Method and device for detecting device colonization

• US 9,228,996 B2
• Filed: 05/31/2013
• Issued: 01/05/2016
• Est. Priority Date: 05/31/2013
• Status: Expired due to Fees

• Current Assignee: Empire Technology Development LLC (Allied Inventors Management, LLC)
• Original Assignee: Empire Technology Development LLC (Allied Inventors Management, LLC)
• Inventors: Peppou, George Charles, Manion, Michael Keoni, Austin, Benjamin Matthew, Millar, Benjamin William, Barens, Benjamin Watson
• Primary Examiner(s): Brusca, John S
• Assistant Examiner(s): Papciak, Sharon M
• Application Number:
  US14/114,738
• Publication Number:
  US 20140356901A1
• Time in Patent Office: 949 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis
• CPC Class Codes: A61B 5/4851 Prosthesis assessment or monitoring
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: A61M 2205/702 automatically during use
• CPC Class Codes: A61M 25/0009 Making of catheters or other medical or surgical tubes
• CPC Class Codes: A61M 25/0017 specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• CPC Class Codes: G01N 2800/00 Detection or diagnosis of diseases
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 33/493 urine

Abstract

Technologies are disclosed for a method and a device for detecting device colonization. Disclosed herein is an indwelling medical device configured to detect a biofilm. The device comprises a substrate configured to contact blood and a detecting material, disposed with the substrate, configured to detect the presence of a biofilm thereon. The detecting material is soluble in blood, removable by kidneys from the blood, and passable to urine by the kidneys for detection in the urine. A method for detecting the growth of a biofilm on an indwelling medical and a method for making an indwelling medical device are also disclosed herein.

Claims

1. An indwelling medical device configured to detect a biofilm, the device comprising:

a substrate configured to contact blood;

a detecting material, disposed in or about the substrate, configured to detect the presence of a biofilm on the indwelling medical device;

the detecting material being soluble in blood, removable by kidneys from the blood, and passable to urine by the kidneys; and

the indwelling medical device being configured to solubilize a sufficient amount of the detecting material, upon a sufficient presence of the biofilm on the indwelling medical device, for detection in the urine to indicate the presence of the biofilm on the indwelling medical device.

2. The indwelling medical device of claim 1 wherein the detecting material is selected from the group consisting of methylene blue, β

-carotene, rifampin, Yellow No. 6, tetracycline, Red No. 40, Red No. 3, Blue No. 2, Evan'"'"'s Blue, Green No. 3, Blue No. 1, indocyanine green, and betanin.

3. The indwelling medical device of claim 1 further comprising a first layer disposed on the substrate.

4. The indwelling medical device of claim 3 further comprising:

a second layer disposed on the first layer, the second layer being degradable in the presence of the sufficient amount of biofilm for the release of the detecting material into the blood.

5. The indwelling medical device of claim 1 wherein the detecting material is visually detectable in the urine.

6. The indwelling medical device of claim 4 wherein the second layer comprises a polymer, mixed polymer, or metal.

7. The indwelling medical device of claim 4 wherein the second layer comprises a biodegradable material.

8. The indwelling medical device of claim 4 wherein the second layer comprises a material selected from the group consisting of starch-based polymers, cellulose-based polymers, PLA, PLG, and PLGA.

9. The indwelling medical device of claim 4 wherein the second layer comprises a protein or albumin.

10. The indwelling medical device of claim 4 wherein the second layer comprises a first polymer and a second polymer;

the first polymer being degraded in the presence of a biofilm; and

the second polymer providing a retaining structure for the biofilm, upon the degradation of the first polymer.

11. The indwelling medical device of claim 10 wherein the second polymer is selected from the group consisting of silicone rubber, polyurethane, and polyethylene.

12. The indwelling medical device of claim 4 wherein the second layer comprises a thin film of iron or magnesium.

13. The indwelling medical device of claim 4 wherein the second layer comprises at least one antimicrobial or antifouling agent.

14. The indwelling medical device of claim 1 wherein the indwelling medical device is an intravenous catheter, central line, arterial line, stent, or wound drain.

15. A system comprising two or more of the indwelling medical devices of claim 1, each the indwelling device comprising a different detecting material, each of the different detecting materials being independently detectable.

16. A system configured to independently detect biofilm on two or more indwelling medical devices, each of the indwelling medical devices comprising:

a substrate configured to contact blood; and

a detecting material disposed in or about the substrate configured to detect the presence of a biofilm;

the detecting material being soluble in blood, removable by kidneys from the blood, and passable to urine by the kidneys;

wherein each of the two or more indwelling medical devices is associated with an independently detectable detecting material, detection of the independently detectable detecting material indicating the indwelling medical device having the biofilm; and

each of the two or more indwelling medical devices being configured to solubilize a sufficient amount of its associated detecting material, upon a sufficient presence of the biofilm on the associated indwelling medical device, for detection in the urine to indicate the presence of the biofilm on the associated indwelling medical device.

17. A method for detecting the growth of a biofilm on an indwelling medical device comprising:

passing blood over a surface of the indwelling medical device;

degrading the surface of the indwelling medical device, with a biofilm, by an amount sufficient to release a detecting material therefrom;

releasing a sufficient amount of the detecting material from the surface of the indwelling medical device into the blood to become detectable in urine; and

detecting the detecting material in the urine.

18. The method of claim 17 wherein the step of degrading the surface of the indwelling medical device comprises degrading at least a portion of the outer surface, contacting the passing blood, of the indwelling medical device by a sufficient amount, prior to the step of releasing the detecting material from the surface of the medical device.

19. The method of claim 18 wherein the step of degrading the surface of the indwelling medical device further comprises exposing an inner layer of the indwelling medical device to the passing blood and the step of releasing a sufficient amount of the detecting material from the surface of the indwelling medical device comprises releasing the detecting material from the inner layer.

20. The method of claim 17 wherein the step of detecting the detecting material in the urine comprises visually detecting the detecting material.

21. A method for making an indwelling medical device comprising:

providing a substrate for use as an indwelling device;

applying a detecting material in or about the substrate of the indwelling medical device;

wherein the detecting material is soluble in blood, removable by kidneys from the blood, and passable to urine by the kidneys; and

the indwelling medical device being configured to solubilize a sufficient amount of the detecting material, upon a sufficient presence of a biofilm on the indwelling medical device, for detection in the urine to indicate the presence of the biofilm on the indwelling medical device.

22. The method for making an indwelling medical device of claim 21 further comprising:

preparing a bath comprising a crystalline solvate dye;

the step of applying a detecting material in or about the substrate comprises coating the substrate of the indwelling medical device with the bath;

drying the substrate coating and crystallizing the dye; and

applying a polymer onto the crystallized dye.

23. The method for making an indwelling medical device of claim 21 further comprising:

preparing a hydrogel and dye material; and

the step of applying a detecting material to the substrate comprises coating the substrate of the indwelling medical device with the hydrogel and dye material.

24. The method for making an indwelling medical device of claim 23 wherein the hydrogel is selected from the group consisting of guanosine and 8-bromoguanosine hydrogel.

25. The method for making an indwelling medical device of claim 23 wherein:

the step of preparing a hydrogel and dye material comprises doping a first polymer with a dye;

the first polymer is water soluble;

the step of applying a detecting material to the substrate comprises coating a substrate of the indwelling medical device with the doped first polymer; and

applying a second polymer onto the coated substrate, wherein the second polymer is degradable in the presence of a sufficient amount of biofilm for the release of a detectable amount of the dye into the blood.

26. The method for making an indwelling medical device of claim 25 wherein the first polymer is PVA.

27. The method for making an indwelling medical device of claim 26 wherein:

the substrate of the indwelling medical device comprises PVC;

the doped first polymer comprises PVA and methylene blue at a concentration of greater than 10% (w/v); and

the step of coating a substrate comprises coating the substrate with the doped first polymer with a coat between 10-1000 micron thick.

28. The method for making an indwelling medical device of claim 26 wherein the step of applying a second polymer comprises applying PLA at a thickness between 10-1000 micron.