel lens, with the associated benefits of such arrangements as will be appreciated by those skilled in the art. It will also be appreciated that the three features  204 ,  205  and  110  now form a continuous passageway through which a gas stream  309  may flow, intercepting the ion stream  308  in the central cavity  310 . The intersection, although shown schematically as being one where the two channels are mutually perpendicular to one another is, it will be appreciated, an example of the type of arrangement that may be used. Alternatives may include arrangements specifically configured to enable a generation of a vortex or any other rotational mixing of the two streams through the angular presentation of one channel to the other. 
       FIG. 4  shows the attachment of the stacked assembly  401  to a third substrate  402  that is desirably formed in a metal. The third substrate again carries a central orifice  405  and in addition an inlet passageway  406  and an outlet passageway  407 . The features  406  and  407  may be formed by conventional machining, using methods that are well known in the art. The two contacting surfaces  403  and  404  are desirably metallised, so that the two substrates may again be attached together by compression bonding or by soldering, so that a hermetically sealed joint is again formed around the periphery of the assembly. 
     It will be appreciated that the combined assembly now provides a continuous passageway for the gas stream  408  that starts and ends in the metal layer, in which connections to an additional inlet and outlet pipe may easily be formed by conventional machining. It will also be appreciated that the ion stream  409  now passes through the metal substrate, which is now sufficiently robust to form part of the enclosure of a vacuum chamber. It will also be appreciated that with the addition of such a chamber, the three regions  410 ,  411  and  412  may be maintained at different pressures. 
       FIG. 5  shows how the assembly  501  may be mounted on the wall of a vacuum chamber  502  using an ‘O-ring’ seal  503 . In use, the inside of the vacuum chamber is evacuated to low pressure, while the outside is at atmospheric pressure. The central cavity  504  is maintained at an intermediate pressure by passing a stream of a suitable drying gas such as nitrogen from an inlet  505  to an outlet  506  connected to a roughing pump. It will be appreciated that the pressure in the central cavity may be suitably controlled using different combinations of inlet pressure and roughing pump capacity and by the relative sizes of the openings  204  and  205 . 
     The flux of ions is provided from a capillary  507  containing a liquid that is (for example) derived from a liquid chromatography system or capillary electrophoresis system in the form of analyte molecules dissolved in a solvent. The flux of ions is generated as a spray  508  by providing a suitable electric field near the capillary. In addition to the desired analyte ions, which it is desired to pass as an ion stream  509  into the vacuum chamber, the spray typically contains neutrals and droplets with a high concentration of solvent. 
     Ions and charged droplets in the spray may be concentrated into the inlet of the assembly by the first lens element carrying the proud feature  510 , which is maintained at a suitable potential by one of the connections  511  provided on external surfaces of the first, second or third wafers. Entering the central chamber  504 , the ion velocities may be thermalised and the spray may be desolvated by collision with the gas molecules contained therein. The gas stream may be heated to promote desolvation, for example by RF heating caused by applying an alternating voltage between two adjacent lens elements and causing an alternating current to flow through the silicon. Alternative mechanisms of achieving heating of the stream may include a heating prior to entry into the interface device where for example it is considered undesirable to actively heat the materials of the interface device. 
     Ions may be further concentrated at the outlet of the assembly by the second lens element and the third element carrying the proud feature  512 , which are also maintained at suitable potentials by the remaining connections  511 . 
     It will be appreciated that more complex assemblies of a similar type may be constructed. For example,  FIG. 6  shows the combination of two etched BSOI substrates  601  and  602  with a third single-layer substrate  603  to form a serial array in the form of a 5-layer assembly  604 . Here the ion stream  605  must pass now through two cavities  606  and  607  at intermediate and successively reducing pressures. The gas therein is again provided by a gas stream taken from an inlet  608  to an outlet  609  by a system of buried, etched channels that pass through the two chambers  606  and  607 . The relative pressure in the two chambers  606  and  607  may be controlled, by varying the dimensions of the connecting orifices  610  and  611 . Such a system corresponds to a two-stage vacuum interface, and it will be apparent that interfaces with even more stages may be constructed by stacking additional layers. 
     Heretofore an interface component in accordance with the teaching of the invention has been described with reference to an exemplary arrangement where a laminated silicon interface is provided to allow transport of an ion stream between atmospheric pressure and vacuum through a pair of orifices sandwiching a chamber held at intermediate pressure. 
     As was described above, such an interface may be constructed from a pair of silicon substrates. Where so constructed, the outer substrate may be fabricated from a silicon-oxide-silicon bilayer, while the inner substrate may be provided in the form of a silicon monolayer. As was described wither reference to  FIGS. 3 and 4 , these two substrates may then be hermetically bonded together, and then bonded to a stainless steel vacuum flange containing a gas channel. As was illustrated with reference to  FIG. 5 , the completed assembly may then be used to couple an ion stream from a spraying device into a vacuum system. The preferential transmission of ions (as opposed to neutrals) is encouraged in such an arrangement by a judicious application of appropriate voltages to the three silicon layers. In the exemplary illustrative embodiments, the outer and inner layers contained field-concentrating features, while the inner layer contained a chamber. The three elements acted together to focus an ion stream emerging from the outer orifice onto the inner orifice. 
     Such an arrangement may be successfully used to effect ion transmission and to obtain mass spectra from the resulting ion stream. The arrangement and performance may however benefit from one or more modifications, the specifics of which will be described as follows. 
     As will be appreciated from the teaching of the invention most features of the interface component may be fabricated using standard patterning, etching and metallisation processes, as will be familiar to those skilled in the art. 
       FIG. 7  shows an alternative arrangement for providing an interface component according to an aspect of the invention. It will be recalled from the discussion of  FIG. 3  that the option of bonding the two surfaces  303 ,  304  together by means of a solder joint was expressed. While such an arrangement does provide the necessary coupling between the two surfaces it does present a possibility of a short circuit being formed by the solder across the isolating layer of oxide  104  between the lower substrate  302  and the lower layer of the upper substrate  301 —this possibility arising from their very close proximity to one another. If such a short circuit is effected then it is difficult to apply a different voltage to the two layers. 
     The arrangement of  FIG. 7  obviates the need to co-locate a soldered joint with an insulating layer. In the arrangement of  FIG. 7 , an upper substrate  701  is configured to contain a laterally isolated electrode  702 , which is suspended inside a perimeter of silicon. The surfaces  703  of the upper substrate and the flange  705  may be coated with a conducting material which is desirably un-reactive and non-oxide forming—gold being a suitable example. Surfaces  704  of the lower substrate  706  may be solder coated. 
     To assemble such an arrangement, each of the two substrates  701 ,  706  may be stacked on the flange  705  and then secured by a melting of the solder  704 , as shown in  FIG. 7   b . Although a short circuit is now always created between the lower substrate  706  and a lower contacting layer  707  of the upper substrate  701 , its existence is immaterial, as the suspended electrode  702  is isolated from these contacted surfaces. By providing an access hole  708  through the upper substrate  701 , a different voltage can now be applied to the suspended electrode  702  via a bond wire  709  passing through the access hole. The utilisation of a suspended electrode also allows the distances between the electrode and the lower substrate to be reduced at the point of the ion path  713 . 
     In the arrangement of  FIG. 1 , a channel  110  was described as passing through a central chamber  109 , to allow the passage of gas during pumping. While such an arrangement suffices to provide for the passage of gas, it is desirable to have a large cross-section area for this passage in order to obtain effective pumping of the intermediate chamber. In the arrangement of  FIG. 1 , this cross section area is difficult to achieve without effecting a removal of most of the walls of the chamber  109 , which could affect the ion focusing capabilities. 
     In the arrangement of  FIG. 7 , it will be noted that the lower substrate  706  is provided with a pair of recess features  711  which are co-located with the suspended electrodes  702  of the upper substrate. The provision of the recess features is advantageous in that it ensures that the suspended electrode does not come into contact with the lower substrate  706  when the two substrates are brought into intimate contact with one another— FIG. 7   b . It will be noted that the recess features  711  are dimensioned sufficiently to avoid electrical contact between the lower substrate and the suspended electrode. A secondary or additional benefit is provided in that the recess features  711  provide a gas flow path  712 . This path can be advantageously used either to remove neutrals or to admit a drying gas, without the need to pass a channel across the layer containing the central chamber. Consequently, the channel may be omitted entirely from this layer. This arrangement may provide more effective ion focussing. 
     In the arrangement of  FIG. 7 , field concentrating features  714 ,  715  in the upper and lower substrates are essentially raised capillaries. In a further modification to the exemplary embodiments heretofore described it is possible to provide improved field concentration and improved momentum separation of ions and neutrals if the outer walls  801 ,  802  of these features are sloped at around 60°, as shown in  FIG. 8   a.    
     It is generally difficult to construct features with well-controlled, continually varying slopes using standard microfabrication processes such as dry etching. However, features with approximately correct slopes may be constructed by crystal plane etching. In silicon, the (111) planes can be shown to etch much more slowly than all other planes in certain wet etchants, for example potassium hydroxide. These planes lie at an angle cos −1 (1/√3)=54.73° to the surface of a (100) oriented wafer, and provide a natural boundary to etched features. The (211) planes also etch relatively slowly. 
     A proud feature  800  whose surfaces consist of four (111) planes and four (211) planes as shown in  FIG. 8   b  may be therefore constructed by etching a (100) wafer carrying a surface mask of etch resistant material such as silicon dioxide, which is patterned to form a square. Such a feature may therefore provide improved field concentration and momentum separation, and could be used independently of an interface component for coupling an ion source to a vacuum system—as will be appreciated by those skilled in the art could the suspended electrode of  FIG. 7 . 
     It will also be appreciated that there is considerable scope for variations in layout and dimension in the arrangements above. For example, it is not necessary for the ion path to be co-linear from input to output, and reduced contamination of the vacuum system may follow from adopting a staggered ion path so that no line of sight exists. Similarly, it is not necessary for both of the orifices to be circular in geometry, and reduced contamination may again arise from (for example) the combination of a first circular orifice with a second circular annular orifice. 
     It will also be appreciated that the silicon parts may be fabricated in a batch process so that the assembly may be provided as a low-cost disposable element. Finally, it will be appreciated that because the entire vacuum interface is now reduced in size, a plurality of similar elements may be constructed as an array on a common substrate. The array may then provide interfaces for a plurality of electrospray capillaries. 
     It will be understood that what has been described herein are exemplary embodiments of microengineered interface components which are provided to illustrate the teaching of the invention yet are not to be construed in any way limiting except as may be deemed necessary in the light of the appended claims. Whereas the invention has been described with reference to a specific number of layers it will be understood that any stack arrangement comprising a plurality of individually patterned semiconducting layers with adjacent layers being separated from one another by insulating layers, and orifice defined within the layers defining a conduit through the stack should be considered as falling within the scope of the claimed invention. 
     Within the context of the present invention the term microengineered or microengineering is intended to define the fabrication of three dimensional structures and devices with dimensions in the order of microns. It combines the technologies of microelectronics and micromachining. Microelectronics allows the fabrication of integrated circuits from silicon wafers whereas micromachining is the production of three-dimensional structures, primarily from silicon wafers. This may be achieved by removal of material from the wafer or addition of material on or in the wafer. The attractions of microengineering may be summarised as batch fabrication of devices leading to reduced production costs, miniaturisation resulting in materials savings, miniaturisation resulting in faster response times and reduced device invasiveness. Wide varieties of techniques exist for the microengineering of wafers, and will be well known to the person skilled in the art. The techniques may be divided into those related to the removal of material and those pertaining to the deposition or addition of material to the wafer. Examples of the former include:
     Wet chemical etching (anisotropic and isotropic   Electrochemical or photo assisted electrochemical etching   Dry plasma or reactive ion etching   Ion beam milling   Laser machining   Eximer laser machining   

     Whereas examples of the latter include:
     Evaporation   Thick film deposition   Sputtering   Electroplating   Electroforming   Moulding   Chemical vapour deposition (CVD)   Epitaxy   

     These techniques can be combined with wafer bonding to produce complex three-dimensional, examples of which are the interface devices provided by the present invention. 
     While the device of the invention has been described as an interface component it will be appreciated that such a device could be provided either separate to or integral with the other components to which it provides an interface between. By using an interface component it is possible to remove impurities or other unwanted components of the emitted spray material from the capillary needle conventionally used with mass spectrometer system. 
     It will be further understood that whereas the present invention has been described with reference to an exemplary application, that of interfacing an ionization source—specifically an electrospray ionization source—with a mass spectrometry system, that interface components according to the teaching of the invention could be used in any application that requires a coupling of an ion beam from an ionization source provided at a first pressure to another device that is provided at a second pressure. Typically this second pressure will be lower than the first pressure but it is not intended to limit the present invention in any way except as may be deemed necessary in the light of the appended claims. 
     Where the words “upper”, “lower”, “top”, bottom, “interior”, “exterior” and the like have been used, it will be understood that these are used to convey the mutual arrangement of the layers relative to one another and are not to be interpreted as limiting the invention to such a configuration where for example a surface designated a top surface is not above a surface designated a lower surface. 
     Furthermore, the words comprises/comprising when used in this specification are to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof.