WO2010004246A1

WO2010004246A1 - Fluid decontamination method and apparatus

Info

Publication number: WO2010004246A1
Application number: PCT/GB2009/001331
Authority: WO
Inventors: Robert Andrew Porter
Original assignee: The Secretary Of State For Innovation Universities & Skills Of Her Majesty's Britannic Government
Priority date: 2008-07-10
Filing date: 2009-05-28
Publication date: 2010-01-14
Also published as: GB0812680D0; GB2461612A; GB0909203D0

Abstract

A sample carrier, such as a test chip (10), is provided with at least a pair of electrodes (38, 40) at the extremities of a sample holding zone (16, 18, 32-36). A power source (52) is operable to supply electrical potential to the electrodes (38, 40), which causes a short circuit in a sample in the sample holding portion, thereby to heat this to a sterilisation temperature. In this manner, contagious elements in a sample can be sterilised. The sample holder is intended to be shorted via electrodes and the contained biological fluid in order to inactivate pathogens.

Description

FLUID DECONTAMINATION METHOD AND APPARATUS

The present invention relates to a method of and apparatus for decontaminating, for example by sterilisation or coagulation, a sample of fluid, in the preferred embodiment to a method and apparatus for decontaminating a blood sample, such as on a carrier device after the performance of a biological assay. Many forms of medical and veterinary treatments and procedures require biological fluid to be extracted from a patient in order to be performed. For example, many conditions are diagnosed by testing a sample of blood for the presence of various antigens. While such tests provide essential diagnoses, the equipment used to perform the tests inevitably presents a potential source of infection once they contain biological fluid. The potentially contaminated equipment is a risk to medical and ancillary workers dealing with medical waste, as well as providing a significant problem for disposal.

Problems of potentially infectious samples are not restricted to extracted samples of biological fluid. For example, many research laboratories conduct experiments on cultures of micro-organisms including bacteria and viruses. When the experiment has been -^; completed, great care must be taken to ensure the micro-organisms are sterilised.

In general equipment of this nature the sample is at best temporarily sealed and then placed in a storage container, such as a bin, for subsequent disposal by incineration or autoclave. In the case of a hypodermic needle, for example, after use the device presents a significant problem by having a sharp infected needle, which requires securing then destruction. While methods have sought to be developed to cover the needle securely after use, for example by locating the needle into a cap or the like, these are not entirely effective and remain a significant risk until the needle has been secured and during the process of doing this. Furthermore, the contents of the syringe remains infectious for the entire time it is in the vicinity of medical staff and other people, that is until it has been removed and destroyed.

Similarly, in the case of a collected sample of biological fluid on a device other than a needle, such as a phial, Petri dish or the like, the sample presents a risk to staff handling the device beyond what is strictly necessary, including while lying in a bin or other collection device awaiting disposal. WO 00/13715 discloses a device for treating a liquid against micro-organisms. It comprises at least two electrodes and has an inlet and an outlet so that circulating liquid can pass through and be subjected to an electric field between the electrodes. JP08051973 discloses a filtration device in which a solution of human blood or plasma is passed between electrodes which apply a pulsed voltage to the solution to destroy viruses. JPl 1322619 discloses filtration equipment in which blood or water is passed between air permeable electrodes with a high potential gradient to inactivate viruses and bacteria.

JP2000300664 is an "external blood processing apparatus" which uses a high frequency alternator through three electrodes to inactivate pathogenic viruses.

The present invention seeks to provide a method of and apparatus for decontaminating a sample of fluid held on or in a carrier device. According to an aspect of the present invention, there is provided a disposable sample holder for holding and decontaminating a liquid sample including a substrate provided with a sample holding zone; and first and second electrical terminals located at the sample holding zone; wherein the electrical terminals are operable to apply electrical energy across a sample in the sample zone so as to heat the sample to a decontamination temperature and render the sample holder safe for disposal.

The term decontamination is intended in this disclosure to include mechanisms by which a sample can be rendered substantially non contagious and can include sterilisation, coagulation of the sample, encapsulation in a gelling agent or the like.

The application of an electrical potential through the substrate of sufficient magnitude and/or duration can destroy all harmful cells in the sample, such as pathogens, antigens and so on, and thus sterilise the sample carrier, making it virtually innocuous for subsequent handling and disposal.

Preferably, the sample holding zone forms a generally closed chamber for the sample. This can minimise the number of surfaces with which the potentially contaminated sample comes into contact. Advantageously, the electrical terminals are operable to raise the sample to a decontamination temperature while the sample is retained substantially stationary in the sample holding zone such that there is no continuous flow of fluid. The sample holding zone can retain the sample after decontamination such that the sample holding zone and the sample can be disposed of together. Advantageously, the first and second electrodes are located at or adjacent extremities of the sample holding zone. This can ensure that the entirety of the sample is reliably destroyed. In an embodiment, electrodes may be located at intermediate positions in the sample holding zone. This can enhance the decontamination effect and/or can be useful in cases where the sample covers only a portion of the sample holding zone, such as on a Petri dish or microscope slide. Furthermore, smaller zones reduce the voltage needed for decontamination, in which case there may be provided an array of electrodes across the sample zone, which electrodes are energised in sequence so as to decontaminate successive parts of the sample.

Advantageously, the apparatus includes a source of electrical power, which source includes first and second electrical terminals connectable to the first and second electrical terminals of the substrate so as to supply electrical energy thereto.

Preferably, the electrical power source is operable to generate a voltage of at least 0.5 volts for a minimum of 2 seconds and more preferably up to 1.2 volts. The unit may generate a voltage of up to around 9 volts, as per some batteries used to power hand held electronic devices. The electrical potential is preferably such as to heat the sample to at least 40 to 50 degrees Centigrade for at least 2 seconds to cause coagulation or decontamination of the sample. The application of such a voltage preferably creates a short circuit through the sample so as to heat this. In the case of a sample of blood, in many instances it should only be necessary to cause this to clot, whereupon the clotted blood presents a negligible risk of contamination. In other cases it may be preferable to decontaminate the sample by in effect sterilisation, that is by killing organisms in the sample. For this purpose heating to 50 degrees Centigrade for two or more minutes may be sufficient although it is envisaged that heat up to 90 or even 100 degrees may be necessary in some circumstances. It is not necessary to produce a large voltage across the sample to achieve such heating, even 0.5 or even 1 volt can be sufficient. It is envisaged in some embodiments that the sample could be provided with a gelling agent which is activated during the heating so as to spread through the sample and to gel, thereby in effect to coagulate, that is tie down, contagious elements of the sample. In a preferred embodiment, the electrical power source forms part of a diagnostic device. In this embodiment, the sample carrier can be sterilised immediately after it has been used in a diagnosis, thus minimising all risks of handling subsequent to this procedure. According to another aspect of the present invention, there is provided apparatus for holding and sterilising a liquid sample including a housing for a substrate, the substrate including a sample holding zone; and first and second electrical terminals locatable at the sample holding zone of the substrate, the apparatus including a source of electrical power operable to apply a potential across the electrical terminals so as to apply electrical energy across a sample in the sample zone.

Such apparatus can sterilise a sample carried on a sample carrier, in the preferred embodiment without requiring the sample carrier to be modified in any way from existing devices. According to another aspect of the present invention, there is provided a method of sterilising a liquid sample provided on a substrate, the substrate including a sample holding zone, the method including the steps of: providing first and second electrical terminals at the sample holding zone; and applying an electrical potential across the first and second electrical terminals thereby to impart electrical energy to the sample so as to heat the sample to a sterilisation temperature while the sample is retained substantially stationary in the sample holding zone such that there is no continuous flow of fluid.

Advantageously, the method includes the step of providing the first and electrical terminals on the substrate.

The method may be carried out subsequent to a diagnosis performed on the sample. Embodiments of the present invention are described below, by way of example only, with reference to the accompanying drawings, in which:

Figure 1 shows an example of a sample carrier for use in effecting medical diagnoses;

Figures 2 to 8 show the use of the sample carrier of Figure 1 in a diagnostic procedure on a patient;

Figure 9 is a schematic diagram of a preferred embodiment of the sample carrier of Figure 1 ;

Figure 10 is a perspective view, in schematic form, of one example of chip receiving interface element of the diagnostic device of Figure 2; Figure 1 1 is a schematic diagram of an embodiment of syringe; and

Figure 12 is a schematic diagram of an embodiment of microscope slide. Referring to Figure 1, there is shown an example of a disposable sample carrier 10 for use in medical testing and in particular for carrying out diagnoses on the blood or other bodily fluid of a patient.

This particular sample carrier 10 forms the subject of the applicant's co-pending British patent applications numbers 0812679.9 filed on 10 July 2008 (Agents' Reference: RJ/N22505) and 0812681.5 filed on 10 July 2008 (Agents' Reference: RJ/N22799), although the present disclosure is not limited to this specific form of sample carrier.

The sample carrier 10 is in the form of a substantially flat chip 12 convenient for handling and for analysis. It includes within its casing 12 a sample holding zone 14, described in further detail below, which includes at least one chamber or area for holding a sample of bodily fluid, as well as a sample inlet 16 and a capillary conduit 18 for drawing a sample to the holding zone 14.

It is equally envisaged that the inlet 16 and capillary conduit 18 could be located at the holding zone 14, for example with these being in the form of a hole in the upper wall of the casing 12 directly into the chamber or chambers of the sample carrier 10.

The sample carrier is typically made of a plastics material and intended for a single use, after which it is disposed.

As is described in the above-mentioned co-pending British patent applications, the sample carrier 10 may be preloaded with one or more analytes for use in identifying elements from a sample and attaching to these a measurable indicator. This may include, for example, an electrical indicator by the generation of a suitable ionised particle, an optical indicator by the generation of a suitable optical effect such as colour or fluorescence, or any other measurable indicator. In such applications, the sample carrier 10 could be termed a test chip. Referring now to Figure 2, there is shown an embodiment of diagnostic unit 20 for analysing the sample in the sample carrier 10 and for providing the user with an indication of the condition or conditions tested by the unit. This unit also forms the subject of the applicant's co-pending British patent applications numbers 0812679.9 filed on 10 July 2008 (Agents' Reference: RJ/N22505) and 0812681.5 filed on 10 July 2008 (Agents' Reference: RJ/N22799), although the present disclosure is not limited to this specific type of diagnostic unit. The unit 20 is a hand-held unit and includes a slot 22 into which the sample carrier 10 is fed. Within the unit 20 there are provided various sensor and processing devices, the nature of which are not relevant to the present disclosure, for sensing one or more parameters of the sample and for displaying a diagnostic result on a display 24. With reference to Figure 3, the diagnostic unit 20 can be used by a medical practitioner, such as a doctor, for diagnosing a patient's condition, for example during a home visit making use of one or more sample carriers 10. As can be seen in Figure 4, the sample carrier or chip 10 is typically protected in a sterile packaging 26 until required for use. In the case of a sample carrier which is preloaded with a particular analyte or analytes, a physician may be provided with a set of sample carriers 10, each for carrying out a different diagnosis on a patient. For example, sample carriers or test chips may be provided with different analytes for testing for different viruses, thus enabling a doctor identify the correct ailment and prescribed the appropriate treatment.

Referring now to Figures 5 to 8, in this medical application, a sample of the patient's blood is obtained, for example by pricking the patient's finger, and this is introduced into the sample carrier 10 via its access inlet 16, whereupon it will be drawn to the holding zone 14 and, in this embodiment, combined with one or more analytes. When inserted into the diagnostic unit 20, the analysis is effected and the device 20, via appropriate sensors and processing capability, with the results displayed on the display 24. Following the diagnosis, the sample carrier 10 is discarded. It will be appreciated that the sample carrier 10 may contain an infectious sample and thus should not be discarded without proper precautions against contamination of others. In a hospital or doctor's surgery. This would typically be in a bin 30 for subsequent incineration. Even then, the risk remains for hospital and surgery staff and anyone else who might be in the vicinity of the bin. In any other environment, for example in a patient's home, the risks are considerably greater.

The embodiments described below provide a system and method for incinerating a sample while on the sample carrier 10, thereby destroying harmful agents in the sample and rendering this virtually innocuous to users. Referring first to Figure 9, there is shown an embodiment of the sample holding zone 14 of the sample carrier or test chip 10 of Figure 1. In this embodiment, the sample holding zone is a generally closed storage chamber including two chambers 32 and 34, the first of which is a mixing chamber 32, while the second chamber 34 is an analysis chamber. A conduit 36 couples the two chambers 32 and 34 to one another, while the capillary feed conduit 18 and the inlet port 16 couple to a position part-way along the joining conduit 36. The arrangement of chambers and conduits allows a sample to be fed thereinto from the inlet 16, whereupon it will pass into the mixing chamber 32 for mixing with one or more analytes. After mixing, the sample is transferred to the analysis chamber 34, for example by means of an electromagnetic force, for subsequent analysis. The sample holding zone being a generally closed storage chamber restricts the movement of the sample and minimises the number of surfaces that are contacted by the potentially contaminated sample.

An example of mechanism for performing the mixing and transfer of samples is disclosed in the above-mentioned co-pending British patent applications as well as in the applicant's earlier filed British patent application number 0723137.6. These functions are not relevant to the disclosure in this patent application.

In this example, the sample carrier 10 is provided with a first set of electrical terminals 38 which, in this embodiment, extend across the entire width of the analysis chamber 34. These are in the first instance used for the measurement of one or more electrical parameters of the sample under analysis. Another electrode or set of electrodes 40 is located at the opposite end of the sample chamber arrangement 14. The electrodes 38 and 40 contact the interior of the sample chambers and thus in use come into contact with the fluid within the chambers. Their positioning with respect to the chamber arrangement is such that the electrodes are positioned at the extremities of the region in which the sample is located in the chip 10. In the embodiment shown in Figure 9, the set of three electrodes 38 are used also for sensing. For the application of a decontamination voltage only one of these electrodes 38 is used, typically the outermost electrode.

Referring now to Figure 10, there is shown one example of carrier interface element or holder 42 of the diagnostic device 20 of Figure 2 and which provides the slot 22 into which a sample carrier 10 can be inserted for processing. The holder 42 includes a housing of non-conductive material, a plastics material for example, within which there are provided first and second electrical terminals 44 and 46 which extend to the inner surface of the slot 22 and in practice will make a reliable electrical contact with respective ones of the terminals 38 and 40 of the sample carrier 10. For this purpose, the terminals 44 and 46 may be sprung loaded.

The terminals 44 and 46 are connected to respective electrical supply wires 48 and 50 which lead to a power supply 52, there being provided a controllable switch 54 for controlling the supply of electrical energy to the electrodes 44 and 46. This switch 54 may be coupled to a button on the diagnostic device 20 for control by a user or may be controlled automatically by the processing system of the diagnostic device 20 itself, for example once this has determined that it has completed an analysis and the sample is no longer required.

It will be apparent that upon closing of the switch 54 an electrical potential will be generated at the terminals 44 and 46 which, by virtue of the coupling to the terminals 38 and 40 of the chip 10, will apply the potential to these terminals as well, so as to generate a potential across and a short circuit through the fluid which is held substantially stationary within the chamber and conduit arrangement 16-36. This short circuit will cause a rise in the temperature of the sample in order to cause harmful elements thereof to be decontaminated. As explained above, the fact that the fluid is held substantially stationary in a generally closed storage chamber minimises the number of surfaces with which the sample comes into contact, and reduces the risk of healthcare staff and patients to exposure to potentially harmful contaminants. Movement would otherwise increase the risk of the spread of infectious materials to other devices and surfaces and increase the number or frequency of exposures for people nearby.

For this purpose, the electrical supply 52 is designed to supply a voltage of sufficient magnitude and duration to raise the temperature of the sample to a sterilisation temperature, thereby to burn organisms in the sample. Preferably, the electrical supply 52 is operable to generate a voltage of at least 0.5 volts negative or positive for a minimum of 2 seconds and preferably up to 1.2 volts. The unit 52 may generate a voltage of up to around 9 volts, as per some batteries used to power hand held electronic devices. The electrical potential is preferably such as to heat the sample to at least 40 to 50 degrees Centigrade for at least 2 seconds to cause coagulation or decontamination of the sample.

The application of such a voltage preferably creates a short circuit through the sample so as to heat this. In the case of a sample of blood, in many instances it should only be necessary to cause this to clot, whereupon the clotted blood presents a negligible risk of contamination. In other cases it may be preferable to decontaminate the sample by in effect sterilisation, that is by killing organisms in the sample. For this purpose heating to 50 degrees Centigrade for two or more minutes may be sufficient although it is envisaged that heat up to 90 or even 100 degrees may be necessary in some circumstances. It is not necessary to produce a large voltage across the sample to achieve such heating, even 0.5 or even 1 volt can be sufficient. However, a higher voltage will result in more heating. The skilled person will appreciate that these are examples only and that other electrical criteria may apply in dependence upon the sample to the decontaminated and the sample carrier itself. For a biological sample, a sterilisation temperature of at least 50 degrees Centigrade is preferred to kill off harmful bacteria and other elements.

Referring again to Figure 7, it will be appreciated that this burning procedure will take place while the chip 10 is still held within the diagnostic unit 20, whereupon the chip 10 will only be removed from the diagnostic unit 20 after the sample has been burned by the electrical energy imparted to it. Thus, when the chip 10 is removed from the diagnostic unit 20 the sample is retained within the sample holding zone and it no longer presents a risk of contamination and is safe for disposal.

The fact that the sample is retained in the sample holding zone means that the sample and chip can be disposed of together thereby facilitating a simple and safe disposal procedure. It will be appreciated that in most instances decontamination can be effected at relatively low temperatures, as long as these are sufficient to kill harmful constituents of the fluid to be sterilised, such as bacteria, viral cells and other antigens; otherwise to decontaminate these, for example by causing the fluid to coagulate.

While the above embodiment has been described in connection with a sample holder 10 and diagnostic unit 20 of the types shown in Figures 1 to 10, the principles are not limited to these embodiments.

For example, Figure 11 shows a disposable syringe 60 of substantially conventional form and provided with a barrel 62, plunger 64 and hypodermic needle 66. The plunger 64 is, in this embodiment, substantially conventional, having a plunger rod connected to a disk shaped seal and an enlarged end for manipulation. It includes, in addition, a metal terminal to the seal 68, extending to within the generally closed chamber 70 in the barrel, a wire 72 an a coupling element 74 at an accessible position. As with the embodiment of test chip 10 of Figure 9, fluid contained within the chamber 70 is held between two electrical terminals, the needle 66 and the terminal 68. Application of electrical energy to the needle 66 and the coupling element 74 can supply an electrical voltage to the contents of the needle while these contents are held substantially stationary to decontaminate by coagulation or sterilisation any contagious substances therein such as bacteria, viral cells or other antigens, for example, leaving the syringe 60 safe for disposal with the contents retained within it.

Not shown in the drawings is a power supply device for providing the electrical energy to the syringe 60. Such apparatus will be apparent to the skilled person from the teachings herein. One embodiment provides a self-contained unit specific for decontamination of syringes by this method.

Figure 12 shows in schematic form an example of a disposable microscope slide 80 having a conventional rectangular substrate 82 of glass or other inert material forming a generally closed chamber and first and second electrical terminals 84, 86 located either side of the substrate. In this example, the terminals 84, 86 are located along the short sides, although they could be located along the long sides and even at intermediate positions, the latter, for example, to decontaminate samples which occupy only a small part of the surface of the substrate.

As with the previous embodiments, application of a suitable electrical potential to the terminals 84 and 86 will cause a short circuit in the sample to heat this while it is held substantially stationary and thereby decontaminate harmful components thereof, whether by way of coagulation of the sample or destruction of the harmful elements, and leave the slide safe for disposal with the sample retained on the substrate.

The described embodiments can offer many advantages over the prior art. For example, since immunoassays are generally designed to determine whether or not and to what extent a particular antigen is present in a biological sample, such tests frequently involve the handling of contaminated fluids. Furthermore, even if the fluid does not return a positive result for the antigen in question, the fluid may still contain other antigens not identified by the test. The described embodiments enables the sample to be decontaminated after the test, to reduce the risk of infection or contamination.

It will be appreciated that the number and location of electrodes and the voltage to which they are raised can be varied according to the dimensions and nature of the device into which they are inserted to ensure an appropriate potential difference can be applied across the sample to be decontaminated.

Decontamination electrodes can be provided in a device which does not otherwise require a source of electrical power. For example, a testing device which performs a chemical assay rather than an electrochemical assay can be provided with an electrode at each side of an analysis region.

It is envisaged that a diagnostic device or other device which can hold a sample carrier could be provided with electrodes which locate directly to the sample holding zone of the sample carrier, without the need for the sample carrier to have its own electrical terminals.

All embodiments can be provided with a generally closed chamber for the sample holding zone and can be operable to raise the sample to a decontamination temperature while the sample is held substantially stationary in the sample holding zone such that there is no continuous flow of fluid. The principles taught herein could also be used on a laboratory-on-a-chip.

Claims

1. A disposable sample holder for holding and decontaminating a liquid sample including a substrate provided with a sample holding zone; and first and second electrical terminals located at the sample holding zone; wherein the electrical terminals are operable to apply electrical energy across a sample in the sample zone so as to heat the sample to a decontamination temperature and render the sample holder safe for disposal.

2. A disposable sample holder according to claim 1, wherein the sample holding zone forms a generally closed storage chamber for the sample.

3. A disposable sample holder according to claim 1 or 2, wherein the electrical terminals are operable to raise the sample to a decontamination temperature while the sample is retained substantially stationary in the sample holding zone such that there is no continuous flow of fluid.

4. A disposable sample holder according to any preceding claim, wherein the sample holding zone retains the sample after decontamination such that the sample holder and sample can be disposed of together.

5. A disposable sample holder according to any preceding claim, wherein decontamination includes coagulation and/or sterilisation.

6. A disposable sample holder according to any preceding claim, wherein the first and second electrodes are located at or adjacent extremities of the sample holding zone.

7. A disposable sample holder according to any preceding claim, including electrodes located at intermediate positions in the sample holding zone.

8. A disposable sample holder according to any preceding claim, wherein the substrate includes one or more chambers constituting the sample holding zone.

9. A disposable sample holder according to any preceding claim, including a source of electrical power, which source includes first and second electrical terminals connectable to the first and second electrical terminals of the substrate so as to supply electrical energy thereto.

10. A disposable sample holder according to claim 9, wherein the electrical power source is operable to generate a potential of at least 0.5 volts.

11. A disposable sample holder according to claim 9 or 10, wherein the electrical power source is operable to supply electrical power to the first and second electrical terminals for a period of at least 2 seconds.

12. A disposable sample holder according to claim 9, 10 or 11, wherein the electrical power source forms part of a diagnostic device.

13. A disposable sample holder according to any preceding claim, including a housing operable to house the substrate at least partially.

14. Apparatus for holding and decontaminating a liquid sample including a housing for a substrate, the substrate including a sample holding zone; and first and second electrical terminals locatable at the sample holding zone of the substrate, the apparatus including a source of electrical power operable to apply a voltage across the electrical terminals so as to apply electrical energy across a sample in the sample zone so as to heat the sample to a decontamination temperature.

15. Apparatus according to claim 14, wherein the electrical terminals are operable to raise the sample to a decontamination temperature while the sample is retained substantially stationary in the sample holding zone such that there is no continuous flow of fluid.

16. Apparatus according to claim 14 or 15, wherein the sample holding zone retains the sample after decontamination such that the sample holder and sample can be disposed of together.

17. Apparatus according to claim 14, 15 or 16, wherein the electrical terminals are operable to connect to electrical terminals provided on the substrate.

18. A method of sterilising a liquid sample provided on a substrate, the substrate including a sample holding zone, the method including the steps of: providing first and second electrical terminals at the sample holding zone; and applying an electrical potential across the first and second electrical terminals thereby to impart electrical energy to the sample so as to heat the sample to a decontamination temperature while the sample is retained substantially stationary in the sample holding zone such that there is no continuous flow of fluid.

19. A method according to claim 18, including the step of providing the first and electrical terminals on the substrate.

20. A method according to claim 18 or 19, wherein the first and second electrodes are provided at or adjacent extremities of the sample holding zone.

21. A method according to claim 18, 19 or 20, including the step of providing electrodes at intermediate positions in the sample holding zone.

22. A method according to any one of claims 18 to 21 , including the step of providing a potential of at least 0.5 volts.

23. A method according to any one of claims 18 to 22, including the step of providing electrical energy to the sample for a period of at least 2 seconds.

24. A method according to any one of claims 18 to 23, wherein the method is carried out subsequent to a diagnosis performed on the sample.