Metal chelate containing compositions for use in chemiluminescent assays

• US 6,180,354 B1
• Filed: 06/06/1995
• Issued: 01/30/2001
• Est. Priority Date: 05/22/1991
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Products GmbH (Siemens AG)
• Original Assignee: DADE Behring Beteiligungs GmbH (Siemens AG)
• Inventors: Singh, Sharat, Ullman, Edwin F.
• Primary Examiner(s): Achutamurthy, Ponnathapura
• Assistant Examiner(s): Monshipouri, Maryam
• Application Number:
  US08/480,430
• Time in Patent Office: 2,065 Days
• Field of Search: 435/6, 435/7.1, 435/7.2, 435/7.21, 435/7.22, 435/7.32, 435/7.5, 435/7.8, 435/7.92, 435/7.93, 436/501, 436/512, 436/513, 436/518, 436/523, 436/524, 436/527, 436/528, 436/533, 436/534, 436/808
• US Class Current: 435/7.1
• CPC Class Codes: C07D 265/30 not condensed with other rings
• CPC Class Codes: C07D 279/12 not condensed with other rings
• CPC Class Codes: C07D 327/06 Six-membered rings
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: G01N 33/533 with fluorescent label
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/5436 with ligand physically entrapped within the solid phase liposomes G01N33/5432; immunological test elements G01N33/54386
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/585 with a particulate label, e.g. coloured latex
• CPC Class Codes: G01N 33/586 Liposomes, microcapsules or cells
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10T 436/13 Tracers or tags

Abstract

Compositions are disclosed comprising (a) a metal chelate wherein the metal is selected from the group consisting of europium, terbium, dysprosium, samarium osmium and ruthenium in at least a hexacoordinated state and (b) a compound having a double bond substituted with two aryl groups, an oxygen atom and an atom selected from the group consisting of oxygen, sulfur and nitrogen wherein one of the aryl groups is electron donating with respect to the other. Such composition is preferably incorporated in a latex particulate material. Methods and kits are also disclosed for determining an analyte in a medium suspected of containing the analyte. The methods and kits employ as one component a composition as described above.

Claims

1. A method for determining an analyte which comprises:

(a) providing in combination (1) a medium suspected of containing an analyte, (2) a photosensitizer capable in its excited state of activating oxygen to a singlet state, said photosensitizer associated with a first specific binding pair (sbp) member, and (3) a composition comprising a latex particulate material having incorporated therein a composition comprising;

(i) a metal chelate comprising a metal selected from the group consisting of europium, terbium, dysprosium, samarium, osmium and ruthenium in at least a hexacoordinated state and

(ii) a compound having the structural portion;

 

wherein X is O, S or N and the valency of N is completed with hydrogen or an organic radical consisting of atoms selected from the group consisting of C, O, N, S, and P and Ar and Ar′

are independently aryl and one of Ar or Ar′

is electron donating with respect to the other, and wherein the broken lines are to hydrogen, an organic radical or are taken together to form a ring, said compound being capable of undergoing a chemical reaction with singlet oxygen to form a metastable intermediate that can decompose with the emission of light within the wavelength range of 250 to 1200 nm,

wherein said latex particulate material has bound thereto a second sbp member that is capable of binding directly or indirectly to said analyte or to said first sbl member,

(b) treating said combination with light to excite said photosensitizer, and

(c) examining said combination for the amount of luminescence emitted therefrom, the amount of said luminescence being related to the amount of analyte in said medium.

2. A kit comprising in packaged combination:

(a) a composition comprising a latex particulate material having incorporated therein a composition comprising;

(i) a metal chelate comprising a metal selected from the group consisting of eurorium, terbium, dysgrosium, samarium, osmium and ruthenium in at least a hexacoordinated state and

(ii) a compound having the structural portion;

 

wherein X is O, S or N and the valency of N is completed with hydrogen or an organic radical consisting of atoms selected from the group consisting of C, O, N, S, and P and Ar and Ar′

are independently aryl and one of Ar or Ar′

is electron donating with respect to the other, and wherein the broken lines are to hydrogen, an organic radical or are taken together to form a ring, said compound being capable of undergoing a chemical reaction with singlet oxygen to form a metastable intermediate that can decompose with the emission of light within the wavelength range of 250 to 1200 nm,

wherein said latex particulate material has bound thereto an sbp member, and

(b) a photosensitizer that is not in said composition and is capable in its excited state of activating oxygen to its singlet state.

3. A method for determining an analyte which comprises:

(a) providing in combination (1) a medium suspected of containing an analyte, (2) a photosensitizer capable in its excited state of activating oxygen to a singlet state, said photosensitizer associated with a specific binding pair (sbp) member, and (3) a suspendible latex particulate material comprising a chemiluminescent compound, said particulate material having bound thereto an sbp member, said chemiluminescent compound having the formula;

wherein X′

is S or NR′

wherein R′

is alkyl or aryl and D and D′

are independently selected from the group consisting of alkyl and alkyl radical,

(b) treating said combination with light to excite said photosensitizer, and

(c) examining said combination for the amount of luminescence emitted therefrom, the amount of said luminescence being related to the amount of analyte in said medium.

4. The method of claim 3 wherein R′

is methyl or phenyl.

5. The method of claim 3 wherein said particulate material comprises a metal chelate comprising a metal selected from the group consisting of europium, terbium, dysprosium, samarium, osmium and ruthenium in at least a hexacoordinated state.

6. A method for determining an analyte which comprises:

(a) providing in combination (1) a medium suspected of containing an analyte, (2) a photosensitizer capable in its excited state of activating oxygen to a singlet state, said photosensitizer associated with a first specific binding pair (sbp) member, (3) a composition comprising a suspendible latex particulate material having incorporated therein a composition comprising (i) a metal chelate comprising a metal selected from the group consisting of europium, terbium, dysprosium, samarium, osmium and ruthenium in at least a hexa coordinated state, and (ii) a chemiluminescent compound, said particulate material having bound thereto a second sbp member that is capable of binding directly or indirectly to said analyte or to said first sbp member, said chemiluminescent compound having the formula;

wherein X′

is S or NR′

wherein R′

is alkyl or aryl and D and D′

are independently selected from the group consisting of alkyl and alkyl radical

(b) treating said combination with light to excite said photosensitizer, and

(c) examining said combination for the amount of luminescence emitted therefrom, the amount of said luminescence being related to the amount of analyte in said medium.

7. The method of claim 6 wherein R′

is methyl or phenyl.

8. The compound of claim 6 wherein alkyl is (CH₂)₆CH₃ or (CH₂)₇CH₃.