Automatic immunological measuring system

• US 5,158,895 A
• Filed: 03/29/1991
• Issued: 10/27/1992
• Est. Priority Date: 03/30/1990
• Status: Expired due to Fees

• Current Assignee: Fujirebio Inc. (H.U. Group Holdings, Inc.)
• Original Assignee: Fujirebio Inc. (H.U. Group Holdings, Inc.)
• Inventors: Watanabe, Fumio, Ashihara, Yoshihiro, Okada, Masahisa, Nishizono, Isao, Wakana, Shin-ichi, Minakawa, Hidetaka, Sakurabayashi, Yasusuke
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Trembley, T. A.
• Application Number:
  US07/677,686
• Time in Patent Office: 578 Days
• Field of Search: 422/63, 422/65, 422/67, 422/82.05, 422/82.08, 435/288, 435/287, 435/291, 435/300, 435/7.1, 435/808, 436/47, 436/49, 436/526, 436/807
• US Class Current: 436/526
• CPC Class Codes: G01N 2035/00534 Mixing by a special element, e.g. stirrer
• CPC Class Codes: G01N 2035/0465 Loading or unloading the conveyor
• CPC Class Codes: G01N 2035/0498 Drawers used as storage or dispensing means for vessels or cuvettes
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/02 using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations G01N35/0098 and G01N35/0099 take precedence
• CPC Class Codes: G01N 35/1079 with means for piercing stoppers or septums
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/113332 with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure

Abstract

An automatic immunoassay apparatus utilizes cartridges each having at least two wells, a first well containing solid phase material carrying antigen or antibody, and a second well containing antibody or antigen labelled with labelling compound. The wells may be sealed with a suitable sealing film before use and the sealing film is broken when the cartridge is to be used. The cartridges are transported to a predetermined position on a steppingly movable reaction line and conveyed thereby at a predetermined interval. While the reaction line steps, a sample, labelled antigen or antibody contained in the second well and substrate, if necessary, are added to the first well and stirred at predetermined timings, and reactions between the sample and a reactive solution are measured under control of a control device having a memory storing operator selectable programs for various measuring methods.

Claims

1. An automatic immunoassay apparatus comprising a sample stocker portion for storing a plurality of samples, a reagent stocker for storing washing solution and diluent, a plurality of reaction cartridges each having at least two wells, a first well of said at least two wells containing solid phase material carrying antigen or antibody, a second well of said at least two wells containing antibody or antigen labelled with labelling compound, a cartridge stocker for storing said plurality of reaction cartridges, a reaction line for conveying said plurality of reaction cartridges successively with a predetermined interval and performing a reaction between the sample and a reactive solution and a measurement of the reaction at predetermined positions along said reaction line, a cartridge transportation mechanism for transporting said plurality of reaction cartridges from said cartridge stocker to a starting portion of said reaction line one by one according to an item to be measured, an aspirating/pouring portion disposed in a predetermined position along said reaction line for individually aspirating the plurality of samples stored in said sample stocker portion and the labelled antigen or antibody contained in said second well of each cartridge and pouring them to said first well of each cartridge to obtain a mixture of them, a stirring portion for stirring the mixture contained in said first well of each cartridge, a bind/free separator for separating reacted substance bound with the solid phase material from non-reacted, free substance, a washing portion for removing the non-reacted, free substance, a measuring portion for measuring any information produced from the labelled compound bound with the solid phase material, an output portion for outputting a result of measurements from said measuring portion, a cartridge disposer arranged around an end of said reaction line for disposing of cartridges whose measurements are completed, and a control portion for controlling the operations of all of said reaction line, said cartridge transportation mechanism, said aspirating/pouring portion, said stirring portion, said bind/free separator, said washing portion, said measuring portion, said output portion for outputting a result of measurements from said measuring portion, and said cartridge disposer.

2. The apparatus claimed in claim 1, wherein said solid phase material comprises magnetic particles and wherein said bind/free separator comprises a magnetic separator.

3. The apparatus claimed in claim 1, wherein said labelling compound is an enzyme.

4. The apparatus claimed in claim 1 or 3, wherein each cartridge is formed of optically transparent, non-magnetic material and said measuring portion comprises an optical measuring device.

5. The apparatus claimed in claim 4, wherein said optical measuring device comprises an upright optical cylinder defined in a bock material between an upper opening and a lower opening having a larger diameter than that of said upper opening formed therein, said upright optical cylinder having a tapered reflective wall, said upper opening being adapted to receive a bottom portion of said first well of each cartridge, a filter disposed below said lower opening of said upright optical cylinder and an upright photo multiplier disposed below said filter for detecting luminance of said first well.

6. The apparatus claimed in claim 1, wherein each cartridge is a resin mold including a rectangular plate portion having opposite notched ends and said at least two wells are positioned side by side along a longitude of said rectangular plate portion and extend downwardly therefrom, said first well of each cartridge being deeper than said second well of each cartridge.

7. The apparatus claimed in claim 6, wherein each cartridge includes a third well containing sample or diluent.

8. The apparatus claimed in claim 6 or 7, wherein said solid phase material comprises an inner wall of said first well of each cartridge.

9. The apparatus claimed in claim 6 or 7, wherein said solid phase material comprises beads.

10. The apparatus claimed in claim 6, wherein said labelling compound is an enzyme.

11. An automatic enzyme immunoassay apparatus comprising, in a first level, cartridge transportation means for transporting rectangular cartridges each having at least two successively arranged wells, a first one of said wells containing solid phase material carrying antigen or antibody and a second one of said wells containing enzyme labelled antigen or antibody, to a predetermined position in said first level one by one in sequence, and lift means for lifting up said rectangular cartridges transported thereto by said cartridge transportation means to a second level one by one;

and, in said second level, a reaction line movable steppingly with a predetermined interval for receiving said rectangular cartridges lifted up thereto by said lift means at a first position set along said reaction line, successively;

pouring means disposed at a second position set along said reaction line for aspirating sample from a sample cassette and pouring it to said first well of said rectangular cartridge moved to said second position;

stirring means disposed at a third position along said reaction line for mixing and stirring said sample, said solid phase material carrying antigen or antibody and said enzyme labelled antigen or antibody in said first well of said rectangular cartridge moved to said third position;

bind/free separation and washing means disposed in a fourth position along said reaction line for performing bind/free separation in said first well of said rectangular cartridge moved to said fourth position and for removing free components thereof;

means disposed at a fifth position along said reaction line for adding substrate to said first well to cause enzyme reaction;

optical measuring means for detecting reaction in said first well of said rectangular cartridge after a predetermined time from a start of said enzyme reaction in said first well of said rectangular cartridge, and cartridge disposer means for picking up said rectangular cartridge from said reaction line after said detection completes and disposing it.

12. A method of enzyme immunoassay measurement, comprising the steps of:

actuating a start button of an input portion of an apparatus to start a driving of a reaction line and to transport cartridges in a cartridge stocker one by one to a start position on said reaction line through a cartridge transportation mechanism and a cartridge lift mechanism;

breaking a seal of said cartridges at a first position on said reaction line successively through a seal breaker;

operating a selection button to select one of a plurality of programs stored in a program memory;

actuating an aspirating/pouring portion to pick up a chip, aspirate a sample therein and pour it into a first well of a cartridge at a second position on said reaction line;

after the chip is disposed, actuating said aspirating/pouring portion again to pick up another chip, aspirate a sample therein and pour it into a second well of said cartridge;

activating a first stirring portion to stir a mixture in said first well of said cartridge at a third position on said reaction line;

performing a B/F separation by a first magnetic B/F separator at a fourth position on said reaction line;

washing out non-reacted free substance by means of a first washing portion at a fifth position on said reaction line;

adding substrate to said first well by a substrate pouring portion and stirring in a second stirring portion at a sixth position on said reaction line; and

measuring a reaction optically by a measuring portion at a seventh position on the reaction line.

13. A method of enzyme immunoassay measurement, comprising the steps of:

actuating a start button of an input portion of an apparatus to start a drive of a reaction line and to transport cartridges in a cartridge stocker one by one to a start position on said reaction line through a cartridge transportation mechanism and a cartridge lift mechanism;

breaking a seal of said cartridges at a first position on said reaction line successively through a seal breaker;

operating a selection button to select one of a plurality of programs stored in a program memory;

actuating an aspirating/pouring portion to pick up a chip, aspirate a sample therein and pour it into a first well of a cartridge at a second position of said reaction line;

after the chip is disposed, actuating said aspirating/pouring portion again to pick up another chip, aspirate a sample therein and pour it into a second well of said cartridge at a third position on said reaction line;

activating a first stirring portion to stir a mixture in said first well of said cartridge at a fourth position on said reaction line;

pouring said sample into said first well of said cartridge at a fifth position on said reaction line;

performing a B/F separation by a first magnetic B/F separator at a sixth position on said reaction line;

washing out non-reacted free substance by means of a first washing portion at a seventh position on said reaction line;

adding substrate to said first well and stirring it at a seventh position on said reaction line; and

measuring a reaction optically by a measuring portion at a seventh position on the reaction line.

14. A method of enzyme immunoassay measurement, comprising the steps of:

actuating a start button of an input portion of an apparatus to start a drive of a reaction line and to transport cartridges in a cartridge stocker one by one to a start position on said reaction line through a cartridge transportation mechanism and a cartridge lift mechanism;

breaking a seal of said cartridges at a first position on said reaction line successively through a seal breaker;

operating a selection button to select one of a plurality of programs stored in a program memory;

pouring a sample into a first well of a cartridge at a second position on said reaction line;

stirring said first well at a third position on said reaction line;

performing a B/F separation and washing at a third position on said reaction line;

adding an enzyme labelled substance to said first well and stirring it at a fourth position on said reaction line;

performing a B/F separation and washing at a fifth position on said reaction line;

stirring said first well at a sixth position on said reaction line;

performing a B/F separation and washing at a seventh position on said reaction line;

adding a substrate to said first well and stirring it at an eighth position on said reaction line; and

measuring a reaction by a measuring portion at a ninth position on said reaction line.

15. A method of enzyme immunoassay measurement, comprising the steps of:

actuating a start button of an input portion of an apparatus to start a drive of a reaction line and to transport cartridges in a cartridge stocker one by one to a start position on said reaction line through a cartridge transportation mechanism and a cartridge lift mechanism;

breaking a seal of said cartridges at a first position on said reaction line successively through a seal breaker;

operating a selection button to select one of a plurality of programs stored in a program memory;

adding diluent to a second well of a cartridge at a second position on said reaction line;

pouring a sample into said second well of said cartridge at a third position on said reaction line;

pouring a portion of a diluted sample in said second well into a first well and stirring it at a fourth position on said reaction line;

performing a B/F separation and washing at a fifth position on said reaction line;

adding an enzyme labelled substance to said first well and stirring it at a sixth position on said reaction line;

performing a B/F separation and washing at a seventh position on said reaction line;

stirring said fist well at an eighth position on said reaction line;

performing a B/F separation and washing at a ninth position on said reaction line;

adding a substrate to said first well and stirring it at a tenth position on said reaction line; and

measuring a reaction by a measuring portion at an eleventh position on said reaction line.