Polymeric particles having a biodegradable gelatin or aminodextran coating and process for making same

• US 5,639,620 A
• Filed: 11/09/1994
• Issued: 06/17/1997
• Est. Priority Date: 10/31/1990
• Status: Expired due to Fees

• Current Assignee: Coulter International Corp.
• Original Assignee: Coulter Corporation (Danaher Corporation)
• Inventors: Burshteyn, Alexander, Gupta, Ravinder K., Siiman, Olavi
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/336,725
• Time in Patent Office: 951 Days
• Field of Search: 427/2, 427/127-131, 427/213.35, 427/215, 427/216, 427/337, 427/338, 427/2.11, 427/2.13, 427/2.14, 428/403, 428/407, 435/5, 435/7.21, 436/173, 436/518, 436/524-526, 436/529, 436/531, 436/532-534
• US Class Current: 435/7.21
• CPC Class Codes: G01N 2446/20 the magnetic material being present in the particle core
• CPC Class Codes: G01N 2446/30 the magnetic material being dispersed in the polymer composition before their conversion into particulate form
• CPC Class Codes: G01N 2446/84 Polymer coating, e.g. gelatin
• CPC Class Codes: G01N 2446/86 the coating being pre-functionalised for attaching immunoreagents, e.g. aminodextran
• CPC Class Codes: G01N 2446/90 characterised by small molecule linker used to couple immunoreagents to magnetic particles
• CPC Class Codes: G01N 33/531 Production of immunochemical test materials
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/5434 using magnetic particle immunoreagent carriers which constitute new materials per se
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: Y10S 977/829 Organic or biological core coated with inorganic shell
• CPC Class Codes: Y10S 977/897 Polymerization
• CPC Class Codes: Y10S 977/898 Enzymatic
• CPC Class Codes: Y10T 428/2991 Coated
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Gelatin and aminodextran coated polymer core particles useful in immunoassays and methods of making the same are disclosed. The preparation of aminodextrans having varying amounts of amine groups is also described, as is a method of crosslinking gelatin and aminodextran without the use of a stabilizer.

Claims

1. Discrete colloidal particles having a surface coating provided with a plurality of pendent functional groups, said particles consisting:

(a) a polymeric, non-gelatin, non-aminodextran core selected from the group consisting of polymeric substances which have surface amine-reactive functional groups and polymeric substances which do not have surface amine-reactive groups;

(b) said coating selected from the group consisting of a type A, acid cured gelatin of Bloom in the range of about 60 to 300 and an aminodextran;

(i) said gelatin coating being crosslinked by a chemical crosslinking agent, or

(ii) said aminodextran coating having a molecular weight in the range of 10,000 to 2 million, and,

(1) always being crosslinked by a chemical crosslinking agent when said aminodextran is coating a core substance which does not have surface amine-reactive groups or

(2) being either not crosslinked or crosslinked by a chemical crosslinking agent when said aminodextran is coating the surface of a core substance which has surface amine-reactive groups and said coating is by covalent coupling of said aminodextran to said core surface by a reaction between said amine-reactive groups and aminodextran amine groups; and

(c) functional groups covalently attached to said gelatin and aminodextran coatings.

2. Particles in accordance with claim 1 wherein said core is in the size range of about 0.1 to about 5.0 microns.

3. Particles in accordance with claim 1 wherein said core is in the size range of about 0.1 to about 1.0 microns.

4. Particles in accordance with claim 1 wherein said core is magnetic.

5. Particles in accordance with claim 1, 2, 3 or 4 wherein said polymeric substance is polystyrene latex.

6. Particles in accordance with claim 5 wherein said core surface has amine-reactive functional groups selected from the group consisting of aldehydes, carboxylic acids and esters and tosyl groups.

7. Particles in accordance with claim 5 wherein said aminodextran is selected from the group consisting of 1X-, 2X-, 3X- and 5X-aminodextran.

8. Particles in accordance with claim 5 wherein said coating is 5X-aminodextran.

9. Particles in accordance with claim 5 wherein the functional groups pendent from said particles are selected from the group consisting of amine groups, sulfhydryl groups, monoclonal antibodies, polyclonal antibodies and biological cells.

10. Colloidal particles comprising:

(a) a core of a non-gelatin, non-aminodextran polymeric substance selected from the group consisting of a polymer-only substance, a polymeric substance embedded with magnetic particles and a polymeric substance coating a magnetic nucleus;

(b) a coating on the surface of the core of (a) selected from the group consisting of a type A, acid cured gelatin of Bloom in the range of about 60 to 300 and an aminodextran having a molecular weight in the range of 10,000 to 2 million;

(c) a substance selected from the group consisting of polyclonal antibodies, monoclonal antibodies and biological cells; and

(d) a bridging group covalently bound to both said gelatin or aminodextran coating and the selected substance of step (c).

11. Particles in accordance with claim 10 wherein said core is in the size range of about 0.1 to 5.0 microns.

12. Particles in accordance with claim 10 wherein said core is in the size range of about 0.1 to 1.0 microns.

13. Particles in accordance with claim 10, 11 or 12 wherein said polymeric material is polystyrene latex.

14. Particles in accordance with claim 13 wherein said aminodextran is selected from the group consisting of 1X-, 2X-, 3X- and 5X-aminodextran.

15. Particles in accordance with claim 13 wherein said aminodextran is 5X-aminodextran.

16. Particles in accordance with claim 13 wherein said bridging group is selected from the group consisting of amine groups, sulfhydryl groups, polyclonal antibodies and monoclonal antibodies.