Luminescent indicator dye and optical sensor

• US 20060121623A1
• Filed: 12/03/2004
• Published: 06/08/2006
• Est. Priority Date: 12/03/2004
• Status: Active Grant

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: He, Huarui, Mortellaro, Mark A., Young, Susanne T.
• Granted Patent: US 8,097,725 B2
• Time in Patent Office: Days
• US Class Current: 436/163
• CPC Class Codes: C07D 221/14 Aza-phenalenes, e.g. 1,8-naphthalimide
• CPC Class Codes: C07D 311/82 Xanthenes
• CPC Class Codes: C07F 5/022 without C-boron linkages
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH

Abstract

The present invention relates to a chemical compound that has applications as a luminescent indicator dye, and to an optical sensor, typically employed for determination of near-neutral pH values of aqueous samples. The optical sensor has particular application in the pH determination of body liquids such as, for example, blood, plasma and serum.

Claims

1. A compound having the general Formula I

wherein

X is a luminophoric moiety,

m means the number 0, 1 or 2, and

R₁, R₂, R₃ and R₄ each independently represent hydrogen, chlorine or fluorine, with the proviso that at least one of R₁, R₂, R₃ and R₄ represent chlorine or fluorine.

2. The compound of claim 1, wherein R₂ and/or R₄ represent chlorine or fluorine, and R₁ and R₃ represent hydrogen.

3. The compound of claim 1, wherein the luminophoric moiety X in the general Formula I

(a) is an amino-naphthalimide group of the general Formula II

in which one of R₅, R₆, R₇, R₈, R₉ and R₁₀ is a group —

NH—

through which X is bound to the group —

(CH₂)_m—

of the compound mentioned in claim 1 of the general Formula I and the remainder and R₁₁ independently are hydrogen, a lipophilic or hydrophilic group or a reactive group for coupling to a polymer;

(b) is a xanthenone group of the general Formula III

in which one of R₁₂, R₁₃, R₁₄, R₁₅, R₁₆, R₁₇, R₁₈, and R₁₉ represents a chemical bond through which X is bound directly (m=0) to the compound mentioned in claim 1 of the general Formula I and the remainder represent —

OH, —

OR₂₇, in which R₂₇ is a hydrophilic or a lipophilic group, —

O—

R₂₈-G, in which R₂₈ is a hydrophilic or a lipophilic group and G a reactive group for coupling to a polymer, or —

(CH₂)_n—

COOH, in which n is a number between 0 and 17, or group or a reactive group for coupling to a polymer;

or

(c) is a group of the general Formula IV

in which one of R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, R₂₅ and R₂₆ is a chemical bond through which X is bound to the group —

(CH₂)_m—

of the compound mentioned in claim 1 of the general Formula I and the remainder independently are hydrogen, a lipophilic or hydrophilic group or a reactive group for coupling to a polymer, or R₂₅ forms an aromatic ring system together with R₂₄ and R₂₁ forms an aromatic ring system together with R₂₂.

5. An optical sensor for determining the pH of aqueous media comprising a luminescent dye, wherein

said luminescent dye is a compound according to claim 1, and

said compound is present in an immobilized form.

6. An optical sensor for determining the pH of aqueous media comprising a luminescent dye, wherein

said luminescent dye is a compound according to claim 2, and

said compound is present in an immobilized form.

7. An optical sensor for determining the pH of aqueous media comprising a luminescent dye, wherein

said luminescent dye is a compound according to claim 3, and

said compound is present in an immobilized form.

9. A method of determining the pH of aqueous media comprising contacting an optical sensor according to claim 5 with said aqueous media.

10. The method of claim 9, wherein said aqueous media is selected from blood, plasma or serum.

11. A method of determining the pH of aqueous media comprising contacting an optical sensor according to claim 6 with said aqueous media.

12. The method of claim 11, wherein said aqueous media is selected from blood, plasma or serum.

13. A method of determining the pH of aqueous media comprising contacting an optical sensor according to claim 7 with said aqueous media.

14. The method of claim 13, wherein said aqueous media is selected from blood, plasma or serum.

4. A compound of the formula

8. An optical sensor for determining the pH of aqueous media comprising a luminescent dye, wherein

said luminescent dye is a compound according to claim 4, and

said compound is present in an immobilized form.

15. A method of determining the pH of aqueous media comprising contacting an optical sensor according to claim 8 with said aqueous media.

16. The method of claim 15, wherein said aqueous media is selected from blood, plasma or serum.