Seamless capsule for synthesizing biopolymer and method for producing the same

• US 6,251,661 B1
• Filed: 11/02/1999
• Issued: 06/26/2001
• Est. Priority Date: 05/14/1997
• Status: Expired due to Term

• Current Assignee: Morishita Jintan Co., Ltd
• Original Assignee: Morishita Jintan Co., Ltd
• Inventors: Yomo, Tetsuya, Yamamoto, Keizo, Urabe, Itaru, Kamaguchi, Ryosei, Sunohara, Hideki, Hatano, Yumi
• Primary Examiner(s): Sisson, Bradley L.
• Application Number:
  US09/432,823
• Time in Patent Office: 602 Days
• Field of Search: 435/6, 435/7.1, 435/91.1, 435/91.2, 435/183, 435/69.1, 536/23.1, 536/24.3, 536/24.33, 536/25.3
• US Class Current: 435/287.2
• CPC Class Codes: B01J 13/04 by physical processes, e.g. drying, spraying
• CPC Class Codes: C12N 11/02 Enzymes or microbial cells immobilised on or in an organic carrier

Abstract

This invention provides a seamless capsule for synthesizing biopolymer, comprising:

(a) an aqueous mixture for synthesizing biopolymer,

(b) a seamless capsule layer encapsulating said aqueous mixture, formed from polysaccharide or protein, and,

(c) a viscous liquid intermediate layer, present between said aqueous mixture and said seamless capsule layer, which is immiscible with water,

wherein said seamless capsule has a diameter of 0.01 to 10.0 mm.

This invention can also provide a method for producing the seamless capsule.

Claims

1. A method for producing a reaction capsule comprising:

concurrently extruding a plurality of concentric layers from a plurality of nozzles into a cooling solution, wherein an inner nozzle extrudes an aqueous reaction mixture comprising components required for synthesizing a polynucleotide or a polypeplide;

an intermediate nozzle extrudes a viscous fluid that is not miscible with water; and

an outer nozzle extrudes an encapsulating polymer layer formed of polysaccharide, protein, or a mixture thereof to form a reaction capsule; and

isolating the reaction capsule from the cooling solution, wherein the flow rate from the nozzles is controlled to produce a capsule having an approximate diameter of 0.1 to 10.0 mm.

2. The method of claim 1, wherein the flow rate is controlled to produce a capsule having an approximate diameter of 3 mm.

3. A reaction capsule produced by a process comprising:

concurrently extruding, a plurality of concentric layers from a plurality of nozzles into a cooling solution, wherein an inner nozzle extrudes an aqueous reaction mixture comprising components required for synthesizing a polynucleotide or a polypeptide;

an intermediate nozzle extrudes a viscous fluid that is not miscible with water; and

an outer nozzle extrudes an encapsulating polymer layer formed of polysaccharide, protein, or a mixture thereof; and

isolating from the cooling solution a reaction capsule, wherein the flow rate from the nozzles is controlled to produce a capsule having an approximate diameter of 0.1 to 10.0 mm.

4. A reaction capsule for producing a nucleic acid or amino acid polymer therein, comprising:

a core comprising an aqueous reaction mixture for producing a nucleic acid or amino acid polymer;

a polymer layer encapsulating the core, the polymer layer formed of polysaccharide, protein, or a mixture thereof; and

an intermediate layer comprising a viscous fluid disposed between the core and the encapsulating polymer layer,

wherein said capsule has a diameter of about 0.01 to about 10.0 mm.

5. The reaction capsule of claim 4, wherein said aqueous mixture comprises components for polymerase chain reaction (PCR).

6. The reaction capsule of claim 4, wherein said aqueous mixture comprises a reverse transcriptase.

7. The reaction capsule of claim 4, wherein said core comprises components for cell free translation.

8. The reaction capsule of claim 4, wherein said core comprises one or more RNA or DNA polymerase.

9. The reaction capsule of claim 4, wherein said core comprises components for nucleic acid transcription and cell free translation.

10. The reaction capsule of claim 4, wherein said polymer layer comprises curdlan, agarose, guaran gum, pectin, sodium alginate, or mixtures thereof.

11. The reaction capsule of claim 10, wherein said polymer layer comprises curdlan, agarose, or a mixture thereof.

12. The reaction capsule of claim 11, wherein said polymer layer comprises a mixture of curdlan and agarose having an approximate weight ratio of 1:

1.

13. The reaction capsule of claim 4, wherein said polymer layer comprises gelatin, albumin, casein, or a mixture thereof.

14. The reaction capsule of claim 4, wherein said polymer layer further comprises a gelling agent.

15. The reaction capsule of claim 14, wherein said gelling agent is calcium chloride, calcium lactate, manganese chloride, aluminum chloride, or mixtures thereof.

16. The reaction capsule of claim 4, wherein said polymer layer further comprises a water-soluble polyol or water-soluble polyol derivative.

17. The reaction capsule of claim 16, wherein said water-soluble polyol or water-soluble polyol derivative is glycerin, polyglycerine, sorbitol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, ethylene oxide-propylene oxide copolymer, oligosaccharide, sugar ester, glyceride, sorbitan ester, or mixtures thereof.

18. The reaction capsule of claim 4, wherein said polymer layer comprises polysaccharide, protein, or mixture thereof in an amount of approximately 50-100% by weight of the total solids content.

19. The reaction capsule of claim 4, wherein said intermediate layer comprises a viscous liquid having a viscosity of 1,000 centipoise or less.

20. The reaction capsule of claim 4, wherein said intermediate layer comprises and emulsifier, an oil, a resin, or mixtures thereof.

21. The reaction capsule of claim 20, wherein said intermediate layer comprises a sucrose fatty acid ester, propylene glycol fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, lecithin, palm oil, silicone oil, liquid paraffin, dl-alpha-tocopherol, polybutylene, polybuten, silicone resin, vinyl acetate, or mixtures thereof.

22. The reaction capsule of claim 21, wherein said intermediate layer comprises a mixture of sucrose fatty acid ester and palm hydrogenated oil in a weight ratio of 1 to 4:

4 to 1.

23. The reaction capsule of claim 22, wherein said weight ratio is 4:

1.