Systems and methods for toxin and chemical detection

Abstract

A detection probe is provided. The detection probe includes a handle assembly having a probe body, a swab detachably couplable to the probe body of the handle assembly and configured to collect a sample, and an assay cartridge configured to receive at least a portion of the swab. The assay cartridge includes a first chamber retaining an assay solvent, a second chamber disposed distal of the first chamber and retaining an assay reagent, and a trap disposed distal of the second chamber. The trap is configured to filter a mixture of the assay solvent, the assay reagent, and the sample collected by the swab and capture tags released from the mixture that are indicative of the presence of toxins in the sample.

Description

SYSTEMS AND METHODS FOR TOXIN AND CHEMICAL DETECTIONBACKGROUND

[0001] The embodiments described herein relate generally to biological agent detection, and, more particularly, detection cartridges for use with ion-mobility spectrometry systems.

[0002] Detecting and identifying biological toxins such as Ricin, Abrin, and Botulinum Neurotoxin presents a unique challenge for assay developers who generally rely on nucleic acid-based detection technologies. While Polymerase Chain Reaction (PCR) or Next- Generation Sequencing (NGS) methods can be designed to detect the genetic material from toxin-producing organisms, they generally cannot directly detect biologically active or live protein-based toxins.

[0003] Various technologies have emerged that either directly detect the toxin or employ functional assays to determine its presence. Direct detection assays can range from simple immuno-based assays to more intricate cell-based assays. However, immune-based assays (e.g., Enzyme Linked Immunosorbent Assay (ELISA), lateral flow, etc.) often necessitate multiple processing steps, or possess low sensitivity, thereby limiting their utility in field settings. On the other hand, functional assays rely on enzymatic activity to detect cleavage products when the toxin is present. While these methods can offer excellent sensitivity and the ability to detect multiple toxins simultaneously, they do require labbased mass spectrometers or fluorescent spectrometers, thereby impeding field deployment.BRIEF DESCRIPTION

[0004] In one aspect, a detection probe is provided. The detection probe includes a handle assembly including a probe body, a swab detachably couplable to the probe body of the handle assembly and configured to collect a sample, and an assay cartridge configured to receive at least a portion of the swab. The assay cartridge includes a first chamber retaining an assay solvent, a second chamber disposed distal of the first chamber and retaining an assay reagent, and a trap disposed distal of the second chamber. The trapis configured to filter a mixture of the assay solvent, the assay reagent, and the sample collected by the swab and captured tags released from the mixture and indicative of the presence of toxins in the sample.

[0005] In another aspect, a detection system is provided. The detection system includes a detector configured to identify a toxic compound, a heater adapter operably coupled to the detector and configured to heat and vaporize a sample, and a detection probe. The detection probe includes a swab operably coupled to the detection probe and configured to collect a sample, and an assay cartridge configured to receive at least a portion of the swab. The assay cartridge includes a first chamber retaining an assay solvent, a second chamber disposed distal of the first chamber and including an assay reagent, and a trap disposed distal of the second chamber. The trap is configured to filter a mixture of the assay solvent, the assay reagent, and the sample collected by the swab and capture tags released from the mixture and indicative of the presence of toxins in the sample.

[0006] In yet another aspect, a method of testing a sample is provided. The method of testing the sample includes collecting a sample using a swab operably coupled to a detection probe, advancing the swab into an assay cartridge to break a seal separating an assay solvent from an assay reagent, effectuating a reaction between a mixture of the assay solvent, the assay reagent, and the sample collected by the swab, and filtering, via a trap of the assay cartridge, the mixture to capture tags released from the assay reagent and indicative of a toxin present in the mixture.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIG. 1 is a schematic view of one embodiment of a detection probe in accordance with the disclosure;

[0008] FIG. 2 is a cross-sectional view of a handle of the detection probe of FIG. 1;

[0009] FIG. 3 is a side view of a probe of the detection probe of FIG. 1;

[0010] FIG. 4 is a side view of a plunger of the detection probe of FIG. 1;

[0011] FIG. 5 is a side view of a swab of the detection probe of FIG. 1;

[0012] FIG. 6 is a cross-sectional view of an assay cartridge of the detection probe of FIG. 1;

[0013] FIG. 7 is a schematic view of one embodiment of an assay reagent that may be used with the assay cartridge of FIG. 6;

[0014] FIG. 8 is a schematic view of another embodiment of an assay reagent that may be used with the assay cartridge of FIG. 6;

[0015] FIG. 9A is a schematic view of an initial state of the assay reagent of FIG. 6;

[0016] FIG. 9B is a schematic view of a toxin cleaving a toxin recognizable peptide of the assay reagent of FIG. 9 A;

[0017] FIG. 9C is a schematic view of cleaved heat-labile small-molecule tags of the assay reagent of FIG. 9B;

[0018] FIG. 10 is a perspective view of one embodiment an ion-mobility spectrometry (IMS) system in accordance with the disclosure;

[0019] FIG. 11 is a perspective view of an IMS detector of the IMS system of FIG. 10 being received within an IMS heater adapter of the IMS system of FIG. 10;

[0020] FIG. 12 is a perspective view of a lid of the IMS heater adapter of FIG. 10 being placed on a body of the IMS heater adapter;

[0021] FIG. 13 A is a schematic view of a sample being collected by the detection probe of FIG. 1;

[0022] FIG. 13B is a schematic view of a swab of the detection probe of FIG. 13A being inserted within the assay cartridge of FIG. 6;

[0023] FIG. 13C is a schematic view of the swab of the detection probe of FIG. 13B submerged within a mixture of an assay solvent, an assay reagent, and the sample collected by the swab;

[0024] FIG. 13D is a schematic view of the detection probe of FIG. 13C illustrating filtering of the mixture of FIG. 13C to capture cleaved heat-labile small-molecule tags within a trap of the assay cartridge of FIG. 13C;

[0025] FIG. 13E is a schematic view of the detection probe of FIG. 13D illustrating removal of a collector of the assay cartridge of FIG. 13D;

[0026] FIG. 13F is a schematic view of the detection probe of FIG. 13E illustrating removal of the assay cartridge of FIG. 13E;

[0027] FIG. 14 is a schematic view of a computing system of the IMS system of FIG. 10;

[0028] FIG. 15A is a flow diagram of a method of testing a sample for toxins in accordance with the disclosure;

[0029] FIG. 15B is a continuation of the flow diagram of FIG. 15 A; and

[0030] FIG. 15C is a continuation of the flow diagram of FIG. 15B.DETAILED DESCRIPTION

[0031] In the following specification and the claims, reference will be made to a number of terms, which shall be defined to have the following meanings.

[0032] The singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise.

[0001] Approximating language, as used herein throughout the specification and claims, is applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as “about”, “approximately”, and “substantially”, is not to be limited to the precise value specified. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value. Here and throughout the specification and claims, range limitations are combined and interchanged, such ranges are identified and include all the sub-ranges contained therein unless context or language indicates otherwise.

[0002] The term “proximal” refers to the portion of the device or component that is closer to the user and the term “distal” refers to the portion of the device or component that is farther from the user. Additionally, terms such as front, rear, upper, lower, top, bottom, and similar directional terms are used as relative terms simply for convenience of description and are not limiting in nature. Further, to the extent consistent, any of the aspects and features detailed herein may be utilized in conjunction with any of the other aspects and features detailed herein.

[0033] The present disclosure is directed to systems and methods for detecting biological toxins using ion-mobility spectrometry (IMS). A detection probe includes a handle assembly having a probe body, a swab detachably couplable to the probe body of the handle assembly and configured to collect a sample, and an assay cartridge configured to receive at least a portion of the swab. The assay cartridge includes a first chamber retaining an assay solvent, a second chamber disposed distal of the first chamber and retaining an assay reagent, and a trap disposed distal of the second chamber. The trap is configured to filter a mixture of the assay solvent, the assay reagent, and the sample collected by the swab and capture tags released from the mixture that are indicative of the presence of toxins in the sample.

[0034] Turning now to the drawings, FIG. 1 illustrates one embodiment of a detection probe in accordance with the disclosure and generally identified by reference numeral 10. The detection probe 10 includes a handle assembly 12, a swab 60 that is configured to be selectively attachable to the handle assembly 12, and an assay cartridge 70 that is configured to be selectively attachable to the handle assembly 12.

[0035] The handle assembly 12 includes a handle 14, a probe body 30 slidably received within the handle 14, and a plunger 40 slidably supported by the handle 14 and in mechanical communication with the probe body 30. With additional reference to FIG. 2, the handle 14 defines an outer surface 16 extending between a first end portion 18 and an opposite second end portion 20. Although generally illustrated as defining a cylindrical profile, it is envisioned that the handle 14 may define any suitable profile, such as rectangular, square, hexagonal, oval, etc., and combinations thereof, without departing from the scope of the disclosure. The handle 14 includes an inner surface 22 defining a cavity 24 configured to slidably receive a portion of the probe body 30 and a portion of the plunger 40. An opening 26 is defined through the second end portion 20 and is in fluid communication with the cavity 24. As will be described in further detail hereinbelow, the opening 26 is configured to receive a portion of the probe body 30. A lumen 28 is defined through the first end portion 18 and is in fluid communication with the cavity 24. As will be described in further detail hereinbelow, the lumen 28 is configured to slidably receiveand slidably support a portion of the plunger 40, enabling the plunger 40 to translate along a longitudinal axis defined by the handle 14.

[0036] With reference to FIGS. 1 and 3, the probe body 30 includes an outer surface 32 extending between a first end portion 34 and an opposite second end portion 36. The probe body 30 is configured to be received within the opening 26 of the handle 14 and is disposed at least partially within the cavity 24 of the handle 14. In this manner, the first end portion 34 is disposed within the cavity 24 and the second end portion 36 is disposed external to and extends distal from, the second end portion 20 of the handle 14. It is envisioned that the probe body 30 may be fixedly coupled to the handle 14 or may be slidably supported within the opening 26 to enable translation of the probe body 30 along the longitudinal axis defined by the handle 14. An annular flange 38 is disposed on, and extends radially outward from, the outer surface 32 of the probe body 30. As will be described in further detail hereinbelow, the annular flange 38 abuts or otherwise contacts a proximal portion of the assay cartridge 70 to limit or otherwise inhibit advancement of the second end portion 36 of the probe within the assay cartridge 70. In this manner, the probe body 30 defines an outer dimension that enables the second end portion 36 of the probe body 30 to be received within a portion of the assay cartridge 70. Although generally described herein as being a flange, it is envisioned that the annular flange 38 may extend about a circumference of the outer surface 32 of the probe body 30 without departing from the scope of the disclosure. In embodiments, the annular flange 38 may include a pair of tabs, may be non-contiguous about the circumference of the probe body 30, may be contiguous about the circumference of the probe body 30, etc. As will be described in further detail hereinbelow, the first end portion 34 of the probe body 30 is configured to abut or otherwise engage a portion of the plunger 40, enabling distal advancement of the plunger 40 to effectuate a corresponding distal advancement of the probe body 30 relative to the handle 14. The second end portion 36 is selectively couplable to the swab 60 enabling selective coupling and decoupling of the swab 60 from the second end portion 36 of the probe body 30, as will be described in further detail hereinbelow. In embodiments, the probe body 30 may define a through-bore 31 extending through the first end portion 34and the second end portion 36 for slidably receiving and translatably supporting the swab 60. In this manner, the swab 60 is permitted to be longitudinally translated relative to the probe body 30 to enable the swab 60 to selectively extend distally from the second end portion 36 and rupture or otherwise break the seal 88 of the assay cartridge 70, as will be described in further detail hereinbelow.

[0037] Continuing with FIG. 1 and with additional reference to FIG. 4, the plunger 40 includes a plunger rod 42 extending between a proximal end portion 44 and an opposite, distal end portion 46. The plunger rod 42 defines an outer dimension enabling the plunger rod 42 to be slidably received within and translatably supported by the lumen 28 of the handle 14. The proximal end portion 44 is selectively engageable, effectuating distal translation of the plunger rod 42 in reaction to a force applied to the proximal end portion 44 in a distal direction, and effectuating proximal translation of the plunger rod 42 in reaction to a force applied to the proximal end portion 44 in a proximal direction. In embodiments, a flange or other engagement feature 48 is defined on the proximal end portion 42. In one non-limiting embodiment, the flange 48 includes an outer dimension that is larger than the lumen 28 of the handle 14 to inhibit or otherwise prevent the distal end portion 42 of the plunger 40 from being received within the cavity 24 of the handle 14. The distal end portion 46 of the plunger rod 42 is configured to abut or otherwise engage the first end portion 34 of the probe body 30. In this manner, distal translation of the plunger 30 effectuates a corresponding distal translation of the probe body 30 relative to the handle 14. It is envisioned that the distal end portion 46 of the plunger may define any suitable profile capable of being received within the cavity 24 of the handle and engaging the first end portion 34 of the probe body 30. In one non-limiting embodiment, the distal end portion 46 defines a radially outward extending flange 50 defining an outer dimension that is complimentary to the dimension of the inner surface 22 of the handle 14 to provide additional support in the radial direction. Although generally described as being two separate components, it is envisioned that the probe body 30 and the plunger 40 may be integral with one another, such as formed from a single piece of material, fixedly coupledto one another, selectively coupled to one another, etc., and combinations thereof, without departing from the scope of the disclosure.

[0038] In embodiments, the detection probe 10 may include a stopper 52 selectively couplable to the plunger 40. It is envisioned that the stopper 52 may be interposed between the proximal end portion 44 of the plunger 40 and the first end portion 18 of the handle 14 to inhibit or otherwise prevent distal translation of the plunger 40 relative to the handle 14. As will be described in further detail hereinbelow, by inhibiting distal translation or movement of the plunger 40, the stopper 52 inhibits accidental piercing of the third seal 95 of the assay cartridge 70 or accidental flow of the mixture of assay solvent 90, the assay reagent 100, and the sample S collected by the swab 30. In this manner, to pierce or otherwise cause the swab 60 to break the third seal 95 (FIGS. 6 and 13C) of the assay cartridge 70, the stopper 52 must first be removed from the plunger 40. Although generally described as being a separate component from the plunger 40, it is envisioned that the stopper 52 may be an integrated component and may be any suitable feature capable of selectively inhibiting distal translation of the plunger 40 relative to the handle 40, such as a detent, a living hinge, a breakaway tab, a selectively actuatable lock, etc., and combinations thereof, without departing from the scope of the disclosure.

[0039] With reference to FIGS. 1 and 5, the swab 60 defines an outer surface 62 extending between a proximal end portion 64 and an opposite, distal end portion 66. The proximal end portion 64 of the swab 60 is removably couplable to the second end portion 36 of the plunger. In this manner, the swab 60 may be secured or otherwise disposed in a sterile or uncontaminated enclosure (not shown) and selectively coupled to the second end portion 36 of the probe body 30 when acquiring and testing a sample. It is envisioned that the swab 60 may be selectively coupled to the probe body 30 in any suitable manner, such as a detent, a press-fit-, a friction-fit, a snap-fit, fasteners, adhesives, hook-and-loop fasteners, etc., and combinations thereof. A sampling surface 68 is disposed on or otherwise defined on the distal end portion 66 of the swab 60. The sampling surface 68 adsorbs, absorbs, or otherwise captures materials, chemicals, or compounds, such as biological toxins, for testing. In embodiments, the sampling surface 68 may be formedfrom or include one or more of a paper-based swab material, Nomex 410, and combinations thereof, and may be rigid or resilient depending upon the design needs of the swab 60. As will be described in further detail hereinbelow, the distal end portion 66 of the swab 60, when advanced in a distal direction, punctures or otherwise breaks the second seal 94 (FIGS. 6 and 13C) of the assay cartridge 70 to mix the materials, chemicals, or compounds captured by the sampling surface with a solution retained within the assay cartridge 70.

[0040] Turning to FIG. 6, the assay cartridge 70 includes a housing 72, an assay solvent 90, one or more assay reagents 100, a trap 110, and a collector 120. The housing 72 includes an outer surface 74 extending between a first end portion 76 and an opposite, second end portion 78. The housing includes an inner surface 80 defining a cavity or receptacle 82. It is envisioned that the receptacle 82 may extend entirely through each of the first end portion 76 and the second end portion 78, only the first end portion 76, only the second end portion 78, or may be entirely contained within the housing 72, without departing from the scope of the disclosure. An annular groove 84 is defined within the inner surface 80 adjacent to the first end portion 76. The annular groove 84 defines an inner dimension that is equal to or greater than the outer dimension of the probe body 30 to enable the probe body 30 to be advanced within the receptacle 82 and / or the space defined within the annular groove 84 (as shown in FIGS. 13B and 13C). The inner surface 80 of the housing 72 of the assay cartridge 70 defines an inner dimension that is equal to or greater than the outer dimension of the outer surface 62 of the swab 60 to enable the swab 60 to be selectively received within the receptacle 82. Although generally illustrated as defining a circular profile, it is envisioned that the receptacle 82 and / or the annular groove 84 may define any suitable profile, and in embodiments, may define features that are selectively engageable with corresponding features defined on one or both of the probe body 30 and swab 60. In one non-limiting embodiment, a flange 86 is disposed on or otherwise defined by the first end portion 76. In operation, the flange 86 abuts or otherwise contacts the annular flange 38 (FIG. 13C) of the probe body 30 to inhibit or otherwise prevent further distal advancement of the housing 14 relative to the housing 72. In embodiments where the plunger 40 abuts or otherwise contacts the swab 60, the flange 86of the housing 72 cooperates with the annular flange 38 of the probe to inhibit distal translation of the probe body 30 relative to the housing 72 and enable or otherwise permit distal translation of the swab 60 relative to the probe body 30 and the housing 72.

[0041] With continued reference to FIG. 6, the housing 72 defines a first chamber 88 within the receptacle 82 storing the assay solvent 90. The first chamber 88 is defined by a first seal or barrier 92 and a second seal 94 that is disposed in spaced relation to the first seal 92. In this manner, the first seal 92 is disposed proximal of the second seal 94. The first seal 92 and the second seal 94 cooperate to define the first chamber 88 and store or otherwise retain the assay solvent 90. Each of the first seal 92 and the second seal 94 are operably coupled to the inner surface 80 of the housing 72 and are breakable and / or able to be pierced or otherwise ruptured by the swab 60 upon the application of a force exceeding a predetermined rupture force of the first seal 92 and the second seal 94. As can be appreciated, the first seal 92 and the second seal 94 inhibits or otherwise prevents unintended or accidental release of the assay solvent 90 to the environment and / or the one or more assay reagents 100. It is envisioned that the first seal 92 and the second seal 94 may be formed from any suitable material, including but not limited to, materials suitable for use with toxins, biologicals, chemical warfare compounds, reagents, etc. In embodiments, the first chamber 88 may be formed as a unitary component or as a standalone component that is selectively retained within the housing 72 (e.g., a cartridge). It is contemplated that the assay solvent 90 may be any suitable solvent, such as a phosphate buffer or other supplemented biological buffers, for collecting the sample of interest S and rehydrate the toxin array reagent 100, which as described in further detail hereinbelow, may be lyophilized or otherwise freeze dried.

[0042] The housing 72 defines a second chamber 96 within the receptacle 82 disposed distal of the first chamber 88. In this manner, the second seal 94 separates or otherwise forms a breakable barrier between the first chamber 88 and the second chamber 96. The second chamber 96 stores or otherwise retains the one or more assay reagents 100 within the housing 72. In embodiments, the second chamber 96 is bounded by the second seal 94 on a proximal end portion and by the trap 110 on a distal end portion. It is envisioned thatthe trap 110 may be separated or otherwise insulated from the second chamber 96 using a third seal 95 (FIG. 6) or may be in direct contact with the one or more assay reagents 100. In this manner, the trap 110 is formed in a manner that inhibits or otherwise prevents the assay reagents 100 from flowing or otherwise percolating through the trap 110. As will be described in further detail hereinbelow, in operation, rupturing or otherwise breaking the first seal 92 and the second seal 94 enables the assay solvent 90 to mix with the one or more assay reagents 100 and release heat-labile small-molecule tags 104 from assay reagents 100 corresponding to respective biological toxins, which can then be detected using the IMS system 200 (shown in FIGS. 10-12).

[0043] With continued reference to FIG. 6, the housing 72 defines a third chamber or trap 110 within the receptacle 82 disposed distal of the second chamber 96. The trap 110 includes a material 112 for capturing or otherwise filtering heat-labile small molecule tags 104 released from the assay reagents when toxins are present in the mixture of the assay solvent 90 and the assay reagents 100. In one non-limiting embodiment, the trap 110 is formed from or retains a desalting resin for trapping or otherwise filtering heat-labile small molecule tags 104 and permitting beads 106 of the assay reagents 100 to pass through the trap 110 and into the collector 120. As can be appreciated, the type of material 112 may be determined or otherwise selected based on the “charge property” of the heat-labile small-molecule tag 104. In embodiments, if the charge of the heat-labile small-molecule tag 104 is positive, then cation-exchange resin may be used to trap the positive heat-labile small-molecule tag 104. In other embodiments, if the charge of the heat-labile smallmolecule tag 104 is negative, then anion-exchange resin may be used to trap the negative heat-labile small-molecule tag 104. As will be described in further detail hereinbelow, the heat-labile small-molecule tags 104 captured by the trap 110 may be transferred or otherwise transported to the IMS system 200 for further processing and detection of biological toxins.

[0044] The collector 120 defines a generally bowl-shaped configuration having an outer surface 122 extending between a proximal end portion 124 and an opposite distal end portion 126. The collector 120 includes an inner surface 128 defining a depression or-l icavity 130 extending through the proximal end portion 124. As will be appreciated, the depression 130 captures or otherwise retains a mixture of assay solvent and assay reagents 100 that have not been filtered by the trap 110. In embodiments, the collector 120 may be detachably coupled to the housing 72 (shown in FIG. 13E). In one non-limiting embodiment, the collector 120 includes an aperture 132 defined through the distal end portion 124 and in open communication with the depression 130 and a corresponding plug or closure 134 for selectively opening and closing the aperture 132 to inhibit or permit the contents of the depression 130 to be drained or otherwise removed from the collector 120.

[0045] With reference to FIGS. 7, 8, and 9A-9C, the one or more assay reagents 100 are toxin mediated cleavage assays including bead immobilized toxin recognizable peptides 102 coupling heat-labile small-molecule tags 104 to beads or another suitable substrate 106. The beads may be formed from any suitable material, and in embodiments, may be formed from an inert material that is coated with or otherwise coupled to peptides 102 corresponding to specific toxins, such as ricin, Abrin, and Botulinum Neurotoxin, which are encoded with a unique toxin specific cleavage site. If a toxin is present, it will selectively cleave the peptide 102 corresponding to the toxin at specific sites, resulting in the release of smaller, heat-labile fragments or small-molecule tags 104 from the beads 106.

[0046] In embodiments, a first reagent 100a includes heat-labile small-molecule tags 104a coupled to the bead 106a by peptides 102a (shown in FIG. 7) recognizable by a first toxin and a second reagent 100b includes heat-labile small-molecule tags 104b coupled to the bead 106b by peptides 102b (shown in FIG. 8) recognizable by a second toxin. In operation, when a sample captured by the swab 60 is mixed with the assay reagents 100a, 100b (FIG. 9A), if the first toxin is present the first toxin 108 will cleave one or more of the heat-labile small-molecule tags 104a corresponding to the first toxin (FIG. 9B), which are then permitted to separate from the bead 106 (FIG. 9C), and the peptides 102b remain coupled to the bead 106b. If the second toxin is present, the second toxin will cleave one or more of the heat-labile small-molecule tags 104b corresponding to the second toxin and the peptides 102a remain coupled to the bead 106a. It is envisioned that the assay reagents100 may utilize a combination of different heat-labile small-molecule tags 104 coupled to the beads 106 using the same type of peptide 102. In this manner, multiple different heat- labile small-molecule tags 104 must be present or otherwise detected to determine if a toxin is present in the sample, thereby requiring multiple simultaneous false positives to generate a false alarm, ensuring a reliable detection system. In embodiments, the assay cartridge 70 may retain five or more assay reagents 100 for detecting five or more different types of toxins (e.g., a multiplex system), although it is envisioned that the assay cartridge 70 may include any number of assay reagents 100 for detecting any number of toxins without departing from the scope of the disclosure.

[0047] As can be appreciated, cell-free or purified biomolecules, such as antibodies, proteins, and peptides, are susceptible to instability because of oxidation, hydrolysis, aggregation, and photolytic degradation, which ultimately lead to reduced efficacy on shipping and long-term storage. In embodiments, the assay reagents 100, including the bead-immobilized toxin-specific peptides 102 and the corresponding small-molecule tags 104 may be lyophilized or otherwise freeze-dried and stored in the assay cartridge 70. In this manner, when the freeze-dried assay reagents 100 are mixed with the assay solvent 90, the assay solvent 90 hydrates and / or solubilizes the freeze-dried assay reagents 100 enabling the toxins captured by the swab 60 to mix with the assay reagents 100. The solubilized, cleaved, heat-labile small-molecule tags 104 are separated and / or otherwise filtered from the beads 106 by the trap 110.

[0048] Referring to FIGS. 10-12, it is envisioned that the detection probe 10 may be utilized by a chemical warfare detection system, which in embodiments, may be an ionmobility spectrometry (IMS) system 200, which may include an IMS detector 202, such as the LCD 4™ marketed and sold by Smiths Detection Group Ltd. The IMS detector 202 is a lightweight and versatile chemical warfare agent (CWA) and toxic industrial chemical (TIC) detector, capable of detecting gas and vapor threats at or below immediately dangerous to life and health (IDLH) levels. In this manner, the IMS detector 202 is handheld and capable of being easily transported. The IMS detector 202 detects CWAs and TICs by separating and identifying ionized molecules present in a gas phase of thetoxin based on the mobility of the molecules in a carrier buffer gas. Although generally described as utilizing the LCD 4™, it is envisioned that the IMS system 200 may utilize any suitable IMS detector, utilizing any suitable IMS principle and / or concept without departing from the scope of the disclosure.

[0049] As can be appreciated, the biological toxins captured by the swab 60 are not in a gaseous or vapor state, but rather, are solids and / or liquids collected from a surface or a deposit of material of interest. As a result, the IMS detector 202 alone is typically unable to detect these solid and / or liquid state toxins. Toxins of this form have been detected using mass spectrometry (MS), such as Endoprep-MS, with the cleavage products, or resulting molecule tags, having a mass of between about 700 and 4000 atomic mass units (AMU). As can be appreciated, molecule tags having such a mass are not typically detected efficiently using IMS. Using the systems and methods described herein, the assay reagents 100 described above may include heat-labile small-molecule tags 104 having a mass of between about 100 AMU and 300 AMU. As can be appreciated, heat-labile smallmolecule tags having an atomic mass in the range of between about 100 AMU and 300 AMU can be effectively observed or otherwise detected using IMS.

[0050] It is envisioned that the IMS system 200 may include a trace detector or heater adapter 204 for vaporizing the solid or liquid phase heat-labile small-molecule tags 104 for detection using IMS. In embodiments, the heater adapter 204 may be the XID adapter marketed and sold by Smiths Detection Group Ltd., although it is envisioned that the heater adapter 204 may be any suitable heater adapter or trace detector capable of vaporizing liquid or solid samples in preparation for use with an IMS detector. The heater adapter 204 defines a heater body 206 defining a receptacle 208 for selectively receiving and retaining the IMS detector 202. In embodiments, the receptacle 208 is in thermal communication with a heater or other heat generating device 210 to vaporize the heat-labile small-molecule tags 104. The heater adapter 204 includes a heater cover or lid 212 that is selectively couplable to the heater body 206 to seal or otherwise close the receptacle 208. In embodiments, the heater cover 212 forms a hermetic seal with the heater body 206. In embodiments, the heater cover 212 defines a cavity 214 (FIG. 12) to accommodate the IMSdetector 202 when the IMS detector 202 is disposed within the receptacle 208. The heater cover 212 includes a port or through-bore 216 (FIG. 12) defined through the heater cover 212 and in open communication with the cavity 214 and / or the receptacle 208. The port 216 is selectively engageable with the detection probe 10 to selectively couple the detection probe 10 to the heater cover 212 for storage and / or testing of a sample. In embodiments, coupling the detection probe 10 to the heater cover 212 forms a hermetic seal. In one nonlimiting embodiment, the assay cartridge 70 is selectively couplable to a portion of the IMS detector 202 or selectively couplable to a portion of the heater adapter 204. In operation, the heater adapter 204 heats or otherwise increases a temperature within the cavity 214 to vaporize or otherwise cause the heat-labile small-molecule tags 104 captured within the trap 110 to become gaseous. The gaseous heat-labile small-molecule tags 104 are then detectable by the IMS detector 202.

[0051] Turning to FIGS. 13A-13F, in operation, the swab 60 of the detection probe 10 is drawn over or otherwise placed in contact with a sample of interest “S” (FIG. 13 A). A portion of the sample of interest S is captured or otherwise retained by the swab 60, at which point the swab 60 and a distal portion of the probe body 30 is advanced within the receptacle 82 of the assay cartridge 70 (FIG. 13B). The detection probe 10 is further advanced until the swab 60 abuts or otherwise contacts the first seal 92 of the assay cartridge 70, at which point a force is applied or otherwise exerted on the detection probe 10, the plunger 40, and / or the assay cartridge 70 to urge the swab 60 and the first seal 92 towards one another. Continued force is applied or otherwise exerted on the detection probe 10, the plunger 40, and / or the assay cartridge 70 until the force exerted on the first seal 92 by the swab 60 exceeds the predetermined rupture force of the first seal 92. Continued force is applied to the detection probe 10, the plunger 40, and / or the assay cartridge 70 to further urge or otherwise push the detection probe 10 and swab 60 in a distal direction until the force exerted on the second seal 94 by the swab 60 exceeds the predetermined rupture force of the second seal 94. In embodiments, the annular flange 38 of the probe body 30 and the flange 86 of the assay cartridge 70 are oriented or otherwise located at positions where when the annular flange abuts or otherwise contacts the flange86, the second seal 94 is broken but further distal advancement of the detection probe 10 and / or the swab 60 within the receptacle 82 is inhibited or otherwise prevented.

[0052] With the second seal 94 ruptured, the sampling surface 68 of the swab 60 and the resultant mixture of the sample of interest S and the assay solvent 90 interacts with the one or more assay reagents 100 retained in the second chamber 96. The reaction between any toxins present within the sample of interest S and the assay reagents 100 causes peptides 102 corresponding to the specific toxin 108 to be cleaved and otherwise detached from its corresponding bead 106, resulting in the release of the heat-labile small-molecule tags 104 associated with the toxin 108.

[0053] After completion of the reaction or after the passage of a predetermined period of time, the stopper 52 of the detection probe 10 is removed and additional force is applied or otherwise exerted on the plunger 40 to urge or otherwise push the swab 60 in a distal direction towards the trap 110 and enable or force the flow of the mixture of the toxins 108, assay solvent 90, assay reagents 100, and cleaved peptides 102 through the trap 110 to filter or otherwise capture the cleaved peptides 102. The remaining mixture 220 of the toxins 108, assay solvent 90, and assay reagents 100 pass through the trap 110 and are received within the collector 120 (FIG. 13D). In embodiments where the trap 110 is separated from the second chamber 96 by the third seal 95, the additional force is applied or otherwise exerted on the plunger 40 to urge or otherwise push the swab 60 in a distal direction towards the trap 110 and break or otherwise puncture the third seal 95 and enable and / or force the mixture through the trap 110 to filter or otherwise capture the cleaved peptides 102.

[0054] With the mixture 220 received within the collector 120, the collector 120 is decoupled from the assay cartridge 70 or the plug 134 is decoupled from the collector 120 to remove or otherwise allow the mixture 220 of undesirable products of the reaction (FIG. 13E) to drain from the assay cartridge 70 and the assay cartridge 70 is removed from the detection probe 10 (FIG. 13F). The removed assay cartridge 70 is then coupled to the IMS detector 202 or the IMS heater 204 (FIGS. 11 and 12), where the assay cartridge 70 is heated by the IMS heater 204 and the heat-labile small-molecule tags 104 are vaporized or otherwise transformed into a gaseous form that can be subjected to IMS by the IMSdetector 202. The heat-labile small-molecule tags 104 within the resultant gas is ionized by the IMS detector 202 and a toxin corresponding to the ionized heat-labile smallmolecule tags 104 is identified.

[0055] With reference to FIG. 14, one or both of the IMS detector 202 or the IMS heater 204 (e.g., the IMS system 200) may include a computing system 800. The computing system 800 includes a computer 802 and in embodiments, a display 804 that is configured to display one or more user interfaces 806. The computing system 800 includes a processor 808 which executes software stored in a memory 810. The memory 810 may store system data 812 associated with various compounds, such as toxins, biologicals, chemical warfare compounds, reagents, etc., the IMS detector 202, the IMS heater 204, etc. and may store one or more software applications 814 and / or algorithms to be executed by the processor.

[0056] In embodiments, the computing system 800 may include a network interface 816 that enables the computing system 800 to communicate with a variety of other devices and system via the Internet. The network interface 816 may connect the computing system 800 to the Internet via a wired or wireless connection. Additionally, or alternatively, the communication may be via an ad-hoc Bluetooth® or wireless network enabling communication with a wide-area network (WAN) and / or a local-area network (LAN). The network interface 816 may communicate with a cloud storage system 818, in which further data may be stored. The cloud storage system 816 may be remote from or on the premises where the sample of interest S was collected or is being tested. In embodiments, an input module 820 receives inputs from an input device, such as a keyboard, a mouse, or voice commands. An output module 822 connects the processor 808 and the memory 810 to a variety of output devices, such as the display 804, which in embodiments, may be a touchscreen display.

[0057] Turning to FIGS. 15A-15C, one embodiment of a method of testing a sample for toxins is illustrated and generally identified by reference numeral 1500. The method includes coupling 1502 a clean or otherwise sterile swab to the detection probe prior to testing a sample of interest. The sampling surface of the swab is brought into contact withthe sample of interest to collect 1504 or otherwise capture a portion of the sample of interest on the sampling surface. The swab, including the collected sample, is advanced or otherwise inserted 1506 within the receptacle of the assay cartridge. The swab and the assay cartridge are advanced or otherwise urged towards one another 1508 to receive the sampling surface within the first chamber and submerge the sampling surface within the assay solvent. In embodiments where the first chamber includes a first seal, the swab and assay cartridge are advanced or otherwise urged towards one another to break or otherwise pierce 1510 the first seal and submerge the sampling surface within the assay solvent. Continued urging or advancement of the swab and the assay cartridge towards one another causes the swab to break or otherwise pierce 1512 the second seal between the first chamber and the second chamber. Optionally, the swab and assay cartridge are further urged towards one another until the annular flange of the detection probe abuts or otherwise contacts 1514 the flange of the assay cartridge to break or otherwise pierce the second seal and inhibit further advancement of the swab within the assay cartridge. Breaking the second seal enables the assay solvent, the assay reagent, and the sample collected by the swab to mix 1516 and hydrate the freeze-dried assay reagent. The mixture effectuates a reaction 1518 between the mixture of the assay solvent, the assay reagent, and the sample collected by the swab. The reaction is permitted to continue for a predetermined period of time 1520, after which the plunger of the detection probe is depressed or otherwise urged in a distal direction to cause the swab to push or otherwise force the mixture through the trap to filter 1522 or otherwise capture heat-labile small-molecule tags cleaved from the assay reagent by toxins present in the mixture. The filtered mixture is captured 1524 in the collector and the heat-labile small-molecule tabs cleaved from the assay reagent are captured by the trap. The collector, with the filtered mixture is removed 1526 from the assay cartridge, or optionally, the plug is removed 1528 from the collector to enable the filtered mixture to drain from the assay cartridge. The assay cartridge, including the heat- labile small-molecule tags captured by the trap, is operably coupled 1530 to one of the detector or the heat adapter. The detector is placed or otherwise retained 1532 within the receptacle of the heat adapter where the detector is in fluid communication with the assaycartridge. The heat adapter heats 1534 the assay cartridge to vaporize the heat-labile smallmolecule tags captured by the trap. The vaporized heat-labile small-molecule tags are in fluid communication with, and received by, the detector. The vaporized heat-labile smallmolecule tags are subjected to 1536 ion-mobility spectrometry by the detector and compared to a table or list of toxic compounds stored in the memory of the computing system and a toxin associated with the heat-labile small-molecule tag is identified 1538.

[0058] It is envisioned that the above-described method may be repeated as many times as necessary and the steps of the method may be performed in any order without departing from the scope of the disclosure.

[0059] Example embodiments of apparatus and systems are described above in detail. The apparatus and systems are not limited to the specific embodiments described herein, but rather, components of systems and / or apparatus may be used independently and separately from other components described herein. Accordingly, the example embodiments can be implemented and used in connection with many other applications not specifically described herein.

[0060] Although specific features of various embodiments of the disclosure may be shown in some drawings and not in others, this is for convenience only. In accordance with the principles of the disclosure, any feature of a drawing may be referenced and / or claimed in combination with any feature of any other drawing.

[0061] This written description uses examples to disclose various embodiments, including the best mode, and also to enable any person skilled in the art to practice the disclosure, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the disclosure is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.

Claims

CLAIMSWhat is claimed is:

1. A detection probe, comprising: a handle assembly comprising a probe body; a swab detachably couplable to the probe body of the handle assembly, the swab configured to collect a sample; and an assay cartridge configured to receive at least a portion of the swab, the assay cartridge comprising: a first chamber retaining an assay solvent; a second chamber disposed distal of the first chamber, the second chamber retaining an assay reagent; and a trap disposed distal of the second chamber, the trap configured to filter a mixture of the assay solvent, the assay reagent, and the sample collected by the swab and capture tags released from the mixture, the tags indicative of the presence of toxins in the sample.

2. The detection probe according to claim 1, wherein the assay reagent retained in the second chamber includes heat-labile small-molecule tags coupled to beads via toxin recognizable peptides.

3. The detection probe according to claim 2, wherein the assay reagent is freeze-dried.

4. The detection probe according to any preceding claim, wherein the second chamber is separated from the first chamber by a selectively breakable seal, wherein when the selectively breakable seal is in a first, un-broken condition, the assay solvent is inhibited from entering the second chamber, and when the seal is in a second, broken condition, the assay solvent is permitted to enter the second chamber.

5. The detection probe according to any preceding claim, wherein the trap is separated from the second chamber by a selectively breakable seal, wherein when in a first, un-broken condition, a mixture of the assay solvent and the assay reagent is inhibited from entering the trap, and when in a second, broken condition, the mixture of the assay solvent and the assay reagent is permitted to enter the trap.

6. The detection probe according to any preceding claim, wherein the handle assembly includes a plunger operably coupled to the swab, wherein distal translation of the plunger effectuates a corresponding distal translation of the swab.

7. The detection probe according to any preceding claim, wherein a through- bore is defined through the probe body, wherein a plunger is operably coupled to the swab through the through-bore to enable distal translation of the plunger to effectuate a corresponding distal translation of the swab relative to the probe body.

8. The detection probe according to any preceding claim, wherein the assay cartridge further comprises a collector disposed distal of the trap, the collector configured to receive the filtered mixture from the trap.

9. The detection probe according to claim 8, wherein the collector is selectively removable from the assay cartridge.

10. The detection probe according to claim 8, wherein the collector comprises a removable plug, the plug configured to, when removed from the collector, permit the received filtered mixture to drain from the collector.

11. A detection system, comprising: a detector configured to identify a toxic compound;a heater adapter operably coupled to the detector, the heater adapter configured to heat and vaporize a sample; and a detection probe, comprising: a swab operably coupled to the detection probe, the swab configured to collect a sample; and an assay cartridge configured to receive at least a portion of the swab, the assay cartridge comprising: a first chamber retaining an assay solvent; a second chamber disposed distal of the first chamber, the second chamber retaining an assay reagent; and a trap disposed distal of the second chamber, the trap configured to filter a mixture of the assay solvent, the assay reagent, and the sample collected by the swab and capture tags released from the mixture, the tags indicative of the presence of toxins in the sample.

12. The detection system according to claim 11, wherein the detector comprises an ion-mobility spectrometry detector.

13. The detection system according to claim 11 or 12, wherein the assay cartridge is selectively removable from the detection probe and selectively receivable within a portion of the detector.

14. The detection system according to any of claims 11 to 13, wherein the heater adapter defines a receptacle configured to receive the detector.

15. The chemical warfare detection system according to any of claims 11 to 14, wherein the second chamber is separated from the first chamber by a selectively breakable seal, wherein when the selectively breakable seal is in a first, un-broken condition, the assay solvent is inhibited from entering the second chamber, and when theseal is in a second, broken condition, the assay solvent is permitted to enter the second chamber.

16. A method of testing a sample, comprising: collecting a sample using a swab operably coupled to a detection probe; advancing the swab into an assay cartridge to break a seal separating an assay solvent from an assay reagent; effectuating a reaction between a mixture of the assay solvent, the assay reagent, and the sample collected by the swab; and filtering, via a trap of the assay cartridge, the mixture to capture tags released from the assay reagent, the tags indicative of a toxin present in the mixture.

17. The method according to claim 16, further comprising mixing the assay solvent and the assay reagent to hydrate freeze-dried small molecule tags within the assay reagent.

18. The method according to claim 16 or 17, further comprising operably coupling the assay cartridge, including the captured tags, to one of an ion-mobility spectrometry (IMS) detector or a heater adapter.

19. The method according to claim 18, further comprising: heating the assay cartridge to vaporize the captured tags; and detecting the captured tags using ion-mobility spectrometry to facilitate identifying the toxin.

20. The method according to any of claims 16 to 19 further comprising: collecting the filtered mixture in a collector of the assay cartridge disposed distal of the trap; and removing the collector from the assay cartridge.

Images