Medical device with integrated biosensor

• US 10,709,360 B2
• Filed: 09/04/2018
• Issued: 07/14/2020
• Est. Priority Date: 09/02/2017
• Status: Active Grant

• Current Assignee: Biocrede, Inc.
• Original Assignee: Biocrede, Inc.
• Inventors: Chen, Hao, Wolf, Alexander, Renehan, Kevin
• Primary Examiner(s): Bloch, Michael R
• Application Number:
  US16/121,405
• Publication Number:
  US 20190069820A1
• Time in Patent Office: 679 Days
• Field of Search: None
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61L 2300/114 Nitric oxide, i.e. NO
• CPC Class Codes: A61M 2202/0275 Nitric oxide [NO]
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence

Abstract

The disclosure concerns medical devices configured to utilize nitric oxide (NO) donor materials to release NO gas upon contact with moisture in order to mitigate bacterial proliferation, coagulation, or a combination thereof, at a site of a biosensor integrated within the medical device. A novel multi-lumen medical device is described, the device having a first lumen for containing the NO donor material and producing the NO gas, and having a second lumen for housing biosensor componentry. A channel between the first and second lumens serves to communicate NO gas from the first lumen to a sensor-volume of the biosensor.

Claims

1. A medical device (100) with integrated bio-sensor, comprising:

a tubular body (101), the tubular body comprising a first lumen (250) and a second lumen (350) therein;

the first lumen comprising a nitric oxide donor material (201) disposed therein, wherein said nitric oxide donor material is configured to release nitric oxide gas;

the second lumen being longitudinally disposed parallel with respect to the first lumen and configured to house componentry of at least a first biosensor (300), the first biosensor having a first sensor-volume (375) associated therewith;

wherein a first nitric oxide channel (275) is disposed between the nitric oxide donor material and the first sensor-volume, the first nitric oxide channel being configured to direct a flow of the nitric oxide gas into the first sensor-volume for preventing bacterial-proliferation, coagulation, or a combination thereof,

wherein the first biosensor and the nitric oxide donor material are each disposed in a distinct lumen of the first and second lumens.

2. The medical device of claim 1, wherein the first bio-sensor comprises:

a working electrode (301) and a reference electrode (321),

the working electrode comprising;

an insulation layer (311) covering at least a portion of the working electrode and configured to restrict diffusion of electroactive interference compounds through the insulation layer;

an analyte reaction layer (312) comprising one or more immobilized or chemically linked antibodies, redox enzymes, or chelators for reacting with one or more corresponding analytes to achieve a detectable signal; and

an analyte diffusion-control layer (313) for regulating diffusion of analytes of interest into the first sensor-volume of the first biosensor;

the reference electrode being positioned in proximity to the working electrode.

3. The medical device of claim 2, wherein each of the working and reference electrodes are coupled to an electrode signal monitoring system.

4. The medical device of claim 2, wherein the insulation layer comprises:

one or more perflourinated sulfonic acid resin-containing sub-layers, and a plurality of electropolymerized sub-layers disposed on an outer surface of the one or more perflourinated sulfonic acid resin-containing sub-layers.

5. The medical device of claim 4, wherein the one or more perflourinated sulfonic acid resin-containing sub-layers comprise sulfonated tetrafluoroethylene and one or more of:

perfluoro (alkyl vinyl ether), sulfonyl acid fluoride, perfluorocycloalkene, vinyl fluoride, vinylidene fluoride, chlorotrifluoroethylene, propylene, hexafluoropropylene, perfluoropropylvinylether, perfluoromethylvinylether, polychlorotrifluoroethylene, perfluoroalkoxy polymer, fluorinated ethylene-propylene, polyethylenetetrafluoroethylene, polyethylenechlorotrifluoroethylene, perfluoroelastomer, tetrafluoroethylene-propylene, polyurethane, polyetheline, silicone or any combination thereof.

6. The medical device of claim 4, wherein the one or more perflourinated sulfonic acid resin-containing sub-layers comprise annealed perflourinated sulfonic acid resin.

7. The medical device of claim 2, wherein the reference electrode comprises:

a coiled wire, the coiled wire being wound about at least a portion of a sleeve surrounding the working electrode for maximizing surface area thereof, or

a conductive trace disposed on the sleeve, wherein the sleeve is disposed between the reference electrode and a wire component of the working electrode.

8. The medical device of claim 2, wherein a thickness of the insulation layer comprises between 0.1 μ

m and 100.0 μ

m.

9. The medical device of claim 2, wherein the reference electrode is positioned between 0.2 mm and 10.0 mm from the analyte reaction layer.

10. The medical device of claim 2, wherein the one or more redox enzymes include:

creatinase, creatine amidohydrolase, sarcosine oxidase, malate oxidase, alcohol dehydrogenase, D-aspartate oxidase, spermine oxidase, NAD(P)H oxidase, urate oxidase, lactate oxidase, alcohol oxidase, pyruvate oxidase, glucose oxidase, glutamate oxidase, choline oxidase, glutathione sulfhydryl oxidase, cholesterol oxidase, histamine oxidase, L-lysine oxidase, L-aspartate oxidase, glycine oxidase, or galactose oxidase.

11. The medical device of claim 2, wherein the analyte diffusion-control layer comprises:

30-70% by weight polyurethane, 20-60% by weight silicone, and up to 50% of one or more of the following;

poloxamer polyol surfactant, polylactic acid, polyglycolide, poly lactic-co-glycolic acid.

12. The medical device of claim 2, wherein at least one of:

the insulation layer, the analyte reaction layer, and the analyte diffusion-control layer, comprises a second nitric oxide donor material.

13. The medical device of claim 1, wherein the nitric oxide donor material is one that is configured to release nitric oxide gas in response to contact with moisture.

14. The medical device of claim 1, wherein said nitric oxide donor material comprises:

diazeniumdiolated diamine, S-nitroso-albumin, S-nitroso-N-penicillamine (SNAP), S-nistrosocystine (CysNO), S-nitrosoglutathione (GSNO), diazeniumdiolated dibutylhexyldiamine (DBHD N202), Diethylenetriamine/nitric oxide adduct (DEAT/NO), Diethylamine NONOate (DEA/NO), Dipropylenetriamine NONOate (DPTA/NO), 6-(2-Hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine (MAHMA/NO) or a combination thereof.

15. The medical device of claim 1, wherein said nitric oxide donor material comprises:

between 0.1% and 4.0% by weight SNAP, and up to 99.9% by weight excipient.

16. The medical device of claim 15, wherein the excipient comprises:

cellulose, crosspovidone, hydroxypropyl cellulose, hydroxylpropyl methyl cellulose, sorbitol, xylitol, povidone (PVP), perfluoroelastomer, perfluorosulfonic acid isomers, ethylene, vinyl fluoride, vinylidene fluoride, chlorotrifluoroethylene, propylene, hexafluoropropylene, perfluoropropylvinylether, perfluoromethylvinylether, silicone, polyethylene, polyurethane, or any combination thereof.

17. The medical device of claim 1, further comprising a second bio-sensor, the second bio-sensor being disposed a first distance (D1) from the first bio-sensor, wherein the first distance comprises between 5.0 mm and 50.0 mm.

18. The medical device of claim 1, further comprising a third lumen, the third lumen being configured to receive one of:

a guidewire or fluid.

19. The medical device of claim 1, further comprising an aperture (330) extending through the tubular body into a portion of the second lumen, wherein the aperture is disposed adjacent to the first sensor-volume.

20. The medical device of claim 19, wherein the medical device comprises an outer layer covering the aperture and portions of the first biosensor exposed therethrough, the outer layer comprising silicone.

21. The medical device of claim 1, further comprising a membrane (285) disposed at the channel separating the first and second lumens;

wherein the membrane comprises silicone.