Abstract:
An apparatus includes a portable housing and a plurality of separately operable microfluidic emitters disposed within the housing. Each microfluidic emitter h an inlet for receiving a liquid and an outlet for emitting a spray. Each microfluidic emitter is movable within the portable housing between a first position in which the outlet of that microfluidic emitter is fully retracted within the portable housing and a second position in which the outlet of that microfluidic emitter projects out of the portable housing. The portable housing with the multiple emitters is adapted to be detachably coupled to another housing portion. This housing portion includes a microfluidic substrate with a channel for transporting an eluent and an outlet aperture for emitting the eluent. The inlet of one of the emitters is detachably coupled to the outlet aperture of the microfluidic substrate.

Description:
RELATED APPLICATION 
     This application claims the benefit of and priority to co-pending U.S. provisional application No. 61/478,713, filed Apr. 25, 2011, titled “Cartridge with Multiple Electrospray Emitters,” the entirety of which is incorporated by reference herein. 
    
    
     FIELD OF THE INVENTION 
     The invention relates generally to liquid chromatography mass-spectrometry instruments. More specifically, the invention relates to multiple emitter interfaces to a microfluidic substrate used by such analytical systems. 
     BACKGROUND 
     High-performance liquid chromatography (HPLC) instruments are analytical tools for separating, identifying, and quantifying compounds. In a typical liquid chromatography analysis, a pump takes in and delivers a mixture of liquid solvents to a sample manager, where the material under analysis, called the sample, awaits injection into the solvents. The sample is the material under analysis. Examples of samples include complex mixtures of proteins, protein precursors, protein fragments, reaction products, and other compounds, to list but a few. The mobile phase, comprised of a sample dissolved in a mixture of solvents, moves to a point of use, such as a column, referred to as the stationary phase. By passing the mobile phase through the column, the various components in the sample separate from each other at different rates and thus elute from the column at different times. 
     The separation techniques of a liquid chromatography (LC) system are often used in combination with one or more additional analysis techniques to produce multidimensional information about a sample. For example, mass spectrometry (MS) can provide molecular weight and structural information. A difficulty associated with combining disparate techniques occurs at the interface between the techniques. For example, the combination of liquid chromatography and mass spectrometry requires effective transport of the sample eluent produced by the liquid chromatography system to the mass spectrometry instrument for analysis. Industry has devised various ionization techniques to achieve this sample eluent transport, including field desorption, thermospray, and electrospray. When used in conjunction with liquid chromatography techniques, many consider electrospray (ESI) to be the ionization method of choice. For electrospray ionization, a union couples the liquid chromatography column to an ESI emitter. A clogged or poorly performing ESI emitter, however, will produce poor data quality and will reduce the productivity of the LC-MS system until the ESI emitter is replaced. 
     SUMMARY 
     In one aspect, the invention features an apparatus comprising a portable cartridge housing including a first housing portion detachably coupled to a second housing portion. The first housing portion includes a microfluidic substrate with a channel for transporting an eluent and an outlet aperture for emitting the eluent. The second housing portion has a plurality of spray units. Each spray unit has an inlet for receiving the eluent, a lumen through which the eluent travels, and an outlet for emitting a spray of the eluent. A first one of the spray units housed within the second housing portion being in fluidic communication with the outlet aperture of the microfluidic substrate. 
     In another aspect, the invention features an apparatus comprising a portable housing, adapted to detachably couple to a cartridge containing a microfluidic substrate, and a plurality of separately operable microfluidic emitters disposed within the housing. Each microfluidic emitter has an inlet for receiving a liquid and an outlet for emitting a spray. Each microfluidic emitter is movable within the portable housing between a first position in which the outlet of that microfluidic emitter is fully retracted within the portable housing and a second position in which the outlet of that microfluidic emitter projects out of the portable housing in response to the portable housing being coupled to the cartridge with the microfluidic substrate. 
     In yet another aspect, the invention features a method replacing a electrospray emitter in a liquid chromatography system that uses a cartridge having a first housing portion detachably coupled to a second housing portion, the first housing portion including a microfluidic substrate with a channel for transporting an eluent and an outlet aperture for emitting the eluent, and the second housing portion having a plurality of electrospray emitters. The method comprises decoupling the second housing portion from the first housing portion, wherein the decoupling removes fluidic communication between an inlet of a first one of the electrospray emitters and an outlet aperture of the microfluidic substrate. After decoupling the second housing portion from the first housing portion, an orientation of the second housing portion relative to the first housing portion is changed such that an inlet of a second one of the electrospray emitters is aligned with the outlet aperture of the microfluidic substrate. After changing the orientation of the second housing portion relative to the first housing portion, the second housing portion is coupled to the first housing portion such that the inlet of the second one of the electrospray emitters is brought into fluidic communication with the outlet aperture of the microfluidic substrate. 
     In still yet another aspect, the invention features an apparatus comprising a portable housing adapted to detachably couple to a cartridge containing a microfluidic substrate and a multilayer structure disposed within the portable housing. The multilayer structure provides a plurality of microfluidic emitters. Each microfluidic emitter has an inlet opening for receiving a liquid, a channel through which the liquid travels, and an outlet orifice for emitting a spray. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above and further advantages of this invention may be better understood by referring to the following description in conjunction with the accompanying drawings, in which like numerals indicate like structural elements and features in various figures. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. 
         FIG. 1  is an isometric view of an embodiment of a microfluidic cartridge having a substrate housing and an emitter case, the substrate housing containing a multilayer substrate with one or more liquid chromatography columns, and the emitter case housing a plurality of spray emitters. 
         FIG. 2  is an exploded view of another embodiment of the microfluidic cartridge showing the emitter case as detached from the substrate housing. 
         FIG. 3  is a side view of the microfluidic cartridge of  FIG. 2  with one side of its housings removed to reveal various components housed with the substrate housing and the emitter case. 
         FIG. 4  is a side view of a spray unit comprising a single emitter. 
         FIG. 5  is a side view of a microfluidic cartridge having a multiple-emitter emitter case coupled to a substrate housing. 
         FIG. 6  is a is a side view a microfluidic cartridge having a multiple-emitter emitter case coupled to a substrate housing, each emitter being coupled to a different liquid chromatography column formed in a substrate within the substrate housing. 
         FIG. 7A  and  FIG. 7B  are end views of another embodiment of a microfluidic cartridge having a multiple-emitter emitter case coupled to a substrate housing,  FIG. 7A  being an end view of the emitter case, and  FIG. 7B  being an end view of the substrate housing coupled to the emitter case. 
         FIG. 7C  is a side view of a substrate housing having a retainer disposed centrally along its edge. 
         FIG. 8A  and  FIG. 8B  are end views of another embodiment of a microfluidic cartridge having a linear multiple-emitter emitter case coupled to a substrate housing,  FIG. 8A  being an end view of the emitter case, and  FIG. 8B  being an end view of the substrate housing coupled to the emitter case. 
         FIG. 9A  and  FIG. 9B  are end views of a linear multiple-emitter emitter case and a substrate housing coupled to the linear-emitter emitter case, respectively, and  FIG. 9C  is a coupling mechanism for guiding the coupling of the multiple-emitter emitter case  16 E to the substrate housing according to another embodiment of a microfluidic cartridge. 
         FIG. 10  is a diagram illustrating a simplified multi-layer construction of the emitter case of  FIG. 9A  and  FIG. 9B . 
         FIG. 11A  and  FIG. 11B  are diagrams of another embodiment of a microfluidic cartridge having a wheel-shaped multiple-emitter emitter case. 
     
    
    
     DETAILED DESCRIPTION 
     Microfluidic cartridges described herein contain multiple spray emitters situated in-line with a microfluidic substrate. At least one of the emitters is operatively connected to an outlet of the microfluidic substrate from which to receive liquid for spraying. An emitter case contains the emitters and is adapted for connection to and disconnection from a frame that houses the microfluidic substrate. The emitter case facilitates the quick replacement of an emitter that is performing poorly or becoming clogged. When an emitter in use becomes clogged, the emitter case can be decoupled from the substrate housing, reoriented to align a different emitter with the outlet of the microfluidic substrate, and then reconnected. This replacement of an emitter may be performed manually by a person or automatically by a mechanical and/or computer-driven mechanism. Quick replacement of a malfunctioning emitter effectively reduces the down time of the LC-MS instrument. 
       FIG. 1  shows an embodiment of a microfluidic cartridge  10  that houses a microfluidic substrate having one or more LC columns and a plurality of electrospray emitters. At least one of the LC columns is operatively coupled to one of the electrospray emitters. This embodiment of microfluidic cartridge  10  has a grip end  12 , a microfluidic substrate housing  14 , and an emitter case  16 , which houses a plurality of electrospray emitters, as described herein. The emitter case  16  is deemed “in-line” with the LC column and is detachable from the rest of the microfluidic cartridge  10 . In this embodiment, a spray tip  18  of one of the emitters extends from one end of the emitter case  16 . The orifice of the emitter tip can be in the range of microns to nanometers in diameter. That the spray tip  18  extends from the emitter case  16  is an indication that its emitter is operatively coupled to an outlet of the microfluidic substrate. 
     Housed within the substrate housing  14  of the microfluidic cartridge is a substantially rigid, ceramic-based, multilayer fluidic substrate (not shown). A channel formed in the layers of the substrate operates as a separation column. Multiple separate channels, each serving as a different separation channel, may be formed. Apertures in the side of the substrate provide openings into each channel through which fluid may be introduced into the column. Fluid passes through the apertures under high pressure and flows toward the emitter coupled at the egress end of the channel. Openings in the side of the substrate housing  14  provide fluidic inlet ports for delivering fluid to the microfluidic substrate. 
     The microfluidic cartridge  10  is adapted for insertion into an installation chamber of an HPLC instrument. When installed in the chamber, a mechanical clamping force urges the microfluidic substrate against fluidic nozzles coupled to the installation chamber. In addition, the spray tip  18  of the emitter is brought into operable communication with mass spectroscopy components of the HPLC instrument. The nozzles deliver fluid to the microfluidic substrate through the fluidic inlet ports of the substrate housing  14 . From the column of the substrate, the separated fluid leaves the cartridge through the spray tip  18 . One example implementation of the microfluidic cartridge  10  can be found in PCT application No. PCT/US2010/026342, titled “Electrospray Interface to a Microfluidic Substrate,” filed on Mar. 5, 2010 and published on Sep. 10, 2010 as International publication No. WO 2010/102194 A1, the entirety of which is incorporated by reference herein. 
       FIG. 2  shows another embodiment of the microfluidic cartridge  10  showing the emitter case  16  as detached from the substrate housing  14 . The detachability provides relative ease in swapping and/or replacing the emitter case, while retaining most or all other microfluidic components of the cartridge. The substrate housing  14  has left and right housing portions  20 - 1 ,  20 - 2  and holds a retainer  22 . Although shown to lie in a same plane as the end of the substrate housing, in some embodiments, the retainer  22  can extend beyond the substrate housing&#39;s end. The emitter case  16  has left and right housing portions  24 - 1 ,  24 - 2 , which define a spray-tip protection feature, namely a bracket that surrounds the tip  18  (the tip does not extend beyond the foremost edge of the protection feature). The left and right housing portions  24 - 1 ,  24 - 2  have latch features  26  for connecting the emitter case  16  to the substrate housing  14 . The latch features  26  allow for detaching the emitter case  16  from the substrate housing  14  when changing emitters, as described herein. Other embodiments can use any suitable attaching features, for example, screws, clips, and magnets. 
       FIG. 3  shows the microfluidic cartridge  10  with the right housing portions  20 - 1 ,  24 - 1  removed to reveal various components housed with the substrate housing  14  and the emitter case  16 . Within the substrate housing  14  is the retainer  22  and a multilayer microfluidic substrate  30  coupled at one edge to the retainer  22 . Formed within the multilayer substrate  30  is an LC column with an egress end that opens at the edge near the retainer  22 . The substrate  30  has a recessed edge portion  56  ( FIG. 4 ) for receiving the retainer  22 . A recessed edge is optionally used, for example, to produce a desirably smooth edge near the orifice and/or to protect the orifice portion of the edge. 
     Housed within the emitter case  16  are one emitter  32 , a spring  34 , and a fitting  36 , which secures the spring  34  to the emitter  32 . (The emitter case of  FIG. 3  has but one emitter  32 , illustrating the various features and general functional principles of each emitter in an emitter case that has multiple emitters.) The spring  34  wraps around a portion of the length of the emitter  32  and is disposed within a compartment  40  sized to hold the spring  34 . The inlet end of the emitter  32  enters an opening in the retainer  22 . The retainer  22  operates to align a lumen of the emitter  32  with the outlet aperture of the microfluidic substrate  30 . The compartment  40  operates as a spring-retaining feature that secures the spring  34  and applies a force to the spring  34  when the detachable emitter case  16  is attached to the substrate housing  14 . Connection produces a face seal between the inlet end of the emitter  32  and the outlet aperture of the microfluidic substrate  30 . Preferably, additional component(s) urge the emitter  32  into contact with the substrate  30  with sufficient force to provide a greater interfacial pressure than the pressure of eluent flowing out of the column from the outlet port of the substrate  30 . Additionally, interior walls of the left housing portion  24 - 2  define a gas passageway  38  for delivery of a gas to surround the spray tip  18 . 
       FIG. 4  shows an embodiment of a spray unit  50  that can be used in a microfluidic cartridge  10 . As used herein, the term “spray unit” is a descriptive convenience not intended to limit the spray unit to any specific set of components or to limit the location of such components. Preferably, the spray unit  50  is defined as only those components associated with the emitter case  16 , although some of the components can reside in the substrate housing  14  whereas other components of the spray unit  50  can reside in the emitter case  16 . In this embodiment, the spray unit  50  includes the emitter  32 , spring  34 , fitting  36 , and a fixed or removable retainer cap  52 . When the spray unit  50  is assembled for operation, the spring  34  and fitting are covered by the cap  52  (that is, from where it appears in  FIG. 4 , the cap  52  slides over the spring  34  and fitting  36  to abut the end of the retainer  22 ). Instead of the compartment  40  of  FIG. 3 , this embodiment of spray unit  50  employs a surface  54  to apply a force to the spring  34  when the detachable emitter case  16  is attached to the substrate housing  14 . 
       FIG. 5  shows an embodiment of a microfluidic cartridge  10 A having an emitter case  16 A with multiple emitters, one of which is coupled to a microfluidic substrate  30 A housed within a substrate housing  14 A. The various details of the housing portions of the microfluidic cartridge  10 A are omitted from  FIG. 5  to focus the description on the salient features. The omitted details are functionally similar to those described in connection with  FIG. 2-4 , requiring some structural modifications within the ability of those of ordinary skill in the art to accommodate the particular embodiments of emitter case  16 A, substrate housing  14 A, and microfluidic substrate  30 A. 
     In this embodiment, the multiple-emitter emitter case  16 A has two emitters  32 - 1 ,  32 - 2  (with accompanying springs, fittings, tips, etc.). One emitter  32 - 1  is coupled at one end to a retainer  22 . This coupling produces a fluidic path from a column  60  formed in a multilayer substrate within the substrate housing  14 A to the tip  18  of the emitter  32 . The act of coupling the emitter case  16 A to the substrate housing that contains the microfluidic substrate  30 A causes the tip  18  to project from the emitter case  16 A, thereby placing the tip  18  into operational position. The other emitter  32 - 2  is in a retracted position, its tip  18  remaining within the emitter case  16 A. The retracted position is the default position of each emitter  32 - 1 ,  32 - 2  before the emitter case  16 A is coupled to the microfluidic substrate  30 A. 
     By having multiple emitters within the microfluidic cartridge  10 A, one emitter can serve as a convenient replacement for the other after the other emitter ceases to function satisfactorily. For example, the emitter  32 - 2  can be the replacement of emitter  32 - 1 . To make the replacement, the emitter case  16 A is decoupled from the substrate housing sufficiently far to break the face seal between the emitter-in-use  32 - 1  and the outlet aperture of the microfluidic substrate  30 A. Decoupling causes the first emitter  32 - 1  to retract within the emitter case  16 A. The emitter case  16 A is then rotated 180 degrees about the axis  62 , and reconnected to the substrate housing  14 A, the inlet end of the emitter  32 - 2  entering the retainer  22  and making a face seal with the microfluidic substrate  30 A. The location of the retainer  22  is offset from the midpoint of the edge of the substrate housing  14 A so that the retainer  22  will be in alignment with one emitter or the other, depending upon the particular orientation of the emitter case  16 A when attached to the substrate housing  14 A. Reconnecting causes the tip of the other emitter  32 - 2  to project from the emitter case  16 A, placing it into operational position. The replacement can be an automated or manual process, a process performed by an LC/MS instrument in which the microfluidic cartridge  10 A is installed or by person. An automated process can also maintain track of which emitters or spray units in the emitter case  10 A have already been used, and notify a user when no replacement emitters are available. 
       FIG. 6  is another simplified view, this one of another embodiment of a microfluidic cartridge  10 B having a multiple-emitter emitter case  16 B coupled to a substrate housing  14 B that houses a multilayer substrate  30 B within which are multiple separately operable columns  60 - 1 ,  60 - 2 . The substrate housing  14 B also has a pair of retainers  22 - 1 ,  22 - 2  (generally,  22 ), which are symmetrically offset from the midpoint of the edge of the substrate housing  14 B. The multiple-emitter emitter case  16 B has two emitters  32 - 1 ,  32 - 2  (generally, emitter  32 ) like the emitter case  16 A of  FIG. 5 . Each emitter  32  is coupled at its inlet end to one of the retainers  22 - 1 ,  22 - 22 . Coupling the emitter case  16 B to the substrate housing  14 B causes the emitters  32  to the project from the emitter case  16 B, placing both emitters  32  into operational position. The coupling of the multiple-emitter emitter case  16 B to the substrate housing  14 B may be reversible; meaning that emitter  32 - 1  can be coupled to either retainer  22 - 1  or to retainer  22 - 2  (with emitter  32 - 2  being coupled to the other retainer). Embodiments of this emitter case  16 B may or may not be detachable from the substrate housing  14 B. Having multiple emitters within the microfluidic cartridge  10 B, one coupled to a different column in the substrate housing  14 B, permits concurrent operation of multiple columns Further, an operator also has the option of using one emitter-column combination as a spare for when the other emitter-column combination becomes unusable (e.g., clogged from use). 
       FIG. 7A  and  FIG. 7B  show another embodiment of a microfluidic cartridge  10 C having a multiple-emitter emitter case  16 C coupled to a substrate housing  14 C shown in  FIG. 7C .  FIG. 7A  is an end view of the emitter case  16 C, and  FIG. 7B  is an end view of the substrate housing  14 C coupled to the emitter case  16 C.  FIG. 7C  shows the substrate housing  14 C having a connector mechanism  22 A (here, similar to retainer  22  of  FIG. 5 ) disposed approximately midpoint on the edge facing the emitter case  16 C, although other locations along the edge are also usable. The outlet aperture of the microfluidic substrate  30 C is aligned with an outlet aperture  75  of the connector mechanism  22 A. Again, the various details of the housing portions of the microfluidic cartridge  10 C are omitted to focus the description on salient features. 
     In  FIG. 7A , the emitter case  16 C has four emitters  32 - 1 ,  32 - 2 ,  32 - 3 , and  32 - 4  (generally,  32 ), their inlets being arranged at the four points of a compass. Other embodiments can have three or greater than four of such emitters. Herein, the arrangement pattern formed by the inlets is abstractly referred to as polygonal; that is, if lines were drawn to connect the emitter inlets, the produced pattern has three (i.e., triangular) or more sides. 
     In  FIG. 7B , the substrate housing  14 C is aligned with and coupled to the emitter  32 - 4 . The inlet end of the emitter  32 - 4  enters the outlet aperture  75  of the connector mechanism  22 A and produces a face seal with the outlet aperture of the microfluidic substrate  30 C. In this configuration, the emitters  32 - 1 ,  32 - 2 , and  32 - 3  are unused and available as replacements. When unused, the emitters are in a retracted position, similar to that shown in  FIG. 5 . To effect a replacement, the emitter case  16 C is decoupled from the substrate housing  14 C, rotated 90 degrees (like a barrel as illustrated by arrow  70 ), and then reconnected to the substrate housing  14 C. The replacement can be an automated or manual process. 
       FIG. 8A  and  FIG. 8B  show another embodiment of a microfluidic cartridge  10 D having a multiple-emitter emitter case  16 D coupled to a substrate housing  14 C ( FIG. 7C ).  FIG. 8A  is an end view of the emitter case  16 D and  FIG. 8B  is an end view of the substrate housing  14 C coupled to the emitter case  16 D. The emitter case  16 D has four emitters  32 - 1 ,  32 - 2 ,  32 - 3 , and  32 - 4  (generally,  32 ) in a linear arrangement running north and south. In an alternative embodiment, the linear arrangement of emitters can run east and west. In  FIG. 8B , the substrate housing  14 C is aligned with and coupled to the emitter  32 - 4 . The inlet end of the emitter  32 - 4  enters the outlet aperture  75  of the connector mechanism  22 A and produces a face seal with the outlet aperture of the microfluidic substrate  30 C. In this configuration, the emitters  32 - 1 ,  32 - 2 , and  32 - 3  are unused and available as replacements. When unused, the emitters are in a retracted position, similar to that shown in  FIG. 5 . To execute a replacement, the emitter case  16 D is decoupled from the substrate housing  14 C, indexed or stepped down (or up) one or more positions, as indicated by arrow  72 , and then reconnected to the substrate housing  14 C. The decoupling breaks the face seal of the emitter-in-use and withdraws the inlet end of the emitter entirely out of the connector mechanism  22 A, out far enough to permit the stepping of the emitter housing  16 D. The replacement can be an automated (computer-driven mechanism) or manual process. 
       FIG. 9A  and  FIG. 9B  show another embodiment of a microfluidic cartridge  10 E having a multiple-emitter emitter case  16 E coupled to a substrate housing  14 C ( FIG. 7C ).  FIG. 9A  is an end view of the emitter case  16 E containing a linear strip  78  of emitters and  FIG. 9B  is an end view of the substrate housing  14 C coupled to the emitter case  16 E. The connector mechanism  22 A has an outlet aperture  75  that is in fluidic communication with the outlet aperture of the microfluidic substrate housed within the substrate housing  14 C. In this embodiment, the face  77  ( FIG. 9C ) of the connector mechanism  22 A provides the leak proof face seal, as described in more detail below. The connector mechanism  22 A can also include alignment pins  79  situated about the outlet aperture  75  for guiding the coupling of the multiple-emitter emitter case  16 E to the substrate housing  14 C, as is generally known to those of ordinary skill in the art. 
     In this embodiment, the linear emitter strip  78  has six emitters  32 A- 1 ,  32 A- 2 ,  32 A- 3 ,  32 A- 4 ,  32 A- 5 , and  32 A- 6  (generally,  32 A) in a linear-strip arrangement running north-south. Although only a single linear column of emitters is shown, another embodiment can have a second linear column of emitters adjacent the first column, with the emitters of that second linear column extending in the opposite direction as those of the first column. The linear emitter strip  78  has an opening  74  for each of the emitters  32 A that provides an inlet port to that emitter  32 A, and pin holes (not shown) next to each opening  74  to receive the pins  79  of the connector mechanism  22 A. The emitter case  16 E has corresponding openings aligned with these openings  74 ; such emitter-case openings can help to align the connector mechanism  22 A and the outlet aperture  75  of the substrate housing  14 C with a given opening  74  when connecting the substrate housing to the emitter case  16 E. From its respective opening  74 , the lumen of each emitter  32 A bends generally orthogonally to project from the side of the emitter case  16 E. In contrast to the emitters  32  of  FIGS. 8A and 8B , which have lumens that will be coaxial with respect to the outlet aperture of the microfluidic substrate when the emitter case  16 E and substrate housing  14 C are joined, the emitters  32 A are orthogonal. (In another embodiment, the lumens or channels of the emitters  32 A can extend coaxially from the inlet openings  74  of the emitters  32 A, to extend from the other side opposite the substrate housing  14 C.) 
     For example,  FIG. 9B  shows the substrate housing  14 C aligned with and coupled to the emitter  32 A- 4 . The face  77  of the connector mechanism  22 A produces a face seal around the opening  74  of the emitter  32 A- 4 . The other emitters  32 A- 1 ,  32 A- 2 ,  32 A- 3 ,  32 A- 5 , and  32 A- 6  in this configuration are unused and available as replacements. To execute a replacement, the emitter case  16 E is decoupled from the substrate housing  14 C, stepped down (or up) one position as indicated by arrow  76 , and then reconnected to the substrate housing  14 C. Instead of moving the emitter case  16 E, the substrate housing  14 C can be stepped up or down. The replacement can be an automated or manual process. 
     The emitter case  16 E can be manufactured and marketed as a separate consumable adapted for connecting to a given substrate housing, and as a dispensable consumable after all of the emitters have been used. The linear strip of emitters  32 A housed within the emitter case  16 E can be constructed with a material particularly suited for making a face seal with the face  77  of the substrate housing  14 C. Examples of such materials include polyimide, PEEK, and VESPEL®. The resulting linear-strip  78  of emitters  32 A has flexibility characteristics similar to those of a flex-circuit. 
       FIG. 10  illustrates a simplified construction of the linear emitter strip  78  of  FIG. 9A  and  FIG. 9B . The linear emitter strip  78  is constructed of layers  80  of a polymeric material, for example, PEEK or of metal, for example, titanium. Multiple of such layers  80  can be used to construct each emitter  32 A. For example, a first layer  80 - 1  can have an inlet port (opening  74 ) behind which a next layer  80 - 2  has a lateral channel  82  formed therein, the channel  82  extending to and opening at the side edge of the layer  80 - 2  and the inlet port  74  opening into one end of the channel  82 . An emitter tip  18  is formed from the edge of the layer  80 - 2 , at the channel opening. A third layer  80 - 3  of material sandwiches the channel layer  80 - 2  between it and the first layer  80 - 1 . The first layer  80 - 1  also has openings for each inlet port of the other emitters  32 A to be constructed. The other emitters  32 A can be similarly constructed. A heating and curing process combines all of the layers. 
       FIG. 11A  and  FIG. 11B  show another embodiment of a microfluidic cartridge  10 F having a multiple-emitter emitter case  16 F, which houses a wheel  100  of emitters, coupled to a substrate housing  14 C ( FIG. 7C ).  FIG. 11A  is an end view of the emitter case  16 F having eight emitters  32 B- 1 ,  32 B- 2 ,  32 B- 3 ,  32 B- 4 ,  32 B- 5 ,  32 B- 6 ,  32 B- 7 , and  32 B- 8  (generally,  32 B) extending from the edge of the circumference of the emitter case  16 F. The emitter wheel  100  also has opening  94  that serves as an inlet port to each of the emitters  32 B. (The emitter case  16 F has corresponding openings aligned with these openings  94 ; such emitter-case openings can help to align the outlet aperture  75  of the substrate housing  14 C with a given opening  94  when connecting the substrate housing to the emitter case.) The lumen of each emitter  32 B turns generally orthogonally from its respective opening  94  and extends to the circumferential edge of the emitter case  16 F. Accordingly, the lumens of the emitters  32 B are primarily orthogonal to the  75  aperture of the substrate housing  14 C. (In another embodiment, the lumens or channels of the emitters  32 B can extend coaxially from the inlet openings  94  of the emitters  32 B and extend from the other side opposite the substrate housing  14 C.) The emitter case  16 F can also have a keyed opening  90  in its center, for use by a mechanical mechanism to turn the emitter case  16 F like a dial when stepping or indexing from one emitter  32 B to the next. 
     The wheel  100  of emitters can be constructed of a polymeric material, for example, PEEK, or of a metal, for example, titanium. If constructed of polymeric material, the wheel  100  of emitters can have flexibility characteristics similar to those of a flex-circuit, and can establish an effective the leakproof face seal with the face  77  of the substrate housing. If constructed of metal, the emitter wheel  100  preferably includes a polymeric gasket  92  that surrounds the openings  94  and produces the leak-proof face seal around the outlet aperture  75  of the substrate housing  14 C with which the gasket  92  comes into contact. Alternatively, the sealing material can be disposed on the face  77  of the substrate housing  14 C around the outlet aperture  75 , which comes into contact with the metal around the opening  94  of the emitter and produces the face seal. Like the emitter case  16 E of  FIG. 9A  and  FIG. 9B , the emitter case  16 F can be manufactured and marketed as a separate consumable adapted for connecting to a given substrate housing and dispensable after all its emitters have been used. 
       FIG. 11B  shows the substrate housing  14 C aligned with and coupled to the emitter  32 B- 7 , as an example. The other emitters  32 B- 1 ,  32 B- 2 ,  32 B- 3 ,  32 B- 5 ,  32 B- 6 , and  32 B- 8  are unused in this configuration and available as replacements. To execute a replacement, the emitter case  16 F is decoupled from the substrate housing  14 C, rotated clockwise or counterclockwise by one or more positions, as indicated by arrow  96 , and then reconnected to the substrate housing  14 C. The rotation can be performed in automated fashion or be a manual process. Construction of the emitter wheel  100  can be achieved in multi-layer fashion similar to that of the linear emitter strip described in connection with  FIG. 10 . 
     Reference in the specification to “one embodiment” or “an embodiment” means that a particular, feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the teaching. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment. 
     While the invention has been shown and described with reference to specific preferred embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the following claims.