IN VIVO IMMUNOASSAY SYSTEM

Abstract

A swallowable in-vivo device comprising a shell defining a cavity of the in-vivo device, the shell being formed with at least one aperture extending through the shell's wall. The in-vivo device is configured for allowing inlet of fluid into the cavity; The in in-vivo device further comprises and immunoassay system accommodated within the cavity and configured for interacting within the fluid; The in-vivo device also comprises at least one breach mechanism covering the at least one inlet for preventing ingress of fluids into the cavity via the inlet; The at least one breach mechanism comprises a film layer configured for reacting with the fluid and designed to be breached after a predetermined amount of exposure time to the GI fluid, corresponding to a desired location along the GI tract.

Claims

1. A swallowable in-vivo device, comprising: a shell defining a cavity of the in-vivo device, the shell being formed with at least one aperture extending therethrough and configured for allowing ingress of fluid into the cavity; an immunoassay system disposed within the cavity and configured for interacting with fluid; and at least one breach mechanism covering the at least one aperture for preventing ingress of fluid into the cavity via the inlet, the at least one breach mechanism including a film layer configured for reacting with the fluid and configured to be breached after a predetermined amount of exposure time to gastrointestinal (GI) fluid of a person, the predetermined amount of exposure time corresponding to travel of the in-vivo device along the person's GI tract to a desired location along the person's GI tract.

2-3. (canceled)

4. The swallowable in-vivo device according to claim 1, wherein the film layer is formed as a stand-alone component.

5. (canceled)

6. The swallowable in-vivo device according to claim 1, wherein the film layer is configured to erode over a period of exposure time to the GI fluid.

7. The swallowable in-vivo device according to claim 1, wherein the film layer is configured to prevent ingress of fluid into the inlet before the film layer is breached.

8. The swallowable in-vivo device according to claim 1, wherein the film layer comprises a combination of at least the following materials: a cut-off active material having a threshold response to a specific substance of the GI fluid or to a specific parameter of the GI fluid; a plasticizer configured, together with the cut-off active material, for forming the film layer; and an auxiliary active material.

9. The swallowable in-vivo device according to claim 8, wherein the cut-off active material is an enteric material configured for reacting with the GI fluid.

10. The swallowable in-vivo device according to claim 8, wherein the cut-off active material remains inactive until a pH level of the GI fluid is one of under or over a threshold pH level.

11. The swallowable in-vivo device according to claim 1, wherein the film layer contains between 40-98% of enteric material.

12. The swallowable in-vivo device according to claim 8, wherein the plasticizer is selected from the group consisting of triethyl citrate glycols, diesters and triesters of acids, diesters and triesters of alcohols, natural oils, and Polyethylene Glycols.

13. The swallowable in-vivo device according to claim 12, wherein the plasticizer is propylene glycol or polyethylene glycol (PEG).

14. The swallowable in-vivo device according to claim 9, wherein the amount of plasticizer in the film layer is the complement of the enteric material to 100%.

15. The swallowable in-vivo device according to claim 8, wherein the amount of plasticizer in the film layer ranges from 60-2%.

16. The swallowable in-vivo device according to claim 8, wherein the auxiliary active material is configured for providing the film layer with additional resilience.

17. The swallowable in-vivo device according to claim 8, wherein the auxiliary active material is a hydro-swelling enteric polymer configured for retaining fluid within the film layer before the film layer is breached.

18. The swallowable in-vivo device according to claim 1, wherein the film layer functions as an indicator that the in-vivo device has reached a desired location along the GI tract.

19. The swallowable in-vivo device according to claim 18, wherein the in-vivo device comprises a sensor behind the film layer, and the film layer is configured to be breached at the desired location along the GI tract, wherein, when the film layer is breached, the fluid triggers the sensor, thereby indicating that the in-vivo device has reached a desired location.

20. The swallowable in-vivo device according to claim 16, wherein the amount of auxiliary active material is provided as being between 2-40% of the combined weight of the cut-off material and the plasticizer.

21-24. (canceled)

25. A film layer configured for being used in an in-vivo device, the film layer comprising: a cut-off active material having a threshold reaction to a substance or parameter of gastrointestinal (GI) fluid of a person; a plasticizer configured, together with the cut-off sensitive material, for forming the film layer; and an auxiliary active material, wherein the film layer is configured to be breached after a predetermined amount of time of exposure to the GI fluid.

26-31. (canceled)

32. A swallowable in-vivo immunoassay device, the immunoassay device comprising: a lateral flow strip extending between a fluid intake end and a distal end, the lateral flow strip including a test pad and a backing card juxtaposed with the test pad, wherein the backing card is made of a material allowing at least partial passage of light therethrough; an illumination module including at least one illumination source configured for directing light towards the backing card; and a sensor module including at least one sensor configured for receiving light from the illumination module, wherein the at least one sensor is positioned such that the test pad is disposed between the at least one sensor and the backing card.

33. The swallowable in-vivo immunoassay device according to claim 32, wherein the test pad includes a test band configured to react with gastrointestinal fluid of a person, thereby changing at least one property of the test band.

34-58. (canceled)

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0082] In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

[0083] FIG. 1A is a schematic view of an immunoassay system in accordance with embodiments of the present invention;

[0084] FIG. 1B is a schematic view of another example of an immunoassay system in accordance with embodiments of the present invention;

[0085] FIG. 1C is a schematic view of still another example of an immunoassay system in accordance with embodiments of the present invention;

[0086] FIG. 1D is a schematic view of yet another example of an immunoassay system in accordance with embodiments of the present invention;

[0087] FIG. 1E is a schematic enlarged view of a detail A shown in FIG. 1D in accordance with embodiments of the present invention;

[0088] FIG. 2 is a schematic plot of values measured by the sensor of the immunoassay system of embodiments of the present invention;

[0089] FIG. 3A is a schematic isometric view of an in-vivo device according to embodiments of the present invention;

[0090] FIG. 3B is a schematic isometric cross-section view of the in-vivo device shown in FIG. 3A, taken along a plane perpendicular to its longitudinal axis in accordance with embodiments of the present invention;

[0091] FIG. 3C is a schematic isometric cross-section view of the in-vivo device shown in FIG. 3A, taken along its longitudinal axis in accordance with embodiments of the present invention;

[0092] FIG. 3D is a schematic isometric view of a single ring used in the construction of the in-vivo device shown in FIGS. 3A to 3C in accordance with embodiments of the present invention;

[0093] FIG. 4A is a schematic isometric view of a breach film in accordance with the embodiments of present invention;

[0094] FIG. 4B is a schematic cross-section view of the breach film shown in FIG. 4A, shown prior to its breach in accordance with embodiments of the present invention;

[0095] FIG. 4C is a schematic cross-section view of the breach film shown in FIG. 4B, shown in a breached condition in accordance with embodiments of the present invention;

[0096] FIG. 5C is a schematic isometric view of an in-vivo device in accordance with another example embodiment;

[0097] FIG. 5B is a schematic isometric view of the arrangement of strips within the in-vivo device of FIG. 5B in accordance with embodiments of the present invention;

[0098] FIG. 5C is a schematic isometric longitudinal cross-section view of the in-vivo device shown in FIG. 5A in accordance with embodiments of the present invention;

[0099] FIG. 6A is a schematic isometric view of an in-vivo device in accordance with a variation on the in-vivo device shown in FIGS. 5A to 5C in accordance with embodiments of the present invention;

[0100] FIG. 6B is a schematic longitudinal cross-section view of the in-vivo device shown in FIG. 6A in accordance with embodiments of the present invention;

[0101] FIG. 6C is a schematic enlarged view of a detail B shown in FIG. 6B in accordance with embodiments of the present invention;

[0102] FIG. 7A is a schematic isometric view of an in-vivo device in accordance with another example embodiment of the present application;

[0103] FIG. 7B is a schematic isometric view of the arrangement of lateral flow strips within the in-vivo device shown in FIG. 7A in accordance with embodiments of the present invention;

[0104] FIG. 7C is a schematic longitudinal cross-section view of the in-vivo device shown in FIG. 7A in accordance with embodiments of the present invention;

[0105] FIG. 8A is a schematic isometric view of an in-vivo device in accordance with another example embodiment of the present application; and

[0106] FIG. 8B is a schematic isometric view of a shell piece of the in-vivo device shown in FIG. 8A in accordance with embodiments of the present invention.

[0107] It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn accurately or to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity, or several physical components may be included in one functional block or element. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements.

DETAILED DESCRIPTION OF EMBODIMENTS

[0108] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those skilled in the art that the present invention can be practiced without these specific details. In other instances, well-known methods, procedures, and components, modules, units and/or circuits have not been described in detail so as not to obscure the invention.

[0109] Attention is first drawn to FIG. 1A in which an immunoassay system is shown, generally designated 1 and comprising a lateral flow strip 2, a light source 4 and a sensor module 6. The lateral flow strip 2 comprises a functional portion 10 and a transparent backing card 20. The functional portion 10 comprises sample pad 12, a test zone 14 with several test bands 16, and an absorbent pad 18, as known per se. The backing card 20 has a first end 22 configured for receiving light therein, and a second end 24.

[0110] The light source 4 comprises an illumination element 30 configured for emitting light into the first end 22 of the transparent backing card 20. The sensor module 2 is disposed on the other side of the lateral flow strip 2, opposite the backing card 20, and comprises a sensor 40 configured for collecting light passing through the functional portion 10 of the lateral flow strip 2.

[0111] As shown in FIG. 1A, when light L is directed to the transparent backing card 20, it enters the first end 22 and passes freely through the backing card 20 resulting in the majority of the light being emitted through the second end 24, with only a small fraction of the light L being directed to the functional portion 10. A certain percentage of that small fraction of light L will be collected by the light sensor 40.

[0112] Turning now to FIG. 1B, another configuration of the immunoassay system is shown, generally designated 1′, in which the backing card 20′ comprises light directing elements 25 in the form of slits/grooves. In this configuration, light L entering the transparent backing card 20′ passes therethrough, and instead of progressing freely, encounters the light directing elements 25, causing dispersion of the light L in all directions. Therefore, in the current example, a considerably greater fraction of the light L is directed towards the functional portion 10, thereby also increasing the amount of light picked up by the sensor 40.

[0113] It is noted that in the present example, the light directing elements are formed along the entire backing card 20′ in order to cause maximal dispersion of the light L, to increase the amount of light L which can be picked up by the sensor 40.

[0114] Turning now to FIG. 1C, another example of the immunoassay system is shown, generally designated 1″, in which the backing card 20″ also comprises light directing elements 25″, with the difference being that these elements 25″ are formed adjacent the test bands 16 of the functional part 10. Thus, when light L is provided to the transparent backing card 20″, it will only undergo dispersion when encountering the light directing elements 25″ at the vicinity of the test bands 16. Thus, the areas of the test bands 16, which are the areas of interest for the sensor, will become more illuminated, while the regions between the test bands 16 will be less illuminated. This configuration may allow a clearer view of the test bands 16.

[0115] Attention is now drawn to FIGS. 1D and 1E, in which yet another example of the immunoassay system is shown, generally designated 1′″, in which the backing card 20′″ is formed with light directing elements 25′″ which are formed with increasing depth along the backing card 20′″. Specifically, in an area proximal to the light source 30, the light directing elements 25′″ extend into a shallow depth of the backing card 20′″, while in an area distal from the light source 30, the light directing elements 25′″ extend deeper into the backing card 20′″. The depth of the light directing elements 25′″ increases continuously.

[0116] One advantage of this configuration is that the light directing elements 25′″ proximal to the light source 30 do not disperse the entire amount of light L entering the backing card 20′″, but rather only the light L4 progressing via an area distal from the functional portion, thereby allowing light L1 progressing via an area proximal to the functional portion to progress and reach an area distal from the light source 30. Such an arrangement may provide a better illumination of the lateral flow strip.

[0117] Turning now to FIG. 2, a chart is shown, plotting the ratio of Red to Green (R/G) wavelengths, denoted as C1 and the Red to Blue (R/B) wavelengths, denoted as C2, as registered by the sensor 40 from the strip LFS. The chart is overlayed on the strip itself for purpose of clarity. It is noted that while the absolute light intensity decays as light L progresses through the backing card 20, using a ratio allows normalizing the values such that they are not affected by said light intensity. It is clearly seen from the plotted chart where the bands of the test zone are located, corresponding to the peaks P1, P2 and P3 of each plot C1 and C2.

[0118] Furthermore, it is also demonstrated that in the specific example of the lateral flow strip LFS tested, the ratio of R/G provides a slightly more distinct indication of the location of the bands than the ratio R/B. However, is should be noted that each LFS may have a unique preferred ratio based on the color change undergone by the test bands located on the strip LFS.

[0119] Attention is now drawn to FIGS. 3A to 3D, in which an in-vivo device is shown, generally designated as 100 and comprising a shell 101 assembled from a first end cap 112, a second end cap 112, and three ring pieces 120. The in-vivo device 100 further comprises three lateral flow strips LFS, each accommodated within one of the ring pieces 120, and three corresponding breach gates in the form of thin films 140, closing an opening allowing ingress of GI fluids into the shell 101.

[0120] Each ring piece 120 is formed as a cylindrical shell 122 defining therein a cavity 121. The inner wall of the shell 122 is formed with a primary holder 124 and two auxiliary holders 126 spaced from the inner wall and defining corresponding primary and auxiliary slots 125 and 127, into which the LFS can be fitted. Under the present example, each LFS is inserted into the slots 125 and 127 to extend circumferentially about the inner wall of the shell 122.

[0121] The width and diameter of the ring pieces 120 is based on the width and length of the LFSs, specifically, the ring piece is at least as wide as the LFS and its inner circumference is at least as long as the LFS. However, it should be understood that other designs may be possible in which each ring piece 120 holds more than on LFS, side by side (i.e. having a width equivalent to two LFSs or more).

[0122] Each ring piece 120 is further formed with an inlet 128 configured for allowing ingress of GI fluids into the cavity of the ring piece 120 to come into contact with the LFS. Each such inlet 128 is sealed off with a thin film 140, preventing such ingress of fluids except under specific conditions as will be discussed with respect to FIGS. 4A to 4C.

[0123] Thus, each ring piece 120, when fitted with its corresponding LFS and sealing film 140, constituted a modular unit of the in-vivo device 100. In the current example, the in-vivo device comprises three such modular units, but it is appreciated that since they are modular, the in-vivo device 100 may comprise more or less ring pieces 120, according to specific requirements, the number of ring pieces and their width defining the length of the in-vivo device. It should also be noted that for in-vivo swallowable use, the length is limited by the side swallowable by a person.

[0124] The shell 101 in-vivo device 100 defines an inner cavity configured for accommodating therein the additionally required mechanical/electrical components of the in-vivo device (not shown), as known per se.

[0125] In operation, when the breach film is dissolved, GI fluid enters the inner cavity 121 of the ring piece 120, coming into contact with the LFS and allowing performing an immunoassay process by reacting with the materials of the LFS, as previously described.

[0126] In accordance with a specific example, the ring pieces 120 may be divided by barriers (not shown), configured for isolating the ring pieces 120 from one another. Under such a design, one of the breach gates 140 may be configured for being breached at a first location of the GI and for performing an immunoassay for the detection of a first substance, while another of the breach gates 140 may be configured for being breached at a second location of the GI, different from the first location, for performing an immunoassay for the detection of a second substance, different from the first substance. Since the ring pieces 140 are isolated from one another, different immunoassay processes can be performed, independently, in different sections of the GI tract.

[0127] It is noted that the above described configuration provides, inter alia, the advantage of easy assembly, as each of the ring pieces 120 can be assembled individually, and it provides complete access to the assembler for inserting the LFS into the slots 125, 127. This is contrary to common in-vivo devices in which the LFS needs to be inserted or pushed-in into a narrow channel, when the in-vivo device is already half-assembled.

[0128] Turning now to FIGS. 4A to 4C, a breach film is shown generally designated 200, in the form of a thin film 202 having a thickness t and dimensions L×W (not marked). The film 202 comprises: [0129] a cut-off active material having a threshold response to a specific substance of the GI fluid or to a specific parameter of the GI fluid; [0130] a plasticizer configured, together with the cut-off sensitive material, for forming said film layer; and [0131] an auxiliary active material.

[0132] The breach film 202 is configured for being exposed to GI fluids GF and for reacting with a certain substance or under certain conditions of the GI, only above a given threshold (either a given concentration of the substance or a level of a certain parameter, e.g. pH).

[0133] As shown in FIG. 4B, when the breach film 202 is under conditions which are below the threshold, the film 202 does not react with the GI fluids, and does not allow slow diffusion into the inlet 128. However, during exposure to the GI fluids GF, the film 202 may retain water therein, owing to the auxiliary active material.

[0134] Turning now to FIG. 4C, when the conditions of the GI fluids GF are above the predetermined threshold with which the film is configured to react, the film 202 is breached almost instantly (as it is already containing a great amount of water), and allows passage of the GI fluids GF into the inlet 128 and from there to the LFS. In this sense, the breach film 202 is configured for functioning as a cut-off breach gate 200, rather than allowing slow diffusion of fluids into the inlet 128.

[0135] Attention is now drawn to FIGS. 5A to 5C, in which another example of an in-vivo device is shown, generally designated 300. The in-vivo device comprises a first end cap 312, a second end cap 314 and an intermediate shell piece 320 interposed between the two caps 312, 314. The first end cap 312 is formed with two inlets 315 configured for allowing ingress of GI fluids into the cavity of the in-vivo device to come into contact with the lateral flow strips LFS accommodated therein.

[0136] With particular reference being made to FIGS. 5B and 5C, the in-vivo device 300 comprises four lateral flow strip LFS, arranged symmetrically about the central axis of the in-vivo device 300. Each of the strips LFS extends the entire length of the in-vivo device 300, with its sample pad located proximal to the inlets 315. Such an arrangement positions the test bands 316 close to the center of the in-vivo device 300, at the widest section thereof, providing the maximal space for a sensor/imager (not shown) to be placed within the in-vivo device facing the bands 316.

[0137] Turning now to FIGS. 6A to 6C, a variation on the in-vivo device 300 is shown, generally designated 300′. The in-vivo device 300′ differs from the device 300 in the geometry of the inlets 315, specifically, the inlets 315′ are designed to have a curvature only about one axis, compared to the inlets 315 which have a spherical surface. This may be particularly useful when using the breach film of the present invention, as it eliminates the need of the breach film, which is generally flat, to assume a spherical configuration. Instead, when using the inlets 315′, the breach film merely needs to bend in a single direction, allowing a more convenient fitting of the breach film to the shell.

[0138] In particular, the inlets 315′ are designed to be indented within the shell and having the desired geometry, such that they are not affected by the overall spherical geometry of the first end cap 312′. As such, the breach film 200 can be neatly placed onto the support 322 and have the edges thereof properly adhered to the supports 322 without any undesired crimps or creases.

[0139] Attention is now drawn to FIGS. 7A to 7C, in which yet another example of an in-vivo device is shown, generally designated as 400 and comprising a shell 412 and an end cap 414, accommodating therein three lateral flow strips LFS, and three breach films 200, sealing off three corresponding inlets 415.

[0140] In the present example, the lateral flow strips LFS are arranged along the body of the in-vivo device 400, with one of their ends, containing the sample pad, juxtaposed with the inlet 415, and the other of their ends being curved across the end cap 414. This configuration may be particularly useful for longer lateral flow strips LFS which cannot fit in their entirety into the limited length of the in-vivo device 400.

[0141] Finally, attention is drawn to FIGS. 8A and 8B, in which another configuration of an in-vivo device is shown, generally designated 500 and comprising a shell made of three shell pieces 520. Similarly to the previously described in-vivo device of FIGS. 3A to 3D, in the present example, the shell pieces 520 are longitudinal, each extending the entire length of the in-vivo device 500, and comprising a part of the first end dome 512 and a part of the second end dome 514. When assembled, the parts of the first and second end domes 512, 514 of the individual shell pieces 520 form together the first and second domes.

[0142] In addition, each shell piece 520 is formed with two brackets 524 spaced from an inner wall of the shell piece 520, forming a slot 525, sufficient for placing therein a lateral flow strip LFS. Thus, the current example provides similar advantages as those of the ring pieces 120 previously shown, allowing convenient access to an assembler of the in-vivo device 500.

[0143] The geometry and configuration of the inlets 515 is similar to that previously shown with respect to FIGS. 6A to 6C.

[0144] Those skilled in the art to which this invention pertains will readily appreciate that numerous changes, variations, and modifications can be made without departing from the scope of the invention, mutatis mutandis.

[0145] It will thus be seen that the objects set forth elsewhere herein, among those made apparent from the preceding description, are efficiently attained and, because certain changes may be made in carrying out the method described elsewhere herein and in the construction(s) set forth without departing from the spirit and scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

[0146] In the foregoing detailed description, numerous specific details are set forth in order to provide an understanding of the invention. However, it will be understood by those skilled in the art that the invention can be practiced without these specific details. In other instances, well-known methods, procedures, and components, modules, units and/or circuits have not been described in detail so as not to obscure the invention. Some features or elements described with respect to one embodiment can be combined with features or elements described with respect to other embodiments.

[0147] Although embodiments of the invention are not limited in this regard, the terms “plurality” and “a plurality” as used herein can include, for example, “multiple” or “two or more”. The terms “plurality” or “a plurality” can be used throughout the specification to describe two or more components, devices, elements, units, parameters, or the like. The term set when used herein can include one or more items. Unless explicitly stated, the method embodiments described herein are not constrained to a particular order or sequence. Additionally, some of the described method embodiments or elements thereof can occur or be performed simultaneously, at the same point in time, or concurrently.

[0148] It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.