Solid-phase microextraction devices and methods of forming

Abstract

A solid-phase microextraction device is disclosed that includes a substrate having a flat surface and a sorbent layer disposed on the flat surface. The flat surface is defined by a base edge, a spray edge disposed distally across the substrate from the base edge, the spray edge including a tapered tip extending away from the base edge, a first lateral edge extending from the base edge to the tapered tip, and a second lateral edge extending from the base edge to the tapered tip, the second lateral edge disposed distally across the substrate from the first lateral edge. The sorbent layer extends a sampling length from the spray edge toward the base edge and includes sorbent particles. A method for forming a solid-phase microextraction device is disclosed that includes applying the sorbent layer onto the flat surface using at least one of screen printing, stencil printing, or additive manufacturing.

Description

[Technical Field]

[0001] (Related Applications) This application claims the benefit of and priority to U.S. Provisional Application No. 62 / 941,325, filed November 27, 2019, entitled "Method for Manufacturing Smart Coated Substrates," which is incorporated herein by reference in its entirety. [Background technology]

[0002] This application is directed to solid-phase microextraction devices and methods for forming solid-phase microextraction devices. In particular, this application is directed to solid-phase microextraction devices that include a sorbent layer disposed across less than the entire width of the device, and methods for forming solid-phase microextraction devices with stencils.

[0003] Coated Blade Spray (CBS) is a solid phase microextraction (SPME)-based analytical technique previously described in the literature (Pawliszyn et al.; U.S. Pat. No. 9,733,234) that facilitates the collection of analytes of interest from a sample and their subsequent direct interface to a mass spectrometry system via a substrate spray event (i.e., electrospray ionization).

[0004] "Coated blade spray," "CBS blade," and "blade device" are used synonymously herein.

[0005] The blade device is typically a thin, flat sheet with a sharp tip (tip angle of approximately 8-50°) and is typically fabricated on a conductive substrate such as stainless steel. As an SPME device, the substrate is a thin, flat sheet with a sharp tip (tip angle of approximately 8-50°) and is typically fabricated on a conductive substrate such as stainless steel. 18The polymer particles are partially coated with an extraction phase consisting of a polymeric extraction material (e.g., silica modified with hydroxyl groups) and a binder (e.g., polyacrylonitrile (PAN)). The function of the polymer particles is to concentrate the analytes of interest from the sample matrix while minimizing interference. The binder simultaneously accomplishes multiple functions, including but not limited to strongly attaching the polymer particles to the solid substrate, protecting the solid substrate from potential adhesion of matrix components, and preventing the concentration of ionic species on the polymer particles. Similarly, the binder provides strong mechanical adhesion of the particles to the surface of the substrate without degrading or masking the analyte collection properties of the extraction particles. When a layer of binder is applied to a solid substrate without the polymeric extraction material / particles, it is known as a primer layer. The process of applying such a primer layer is called "priming." For direct mass spectrometry (MS) applications, thin coatings that promote rapid capture and release of target analytes have been preferred. As a direct connection to MS instruments, CBS instruments require pre-wetting of the extraction material to elute the analytes collected on it. A differential potential is then applied between the uncoated area of ​​the substrate and the inlet of the MS system, generating an electrospray at the tip of the CBS device.

[0006] Known methods for fabricating CBS devices include dip coating and spray coating. Additional known methods for fabricating CBS devices include sputtering, spin coating, doctor blading, sol-gel chemistry, and electrospinning. For flat substrates, dip coating has been the preferred method because it can form a uniform, thin coating while minimizing waste of coating slurry, as only the coating binder deposited on the surface of the substrate is removed from the bulk slurry. Automation of dip coating is readily available, and this methodology can be used to coat one or multiple devices at a time. While the dip coating process offers several advantages, such as ease of automation, this process can lead to coating the tip of the substrate, which can subsequently interfere with the device's ability to generate electrospray. Furthermore, the dip coating method is not suitable for selectively applying a coating to specific areas of a substrate because the entire substrate is immersed in the coating slurry. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] U.S. Patent No. 9,733,234 Summary of the Invention [Problem to be solved by the invention]

[0008] A manufacturing problem that arises when preparing thin layers of open particle beds is the potential chemical incompatibility between the particles and the solvent used in the coating slurry. If the particles are incompatible with the slurry solvent when the slurry is at rest, differences in density, polarity, and size can cause rapid settling or separation. This problem is commonly observed in processes using low-viscosity slurries, such as dip coating.

[0009] The dip technique for depositing adsorbent beds onto CBS device substrates requires a slurry with sufficiently low viscosity to deposit a uniform, thin layer of particles (≤30 μm). Dilute liquid slurries specified for dip procedures require continuous agitation to maintain particle distribution. Low viscosity slurry formulations affect particle distribution both during agitation (mixing) and at rest (without agitation). Careful attention must be paid to tailoring the slurry composition to allow for (1) uniform particle distribution in solution (effective bonding of the resulting hardened bed to the underlying substrate) and (2) a means to dip-coat a thin, uniform layer of particles. This complex specification matrix can limit the selection of particle and solvent viscosity combinations.

[0010] In some cases (e.g., two particle types with extremely opposite chemical polarities), the ability to create a homogeneous, low-viscosity mixture is very limited. It is preferable for the volume of slurry to be stationary (i.e., the mixing agitation is shut off) during the dipping process. Mixtures of particles with significantly different densities, sizes, polarities, or other physical or chemical properties can rapidly separate or settle when the slurry is at rest. The lower the viscosity, the faster the separation rate. In general, the higher the viscosity, the thicker the coating when the blade substrate is dipped.

[0011] While other methods, such as spray coating and sputtering, can be used to achieve spatial resolution and distribution of extractive coatings (<100 µm), these methods are difficult to automate, tedious, and potentially wasteful. Therefore, a coating process is needed that ensures not only reproducible device-to-device coverage but also precise coating limits that enable reproducible uncoated chips on smart substrates. [Means for solving the problem]

[0012] In one exemplary embodiment, a solid-phase microextraction device includes a substrate having a first plane and a first sorbent layer disposed on the first plane. The first plane is defined by a base edge, a spray edge disposed distally across the substrate from the base edge, the spray edge including a tapered tip extending away from the base edge, a first lateral edge extending from the base edge to the tapered tip, and a second lateral edge extending from the base edge to the tapered tip, the second lateral edge disposed distally across the substrate from the first lateral edge. The first sorbent layer extends a sampling length from the spray edge toward the base edge and includes first sorbent particles. The first sorbent layer is disposed along the sampling length across less than the entire width of the first plane from the first lateral edge to the second lateral edge.

[0013] In another exemplary embodiment, a method for forming a solid-phase microextraction device includes applying a first sorbent layer including first sorbent particles to a first planar surface of a substrate. The first planar surface is defined by a base edge, a spray edge disposed distally across the substrate from the base edge, the spray edge including a tapered tip extending away from the base edge, a first lateral edge extending from the base edge to the tapered tip, and a second lateral edge extending from the base edge to the tapered tip, the second lateral edge disposed distally across the substrate from the first lateral edge. The first sorbent layer extends a sampling length from the spray edge toward the base edge. Applying the first sorbent layer to the first planar surface includes applying the first sorbent particles to the first planar surface by at least one of screen printing, stencil printing, or additive manufacturing. [Brief explanation of the drawings]

[0014] [Figure 1A] FIG. 1 illustrates a CBS device having a bed of adsorbent particles coated on a portion of the surface of a solid substrate, according to one embodiment of the present disclosure. [Figure 1B]FIG. 1 illustrates a CBS device having a bed of adsorbent particles coated on a portion of the surface of a solid substrate that is less than the full width of the surface, according to one embodiment of the present disclosure. [Figure 1C] FIG. 1 illustrates a CBS apparatus having a primer layer applied to a portion of a solid substrate and a bed of adsorbent particles applied to the primer layer over a portion of the surface of the solid substrate that is less than the full width of the surface, according to one embodiment of the present disclosure. [Figure 1D] FIG. 1 illustrates a CBS apparatus having a primer layer applied to a portion of a solid substrate, a first bed of adsorbent particles applied to the primer layer over a portion of the first surface of the solid substrate that is less than the full width of the first surface, and a second bed of adsorbent particles applied to the primer layer over a portion of the second surface of the solid substrate that is less than the full width of the second surface, according to one embodiment of the present disclosure. [Figure 1E] FIG. 1 illustrates a CBS device having a first bed of adsorbent particles and a second bed of adsorbent particles applied to a portion of a surface of a solid substrate according to one embodiment of the present disclosure. [Figure 1F] FIG. 1 illustrates a CBS device having a primer layer applied to a solid substrate and a bed of adsorbent particles applied to the primer layer over a portion of the surface of the solid substrate that is less than the full width of the first surface, according to one embodiment of the present disclosure. [Figure 1G] FIG. 1 illustrates a CBS apparatus having a primer layer applied to a solid substrate and an adsorbent particle bed applied to the primer layer over a portion of the surface of the solid substrate that is less than the full width of the surface, such that the adsorbent particle bed is sharper than the tapered portion of the solid substrate, according to one embodiment of the present disclosure. [Figure 2] FIG. 1 illustrates a CBS device having a first bed of adsorbent particles applied to a first portion of a surface of a solid substrate, a second bed of adsorbent particles applied to a second portion of the surface of the solid substrate that is less than the entire width of the surface, and a third bed of adsorbent particles applied to a third portion of the surface of the solid substrate that is less than the entire width of the surface, according to one embodiment of the present disclosure. [Figure 3A] 1 is a photograph of each of four replicate CBS devices having a bed of adsorbent particles applied to a portion of the surface of a solid substrate less than the full width of the surface, according to an embodiment of the present disclosure. [Figure 3B]1 is a photograph of each of four replicate CBS devices having a bed of adsorbent particles applied to a portion of the surface of a solid substrate less than the full width of the surface, according to an embodiment of the present disclosure. [Figure 3C] 1 is a photograph of each of four replicate CBS devices having a bed of adsorbent particles applied to a portion of the surface of a solid substrate less than the full width of the surface, according to an embodiment of the present disclosure. [Figure 4] 1 illustrates a CBS device having a bed of adsorbent particles coated on a portion of a surface of a solid substrate, the bed including a single type of adsorbent particles, according to one embodiment of the present disclosure. [Figure 5] 1 illustrates a CBS device having a bed of adsorbent particles coated on a portion of a surface of a solid substrate, the bed including two types of adsorbent particles, according to one embodiment of the present disclosure. [Figure 6] 1 illustrates a CBS device having a bed of adsorbent particles coated on a portion of a surface of a solid substrate, the bed including three types of adsorbent particles, according to one embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0015] Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same parts.

[0016] Disclosed herein are solid-phase microextraction devices including a sorbent layer disposed across less than the entire width of the device, and methods for forming solid-phase microextraction devices using stencil techniques. The disclosed devices and methods enhance the spatial resolution of extraction coatings, facilitate sophisticated combinations of complex coating geometries and coating chemistries on substrates, reduce waste, increase production capacity, or a combination thereof, compared to devices and methods that do not include one or more of the features disclosed herein.

[0017] As used herein, "about" refers to a ±50% variation of the value modified by "about," unless specifically indicated to the contrary.

[0018] As used herein, "solid-phase microextraction" includes, but is not limited to, a solid substrate coated with a polymeric sorbent coating, which may include metal particles, silica-based particles, metal-polymer particles, polymer particles, or combinations thereof that are physically or chemically attached to the substrate. In some non-limiting examples, the solid substrate has at least one depression or protrusion disposed on its surface, and the substrate includes at least one polymeric sorbent coating disposed in or on the at least one depression or protrusion. The term "solid-phase microextraction" further includes a solid substrate having at least one depression or protrusion that includes at least one magnetic component for collecting magnetic particles or molecules on the solid substrate.

[0019] In contrast to dip coating, spray coating, sputtering, spin coating, doctor blading, sol-gel chemistry, and electrospinning, stencil techniques such as, but not limited to, screen printing and stencil printing, can be adapted to provide thin coatings and high spatial resolution distribution (<100 μm) of the extracted coating. Additive manufacturing techniques such as, but not limited to, binder jet three-dimensional printing, stereolithography, fused capillary additive manufacturing, or combinations thereof may be used instead of stencil techniques.

[0020] In screen printing, a woven screen (e.g., stainless steel mesh) is attached to a frame under tension, and the pattern to be printed on the substrate is generated by selectively filling portions of the screen with an emulsion that is impermeable to the coating solution. Screen printing requires a viscous coating solution with low volatility, which results in a thicker coating compared to dip coating or spin coating. The wet thickness of the coating is determined by the inter-thread volume of the mask and the thickness of the screen. Other factors, such as the snap-off distance, the force with which the squeegee is pressed into the screen, and the viscosity of the solution, also play a role. The screen printing process utilizes a fixture to which the substrate is attached. The fixture typically consists of multiple ducts, which secure the part to the fixture after activating vacuum suction. Such a fixture limits part movement during the screen printing process and ensures repeatable printing from part to part. Unlike dip coating, screen printing is well-suited to creating well-defined shapes with high resolution. Although screen printing provides lower spatial resolution than inkjet printing, it is significantly faster and more amenable to mass production than inkjet printing, and provides sufficient spatial resolution for the applications described herein. Furthermore, screen printing can apply to only one side of a substrate at a time, facilitating the creation of three-dimensional complexity on flat areas of the substrate.

[0021] In contrast to screen printing, stencil printing is typically performed on metal or plastic sheets by either photoetching, laser cutting, or a combination thereof. Furthermore, a very low-volatility cement-like slurry (essentially a paste with a viscosity of at least 1,000 cP or at least 2,000 cP) is required to coat the surface. Furthermore, a tensioned frame is not required, as a squeegee applies the coating to each opening, and the coating thickness is determined by the thickness of the stencil. Similar to screen printing, a fixture to which the substrate is attached is used to prevent the part from moving during the printing process, thus ensuring repeatable printing across machines. Unlike dip coating, stencil printing is suitable for creating well-defined geometric shapes with high resolution. While the spatial resolution achieved with stencil printing is lower than that achieved with inkjet printing, stencil printing is significantly faster than inkjet printing, amenable to mass production, and provides sufficient spatial resolution for the applications described herein. Furthermore, stencil printing can be applied to only one side of the substrate at a time, facilitating the creation of three-dimensional complexity on flat areas of the substrate.

[0022] Appropriately coated areas of a solid substrate can be used to collect molecules of interest from a sample, and the coated solid substrate can then be interfaced with an analytical instrument for measurement of the molecules. A slurry composed of particles, binders, additives, and solvents can be placed on the solid substrate by stencil techniques or additive manufacturing to form the coating necessary for molecule collection. After applying the slurry to the solid substrate, the substrate slurry can be dried at a constant temperature to evaporate the solvent and attach the binder to the surface of the solid substrate, thereby adhering the particles to the solid substrate.

[0023] The methods disclosed herein allow for particle beds to be deposited on flat substrates. In particular, the shape of the particle bed can differ from that of the underlying substrate, resulting in a small coating area relative to the planar surface area. The particle bed shape can include pads or channel regions, or other shapes, designed to direct the flow of elution / ionization solvent along a localized portion of the CBS device, ultimately terminating in a tapered tip on one of the flat surfaces of the substrate. The area of ​​the CBS device lacking the particle bed can simply be bare substrate, a primed substrate, or a substrate covered with a second, different coating that is confined to the "negative space" of the blade relative to the adsorbent particle bed.

[0024] For complex adsorbent bed geometries to effectively direct the flow of elution solvent from one region of a CBS device to another, it is desirable for the elution solvent to be confined to the adsorbent bed region and not wicked onto the adjacent exposed substrate. One novel approach to confining the elution solvent to the adsorbent bed region is to use a substrate with a different chemical polarity than the elution solvent and the adsorbent bed. This allows the elution solvent to move freely along the adsorbent bed region while suppressing or preventing contact with the substrate region.

[0025] The particle-to-solvent ratio affects the viscosity of the slurry. Coating techniques that inherently use high-viscosity slurries are less dependent on the composition ratio. For example, stenciling techniques use high-viscosity slurries. High viscosity reduces the movement of individual particles when the slurry is at rest. Thus, the higher viscosity used in stenciling facilitates the homogeneous suspension of particles with different surface properties, densities, sizes, and chemical polarities for extended periods, thus promoting a uniformly and homogeneously distributed particle mixture in the adsorbent bed.

[0026] Stenciling also facilitates the formation of complex-shaped sorbent particle beds on the CBS device substrate, providing a pathway to additional flow-based features in the CBS device. More complex bed geometries, such as channels, additional reservoir regions, and narrower channels toward the tip region, offer the ability to improve analytical signal, additional steps in sample preparation using the CBS device as a reaction vessel, or a combination thereof.

[0027] When the solvent molecules contain both polar and non-polar moieties, the additive particles can adjust the bulk polarity of the slurry. Relevant physical properties include the viscosity, vapor pressure, and bulk polarity of the slurry. The physical properties of the resulting cured bed can include bulk polarity, chemical reactivity, bed-to-substrate bonding effect, long-term bed stability, and adsorbent compatibility with a wider range of elution solvents.

[0028] If the polarity of the primer layer is essentially the same as the solvent used in depositing the adsorbent particle bed layer, the polarity characteristics of the adsorbent particle bed and the underlying primer will be very similar.

[0029] In CBS device designs using more complexly shaped adsorbent particle beds, the adsorbent particle bed area is typically a portion of the surface area of ​​the underlying CBS device. Therefore, when solvent is applied to the adsorbent particle bed area, there may be exposed substrate available for elution solvent. Unless there is a sufficient mechanical or chemical barrier to the elution solvent, the solvent may migrate from the adsorbent particle bed area to the substrate itself. This migration behavior is often undesirable, especially when the adsorbent particle bed design is configured to direct solvent flow from one confined region of the adsorbent particle bed to another.

[0030] One particular goal when stenciling an adsorbent particle bed pattern onto a CBS device substrate is to localize the liquid within the adsorbent particle bed itself. This provides a means for the liquid to travel along a predetermined route on the CBS device substrate. The localized flow path can be achieved by channels cut into the CBS device substrate or by physical barriers (such as walls) constructed on the CBS device substrate surface and adsorbent particles packed within the resulting channels.

[0031] Localized flow paths can also be achieved by forming an inherent liquid barrier between the adsorbent particle bed and the substrate of the CBS device based on differences in hydrophilicity and polarity, or between the adsorbent particle bed and the primer layer if a primer coating is first applied to the substrate. The inherent liquid barrier can rely on differences in hydrophilicity and polarity between the adsorbent bed and the underlying surface, with the polarity of the elution solvent being similar to the adsorbent bed compared to the underlying substrate. The elution solvent interacts only with the particle bed and does not flow into the negative space regions on the substrate.

[0032] A primer layer that chemically adheres to the substrate and chemically adheres to the adsorbent particles can enhance the bonding of the adsorbent particle bed to the substrate. The primer can be chemically similar to the adsorbent particles, thereby reducing the difference in hydrophilic polarity.

[0033] 1A , in one embodiment, a method for forming a solid-phase microextraction device 100 includes applying a first sorbent layer 102 including first sorbent particles 104 onto a first planar surface 106 of a substrate 108. The solid-phase microextraction device 100 may be a CBS device 110. The first planar surface 106 is defined by a base edge 112, a spray edge 114 disposed distally across the substrate 108 from the base edge 112, the spray edge 114 including a tapered tip 116 extending away from the base edge 112, a first lateral edge 118 extending from the base edge 112 to the tapered tip 116, and a second lateral edge 120 extending from the base edge 112 to the tapered tip 116, the second lateral edge 120 disposed distally across the substrate 108 from the first lateral edge 118. The tapered tip 116 may terminate in a tip end 122. The tip end 122 may be a sharp point, a rounded point, or a combination thereof. The first sorbent layer 102 extends a sampling length 124 from the spray edge 114 toward the base edge 112. Applying the first sorbent layer 102 to the first planar surface 106 includes applying the first sorbent particles 104 to the first planar surface 106 by at least one of screen printing, stencil printing, or additive manufacturing.

[0034] Suitable dimensions for the solid phase microextraction device 100 include, but are not limited to, about 2.5 mm wide by about 42 mm long by about 0.35 mm thick.

[0035] The substrate 108 may be formed of any suitable material, including, but not limited to, stainless steel, wood, a polymer, a conductive polymer, a metal, a metal alloy, a plastic-metal composite, or a combination thereof.

[0036] Applying the first adsorbent layer 102 may include applying a slurry including the first adsorbent particles 104, a binder, and a solvent. Applying the first adsorbent layer 102 may further include removing the solvent by drying to form the first adsorbent layer 102. Suitable adsorbent particles include C 18 Suitable sorbent particles include, but are not limited to, polymer particles such as silica modified with functional groups. Alternatively, suitable sorbent particles may include any other sorbent particles known in liquid chromatography, gas chromatography, or sample preparation techniques. Suitable binders include, but are not limited to, polyacrylonitrile, polydimethylsiloxane (PDMS), polyvinylidene difluoride (PVDF), copolymers of tetrafluoroethylene and 2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole, NAFION, or combinations thereof.

[0037] The first adsorbent particles 104 may include conductive particles, magnetic particles, or both.

[0038] The first adsorbent layer 102 has a maximum density of 1.5 g / cm 3 and an organic material having a first bulk density of at least 4.0 g / cm 3 and an inorganic material having a second bulk density of

[0039] 1B , in one embodiment, the first adsorbent layer 102 is disposed along the sampling length 124 across less than the entire width 126 of the first flat surface 106 from the first lateral edge 118 to the second lateral edge 120. Alternatively, as seen in FIG. 1A , the first adsorbent layer 102 may be disposed along the sampling length 124 across the entire width 126 of the first flat surface 106 from the first lateral edge 118 to the second lateral edge 120. Recession of the first adsorbent layer 103 from the first lateral edge 118 and the second lateral edge 120 leaves an exposed strip 138 of the substrate 108 (or primer 128, if present) along the first adsorbent layer 102.

[0040] Referring to FIG. 1C , in one embodiment, a primer layer 128 is disposed between the substrate 108 and the first adsorbent layer 102. The term "primer layer" may be used interchangeably with the term "protective layer." The primer layer 128 may provide an intermediate layer that facilitates bonding of the first adsorbent layer 102 to the substrate 108, particularly when the substrate 108 and the first adsorbent layer 102 are incompatible or partially incompatible with each other. The primer layer 128 may also provide a protective layer to prevent sample interaction with the underlying substrate 108 when the solid-phase microextraction device 100 is immersed in the sample. Thus, the primer layer 128 may be advantageous when the substrate 108 promotes undesired adsorption of sample matrix or promotes undesired chemical reactions with sample components. The composition of primer layer 128 may include, but is not limited to, an organic polymer, an organic self-assembled monolayer, a metal oxide, a metal, a metalloid, or a combination thereof, such as PAN, PDMS, PVDF, a copolymer of tetrafluoroethylene and 2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole, NAFION, or a combination thereof. Application of primer layer 128 to substrate 108 may use any coating technique known in the art or the stencil techniques described herein.

[0041] 1D , in one embodiment, the solid-phase microextraction device 100 further includes a second sorbent layer 130 including second sorbent particles 132 disposed on a second planar surface 134 of the substrate 108 and extending from the spray edge 114 toward the base edge 112. The second sorbent particles 132 may be compositionally different from or identical to the first sorbent particles 104. As used herein, "compositionally different" includes the material composition of the sorbent particles themselves, the binder composition that attaches the sorbent particles, the concentration of sorbent particles per unit area of ​​the sorbent layer, the mixing ratio of different sorbent particles within the sorbent layer, or a combination thereof. The second sorbent layer 130 may be disposed along the sampling length 124 across less than the entire width 136 of the second flat surface 134 from the first lateral edge 118 to the second lateral edge 120 (as shown), or may be disposed along the sampling length 124 across the entire width 136 of the second flat surface 134 from the first lateral edge 118 to the second lateral edge 120 (not shown). Incorporating different sorbent layers may simultaneously selectively chemically extract different analytes from a sample or apply different elution or ionization processes. Elution and analysis of molecules captured in the first sorbent layer 102 and the second sorbent layer 130 may utilize a single elution solvent compatible with both, thereby contributing to a single analysis, or may utilize separate elution solvents for each layer, such that the elution solvent can be delivered in serial or parallel analytical fashion.

[0042] 1E, in one embodiment, the solid-phase microextraction device 100 further includes a second sorbent layer 130 including second sorbent particles 132 disposed on the first planar surface 106 and extending from the spray edge 114 toward the base edge 112, the second sorbent particles 132 being compositionally different from the first sorbent particles 104. The first sorbent layer 102 and the second sorbent layer 130 may be disposed together across less than the entire width 126 (not shown), or may be disposed across the entire width 126 of the first planar surface 106 from the first lateral edge 118 to the second lateral edge 120 along the sampling length 124 (as shown). The two discreet sorbent layers may simultaneously chemically selectively extract different analytes from the same sample. Subsequent elution and analysis may use a single elution solvent compatible with both adsorbent layers, with both layers simultaneously contributing to a single analysis, or elution solvents delivered in a serial or parallel analytical manner, with a first elution solvent compatible with the first adsorbent layer 102 and a second elution solvent compatible with the second adsorbent layer 130.

[0043] 1F, in one embodiment, a solid-phase microextraction device 100 has a first sorbent layer 102 that includes two finger regions 140 extending from a tapered tip 116. These finger regions 140 can serve as reservoirs for an elution solvent that, after application, is wicked up into the tapered tip 116 and ultimately sprayed into a mass spectrometer. These finger regions 140 can also provide for the application of other liquids, such as an elution solvent containing an internal standard, an elution solvent containing a reagent that increases the target analyte signal, or an elution solvent with different physicochemical properties that facilitate the elution of other analytes from the first sorbent layer 102.

[0044] 1G, in one embodiment, the first adsorbent layer 102 includes a sharp taper 142 relative to the tapered tip 116. In this manner, the sharp taper 142 controls the focused flow of elution solvent to the tip end 122. The electric field required to generate the electrospray cone can be determined by the shape of the tapered tip 116 of the substrate 108.

[0045] 2 , in one embodiment, the first adsorbent layer 102 includes a first portion 200 including first adsorbent particles 104 and a second portion 202 including second adsorbent particles 132, where the first adsorbent particles 104 are compositionally different from the second adsorbent particles 132. The first adsorbent layer 102 may further include a third portion 204 including third adsorbent particles 206, where the third adsorbent particles 206 are compositionally different from the first adsorbent particles 104 and the second adsorbent particles 132. The first portion 200 may be disposed between the spray edge 114 and each of the second portion 202 and the third portion 204. Each of the different portions of the first adsorbent layer 102 may have a different thickness or a uniform thickness.

[0046] Figures 3A, 3B, and 3C show photographs of three complex adsorbent bed designs applied to solid-phase microextraction devices 100. The adsorbent composition is a mixture of PAN and hydrophilic-lipophilic-balanced (HLB) particles (silver-coated hollow glass microspheres in Figure 3A and hollow glass microspheres in Figures 3B and 3C). Each photograph shows four replicate solid-phase microextraction devices 100. Figure 3A shows a complex solid-phase microextraction device 100 with two finger regions 140 similar to those described in Figures 1F and 2. The application of the first and second portions 200 and 202 was performed separately using separate stencils, and the final shape is a combination of the two layers. Figures 3B and 3C illustrate designs for controlling the flow of elution solvent along the first adsorbent layer 102 as the solvent migrates to the tip end 122. In all three cases, the shape of the first adsorbent layer 102 is defined by the first adsorbent layer 102 itself, not the substrate 108.

[0047] 4 shows a solid-phase microextraction device 100 having a primer layer 128 and a first sorbent layer 102. A close-up 400 of the first sorbent layer 102 shows one sorbent particle type 402 immobilized in place with a binder 404.

[0048] 5 shows a solid-phase microextraction device 100 with two sorbent particle types immobilized in a first sorbent layer 102. A close-up 400 of the first sorbent layer 102 shows one sorbent particle type 402 and a second particle type 500, both immobilized in place with a binder 404.

[0049] Figure 6 shows a solid-phase microextraction device 100 with three sorbent particle types immobilized in a first sorbent layer 102. A close-up 400 of the first sorbent layer 102 shows one sorbent particle type 402, a second particle type 500, and a third particle type 600, all immobilized in place with a binder 404. Figure 6 shows particles with significantly different sizes uniformly distributed throughout the first sorbent layer 102. The high viscosity, paste-like slurry used in the stencil technique can provide a homogenous layer of significantly different particle sizes, concentrations, and densities. [Example]

[0050] A comparative exemplary CBS device 110 was prepared using a dip-coat technique.

[0051] Inventive CBS devices 110 in Examples 1-5 were stencil printed. For each such CBS device 110, the first planar surface 106 of the substrate 108 was roughened by either chemically etching the first planar surface 106 with HCl or sandblasting the first planar surface 106 with silicon carbide particles. Surface profilometry indicates that both roughening techniques resulted in similar levels of roughness. The roughened substrate 108 was dip-primed with PAM / DMF stock solvent and heated to 150°C for 2 minutes. A particle slurry was formulated using adsorbent particles as described in Table 1.

[0052] Materials used in the manufacture of CBS devices [Table 1]

[0053] The stencil particle bed geometries shown in Figures 3A, 3B, and 3C were created using an HDI stencil system and heated to 150 °C for 2 minutes. The final bed thickness was approximately 30 μm. Visual inspection using a microscope at 10x magnification showed uniform particle distribution for all particle types across the entire adsorbent bed area.

[0054] The equipment used included a Harry Manufacturing Inc. (Lebanon, NJ) Model MSP-053 screen printer and a Harry Manufacturing Inc. (Lebanon, NJ) 50 μm thick stainless steel 8″×10″ aluminum frame stencil.

[0055] Table 2. CBS devices illustrated in Figures 3A, 3B, and 3C and fabricated using the stencil technique described herein. [Table 2]

[0056] While the foregoing specification illustrates and describes exemplary embodiments, those skilled in the art will recognize that various changes can be made and equivalents can be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications can be made to adapt a particular situation or material to the teachings of the invention without departing from essential scope thereof. Therefore, it is not intended that the invention be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but the invention is intended to include all embodiments falling within the scope of the appended claims.

Claims

1. 1. A solid phase microextraction device comprising: A substrate having a first plane and a second plane opposite the first plane, wherein the first plane and the second plane are: a base edge; a spray edge positioned distally across the substrate from the base edge, the spray edge including a tapered tip extending away from the base edge; a first lateral edge extending from the base edge to the tapered tip between the first plane and the second plane; a substrate defined by a second lateral edge extending from the base edge to the tapered tip between the first plane and the second plane, the second lateral edge being disposed distally across the substrate from the first lateral edge; a first sorbent layer disposed on the first plane and extending a sampling length from the spray edge toward the base edge, the first sorbent layer comprising first sorbent particles; the first adsorbent layer is disposed across less than the entire width of the first plane from the first lateral edge to the second lateral edge along the sampling length such that an exposed strip of the substrate, or of the primer, if present, exists along the first adsorbent layer; the first adsorbent layer includes at least one shape selected from the group consisting of a channel, a reservoir region, a channel that narrows toward the tapered tip, a finger region, or a taper that is sharper than the tapered tip; Solid-phase microextraction device.

2. 10. The solid-phase microextraction device of claim 1, further comprising a second sorbent layer disposed on the first plane and including second sorbent particles extending from the spray edge toward the base edge, the second sorbent particles being compositionally different from the first sorbent particles.

3. 3. The solid-phase microextraction device of claim 2, wherein the first and second sorbent layers together span less than the entire width of the first plane from the first lateral edge to the second lateral edge along the sampling length.

4. A solid-phase microextraction device as described in claim 1, further comprising a second adsorbent layer disposed on the second plane and including second adsorbent particles extending from the spray edge toward the base edge.

5. 5. The solid phase microextraction device of claim 4, wherein the second sorbent particles are compositionally different from the first sorbent particles.

6. 5. The solid-phase microextraction device of claim 4, wherein the second sorbent particles are compositionally identical to the first sorbent particles.

7. 5. The solid-phase microextraction device of claim 4, wherein the second sorbent layer is disposed along the sampling length across less than the entire width of the second plane from the first lateral edge to the second lateral edge.

8. 10. The solid-phase microextraction device of claim 1, wherein the first sorbent layer comprises a first portion comprising first sorbent particles and a second portion comprising second sorbent particles, the first sorbent particles being compositionally different from the second sorbent particles.

9. 9. The solid-phase microextraction device of claim 8, wherein the first sorbent layer further comprises a third portion comprising third sorbent particles, the third sorbent particles being compositionally different from the first sorbent particles and the second sorbent particles.

10. 10. The solid-phase microextraction device of claim 9, wherein the first portion is disposed between the spray edge and each of the second portion and the third portion.

11. The first adsorbent layer has a density of up to 1.5 g / cm ３ and an organic polymer having a first bulk density of at least 5.0 g / cm ３ and an inorganic material having a second bulk density of

12. 10. The solid-phase microextraction device of claim 1, wherein the first sorbent particles comprise at least one of conductive particles or magnetic particles.

13. 10. The solid phase microextraction device of claim 1, further comprising a primer layer disposed between the substrate and the first sorbent layer.

14. 1. A method for forming a solid phase microextraction device, comprising: applying a first adsorbent layer comprising first adsorbent particles onto a first planar surface of a substrate; the substrate has the first plane and a second plane opposite the first plane; The first plane and the second plane are a base edge; a spray edge positioned distally across the substrate from the base edge, the spray edge including a tapered tip extending away from the base edge; a first lateral edge extending from the base edge to the tapered tip between the first plane and the second plane; a second lateral edge extending from the base edge to the tapered tip between the first plane and the second plane, the second lateral edge being positioned distally across the substrate from the first lateral edge; the first sorbent layer is disposed on the first plane and extends a sampling length from the spray edge toward the base edge, the first sorbent layer including first sorbent particles; the first adsorbent layer is disposed across less than the entire width of the first plane from the first lateral edge to the second lateral edge along the sampling length such that an exposed strip of the substrate, or of the primer, if present, exists along the first adsorbent layer; the first adsorbent layer includes at least one feature selected from the group consisting of a channel, a reservoir region, a channel that narrows toward the tapered tip, a finger region, or a taper that is sharper than the tapered tip; The method, wherein applying the first adsorbent layer to the first planar surface comprises applying the first adsorbent particles to the first planar surface by at least one of screen printing, stencil printing, or additive manufacturing.

15. The method of claim 14 , wherein applying the first adsorbent layer comprises screen printing the first adsorbent particles onto the first planar surface.

16. 15. The method of claim 14, wherein applying the first adsorbent layer comprises stencil printing the first adsorbent particles onto the first flat surface.

17. 15. The method of claim 14, wherein applying the first sorbent layer comprises applying the first sorbent particles onto the first planar surface by additive manufacturing.

18. The method of claim 14, wherein applying the first adsorbent layer comprises applying a slurry comprising the first adsorbent particles, a binder, and a solvent.

19. The method of claim 14, wherein applying the first adsorbent layer further comprises removing the solvent by drying to form the first adsorbent layer.

Images