System, detection unit and kit for the detection of biomolecules and compositions comprising such biomolecules

Abstract

An aspect of the disclosure provides a system (1) for detection of a target biomolecule (12) or a composition comprising a target biomolecule (12), the system (1) comprising: an active material (3) configured to react with the target biomolecule (12), or with the composition comprising a target biomolecule (12), to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination; an applicator (5) configured to deliver the active material (3) to an article (4) for detection of the target biomolecule (12), or of the composition comprising a target biomolecule (12); a light source (7) configured to illuminate the article (4) with wavelengths selected to excite the dual fluorescence; and, an optical detector (9, 11) configured to detect a component of the dual fluorescence.

Description

[0001]Method and Apparatus Field of Invention The present invention relates to methods and apparatus, and more particularly to methods and apparatus for the detection of biomolecules and compositions comprising such biomolecules, and still more particularly to methods and apparatus for the detection of biological warfare agents for use by personnel in areas where such agents may have been dispersed. Background The possibility of hostile militaries or terrorist groups developing and using biological weapons is a persistent threat. Detection of hazardous agents, such as biological and chemical weapons, represents a complex and difficult technical problem. The circumstances in which it is necessary to detect such agents add further difficulty. In addition, the personnel and / or resources available for the purpose may be extremely limited. For example, whilst reliable biological assays may be performed in the laboratory by a scientist, biological warfare agents may be deployed in circumstances where it is only appropriate for military or emergency services personnel to be present. It may also not be possible to provide sufficient numbers of such personnel with the training needed to conduct such assays and, of course, there may be other urgent demands on their time and attention – such as caring for and evacuating people from the field in which such agents are suspected of having been used. Articles, such as surfaces in environments where personnel must operate, may become contaminated with warfare agents, such as biological agents and it may not be possible to tell when a surface is carrying such an agent. This can present a hazard for those personnel and worsens the risk that contamination by the agent might spread. Generally, such contamination is not noticeable and personnel may only become aware of its presence after they have themselves come into contact with the agent, it has taken effect, and the contamination has been spread. There is however currently no solution to the problem of how to detect contamination of an article with a biological agent in a way that is simple and reliable for emergency services and military personnel to use and carry in the field. Summary Aspects and embodiments of the present disclosure are set out in the appended claims and aim to address the above technical problem and other technical problems. Embodiments employ an active material configured to react with a target biomolecule, or with a composition comprising a target biomolecule, to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination. In an aspect there is provided a system for detection of a target biomolecule or a composition comprising a target biomolecule, the system comprising: an active material configured to react with the target biomolecule, or with the composition comprising a target biomolecule, to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination; an applicator configured to deliver the active material to an article for detection of the target biomolecule, or of the composition comprising a target biomolecule; a light source configured to illuminate the article with wavelengths selected to excite the dual fluorescence; and, an optical detector configured to detect a component of the dual fluorescence. In some embodiments the active material comprises an antibody labelled with a reporter group that emits a detectable signal. The reporter group may be a fluorescent dye. The fluorescent dye may be configured to emit infrared light, such as near-infrared (NIR) light. Embodiments may emit wavelengths >700 nm. Embodiments of the disclosure provide a visualization tool for biological agents using near-infrared dye conjugated with a BWA- specific fluorescent immunoassay reagent. The immunoassay reagent may be configured so that the fluorescence intensity increases upon antigen-dependent removal of a fluorophore. The immunoassay reagent may be configured so that, after antigen addition, the antibody moves spatially to interact with the antigen which results in increased fluorescence emission. In an embodiment the active material comprises a near-infrared fluorophore conjugated with an agent specific fluorescent immunoassay reagent (e.g. specific to a particular biological warfare agent). These and other embodiments offer one way for the active material to provide a dual fluorescence. The active material may be configured to emit infra-red light (such as near-infrared light) when excited by light of a first wavelength, such as 777nm light and may also emit a visible fluorescence (such as a red fluorescence) when excited when excited by light of a second wavelength, such as 540 nm. The active material may comprise this conjugated immunoassay which may be freeze-dried. This may provide a lyophilised component of the active material. The active material may be provided with a liquid medium in an applicator, wherein the liquid medium is configured for activating the active material. The active material may comprise an amine-reactive dye such as Dylight800 (RTM). The applicator may comprise an actuatable compartment holding one of the lyophilised component and the liquid medium. The actuatable compartment may be configured so that actuating the actuatable compartment mixes the lyophilised component and the liquid medium to activate the active material. The liquid medium may comprise an assay buffer, such as phosphate buffer, to resuspend the lyophilised components for spraying to the target surface. In an embodiment the system may be provided as a standalone unit, in which the optical detector and the applicator are assembled together to provide a single unit, such as a single integrated unit. An aspect of the disclosure therefore provides a bio-visualisation system, for visualisation of presence of a target biomolecule, or a composition comprising the target biomolecule, the system comprising: a body carrying at least one of: (i) an applicator; and (ii) an applicator coupling for coupling an applicator to the body; wherein said applicator is configured to deliver an active material to an article for detection of the target biomolecule, or of the composition comprising a target biomolecule, wherein the active material is configured to react with the target biomolecule, or with the composition comprising a target biomolecule, to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination; and the body also carries, a light source configured to illuminate the article with wavelengths selected to excite the dual fluorescence; and, an optical detector configured to detect a component of the dual fluorescence. The applicator coupling may comprise a part of the unit configured to hold an applicator in place top be carried by the unit. A further aspect of the disclosure provides a bio-visualisation system, for visualisation of presence of a target biomolecule, or a composition comprising the target biomolecule, the system comprising: a body carrying an applicator configured to deliver an active material to an article for detection of the target biomolecule, or of the composition comprising a target biomolecule and at least one of (i) a container and a (ii) a container coupling for coupling a container of the active material to the system; wherein said container is configured to provide to the applicator, when coupled to the system, a supply of active material configured to react with the target biomolecule, or with the composition comprising a target biomolecule, to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination; and the body also carries, a light source configured to illuminate the article with wavelengths selected to excite the dual fluorescence; and, an optical detector configured to detect a component of the dual fluorescence. The container may be provided by a replaceable cartridge. Such a system may comprise one or more replaceable cartridges, each of which contains an active material configured to react to the presence of a target biomolecule or composition comprising such a target biomolecule. The reaction may give rise to the dual fluorescence. The container coupling may comprise a cartridge receiving area in which the cartridge can be held to enable a fluid coupling to be provided between the active material held in the cartridge and the applicator. The applicator may comprise a spray for delivery of the active material to a surface of the article. The optical detector may be provided by an imaging device, which may comprise one or more image sensors, for imaging a wavelength of the dual fluorescence. The dual fluorescence may comprise a visible fluorescence and an infrared fluorescence. The optical detector and the light source may be provided in a single integrated unit. The optical detector may be provided by an infrared camera and / or a headset configured to be worn by a user of the device. The single integrated unit may further comprise the applicator. The active material may be held in a replaceable cartridge in the single integrated unit, for example the replaceable cartridge may comprise the actuatable compartment. The active material may comprise an antibody and the target biomolecule may be an antigen of the antibody. The target biomolecule or composition comprising the target biomolecule may be a biological warfare agent (BWA). In an aspect there is provided a detection unit for detection of a target biomolecule or a composition comprising a target biomolecule, the detection unit comprising: a cartridge receiving area for receiving a replaceable cartridge of an active material configured to react with the target biomolecule, or with the composition comprising a target biomolecule, to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination; an applicator configured to deliver the active material from the cartridge to an article for detection of the target biomolecule, or of the composition comprising a target biomolecule; a light source configured to illuminate the article with wavelengths selected to excite the dual fluorescence; and, an optical detector configured to detect the infrared fluorescence. The optical detector may be provided by an infrared camera for imaging infrared fluorescence. It may be carried in a headset which may comprise an eyepiece such as goggles for displaying images to the user. The dual fluorescence may comprise an infrared fluorescence and a visible fluorescence. Embodiments provide a kit comprising any of the detection units described or claimed herein and at least one replaceable cartridge of the active material. The at least one replaceable cartridge may comprise a plurality of said cartridges each comprising a different active material configured to detect a different corresponding one of a plurality of target biomolecules. The active material may comprise a lyophilised component and a liquid medium. The, or each, replaceable cartridge may comprise an actuatable compartment holding one of the lyophilised component, and the liquid medium. Actuating the actuatable compartment may activate the active material, for example by mixing the liquid medium with the lyophilised component. The applicator may comprise a spray for delivery of the active material to a surface of the article. The disclosure provides an antibody-based biological-warfare agent (BWA) visualization tool. The active material may comprise a sprayable immunoassay that glows visibly, and in the infrared, in the presence of a particular wavelength of light to pinpoint the physical location of contaminated surfaces. Embodiments provide a definitive biological identifier perhaps with almost ‘zero’ false alarm rates. For example, purified specific antibodies may be used for target recognition, and they may be specific to a target antigen. The detection units of the present disclosure may be provided in wearable systems, integrated into or carried by uniforms, tactical gear, and vehicles, such as combat vehicles and unmanned vehicles including robots and UAVs. Brief Description of Drawings Embodiments of the disclosure will now be described in detail with reference to the accompanying drawings, in which: Figure 1 shows a very schematic illustration of a system for detecting presence of a target biomolecule when the system is in use; Figure 2 shows a schematic illustration of three different embodiments of a system according to the present disclosure, these are shown in Fig. 2A, Fig. 2B and Fig.2C respectively. In the drawings like reference numerals are used to indicate like elements. Specific Description Figure 1 shows a system 1 for detecting presence of a target biomolecule 12 on an area 2 of an article 4. The system may work by the area 2 of the article 4 being sprayed with the active material 3. The active material may provide a dual fluorescence in the presence of the target molecule so that it can be seen by the naked eye and also detected by an infrared sensor. The system 1 comprises a unit 21 which includes an imaging device 9, 11 and a light source 7. The unit 21 further comprises a controller 13, a communications interface 15, and a display 17. The imaging device 9, 11 comprises an optical detector 9, such as an image sensor chip. The optical detector 9 may comprise two such image sensors each sensitive to light of a different wavelength range. For example, it may comprise a first image sensor sensitive to light in an infrared wavelength band. A second image sensor may also be included in the optical detector 9, which is sensitive to light in a visible wavelength band, such as a red wavelength band. The imaging device 9, 11 may comprise optics 11 configured to collect light from an imaging field of view and provide an image of the imaging field of view at the optical detector 9. The sensors of the optical detector 9 and the optics 11 may be configured to provide both visible wavelength image of the imaging field of view of the optics 11 and an infrared image of that same imaging field of view. The light source 7 is configured to illuminate the imaging field of view with light in at least one and optionally two selected wavelength bands. For example, the light source 7 may be configured to provide illumination in a first wavelength band, and a second wavelength band which may be different from the first wavelength band. The first wavelength band may comprise an infrared band, such as near infrared for example including a wavelength of 777nm. The second wavelength band may comprise visible light, which may be green and may include illumination having a wavelength of 540nm. Examples of such light sources include LEDs. Two such types of LEDs may be provided in the light source 7, one type for each wavelength band. The optical detector 9 is connected to the controller 13, for providing electronic signals, e.g. image data, to the controller 13 based on an infrared image on the image sensor and optionally also a visible light image. The controller 13 is also connected to the communications interface 15 and to the display 17. The system 1 also comprises an applicator 5, which in the example illustrated in Figure 1 comprises a spray device for providing a spray of the active material. It may comprise a spray nozzle for spraying a liquid. The applicator 5 is coupled to receive an active material 3 from a container, such as a replaceable cartridge 23. This container may comprise an actuatable compartment 19. The container 23 may hold the active material 3 separate and a liquid medium. The actuatable compartment 19 may keep the active material 3 separate from the liquid medium and may be actuatable to allow the liquid to be mixed with the active material 3 and also to be provided to the applicator 5. The active material may comprise lyophilised component, such as a freeze-dried powder. Typically, the active material 3 is configured so that mixing it with the liquid medium causes it to become activated for interaction with the target biomolecule. The active material 3 is configured so that, when activated by the liquid medium and illuminated by selected wavelengths it will fluoresce. Typically, the wavelengths which stimulate the active material to fluoresce correspond to wavelength bands provided by the illumination light source 7. The active material may comprise a near-infrared fluorophore conjugated with an agent specific fluorescent immunoassay reagent. The immunoassay reagent may be configured so that the fluorescence intensity increases upon antigen-dependent removal of a fluorophore. The immunoassay reagent may be configured so that, after antigen addition, the antibody moves spatially to interact with the antigen which results in increased fluorescence emission. For example, the antigen may be a particular biological warfare agent, or a class of such agents. Accordingly, the immunoassay reagent may be specific to that particular biological warfare agent, or a class of such agents. The controller 13 generally comprises a processor configured to control the communications interface and / or the display 17 of the unit 21. The display 17 may comprise any electronic display for showing an image of the imaging field of view. The image may indicate, to an operator of the device, the arrangement of the active material 2 in the imaging field of view. The communications interface 15 may comprise any wired of wireless communications interface. Typically, the communications interface 15 is operable to communicate over a wide area network (WAN) or a local area network (LAN). The controller 13 may be configured to communicate image data via the communications interface 15 to a remote device. The controller 13 may be further configured to provide a composite image comprising infrared image data (obtained from the infrared image sensor of the optical detector 9) and second image data obtained from a visible wavelength image sensor of the optical detector 9. Such a composite image may comprise a representation of the infrared image superimposed on the visible wavelength image to show disposition of the target biomolecule 2 in the imaging field of view. This may assist the user of the device in accurately determining the disposition of target biomolecule with reference to other objects visible in the field of view. In operation a user of the device may operate the actuatable compartment 19 to allow the liquid medium and lyophilised component 3 to mix. He or she may then operate the applicator 5 to provide a spray of the active material 3 to cover an area 2 of the article 4 which may be suspected of being contaminated with the target biomolecule 12. The user may then operate the unit 21 so that the light source 7 illuminates the article 4. He or she may then cause the controller 13 to operate the imaging device 9, 11 to collect an image of the imaging field of view. The imaging device 9, 11 then collects an image of the imaging field of view and the sensors 9 convert the image-to-image data for provision to the controller 13. The controller 13 may control the display 17 to show the image. As explained above this image may comprise a composite image assembled from (a) an infrared image and (b) an image collected using visible wave lengths. The controller 13 may also provide either the infrared image, or the visible image, or the composite image, or any combination of these three types of image data to the communications interface 15 for communication to a remote device. The controller 13 may be operable by a user command to send the image data via the communications interface 15. It will be appreciated in the context of the present disclosure that the communications interface 15 is optional. In addition, although the optical detector 9 is shown in the drawings as comprising two components, one for infrared frequent wavelengths and one for visible wavelengths. The visible wavelengths detector is optional. The unit 21 may simply comprise an infrared optical detector, and the user may rely on a visible wavelength component of the jewel fluorescence to indicate the disposition of the target biomolecule in the area. In addition, the light source 7 has been described as comprising two separate wavelength bands but it is possible that illumination may be provided by a single wide band illumination source comprising wavelengths to stimulate both aspects of the dual fluorescence of the active material 3. The applicator 5 is described as a spray and the use of sprays in the systems described herein have advantages. For example, they can provide broad and even application of the active material without the need for an operator of the system to touch the surface. However, other types of applicators may also be used. Examples include droppers, sticks, swabs, and brushes. In addition, Figure 1 illustrates the applicator 5 and the unit 21 as being separate and it is envisaged that these components may be made and sold separately. In addition, generally the system may be sold without the active material. The active material may also be sold separately, possibly in a removable and replaceable cartridge which is configured to provide a supply of active material to the applicator 5. However, the applicator 5, the container 23, and the unit 21 may be integrated into a single standalone unit. Figure 2 provides three examples of such a configuration. In the example shown in Figure 2a a detection unit 30 comprises a body which houses all the same components as the unit 21 described above with reference to Figure 1. In addition, the applicator 5, 23 is integrated into the body of the detection unit 30. The container 23 which is coupled to provide a supply of active material to the applicator may be refillable. Figure 2b shows a detection unit 30’ which comprises a cartridge receiving area 32 which is configured to hold an applicator 5, 23 in position against the body of the detection unit 30’. In this way the detection unit 30’ can carry the applicator as part of a single integrated unit but the applicator 5 with container 23 can easily be removed for use in applying the active material to an article to be tested. Figure 2c illustrates a further detection unit 30’’ in which the applicator 5, which may be a spray nozzle and / or pump, is integrated into the body of a detection unit 30’’. In this configuration the cartridge receiving area 32’ is configured to receive the container 23 comprising the active material. When the container / cartridge 23 is provided into this cartridge receiving area 32’ then it is connected to the applicator 5 to allow the applicator 5 to take active material from inside the container to be applied in front of the detection unit 30’’ (in the imaging field of view of the optics 11 of that imaging device). In any of these three examples the cartridge 23 of active material may be removeable and replaceable. Accordingly, a user of the device may open the body of the unit 30 and load a cartridge into a cartridge receiving area 20 of the unit 30. This may be done manually by the user and without any modification of the unit 30. Embodiments may provide a definitive biological identifier with a ‘zero’ false alarm rate, such alarm rate may be achieved by purified antibody used as a target recognition active material, which is specific to its target antigen. Embodiments of the system provide a visualization tool for agents such as biological agents, for example biological warfare agents (BWA). The active material may comprise near-infrared dye conjugated with a BWA-specific fluorescent immunoassay reagent. It may comprise a fluorescent antibody whose fluorescent intensity increases in an antigen-concentration-dependent manner. The immunoassay reagent may be configured so that the fluorescence intensity increases upon antigen-dependent removal of a fluorophore. The immunoassay reagent may be configured so that, after antigen addition, the antibody moves spatially to interact with the antigen which results in increased fluorescence emission. The immunoassay reagent may be configured so that the target biomolecule is an antigen of the antibody. The active material may comprise a near-infrared fluorophore conjugated with a BWA-specific fluorescent immunoassay reagent. These and other embodiments offer one way for the active material to provide a dual fluorescence. For example, the active material may be configured so that upon reaction with the target biomolecule it will emit infra-red light (such as near-infrared light) when excited by light of a first wavelength, such as 777nm light and may also emit a visible fluorescence (such as a red fluorescence) when excited when excited by light of a second wavelength, such as 540 nm. The active material may comprise this conjugated immunoassay which may be freeze-dried. This may provide a lyophilised component of the active material. The active material may be provided with a liquid medium in an applicator, wherein the liquid medium is configured for activating the active material. The applicator may comprise an actuatable compartment holding one of the lyophilised component and the liquid medium. The actuatable compartment may be configured so that actuating the actuatable compartment mixes the lyophilised component and the liquid medium to activate the active material. The applicator may be configured to provide a spray of the active material onto an area, such as an area of an article or environment where it is desired to detect the target molecule. For example, the spray may be provided by a spray of a liquid medium carrying the active material. The optical detector may comprise an imaging device, such as a camera configured to sense light of at least one wavelength range corresponding to a wavelength range of a fluorescence of the active material. The fluorescence may comprise an infrared wavelength range, such as at least 770nm. Embodiments of the system be configured to provide images in which fluorescence from the active material (indicating presence of the target biomolecule) are detectable. Any feature of any one of the examples disclosed herein may be combined with any selected features of any of the other examples described herein. For example, features of methods may be implemented in suitably configured hardware, and the configuration of the specific hardware described herein may be employed in methods implemented using other hardware. It will be appreciated from the discussion above that the embodiments shown in the Figures are merely exemplary, and include features which may be generalised, removed or replaced as described herein and as set out in the claims. With reference to the drawings in general, it will be appreciated that schematic functional block diagrams are used to indicate functionality of systems and apparatus described herein. For example, the display is shown as being connected to the body of the unit 21, but it may be provided separately, such as in a wearable device. Examples include a head-up display in a visor of a helmet or in goggles, such as night vision goggles. It will be appreciated however that the functionality need not be divided in this way, and should not be taken to imply any particular structure of hardware other than that described and claimed below. The function of one or more of the elements shown in the drawings may be further subdivided, and / or distributed throughout apparatus of the disclosure. In some embodiments the function of one or more elements shown in the drawings may be integrated into a single functional unit. In some examples the functionality of the controller 13 may be provided by a general purpose processor, which may be configured to perform a method according to any one of those described herein. In some examples the controller may comprise digital logic, such as field programmable gate arrays, FPGA, application specific integrated circuits, ASIC, a digital signal processor, DSP, or by any other appropriate hardware. In some examples, one or more memory elements can store data and / or program instructions used to implement the operations described herein. Embodiments of the disclosure provide tangible, non-transitory storage media comprising program instructions operable to program a processor to perform any one or more of the methods described and / or claimed herein and / or to provide data processing apparatus as described and / or claimed herein. The controller may comprise an analogue control circuit which provides at least a part of this control functionality. An embodiment provides an analogue control circuit configured to perform any one or more of the methods described herein. The above embodiments are to be understood as illustrative examples. Further embodiments are envisaged. It is to be understood that any feature described in relation to any one embodiment may be used alone, or in combination with other features described, and may also be used in combination with one or more features of any other of the embodiments, or any combination of any other of the embodiments. Furthermore, equivalents and modifications not described above may also be employed without departing from the scope of the invention, which is defined in theaccompanying claims.

Claims

Claims:

1. A system for detection of a target biomolecule or a composition comprising a target biomolecule, the system comprising: an active material configured to react with the target biomolecule, or with the composition comprising a target biomolecule, to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination; an applicator configured to deliver the active material to an article for detection of the target biomolecule, or of the composition comprising a target biomolecule; a light source configured to illuminate the article with wavelengths selected to excite the dual fluorescence; and, an optical detector configured to detect a component of the dual fluorescence.

2. The system of claim 1 wherein the active material comprises a lyophilised component and a liquid medium is provided in the applicator.

3. The system of claim 2 wherein the applicator comprises an actuatable compartment holding one of the lyophilised component and the liquid medium.

4. The system of claim 3 wherein actuating the actuatable compartment mixes lyophilised component and the liquid medium to activate the active material.

5. The system of any preceding claim wherein the applicator comprises a spray for delivery of the active material to a surface of the article.

6. The system of any preceding claim wherein the optical detector is provided by an imaging device for imaging a wavelength of the dual fluorescence.

7. The system of any preceding claim wherein the dual fluorescence comprises a visible fluorescence and an infrared fluorescence.

8. The system of any preceding claim wherein the optical detector and the light source are provided in a single integrated unit.

9. The system of claim 8 wherein the optical detector is provided by an infrared camera.

10. The system of claim 8 or 9 wherein the single integrated unit further comprises the applicator.

11. The system of claim 10 wherein the active material is held in a replaceable cartridge in the single integrated unit, for example wherein the replaceable cartridge comprises the actuatable compartment.

12. The system of any preceding claim wherein the active material comprises an antibody and the target biomolecule is an antigen of the antibody.

13. The system of claim 12 wherein the target biomolecule or composition comprising the target biomolecule is a biological warfare agent (BWA).

14. A detection unit for detection of a target biomolecule or a composition comprising a target biomolecule, the detection unit comprising:a cartridge receiving area for receiving a replaceable cartridge of an active material configured to react with the target biomolecule, or with the composition comprising a target biomolecule, to provide a dual fluorescence, wherein the dual fluorescence is excitable by illumination; an applicator configured to deliver the active material from the cartridge to an article for detection of the target biomolecule, or of the composition comprising a target biomolecule; a light source configured to illuminate the article with wavelengths selected to excite the dual fluorescence; and, an optical detector configured to detect the infrared fluorescence.

15. The detection unit of claim 14 wherein the optical detector is provided by an infrared camera for imaging infrared fluorescence.

16. The detection unit of claim 14 or 15 wherein the dual fluorescence comprises an infrared fluorescence and a visible fluorescence.

17. A kit comprising the detection unit of any of claims 14 to 16 and at least one replaceable cartridge of the active material.

18. The kit of claim 17 wherein the at least one replaceable cartridge comprises a plurality of said cartridges each comprising a different active material configured to detect a different corresponding one of a plurality of target biomolecules.

19. The detection unit of any of claims 14 to 16 or the kit of claim 17 or 18 wherein the active material comprises a lyophilised component and a liquid medium.

20. The detection unit or kit of claim 19 wherein the, or each, replaceable cartridge comprises an actuatable compartment holding one of the lyophilised component and the liquid medium.

21. The detection unit or kit of claim 20 wherein actuating the actuatable compartment activates the active material.

22. The detection unit or kit of claim 21 wherein the applicator comprises a spray for delivery of the active material to a surface of the article.

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