Patent Publication Number: US-2009218287-A1

Title: Solid phase extraction apparatuses and methods

Description:
PARTIES TO A JOINT RESEARCH AGREEMENT 
     US Synthetic Corporation and Brigham Young University are parties to a joint research agreement. 
     BACKGROUND 
     Solid phase extraction (“SPE”) is a well-known technique for concentrating and/or purifying a liquid sample for analysis. Many conventional SPE apparatuses include a syringe or syringe-like body in which a stationary phase is disposed. Using positive pressure from a plunger or application of a vacuum, a liquid sample can be passed through the stationary phase. The stationary phase selectively adsorbs at least one type of analyte of the liquid sample as the liquid sample is passed through the stationary phase. The at least one type of analyte is typically extracted by washing the stationary phase with a solvent having an affinity for the adsorbed at least one type of analyte and collecting the solvent including the at least one type of analyte. Chemical analysis may then be performed on the collected solvent and analyte using, for example, chromatography or another analytical technique. 
     The stationary phase is typically composed of silica particles having selected functional groups bonded to surfaces of the silica particles that are formulated to bond with specific analytes. Chemical stability of the stationary phase is a concern because the liquid samples and/or solvents used in SPE processes can chemically interact with the stationary phase. In addition to possibly degrading the stationary phase, such chemical interaction can reduce the accuracy of any subsequent chemical analysis performed on the isolated analyte. Despite the availability of many different types of stationary phases, manufacturers and users of SPE apparatuses continue to seek improved stationary phases suitable for SPE that are more chemically resistant to aggressive liquid samples and/or solvents commonly used in SPE processes. 
     SUMMARY 
     Embodiments of the present invention relate to SPE apparatuses that include a sintered polycrystalline diamond (“PCD”) stationary phase and methods of performing SPE using a sintered PCD stationary phase. In one embodiment of the present invention, a method of capturing at least one constituent from a liquid sample is disclosed. A liquid sample may be flowed through an SPE stationary phase that comprises sintered diamond grains. At least a portion of the at least one constituent of the liquid sample may be captured in the SPE stationary phase as the liquid sample flows through the SPE stationary phase. In certain embodiments of the present invention, the at least one constituent (e.g., one or more types of analytes) captured in the SPE stationary phase may be eluted from the stationary phase. 
     In another embodiment of the present invention, an SPE cartridge includes a housing that comprises a proximal first end including a housing inlet, a distal second end including a housing outlet, and an interior space extending between the housing inlet and the housing outlet. An SPE stationary phase may be positioned within the interior space and includes an inlet and an outlet. The SPE stationary phase comprises a mass of sintered diamond grains including a plurality of passageways extending therethrough between the inlet and the outlet. In an embodiment of the present invention, the housing inlet may exhibit a lateral dimension that is greater than that of a lateral dimension of the housing outlet. In another embodiment of the present invention, the diamond grains of the SPE stationary phase include interior diamond grains surfaces that define the passageways, with at least some of the interior diamond grains surfaces being etched. 
     In yet another embodiment of the present invention, an SPE apparatus comprises an SPE stationary phase disk including an inlet face and an opposing outlet face. The SPE stationary phase disk comprises a mass of sintered diamond grains including a plurality of passageways extending therethrough between the inlet face and the outlet face. The SPE apparatus further comprises a holder configured to hold at least the SPE stationary phase disk so that a fluid can pass through the SPE stationary phase disk. The SPE apparatus also may include a container configured to be in fluid communication with the outlet face of the SPE stationary phase disk. 
     In other embodiments of the present invention, an SPE stationary phase of an SPE apparatus may comprise un-sintered diamond particles. For example, in one embodiment, an SPE stationary phase of an SPE apparatus may be in form of a mass of un-sintered diamond particles with exterior surfaces of the diamond particles being etched to increase the surface area thereof. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The drawings illustrate several embodiments of the present invention, wherein identical reference numerals refer to identical elements or features in different views or embodiments shown in the drawings. 
         FIG. 1A  is a cross-sectional view of an SPE apparatus including a PCD stationary phase according to one embodiment of the present invention. 
         FIG. 1B  is a cross-sectional view of the SPE apparatus shown in  FIG. 1A  including a filter positioned adjacent to an inlet of the PCD stationary phase and a seal element extending peripherally about the PCD stationary phase according to another embodiment of the present invention. 
         FIG. 2A  is a perspective view of the PCD stationary phase shown in  FIG. 1 . 
         FIG. 2B  is top plan view of the PCD stationary phase shown in  FIG. 2A . 
         FIG. 2C  is a cross-sectional view of the PCD stationary phase shown in  FIG. 2A  taken along line  2 C- 2 C. 
         FIG. 3A  is a schematic cross-sectional view that illustrates passing a liquid sample through the PCD stationary phase shown in  FIG. 1  using a plunger so that one or more constituents of the liquid sample may be captured by the PCD stationary phase according to one embodiment of the present invention. 
         FIG. 3B  is a schematic cross-sectional view that illustrates passing an eluting solution through the PCD stationary phase shown in  FIG. 1  using a plunger to elute the one or more constituents captured by the PCD stationary phase according to one embodiment of the present invention. 
         FIG. 4  is a schematic cross-sectional view that illustrates drawing an eluting solution through the PCD stationary phase shown in  FIG. 1  using a vacuum pump to elute the one or more constituents captured by the PCD stationary phase according to one embodiment of the present invention. 
         FIG. 5  is a partial, exploded perspective view of an SPE apparatus according to yet another embodiment of the present invention. 
         FIG. 6  is a side elevation view showing the SPE apparatus of  FIG. 5  assembled. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of the present invention relate to SPE apparatuses that include a sintered PCD stationary phase and methods of performing SPE to capture at least one constituent of a liquid sample using a sintered diamond stationary phase. The disclosed SPE apparatuses may be used for concentrating and/or purifying a liquid sample prior to performing chemical analysis, such as chromatography, mass spectrometry, or another suitable analytical technique. 
       FIG. 1A  is a cross-sectional view of an SPE apparatus/cartridge  100  configured to concentrate and/or purify a liquid sample according to one embodiment of the present invention. The SPE cartridge  100  comprises a housing  102  including a proximal first end  106  having a housing inlet  108  and a distal second end  110  having a housing outlet  112 . An interior space  113  defined by the housing  102  extends between the housing inlet  108  and the housing outlet  112 , and the interior space  113  is also in communication with the housing inlet  108  and the housing outlet  112 . In the illustrated embodiment, the housing inlet  108  may exhibit a lateral dimension  114  (e.g., a diameter) that is greater than that of a lateral dimension  116  (e.g., a diameter) exhibited by the housing outlet  112 . However, in other embodiments, the lateral dimension  114  of the housing inlet  108  may be equal to or less than the lateral dimension  116  of the housing outlet  112 . The housing  102  may be formed from a polymeric material (e.g., polypropylene), a ceramic (e.g., a glass or other inorganic material), or another suitable material. 
     Still referring to  FIG. 1A , a PCD stationary phase  118  may be positioned within the interior space  113 . The PCD stationary phase  118  includes an inlet  120  and an outlet  122  through which a liquid (e.g., a liquid sample or an eluting solution) may flow between. In the illustrated embodiment, the PCD stationary phase  118  is depicted as a cylindrical body. However, the PCD stationary phase  118  may exhibit any suitable geometry, without limitation, such as a disk-shaped geometry. A frit or filter (not shown) may be positioned adjacent to the outlet  122  to help retain the stationary phase  118  in the housing  102 , if desired. Referring to  FIG. 1B , in certain embodiments of the present invention, a filter  124  may be positioned adjacent to the inlet  120  of the PCD stationary phase  118  to help prevent any particulate matter contained in a liquid sample from clogging the PCD stationary phase  118 . Additionally, a seal member  126  may extend peripherally about the PCD stationary phase  118  to form a seal between the PCD stationary phase  118  and an interior of the housing  102  to help prevent a liquid sample from flowing between the interior of the housing  102  and the PCD stationary phase  118 . The seal member  126  may comprise a polymeric material (e.g., a heat-shrink polymeric sleeve), a curable material, a metallic material, or any material capable of inhibiting flow of fluid between the housing  102  and the PCD stationary phase  118 . The housing  102  may be formed about, molded to, or otherwise sealed to the PCD stationary phase  118 . 
       FIGS. 2A-2C  are perspective, top plan, and cross-sectional views, respectively, of the PCD stationary phase  118  shown in  FIGS. 1A and 1B . The PCD stationary phase  118  comprises a mass of sintered diamond grains including a network of at least partially interconnected pores that form a plurality of passageways  200  (shown in phantom in  FIG. 2A ). The passageways  200  extend between the inlet  120  and the outlet  122  and are structured to enable fluid (e.g., a liquid or gas) to flow through the inlet  120  and out of the outlet  122  (or vice versa). The PCD stationary phase  118  provides a highly chemically-resistant stationary phase that may exhibit a relatively high internal surface area and flow rate for a given pressure compared to a mass of unsintered diamond particles. Further, the PCD stationary phase  118  may be easier to handle and be capable of withstanding higher pressures than a mass of unsintered diamond particles. 
     The operation of the SPE cartridge  100  is best understood with reference to  FIGS. 3A and 3B . Referring to  FIG. 3A , a liquid sample  300  (e.g., an aqueous solution or an organic solution) may be disposed within the interior space  113  of the housing  102 . The liquid sample  300  may include a matrix with one or more types of analytes dissolved therein and/or dispersed therethrough. The liquid sample  300  may be urged through the PCD stationary phase  118  using, for example, a plunger  302  that is axially displaced within the interior space  113  of the housing  102 , a syringe (not shown), or another pressure-generating device configured to generate pressure capable of urging the liquid sample  300  (e.g., positive pressure). In other embodiments of the present invention, compressed air or other gas flowed through a pressurized air line (not shown) may be used to force the liquid sample  300  through the PCD stationary phase  118 . As the liquid sample  300  passes through the PCD stationary phase  118 , at least one constituent  304  (e.g., at least one type of analyte) of the liquid sample  300  may selectively bind to the PCD stationary phase  118  within the passageways  200  ( FIGS. 2A-2C ). In certain embodiments of the present invention, the PCD stationary phase  118  is formulated to preferentially bind to a plurality of different constituents (e.g., a plurality of different types of analytes) of the liquid sample  300 . A matrix  306  of the liquid sample  300  does not bind to the PCD stationary phase  118  and exits through the outlet  122  of the PCD stationary phase  118  and the housing outlet  112  of the housing  102 . The matrix  306  may be a solvent in which the at least one constituent is dissolved in or another liquid that acts as a carrier medium for the at least constituent. The matrix  306  may be repeatedly urged through the PCD stationary phase  118 , if desired. 
     Still referring to  FIG. 3A , the SPE cartridge  100  may be connected to a container  308  (e.g., a suction flask) via, for example, a gasket  310 . The container  308  may hold a collection tube  312  that collects the matrix  306  that flows through the PCD stationary phase  118  and out of the housing outlet  112 . The container  308  may further include a vacuum port  313  (shown with a plug  315  inserted therein) configured to be operably connected to a vacuum pump (not shown). In one mode of operation according to an embodiment of the present invention, the SPE cartridge  100  may be used to purify the liquid sample  300 . In such an embodiment, the matrix  306 , which may include many different components, may be further analyzed using chromatography, mass spectrometry, or another suitable technique. 
     Referring to  FIG. 3B , in a second mode of operation according to another embodiment of the present invention, the SPE cartridge  100  may be employed to capture one or more selected analytes. In such an embodiment, the collection tube  312  may be removed and replaced with a cleaned or different collection tube  314 . The at least one constituent  304  (i.e., at least one type of analyte) captured by the PCD stationary phase  118  may be eluted by passing an eluting solution  316  disposed within the interior space  113  of the housing  102  through the PCD stationary phase  118  using the plunger  302 . The eluting solution  316  may exhibit a selectivity to preferentially remove or dissolve the at least one constituent  304  (or multiple different analytes) bound to the internal surfaces of the diamond grains defining the passageways  200  ( FIGS. 2A-2C ). The eluting solution  316  and the at least one constituent  304  dissolved therein or dispersed therethrough collected in the collection tube  314  may be analyzed using, for example, chromatography, mass spectrometry, or another suitable analytical technique. 
     Referring to  FIG. 4 , in other embodiments of the prevent invention, the liquid sample  300  and the eluting solution  316  may be urged through the PCD stationary phase  118  using a vacuum pump (i.e., negative pressure). For example, in another embodiment of the present invention illustrated in  FIG. 4 , a vacuum pump  400  may be operably connected to the vacuum port  313  of the container  308  via a fluid line  402  that is configured to draw, for example, the eluting solution  316  (or the liquid sample  300 ) through the PCD stationary phase  118 . 
     In yet another embodiment of the present invention, the liquid sample  300  and/or the eluting solution  316  may be separately urged through the PCD stationary phase  118  by centrifuging the SPE cartridge  100  containing the liquid sample  300  or the eluting solution  316 . For example, a number of the SPE cartridges  100  may be simultaneously rotated in a centrifuge to elute at least one type of analyte from a stationary phase. 
     In certain embodiments of the present invention, multiple SPE cartridges  100  may be used in conjunction with a vacuum manifold apparatus that may be conventional in construction. Such a vacuum manifold apparatus may include provisions for simultaneously processing multiple SPE cartridges  100 . In other embodiments of the present invention, an SPE apparatus may be configured as a well plate including a plurality of wells, with each well configured similarly to the SPE cartridge  100 . For example, each well may be defined by a housing similarly configured to the housing  102  shown in  FIG. 1  that are each integrally formed with each other. It is also contemplated that in other embodiments of the present invention, the SPE cartridge  100  may be integrated into a chromatography system or other analytical instrument. For example, the liquid sample  113  may be purified in situ by the SPE cartridge  100  prior to being analyzed by, for example, a liquid chromatography unit of a liquid chromatography system. 
     Turning again to  FIGS. 2A-2C , in one embodiment of the present invention, interior surfaces of the diamond grains that define the passageways  200  are capable of capturing certain types of chemicals. For example, the interior surfaces of the diamond grains may include hydroxyl groups bonded thereto capable of selectively bonding with certain hydrophilic chemical liquid samples flowed through the passageways  200  of the PCD stationary phase  118 . U.S. Patent Application Publication US2004/0118762 to Xu et al., the disclosure of which is incorporated herein in its entirety by this reference, discloses methods for functionalizing diamond surfaces that are chemically stable in highly basic solutions. 
     In yet another embodiment of the present invention, a selected stationary phase (e.g., a liquid, an adsorbent, or another substance) may at least partially coat or cover interior diamond surfaces of the PCD stationary phase  118  that define the passageways  200 . Examples of suitable stationary phases that may be disposed within the passageways  200  are polymeric stationary phases, porous graphitized carbon, C 6  hydrocarbons, C 8  hydrocarbons, C 12  hydrocarbon, C 18  hydrocarbons, cyclohexyl, phenyl, amino, carboxyl, sulfonic acid, quarternary amine, or another suitable stationary phase. Accordingly, as used herein, the phrase “stationary phase” may encompass a mass of sintered diamond grains or a mass of un-sintered diamond particles in which interior surfaces of the diamond grains or diamond particles may be functionalized. As used herein, the phrase “stationary phase” may also encompass a mass of sintered diamond grains or a mass of un-sintered diamond particles including a stationary phase disposed therein. In yet a further embodiment of the present invention, interior surfaces of the diamond grains that define the passageways  200  may be etched to be roughened and increase the surface area thereof, which enables higher loading of the PCD stationary phase  118  per unit volume compared to when the diamond grains are not etched. 
     The PCD stationary phase  118  shown in FIGS.  1 A and  2 A- 2 C may be formed by sintering diamond particles having a selected particles size distribution. For example, prior to sintering, the diamond particles may have an average particle size from about 1 nm to about 1000 μm, and more typically from about 2 μm to about 150 μm. In one embodiment of the present invention, the PCD stationary phase  118  is formed by sintering diamond particles using an ultra-high pressure, ultra-high temperature (“HPHT”) process. The sintering may be effected in an ultra-high pressure press at process conditions of, for example, a pressure of at least about 20 kilobar (e.g., about 40 kilobar to about 70 kilobar) and a temperature of at least about 500° C. (e.g., about 1000° C. to about 1600° C.) for a time sufficient to consolidate and form a coherent mass of bonded diamond grains. The size of the passageways  200  formed in the PCD stationary phase  118  may be controlled, predominately, by proper selection of the diamond particle size and sintering pressure. For example, each passageway  200  may exhibit a lateral dimension (e.g., a diameter) of about 10 angstroms to about 1000 μm. 
     The interior surfaces of the diamond grains that define the passageways  200  may be etched to be roughened and increase the surface area thereof by exposing the interior surfaces to a suitable etchant. For example, suitable etchants capable of etching diamond include, but are not limited to, plasma etching (e.g., plasma activated hydrogen, inductively coupled plasma oxygen etching, or a SF6/O 2  plasma mixtures), oxygen etching (e.g., molecular oxygen, water vapor, oxygen plasma, or molten KNO 3 ) and molten rare earth metal(s) (e.g., lanthanum, cerium, or alloys thereof). However, in another embodiment of the present invention, the diamond particles may be exposed to one or more of the aforementioned etchants and, subsequently, subjected to a HPHT sintering process to form the PCD stationary phase  118 . In such an embodiment, the interior surfaces of the diamond grains that define the passageways  200  may retain an etched surface despite being subjected to the HPHT processing. 
     Further embodiments of the present invention are directed to an SPE apparatus that employs a PCD stationary phase disk. A stationary phase disk may be utilized for relatively large volume liquid samples and/or relatively high flow rates compared to the PCD stationary phase  118  shown in  FIG. 1A  that is configured as an elongated body.  FIGS. 5 and 6  are a partial, exploded perspective view and a side elevation view, respectively, of an SPE apparatus  500  that employs a PCD stationary phase disk  501  according to yet another embodiment of the present invention. Referring to  FIG. 5 , the SPE apparatus  500  includes a funnel  502 , a base  504 , and the PCD stationary phase disk  501  received within the base  504 . In certain embodiments of the present invention, a disk support  506  in the form of a metal screen or other porous medium may be provided on which the PCD stationary phase disk  501  may be supported within the base  504 . The funnel  502  includes an inlet  508  and an outlet  510  and the base  504  also includes an inlet  512  and an outlet  514 . The outlet  510  of the funnel  502  may be located proximate to a flange  516  (as illustrated), and the inlet  512  of the base  504  may be located proximate to a flange  518 . The PCD stationary phase disk  501  comprises a mass of sintered diamond grains defining passageways (not shown) extending between an inlet face  520  and an opposing outlet face  522  thereof. The PCD stationary phase disk  501  may be made from the same or similar materials and may be manufactured according to the same or similar processes as the PCD stationary phase  118  shown in FIGS.  1  and  2 A- 2 C. 
       FIG. 6  shows the SPE apparatus  500  assembled. The SPE apparatus  500  further includes a holder  524  (e.g., a spring clamp or other suitable clamp) configured to clamp and hold the flange  516  of the funnel  502  and the flange  518  of the base  504  so that the outlet  510  of the funnel  502  is in fluid communication with the PCD stationary phase disk  501  disposed within the base  504 , the outlet  514  of the base  504 , and a low pressure chamber defined by a container  526  (e.g., a suction flask). A gasket  528  or other seal element may be used to generally seal the low pressure chamber of the flask  526  from the ambient environment. A vacuum pump  530  may be operably coupled to the low pressure chamber of the container  526 . If desired, a collection tube  532  may be contained within low pressure chamber  526  to collect fluids, such as a liquid sample and/or an eluting solution. 
     The operation of the SPE apparatus  500  is similar to the operation of the SPE cartridge  100 . For example, a liquid sample may be poured into the funnel  502  and drawn through the PCD stationary phase disk  501  using the vacuum pump  530  so that at least one constituent (e.g., at least one type of analyte) of the liquid solution may be captured by the PCD stationary phase disk  501 . A matrix of the liquid sample may be collected in the collection tube  532 . If desired, the collection tube  532  may be cleaned or replaced, and then the at least one constituent captured by the PCD stationary phase disk  501  may be eluted by drawing an eluting solution poured into the funnel  502  through the PCD stationary phase disk  501 . The eluting solution and the eluted at least one constituent may also be collected in the collection tube  532  and further analyzed using a suitable analytical technique. 
     The stationary phases of the SPE apparatuses  100  and  500  are described above as being a mass of sintered diamond grains. However, in other embodiments of the present invention, the stationary phase may be in form of a mass of un-sintered diamond particles with exterior surfaces of the diamond particles being etched in accordance with the aforementioned etching techniques. 
     Although the present invention has been disclosed and described by way of some embodiments, it is apparent to those skilled in the art that several modifications to the described embodiments, as well as other embodiments of the present invention are possible without departing from the spirit and scope of the present invention. Additionally, the words “including,” “having,” and variants thereof (e.g., “includes” and “has”) as used herein, including the claims, shall have the same meaning as the word “comprising” and variants thereof (e.g., “comprise” and “comprises”) and mean “including, but not limited to.”