WO2008012566A2

WO2008012566A2 - Oral fluid collection device, system and method

Info

Publication number: WO2008012566A2
Application number: PCT/GB2007/050389
Authority: WO
Inventors: Ahmed Jehanli; Gordon Jowett
Original assignee: Cozart Boiscience Limited
Priority date: 2006-07-25
Filing date: 2007-07-09
Publication date: 2008-01-31
Also published as: GB2440353A; GB2440353B; WO2008012566A3; GB0614740D0

Abstract

An oral fluid collection device comprises an elongate shaft (2), the shaft being substantially hollow at one end (4) and having an opening at that end. A pad of absorbent material (3) is attached to an outer surface of said shaft (2) at or adjacent to said opening and a wick (5) located inside the hollow end of the shaft. Said wick (5) is at least partially coated or impregnated with a soluble dye (6) for the purpose of providing a fluid adequacy indication during use.

Description

ORAL FLUID COLLECTION DEVICE, SYSTEM AND METHOD

Field of the invention

The invention describes a method, device and system for collecting oral fluid for the purpose of detecting analytes in the fluid using for example point-of-care and laboratory-based tests.

Background of The Invention

In recent years, oral fluid has been proposed as an alternative diagnostic matrix to blood and urine for the detection of analytes such as antibodies, antigens, hormones and pharmaceutical drugs including drugs of abuse (Choo and Huestis (2004) "Oral fluid as a diagnostic tool", Clinical Chemistry and Laboratory Medicine, volume 42, pages 1273-1287). Oral fluid is easily accessible by non-invasive means, does not require experience in collection as is the case with blood, and can be easily collected under observation. Oral fluid has been used successfully for therapeutic drug monitoring (methadone treatment of heroin addiction), detection of drugs of abuse in drug treatment clinics and work place, testing and detection of bacterial and viral infection, e.g., helico bacter and HIV. Oral fluid can be used both for point-of-care and laboratory-based testing. It has been proposed as the matrix of choice for roadside testing for drugs of abuse, e.g. by the police.

It is desirable that the procedure for using oral fluid as a diagnostic matrix should involve a rapid collection phase (important for on-site testing), the collection of a sufficient volume for immediate and subsequent analysis, and the ability to extract the analyte under investigation from the oral fluid.

Usually, oral fluid is collected by placing some form of an absorbent material in the mouth followed by extraction of the oral fluid from the absorbent material, which can be made of cotton, cellulose, rayon or any other suitable material. There are several devices described in the prior art for the collection of oral fluid. For example, WO2006064285 describes an analyte collection apparatus that can be used for collecting oral fluid. However, this device has no means of indicating that sufficient volume has been collected. Other patent documents US6652481, US6022326, US5335673, EP0734686, EP0418739, EP0056241, EP1389445, WO03/028889 and WO9418891 describe various devices for the collection of oral fluid that have some limitations in term of lack of volume adequacy indicator, not providing sufficient volume and slow collection time.

US patent 5260031 describes a saliva collection device with a volume adequacy indicator. However, this device has the problem that it may take a relatively long time to collect an adequate volume of oral fluid. Furthermore, the device requires the use of a serum filter (as described in US patent 5786227) to extract the oral fluid from the pad. This adds to the cost of the procedure and involves several time-consuming steps.

Summary of the Invention

Addressing the needs of both on-site testing and laboratory-based testing, we have developed a simple device that combines rapid collection of an adequate volume of oral fluid with ease of obtaining the oral fluid for further analysis by on-site and laboratory-based testing.

According to a first aspect of the present invention there is provided an oral fluid collection device comprising: an elongate shaft, the shaft being substantially hollow at one end and having an opening at that end; a pad of absorbent material attached to an outer surface of said shaft at or adjacent to said opening; and a wick located inside the hollow end of the shaft, said wick being at least partially coated or impregnated with a soluble dye for the purpose of providing a fluid adequacy indication during use, said pad and said wick being made of dissimilar materials.

Other aspect of the present invention are set out in the accompanying claims. Brief Description of the Drawings

Figure 1 shows a perspective view of an oral fluid collection device having a fluid adequacy indicator; Figure 1 a shows a perspective view of a wicking rod of the device of Figure 1 ;

Figures 2 and 2a illustrate first and second states of operation of the device of Figure l;

Figure 3 shows a perspective view of a fluid release widget of a collection tube;

Figures 3a and 3b show perspective views of a collection tube in first and second use states;

Figures 4a to 4c show cross-sectional views of a collection system in respective use states; and

Figure 5 shows a perspective view of a fluid collection device according to a second embodiment of the invention.

Description of the Invention

Figure 1 illustrates an oral fluid collection device comprising a hollow transparent polypropylene shaft/ handle or tube 2 with a cotton or rayon swab 3 spun onto a lower end 4 of the shaft. The swab is shown transparent in the figure although in practice it will be opaque. The weight of the cotton swab determines the volume of oral fluid to be collected, with about 0.07g allowing volumes of 0.3-0.4mL to be collected and about 0.2g allowing approximately 1.OmL to be collected. A liquid-permeable wick or wicking rod 5 (Figure Ia) of chemically cross-linked polyester fibres (where the degree of crosslinking determines the porosity of the material) is inserted into the handle 2 through an upper open end and is pushed down through the handle until it is in contact with the swab 3. The rod is made with a diameter to allow a snug fit into the handle.

The wicking rod 5 has a small amount of food dye (examples: Super Cook Blue or Green food colouring, Supercook, Sherburn-in-Elmet, Leeds, UK; Royal Blue food colouring, Sugerflair Colours Limited, Benfleet, Essex, England) 6 applied either as a line around the circumference of the rod or at the end of the rod that will be in contact with the swab. The dye is allowed to dry prior to insertion of the rod into the handle. In both cases the dye is hidden by the swab and cannot be seen once the device is fully assembled (Figure 2).

An efficient manufacturing process for the device comprises first weaving the swab onto the shaft in situ. To aid attachment of the swab to the shaft, a small amount of adhesive may first be applied to the shaft. The adhesive is chosen to suit the intended purpose, i.e. it must be non-toxic and must not contaminate any test sample. In addition, a glaze may be applied over the surface of the weaved swab to prevent disintegration of the swab in use. Following weaving of the swab, the wicking rod is then inserted through the shaft, from the top end, until it reaches the swab end. The dye may previously have been applied to the rod using, for example, a process similar to ink-jet printing.

The device is used by inserting the swab part in the mouth, wiping the gums, tongue and the inside of the cheeks. As the swab is wetted with oral fluid the liquid eventually passes to the wicking rod, whereupon the dye is hydrated and moves up the wicking rod via the capillary action of the fluid. As the (now coloured) liquid wicks up the fibre rod, the colour appears from "inside" the swab head and is visible through the transparent walls of the polypropylene shaft/handle. The movement of the coloured liquid to the end of the wicking rod is used as an indication that a sample of oral fluid has been successfully collected 5a (Figure 2a).

It is noted that a reason for using different materials for the wicking rod and the swab is to allow the collection time to be accelerated or decelerated while keeping the swab the same. By selecting a wicking rod material with middle density (middle porosity), it can be ensured that the dye will not become hydrated and quickly move to the end of the wicking rod before an adequate volume has been collected. Furthermore, this feature obviates the problem of users cheating the system by blowing air through the swab (in the case of a high porosity wicking rod, water vapour in the air may cause the dye to be hydrated and move sufficiently up the rod to indicate a positive result). By using different materials for the swab and the wicking rod and having them "discontinuous" cheating can be substantially prevented. The oral fluid is recovered from the device as follows: An insert or widget 8 (Figure 3) is constructed from polypropylene or polystyrene material in the shape of a conical tube with external ridges 9 and feet 8a in such a way to allow it to fit snugly inside a collection tube 7 (Figure 3a). The collection tube contains an oral fluid extraction buffer solution 10. As the collector 1 is inserted inside the tube 7, the swab end is squeezed into the widget 8, causing the oral fluid to be released out from the swab into the buffer (Figure 3b). The tube can then be sealed with the collector inside, and sent to a laboratory for analysis. Alternatively, the swab is held in place by the widget 8 which in turn, is held in the tube by the external ridges 9. This allows pouring of the buffer/oral fluid mixture into suitable containers that can then be sent to the laboratory for analysis.

Figures 4a-c are a cross-section cut illustration of this procedure. The insert is shaped as a conical tube with the lower inside diameter being 1-2 mm less than the upper inside diameter. This configuration aids in the squeezing and compressing of the swab, resulting in a greater release of oral fluid from the swab. The insert can even be made in a V- shape configuration to allow it to fit into V-shaped bottles or containers. The ridges 9 are added to the structure to allow the insert to be held by friction inside the tube. Feet 8a and the intervening spaces allow circulation and mixing of the released oral fluid with the buffer solution.

The widget can be constructed with any other shape to fit into the required container. This may be a dropper bottle which would conveniently allow a test sample to be dropped onto, for example, a lateral flow test device.

A modification of the device is illustrated in Figure 5. In this case, the shaft/ handle 2 is scored around the circumference at a point 11 corresponding to the end of the wicking rod 5, thereby weakening the shaft at this point. This allows the upper part of the handle to be snapped off after inserting the swab end into a suitable bottle or container with or without a widget. For example the swab may be snapped into a dropper bottle containing an appropriate buffer to extract analyte from the swab and apply the mixture to a suitable on-site testing device like a lateral flow based test device. This arrangement allows the collection device to be used even with relatively short containers. Embodiments of the present invention have one or more of the following advantages:

• The collection device allows easy and rapid collection of a sufficient volume of oral fluid. • The volume collected depends on the weight of the cotton material used in the swab and so can be easily varied depending upon the chosen application. By varying the porosity of the wicking rod, and removing the device from the moth when the fluid adequacy indicator indicates that collection is complete, it is equally possible to vary the collected volume up to the maximum capacity of the swab.

• The wicking rod provides an indicator or proof of collecting a sample with a more defined volume.

• The insert/widget serves to extract the oral fluid without the need to use centrifugation or filtration.

Example 1:

The collection device was constructed with 0.07g of cotton swab. Oral fluid was collected from drug-free volunteers using the device. Collection time and volume when the dye reached the end of the wicking rod were recorded. The results obtained (Table 1) showed that the device allowed rapid collection (average time: 36 seconds ) of fairly consistent volume of oral fluid (average volume: 0.35mL) which is ideal for on-site tests. The same experiment was repeated using a 0.2g swab (Table 2). The average collection time and volume were 55 seconds and about 1.OmL. This volume is more than sufficient for laboratory-based screening and confirmation analyses.

Example 2:

Drug recovery from the device was evaluated as follows: Oral fluid was collected by expectoration from a number of drug-free volunteers. The oral fluid was spiked with drugs (morphine, methadone, cannabis, temazepam, amphetamine, methamphetamine, ecstasy and cocaine at lOOng/mL each). 1 mL of the oral fluid was taken up by the device then processed as described in Figure 3. Drug concentration in the original oral fluid and the oral fluid recovered from the device was measured using enzyme immunoassay. Drug recovery for all the drugs was over 90%. It will be appreciated by the person of skill in the art that various modifications may be made to the above described embodiments without departing from the scope of the present invention.

Table 1 Oral fluid collection volume and time using 0.07g swab.

Table 2 Oral fluid collection volume and time using 0.2Og swab.

Claims

1. An oral fluid collection device comprising: an elongate shaft, the shaft being substantially hollow at one end and having an opening at that end; a pad of absorbent material attached to an outer surface of said shaft at or adjacent to said opening; and a wick located inside the hollow end of the shaft, said wick being at least partially coated or impregnated with a soluble dye for the purpose of providing a fluid adequacy indication during use, said pad and said wick being made of dissimilar materials.

2. A device according to claim 1, wherein said wick is coated or impregnated with a soluble dye at a first location of the wick and the absorption of fluid by the wick causes the dye to dissolve and flow along the wick in a direction away from said opening.

3. A device according to claim 2, said shaft being substantially transparent in the region of said wick.

4. A device according to claim 3, wherein said pad obscures a portion of the wick coated or impregnated with said soluble dye.

5. A device according to any one of the preceding claims, wherein said pad is made of cotton.

6. A device according to any one of the preceding claims, wherein said wick is made of a porous polymer material.

7. A device according to any one of the preceding claims, wherein said wick has a generally cylindrical shape conforming substantially to an inner hollow space of said shaft.

8. An oral fluid collection device comprising: an elongate shaft, the shaft being substantially hollow at one end and having an opening at that end; a pad of absorbent material attached to an outer surface of said shaft at or adjacent to said opening; and a wick located inside the hollow end of the shaft, said wick being at least partially coated or impregnated with a soluble dye for the purpose of providing a fluid adequacy indication during use, wherein said shaft is weakened at a point along its length to allow an upper portion of the shaft to be snapped off from a lower portion to which said pad is attached.

9. A device according to claim 8, the shaft being weakened by a score around its circumference.

10. A device according to claim 8 or 9, said shaft being weakened at a point substantially adjacent to an end of said wick.

11. An oral fluid collection system comprising a collection device according to any one of the preceding claims, a collection container arranged to receive at least an end of the device to which said pad is attached, and a compression member located in said container and arranged to receive said pad of the device when the device is inserted into the container and to cause said pad to be squeezed to remove fluid therefrom.

12. A system according to claim 11, wherein said compression member is generally cylindrical having a central passage extending therethrough for receiving the pad of the device, the central passage being generally conical in shape such that it is wider at its receiving mouth than at its distal end.

13. A method of manufacturing an oral fluid collection device comprising: weaving a pad onto an end of an elongate shaft; either before or after said weaving step, inserting a wick into a hollow passage within said shaft through an opening at one end thereof, said wick being at least partially coated or impregnated with a dye.

14. A method according to claim 13 and comprising coating an end of said shaft with an adhesive prior to weaving said cotton pad atop the coated end.

15. A method according to claim 13 or 14 and comprising applying a glaze to the weaved pad.

16. A method according to any one of claims 13 to 15, wherein said pad is weaved from cotton or rayon.