Cell sampling device

Abstract

A swallowable cell sampling device comprising an abrasive material capable of collecting cells from the surface of the oesophagus is described. The swallowable cell sampling device may include an apparatus for retrieval comprising a cord. Moreover, the cord may be attached to the abrasive material with a hitch knot. Additionally, kits and methods involving the same are described.

Claims

1. A swallowable cell sampling device comprising: an abrasive and sponge-like material capable of collecting cells from a surface of a human esophagus; a means for retrieval comprising a cord; an attachment loop formed by looping the cord around a central portion of the abrasive material; and a hitch knot adjustably securing the attachment loop such that during retrieval of the cell sampling device, tightening of the attachment loop compresses the central portion of the abrasive material while an outer diameter of the abrasive material remains substantially constant.

2. The device according to claim 1, wherein the hitch knot is a double overhand knot.

3. The device according to claim 1, wherein the abrasive material is compressible.

4. The device according to claim 1, wherein the abrasive material comprises reticulated polyurethane.

5. The device according to claim 1, wherein the abrasive material is compressed and wherein the abrasive material is retained in a compressed state by a soluble capsule.

6. The device according to claim 5, wherein the soluble capsule comprises a gelatin capsule.

7. The device according to claim 6, wherein the capsule is capable of dissolution and the abrasive material is capable of reverting to its uncompressed size within 5 minutes upon immersion in water at 30 degrees Celsius.

8. The device according to claim 1, wherein the cell sampling device further comprises an unswallowable element coupled with the cord at an end distal from the abrasive material.

9. A kit comprising a device according to claim 1, and at least one reagent for use in detecting a cellular marker.

10. The kit according to claim 9, wherein the cellular marker is selected from the group consisting of Mcm2 and TFF3.

11. The kit according to claim 9, wherein the cellular marker is selected from the group consisting of ABP1, DCC, HOX C10, KCNE3, LAMC2m MUC13, MUC17, NMUR2, PICR, TCPAN1, and HOXB5.

12. The kit according to claim 9 wherein the cellular marker is selected from the group consisting of RNF2I7, CCL28, AGR3, CFTR, PAQR5, BNIP3, GOLM1, PLA2G10, KCNK5, MLSTD1, slc16a7, NFE2L2, CGNL1, CALML4, ACSL5, KRT8, TMC7, FAT, CES3, SLAC7A7, REG4, CATSPERB, TSPAN3, SLC37A1, GPRC5A, GPT2, PAIP2B, TRIM29, IL18, HSD17B11, GSDML, TACSTD1, HSD17B2, KRT7, CLIC6, ATP2C2, HEPH, TPD52L1, HOXB6, PLS1, IL1RN, NT5E, CAB39L, S100A14, GDA, TRIM31, ARPC1B, SLC16A1, TMC5, CPEB2, LOC93432, FS, VLDLR, GCNT3, MBOAT2, CPS1, GALM, DGKD, FAM102B, LYN, SFN, GALNT7, EMP1, CSTB, RHOC, F1114959, SNRPN, ANKS4B, PCLKC, ADH7, LYZ, S100A16, SLC6A20, SCNN1G, HKDC1, SLC7A2, SPG20, 37681, FGFBP1, CA9, RDX,SAMD9, RDX, SAMD9, SERPINB5, NMU, CLRN3, SLC9A4, VTCN1, LOC339977, FUT9, GALNT5, NR5A2, OLFM4, LY75, SCPEP1, TACSTD2, MYO1A, BTNL8, VIL1, SLC28A2, DPP4, AZGP1, CDH17, NPNT, ALDH1AI, ATP13A4, ATP7B, IL2RG, POSTN, FCGBP, GPA33, DSC2, COL6A3, VNN1, SLP1, AIM1, PRKAA2, GUCY2C, P13, TIMP1, APOL1, ANPEP, SLC34A2, DMBT1, RGS2, PAPSS2, BCM01, ADH6, TM4SF20, CHST5, HHLA2, FABP1, SNORD116-21, MYO7B, MIA, MEP1A, SLC3AI, PLACE, TFPI, PGC, MUC2, LIPF, FABP2, SI, SLC17A4, GSTA1, PDZK1, RAB3B, REGIA, SPINK4, CXCL1, GKN1, BTNL3, ADH4, ALDOB, CXCL2, SLC263, MMPI, UPK1B, MEP1B, CA1, and PRSS7.

13. A method for aiding a diagnosis of Barrett's esophagus or Barrett's associated dysplasia in a subject, the method comprising collecting cells from a surface of an esophagus of the subject with a device according to claim 1 and assaying the cells for a cellular marker, wherein detection of such a marker indicates increased likelihood of a presence of Barrett's esophagus or Barrett's associated dysplasia.

14. The method of claim 13, wherein the cellular marker is selected from the group consisting of Mcm2 and TFF3.

15. The method of claim 13, wherein the cellular marker is selected from the group consisting of ABP1, DCC, HOX C10, KCNE3, LAMC2m MUC13, MUC17, NMUR2, PICR, TCPAN1, and HOXB5.

16. The method of claim 13, wherein the cellular marker is selected from the group consisting of RNF217, CCL28, AGR3, CFTR, PAQR5, BNIP3, GOLM1, PLA2G10, KCNK5, MLSTD1, slc16a7, NFE2L2, CGNL1, CALML4, ACSL5, KRT8, TMC7, FAT, CES3, SLAC7A7, REG4, CATSPERB, TSPAN3, SLC37A1, GPRC5A, GPT2, PAIP2B, TRIM29, IL18, HSD17B11, GSDML, TACSTD1, HSD17B2, KRT7, CLIC6, ATP2C2, HEPH, TPD52L1, HOXB6, PLS1, URN, NT5E, CAB39L, S100A14, GDA, TRIM31, ARPCIB, SLC16A1, TMC5, CPEB2, LOC93432, FS, VLDLR, GCNT3, MBOAT2, CPS1, GALM, DGKD, FAM102B, LYN, SFN, GALNT7, EMP1, CSTB, RHOC, FLJ14959, SNRPN, ANKS4B, PCLKC, ADH7, LYZ, S100A16, SLC6A20, SCNN1G, HKDC1, SLC7A2, SPG20, 37681, FGFBP1, CA9, RDX, SAMD9, RDX, SAMD9, SERPINB5, NMU, CLRN3, SLC9A4, VTCN1, LOC339977, FUT9, GALNT5, NR5A2, OLFM4, LY75, SCPEPI, TACSTD2, MYO1A, BTNL8, VIL1, SLC28A2, DPP4, AZGP1, CDH17, NPNT, ALDH1A1, ATP13A4, ATP7B, IL2RG, POSTN, FCGBP, GPA33, DSC2, COL6A3, VNN1, SLP1, AIM1, PRKAA2, GUCY2C, P13, TIMP1, APOL1, ANPEP, SLC34A2, DMBT1, RGS2, PAPSS2, BCM01, ADH6, TM4SF20, CHST5, HHLA2, FABP1, SNORD1 16-21, MYO7B, MIA, MEP1A, SLC3AI, PLAC8, TFPI, PGC, MUC2, LIPF, FABP2, SI, SLC17A4, GSTA1, PDZK1, RAB3B, REG1A, SPINK4, CXCL1, GKN1, BTNL3, ADH4, ALDOB, CXCL2, SLC26A3, MMPI, UPK1B, MEP1B, CA1, and PRSS7.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) FIG. 1 shows an exemplary construction of a cell sampling device with a cord under a surface of an abrasive material sponge in accordance with various embodiments.

(2) FIG. 2 shows an exemplary construction of a cell sampling device with a cord under a surface of an abrasive material sponge in accordance with various embodiments.

(3) FIG. 3 shows an illustration of an exemplary cell sampling device of the invention in accordance with various embodiments.

(4) FIG. 4 shows an illustration of an exemplary cell sampling device of the invention in accordance with various embodiments.

EXAMPLES

Example 1

Construction of Device

(5) An exemplary device has the following features or components abrasive material: Sponge 105 (composition: reticulated polyurethane; density: 10 ppi; shape: spherical; diameter: 3 cm; supplier: Foam Conversion Ltd, Kempston, Bedforshire, UK) means for retrieval: Cord 110 (reference: White Force Fiber Code F500-W; size: No 2; supplier: Teleflex Medical, USA) soluble capsule 125 (reference: Gelatin Capsule; size: 00; supplier: Capsuline Inc., USA) unswallowable element 130: Cardboard retaining the loose end of the cord 110 (supplier: Medical Wire & Equipment Ltd, UK)

(6) The device is optionally packaged: Packaging (composition: sealed polythene bag; supplier: Medical Wire & Equipment Ltd, UK)

(7) The device may be irradiated with a minimum dose of 17 kGy, which is at a level necessary to clean the device but not sterilise it. The device may be optionally irradiated with a sterilizing dose of radiation.

(8) The knot 120 used in tying the thread 110 through and out of the capsule sponge 105:

(9) Free end of 111 the thread 110 is passed in to the open sponge 105 in such a way that the thread 110 forms a small loop 112 with in the sponge 105 just below the surface as shown in the FIG. 1.

(10) The free end 111 of the thread 110 is brought out and a loop is made using two overhand knots 113, 114 (noose) one after the other (double overhand knot 120).

(11) Note that it is basically two overhand knots 1134, 114, with the second overhand knot 113 acting as a stop-knot.

(12) The other free end 115 of the thread 110 is passed through this loop and pulled tight as in FIG. 2.

(13) At least 1 cm length is left at the free end 111 of thread 110 after the knot 120.

(14) The cord 110 runs under the surface of the sponge 105. The cord 110 may optionally run through deep in the centre of the sponge 105 sphere.

(15) The short loose end 111 of the cord 110 is at least 1-centimeter-long.

(16) The long loose end 115 of the cord 110 shall be wound round and attached to an unswallowable element 130 which comprises a flat piece of cardboard (5-centimeter-long and 3-centimeter-wide) as shown in FIG. 3.

(17) 80 centimeters of cord 110 shall be allowed for each sponge kit, including the knot 120.

(18) The assembled device is then encapsulated into the soluble capsule 125 as shown in FIG. 4.

Example 2

Further Properties and Features

(19) Devices of the invention may be tested to check their performance and properties.

(20) Devices may be tested as follows: measure the length of the cord from the end to the outer surface of the capsuleit should be 60 centimeters minimum look for any breaks on the outside of the capsuleany breaks should be remedied calculate the time taken for the capsule to dissolve and the sponge to open in warm water at 30 degree C.it should be 5 minutes maximum measure the size of the loop inside the sponge check the loopshould be just below the surface of the sponge measure the free end of the cord after the knotit should be 1 centimeter in length minimum check that the knot complies with specifications set out herein measure the diameter of the sponge once the capsule dissolved after 5 minutesit should be 3 centimeters measure the weight the cord can hold before either tearing the sponge apart or the thread getting undone from the spongethe cord should hold 2.4 kg minimum

Example 3

Comparative Data

(21) Devices according to the present invention were tested as above. Known (old) devices were tested in parallel to demonstrate the technical advantages of the device of the invention.

(22) Exemplary features of a device according to the present invention include the following: Sponge: Shaperound Diameter3cm Capsule: Uniform shape and size Not have any breaks and sharp ends Dissolves in 30 degree centigrade water within 5 minutes Retrieval means: Cord White colour thread Minimum length of cord60 cms Smooth on the surface Loop inside the spongeshould loop just below the surface Free end of the cord after the knotminimum of 1 cm KnotDouble hitch knot and complies with the specifications given Break resistantMinimum requirement of 2.4 kg Cord tethered to unswallowable element such as cardboard to prevent swallowing

(23) Test performance of the known sponge (old sponge) in vitro:

(24) TABLE-US-00005 Loop Fate when Sponge Length Time taken inside Free Weight max. size of cord Capsule to open in the end of Knot with- tension when No in cm outside H20 at 30 C. sponge thread specification stood exceeded opened 1 77.5 Larger 6 min 11 sec Fine 0.7 cm Fine 1.42 kg Thread 3 cm size, broke Broken 2 75.5 Fine 4 min 54 sec Fine 0.8 cm Fine 2.11 kg Thread 3 cm broke 3 77 Fine 6 min 02 sec Small 0.8 cm Fine 3.10 kg Thread 2.8 cm broke 4 77 Fine 6 min 29 sec Fine 0.8 cm Fine 2.51 kg Thread 2.5 cm broke 5 77.5 Fine 4 min Fine 0.7 cm Fine 2.19 kg Thread 3 cm broke 6 78 Fine 6 min 20 sec Fine 0.8 cm Fine 2.65 kg Thread 2.8 cm broke 7 78.5 Fine 6 min 29 sec Small 0.9 cm Fine 2.41 kg Thread 2.5 cm broke 8 77 Fine 5 min 49 sec Fine 0.8 cm Fine 2.43 kg Thread 3.1 cm broke 9 76 Fine 3 min 02 sec Fine 2 cm Fine 2.38 kg Thread 2.8 cm broke 10 78 Fine 4 min 32 sec Fine 2 cm Fine 2.41 kg Thread 2.8 cm broke

(25) Performance of the device of the invention (new sponge) in vitro:

(26) TABLE-US-00006 Loop Fate when Sponge Length Time taken inside Free Weight maximum size of cord Capsule to open in the end of Knot with- tension when No in cm outside H20 at 30 C. sponge thread specification stood exceeded opened 1 69 Fine 2 min 06 sec Fine 1 cm Fine 3.5 kg Tore 3 cm through the sponge 2 67 Fine 2 min 09 sec Fine 1.5 cm Fine 5.8 kg Same as 3 cm above 3 66 Fine 3 min 53 sec Small 1.5 cm Fine 4.06 kg Same as 3 cm above 4 64 Fine 3 min 06 sec Fine 1.7 cm Fine 4.89 kg Unable to 3 cm break 5 68 Fine 3 min Fine 1.7 cm Fine 5.7 kg Unable to 3 cm break or separate 6 68 Fine 2 min 09 sec Fine 1.6 cm Fine 5.67 kg Unable to 3 cm break 7 66 Fine 2 min 22 sec Small 2 cm Fine 4.35 kg Tore 3 cm through the sponge 8 67 Fine 3 min 30 sec Fine 2 cm Fine 2.78 kg Same as 3 cm above 9 66 Fine 3 min 02 sec Fine 2 cm Fine 5.9 kg Same as 3 cm above 10 68 Fine 4 min 32 sec Fine 2 cm Fine 5.49 kg Unable to 3 cm break or separate from the sponge

IN SUMMARY

(27) Thus it can be seen that the old (known) device is inferior in several respects. The

(28) TABLE-US-00007 Median Time length taken Loop Sponge of to inside Free size Fate when chord open Capsule the end when max in cm in H20 outside sponge of Knot Weight fully tension (Range) at 30 C. (Range) (Range) thread specification withstood open exceeded Old 77 cm 6.02 sec Fine Fine 0.8 cm Variable 2.41 kg 2.8 cm Thread Sponge (75-78.5 cm) (4 to (0.7 to knots (1.42 kg (2.5 to snapped in Kit 6.29 sec) 0.9 cm) to 3.10 kg) 3 cm) all 10 tests New 67 cm 3.01 min Fine Fine 1 cm Two half 4.62 kg 3 cm Majority - Sponge (64 to (2.06 hitch (2.78 to thread tore Kit 69 cm) to 4.32 min) knot 5.8) through the sponge
advantageous performance of the device of the invention can be clearly appreciated.

(29) In addition it should be noted that in in vivo tests, there have been no losses of the device in subjects, as compared to the known old device which has regularly been lost in subjects.

(30) All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described aspects and embodiments of the present invention will be apparent to those skilled in the art without departing from the scope of the present invention. Although the present invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are apparent to those skilled in the art are intended to be within the scope of the following claims.