Point-of-care devices and methods for detecting the infectious status of wounds - Patents.com

Abstract

The wound sampling device for detecting an infectious condition can be used as a point-of-care device that can be placed at a wound site and can detect an infectious marker, infectious condition, or wound healing condition by displaying a visible signal, such as a color change.

Description

[Technical field]

[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of U.S. Provisional Application No. 62 / 952,833, filed December 23, 2019, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Wound healing is a complex and dynamic process. Since microbial or pathogenic infections are detrimental to the wound healing process, it is important to detect an infectious state of the wound as early as possible.

[0003] Currently, when healthcare professionals (HCPs) suspect that a wound may be infected, they swab the suspected wound area and collect a sample of wound fluid for microbiological analysis. HCPs may suspect a wound infection, for example, if there is increased periwound redness, wound exudate / pus, presence of foul odor, increased swelling, tenderness, pain, and / or periwound temperature / fever. However, in most chronic non-healing wounds, such signs of infection are often masked and not very obvious to healthcare professionals.

[0004] A sample of exudate is typically taken from the entire wound using a sterile swab. After the sample has been collected with the swab (i.e., absorbed by the swab), the swab is typically placed in a sterile vial containing a medium that maintains the viability of the microorganisms during transport to the laboratory. The typical process for taking such a sample is to examine the wound site, break open the sterile package containing the swab, swab the wound site with the swab, and then place the swab back into the vial so that the sampling area of ​​the swab is submerged in the maintenance medium. The sample vial is then sent to a laboratory where the contents of the swab are cultured in various microbial culture media for the presence of microorganisms (mainly bacteria and yeast). Microbiological analysis then involves identifying potential pathogenic microorganisms and, if deemed appropriate, performing antibiotic susceptibility testing. Laboratory testers attempt to grow the sample and, if a positive result is obtained, test the sample against various antibiotics. The results are then reported to the healthcare professional, who prescribes the appropriate treatment.

[0005] The process of microbiological analysis of wound swabs in laboratories is complex, expensive and time-consuming (typically 2–5 days). Moreover, such test results are not consistently reliable. For example, laboratory test results indicating the presence of potential pathogens (e.g., Staphylococcus aureus, Pseudomonas aeruginosa) do not necessarily mean that the wound is actually infected. This may lead health care professionals to prescribe antibiotics based solely on the presence of potential pathogens, even when these microorganisms do not actually cause infection. Thus, the incidence of false-positive results is problematic.

[0006] Thus, current practices for determining the infection status of a wound (i.e., microbiological results and clinical signs of infection) are prone to error and may lead to inappropriate treatment (e.g., antibiotic therapy when it is not indicated). A solution to the above problems is still needed to assist healthcare professionals in determining the initial wound infection status. More specifically, a device is needed that allows healthcare professionals to perform analysis of potential wound infections quickly and at the point-of-care (rather than sending samples to a laboratory for testing). The proposed solution would allow healthcare professionals to obtain test results at the point-of-care within minutes that more accurately indicate the infection status of the wound. Summary of the Invention

[0007] The present disclosure provides a device and method for rapid point-of-care detection of wound infection status. In one aspect of the disclosure, a device for detecting wound infection is provided, the device comprising: (a) an indicator unit; and (b) a swab unit, the indicator unit comprising: (i) a sensor tube having a proximal opening; and (ii) a sensor located within the sensor tube; and the swab unit comprising: (i) a swab shaft having a proximal end and a distal end; (ii) a swab tip located at the distal end of the swab shaft; and (iii) a swab handle connected to the swab shaft at the proximal end of the swab shaft and configured to sealingly engage the proximal opening of the sensor tube. In certain embodiments, the sensor comprises a carrier material and at least one substrate operable to undergo a visible color change in response to the expression of a specific infection marker present in wound fluid. In some embodiments, the sensor comprises at least two substrates, each operable to undergo a visible color change in response to the expression of a different marker present in wound fluid. The carrier material may comprise, for example, paper, cellulose, cellulose derivatives, viscose, polyamide, polyester, polyacrylate, cloth, sodium carboxymethylcellulose fiber, or paperboard. The swab tip may comprise, for example, cellulose, modified cellulose, polyurethane foam, polyester, silk, wool, nylon, polypropylene, elastane, or mixtures thereof.

[0008] In some embodiments, the indicator unit further comprises a sensor-retaining insert sealingly engaged to the distal end of the sensor tube, the sensor being attached to the sensor-retaining insert. In some embodiments, the sensor-retaining insert defines a cavity configured to receive the swab tip when the swab unit is sealingly engaged to the indicator unit. In some embodiments, the sensor-retaining insert comprises at least one structural feature within or adjacent to the cavity that guides the swab tip into a desired position aligned with the sensor in the sensor-retaining insert. The at least one structural feature may be, for example, one or more rib structures, sloped cavity walls, and combinations thereof.

[0009] In certain embodiments, the sensor comprises a member selected from the group consisting of an enzyme-responsive indicator, a reagent that is a source of peroxide, an enzyme capable of converting a color reaction, a pH indicator, a total protein detection reagent, a moisture detection reagent, and combinations thereof. One example of a pH indicator that may be used is a pH-sensitive reagent. In some embodiments that include an enzyme-responsive indicator, the enzyme-responsive indicator comprises a moiety capable of producing a visible color or a detectable electronic change upon interaction with one or more target enzymes. The moiety may be, for example, a peroxidase substrate, an arylamine, an aminophenol, an indoxyl, a neutral dye, a charged dye, a nanoparticle, a colloidal gold particle, and combinations or analogs thereof.

[0010] In some embodiments, the swab handle defines a fluid chamber, and the swab handle is operable to receive a fluid in the fluid chamber and to expel the fluid into the sensor tube after the swab tip is positioned within the sensor tube. In some embodiments, the fluid chamber receives about 500 μL, about 1 mL, about 1.5 mL, about 2 mL, about 2.5 mL, about 3 mL, about 3.5 mL, or about 4 mL of fluid.

[0011] In some embodiments including a liquid chamber, the swab handle is configured to manually expel the liquid from the liquid chamber. In some embodiments, the swab handle includes a retaining element configured to couple to the sensor tube and defining a cavity, and a movable element retained within the cavity of the retaining element and movable relative to the retaining element. In some embodiments, the liquid chamber is contained within the movable element. In some embodiments, the movable element further includes a liquid chamber seal, and the swab handle further includes a piercing member fixedly attached to the retaining element, such that moving the movable element from a proximal position to a distal position causes the piercing member to pierce the liquid chamber seal and expel the liquid into the sensor tube. The liquid chamber seal may be, for example, a metal foil or a plastic film. In some embodiments, the swab shaft is fixedly attached to the retaining element such that a proximal end of the swab shaft extends into the cavity of the retaining element, and the piercing member comprises the proximal end of the swab shaft. In certain embodiments, the swab shaft comprises a tube having a longitudinal passage formed therethrough, and after the liquid chamber seal is pierced, the liquid chamber is in fluid communication with the sensor tube through the longitudinal passage. In yet other embodiments, the swab shaft defines a radial opening at a distal end adjacent the swab tip, and after the liquid chamber seal is pierced, the liquid chamber is in fluid communication with the sensor tube through the longitudinal passage and the radial opening. In some embodiments, the swab handle further comprises a locking mechanism operable to restrict proximal movement of the movable element after the liquid chamber seal is pierced.

[0012] In other embodiments including a liquid chamber, the swab handle is configured to automatically expel the liquid from the liquid chamber when the swab handle of the swab unit sealingly engages the proximal opening of the sensor tube. In some embodiments, the swab handle comprises a liquid chamber seal located at a distal end of the liquid chamber, and the indicator unit further comprises a piercing member fixedly attached to the sensor tube in a position such that the tip contacts the liquid chamber seal only when the tip is inserted into the sensor tube, such that insertion of the tip into the sensor tube causes the piercing member to pierce (through) the liquid chamber seal and expel the liquid into the sensor tube. In some embodiments, the piercing member is a piercing ring.

[0013] In another aspect, the present disclosure provides a method of detecting a marker in a wound, the method comprising: (a) contacting the wound with a swab tip of any detection device disclosed herein; (b) inserting the swab tip into the sensor tube to sealingly engage the swab unit with the indicator unit; and (c) monitoring the sensor for a change. In some embodiments, the change is a color change, a fluorescent signal, a luminescent signal, or an electrical change. In some embodiments, the sensor comprises a carrier material and at least one substrate operable to undergo a visible color change in response to expression of a particular infection marker present in wound fluid released from the swab tip. In some embodiments, the method further comprises (d) comparing the signal to a standard or control to determine the level of the marker. In some embodiments, the device comprises a movable element, the method further comprises, following step (b), pressing the movable element. In some embodiments, step (b) comprises contacting the swab tip of the swab unit with the sensor of the indicator unit. In some embodiments, step (b) results in piercing a liquid seal. In some embodiments, the piercing of the liquid seal releases liquid into the sensor tube.

[0014] Further configurations, features, and embodiments of the present disclosure will become apparent from the detailed description herein.

[0015] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief description of the drawings]

[0016] [Figure 1] FIG. 1 shows a schematic diagram of one wound sampling device embodiment comprising a swab unit and an indicator unit. [Diagram 2] FIG. 1 shows a top view of an embodiment of a wound sampling device including a swab unit inserted into an indicator unit. [Diagram 3] FIG. 3 shows a side cross-sectional view of the embodiment shown in FIG. 2. [Figure 4] FIG. 4 shows a perspective view of the indicator unit of the embodiment shown in FIGS. 2 and 3. [Diagram 5] 4 shows a swab unit of the embodiment shown in FIGS. 2 and 3. [Figure 6] FIG. 4 shows a side cross-sectional view of the sensor retaining insert of the embodiment shown in FIGS. 2 and 3. [Figure 7] FIG. 4 shows a side cross-sectional view of a swab tip inserted into the sensor-retaining insert of the indicator unit of the embodiment shown in FIGS. 2 and 3. [Figure 8] FIG. 4 shows a top cross-sectional view of a swab tip inserted into the sensor-retaining insert of the indicator unit of the embodiment shown in FIGS. 2 and 3. [Figure 9] FIG. 4 shows a perspective view of the sensor retaining insert of the embodiment shown in FIGS. 2 and 3. [Figure 10] FIG. 4 shows a side view of the sensor retaining insert of the embodiment shown in FIGS. 2 and 3. [Figure 11] FIG. 4 illustrates an end view of the sensor retaining insert of the embodiment shown in FIGS. 2 and 3. [Figure 12] 13 shows a top view of yet another wound sampling device embodiment including a swab unit inserted into an indicator unit. [Figure 13] 13 shows a side cross-sectional view of the embodiment shown in FIG. 12. [Figure 14] FIG. 14 shows a perspective view of the indicator unit of the embodiment shown in FIGS. 12 and 13. [Figure 15] 14 shows a swab unit of the embodiment shown in FIGS. 12 and 13. [Figure 16] FIG. 14 is a cross-sectional view of the swab unit of the embodiment shown in FIGS. 12 and 13, with respect to the proximal end of the swab shaft, shown inserted into the proximal end of the sensor tube. [Figure 17] FIG. 14 shows the configuration of the movable elements of the handle of the swab unit of the embodiment shown in FIGS. 12 and 13, and also shows the liquid chambers defined therein. [Figure 18] 1 shows the development of liquid from the liquid chamber. [Figure 19] 13 shows yet another embodiment of a wound sampling device, the swab unit of which allows for automatic deployment of liquid from the liquid chamber upon insertion of the swab unit into the indicator unit. [Figure 20] 13 shows an indicator unit of a wound sampling embodiment that allows for automatic deployment of liquid from the liquid chamber upon insertion of the swab unit into the indicator unit. [Figure 21] 21 shows cross-sectional views of the tip of the swab unit shown in FIG. 19 and the indicator unit shown in FIG. 20 at various stages of engagement. [Figure 22] 21 shows cross-sectional views of the tip of the swab unit shown in FIG. 19 and the indicator unit shown in FIG. 20 at various stages of engagement. [Figure 23] 21 shows cross-sectional views of the tip of the swab unit shown in FIG. 19 and the indicator unit shown in FIG. 20 at various stages of engagement. [Figure 24] 21 shows cross-sectional views of the tip of the swab unit shown in FIG. 19 and the indicator unit shown in FIG. 20 at various stages of engagement. [Diagram 25] 20 shows an enlarged cross-sectional image of a portion of the swab unit shown in FIG. 19. [Figure 26] 20 shows a cross section of the swab shaft of the swab unit shown in FIG. 19. [Figure 27] 21 shows a perforated ring of the indicator unit shown in FIG. 20. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] [Definition] As used herein, the term "wound" refers to damage to living tissue, which may be caused, for example, by a cut, blow, or other impact, typically an impact that cuts, tears, or otherwise damages the skin. Examples of wounds include, but are not limited to, abdominal wounds (as a result of surgery, trauma, trunk incision, fascial incision, or other conditions), other large wounds, or incision wounds, lacerations, acute wounds, chronic wounds, subacute wounds, lacerations, traumatic wounds (such as from orthopedic trauma), skin flaps and skin grafts, lacerations, abrasions, contusions, burns, diabetic ulcers, pressure ulcers, fistulas, surgical wounds, traumatic and venous ulcers, fractures, and the like. Wounds may also include deep tissue damage. Deep tissue damage is a term proposed by the National Pressure Ulcer Advisory Committee (NPUAP) to describe a unique form of pressure ulcer. These ulcers have been described by clinicians for many years with terms such as purple pressure sores, ulcers that can worsen, and bruises over bony prominences.

[0018] The wound may be a chronic or acute injury. The disclosed technology may be used for acute or chronic wounds. Acute wounds usually occur as a result of surgery or trauma and usually go through certain known healing stages within a predicted time frame. Chronic wounds often start as acute wounds, and if the healing stages of acute wounds are not followed, the acute wound may become a chronic wound, resulting in a prolonged recovery. The transition from acute to chronic wounds is thought to be due in some cases to the patient having a weakened immune system. Chronic wounds may include, for example, venous ulcers (such as those occurring on the legs), diabetic ulcers (e.g., foot or ankle ulcers), peripheral arterial disease, pressure ulcers, or epidermolysis bullosa (EB), which account for the majority of chronic wounds and primarily affect the elderly.

[0019] Wounds that are considered to be prone to infection are chronic and / or other wounds in elderly people and / or patients who may have: type 1 or type 2 diabetes, Wounds caused by dirty or bacteria-laden objects Bite wounds Wounds that contain debris or the entire object that caused the wound Large or deep wounds Wounds with jagged edges Wounds that are chronic in nature because the wound site is open and the patient is likely to have a compromised immune system

[0020] Throughout this disclosure, various quantities, sizes, dimensions, ratios, etc. are presented in a range format. It should be understood that the description of quantities in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of any embodiment. Thus, the description of a range should be considered to specifically disclose all possible subranges and all individual numerical values ​​within that range, unless the context clearly dictates otherwise. For example, description of a range such as 1-6 should be considered to specifically disclose subranges such as 1-3, 1-4, 1-5, 2-4, 2-6, 3-6, etc., and individual values ​​within those ranges, such as 1.1, 2, 2.3, 4.62, 5, and 5.9. This applies regardless of the breadth of the range. The upper and lower limits of these intervening ranges may be independently included in the smaller ranges and are also included in the disclosure, subject to any specifically excluded limits in the stated ranges. Where a stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure, unless the context clearly dictates otherwise.

[0021] The terms used herein are for the purpose of describing particular embodiments only and are not intended to limit any embodiment. As used herein, the singular forms are intended to include the plural forms unless the context clearly indicates otherwise. Furthermore, the terms "comprises" and "comprises" as used herein will be understood to specify the presence of stated features, integers, steps, operations, elements, and / or components, but will not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0022] Unless specifically stated or clear from the context, as used herein, the term "about" in reference to a number or range of numbers is understood to mean including the stated number and 10% above and below that number, or 10% below the lower limit and 10% above the upper limit of the stated range.

[0023] [Wound sampling device] Described herein are wound sampling devices for detecting the infectious state of a wound and methods of using the wound sampling devices. The wound sampling devices and wound infection detection devices disclosed herein may be for use on a human or animal body. The wound sampling devices described herein may be used as point-of-care devices for detecting the infectious state of a wound, thereby eliminating problems associated with prior art methods of determining the infectious state of a wound, such as sending samples to a laboratory for analysis, which results in significant delays in detecting the infection. In some embodiments, the wound sampling device reacts with wound exudate or wound fluid to detect the infection of the wound through a visible or otherwise detectable change. In some embodiments, the detectable change is a color change. In a preferred embodiment, the color is easily distinguishable from the general color of the wound or body fluid.

[0024] The wound sampling device according to the present disclosure includes two components: (i) an indicator unit including a sensor tube having a proximal opening and a sensor located within the sensor tube, and (ii) a swab unit including a swab shaft having a proximal end and a distal end, a swab handle connected to the proximal end of the swab shaft, and a swab tip located at the distal end of the swab shaft. In the embodiment shown in the figures, the sensor is located at the distal end of the sensor tube. However, it should be understood that the sensor may be located at other locations within the sensor tube without departing from the inventive concepts disclosed herein. The sensor comprises a substrate or combination of substrates operable to undergo a detectable change, e.g., a visible color change, in response to the expression of a particular infection marker (e.g., pH) present in the wound fluid. As used herein, the term "marker" or "infection marker" refers to any substance or characteristic of a substance that is desired to be detected, and in some embodiments includes a host marker, such as a biomarker, indicative of infection of the wound. The swab handle is configured to sealingly engage the proximal opening of the sensor tube in an orientation such that the swab tip is disposed within the sensor tube. The swab shaft has a length such that the swab tip is adjacent and / or in contact with a sensor within the sensor tube when the swab handle is engaged with the proximal opening of the sensor tube. In this configuration, the swab unit is operable to deliver a sample from the wound into contact with the sensor, and a medical practitioner can determine whether a marker is present in the fluid by determining whether the sensor undergoes a detectable change.

[0025] FIG. 1 shows a schematic diagram of one embodiment of a wound sampling device according to the present disclosure. The device 20 includes an indicator unit 30 and a swab unit 40. The indicator unit 30 includes a sensor tube 32 having a proximal opening 34 and a sensor 36 disposed within the sensor tube 32 at a distal end 38 of the sensor tube 32. The sensor 36 may be, for example, a quantity of an active substance (substrate) that undergoes a visible change when contacted with a marker. The active substance may be disposed at the distal end of the sensor tube 32 in a variety of ways. For example, the active substance may be coated on the inner surface of the sensor tube 32 at the distal end of the sensor tube 32 or may be supported on a carrier material disposed within the sensor tube 32 at the distal end of the sensor tube 32. For example, suitable carrier materials may be paper, cellulose, cellulose derivatives, viscose, polyamide, polyester, polyacrylate, cloth, sodium carboxymethylcellulose fiber (commercially available from ConvaTec under the registered trademark "Hydrofibre"), paperboard, or other similar polymers useful as fibers, or any combination thereof. If the active agent is supported on a carrier material, the carrier material may optionally be attached to the inner surface of the sensor tube 32 or held in place by friction. Alternatively, the carrier material may be loosely contained within the sensor tube 32. In one preferred embodiment, the sensor tube 32 is constructed from a transparent or translucent material such that the visible change that occurs when the sensor 36 contacts the marker is visually detectable.

[0026] The swab unit 40 includes a swab tip 41, a swab shaft 43, and a handle (swab handle) 45. The swab tip 41 may be formed of any suitable absorbent material, for example, a flocked type swab tip. In certain embodiments, the swab tip 41 is made of one or more of cotton, polyurethane foam, polyester, rayon, and nylon. In some cases, the absorbent swab tip is made of cellulose (e.g., lyocell), modified cellulose (e.g., viscose or rayon), polyester, silk, wool, nylon, polypropylene, elastane, or mixtures thereof. In some embodiments, the swab shaft 43 includes a scale that may be, for example, stamped, embossed, or printed on the swab shaft 43. In some examples, the scale functions to facilitate measurement of wound depth. FIG. 1 shows the device 20 with the swab unit only partially inserted into the indicator unit 30, and shows a schematic of the positioning of these components just prior to being connected to one another.

[0027] To use the wound sampling device disclosed herein, a liquid specimen is first collected from the wound. Briefly, one suitable method for collecting a liquid specimen from a wound is swabbed by gently rotating the swab shaft between the fingers with the swab tip in contact with the wound. The swab tip is moved edge to edge across the wound in a 10-point zigzag pattern while exerting sufficient pressure to draw fluid from within the wound tissue. The swab unit is then secured to the indicator unit by inserting the swab tip into the proximal opening of the sensor tube and engaging the swab handle with the sensor tube such that the swab tip contacts the liquid specimen with the sensor.

[0028] In another embodiment shown in Figures 2-5, a variation is shown in which the indicator unit comprises a sensor tube, a sensor, and a sensor-retaining insert. For efficient manufacturing, in this embodiment, a sensor tube is provided having a proximal opening and a distal end, and a sensor is disposed at the distal end of the sensor tube by fastening the sensor to a sensor-retaining insert that is inserted into and tightly secured to the distal end of the sensor tube. In certain embodiments, the sensor-retaining insert may optionally comprise internal ribs, internal struts, internal surfaces, or other structures for guiding the swab tip as it enters the sensor-retaining insert to achieve the desired juxtaposition of the swab tip and the sensor. As shown in Figures 2-5, the device 200 comprises an indicator unit 300 and a swab unit 400. Figure 2 shows a side view of the device 200 with the swab unit 400 inserted and connected to the indicator unit 300. A cross-sectional view of the device 200 in the same orientation is shown in Figure 3.

[0029] In Fig. 4, the indicator unit 300 of the device 200 is shown separated from the device 200. As can be seen more clearly in Fig. 4, the indicator unit 300 comprises a sensor tube 303, a sensor 301, and a sensor-retaining insert 305. In the illustrated embodiment, the proximal end 310 of the sensor tube 303 is configured to form a shoulder 315 where both the outer and inner diameters of the sensor tube 303 are each reduced to a smaller diameter at a segment 316 of the sensor tube 303, as shown more clearly in Fig. 3. The segment 316 is sized and configured to seat within a radial channel 406 formed in a handle (swab handle) 405 of the swab unit 400. As will be discussed further below, such positioning is just one option for achieving a sealing engagement of the indicator unit 300 to the swab unit 400 after the swab unit has been used to obtain a sample.

[0030] The sensor 301 and the sensor-retaining insert 305 are disposed in and retained within the distal end 320 of the sensor tube 303. Details of the sensor-retaining insert 305 of this embodiment are shown in FIGS. 6-11. FIG. 6 shows a cross-sectional view of the sensor-retaining insert 305. The sensor-retaining insert 305 comprises a pair of opposed and united rib structures 330, the sensor 301, and one or more angled walls 340. One of the rib structures 330 is shown in FIG. 6. The rib structures 330 and the angled walls 340 guide the position of the swab tip 401 when inserted into the indicator unit 300, allowing for proper spacing and alignment of the swab tip 401 within the sensor-retaining insert 305. The angled walls 340 also allow the swab tip 401 to be pressed in such a way that it contacts the sensor 301 and aids in fluid transfer to the sensor 301. While this embodiment includes the rib structure and angled wall described above to achieve alignment and positioning of the swab tip 401 relative to the sensor 301, alternative structures to achieve this function are contemplated and such alternative structures may be substituted for the rib structure 330 and / or angled wall 340 of this embodiment without departing from the invention. For example, in some alternative embodiments, the sensor-retaining insert defines an internal cavity that is conical in shape or tapered at a first end relative to a second end. In some embodiments, the sensor-retaining insert includes at least one protrusion on an inner surface of the sensor-retaining insert. In some embodiments, the sensor-retaining insert includes at least one, two, three, four, five, six, seven, eight, or more than eight protrusions on an inner surface of the sensor-retaining insert. Alternatively, such structures are omitted in some embodiments. The sensor-retaining insert 305 may be transparent or translucent. In some cases, the sensor-retaining insert 305 is a transparent molded part.

[0031] 5 shows the swab unit 400 of the device 200. The swab unit 400 includes a swab tip 401, a swab shaft 403, and a handle (swab handle) 405. In certain embodiments, the swab tip 401 is made of one or more of cotton, polyurethane foam, polyester, rayon, and nylon. In some cases, the absorbent swab tip is made of cellulose (e.g., lyocell), modified cellulose (e.g., viscose or rayon), polyester, silk, wool, nylon, polypropylene, elastane, or mixtures thereof. The swab shaft 403 may include a scale. In some cases, the scale is stamped, embossed, or printed. In some cases, the scale functions to facilitate measurement of wound depth.

[0032] In some embodiments, when the swab unit 400 is inserted into the indicator unit 300, the handle 405 forms a liquid-tight and / or air-tight seal with the sensor tube 303. In some embodiments, the device 200 includes features that prevent the indicator unit 300 from being separated from the swab unit 400 by a user when the swab unit 400 is fully inserted into the indicator unit 300 and seated in place. In some embodiments, the device includes a locking mechanism. In some embodiments, the locking mechanism includes a one-way ratchet or snap feature. In some cases, the locking mechanism includes a luer lock or locking pin. In the embodiment shown in FIGS. 2-11, the swab unit 400 is locked when inserted into the indicator unit 300 as a result of engagement between a flange 415 formed on the handle 405 and a shoulder 315 formed on the proximal end 310 of the sensor tube 303. As described above, the segment 316 of the sensor tube 303 is sized and configured to seat within the radial channel 406 formed in the handle 405 of the swab unit 400. A flange 415 is positioned distal to the radial channel 406, the flange 415 having a diameter greater than the inner diameter of the segment 316. This allows the flange 415 to deflect through the lumen of the segment 316 when the handle 405 engages the proximal end 310 of the indicator unit 300 and is forced to seat and seal the swab unit 400 against the indicator unit 300, and when the flange 415 extends distally beyond the shoulder 315, the flange 415 snaps into place and engages the shoulder 315, sealing the swab unit 400 against the indicator unit 300, as shown most clearly in FIG. 3. In some embodiments, the flange 415 is a radial flange that extends around the entire circumference of the handle 405. In other embodiments, the flange 415 may not extend around the entire circumference of the handle 405, but rather may be comprised of one or more smaller flanges located at only one or more locations around the circumference of the handle 405.

[0033] The sensor tube, sensor-retaining insert, swab shaft, and swab handle of the devices described herein may be injection molded, blow molded, or 3D printed and then assembled as described herein, or the indicator unit may be injection molded, blow molded, or 3D printed as a single piece. In some cases, the indicator unit is 3D printed. In some embodiments, the indicator unit is sterile. In some embodiments, the indicator unit is not sterile. The sensor tube 303 may be opaque. In some embodiments, the sensor tube 303 is clear. In some embodiments, the sensor tube 303 is blow molded.

[0034] The sensors, sensor tubes, sensor-retaining inserts, swab shafts, and swab handles of the devices described herein can be made of a variety of materials. The sensors may comprise paper, cellulose, cellulose derivatives, viscose, polyamide, polyester, polyacrylate, cloth, sodium carboxymethylcellulose fiber (commercially available from ConvaTec under the registered trademark "Hydrofibre"), paperboard, or other similar polymers useful as fibers, or any combination thereof. In some cases, the sensors are made of paper. In some cases, the sensors are made of filter paper. In some cases, the sensor tubes are made of polyolefins, polypropylene, polyethylene, polyurethane, polyamide, polystyrene, ethylene-vinyl alcohol (EVOH), acrylonitrile (PAN), polyvinyl chloride (PVC), or polyvinylidene chloride (PVDC), polyacrylates (e.g., (1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)]diacrylate). In some cases, the sensor tubes include polypropylene. In some cases, the sensor-retaining insert is comprised of polyolefin, polypropylene, polyethylene, polyurethane, polyamide, ethylene-vinyl alcohol (EVOH), acrylonitrile (PAN), polyvinyl chloride (PVC), or polyvinylidene chloride (PVDC), polyacrylate (e.g., (1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)]diacrylate). In some cases, the sensor-retaining insert includes polypropylene.

[0035] In some cases, the absorbent swab tip comprises a non-gel-forming polymer. In some cases, the absorbent swab tip comprises cellulose (e.g., lyocell), modified cellulose (e.g., viscose or rayon), polyester, silk, wool, nylon, polypropylene, elastane, or mixtures thereof.

[0036] In some cases, the absorbent swab tip comprises a gel-forming polymer or sodium carboxymethylcellulose fibers (commercially available from ConvaTec under the registered trademark "Hydrofibre"). Gel-forming polymers include polymers derived from cellulose, carboxymethylcellulose (CMC), carboxyethylcellulose, oxidized cellulose (or derivatives thereof), cellulose ethylsulfonate, other chemically modified celluloses, pectins, alginates, chitosan, modified chitosan, hyaluronic acid, polysaccharides, or gums, or any combination thereof. In some embodiments, the absorbent swab tip comprises polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl ether, polyurethane, polyacrylate, polyacrylamide, collagen, gelatin, or mixtures thereof. In some embodiments, the absorbent swab tip comprises fibers of a gel-forming polymer. In some embodiments, the absorbent swab tip comprises a nonwoven layer of gel-forming fibers. In one embodiment, the gel-forming fibers comprise sodium carboxymethylcellulose fibers.

[0037] The swab handle 405 and swab shaft 403 can comprise a variety of materials. In some cases, the swab handle 405 is made of polyolefin, polypropylene, polyethylene, polyurethane, polyamide, polystyrene, ethylene-vinyl alcohol (EVOH), acrylonitrile (PAN), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), or polyacrylate (e.g., (1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)]diacrylate). In some cases, the swab shaft 403 comprises polypropylene.

[0038] In some embodiments, the swab tip 401 has a circumference that is less than the circumference of the sensor tube. In some embodiments, the circumference of the swab tip is at least or about 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 centimeters (cm), or greater than 0.8 centimeters (cm). In some embodiments, the length of the swab tip is at least or about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, or 8 centimeters (cm), or greater than 8 centimeters (cm). In some embodiments, the swab shaft comprises a circumference that is less than the circumference of the sensor tube. In some embodiments, the circumference of the swab shaft is at least about or greater than 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 centimeters (cm). In some embodiments, the length of the swab shaft is at least about or greater than 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 centimeters (cm). In some embodiments, the circumference of the sensor tube is at least or about 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, or 6 centimeters (cm), or greater than 6 centimeters (cm).

[0039] The sensor 301 may exhibit a change when activated or contacted by a particular substance or condition (i.e., a marker). For example, the change may be a color change. In some embodiments, the change is a color, a number, a symbol, or other visible or observable marker. In some embodiments, the color change is a change from a first color to a second color, from colorless to a color, or from a color to colorless. The sensor may include a reagent (substrate) for effecting the change. In some embodiments, the reagent for effecting the change is immobilized on a carrier material. In some embodiments, the sensor includes one or more components for effecting the change selected from the group consisting of an enzyme-reactive indicator, a reagent that is a source of peroxide, a reductase, an oxidase, an enzyme capable of converting a color reaction, a pH indicator, a total protein detection reagent, and a moisture detection reagent. In some embodiments, the reagent that is a source of peroxide is selected from peroxyacid, sodium percarbonate, and a peroxide-generating oxidase, such as glucose oxidase or lactate oxidase. In some embodiments, the enzyme that can assist in converting a color reaction is selected from peroxidase and laccase. In some embodiments, the enzyme-responsive indicator comprises a moiety capable of producing a visible color or a detectable electronic change upon interaction with one or more target enzymes. In some embodiments, the moiety is a peroxidase substrate, an arylamine, an aminophenol, an indoxyl, a neutral dye, a charged dye, a nanoparticle, a colloidal gold particle, or an analog thereof. In some embodiments, the sensor comprises a pH-sensitive moiety that exhibits a visible color change. In some embodiments, the pH-sensitive moiety exhibits a visible color change at alkaline pH. In some embodiments, the pH-sensitive moiety exhibits a visible color change at neutral pH. In some embodiments, the pH-sensitive moiety exhibits a visible color change at acidic pH. In some embodiments, the immobilized reagent comprises one or more antibodies and / or antibody conjugates. In some embodiments, the immobilized reagent comprises an unbound cell surface receptor.

[0040] In some embodiments, wound pH can affect many factors of wound healing, such as angiogenesis, protease activity, oxygen release, and bacterial toxicity. Chronic non-healing wounds may have an elevated alkaline environment, as do acute wounds in the early stages of healing. As wounds progress toward healing, wound pH usually moves toward neutral and then acidic. Monitoring wound pH can help assess wound status (such as infection or no infection) and determine wound response to treatment.

[0041] In some embodiments, the pH sensitive portion exhibits a visible color change at pH=7.2-9.5. The color change is believed to be due to the progression of an infection. In some embodiments, the pH sensitive portion exhibits a visible color change at pH=7.2-9.0. In some embodiments, the pH sensitive portion exhibits a visible color change at pH=7.2-8.5. In some embodiments, the pH sensitive portion exhibits a visible color change at pH=7.2-8.0. In some embodiments, the pH sensitive portion exhibits a visible color change at pH=7.5-8.5. In some embodiments, the pH sensitive portion exhibits a visible color change at pH=7.5-9.0. In some embodiments, the pH sensitive portion exhibits a visible color change at pH=8.0-9.0.

[0042] In some embodiments, the pH sensitive moiety exhibits a visible color change at an acidic or neutral pH. For example, the pH sensitive moiety exhibits a visible color change at a pH between 4.5 and about 7. A pH in this range is believed to indicate no or minimal infection. Minimal infection would be in the pH range of 6-7, or 6.5-7.

[0043] In some embodiments, the pH sensitive moiety is selected from Bromothymol Blue, Phenol Red, Bromophenol Red, Chlorophenol Red, Thymol Blue, Bromocresol Green, Bromocresol Purple, Nitrazine Yellow, or other sulfophthalein dyes. In one embodiment, the pH sensitive moiety has a strong dark color change, including, for example, Bromocresol Purple.

[0044] In some embodiments, the sensor indicates a change upon detecting one or more markers, such as biomarkers. In some embodiments, the sensor indicates a change upon detecting one marker. In some embodiments, the sensor indicates a change upon detecting two markers. In some embodiments, the sensor indicates a change upon detecting three markers. In some embodiments, the sensor indicates a change upon detecting four markers. In some embodiments, the sensor indicates a change upon detecting five markers. In some embodiments, the sensor indicates a change upon detecting six markers. In some embodiments, the sensor indicates a change upon detecting seven markers. In some embodiments, the sensor indicates a change upon detecting eight markers. In some embodiments, the sensor indicates a change upon detecting nine markers. In some embodiments, the sensor indicates a change upon detecting ten markers. Typically, the sensor can detect one to three markers. In one embodiment, the sensor can detect two to five, or two to three markers. In a further embodiment, the sensor can detect three markers.

[0045] In some embodiments, the sensors described herein exhibit a rapid change, in some cases occurring within at most or about 10 seconds, 20 seconds, 30 seconds, 40 seconds, 50 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, or 10 minutes.

[0046] In some embodiments, the sensor comprises a carrier material having multiple sections, each section comprising a substrate immobilized thereon for detection of a different marker.

[0047] Provided herein is a method for using a wound sampling device as described herein. In some embodiments, the method includes swabbing a wound using a swab unit, inserting the swab unit into an indicator unit, and reading a change in a sensor of the indicator unit. In some embodiments, the change is a color change. In some embodiments, inserting the swab unit into the indicator unit includes contacting the swab tip with a sensor. In some embodiments, the change is a color, a number, a symbol, or other visible or observable marker. In some embodiments, the color change is from a first color to a second color, from colorless to a color, or from a color to colorless.

[0048] A liquid sample obtained from a wound often contains sufficient moisture to achieve a desired degree of contact between the liquid sample and the sensor when the swab unit is inserted into the indicator unit such that the swab tip contacts the sensor, thereby reliably identifying the presence or absence of a marker in the liquid sample. However, for detection of certain markers, it is desirable to provide a liquid, such as sterile water or other aqueous humor, to the swab tip and / or sensor. Such liquid delivery may be accomplished by providing a reservoir of water within a chamber defined by the swab handle of the wound sampling device, according to certain embodiments of the present disclosure. In some embodiments, the liquid within the liquid chamber may be manually released. In other embodiments, the liquid within the liquid chamber may be automatically released upon engagement of the swab unit with the indicator unit.

[0049] 12-18 show one embodiment of a device capable of manually releasing liquid in a liquid chamber as described above. Device 500 shown in FIGS. 12 and 13 includes indicator unit 600 and swab unit 700. Swab unit 700 includes swab tip 701, swab shaft 703, and swab handle 705, where swab handle 705 defines liquid chamber 750. A perspective view of swab unit 700 of device 500 is shown in FIG. 15. Swab tip 701 may include nylon or any other absorbent material described herein. In some cases, swab tip 701 includes cellulose (e.g., lyocell), modified cellulose (e.g., viscose or rayon), polyester, silk, wool, nylon, polypropylene, elastane, or mixtures thereof. Swab shaft 703 may include a scale. In some embodiments, the scale is stamped or embossed. In some embodiments, the scale functions to facilitate measurement of wound depth.

[0050] A cross-sectional view of the device of FIG. 12 is shown in FIG. 13. Indicator unit 600 may have similar features as those described above for indicator units 30, 300. However, in the illustrated embodiment, proximal end 610 of indicator unit 600 does not include a shoulder with reduced outer and inner diameters, but rather includes a simple open end as shown in FIG. 14, and indicator unit 600 includes sensor 601, sensor retaining insert 603, and sensor tube 605. In the illustrated embodiment, handle 705 includes portion 773 configured to form a liquid-tight and / or air-tight seal with sensor tube 605 when portion 773 of swab unit 700 is inserted into proximal end 610 of indicator unit 600.

[0051] 16 provides a more detailed view of the handle 705 and its relationship to the swab shaft 703. The handle 705 of the swab unit 700 includes a movable element 760 that is retained within and movable relative to a retaining element 770 of the swab handle 705. The movable element 760 defines a fluid chamber 750.

[0052] 17 shows the structure of the movable element 760 more clearly. The movable element 760 comprises a body 761, which may be, for example, a molded or 3D printed plastic part defining an outer structure 762 for engaging the retaining element 770. The body 761 also defines sides and one end of an interior liquid chamber 750 in which the liquid 755 is contained. The other end of the liquid chamber 750 is defined by a liquid chamber seal 764 that seals the open end of the body 761. The seal 764 may include, for example, an aluminum foil seal. Further examples of suitable seals include, but are not limited to, other metal foils, plastic films, membranes, ball valves, duckbill valves, other check valves, or combinations thereof.

[0053] The retaining element 770 may be, for example, a molded or 3D printed plastic part and defines a cavity 772 sized and configured to receive the tip 763 of the movable element 760. The retaining element 770 is also inserted into the proximal end 610 of the sensor tube 605. The tip 773 of the retaining element 770 defines an axial bore through which the proximal end of the swab shaft 703 extends partway into the cavity 772 at a predetermined position relative to the retaining element 770. The surface of the retaining element 770 that defines the cavity 772 includes a surface structure that interacts with a structure 762 on the movable element 760 to retain the tip 763 of the movable element 760 within the cavity in a non-deployed position. This keeps the liquid chamber seal 764 spaced from the base end 704 of the swab shaft 703 until sufficient pressure is applied to the movable element 760 in the direction indicated by arrow 780 in FIG. 16 to move the movable element 760 in the tip (distal) direction, thereby deploying the liquid contained in the liquid chamber 755.

[0054] In device 500, swab shaft 703 is formed as a hollow tube having a proximal opening 704 and a small opening 702 adjacent swab tip 701 that is in fluid communication with the lumen of swab shaft 703. In the illustrated embodiment, proximal end 704 of swab shaft 703 defines a sharp edge that operates to break liquid chamber seal 764 when movable element 760 is moved as described above. Breaking of liquid chamber seal 764 by proximal end 704 of swab shaft 703 causes proximal end 704 to enter liquid chamber 750, thereby causing liquid contained therein to enter the lumen of hollow shaft 703 and flow distally toward opening 702, through which liquid wets swab tip 701 and / or sensor 601 positioned in contact with swab tip 701.

[0055] 18 illustrates the use of the device 500. In some cases, a surface structure 762 on the tip (distal portion) 763 of the movable element 760 and a surface structure on the surface of the retaining element 770 that defines the cavity 772 engage with each other to inhibit the movable element 760 from being pulled out of the cavity 772. In some cases, the movable element 760 is configured to slide within the cavity 772 of the retaining element 770 when pressed. When the movable element 760 of the device is pressed, the proximal end 704 of the swab shaft 703 contacts the liquid chamber seal 764 and breaks the seal 764, thereby allowing liquid to be expelled through the lumen of the swab shaft 703 and the opening 702 into the sensor tube 605 to contact the swab tip 701 and / or the sensor 601. The swab unit 700 can be locked when inserted into the indicator unit. In some embodiments, the locking mechanism includes a one-way ratchet or snap feature. Additionally, movable element 760 may be locked once moved to the compressed position by operation of surface structure 762 on tip 763 of movable element 760 and surface structures on a surface of retaining element 770 that define cavity 772 .

[0056] In an alternative embodiment, the swab shaft 703 extends to or into the cavity 772 and acts as a conduit for liquid to travel from the liquid chamber 750 to the swab tip 701 and / or sensor 601, but does not function to penetrate the liquid chamber seal 764. In such an embodiment, another piercing structure (piercing structure) may be attached to the retaining element 770 within the cavity 772, which may be configured to pierce the liquid chamber seal 764 when the movable element 760 is manually compressed.

[0057] Although one example of manually delivering liquid to the sensor tube is detailed herein, various alternative structures for manually delivering liquid from the handle of the swab unit to the sensor tube are contemplated. For example, in some embodiments (not shown), the swab handle includes a piercing member and plunger to not only pierce the liquid seal, but also to compress and propel the liquid into the sensor tube 605. In some embodiments, when the movable element is pressed downward, the piercing member is released to pierce the seal via a spring-loaded mechanism or other configuration.

[0058] In some embodiments, a method of using a wound sampling device described herein includes swabbing the wound with a swab unit, inserting the swab unit into the indicator unit, manually expelling liquid from the liquid chamber into a sensor tube, and reading a change in the device or sensor. In some embodiments, inserting the swab unit into the indicator unit includes contacting the sensor with the swab. In some embodiments, the change is a color change. In some embodiments, the change is a color, number, symbol, or other visible or observable marker. In some embodiments, the color change is from a first color to a second color, from no color to a color, or from a color to no color. In some embodiments, expelling liquid includes pushing a movable member to puncture a seal in the liquid chamber.

[0059] As shown in Figures 19-27, a wound sampling device 800 according to another embodiment of the present disclosure is operable to deliver water to a swab tip and / or a sensor device. The device 800 comprises an indicator unit 900 and a swab unit 1000 having a handle 1007 defining a liquid chamber and configured to automatically deploy liquid when the swab unit 1000 is seated on the indicator unit 900. Figure 19 shows the swab unit 1000 of the device 800. The swab unit 1000 includes a swab tip 1001, a swab shaft 1003, a liquid chamber seal 1005, and a swab handle 1007 defining a liquid chamber 1050. The swab tip 1001 may comprise nylon or other absorbent material as described herein. In some cases, the swab tip 1001 comprises cellulose (eg, lyocell), modified cellulose (eg, viscose or rayon), polyester, silk, wool, nylon, polypropylene, elastane, foam, or mixtures thereof.

[0060] Cross-sectional views illustrating various features of device 800 are provided in Figures 21-24. Figure 21 shows a cross-section of device 800, which includes a sensor tube 905, a perforation ring 901 attached to the sensor tube 905, a liquid chamber seal 1005 that forms an end of a liquid chamber 1050 that contains a sterile liquid, a swab shaft 1003, and a handle (swab handle) 1007. Figure 22 shows a close-up image of the proximal end of device 800. The handle 1007 of the swab unit 1000 forms a liquid-tight and / or air-tight seal with the sensor tube 905 of the indicator unit 900 when the swab unit 900 is inserted into the sensor tube 905.

[0061] 25-26 show cross-sectional views of components of device 800, and FIG. 27 shows a perspective view of piercing ring 901. Device 800 includes a seal 1005 and a swab shaft cross-section 1003 having a shape as seen in FIG. 26. In alternative embodiments, the cross-sectional shape is triangular, square, circular, oval, or star-shaped. In some cases, the cross-sectional shape of the swab shaft 1003 is configured to enhance the flow of liquid from the liquid chamber along the swab shaft after the seal is pierced or opened, thereby allowing liquid to flow from the swab shaft 1050 to the swab tip 1001. Examples of suitable seals include, but are not limited to, foils, ball valves, films, membranes, duckbill valves, or other check valves.

[0062] The swab units used in the devices described herein may include a handle (swab handle) having structure (not shown) to allow rotation of the swab when inserted into the indicator unit. In some cases, the structure is a helical structure, such as a screw. In some cases, these structures allow for the transfer of fluid to the sensor.

[0063] The upper end of the piercing ring 901 includes at least one sharp piercing edge that contacts and pierces the liquid chamber seal 1005 when the swab unit 1000 is inserted into the indicator unit 900 .

[0064] The fluid chamber may be any shape, including a cylinder. In some embodiments, the fluid chamber 1207 surrounds a space configured to receive the end of a swab shaft 1209. In some such embodiments, a handle (swab handle) is attached to the swab shaft that is inserted into the space.

[0065] Regarding embodiments where liquid is delivered to the sensor tube, in some embodiments, the liquid is water. In other embodiments, the liquid is a buffer. The buffer may include an enzyme, a salt, or a substrate. The amount of liquid may be at least or about 500 μL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, 3 mL, 3.5 mL, 4 mL, or 5 mL, or may be greater than 5 mL. In some cases, the amount of liquid is in the range of about 500 μL to about 5 mL, in the range of about 1 mL to about 4 mL, in the range of about 1.5 mL to about 3.5 mL, or in the range of about 2 mL to about 3 mL.

[0066] The sensor may include one or more components selected from the group consisting of an enzyme reactive indicator, a reagent that is a source of peroxide, an enzyme capable of converting a color reaction, a pH indicator, a total protein detection reagent, and a moisture detection reagent. The change may be indicative of treatment of a wound, diagnosis of a wound, monitoring of a wound condition, a healing process, or detection of an infection marker of a wound.

[0067] In some cases, a method of using a wound sampling device described herein includes using a swab unit to swab the wound, inserting the swab unit into the indicator unit, automatically releasing liquid from the liquid chamber into the sensor tube, and reading a change in the device or sensor. In some embodiments, the indicator unit includes a piercing member. In some embodiments, the seal is pierced to release liquid in the liquid chamber. In some embodiments, the seal is pierced when the swab unit is inserted into the indicator unit. For example, the seal is pierced when the swab unit is pressed into the indicator unit, and contact between the swab unit and the indicator unit pierces the seal. In some embodiments, when the swab unit is inserted into the indicator unit, a piercing ring or other piercing element breaks the liquid chamber seal and liquid is ejected. In some embodiments, inserting the swab unit into the indicator unit includes contacting a sensor with the swab. In some embodiments, the change is a color change. In some embodiments, the change is a color, a number, a symbol, or other visible or observable marker, hi some embodiments, the color change is from a first color to a second color, from no color to a color, or from a color to no color.

[0068] In some embodiments, the swab unit handle, or a portion of the swab unit handle, is pressed into the indicator unit and rotated to lock into the tube. The handle of the swab unit may be rotated at least or about 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees, 100 degrees, 120 degrees, 140 degrees, 160 degrees, 180 degrees, 200 degrees, 220 degrees, 240 degrees, 260 degrees, 280 degrees, 300 degrees, 320 degrees, 340 degrees, or 360 degrees until the indicator unit is locked. In some embodiments, the swab unit handle is rotated an additional 360 degrees until the indicator unit is locked. In other embodiments, the swab unit handle is not pressed into the indicator unit, but rather the swab unit is sealingly attached to the indicator unit in the appropriate orientation using another attachment mechanism. In some cases, locking the handle in or to the indicator unit forms an air-tight and / or liquid-tight seal between the handle and the indicator unit, which may help to retain liquids or samples within the sealed device.

[0069] [How to use] In some embodiments, the devices and methods described herein are used to indicate the infection status of a wound, for example, whether the wound is infected. In some embodiments, the devices and methods disclosed herein detect biological markers or targets known to be associated with or indicative of infection in bodily fluids. In some embodiments, the bodily fluid is blood, plasma, serum, cerebrospinal fluid, saliva, urine, or wound exudate. In some embodiments, the bodily fluid is wound exudate. In some embodiments, the devices and methods described herein are used to diagnose chronic wounds. In some embodiments, the devices and methods described herein are used to indicate the need for treatment of chronic wounds. In some embodiments, the devices and methods described herein are used to indicate the need for treatment of surgical or acute wounds. In some embodiments, the devices and methods described herein are used to monitor the condition of a wound or surgical site and its healing process or condition. In some embodiments, the devices and methods described herein are used to detect the pH and / or presence of markers of infection in a wound.

[0070] The methods for using the wound sampling device described herein can be used to detect wound markers. For example, markers of the wound healing process are detected using the devices described herein. Detection of the wound marker can be indicated by a visible change. In some embodiments, the visible change is color. In some embodiments, the color is selected from dark blue, dark green, and black. It will be apparent to one skilled in the art that the signaling effect of the color change will depend on the circumstances and practical considerations of the interfering colors form the wound itself. In some embodiments, the visible change is fluorescent or luminescent, or mediated by physical means such as electricity, refraction, gas evolution, polymer state change, etc.

[0071] In some embodiments, the wound marker is a host marker in wound fluid.As used herein, the term host refers to a patient or animal with a wound.For example, the device and method described herein include one or more chemical substrates that react with host biomarkers in wound fluid, such as substrates that react with myeloperoxidase (MPO), peroxidase, elastase, lysozyme, protease, cathepsin G, catalase, lipase, or elastase in wound fluid.

[0072] In some embodiments, microbial infection is detected via a host immune response using a device as described herein. Examples of microorganisms that may elicit a host immune response include, but are not limited to, bacteria, yeast, fungi (also called molds), and viruses. In one embodiment, the microorganism can be a gram-negative bacterium (e.g., Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Bacteroides). In another embodiment, the microorganism can be a gram-positive bacterium (e.g., Staphylococcus, Streptococcus, Clostridium, Peptostreptococcus). In one embodiment, the microorganism can be a combination of gram-positive and gram-negative bacteria. In one embodiment, the microorganism can be a combination of aerobic and anaerobic bacteria.

[0073] [Example] The following examples are given for the purpose of illustrating various embodiments of the present invention and are not meant to limit the present invention in any way. The examples, together with the methods described herein, are representative of currently preferred embodiments and are provided by way of example only and are not intended to limit the scope of the present invention. Modifications therein and other uses that fall within the spirit of the invention as defined by the scope of the claims will occur to those skilled in the art.

[0074] [Example 1: Indicator tube and swab handle] The device 200 shown in Figures 2-3 and described herein is used by wiping the wound with the absorbent swab tip 401 of the swab unit 400 and then inserting the swab unit 400 into the indicator unit 300. The device may contact a bodily fluid such as blood, plasma, serum, cerebrospinal fluid, saliva, urine, or wound exudate. The absorbent swab tip 401 then contacts the sensor 301 in the sensor-retaining insert 305. The sensor-retaining insert may include a sloped wall structure as seen in Figures 6-8. This allows the sloped wall structure to squeeze any material, such as liquid or exudate, on the absorbent swab tip and transfer it to the sensor when the swab shaft is inserted into the indicator tube.

[0075] Following transfer of the liquid from the swab shaft to the sensor, a change is read. The change may be read after 30 seconds. Optionally, the change is read after up to 5 minutes. The change may be a color change. Optionally, the change is a color, number, symbol, or other visible or observable marker. The sensor may include one or more components selected from the group consisting of an enzyme reactive indicator, a reagent that is a source of peroxide, an enzyme capable of converting a color reaction, a pH indicator, a total protein detection reagent, and a moisture detection reagent. The change may be indicative of wound treatment, wound diagnosis, wound status monitoring, the healing process, or detection of a wound infection marker.

[0076] Example 2: Swab Handle with Indicator Tube and Fluid Chamber for Manual Deployment The device 500 shown in Figures 12-13 and described herein is used by swabbing the wound with the absorbent swab tip 701 of the swab unit 700, followed by inserting the swab unit 800 into the indicator unit 700. The device may come into contact with a bodily fluid, such as blood, plasma, serum, cerebrospinal fluid, saliva, urine, or wound exudate. The movable element 760 is then depressed for fluid deployment. As the movable element of the device is depressed, the proximal end of the swab shaft 703 breaks the fluid chamber seal and fluid is delivered to the swab tip.

[0077] Following transfer of the liquid from the swab shaft to the sensor, a change is read. The change may be read after 30 seconds. Optionally, the change is read after up to 5 minutes. The change may be a color change. Optionally, the change is a color, number, symbol, or other visible or observable marker. The sensor may include one or more components selected from the group consisting of an enzyme reactive indicator, a reagent that is a source of peroxide, an enzyme capable of converting a color reaction, a pH indicator, a total protein detection reagent, and a moisture detection reagent. The change may be indicative of wound treatment, wound diagnosis, wound status monitoring, the healing process, or detection of a wound infection marker.

[0078] Example 3: Swab handle with indicator tube and liquid chamber for automatic deployment The device 800 shown in Figures 19-27 and described herein is used by swabbing a wound with the absorbent swab tip 1001 of the swab unit 1000 and subsequently inserting the swab unit 1000 into the indicator unit 900. The device may come into contact with a bodily fluid such as blood, plasma, serum, cerebrospinal fluid, saliva, urine, or wound exudate. The absorbent swab tip 1001 then comes into contact with the sensor 901. The liquid is automatically expelled. When the swab unit is inserted into the indicator tube, the perforation ring breaks the liquid chamber seal and the liquid is expelled (see Figures 21-24).

[0079] Following transfer of the liquid from the swab shaft to the sensor, a change is read. The change may be read after 30 seconds. Optionally, the change is read after up to 5 minutes. The change may be a color change. Optionally, the change is a color, number, symbol, or other visible or observable marker. The sensor may include one or more components selected from the group consisting of an enzyme reactive indicator, a reagent that is a source of peroxide, an enzyme capable of converting a color reaction, a pH indicator, a total protein detection reagent, and a moisture detection reagent. The change may be indicative of wound treatment, wound diagnosis, wound status monitoring, the healing process, or detection of a wound infection marker.

[0080] As will be understood from the description herein and the associated drawings, the present disclosure contemplates various aspects and embodiments, examples of which include, but are not limited to, the aspects and embodiments listed below.

[0081] 1. A device for detecting infection of a wound, comprising: an indicator unit and a swab unit, the indicator unit comprising a sensor tube having a proximal opening and a sensor located within the sensor tube, the swab unit comprising a swab shaft having a proximal end and a distal end, a swab tip located at the distal end of the swab shaft, and a swab handle connected to the swab shaft at the proximal end of the swab shaft and configured to sealingly engage the proximal opening of the sensor tube.

[0082] A method for detecting a marker in a wound, comprising: (a) contacting the wound with the swab tip of a device according to any embodiment disclosed herein; (b) inserting the swab tip into the sensor tube to sealingly engage the swab unit with the indicator unit; and (c) monitoring a change in the sensor.

[0083] Any other embodiment of the device or method disclosed herein, wherein the sensor comprises a carrier material and at least one substrate operable to undergo a visible color change in response to expression of specific infection markers present in wound fluid.

[0084] Any other embodiment of the device or method disclosed herein, wherein the sensor comprises at least two substrates, each substrate operable to undergo a visible color change in response to expression of a different marker present in the wound fluid.

[0085] The apparatus or method according to any other embodiment disclosed herein, comprising a carrier material, wherein the carrier material comprises at least one material selected from the group consisting of paper, cellulose, cellulose derivatives, viscose, polyamide, polyester, polyacrylate, cloth, sodium carboxymethylcellulose fiber, and paperboard.

[0086] Any other embodiment of the device or method disclosed herein, wherein the indicator unit further comprises a sensor-retaining insert sealingly engaged to a distal end of the sensor tube, and the sensor is attached to the sensor-retaining insert.

[0087] Any other embodiment of a device or method disclosed herein including a sensor-retaining insert, wherein the sensor-retaining insert defines a cavity configured to receive the swab tip when the swab unit is sealingly engaged to the indicator unit.

[0088] Any other embodiment of a device or method disclosed herein including a sensor-retaining insert defining a cavity configured to receive the swab tip when the swab unit is sealingly engaged with the indicator unit, wherein the sensor-retaining insert has at least one structural feature within or adjacent to the cavity that guides the swab tip into a desired position aligned with the sensor in the sensor-retaining insert.

[0089] Any other embodiment of the device or method disclosed herein including at least one structural feature that guides the swab tip into the sensor-retaining insert, wherein the at least one structural feature is selected from a rib structure, a sloped cavity wall, and combinations thereof.

[0090] Any other embodiment of the device or method disclosed herein, wherein the swab tip is made of cellulose, modified cellulose, polyurethane foam, polyester, silk, wool, nylon, polypropylene, elastane, or mixtures thereof.

[0091] Any other embodiment of the device or method disclosed herein, wherein the sensor comprises a member selected from the group consisting of an enzyme reactive indicator, a reagent that is a source of peroxide, an enzyme capable of converting a color reaction, a pH indicator, a total protein detection reagent, a moisture detection reagent, and combinations thereof.

[0092] The device or method according to any other embodiment disclosed herein comprising a pH indicator, wherein the pH indicator comprises a pH sensitive reagent.

[0093] Any other embodiment of the device or method disclosed herein comprising an enzyme reactive indicator, the enzyme reactive indicator comprising a moiety capable of producing a visible color or a detectable electronic change upon interaction with one or more target enzymes.

[0094] Any other embodiment of the device or method disclosed herein comprising an enzyme-responsive indicator having a moiety capable of producing a visible color or a detectable electronic change, said moiety being selected from the group consisting of peroxidase substrates, arylamines, aminophenols, indoxyls, neutral dyes, charged dyes, nanoparticles, colloidal gold particles, and combinations or analogs thereof.

[0095] Any other embodiment of the device or method disclosed herein, wherein the swab handle defines a liquid chamber, the swab handle operable to receive liquid in the liquid chamber and to expel the liquid into the sensor tube after the swab tip is positioned within the sensor tube.

[0096] Any other embodiment of the device or method disclosed herein including a swab handle defining a liquid chamber, wherein the swab handle is configured to manually expel the liquid from the liquid chamber.

[0097] Any other embodiment of the device or method disclosed herein, wherein the swab handle comprises a retaining element configured to couple to the sensor tube and defining a cavity, and a movable element retained within the cavity of the retaining element and movable relative to the retaining element.

[0098] The apparatus or method according to any other embodiment disclosed herein, wherein the liquid chamber is contained within the movable element.

[0099] Any other embodiment of the device or method disclosed herein, wherein the movable element further comprises a liquid chamber seal, and the swab handle further comprises a piercing member fixedly attached to the retaining element, and moving the movable element from a proximal position to a distal position causes the piercing member to pierce the liquid chamber seal and release the liquid into the sensor tube.

[0100] The apparatus or method according to any other embodiment disclosed herein, wherein the liquid chamber seal comprises a member selected from the group consisting of a metal foil and a plastic film.

[0101] Any other embodiment of the device or method disclosed herein, wherein the swab shaft is fixedly attached to the retaining element such that a proximal end of the swab shaft extends into the cavity of the retaining element, and the piercing member comprises the proximal end of the swab shaft.

[0102] Any other embodiment of the device or method disclosed herein, wherein the swab shaft includes a tube having a longitudinal passage formed therethrough, and after the liquid chamber seal is pierced, the liquid chamber is in fluid communication with the sensor tube through the longitudinal passage.

[0103] Any other embodiment of the device or method disclosed herein, wherein the swab shaft defines a radial opening (an opening extending radially through the swab shaft) at a distal end near the swab tip, and after the liquid chamber seal is pierced, the liquid chamber is fluidly connected to the sensor tube through the longitudinal passage and the radial opening.

[0104] Any other embodiment of the device or method disclosed herein, further comprising a locking mechanism operable to restrict proximal movement of the movable element after the liquid chamber seal is pierced.

[0105] Any other embodiment of the device or method disclosed herein, wherein the swab handle is configured to automatically release the liquid from the liquid chamber when the swab handle of the swab unit sealingly engages the proximal opening of the sensor tube.

[0106] Any other embodiment of the device or method disclosed herein, wherein the swab handle comprises a liquid chamber seal located at a tip of the liquid chamber, and the indicator unit further comprises a piercing member fixedly attached to the sensor tube in a position such that the tip contacts the liquid chamber seal only when the tip is inserted into the sensor tube, and insertion of the tip into the sensor tube causes the piercing member to pierce (penetrate) the liquid chamber seal and release the liquid into the sensor tube.

[0107] The device or method according to any other embodiment disclosed herein, wherein the piercing member is a piercing ring.

[0108] Any other embodiment of the device or method disclosed herein, wherein the liquid chamber contains about 500 μL, about 1 mL, about 1.5 mL, about 2 mL, about 2.5 mL, about 3 mL, about 3.5 mL, or about 4 mL of liquid.

[0109] The method according to any other embodiment disclosed herein, wherein the marker is a host biomarker.

[0110] The method according to any other embodiment disclosed herein, wherein the change is a color change, a fluorescent signal, a luminescent signal, or an electrical change.

[0111] The method according to any other embodiment disclosed herein, wherein the sensor comprises a carrier material and at least one substrate operable to undergo a visible color change in response to expression of specific infection markers present in wound fluid released from the swab tip.

[0112] The method according to any other embodiment disclosed herein, further comprising the step of (d) comparing the signal to a reference or control to determine the level of the marker.

[0113] The method according to any other embodiment disclosed herein including a movable element, further comprising, following step (b), pressing the movable element.

[0114] The method according to any other embodiment disclosed herein, wherein step (b) comprises contacting the swab tip of the swab unit with the sensor of the indicator unit.

[0115] The method according to any other embodiment disclosed herein, wherein the step of (b) results in piercing the liquid seal.

[0116] The method according to any other embodiment disclosed herein, wherein the piercing of the liquid seal releases liquid into the sensor tube.

[0117] Although embodiments of the present disclosure have been shown and described herein, it should be understood by those skilled in the art that the above-mentioned embodiments are provided by way of example only. Various modifications, changes, and substitutions may be made by those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be used in implementing the present invention. The claims define the scope of the present invention, and it is intended that methods and structures within the scope of the claims and their equivalents be covered thereby.

Claims

1. 1. A device for detecting infection in a wound, comprising: (a) an indicator unit; and (b) a swab unit, The indicator unit comprises: (i) a sensor tube having a proximal opening; (ii) a sensor located within the sensor tube; The swab unit comprises: (i) a swab shaft having a proximal end and a distal end; (ii) a swab tip located at the distal end of the swab shaft; (iii) a swab handle connected to the swab shaft at the proximal end thereof and configured to sealingly engage the proximal opening of the sensor tube; A device, wherein the swab handle defines a liquid chamber, the swab handle operable to receive liquid in the liquid chamber and to expel the liquid into the sensor tube after the swab tip is positioned within the sensor tube.

2. 10. The device of claim 1, wherein the sensor comprises a carrier material and at least one substrate operable to undergo a visible color change in response to the expression of specific infection markers present in wound fluid.

3. 3. The device of claim 2, wherein the sensor comprises at least two substrates, each substrate operable to undergo a visible color change in response to expression of a different marker present in wound fluid.

4. 10. The apparatus of claim 1, wherein the indicator unit further comprises a sensor-retaining insert sealingly engaged to a distal end of the sensor tube, the sensor being attached to the sensor-retaining insert.

5. The device of claim 4 , wherein the sensor-retaining insert defines a cavity configured to receive the swab tip when the swab unit is sealingly engaged with the indicator unit.

6. 6. The device of claim 5, wherein the sensor-retaining insert includes at least one structural feature within or adjacent to the cavity that guides the swab tip into a desired position in the sensor-retaining insert aligned with the sensor.

7. The apparatus of claim 6 , wherein the at least one structural feature is selected from a rib structure, a sloped cavity wall, and combinations thereof.

8. The device of claim 1 , wherein the swab handle is configured to manually expel the liquid from the liquid chamber.

9. 9. The device of claim 8, wherein the swab handle comprises a retaining element configured to couple to the sensor tube and defining a cavity, and a movable element retained within the cavity of the retaining element and movable relative to the retaining element.

10. The apparatus of claim 9 , wherein the liquid chamber is contained within the movable element.

11. 11. The device of claim 10, wherein the movable element further comprises a liquid chamber seal and the swab handle further comprises a piercing member fixedly attached to the retaining element, and wherein moving the movable element from a proximal position to a distal position causes the piercing member to pierce the liquid chamber seal and release the liquid into the sensor tube.

12. The apparatus of claim 11 , wherein the liquid chamber seal comprises a member selected from the group consisting of metal foils and plastic films.

13. 13. The device of claim 12, wherein the swab shaft is fixedly attached to the retaining element such that a proximal end of the swab shaft extends into the cavity of the retaining element, and the piercing member comprises the proximal end of the swab shaft.

14. 14. The device of claim 13, wherein the swab shaft includes a tube having a longitudinal passage formed therethrough, and after the liquid chamber seal is pierced, the liquid chamber is in fluid communication with the sensor tube through the longitudinal passage.

15. 15. The device of claim 14, wherein the swab shaft defines a radial opening at a distal end adjacent the swab tip, and after the liquid chamber seal is pierced, the liquid chamber is in fluid communication with the sensor tube through the longitudinal passage and the radial opening.

16. The device of claim 11 , further comprising a locking mechanism operable to restrict proximal movement of the movable element after the liquid chamber seal is pierced.

17. 2. The device of claim 1, wherein the swab handle is configured to automatically release the liquid from the liquid chamber when the swab handle of the swab unit sealingly engages the proximal opening of the sensor tube.

18. 18. The device of claim 17, wherein the swab handle comprises a liquid chamber seal located at a tip of the liquid chamber, and the indicator unit further comprises a piercing member fixedly attached to the sensor tube in a position such that the tip contacts the liquid chamber seal only when the tip is inserted into the sensor tube, and insertion of the tip into the sensor tube causes the piercing member to pierce the liquid chamber seal and release the liquid into the sensor tube.

19. The device of claim 18 , wherein the piercing member is a piercing ring.

20. 1. A method for detecting a marker in a wound, comprising: (a) contacting the wound with the swab tip of a device according to any one of claims 1 to 19; (b) inserting the swab tip into the sensor tube to sealingly engage the swab unit with the indicator unit; (c) monitoring the sensor for changes; The apparatus comprises a movable element; The method further comprises, following step (b), pressing the movable element.

21. The method of claim 20 , wherein the marker is a host biomarker.

22. 21. The method of claim 20, wherein the change is a color change, a fluorescent signal, a luminescent signal, or an electrical change.

23. 21. The method of claim 20, wherein the sensor comprises a carrier material and at least one substrate operable to undergo a visible color change in response to the expression of a specific infection marker present in wound fluid released from the swab tip.

24. 24. The method of claim 23, further comprising the step of: (d) comparing said alteration to a standard or control to determine the level of said marker.

25. 21. The method of claim 20, wherein step (b) comprises contacting the swab tip of the swab unit with the sensor of the indicator unit.

26. 21. The method of claim 20, wherein step (b) results in piercing a liquid chamber seal located at a distal end of the liquid chamber.

27. 27. The method of claim 26, wherein the piercing of the liquid chamber seal releases liquid into the sensor tube.

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