Patent Publication Number: US-6911182-B2

Title: Device for placement of effluent

Description:
BACKGROUND OF THE INVENTION 
     The present disclosure relates to devices for placement of effluents on substrates. In particular embodiments, the present disclosure relates to devices for controlled placement of effluents that have been processed, either mechanically or electrically, to separate the effluents into their constituent molecules. In some embodiments, the present disclosure relates to devices for placement on substrates of effluents that are to be analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectroscopy (MALDI/TOF/MS). 
     The analysis of samples utilizing analytical chemistry techniques frequently requires the samples to be subjected to a number of successive techniques in order to obtain the desired information. This is particularly true when the sample to be analyzed includes biological molecules, such as polypeptides, proteins, lipids, polynucleotides, and/or polysaccharides. For example, it is common to initially subject a sample containing biological molecules to a chromatography technique in order to separate the constituent molecules of the sample into a number of liquid fractions collected from the effluent of the chromatography system (e.g. effluent from electrically driven devices, such as CE and CEC devices, or pump driven devices, such as capillary LC and micro-LC). Thereafter, each fraction can be subjected to a subsequent analytical technique in order to obtain additional information about the biological molecules contained therein. For example, each fraction can be subjected to an analytical technique such as, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance. Accordingly it is often necessary to transfer analytical samples from one analytical apparatus to another (e.g. from a chromatography apparatus to a mass spectrometry apparatus) in order to obtain the desired information. Therefore, an apparatus and method for transferring samples from one analytical apparatus to another is desirable. 
     SUMMARY OF THE INVENTION 
     A device for placement of effluents in accordance with the present invention comprises one or more of the following features or combinations thereof: 
     A substrate positioner is provided to support and position a substrate on which effluent is to be deposited. The substrate positioner may be an X-Y table or a reel-to-reel tape drive. A deposition conduit having a first opening through which the effluent enters the conduit and having a second opening through which effluent exits the conduit is provided. A conduit positioner configured to move an exit end of the conduit relative to the substrate is provided. The conduit positioner may have a pivotable arm to which the deposition conduit is coupled. The conduit positioner may also have a driver coupled to the arm to pivot the arm. The driver may be a motor and a cam coupled to an output shaft of the motor. The driver may be a linear stepper motor or a solenoid. The conduit positioner may move the exit end of the conduit between a raised position in which surface tension in the effluent adjacent the second opening prevents the effluent from separating away from the exit end of the deposition conduit and a lowered position in close proximity to the substrate so that effluent adjacent the second opening contacts and adheres to the substrate. The exit end of the deposition conduit may be exposed to the ambient atmosphere. 
     In some embodiments, the substrate positioner and the conduit positioner have a first mode of operation and a second mode of operation. In the first mode of operation a substantially continuous line, film, or trace of effluent is deposited on the substrate and in the second mode of operation, discrete spots or aliquots of effluent are deposited on the substrate. The substrate may comprises a plate or a tape. The plate and/or tape may be adapted for use with a MALDI MS apparatus. 
     Additional features of the invention will become apparent to those skilled in the art upon consideration of the following detailed description of illustrative embodiments exemplifying the best mode of carrying out the invention as presently perceived. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The detailed description particularly refers to the accompanying figures in which: 
         FIG. 1  is a diagrammatic view showing a fluid treatment device having a container filled partially with a first fluid, a pressure source for pressurizing the container, a fluid source for delivering via a delivery conduit a second fluid to a junction member situated within the container, and a deposition conduit coupled to the junction member to receive a mixture of the first and second fluids, and also showing a conduit positioner coupled to a lower end of the deposition conduit outside the container to position the lower end of the deposition conduit relative to a substrate that is coupled to a substrate-support apparatus; 
         FIG. 2  is a perspective view of the junction member and portions of the delivery conduit and the deposition conduit coupled to the junction member showing a mixing space defined between the lower end of the delivery conduit and the upper end of the deposition conduit and showing a pair of openings in the junction member communicating with the mixing space; 
         FIG. 3  is a diagrammatic view, similar to  FIG. 1 , showing an alternative fluid treatment device having a source of nitrogen pressurizing a container filled partially with a matrix material, a liquid chromatography apparatus coupled via a separation conduit to an intermediate sleeve, a delivery conduit extending between the intermediate sleeve and a junction member situated in the container, and a deposition conduit coupled to the junction member to receive a mixture of the matrix material and a fluid carrying an analyte; 
         FIG. 4  is a diagrammatic view, similar to  FIG. 3 , showing another alternative fluid treatment device having a source of nitrogen pressurizing a container filled partially with a matrix material, a capillary electrochromatography (CEC) apparatus coupled via a delivery conduit to a junction member situated in the container, and a deposition conduit coupled to the junction member to receive a mixture of the matrix material and a fluid carrying an analyte; 
         FIG. 5  is a diagrammatic view showing a conduit positioner having a pivotable arm that is driven by a cam mounted to an output shaft of a motor of the conduit positioner, the conduit positioner having a coupler for coupling a first end of the arm to a lower end of a deposition conduit that extends from a fluid treatment device, and a MALDI plate situated beneath the lower end of the deposition conduit and being moved in orthogonal horizontal directions so that effluent exiting the lower end of the deposition conduit is deposited on the MALDI plate in a substantially continuous, serpentine pattern; 
         FIG. 6  is a diagrammatic view showing the conduit positioner of  FIG. 5  being operated to deposit spots of effluent on a tape that is advanced by a reel-to-reel machine from a first reel to a second reel; 
         FIG. 7  is top plan view of the MALDI plate of  FIG. 5  after effluent is deposited thereon in the serpentine pattern; 
         FIG. 8  is a top plan view of a MALDI plate showing a pattern of spots of effluent deposited on the MALDI plate by the conduit positioner of  FIG. 5  when the motor is operated to cyclically pivot the arm to raise and lower the lower end of the deposition conduit relative to the MALDI plate; 
         FIG. 9  is a top plan view of a portion of the tape of  FIG. 6  showing a pattern of spots of effluent deposited on the tape by the conduit positioner when the motor is operated to cyclically pivot the arm to raise and lower the lower end of the deposition conduit relative to the tape; 
         FIG. 10  is graph of a CEC-MALDI analysis of N-glycans derived from Ribonuclease B showing an “a” trace depicting a mass spectrum of a mixture of the N-glycans and showing “b-f” traces depicting the spectra of different aliquots deposited on a MALDI plate after CEC separation; and 
         FIG. 11  is a graph of a CEC-MALDI analysis of Dextrin showing an “a” trace depicting a mass spectrum of the Dextrin mixed with a matrix material and showing “b-f” traces depicting the spectra of different aliquots deposited on a MALDI plate after CEC separation. 
     
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS 
     A fluid treatment device  10  has a container or vial  12  filled partially with a first fluid  14 , a pressure source  16  for pressurizing container  12  through a pressure conduit  18 , a fluid source  20 , and a delivery conduit  22  through which a second fluid (not shown) flows from fluid source  20  into an interior region  24  of container  12  as shown in FIG.  1 . Device  10  further comprises a junction member  26  that is situated in interior region  24  of container  12 . Conduit  22  is coupled to junction member  26 . Device  10  also has a deposition conduit  28  that is coupled to junction member  26  and that exits container  12 . First fluid  14  and the second fluid from source  20  are mixed together within junction member  26  and are moved out of container  12  through conduit  28 . A set of nuts  23  provide a fluid-tight connection between respective conduits  18 ,  22 ,  28  and container  12 . Nuts  23  thread into the various apertures (not shown) that are formed in container  12  for passage of conduits  18 ,  22 ,  28  therethrough. 
     A conduit positioner  30  is coupled to a lower region of conduit  28  and is operable to position conduit  28  relative to a substrate  32  or any other suitable fluid receiver which is configured to receive the mixture of fluids from conduit  28 . The terms “substrate” and “fluid receiver” are used herein interchangeably. In some embodiments, substrate  32  is coupled to a substrate positioner  33  that is operable to position substrate  32  relative to conduit  28 . In other embodiments, substrate positioner  33  is omitted. 
     In some embodiments, junction member  26  comprises a connection sleeve, shown in  FIG. 2 , which is tubular and which is sometimes referred to herein as “sleeve  26 .” Sleeve  26  has an inner surface  34  that defines an axially extending, main passage between a first end  36  and a second end  38  of sleeve  26 . Sleeve  26  also has one or more openings  40  that extend from an outer surface  42  of sleeve  26  to surface  34 . In the illustrative embodiment, sleeve  26  has two openings  40  that are bounded by cylindrical surfaces  42  which are formed about midway between ends  36 ,  38  of sleeve  26  and which extend through sleeve  26  in perpendicular relation with the main passage defined by surface  34 . Also in the illustrative embodiment, surfaces  34 ,  42  are cylindrical. 
     An exit end  46  of conduit  22  is received in an upper portion of the main passage of member  26  and an entrance end  48  of conduit  28  is received in a lower portion of the main passage of member  26  as shown in FIG.  2 . Ends  46 ,  48  of conduits  22 ,  28 , respectively, are positioned within the main passage of member  26  such that a downwardly facing end surface  50  of conduit  22  is spaced from an upwardly facing end surface  52  of conduit  28  to define a mixing space  54  therebetween. Thus, illustrative sleeve  26  is oriented vertically having the main passage extending vertically and having openings  40  extending horizontally. Mixing space  54  is in fluid communication with interior region  24  of container  12  through openings  40 . Sleeve  26  holds end  46  of conduit  22  and end  48  of conduit  28  in alignment. Sleeve  26  may be omitted in embodiments having rigid conduits  22 ,  28  that are held in alignment by nuts  23  or by other mechanisms suitable for maintaining the alignment of conduits  22 ,  28 . It is within the scope of this disclosure for end  46  of conduit  22  to abut end  48  of conduit  28  and for either or both of end surfaces  50 ,  52  to have notches, grooves, channels, or the like to provide fluid communication between interior region  24  of container  12  and passages  56 ,  62  of conduits  22 ,  28  respectively. 
     Container  12  is filled with enough fluid  14  to ensure that an upper surface  58  of fluid  14  is above openings  40  in junction member  26 . However, container  12  is not completely filled with fluid  14  so that the portion of interior region  24  of container above surface  58  is pressurizable by pressure source  16 . Thus, the lower end of conduit  18  terminates in space  24  above surface  58  of fluid  14  as shown in FIG.  1 . Illustratively, a cap  60  is coupled to container  12  to block an inlet port (not shown) through which fluid  14  is introduced into container  12  when cap  60  is removed. Pressurization of interior region  24  of container  12  by pressure source  16  forces a quantity of fluid  14  to move through opening  40  into mixing space  54 . In addition, fluid source  20  is operable to move the second fluid through an internal passage  56  of conduit  22  and into mixing space  54  where the second fluid mixes with fluid  14 . The pressure created in interior region  24  of container  12  causes the mixture of the first fluid  14  and the second fluid to move downwardly through an internal passage  62  of conduit  28 . The mixture of the first fluid  14  and the second fluid exits the lower end of conduit  28  as an effluent for further handling and/or processing and/or analysis as desired. 
     It is contemplated by this disclosure, that the first fluid  14  and the fluid from fluid source  20  may be any desired fluids that are to be mixed together for any subsequent use. However, fluid treatment devices in accordance with the teachings of this disclosure are especially useful in treating separation effluent from either mechanically or electrically driven separations for subsequent use and analysis. In some fluid treatment devices, fluid source  20  comprises a separation apparatus that operates to separate an analyte into its constituent molecules. In some of these fluid treatment devices, the first fluid  14  in container  12  serves as a treatment liquid that may be used to change the pH, density, or ionic strength of the second fluid, for example. As also contemplated herein, the treatment liquid in container  12  may comprise a buffer material and/or a matrix material that is added to an analyte to create an effluent for subsequent MALDI MS analysis of the effluent. 
     Referring now to  FIG. 3 , an alternative fluid treatment device  110  that uses liquid chromatography is provided. Device  110  is similar to device  10  in many respects and therefore, like reference numerals used to denote elements of device  110  that are substantially similar to like elements of device  10 . One difference between device  10  and device  110  is that the generic pressure source  16  of device  10  is replaced in device  110  with a source  116  of pressurized nitrogen. It is understood that any non-reactive, ideal gas may be used in lieu of nitrogen to pressurize container  12 . Another difference between device  10  and device  110  is that the generic fluid source  20  of device  10  is replaced in device  110  with a liquid chromatography apparatus  120 , a separation conduit  122 , and an intermediate sleeve  124 . Furthermore, a stationary phase material is packed in conduit  122  of device  110 . Apparatus  120  includes equipment, such as an Agilent 110 series liquid chromatography pump for moving an analyte into conduit  122  and a splitter for controlling the flow of the analyte into conduit  122 . 
     In some fluid treatment device embodiments using liquid chromatography, packed capillary columns are coupled directly to sleeve  26  in the same manner as described above regarding connection of conduit  22  to sleeve  26 . In embodiments having a micro column, intermediate sleeve  124  is used prior to interfacing with sleeve  26  as shown in FIG.  3 . Illustratively, sleeve  124  connects conduit  122  to conduit  22 . In some fluid treatment devices using liquid chromatography, fluid  14  is a matrix material that is mixed in space  54  of sleeve  26  with the effluent carrying an analyte from apparatus  120 . In such embodiments, the resultant, mixed effluent may be deposited on a MALDI plate  132  and then analyzed by MALDI/TOF/MS. Illustrative plate  132  is made from stainless steel, for example. 
     Referring now to  FIG. 4 , an alternative fluid treatment device  210  that uses capillary electrochromatography (CEC) is provided. Device  210  is similar to devices  10 ,  110  in many respects and therefore, like reference numerals used to denote elements of device  210  that are substantially similar to like elements of devices  10 ,  110 . In lieu of generic fluid source  20  of device  10  and elements  120 ,  122 ,  124  of device  110 , device  210  has a container  212  that contains a fluid  214  which flows from container  212  through conduit  22  to junction member  26  in container  12 . Device  210  also has a power supply  216 , such as a high voltage power supply of the type available from Spellman High Voltage Electronics of Plainview, N.J. Power supply  216  outputs an electrical potential that is adjustable, in some embodiments, between 0 Volts and 40 kilovolts and that is applied to fluid  214  via an electrode  218  which is immersed in fluid  214 . In some embodiments, electrode  218  is made of platinum. Fluid  214  is electrically conductive and becomes electrically charged by the electrical potential applied thereto. 
     Another difference between device  210  and devices  10 ,  110  is that device  210  has an auxiliary pressure conduit  220  through which pressurized nitrogen gas is communicated from conduit  18 , or alternatively from source  116 , to an interior region  222  of container  212 . Specifically, pressurized nitrogen gas is introduced into container  212  above an upper surface  224  of fluid  214 . It is understood that any non-reactive, ideal gas may be used in lieu of nitrogen to pressurize container  212 . An entrance end  226  of conduit  22  is submerged in fluid  214  and pressurization of container  212  is substantially equalized with pressurization of container  12 . The electrical potential created by power supply  216  causes a quantity of electrically charged fluid  214  to moves through end  226 , into passage  56  of conduit  22 , and then on to junction member  26 . Illustrative junction member  26  of device  210  is made from a material that is an electrical insulator, such as a Silica Seal Tight™ sleeve available from Upchurch Scientific of Oak Harbor, Wash. In alternative embodiments, junction member  26  is made from other materials suitable for holding ends  46 ,  48  of conduits  22 ,  28 , including electrically conductive materials. 
     Device  210  has an electrode  228  that is immersed in fluid  14  and that is coupled electrically to ground. In some embodiments, electrode  228  is made of platinum. Fluid  14  used in device  10  is a buffer material and/or matrix material that is electrically conductive. Thus, an electrical pathway forming a complete electrical circuit is provided via power supply  216 , electrode  218 , fluid  214  in container  212  and in conduit  22 , a mixture of fluid  214  and fluid  14  in mixing space  54  of sleeve  26 , fluid  14  in container  12 , and electrode  228 . Power supply  216  and electrode  228  are both coupled electrically to ground. The mixture of fluid  14  and fluid  214 , which includes an analyte, produces a resultant effluent  230  that is moved through conduit  28  and deposited on an ungrounded MALDI plate  132  for subsequent analysis by MALDI/TOF/MS. Conduit  28  and plate  132  are excluded from the electrical pathway of device  210  and therefore, need not be grounded. 
     An additional set of nuts  223  are included in device  210  to provide fluid-tight connections between electrodes  218 ,  228  and respective containers  212 ,  12 , between conduit  220  and container  212 , and between conduit  22  and a cap  260  that is coupled to container  212  as shown in FIG.  4 . Nuts  223  thread into the various apertures (not shown) that are formed in containers  12 ,  212  and in cap  260  for passage of respective electrodes  218 ,  228  and conduits  22 ,  220  therethrough. Cap  260  blocks an inlet port (not shown) through which fluid  214  is introduced into container  212  when cap  260  is removed. In alternative embodiments of device  210 , capillary electrophoresis (CE) techniques are used for separation of an analyte into its constituent molecules in lieu of the disclosed capillary electrochromatography techniques. 
     In some embodiments in which an analyte is separated into its constituent molecules, such as the embodiment shown in  FIG. 4 , conduit  22  has an outside diameter (o.d.) of 365 micrometers (μm), has an inside diameter (i.d.) (i.e., the diameter of passage  56 ) of 100 μm, and is made from fused silica that is coated with polyamide to provide a high degree of flexibility. In the embodiments of  FIG. 4 , conduit  28  has an o.d. of 365 μm, has an i.d. (i.e., the diameter of passage  62 ) of 25 μm, and is also made from fused silica coated with polyamide. Further details regarding procedures for preparing conduits  22 ,  28  may be found in the following publications which are hereby incorporated by reference herein: Palm, A. and Novotny, M. V.  Anal. Chem . 1997, 69, 4499-4507; Que A. H., Palm, A., Baker, A. G., and Novotny, M. V.  J. Chromatogr. A  2000, 877, 379-391. Fused silica is available from Polymicro Technologies of Phoenix, Ariz. In alternative embodiments, including devices  10 ,  110 , conduits  22 ,  28  may be made from other materials, such as stainless steel or polyethylketone (PEEK). 
     Also in the embodiment of  FIG. 4 , junction member  26  has an o.d. of {fraction (1/16)} inch (1587.5 μm) and has an i.d. of 330 μm. Thus, conduits  22 ,  28  having an o.d. of 365 μm are press fit into connection sleeve  26  having an i.d. of 330 μm. In addition, the i.d. of conduit  22  is approximately four times the size of the i.d. of conduit  28  in the illustrative embodiment of FIG.  4 . In the embodiment of  FIG. 4 , openings  40  are formed through junction member  26  by using a drill bit having an o.d. of 400 μm. Thus, the i.d. of openings  40  are approximately 400 μm. Prior to insertion of ends  46 ,  48  of conduits  22 ,  28 , respectively, into the main passage of connection sleeve  26 , a capillary or strand (not shown) having an o.d. of 160 μm is inserted through openings  40 . Thereafter, ends  46 ,  48  of conduits  22 ,  28 , respectively, are inserted into the main passage of connection sleeve  26  until end surfaces  50 ,  52  of conduits  22 ,  28 , respectively, contact the 160 μm o.d. capillary. Once ends  46 ,  48  of conduits  22 ,  28 , respectively, are positioned in the main passage of connection sleeve  26 , the 160 μm o.d. capillary is removed from passages  40 . Thus, the 160 μm o.d. capillary acts as a gauge to ensure that end surfaces  50 ,  52  of conduits  22 ,  28 , respectively, are spaced apart by approximately 160 μm. 
     In some embodiments, container  12  is made from Delrin® material and has the following dimensions: 2.25 inches in height, 1.5 inches in width, and 1.25 inches in depth. In such embodiments, a 0.5 inch hole may be drilled into the center of container  12  to contain fluid  14 , such as a buffer and/or matrix material. Container  212  may also be made from Delrin® material and have dimensions similar to container  12 . In addition, Teflon® o-rings may be used to seal and sustain the pressures applied to containers  12 ,  212 . These o-rings may be present between cap  60  and container  12  and between cap  260  and container  212 . In addition, nuts  23 ,  223  have sleeves that seal against the respective conduits  18 ,  22 ,  28 ,  220  and electrodes  218 ,  228  when nuts  23 ,  223  are tightened in a manner well-known to those skilled in the art. 
     The pressure applied to container  12  by source  16  or source  116 , as the case may be, affects the rate at which effluent flows from deposition conduit  28 . In some embodiments, the pressure applied to the interior region  24  of container  12  is variable between 5 and 30 pounds per square inch (p.s.i.). In addition, the rate at which fluid enters mixing space  54  through conduit  22  is controllable by, for example, varying the manner in which source  20  is operated, such as by varying a pressure differential between source  20  and container  12  (in the case of device  10 ); varying the pump speed of apparatus  120 , varying the amount that one or more valves of apparatus  120  is opened or closed, or varying the operation of the splitter of apparatus  120  (in the case of device  110 ); or varying the electrical potential applied to electrode  218  by power supply  216  (in the case of device  210 ). 
     In embodiments having conduits  22 ,  28  and sleeve  26  dimensioned as described above, the fluid  14  flows through openings  40  into mixing space  54  at a rate of approximately 160 nanoliters per minute, the fluid from the liquid chromatography apparatus of  FIG. 3  flows through conduit  22  into mixing space  54  at a rate of approximately 150 nanoliters per minute, and the fluid from the capillary electrochromatography apparatus of  FIG. 4  flows through conduit  22  into mixing space  54  at a rate of approximately 40 nanoliters per minute. It should be appreciated that the diameter or size of openings  40 , the number of openings  40 , the diameter or size of passage  56 , the diameter or size of passage  62 , the size of mixing space  54 , the spacing between end surfaces  50 ,  52 , the viscosity of the first fluid, and the viscosity of the second fluid all have an effect on the rate at which the effluent mixture of the first and second fluids flow from conduit  28 . The above-listed parameters also have an effect on the proportions of the first and second fluids in the effluent mixture emerging from conduit  28 . By routine experimentation, desired flow rates of effluent emerging from conduit  28  and desired proportions of the first and second fluids in the effluent emerging from conduit  28  may be obtained. 
     In one embodiment of device  210 , a stationary phase material packed into conduit  22  consisted of 5% T, 60% C {Hjerten&#39;s designation (Hjerten, S.  Arch. Biochem. Biophys . 1962 , Supl  1, 147-151) defines T and C and is hereby incorporated by reference herein}, 3% polyethylene glycol (PEG, MW 10,000), 40% 2-cyanoethylacrylate (CEA) and 10% vinylsulfonic acid. In this embodiment, a monomer solution or reaction mixture may be prepared by dissolving 10.0 milligrams (mg) acrylamide, 30 mg N,N′-methylene-bis-acyrlamide, 16.0 microliters (μL) CEA, 12.4 μL vinylsulfonic acid and 30 mg PEG in 0.5 milliliters (mL) formamide and 0.5 mL 100 millimoles (mM) Tris −150 mM boric acid (pH 8.2). Also in this embodiment, polymerization may be initiated using 4 μL of 20% (v/v) N,N,N′,N′-tetramethylenediamine (TEMED) and 4 μL of 40% ammonium persulfate added to 0.5 mL of the above monomer solution heated to 50 degrees Celsius. This polymerization proceeds for a fairly lengthy period of time, such as overnight, at room temperature. Subsequently, conduit  22  with such stationary phase material is flushed and conditioned using a solution consisting of 50:50 (v/v) acetonitrile: 5 mM phosphate buffer at pH 3.0. Acrylamide and N,N′-methylene-bis-acrylamide are available from BioRad Laboratories of Hercules, Calif. Ammonium persulfate, TEMED, 3-methacryloxypropyltrimethoxysilane (Bind-Silane), and PEG are available from Sigma Company or St. Louis, Mo. Vinylsulfonic acid (sodium salt, 25% (v/v)), CEA, and formamide are available from Aldrich of Milwaukee, Wis. 
     As mentioned above, conduit positioner  30  is coupled to a lower region of conduit  28  and is operable to position conduit  28  relative to any suitable fluid receiver, such as substrate  32  or MALDI plate  132 , and the fluid receiver is coupled to a substrate positioner  33  that is operable to position the fluid receiver relative to conduit  28 .  FIGS. 5 and 6  show fluid treatment device  10  being used with positioners  30 ,  33 . However, any fluid treatment device, including devices  10 ,  110 ,  210  disclosed herein, may be used with positioners  30 ,  33  to deposit effluent, such as effluent emerging from conduit  28 , on a fluid receiver. Illustratively, conduit positioner  30  comprises an arm  70 , a coupler  72  that couples the lower region of conduit  28  to a first end  74  of arm  72 , and a driver  76  that acts upon a second end  78  of arm  70  to pivot arm  70  about a pivot axis  80  as shown in FIG.  5 . In some embodiments, the orientation of coupler  72  relative to arm  70  is adjustable to change the orientation of the lower end of conduit  28  relative to arm  70 . 
     Operation of driver  76  pivots arm  70  about axis  80  to move the lower end of conduit  28  between a raised position and a lowered position. Illustrative driver  76  comprises a motor  82  and a cam  84  that is mounted to an output shaft  86  of motor  82 . Operation of motor  82  rotates output shaft  86  along with cam  84  so that a cam surface  88  of cam  84  wipes against a bottom surface  90  of arm  70 , thereby pivoting arm about axis  80 . Substrate positioner  30  has a biaser (not shown), such as a torsion spring or tension spring, that acts between arm  70  and some other stationary structure, such as illustrative flange  92  to which arm  70  is pivotably coupled, to bias end  78  of arm  70  into engagement with cam  84 . In some alternative embodiments, driver  76  comprises a linear stepper motor, and in other alternative embodiments, driver  76  comprises a solenoid. 
     In one mode of operation of positioners  30 ,  33 , arm  70  is pivoted by driver  76  to a first orientation having the lower end of conduit  28  in the lowered position, either touching or in close proximity to the fluid receiver, such as illustrative MALDI plate  132 , and then arm  70  is held stationary by driver  76 . When arm  76  is held stationary in the first orientation, substrate positioner  33  may then be operated to maneuver the fluid receiver beneath the lower end of conduit  28  so that a substantially continuous line, film, or trace of effluent is deposited on the fluid receiver in a desired pattern. In an illustrative example of the first mode of operation of positioners  30 ,  33 , shown in  FIGS. 5 and 7 , continuous trace  94  is deposited on MALDI plate  132  in a serpentine pattern. 
     In a second mode of operation of positioners  30 ,  33 , arm  70  is cyclically reciprocated between the first orientation and a second orientation so that the lower end of conduit  28  is cycled repeatedly between the lowered position, either touching or in close proximity to the fluid receiver, and the raised position, spaced from the fluid receiver by a sufficient distance to prevent effluent from being deposited on the fluid receiver. Such reciprocation of arm  70  occurs, for example, when shaft  86  and cam  84  are continuously rotated. As the lower end of conduit  28  is cycled between the raised and lowered positions, substrate positioner  33  may be operated to index the fluid receiver in a desired manner so that spots or aliquots  96  of effluent are deposited on the fluid receiver in a desired two-dimensional array. An example of such a two dimensional array of aliquots  96  deposited on MALDI plate  132  is shown in FIG.  8 . 
     According to this disclosure, positioners  30 ,  33  and conduit  28  cooperate to provide a device for placement of effluent on a substrate or any other suitable fluid receiver. The effluent may be delivered to conduit  28  by any means, including the fluid treatment devices disclosed herein. In one illustrative embodiment, positioner  33  comprises an X-Y table  98 , as shown diagrammatically in  FIG. 5 , and in another embodiment, positioner  33  comprises a reel-to-reel tape drive  100 , as shown in FIG.  6 . X-Y table  98  supports the fluid receiver, such as plate  132 , for bidirectional horizontal movement in an x-direction, indicated by double-headed arrow  102  in  FIG. 5 , and in a y-direction, indicated by double-headed arrow  104  in FIG.  5 . Y-direction  104  is orthogonal to x-direction  102 . Flange  92  and drive  76  may be coupled to X-Y table  98  as shown diagrammatically in FIG.  5 . Alternatively, flange  92  and drive  76  may be coupled to some other structure adjacent table  98 . 
     Reel-to-reel tape drive  100  comprises a housing  150 , a source reel  152  supported for rotation relative to housing  150 , a destination reel  154  supported for rotation relative to housing  150 , and a motor-driven capstan pinch roller assembly  156  that operates to move a polymer tape  232  from reel  152  to reel  154  across a tape-support member  158 . In this embodiment, tape  232  serves as the fluid receiver. Assembly  156  includes a motor  160 , an upper roller  162 , and a lower roller  164 . Tape  232  is routed between rollers  162 ,  164  in contact therewith. At least one of rollers  162 ,  164  is driven by motor  160  to feed tape  232  across member  158 . In alternative embodiments, drive  100  has at least one motor in housing  150  that drives one or both reels  152 ,  154  to move tape  232  from reel  152  to reel  154  across member  158 . Flange  92  and drive  76  may be coupled to housing  150  of drive  100  or to some other structure adjacent drive  100 . 
     In the first mode of operation, in which arm  70  is held stationary in the first orientation, effluent exiting conduit  28  is deposited on tape  232  as a substantially continuous straight-line trace as tape  232  is driven from reel  152  to reel  154 . In the second mode of operation, in which arm  70  is reciprocated cyclically between the first and second orientations, effluent exiting conduit  28  is deposited on tape  232  as a series of spots or aliquots  96  as tape  232  is driven from reel  152  to reel  154 . An example of spots  96  on a segment of tape  232  produced by the second mode of operation is shown in FIG.  9 . 
     In the illustrative examples of  FIGS. 7-9 , the effluent of trace  94  and spots  96  comprises an α-cyano-4-hydroxycinnamic acid solution in acetonitrile/water at a concentration of 10 milligrams per milliliter (mg/ml). The diameters of spots  96  in the examples of  FIGS. 8 and 9  are approximately 70 μm. However, varying the speed that drive  76  moves arm  70  between the first and second orientations and varying the speed of the fluid receiver, such as plate  132  or tape  232 , affects the spot position, spacing, and size. In some embodiments, conduit positioner  30  and substrate positioner  33  have separate controllers (i.e. computers, microcontrollers, programmable logic controllers, microprocessors, and the like) and associated user inputs to permit users to control positioners  30 ,  33  separately. Software may be stored in memory devices of such controllers and executed by the controllers to command the operation of positioners  30 ,  33 . In other embodiments, a single controller and associated user inputs are coupled to both positioners  30 ,  33  to coordinate the operation of positioners  30 ,  33  simultaneously. 
     Fluid treatment devices  10 ,  110 ,  210  operate such that effluent emerges continuously from the lower end of conduit  28  due to the continuous pressurization of container  12  by source  16  or source  116 , as the case may be. Thus, when the lower end of conduit  28  is held by arm  70  away from the fluid receiver, surface tension of the effluent adjacent the opening in the lower end of conduit  28  prevents the effluent from separating from the lower end of conduit  28 . When the lower end of conduit  28  moves into the lowered position, the effluent adjacent the opening in the lower end of conduit  28  contacts and adheres to the fluid receiver, such as substrate  32 , plate  132 , or tape  232 . 
     The positioners  30 ,  33  disclosed herein allow for the controlled, high-volume, high-speed, automated placement of effluents on fluid receivers, such as substrates, plates, and tapes. When used with fluid treatment devices, such as devices  110 ,  210 , having separator apparatus that separates analytes into constituent molecules, positioners  30 ,  33  are able to produce quickly, a large number of samples to be analyzed using MALDI/TOF/MS. In addition, due to pressurization of container  12 , which results in effluent moving from mixing space  54  through conduit  28 , deposition of the effluent emerging from conduit  28  on fluid receivers may take place in the ambient atmosphere. This is in contrast to some prior art systems in which effluent is deposited on MALDI plates in a vacuum. 
     Illustrative substrate positioner  33 , therefore, serves as a moveable, controllable workpiece holder and illustrative conduit positioner  30  serves as a moveable, controllable holder for a sample-dispensing conduit  28  for preparing samples for MALDI MS analysis. Information stored in memory devices of the controllers associated with positioners  30 ,  33  may be combined with or correlated to information about the source and/or test results of various traces, portions, or aliquots of the sample material that is stored in a database resident on another computer device. 
     As mentioned previously, the fluid treatment devices and the effluent placement devices disclosed herein are used to deposit effluent on a substrate for subsequent analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF/MS). Effluents deposited on substrates in the manner described herein may also be analyzed with MS analyzers employing other techniques, such as, for example, quadrapole time-of-flight (QTOF) techniques, Fourier transform ion cyclotron resonance (FTICR) techniques, and ion trap (IT) techniques. In some such embodiments, the effluent placed on the substrate comprises a mixture of an analyte and a matrix material. Examples of graphs produced by MALDI/TOF/MS are shown in  FIGS. 10 and 11 . The mass spectra examples in  FIGS. 10 and 11  were produced with a Voyager-DE™ RP Biospectrometry™ Workstation instrument which was equipped with a pulsed nitrogen laser (337 nanometers) and which is available from Applied Biosystems of Framingham, Mass. The MALDI mass spectra were acquired at 25 kV and 18 kV accelerating voltage in the positive-ion mode, while the low-mass gate was used to discard ions with m/z values of less than 400. All acquired spectra were smoothed by applying a 19-point Savitzky-Golay smoothing routine, such as is described in Savitzky, A.; Golay, M. J. E.  Anal. Chem ., 1964, 36, 1627-1638 which is hereby incorporated by reference herein. The instrument was calibrated with a standard dextrin ladder. 
     The example shown in  FIG. 10  is graph of a CEC-MALDI analysis of N-glycans derived from Ribonuclease B showing an “a” trace depicting a mass spectrum of a mixture of the N-glycans and showing “b-f” traces depicting the spectra of different aliquots deposited on a MALDI plate after CEC separation. The example shown in  FIG. 11  is a graph of a CEC-MALDI analysis of Dextrin showing an “a” trace depicting a mass spectrum of the Dextrin mixed with a matrix material and showing “b-f” traces depicting the spectra of different aliquots deposited on a MALDI plate after CEC separation. Ribonuclease B is available from Sigma Company of St. Louis, Mo. Dextrin DE 10 is available from Fluka of Buchs, Switzerland. 
     Although the invention has been described in detail with reference to certain illustrative embodiments, variations and modifications exist with the scope and spirit of this disclosure as described and defined in the following claims.