RELATED APPLICATION

This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 63/040,078 filed June 17, 2020, the entire contents of which is incorporated herein by reference in its entirety.

GOVERNMENT SUPPORT

This invention was funded by the National Institutes of Health. The United States Government has certain rights in this invention.

FIELD OF THE INVENTION

The disclosed embodiments generally relates to methods and devices for collecting saliva from the parotid glands in the mouth.

BACKGROUND OF THE INVENTION

Generally fifty percent of saliva is produced by the parotid glands, the secretions of which reach the mouth through Stenson's ducts, which terminate in easily visible orifices on the inside of the cheek. Parotid secretion is quite similar, chemically, to tears. In common with other secretions, such as tears, milk, gut and lung secretions, saliva is a complex mixture of numerous types of proteins including enzymes, secretory immunoglobulins, and proteins such as lysozyme, lactoferrin and peroxidase. The immune processes of the circulating system, particularly lymphocytes and components of blood plasma, defend against microorganisms which attack through the circulatory system. Similarly immune processes in the secretory system defend our mucosal tissues from invading microorganisms. Similar to the analysis of immune reactions in the blood for providing information about abnormalities within reach of circulating blood, analysis of salvia secretions can indicate information regarding immunity.

Dental researchers have long been interested in the analysis of saliva, hoping to understand the role played by its constituents in controlling the organisms which cause dental caries and peridontal disease. In recent years, as automated clinical analysis of body fluids (particularly blood and urine) has become routine, biochemists have become interested in analyzing the components of the secretory system. Such analysis may provide information about the body's state of mobilization against specific pathogens. It can also illuminate biological processes such as drug metabolism and electrolyte balance.

Saliva in the mouth is contaminated with bacteria, food detritus, and sloughed- off epithelial cells. What has been long sought for by dental researchers, and more recently by clinical biochemists and immunologists, is a convenient way to non- invasively collect a sample of pure saliva as it is secreted by the glands which produce it. The most convenient source of such a sample is the parotid gland, which secretes about half of the saliva through Stenson's duct. Stenson's duct empties into the buccal cavity on the inside of the cheek. The secretion of the parotid gland from a given subject, as it comes from Stenson's duct, is a water-clear, nearly sterile fluid of consistent composition.

SUMMARY OF THE INVENTION

In one aspect, a purpose of the illustrated embodiments is to provide for collection of samples of saliva using a device disposed within the mouth during the collection process. Particularly, a purpose is for providing a device for collecting saliva secreted by the parotid glands, which when put in place over Stenson's duct, will not easily become dislodged by movement of the subject's mouth while the sample is collecting in the device.

In a one aspect, a device for the collection of saliva is provided which is configured to 1) collect a saliva sample from a patient and 2) store or dispense the collected saliva sample.

In certain embodiments, the device is configured to fit within a patient’s mouth. For instance, in certain aspects, a device may have a longest dimension of 4 iches, 3.5 inches, 3 inches, 2.5 inches, 2 inches, 1.9, inches, 1.8 inches, 1.7 inches, 1.6 inches, 1.5 inches, 1.4 inches, 1.3 inches, 1.2 inches, 1.1 inches, 1 inch, 0.9 inches, 0.8 inch, 0.7 inch, 0.6 inch or 0.5 inch or less. In certain aspects, a longest dimension of the device does not include any entry or exit portals, inlet or outlet flow lines or conduits and other such links.

In certain embodiments, the device is a substantially unitary apparatus, where the collection and dispensing features are contained within a single device.

In other embodiments, the device may include separate, coordinated apparatus. For instance, a saliva collection apparatus may be positioned within a patient’s mouth during use of the device and collected saliva delivered to a reservoir device outside of the patient’s mouth. In a further configuration, at least a portion of a salvia collection device may be external to the patient, for example where a collection tube that can provide negative pressure is inserted within the patient’s mouth and the collected saliva is retained in a reservoir or sample vessel.

In a further aspect, a device for the collection of saliva is provided which includes a body member having exterior portion bifurcated to define an inner chamber and an outer chamber. The outer chamber is configured to provide negative pressure for attaching the body member against an interior cheek portion of a patient. The inner chamber is configured to collect salvia when the device is attached to the interior cheek portion of the patient. The inner chamber has a top portion relative to a top portion of the patient’s mouth and a bottom portion relative to a bottom portion of the patient’s mouth when attached to the patient’s cheek. The bottom portion defines a beveled fluid aperture in fluid communication with an interior portion of the body member such that salvia collected from the patient’s cheek in the inner chamber flows to the interior portion of the body member, which flows outwardly from the body member for collection thereof.

In a further aspects, methods are provided for collecting salvia from a patient, comprising using a device as disclosed herein, for example where a portion of the device is placed within the patient’s mouth. Suitably, a negative pressure is applied within the patient’s mouth to collect salvia.

The present devices and methods may be used for a variety of therapeutic and diagnostic applications including to assess parotid gland function. The present methods and devices also may be used to assess the extent or amount of parotid gland secretion or other salivary gland secretion. In particular, the present devices and methods may be used to treat a patient suffering from or suspected of suffering from paratoid salivary hypofunction, Sjogem’s syndrome or Sicca syndrome and/or other diseases or disorders with salivary gland involvement. The present devices and methods also may be used to treat or assess a patient suffering from or suspected of suffering from xerostomia, including radiation-induced xerostomia or chemical or drug induced or associated xerostomia. In the present therapeutic and diagnostic methods, for instance a saliva sample suitably can be collected from a patient using a present device and/or method and the collected sample assessed for such a disease or disorder, for example if a particular biomarker for the disease or disorder is present in the sample. The progress of a particular therapy for such a disease or disorder also may be monitored using a present device and/or method, for instance to assess whether a particular biomarker for the disease or disorder is reduced in a collected saliva sample over the course of the therapy.

Treatment kits also are provided and may comprise (a) a device as disclosed herein and (b) instructions for use of the device to diagnosis or treat a disease or disorder such as those disclosed herein, including those with salivary gland involvement.

The purpose and advantages of the below described illustrated embodiments will be set forth in and apparent from the description that follows. Additional advantages of the illustrated embodiments will be realized and attained by the devices, systems and methods particularly pointed out in the written description and claims hereof, as well as from the appended drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying appendices and/or drawings illustrate various non-limiting, example, inventive aspects in accordance with the present disclosure:

FIG. 1 is a top planar view of a device for collection of salvia in accordance with an illustrated embodiment;

FIG. 2 is a side planar view taken along lines A-A of the device of FIG. 1;

FIG. 3 is a side planar view taken along lines B-B of the device of FIG. 1;

FIG. 4 is a side planar view taken along lines C-C of the device of FIG. 1; FIG. 5 is a side planar view taken along lines D-D of the device of FIG. 1; FIG. 6 is a bottom planar partial cutaway view of the device of FIG. 1; FIG. 7 is atop perspective view of the device of FIG.1;

FIGS. 8 and 9 are a sectional perspective views of the device of FIG. 1; FIG. 10 illustrates use of the device of FIG. 1 for collecting saliva from a patient; and

FIG. 11 illustrates the device of FIG. 1 coupled to a vacuum apparatus.

DETAILED DESCRIPTION

The illustrated embodiments are now described more fully with reference to the accompanying drawings wherein like reference numerals identify similar structural/functional features. The illustrated embodiments are not limited in any way to what is illustrated as the illustrated embodiments described below are merely exemplary, which can be embodied in various forms, as appreciated by one skilled in the art. Therefore, it is to be understood that any structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representation for teaching one skilled in the art to variously employ the discussed embodiments. Furthermore, the terms and phrases used herein are not intended to be limiting but rather to provide an understandable description of the illustrated embodiments.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the illustrated embodiments. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges is also encompassed within the illustrated embodiments, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either both of those included limits are also included in the illustrated embodiments.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the illustrated embodiments, exemplary methods and materials are now described.

It must be noted that as used herein and in the appended claims, the singular forms “a”, “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a stimulus” includes a plurality of such stimuli and reference to “the signal” includes reference to one or more signals and equivalents thereof known to those skilled in the art, and so forth.

With reference now to the illustrated embodiments depicted in FIGS. 1-11, it is to be understood and appreciated the following description of the illustrated embodiments are for illustrative purposes and are not to be construed as limiting it.

Starting with FIG. 1, shown is a top planar view of a device for collecting salvia samples from a patient 100 (FIG. 10), designated generally by reference numeral 10. It is to be appreciated that FIG. 1 illustrates a first side of the device 10, while FIG. 2 illustrates an opposing back side of the device 10. It is to be further appreciated that while shown to have a circular configuration in the illustrated embodiments of FIGS. 1-11, device 10 may be of any convenient and suitable shape configured to be large enough to enable easy placement preferably over a patient’s parotid gland (e.g., Stenson's duct), yet not so large as to allow enough cheek to bulge into the device 10 to relieve the negative pressure which holds the device 10 in place, or to severely limit the volume of its salvia reservoir 50. Preferably, the edges of the device 10 are smooth to prevent leakage of air into the device 10, and loss of the negative pressure which holds it in place. The dimensions of the device 10 are preferably as such to allow a comfortable fit in a patient’s mouth 110, and at the same time allow sufficient volume for the reservoir 50. The device 10 may be made of any material which which is compatible with the oral environment. For instance, the device 10 may be fabricated from gas sterilizable plastics, such as Delrin.

FIG. 1 also depicts a dimension a of composite device 10 that includes conduits 45, 55 as well as longest dimension of the device b (i.e. the longest dimension b being the length of the device that does not include conduits 45, 55 or other flow lines as discussed above). As discussed above, a device suitably may have for example a longest dimension b as shown in FIG. 1 of 4 inches or less, 3.5 inches or less, 3 inches or less, 2.5 inches or less, 2 inches or less, 1.9, inches or less, 1.8 inches or less, 1.7 inches, or less 1.6 inches or less, 1.5 inches or less, 1.4 inches or less, 1.3 inches or less, 1.2 inches or less, 1.1 inches or less, 1 inch or less, 0.9 inches or less, 0.8 inch or less, 0.7 inch or less, 0.6 inch or less, or 0.5 inch or less.

Description of the device 10 is now provided with general reference to FIGS. 1-9. Device 10 generally has body member 10 having a front side exterior portion bifurcated to define an inner chamber (e.g, a salvia reservoir) 50 and an outer vacuum chamber 40. With particular reference to FIGS 7-9, the inner chamber 50 is defined by a first inner circular wall 16 upstanding from a surface (end) portion 18 of the front exterior portion of the body member 14. The exterior outer vacuum chamber 40 is formed by a second outer circular wall 20 upstanding from a surface (end) portion 18 of the front exterior portion of the body member 14 wherein the first 16 and second circular walls 20 are preferably concentric such that the diameter of the second wall 20 is greater than the diameter of the first 16 circular wall. In accordance with an illustrated embodiment, the circular body member 14 preferably has approximately a 1” diameter and each first and second wall 16, 20 extends from the front surface 18 of the body member 14 at a distance of approximately .07” inch, which is sufficient for sampling saliva in most patient’s mouths.

With regard to the outer chamber 40, it is preferably configured to provide (and retain) negative pressure for attaching the front side of the body member 14 of the device 10 against an interior cheek portion 112 of a patient 100 for collecting a salvia sample therefrom, as further described below. And with regard to the inner salvia reservoir chamber 50, it is configured to collect salvia when the device 10 is attached against the interior cheek portion 112 of the patient 100, whereby the inner chamber 50 has a top portion 22 relative to a top portion of the patient’s mouth 110 and a bottom portion 24 relative to a bottom portion of the patient’s mouth 110 when attached to the patient’s cheek 112. The bottom portion 24 of the interior chamber 50 defines a fluid aperture 26 in fluid communication with a first interior channel 28 defined in the body member 10 (FIG. 9) such that salvia collected from the patient’s cheek 112 in the inner salvia reservoir chamber 50 flows into the interior fluid channel 28 defined in the body member 14 of the device 10.

With specific regard to the fluid aperture 26, it is defined in a bottom portion of the inner fluid reservoir chamber 50 when the device 10 is positioned against a patient’s cheek 112, as best shown in FIG. 10. For instance, the fluid aperture 26 is preferably provided in the inner fluid reservoir chamber 50 at approximately a 45 degree angle relative to X and Y axis’ defined by the inner fluid reservoir chamber 50, as shown in FIG. 10. A noted advantage of this positioning of the fluid aperture 26 is that salvia is optimally collected in a salvia collection apparatus 160 since salvia is collected soon after it enters the inner fluid reservoir chamber 50 via the bottom positioning of the fluid aperture 26 in the inner fluid reservoir chamber 50.

The outer vacuum chamber 40 defines the vacuum aperture 12 on its bottom surface portion 30, which vacuum aperture 12 extends into, and is in fluid communication with, a second interior channel 32 defined in the body member 10 (FIG. 8) such that vacuum pressure supplied by the second interior channel 32 supplies a negative vacuum pressure in the outer chamber 40 sufficient to maintain the device 10 against a patient’s cheek 112 when collecting saliva in the inner chamber 50. Preferably, each of the vacuum aperture 12 and fluid aperture 26 are formed with a beveled configuration. As best shown in FIG. 1, the aforesaid first 28 and second 32 channel members are preferably defined parallel to one another in the body member 14 of the device 10.

In accordance with the illustrated embodiments, the device 10 preferably includes a manifold member 34 extending outwardly from a side portion of the body member 14. As best shown in FIG. 1, preferably the aforementioned first interior fluid channel 28 and second interior channel 32 extend through the manifold 34 forming respective first 36 and second open ends 36, 38 formed at the end portion of the manifold member 34. First and second elongate conduits 45, 55 are coupled to the device 10, preferably via the manifold member 34. The length c of conduits 45, 55 suitably may vary and may be for example 4 inches or less, 3.5 inches or less, 3 inches or less, 2.5 inches or less, 2 inches or less, 1.9, inches or less, 1.8 inches or less, 1.7 inches, or less 1.6 inches or less, 1.5 inches or less, 1.4 inches or less, 1.3 inches or less, 1.2 inches or less, 1.1 inches or less, 1 inch or less, 0.9 inches or less, 0.8 inch or less, 0.7 inch or less, 0.6 inch or less, or 0.5 inch or less. Suitable cross-sectional length or width dimensions (i.e. perpendicular to longest dimension a in FIG. 1) also may suitably vary. For instance, a cross-sectional dimension or width (shown as cross-section width d in FIG. 1) perpendicular to a longest dimension of the device suitably may be for example 4 inches or less, 3.5 inches or less, 3 inches or less, 2.5 inches or less, 2 inches or less, 1.9, inches or less, 1.8 inches or less, 1.7 inches, or less 1.6 inches or less, 1.5 inches or less, 1.4 inches or less, 1.3 inches or less, 1.2 inches or less, 1.1 inches or less, 1 inch or less, 0.9 inches or less, 0.8 inch or less, 0.7 inch or less, 0.6 inch or less, or 0.5 inch or less. In FIG. 1, a cross-sectional dimension or width is illustrated as d. In certain aspects, a longest dimension and perpendicular cross-sectional width may be the same or approximately the same, for example the cross-sectional dimension or width may be at least 60, 70, 80, 90, 95 percent or more of the longest dimension of the device. In certain preferred embodiments, the cross-sectional width of the device (shown as d is FIG. 1) is between 50 and 100 percent of the longest dimension (shown as b in FIG.

1) of the device. In additional preferred embodiments, the cross-sectional width (shown as d is FIG. 1) of the device is between 10, 20, 30, 40 or 50 percent and 60,

70, 80, 90 or 100 percent of the longest dimension (shown as b in FIG. 1) of the device.

With regard to the first elongate conduit 45, a distal end 47 of the first elongate conduit 45 is received within the first open end 36 of the manifold member 34 so as to be in fluid communication with the interior fluid channel 28 of the body member 14 such that saliva collected in the inner saliva reservoir chamber 50 flows through the fluid aperture 26, into the first fluid channel 28 and through the first elongate conduit 45 so as to be collected from a proximal end 49 of the first elongate conduit 45 (as best shown in FIG. 9). And with regard to the second elongate conduit 55, a distal end 57 of the second elongate conduit 55 is received within the second open end 38 of the manifold member 34 so as to be in fluid (vacuum) communication with the interior vacuum channel 32 of the body member 14 such that a vacuum (negative pressure) is applied to the outer vacuum chamber 40 of the device 10 via a vacuum apparatus 150 preferably coupled to a proximal end 49 of the second elongate conduit 55 (as best shown in FIG. 8). Each of the first and second elongate conduits 45, 55 is preferably formed of suitable sterilizable surgical metal.

It is to be understood the proximal end 49 of the first fluid elongate conduit 45 is operatively associated with any suitable salvia collection device 160 for collecting the saliva collected in the inner salvia reservoir chamber 50 of the device 10. With regard to the second elongate conduit 55, its proximal end 59 is preferably operatively associated a vacuum apparatus 150 (e.g., hand operated or electro-mechanical) for supplying the vacuum (negative pressure) to the device 10, as mentioned above (and as shown in FIG. 11).

With the certain illustrated embodiments for the device 10 for collecting salvia samples described above with reference to FIGS. 1-9, its method of use will now be described with reference to FIG. 10 (and with continuing reference to FIGS. 1-9). As shown in FIG. 10, the device 10 as described above is preferably utilized to collect saliva secretion of the parotid gland 114 which includes inserting the device 10 in a patient’s mouth 110, against the side of the cheek 112 (preferably adjacent the parotid gland 114). With the first and second elongate conduits 45, 55 extending outwardly from the patient’s mouth 110, negative pressure is applied in an outer chamber 40 of the saliva collection device 10 for attaching the body member 14 against the patient’s cheek 112. The negative pressure applied by the outer chamber 40 of the device 10 is supplied via actuation of a vacuum apparatus 150 coupled to a proximal end 59 of the second elongate conduit 55.

With the device 10 now adhered to the patient’s cheek 112, preferably adjacent the parotid gland 114, salvia which secretes from the parotid gland 114 is collected in the inner salvia reservoir chamber 50 of the device 10. This collected salvia then flows through the fluid aperture 26 formed in the inner chamber 50, through the interior fluid channel 28 formed in the body member 14 so as to then flow through the first elongate conduit 45 coupled to the device 10. The flowing salvia then flows out of the proximal end 49 of the second elongate conduit 55, and preferably into a suitable salvia collection apparatus 160. Diagnosis is then conducted upon the salvia collected in the collection apparatus 160.

With certain illustrated embodiments described above, it is to be appreciated that various non-limiting embodiments described herein may be used separately, combined or selectively combined for specific applications. Further, some of the various features of the above non-limiting embodiments may be used without the corresponding use of other described features. The foregoing description should therefore be considered as merely illustrative of the principles, teachings and exemplary embodiments of this invention, and not in limitation thereof.

It is to be understood that the above-described arrangements are only illustrative of the application of the principles of the illustrated embodiments. Numerous modifications and alternative arrangements may be devised by those skilled in the art without departing from the scope of the illustrated embodiments, and the appended claims are intended to cover such modifications and arrangements.