Device, System And Method For Processing A Sample

Abstract

A device for processing a sample comprises a blister defined by first and second walls. The first wall is flexible allowing the blister to be divided into one or more sealed regions by an external pressure applied to a portion of the first wall. The external pressure is applied in the form of a 2-dimensional shape to form a sealed region having that shape.

Claims

1-31. (canceled)

32. A method of processing a sample in a device having a single blister only, the blister defined between a first wall and a second wall, in which at least the first wall is flexible such that the blister can be divided into one or more sealed chambers by an external pressure applied to a portion of the first wall that urges the first wall towards the second wall, the method comprising: applying a localised external pressure in the form of a two dimensional shape to urge the first wall towards the second wall to form first and second sealed chambers within the blister, introducing a liquid sample to the first sealed chamber, and removing the localised external pressure, so that the blister becomes undivided, and to open the seal between the first and second sealed chambers.

33. A method according to claim 32, further comprising: preloading the blister with dried reagents held at predetermined locations and, after applying the localised external pressure, a first reagent is located in the first sealed chamber and a second reagent is located in the second sealed chamber.

34. A method according to claim 32, further comprising: incubating, heating or mixing in the first sealed chamber before the seal is opened between the first and second sealed chambers.

35. A method according to claim 32, wherein the localised external pressure is applied by a shaped platen or tool.

36. A method according to claim 32, wherein more than two sealed chambers are formable within the blister.

37. A method according to claim 35, wherein a plurality of tools or platens are used to apply the localized external pressure to form more than two sealed chambers within the blister.

38. A method according to claims 36, further comprising: opening the seals separating each of the more than two sealed chambers in sequence to allow the sample to communicate with each chamber in order as it is processed.

39. A method according to claim 35, further comprising: mixing the sample by oscillation of the tool or platen against the first wall.

40. A method according to claim 32, wherein the device contains a liquid buffer or reagent contained in a sachet that is located in the blister, the liquid being releasable by the application of an external pressure to the sachet.

41. A method according to claim 32, wherein the sample is moveable within the blister by the application of an external pressure from a tool or platens.

42. A method according to claim 32, wherein the sample undergoes a protocol suitable for amplification of a nucleic acid or genetic material.

43. A method according to claim 32 further comprising: analysing a sample processed by the method.

44. A method according to claim 43, wherein, the analysing comprises: contacting the processed sample with a test strip located within the device.

45. A method according to claim 32, further comprising: loading the device into a machine for automatically performing the processing on the sample.

46. A method according to claim 45 further comprising: removing the device containing a sample processed by the method from the machine; and disposing of the sample.

47. A method according to claim 32, further comprising: decontaminating the device.

48. A method according to claim 32, wherein an external pressure is applied to a portion of the first wall to isolate or separate a predetermined volume of liquid within the blister.

49. A method according to claim 32, further comprising: applying a vacuum to the blister to facilitate introduction of the sample and/or transfer of liquid within the device and/or mixing of reagents and the sample and/or sealing portions of the device and/or locating objects within the device.

50-54. (canceled)

55. A method according to claim 32 in which the blister is sealed from the external environment.

Description

DESCRIPTION OF SPECIFIC EMBODIMENTS

[0072] Embodiments of the invention will now be described by way of example with reference to the accompanying drawings in which:

[0073] FIG. 1 is an exploded view of a device according to an embodiment of the invention;

[0074] FIG. 2 is a view of the device of FIG. 1 from the front and from the side showing the location of various reagents and ports;

[0075] FIG. 3 is a view of the device of FIG. 1 from the front and from the side, the side view showing the device as loaded into a machine with pressure seals being formed by tubular platens

[0076] FIG. 4 shows a front view and a side view of a sample being introduced into a device according to FIG. 1;

[0077] FIG. 5 illustrates the introduction of a mixing/heating platen;

[0078] FIG. 6 illustrates the use of a mixing platen;

[0079] FIG. 7 illustrates the use of a mixing platen;

[0080] FIG. 8 illustrates the removal of a platen to allow the sample to communicate with a second reagent;

[0081] FIG. 9 illustrates the use of a platen to move the sample towards the second reagent;

[0082] FIG. 10 and FIG. 11 illustrate the use of a roller element to liberate liquid from a sachet; and

[0083] FIG. 12 illustrates the removal of a seal around an exit port allowing the processed sample to contact an assay strip.

[0084] FIG. 13A illustrates a front view a device according to a second embodiment of the invention.

[0085] FIG. 13B illustrates a side view of a device according to the second embodiment of the invention.

[0086] FIG. 14 illustrates perspective views of a device according to the invention.

[0087] FIG. 1 is an exploded view of a device embodying aspects of the invention. The device 10 comprises a base moulding or base plate 20 having a first side 21 and a second side 22 (not visible in FIG. 1). The base moulding is made of polypropylene but could he made of any suitable material, for example any substantially rigid polymer. A gasket 30 is fixed or formed, for example by overmoulding, on the first face 21 of the base plate. The gasket is made of a softer, more rubber like, polymer material than polypropylene, for instance, a thermoplastic elastomer (TPE) such as Dryflex® manufactured by VTC TPE Group or similar materials manufactured by companies such as Kralberg or Plastic Technology Service Limited (PTS). The gasket is formed with depressions (31, 32 & 33) in order to locate objects within the device. The device further comprises a flexible film 40 that is attached to the first face of the base moulding and forms a blister 50 having the flexible film as a first wall and the base plate as a second wall. The blister 50 is formed with the gasket 30 substantially disposed inside the blister. The flexible film may be any suitable film, for example a thermoformed film having predetermined moisture and vapour barrier properties. A preferred example of a suitable film is Aclar®. Aclar® is a trade name for polychlorotrifluoroethylene (PCTFE).

[0088] A further example of a suitable film material is a polypropylene (PP) based flexible film such a TEKNIFLEX® MED 3014-0080. Such PP films may not have the moisture protection properties as specialist films such as Aclar® but may stretch and seal more effectively and be cheaper. Any reduction in moisture protection provided by a flexible film can be overcome by sealing the device in a foil bag for transport and storage.

[0089] The flexible film has thermoformed dimples to locate objects within the blister.

[0090] The device further comprises an assay cover 60 that is fixed to the rear face of the plate and defines an assay chamber or analysis chamber 70. Both the interiors of the blister 50 and the assay chamber 70 are thus sealed from the external environment. An exit port 100 defined through the base plate provides communication between the blister and the assay chamber.

[0091] The blister 50 has a plurality of location points defined by depressions in the gasket and corresponding dimples in the flexible film for locating reagents within the blister (for example at 51 & 52). The dimples prevent the reagents from substantially shifting position within the blister, which at this stage is a single chamber.

[0092] FIG. 2 shows front and side projections of the device and illustrates the locations within the device of a first freeze-dried reagent 200, a second freeze-dried reagent 210, a third freeze-dried reagent 220, a fourth freeze-dried reagent 230 and a liquid detection buffer contained within a sachet 240. The freeze-dried reagents and the sachet of liquid are located in the device during its manufacture and prior to the blister 50 being sealed. This advantageously avoids the need for handling of reagents on site where sample processing is to be performed or the need to open the device on site, and may thus reduce the potential for contamination.

[0093] As the film is flexible it is possible to apply an external pressure urging a portion of the film towards the base plate and against the gasket material thereby forming a localised seal. FIG. 3 shows front and side projections of the device and illustrates the position of three separate seals for producing sealed regions within the blister during the processing of a sample. The seal positions shown are an outer seal 300 that bounds the first and second freeze-dried reagents, an inner seal 310 that bounds the second freeze-dried reagent thereby separating it from the first freeze-dried reagent within the outer seal and an outlet seal 320 that provides a seal around the exit port leading to the assay chamber.

[0094] The side view of FIG. 3 illustrates the device when loaded into a machine and also illustrates the use of two platens, first platen 400 and second platen 410, to create the inner and outer seal. Both first platen 400 and second platen 410 are substantially tubular and separately actuatable with second platen 410 being actuatable within the bore of the first platen 400.

[0095] The following steps describe the use of the device to perform a nucleic add amplification and detection protocol.

[0096] Step 1; The device is loaded into a machine in a vertical direction for the automatic processing of a sample as shown in the Figures and the seals (300, 310, 320) are applied to the blister by application of external forces by a plurality of platens (400,410, third platen not shown). See FIG. 3.

[0097] Step 2; A sample is introduced into the blister via an access port 110 defined through the base plate; see FIG. 4. The access port may comprise a rubber septum and a syringe may therefore be used to introduce the sample.

[0098] Step 3; The liquid sample contacts and reacts with the first reagent 200 (see FIG. 4). The mixture comprising the liquid sample and the first reagent is prevented from accessing the third and fourth freeze-dried reagents by the seal formed by pressure exerted by the first platen 400, and from communicating with the second freeze-dried reagent by the seal formed by pressure exerted by the second platen 410,

[0099] Step 4; A mixing and heating platen or plunger 420 is introduced through the bore or lumen of the first platen as illustrated in FIG. 5. Mixing may be affected by oscillation of the mixing/heating platen 420 as shown In FIGS. 6 and 7.

[0100] Step 5; The mixing/heating platen 420 is held over the blister in contact with the film in order to perform a heating and incubation step of the processing protocol.

[0101] Step 6; After appropriate mixing, heating and incubation has been performed on the sample, the second platen 410 is removed allowing the sample to contact the second freeze-dried reagent; see FIG. 8.

[0102] Step 7; In order to force the liquid sample to contact the second freeze-dried reagent, the mixing/heating platen 420 is reintroduced and squeezes the liquid sample into the region of the blister occupied by the second freeze-dried reagent, (FIG. 9). Mixing may again occur by oscillation of the mixing/heating platen.

[0103] Step 8; A cam or roller 430 is applied to the blister in the region in which the sachet is located; see FIGS. 10 and 11. The cam or roller causes a pressure to build against a frangible and of the sachet 241, causing the liquid to be liberated into the blister where it reacts with the second and third freeze-dried reagents. This liberating pressure may alternatively be applied by a reciprocating platen or plunger acting to apply pressure to the sachet.

[0104] Step 9; The first platen is removed to allow the sample to contact liquid liberated from the sachet. This is illustrated in FIG. 11.

[0105] Step 10; After any further mixing or processing (for example incubation) has occurred to produce a processed sample, the final seal 320 Is removed to allow the processed sample to enter the assay chamber 70 where it contacts an assay strip 71; see FIG. 12, which shows front and rear projections of the device.

[0106] Step 11; The results of the test are visually shown by the assay strip through the assay cover.

[0107] Step 12; The device is removed from the machine and disposed of.

[0108] It should be clear that different protocols can be used in a device according to the invention. For example, either the first or the second dried reagent may be omitted and, therefore, only the inner seal or only the outer seal from the above example need be formed. If only one such seal is formed it could be circular, or oval, or any other suitable two-dimensional shape. FIG. 13A illustrates such a device in which only two pressure seals are formed, the first 1300 defines a first sealed region 1310 surrounding reagent 1305 within the device 1400, and the second 1320 forms a second sealed region 1330 surrounding an exit port.

[0109] FIG. 13B illustrates the device of FIG. 13A viewed from the side. This figure illustrates a hinged cover 1410 that protects the front face 1405 of the device during transit and handling. The hinged cover opens when the device is inserted into a processing machine.

[0110] FIG. 14 illustrates a further embodiment of a device according to the invention. The device 1500 has a solid base-plate 1510 incorporating a finger grip 1515 for facilitating handling. A blister 1512 containing reagents is formed on the base-plate from a flexible material. The blister is protected during transit and handling by a hinged cover 1520. The cover is connected to the base-plate at a hinge 1521 and is held in place by snap-fit connections 1522 that engage with corresponding features 1523 defined in the base-plate.

[0111] In a further embodiment of the invention the device may comprise a vacuum port for withdrawing air from the blister prior to processing the sample. The vacuum port may comprise a rubber septum spanning a hole in the base plate. If a vacuum is to be applied to a device it may be advantageous to select a film for forming a wall of the blister that has suitable barrier properties, for example a film that is substantially gas impermeable.