Oxygen sensors

• US 9,867,560 B2
• Filed: 06/22/2016
• Issued: 01/16/2018
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Profusa, Inc.
• Original Assignee: Profusa, Inc.
• Inventors: Gamsey, Soya, Wisniewski, Natalie, Helton, Kristen, McMillan, William
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US15/189,448
• Publication Number:
  US 20160374601A1
• Time in Patent Office: 573 Days
• CPC Class Codes: A61B 2503/40 Animals
• 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 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: A61K 49/0036 Porphyrins used in photodynamic therapy A61K41/0071 or A61K41/0076; used as targeting group or modifying agent for targeting a therapeutic compound A61K47/546
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/0073 semi-solid, gel, hydrogel, ointment
• CPC Class Codes: C07F 15/0066 without a metal-carbon linkage
• CPC Class Codes: C09K 11/06 containing organic luminescent materials
• CPC Class Codes: C09K 2211/185 of the platinum group, i.e. Os, Ir, Pt, Ru, Rh or Pd
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 2333/904 acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath

Abstract

Oxygen sensing luminescent dyes, polymers and sensors comprising these sensors and methods of using these sensors and systems are provided.

Claims

1. A method for detecting an analyte comprising placing a tissue-integrating sensor comprising a polymer, wherein said polymer comprises one or more residues of a luminescent dye, and wherein the luminescent dye is a photostable porphyrin dye and has excitation and emission spectra in the NIR optical window of a mammalian skin

wherein the luminescent dye is a compound having the formula:

2. The method of claim 1 wherein M is Pd.

3. The method of claim 1 wherein M is Pd, R² and R³ are fused to form a benzene ring, and R¹ and R⁷ are both C(O)NH(CH₂)₂OC(O)C(CH₃)CH₂.

4. The method of claim 1 wherein the luminescent dye has an absorption maximum between 500 nm and 900 nm and an emission maximum between 600 nm and 1000 nm.

5. The method of claim 1 wherein the residue of the luminescent dye is present at a concentration from about 0.01 mM to about 5 mM.

6. The method of claim 1 wherein the residue of the luminescent dye is present at the concentration of about 1 mM.

7. The method of claim 1 wherein the polymer further comprises the residues of HEMA.

8. The method of claim 1 wherein the polymer is a hydrogel.

9. The method of claim 1 wherein the analyte is oxygen.

10. The method of claim 1 wherein the sensor generates detectable luminescent signal when placed under the skin of a mammalian subject.

11. The method of claim 10 wherein the sensor generates detectable luminescent signal when placed up to about 5 mm deep under the skin of a mammalian subject.

12. The method of claim 11 wherein the sensor generates detectable luminescent signal when placed more than 1 mm deep under the skin of a mammalian subject.

13. The method of claim 10 wherein the mammalian subject is a human.

14. The method of claim 10 wherein the sensor is stable in a mammalian tissue for longer than 1 week.

15. The method of claim 1 further comprising an oxidase.

16. The method of claim 15, wherein the oxidase is a glucose oxidase, ethanol oxidase, lactate oxidase, pyruvate oxidase, bilirubin oxidase, or histamine oxidase.

17. The method of claim 15 wherein the analyte is oxygen consumed by the oxidase.

18. The method of claim 16 wherein the oxidase is a glucose oxidase, ethanol oxidase, lactate oxidase, pyruvate oxidase, bilirubin oxidase, or histamine oxidase.

19. The method of claim 18 wherein the sensor is tissue-integrating.

20. The method of claim 1 wherein R² and R³ are fused to form an aryl.

21. The method of claim 1 wherein R² and R³ are fused to form a heteroaryl.

22. The method of claim 1 wherein R² and R³ are fused to form a cycloalkenyl.

23. The method of claim 1 wherein and R¹ and R⁷ are both C(O)X—

(CH₂)_n—

YC(O)C(R⁴)CH₂.

24. The method of claim 4 wherein the luminescent dye has an absorption maximum between 500 nm and 800 nm.

25. The method of claim 4 wherein the luminescent dye has an emission maximum between 650 nm and 900 nm.