Taylor cone emitter device storage apparatus, Taylor cone emitter device storage apparatus system, and method for analyzing sample aggregates.

Abstract

A Taylor cone emitter device storage is disclosed, the Taylor cone emitter device storage including a storage plate, a storage wall extending from the storage plate, an array of orifices, and an array of clock structure interfaces disposed within the storage plate. The array of orifices receives and holds an array of Taylor cone emitter devices. The array of clock structure interfaces directs the clock structures of the array of Taylor cone emitter devices into a predetermined radial orientation. The storage walls surround a periphery of a substrate chamber configured to receive a microtiter array tray, each having an array of solid phase microextraction devices disposed within separate wells of the microtiter array tray. A Taylor cone emitter device storage system is disclosed, the Taylor cone emitter device storage system including a microtiter array tray, an array of Taylor cone emitter devices, and a Taylor cone emitter device storage system. A method is disclosed for analyzing a collection of samples using the Taylor cone emitter device storage system.

Description

Technical Field

[0001]

[0001] This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 183,240 entitled "A Container-Multiwell Plate Assembly for Housing Solid Phase Microextraction Devices" filed on May 3, 2021, and U.S. Provisional Patent Application No. 63 / 183,281 entitled "Apparatus and Method for Analyzing a Sample" filed on May 3, 2021, each of which is incorporated herein by reference in its entirety.

[0002]

[0002] The present application relates to a Taylor cone emitter device storage apparatus, a Taylor cone emitter device storage apparatus system, and a method for analyzing an aggregate of samples using the Taylor cone emitter device storage apparatus system. In particular, the present application relates to a Taylor cone emitter device storage apparatus, a Taylor cone emitter device storage apparatus system, and a method for analyzing an aggregate of samples using the Taylor cone emitter device storage apparatus system, wherein the Taylor cone emitter device storage apparatus receives an array of distributed Taylor cone emitter devices for interfacing with a microtiter array tray.

Background Art

[0003]

[0003] Taylor cone emitter devices

[0004]

[0004] A Taylor cone emitter device is a device capable of forming a Taylor cone in the presence of a liquid and under the influence of an electric field. The Taylor cone may contain a target chemical analyte species. Taylor cone emitter devices include, inter alia, electrospray needles, coated blade spray devices (described below), paper spray devices, adsorbent-coated electrodes, SPME tips, and porous molded probes.

[0005]

[0005] "Electrical surface charge" is the charge generated on a surface when a voltage is applied to an emitter or conductor. Surface charge is concentrated in areas with the highest curvature. Therefore, sharp edges or pointed tips can be used to increase the local charge density. The electric field on a metal surface arises from the surface charge and is perpendicular to the surface, and its intensity is proportional to the surface charge density. The electric field gradient is the rate at which the electric field decreases, and the electric field gradient is strongest at such edges, lines, and points. Regions with high electric field gradients are most likely to produce Taylor cones from the solvent applied.

[0006]

[0006] Preferably, the Taylor cone is localized to a specific region of the emitter, in particular to a location where the cone released from the emitter is positioned to facilitate the collection of ionized particles generated from the cone into a mass spectrometer or other ionized particle analyzer.

[0007]

[0007] The Taylor cone emitter has a shape that is capable of generating a region with a high electric field gradient in order to form a Taylor cone.

[0008]

[0008] In order to localize the Taylor cone, the emitter device shape may include, but does not necessarily include, regions having a small radius of curvature, such as sharp points or edges. The localized electric field can also be achieved by a convex portion having a thin cross-section, small diameter, or high aspect ratio, as in the case of a rod or cone.

[0009]

[0009] The Taylor cone emitter may be produced in the form of a layer or coating from a single material (substrate) or from two or more materials, and at least a portion of the top surface helps to collect and release the substance to be analyzed.

[0010]

[0010] A suitable material for collecting the substance to be analyzed may collect the substance to be analyzed from a large sample. The collection mechanism may be adsorption, decomposition, absorption, or specific binding (e.g., antigen-antibody binding, selection of pore shape and size such as metal-organic structures).

[0011]

[0011] The inherent uppermost surface of the emitter can serve as the material for collecting the substance to be analyzed, or the material for collecting the substance to be analyzed can be applied to the uppermost surface. Known applicable materials include adsorption beds formed by particles and irregular or conformal continuous coatings. The material for collecting the substance to be analyzed may be porous or non-porous. The collection material may be permeable or impermeable. Typically, the collection material is chemically compatible with the sample and solvent employed to produce the Taylor cone.

[0012]

[0012] Covered blade device

[0013]

[0013] Coated blade spray ("CBS") is a solid-phase microextraction ("SPME")-based analytical technique previously described in the literature (Pawliszyn et al., U.S. Patent No. 9,733,234) that facilitates the collection of the target analyte from a sample and subsequent direct interface to a mass spectrometer via a substrate spray event (i.e., electrospray ionization). Solid-phase microextraction devices are typically in the form of Taylor cone emitter devices that have a substrate suitable for holding the sample. CBS devices typically have a region with a small radius of curvature, such as a sharp point or edge.

[0014]

[0014] "Coated blade spray," "CBS blade," and "blade device" are used synonymously in this specification.

[0015]

[0015] CBS-based chemical analysis has two basic stages: (1) collection of the substance to be analyzed, and (2) instrumental analysis thereafter. Collection of the substance to be analyzed is performed by directly immersing the adsorbent-coated end of a blade device in the sample. In the case of liquid samples, the extraction step is generally performed using the sample contained in a vial or well plate.

[0016]

[0016] After collecting the substance to be analyzed, the blade device is removed from the sample and, after a series of washing steps, is presented to the inlet of the mass spectrometer ("MS") for analysis. In this configuration, the blade device undergoes several transfer steps. Therefore, reliable placement of the blade device for each of these steps is important for both manual and robotically automated handling environments.

[0017]

[0017] As a direct-to-MS chemical analysis device, the blade device requires pre-wetting of the extractable substance to release the collected substance to be analyzed and facilitate the electrospray ionization process (formation of the Taylor cone). Subsequently, a potential difference is applied between the uncoated area of ​​the substrate and the inlet of the MS system to generate an electron spray at the tip of the CBS device. To ensure reliable run-to-run accuracy, the electric field between the blade and the MS system must be reproducibly formed. Therefore, proper placement of the blade device relative to the MS skimmer cone opening, including radial (or rotational) orientation of the blade device, is extremely important. [Overview of the Initiative]

[0018]

[0018] Generally, the blade portion of a blade device has two sides, an upper side and a lower side. In some cases, different adsorbent coatings may be present on each of the flat sides of the blade, and therefore two sample analyses may be performed in sequence: first, an analysis of the upper side, followed by a second analysis of the lower side. In other examples, the same adsorbent coating may be present on each of the flat sides of the blade, and therefore two sample analyses may be performed in sequence but in different instruments: first, an analysis of the upper side in instrument A, followed by a second analysis of the lower side in instrument B. In any case, the radial orientation of the blade is also important.

[0019]

[0019] The above disclosure describes the manual handling of individual blade devices to properly position them in the inlet portion of a mass spectrometer. Other examples describe one-dimensional and two-dimensional arrays of blade devices in a large holder. These embodiments include a rigid support capable of accommodating two or more blade devices. An example of this arrangement configuration is included in U.S. Patent No. 7,259,019. These examples are generally aligned to standard laboratory sampling plastic products, most commonly microtiter array trays having an 8 × 12 well arrangement configuration, with each well having a central portion of approximately 9 mm. High-density trays with smaller sample wells positioned closer to each other are also commercially available to maintain the footprint of a standard sample tray.

[0020]

[0020] Because there is a single entry point to the MS device, the sample analysis stage is still a sequential processing process when using these array-based designs. Selected blade devices in a large array are arranged for electrospray ionization. This design has the disadvantage that the entire array of blade devices is also placed almost in close proximity to the MS, which creates a considerable risk of electrical and / or chemical crosstalk between adjacent blade devices during the electrospray ionization process. This, in turn, is particularly detrimental to chain-of-custody sample analysis applications such as clinical and forensic screening of biological fluids.

[0021]

[0021] Incorporated herein by reference, PCT application PCT / US2020 / 047201, which entered the national phase in the United States and was published as U.S. Patent Application No. 2021 / 0055192, advances the current art by disclosing a CBS device in that PCT application, in which a close-arranged array configuration is maintained during the sample extraction process using a standard microtiter array tray, and individual blade devices are introduced into the ionization region of a mass spectrometer while maintaining the radial arrangement of the blades throughout the entire sample collection-to-analysis process.

[0022]

[0022] Description of the micropipette device

[0023]

[0023] A common laboratory tool for transporting precise volumes of liquid is the micropipette. Examples of this configuration include U.S. Patent Nos. 4,284,604, 5,650,124, and 7,421,913. Micropipettes employ various mechanisms to draw a predetermined volume of liquid into the device and then meter and dispense the liquid. Precise volume capacities for standard pipettes range from 0.1 μL to 10 mL. To reduce the risk of sample contamination, disposable pipette tips are used. The micropipette tip is installed in the pipette by pushing the pipette tip into it, and friction holds the tip in place. After the liquid has been metered and dispensed, the tip is removed from the end of the pipette, and the entire process is repeated.

[0024]

[0024] When many liquid transfer steps are performed for a highly parallel process, micropipette devices employing two or more liquid metering and dispensing channels are available. An example of this arrangement configuration is included in U.S. Patent No. 5,021,217. These devices still employ a friction fitting attachment mechanism for disposable tips.

[0025]

[0025] For clarity, the terms “pipette,” “pipettor,” “micropipettor,” and “multichannel pipettor” are used synonymously in this specification. The terms “pipette tip” and “micropipette tip” are also used synonymously.

[0026]

[0026] An equivalent volume of liquid is drawn out and dispensed from each tip. The tip positions in the pipette array are aligned with the tip positions in the storage rack to facilitate installation.

[0027]

[0027] Since the multi-channel pipette device is used with pipette tips in storage racks of one-dimensional arrays and two-dimensional arrays, a row of disposable tips can be installed in parallel on a micropipette.

[0028]

[0028] The micropipette technology is also adapted to robotic systems, in which the entire liquid transfer sequence is the same as that adopted for manual units, but is automated.

[0029]

[0029] Since micropipettes are ubiquitous in laboratories, it is advantageous to maintain the compatibility of the CBS device with the physical dimensions of micropipette technology for both manual use and integration into robotic automation setups.

[0030]

[0030] Micropipette tip

[0031]

[0031] Since many applications employing micropipettes are sensitive to chemical contamination, disposable single-use pipette tips are available. A standard micropipette tip is loaded onto a pipetter device by centering the device over the docked tip and gently driving the device into the opening of the tip. The tip is secured by friction and is ready for use. After use, the contaminated microtiter tip is removed from the device by a tip ejector, typically a slidable sheath around the shaft of the device that engages the upper lip of the disposable tip and pushes to overcome the frict connection. Examples of modified pipette tips for sample extraction include U.S. Patent No. 7,595,026.

[0032]

[0032] A common micropipette tip is conical and has no radial orientation requirements for normal operation.

[0033]

[0033] Conductive tips are used to prevent carryover in automated pipetting robots. An example of a conductive tip is the addition of graphite to the raw material polypropylene, which makes the pipette tip electrically conductive and gives the tip an opaque black appearance. An alternative embodiment in which a portion of the pipette tip is conductive is described in U.S. Patent No. 9,346,045. The relative position of the tip in the robotic workstation is identified by measuring the capacitance. The filling level of the liquid in the tip can be determined in the sample and reagent containers by measuring the current, so the immersion depth of the tip can be adjusted to match the filling level.

[0034]

[0034] In standard sample collection and handling practices, tip replacement is frequent, so multiple tips are stored in racks that protect the tips from environmental contamination. To accommodate the array position standards described above, bulk storage of disposable tips generally employs 8 × 12, 96 tip arrays, or multiples of 96 tips, with a standard tip center-to-center position. This allows for direct loading into multichannel pipette devices and maintains standard rack footprint in the laboratory and on automation workstation platforms.

[0035]

[0035] The rack container for housing the micropipette tip does not include any elements that maintain the radial orientation of a standard pipette tip.

[0036]

[0036] Microtiter array tray

[0037]

[0037] Industry standard microtiter array trays (also known as “microtiter plates”, “microplates”, “microwell plates”, and “multiwells”) are formed in accordance with ANSI SLAS 1-2004(R2012), “Microplate Footprint Dimensions”, ANSI SLAS 2-2004(R2012), “Microplate Height Dimensions”, ANSI SLAS 3-2004(R2012), “Microplate Bottom Outside Flange Dimensions”, ANSI SLAS 4-2004(R2012), “Microplate Well Positions”, and ANSI SLAS 6-2012, “Microplate Well Bottom Elevation”. Microtiter array trays are often docked or otherwise engaged with laboratory equipment in which the wells are accessed by automation. Common automation processes for accessing microtiter wells include liquid metering and dispensing. In many automation systems, multiple microtiter array trays are docked together, requiring precise knowledge of the well positions relative to each other and to neighboring microtiter array trays. Microtiter array trays have standardized values ​​for tray length and tray width. Microtiter array trays may optionally have recessed tray walls from the tray skirt. Industry standard dimensions are 127.71 mm long × 85.43 mm wide × 14.10 mm high. Microtiter array trays generally have 6 (2 × 3), 12 (3 × 4), 24 (4 × 6), 48 (6 × 8), 96 (8 × 12), or 384 (16 × 24) wells of various volumes, as well as other arrays described in the standards. The volume is determined by the number, size, and depth of the wells. The tray footprint of these microtiter trays is specified in the relevant ANSI standards. [Means for solving the problem]

[0038]

[0038] In one exemplary embodiment, the Taylor cone emitter device storage device includes a storage device plate, a storage device wall extending from the storage device plate, an array of orifices disposed within the storage device plate, and an array of clock structure interfaces disposed within the storage device plate. The storage device wall extends from the storage device plate and surrounds the substrate chamber. Each of the array of orifices is configured to receive and hold the substrate and receiving mount of one Taylor cone emitter device in the array of Taylor cone emitter devices. The array of clock structure interfaces guides the clock structure of each Taylor cone emitter device in the array of Taylor cone emitter devices into a predetermined radial orientation, thereby configuring the array of clock structure interfaces to fix each of the array of Taylor cone emitter devices in the predetermined radial orientation. The substrate chamber is configured to at least partially receive the microtiter array tray and to receive the substrate of each Taylor cone emitter device in the array of Taylor cone emitter devices, with the substrate and tapered tip extending from the substrate being distanced from any adjacent Taylor cone emitter devices in the array of Taylor cone emitter devices placed within the storage device wall or Taylor cone emitter device storage device. An array of orifices placed within the storage device plate is distributed in alignment with the microtiter array tray, so that each of the array of Taylor cone emitter devices is placed in a separate well of the microtiter array tray when the microtiter array tray is at least partially received by the substrate chamber.

[0039]

[0039] In another exemplary embodiment, the Taylor cone emitter device storage system includes a microtiter array tray having an array of wells, an array of Taylor cone emitter devices, and a Taylor cone emitter device storage device. Each of the arrays of Taylor cone emitter devices includes a substrate having at least one flat surface, an adsorbent layer disposed on at least a portion of the at least one flat surface, a tapered tip extending from the substrate, a receiving mount configured for removable mounting to a mounting portion of a receiving device, and a clock structure configured for fixing the radial orientation of the flat surface to the receiving device. The Taylor cone emitter device storage device includes a storage device plate, a storage device wall extending from the storage device plate, an array of orifices disposed within the storage device plate, and an array of clock structure interfaces disposed within the storage device plate. The storage device wall surrounds the substrate chamber. Each of the arrays of orifices is configured to receive and hold the substrate and receiving mount of one Taylor cone emitter device of the array of Taylor cone emitter devices. The array of clock structure interfaces guides the clock structure of each Taylor cone emitter device in the array of Taylor cone emitter devices to a predetermined radial orientation, thereby configuring the array of clock structure interfaces to fix each of the Taylor cone emitter devices in the predetermined radial orientation. The substrate chamber is configured to receive at least partially the microtiter array tray and to receive the substrate of each Taylor cone emitter device in the array of Taylor cone emitter devices, with the substrate and tapered tip being distanced from contact with any adjacent Taylor cone emitter devices in the array of Taylor cone emitter devices located within the storage device wall or Taylor cone emitter device storage device.The array of orifices, positioned within the storage device plate, is distributed in alignment with the microtiter array tray, so that each of the arrays of Taylor cone emitter devices is positioned in a separate well of the array of wells when the microtiter array tray is at least partially received by the substrate chamber.

[0040]

[0040] In another exemplary embodiment, a method for analyzing a sample aggregate includes arranging a plurality of sample-exposed Taylor cone emitter devices as an array of Taylor cone emitter devices within a Taylor cone emitter device storage apparatus. Each of the Taylor cone emitter device arrays includes a substrate having at least one flat surface, an adsorbent layer disposed on at least a portion of the at least one flat surface, a tapered tip extending from the substrate, a receiving mount configured for removable attachment to a mounting portion of a receiving device, and a clock structure configured for fixing the radial orientation of the flat surface to the receiving device. The Taylor cone emitter device storage apparatus includes a storage apparatus plate, a storage apparatus wall extending from the storage apparatus plate, an array of orifices disposed within the storage apparatus plate, and an array of clock structure interfaces disposed within the storage apparatus plate. The storage apparatus wall surrounds the substrate chamber. Each of the orifice arrays is configured to receive and hold the substrate and receiving mount of one of the Taylor cone emitter devices in the array of Taylor cone emitter devices. The array of clock structure interfaces guides the clock structure of each Taylor cone emitter device in the array of Taylor cone emitter devices to a predetermined radial orientation, thereby configuring the array of clock structure interfaces to fix each of the Taylor cone emitter devices in the predetermined radial orientation. The substrate chamber is configured to at least partially receive the microtiter array tray and to receive the substrate of each Taylor cone emitter device in the array of Taylor cone emitter devices, and the substrate and the tapered tip extending from the substrate are located far from contact with any adjacent Taylor cone emitter devices in the array of Taylor cone emitter devices located in the storage device wall or within the Taylor cone emitter device storage device.An array of orifices placed within a storage device plate is distributed in alignment with a microtiter array tray, thereby placing each array of Taylor cone emitter devices in a separate well of the array of wells in the microtiter array tray when the microtiter array tray is at least partially received by the substrate chamber. The method further includes: placing a first microtiter array tray at least partially within the substrate chamber; preparing an array of Taylor cone emitter devices for analysis within the Taylor cone emitter device storage device; withdrawing each array of Taylor cone emitter devices from the Taylor cone emitter device storage device and analyzing each array of Taylor cone emitter devices by a first analytical method for screening for predetermined sample characteristics; sorting the array of Taylor cone emitter devices based on predetermined sample characteristics to form a compacted array of Taylor cone emitter devices; and performing a second analytical method on the compacted array of Taylor cone emitter devices. [Prior art documents] [Patent Documents]

[0041] [Patent Document 1] U.S. Patent No. 9,733,234 [Patent Document 2] U.S. Patent No. 7,259,019 [Patent Document 3] U.S. Patent Application Publication No. 2021 / 0055192 [Patent Document 4] U.S. Patent No. 4,284,604 [Patent Document 5] U.S. Patent No. 5,650,124 [Patent Document 6] U.S. Patent No. 7,421,913 [Patent Document 7] U.S. Patent No. 5,021,217 [Patent Document 8] U.S. Patent No. 7,595,026 [Patent Document 9] U.S. Patent No. 9,346,045 [Brief explanation of the drawing]

[0042] [Figure 1]

[0041] This figure shows an industry-standard microtiter array tray. [Figure 2(a)]

[0042] Figure 2(a) is a side view of a Taylor cone emitter device having fin elements for radial orientation control, housed in a storage container, according to an embodiment of the present disclosure. [Figure 2(b)] Figure 2(b) is a front view of a Taylor cone emitter device having fin elements for radial orientation control, housed in a storage container, according to an embodiment of the present disclosure. [Figure 2(c)] Figure 2(c) is a perspective view of a Taylor cone emitter device having fin elements for radial orientation control, housed in a storage container, according to an embodiment of the present disclosure. [Figure 3(a)]

[0043] Figure 3(a) is a top view of a Taylor cone emitter device storage apparatus having three embodiments of mechanical elements for facilitating the control of radial orientation of a Taylor cone emitter device having fin elements. [Figure 3(b)] Figure 3(b) is a side view of a Taylor cone emitter device storage apparatus comprising three embodiments of mechanical elements for facilitating the control of radial orientation of a Taylor cone emitter device having fin elements. [Figure 4]

[0044] This figure shows an embodiment of a Taylor cone emitter device storage apparatus having three exemplary properly docked Taylor cone emitter devices having fin elements. [Figure 5(a)]

[0045] Figure 5(a) is an exploded view of a first exemplary Taylor cone emitter device storage apparatus according to an embodiment of the present disclosure. [Figure 5(b)] Figure 5(b) is an assembly diagram of a first exemplary Taylor cone emitter device storage apparatus according to an embodiment of the present disclosure. [Figure 6(a)]

[0046] Figure 6(a) is an exploded view of a second exemplary Taylor cone emitter device storage apparatus according to an embodiment of the present disclosure. [Figure 6(b)] Figure 6(b) is an assembly diagram of a second exemplary Taylor cone emitter device storage apparatus according to an embodiment of the present disclosure. [Figure 7]

[0047] This figure shows a method for analyzing a sample aggregate according to the embodiments of this disclosure. [Figure 8]

[0048] This figure shows a method for forming an array of compacted Taylor cone emitter devices while analyzing a sample aggregate according to an embodiment of the present disclosure. [Modes for carrying out the invention]

[0043]

[0049] Wherever possible, the same reference numerals are used to represent the same parts throughout the drawing.

[0044]

[0050] Compared to storage devices, systems, and methods lacking at least one of the structural components described herein, the storage devices, systems, and methods of this embodiment reduce sample processing and analysis time, increase test throughput, facilitate simultaneous processing of multiple samples, increase screening efficiency, increase compaction of screened samples, increase space efficiency, or a combination thereof.

[0045]

[0051] As used herein, "about" indicates a ±15% variance of the value modified by "about," unless otherwise indicated.

[0046]

[0052] As used herein, “Taylor cone emitter” includes, but is not limited to, articles capable of forming a Taylor cone, including, but not limited to, solid-phase microextraction devices or CBS devices. Taylor cone emitter devices may, but are not required to have, sharp edges or pointed tips. Solid-phase microextraction devices are a form of Taylor cone emitter devices, but not all Taylor cone emitter devices are solid-phase microextraction devices.

[0047]

[0053] As used herein, “solid phase microextraction” includes, but is not limited to, a solid substrate coated with a polymer adsorbent coating, the coating may include metal particles, silica-based particles, metal-polymer particles, polymer particles, or a combination thereof, physically or chemically attached to the substrate. In some non-limiting examples, the solid substrate has at least one recess or protrusion disposed on the surface of the substrate, and the substrate includes at least one polymer adsorbent coating disposed in or on the at least one recess or protrusion. The term “solid phase microextraction” further includes a solid substrate having at least one recess or protrusion accommodating at least one magnetic component for collecting magnetic particles or magnetic molecules on the solid substrate.

[0048]

[0054] Figure 1 shows a commercially available, industry-standard microtiter array tray 100 having 96 wells 130. The microtiter array tray 100 has standardized values ​​for tray length 110 and tray width 120, establishing the tray mounting area of ​​the tray skirt 141. The microtiter array tray 100 may optionally have a recessed tray wall 142 from the tray skirt 141. The position of the wells 130 is indicated by the well center 132 and the center-to-center position of two adjacent wells 131.

[0049]

[0055] Referring to Figures 2(a)-(c), where the Taylor cone emitter device 200 is a solid-phase trace extraction vise, the basic elements of the Taylor cone emitter device 200 include a substrate 230 having at least one flat surface 235, an adsorbent layer 240 disposed on at least a portion of the at least one flat surface 235, a tapered tip 245 extending from the substrate 230 toward the analytical end of the device 200, and a receiving mount 210 configured for removable mounting to the mounting portion of the receiving device. The substrate 230 can have any suitable dimensions, including, but not limited to, about 4 mm wide × about 40 mm long × about 0.5 mm thick. The substrate 230 can be made from any suitable material, including, but not limited to, conductive materials such as stainless steel. The adsorbent layer 240 can be made from, but not limited to, polymer particles (e.g., C 18 The extract phase adsorbent may include silica modified with a group and a binder (e.g., polyacrylonitrile).

[0050]

[0056] In one embodiment, the Taylor cone emitter device 200 is a CBS device 300 adapted to standard pipette tip dimensions. The blade portion 220 is equipped with a cup as a receiving mount 210 configured to be attached to a mounting portion 104 on the pipette end 109. The receiving mount 210 is fixed to a substrate 230 and is positioned opposite the adsorbent layer 240 and the tapered tip portion 245. The inner surface of the receiving mount 210 is molded to employ a friction fitting mechanism that is compatible with standard commercially available pipette tip cups. As an alternative to or in addition to the friction fitting mechanism, any suitable mechanism for mounting the receiving mount 210 to the mounting portion 104 may be employed, including, but not limited to, a magnetic connector, an expandable compression O-ring, or a combination thereof. The receiving mount 210 may be made from an electrically insulating polymer compatible with standard pipette tips, such as polypropylene, or from an electrically conductive polymer, such as carbon-impregnated polypropylene, but not limited to.

[0051]

[0057] In one embodiment, the Taylor cone emitter device 200 includes a clock structure 305 configured to fix the radial orientation of a flat surface 235 relative to the receiving device 100. “Clocking” is intended to imply the passage of hands around an analog clock face as a paradigm for indicating the radial orientation of the flat surface 235. In one embodiment, the clock structure 305 includes at least one of a recess or a protrusion corresponding to at least one of a complementary protrusion or concave of the receiving device, thereby restricting the radial orientation of the Taylor cone emitter device 200 relative to the receiving device to a predetermined number of radial positions when the Taylor cone emitter device 200 is mounted on the receiving device. The predetermined number of radial positions may consist of a single radial position, two radial positions, or any suitablely large number of radial positions. The Taylor cone emitter device 200 may include a visual marker of the radial orientation of at least one flat surface 235 on the receiving mount 210. Such visual markers can be useful in indicating the radial orientation of at least one flat surface 235 when the flat surface 235 itself is not visible.

[0052]

[0058] In one embodiment, the Taylor cone emitter device 200 is a pipette-compatible CBS device 300, the receiving mount 210 is a pipette tip receiving mount 210, and the mounting portion 104 is a pipette tip mounting portion 104 configured to removably engage with the pipette tip receiving mount 210. As used herein, “removable” indicates a configuration for removal without damage. The receiving device may include, but is not limited to, any suitable device including a pipette or Taylor cone emitter device operating device.

[0053]

[0059] In one embodiment, the receiving mount 210 has two fin protrusions 310 that extend equidistant from the receiving mount 210 and function as a clock structure 305. The presence of the two fin protrusions 310 in this configuration reduces the radial position state 320 of the blade to two separate equivalent positions (i.e., 0° and 180°). The two-fin design shown herein is for illustrative purposes only; other configurations employing more or fewer fins may be employed, or other structures on the receiving mount 210 may be conceivable that restrict the radial rotation of the Taylor cone emitter device 200 when engaged with the mounting portion. To control the radial position, the fin protrusions 310 engage with the receiving device in a lock-and-key arrangement.

[0054]

[0060] Figures 3(a), 3(b), and 4 show a conventional Taylor cone emitter device storage device 400 for oriented the Taylor cone emitter device 200 while docked. The Taylor cone emitter device storage device 400 includes a storage device wall 405 surrounding and defining a chamber 401; a plurality of orifices 420 disposed in the storage device wall 405, each of which is configured to receive and hold the base 230 and receiving mount 210 of the Taylor cone emitter device 200; and a plurality of clock structure interfaces 406 disposed in the storage device wall 405, each of which is configured to guide the clock structure 305 of the Taylor cone emitter device 200 into a predetermined radial orientation and fix the Taylor cone emitter device 200 in the predetermined radial orientation. Chamber 401 is configured to receive the base 230 of the Taylor cone emitter device 200, with the base 230 and the tapered tip 245 extending from the base 230 being at a distance from any adjacent Taylor cone emitter devices 200 located in the storage device wall 405 or the Taylor cone emitter device storage device 400.

[0055]

[0061] As shown, the Taylor cone emitter device storage device 400 includes two slits 410 as a clock structure interface 406, which are radially oriented and aligned with the clock structure 305 of the CBS device 300. As shown, the tapered portion of the blade fin 310 provides a further mechanism to assist in the successful docking of the CBS device 300, which is slightly offset with respect to the axial center of the tapered tip 245 and orifice 420 of the Taylor cone emitter device storage device 400. As shown, the clock structure interface 406 includes a guide projection 430 surrounding the orifice 420 to facilitate the proper alignment of the CBS 300 when the CBS 300 is docked to the Taylor cone emitter device storage device 400. If the CBS device 300 is radially off-axis with respect to the orientation of the clock structure 305 with respect to the clock structure interface 406, the guide projection 430 is joined so as to taper toward point 432 and form a valley shape 435 at the base of the orifice 420. The tapered portion of the guide projection 430 provides a mechanism for guiding and repositioning the off-axis CBS device 300 so that the CBS device 300 is properly positioned while docked in the Taylor cone emitter device storage device 400.

[0056]

[0062] Referring to Figures 5(a), 5(b), 6(a), and 6(b), in one embodiment, the Taylor cone emitter device storage system 500 includes a microtiter array tray 100 having an array of wells 130, an array of Taylor cone emitter devices 200, and a Taylor cone emitter device storage device 400. The Taylor cone emitter device storage device 400 includes a storage device plate 510, a storage device wall 405 extending from the storage device plate 510 and surrounding a substrate chamber 401, an array of orifices 420 disposed within the storage device plate 510, and an array of clock structure interfaces 406 disposed within the storage device plate 510. Each of the array of orifices 420 is configured to receive and hold the substrate 230 and receiving mount 210 of one of the Taylor cone emitter devices 200 in the array of Taylor cone emitter devices 200. The array of clock structure interfaces 406 guides the clock structure 305 of each Taylor cone emitter device 200 in the array of Taylor cone emitter devices 200 into a predetermined radial orientation, thereby configuring the array of clock structure interfaces 406 to fix each of the Taylor cone emitter devices 200 in the predetermined radial orientation. The substrate chamber 401 is configured to at least partially receive the microtiter array tray 100 and to receive the substrate 230 of each Taylor cone emitter device 200 in the array of Taylor cone emitter devices 200, with the substrate 230 and tapered tip 245 being distanced from any adjacent Taylor cone emitter devices 200 in the array of Taylor cone emitter devices 200 located within the storage device wall 405 or the Taylor cone emitter device storage device 400. The array of orifices 420 arranged within the storage device plate 510 is distributed in alignment with the microtiter array tray 100, so that each of the arrays of Taylor cone emitter devices 200 is placed in a separate well 130 of the array of wells 130 when the microtiter array tray 100 is at least partially received by the substrate chamber 401.The Taylor cone emitter device 200 may be a CBS device 300. The receiving mount 210 may be a pipette tip receiving mount 210.

[0057]

[0063] In one embodiment, when assembled, the microtiter array tray 100 and the Taylor cone emitter device storage device 400 have a combined installation area equal to the installation area of ​​the microtiter array tray 100 alone.

[0058]

[0064] In one embodiment, the Taylor cone emitter device storage system 500 includes a storage device cover 520 configured to cover and install a storage device plate 510 in order to secure an array of Taylor cone emitter devices 200 within an array of orifices 420.

[0059]

[0065] Referring to Figures 5(a) and 5(b), in one embodiment, the storage device wall 405 is configured to fit across the microtiter array tray 100 in peripheral contact with the peripheral surface 142 of the microtiter array tray and the internal surface 530 of the storage device wall 405.

[0060]

[0066] Referring to Figures 6(a) and 6(b), in another embodiment, the Taylor cone emitter device storage apparatus 400 further includes a storage apparatus base 600 having a cavity 610 configured to receive a microtiter array tray 100, and a storage apparatus wall 405 configured to engage with the storage apparatus base 600 and, together with a storage apparatus plate 510, define a base chamber 401, and the microtiter array tray 100 is fully positioned within the base chamber 401. In a further embodiment, the storage apparatus base 600 includes a storage apparatus shelf 620 on which the storage apparatus wall 405 sits, and a storage apparatus base footing 630, which extends below the storage apparatus base 600 and has the same footprint as the microtiter array tray 100.

[0061]

[0067] Referring to Figure 7, in one embodiment, a method for analyzing a sample aggregate includes arranging a plurality of sample-exposed Taylor cone emitter devices 200 as an array of Taylor cone emitter devices 200 in a Taylor cone emitter device storage device 400, at least partially arranging a first microtiter array tray 100 in a substrate chamber 401, and preparing the array of Taylor cone emitter devices 200 for analysis in the Taylor cone emitter device storage device 400. Each of the arrays of Taylor cone emitter devices 200 is withdrawn from the Taylor cone emitter device storage device 400 and analyzed by the first analytical method for screening for predetermined sample characteristics. The arrays of Taylor cone emitter devices 200 are then sorted based on predetermined sample characteristics, and the arrays of Taylor cone emitter devices 200 are compacted until they become compacted arrays, eliminating Taylor cone emitter devices 200 that lack the predetermined sample characteristics. The second analytical method is performed on an array of compacted Taylor cone emitter devices 200.

[0062]

[0068] The first analytical method includes, but is not limited to, any suitable method, mass spectrometry via a direct interface. The second analytical method includes, but is not limited to, any suitable method, liquid chromatography, hybrid chromatography-mass spectrometry, capillary electrophoresis, mass spectrometry-based immunoassay, or a combination thereof.

[0063]

[0069] Preparing an array of Taylor cone emitter devices 200 for analysis may include placing a first rinse solution into the array of wells 130 of a first microtiter array tray 100, partially immersing the array of Taylor cone emitter devices 200 in the first rinse solution, and removing the first microtiter array tray 100. The first rinse solution may include, but is not limited to, any suitable aqueous or non-aqueous solution suitable for cleaning the Taylor cone emitters prior to immersion in the sample. The Taylor cone emitter device storage apparatus 400 may be agitated while the array of Taylor cone emitter devices 200 is partially immersed in the first rinse solution. After removing the first microtiter array tray 100 from the Taylor cone emitter device storage apparatus 400, the array of Taylor cone emitter devices 200 may be dried. After the first microtiter array tray 100 is removed, it may be replaced with a second microtiter array tray 100 in the Taylor cone emitter device storage device 400. After the first microtiter array tray 100 is removed and before each of the arrays of Taylor cone emitter devices 200 is analyzed, the first microtiter array tray 100 may be replaced in the Taylor cone emitter device storage device 400 with a second microtiter array tray 100 having the extraction solution in an array of wells 130, and the Taylor cone emitter device storage device 400 may be agitated. After analyzing each of the Taylor cone emitter device 200 arrays using the first analytical method, the second microtiter array tray 100 may be replaced with a third microtiter array tray 100 having the second rinse solution inside the array of wells, and the array of Taylor cone emitter devices 200 may be partially immersed in the second rinse solution and optionally agitated. The second rinse solution may include, but is not limited to, any suitable aqueous or non-aqueous solution suitable for cleaning the Taylor cone emitters after immersion in the sample.

[0064]

[0070] Referring to Figure 8, multiple microtiter array trays 100 may be screened to distinguish between positive samples 810 and negative samples 820 from untested samples 800 by the method shown in Figure 7, the positive samples 810 may then be compacted into the microtiter array trays 100, and any remaining wells 130 may be left empty 830.

[0065]

[0071] While the above specifications are described with reference to exemplary embodiments, it will be understood by those skilled in the art that various modifications can be made and equivalents can be substituted for their elements without departing from the scope of the invention. Furthermore, many modifications can be made to adapt the teachings of the invention to specific situations or materials without departing from the essential scope of the invention. Thus, it is intended that the invention is not limited to the specific embodiments disclosed as the best mode intended for carrying out the invention, but rather that the invention includes all embodiments that fall within the scope of the appended claims.

Claims

1. A method for analyzing a sample aggregate, This involves arranging multiple sample-exposed Taylor cone emitter devices as an array of Taylor cone emitter devices inside a Taylor cone emitter device storage device, Each of the arrays of Taylor cone emitter devices is A substrate having at least one flat surface, An adsorbent layer disposed on at least a portion of the at least one flat surface, A tapered tip portion extending from the base, A receiving mount configured for removable mounting to the receiving device's mounting section, and Includes a clock structure configured to fix the radial orientation of the flat surface relative to the receiving device, The Taylor cone emitter device storage apparatus is Storage device plate, A storage device wall extending from the aforementioned storage device plate and surrounding the base chamber, An array of orifices disposed inside the storage device plate, wherein each of the orifices is configured to receive and hold the substrate and receiving mount of one Taylor cone emitter device of the array of Taylor cone emitter devices, and An array of clock structure interfaces disposed inside the storage device plate, the array of clock structure interfaces is configured to guide the clock structure of each Taylor cone emitter device of the array of Taylor cone emitter devices to a predetermined radial orientation, thereby fixing each of the Taylor cone emitter devices in the predetermined radial orientation, The substrate chamber is configured to at least partially receive the microtiter array tray and to receive the substrate of each Taylor cone emitter device of the array of Taylor cone emitter devices, wherein the substrate and the tapered tip extending from the substrate are located at a distance from any adjacent Taylor cone emitter devices of the array of Taylor cone emitter devices located inside the storage device wall or the Taylor cone emitter device storage device. The array of orifices, arranged inside the storage device plate, is distributed in alignment with the microtiter array tray, so that each of the arrays of Taylor cone emitter devices is positioned inside a separate well of the array of wells of the microtiter array tray when the microtiter array tray is at least partially received by the substrate chamber. By arranging multiple sample-exposed Taylor cone emitter devices, The first microtiter array tray is placed at least partially inside the substrate chamber, To prepare the array of Taylor cone emitters for analysis inside the Taylor cone emitter device storage apparatus, In order to screen for predetermined sample characteristics, each of the Taylor cone emitter devices in the array is withdrawn from the Taylor cone emitter device storage device, and each of the Taylor cone emitter devices in the array is analyzed by the first analytical method. Based on the predetermined sample characteristics, the array of Taylor cone emitter devices is sorted to form a compacted array of Taylor cone emitter devices. The second analytical method is performed on the array of compacted Taylor cone emitter devices. Methods that include...

2. The method according to claim 1, wherein the Taylor cone emitter device storage device further includes a storage device cover configured to cover the storage device plate in order to secure the array of Taylor cone emitter devices inside the array of orifices.

3. The method according to claim 1, wherein the first analytical method is a mass spectrometry method via a direct interface.

4. The method according to claim 1, wherein the second analytical method is selected from the group consisting of liquid chromatography, hybrid chromatography-mass spectrometry, capillary electrophoresis, mass spectrometry-based immunoassay, and combinations thereof.

5. The method according to claim 1, wherein preparing the array of Taylor cone emitter devices for analysis includes placing a first rinse solution inside the array of wells of the first microtiter array tray, partially immersing the array of Taylor cone emitter devices in the first rinse solution, and removing the first microtiter array tray.

6. The method according to claim 5, wherein the Taylor cone emitter device storage apparatus is agitated while the array of Taylor cone emitters is partially immersed in the first rinse solution.

7. The method according to claim 5, wherein after the first microtiter array tray is removed, the array of Taylor cone emitter devices is dried.

8. The method according to claim 5, wherein, after the first microtiter array tray is removed, the first microtiter array tray is replaced with a second microtiter array tray inside the Taylor cone emitter device storage apparatus.

9. The method according to claim 5, wherein, after the first microtiter array tray is removed and before each of the arrays of Taylor cone emitter devices is analyzed, the first microtiter array tray is replaced inside the Taylor cone emitter device storage apparatus with a second microtiter array tray having an extraction solution inside the array of wells, and the Taylor cone emitter device storage apparatus is agitated.

10. The method according to claim 9, wherein after analyzing each of the Taylor cone emitter device arrays using the first analytical method, the second microtiter array tray is replaced with a third microtiter array tray having a second rinse solution inside the array of wells, and the Taylor cone emitter device array is partially immersed in the second rinse solution.

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