Automated analyzer having magnetic isolation device and method using the same

• US 5,741,708 A
• Filed: 06/02/1995
• Issued: 04/21/1998
• Est. Priority Date: 03/04/1991
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Chiron Corporation (Bayer AG)
• Inventors: Whitesel, Mary Beth, Klingshirn, Frank C., Lewis, Scott C., Carey, Glen A.
• Primary Examiner(s): Le, Long V.
• Application Number:
  US08/460,091
• Time in Patent Office: 1,054 Days
• Field of Search: 422/63-67, 422/81, 422/100, 422/101, 422/102, 436/43, 436/47, 436/48, 436/49, 436/54, 436/174, 436/175, 436/177, 436/179, 436/180
• US Class Current: 436/49
• CPC Class Codes: B01L 2300/0854 Double walls
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: G01N 2035/00386 using fluid heat transfer medium
• CPC Class Codes: G01N 2035/00396 where the fluid is a liquid
• CPC Class Codes: G01N 2035/00524 Mixing by agitating sample carrier
• CPC Class Codes: G01N 2035/00752 bar codes
• CPC Class Codes: G01N 2035/0441 for samples
• CPC Class Codes: G01N 2035/0443 for reagents
• CPC Class Codes: G01N 2035/0465 Loading or unloading the conveyor
• CPC Class Codes: G01N 2035/0484 Belt or chain
• CPC Class Codes: G01N 2035/0486 Gearing, cams
• CPC Class Codes: G01N 2035/1025 Fluid level sensing
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• 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 35/021 having a flexible chain, e.g. "cartridge belt", conveyor for reaction cells or cuvettes
• CPC Class Codes: G01N 35/025 having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: G01N 35/1065 Multiple transfer devices
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 215/01 Fins
• CPC Class Codes: Y10S 215/03 : Medical
• CPC Class Codes: Y10S 215/08 : Mixing
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 : with step of insertion or removal from test line
• 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
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

An analyzer for performing automated assay testing. The analyzer includes a storage and conveyor system for conveying cuvettes to an incubation or processing conveyor, a storage and selection system for test sample containers, a storage and selection system for reagent containers, sample and reagent aspirating and dispensing probes, a separation system for separating bound from unbound tracer or labeled reagent, a detection system and date collection/processing system. All of the subunits of the machine are controlled by a central processing unit to coordinate the activity of all of the subunits of the analyzer. The analyzer is specifically suited for performing heterogeneous binding assay protocols, particularly immunoassays.

Claims

1. An automated analyzer having a cuvette conveyed along an event path, said analyzer comprising a means for isolating a detectable product, wherein said detectable product is present in said cuvette having a bottom wall, a side wall and an open top and said detectable product is formed by a reaction between a test sample, a labeled reagent and a solid-phase reagent which has paramagnetic particles, said means for isolating said detectable product comprising:

(a) first magnetic means along said event path for attracting said paramagnetic particles against the side wall of said cuvette, said magnetic means comprising a first upstream magnet for creating a first magnetic field at a first level along the side wall of the cuvette, and a second downstream magnet for creating a second magnetic field at a second level along the side of the cuvette which is below said first level for positioning said paramagnetic particles below an upper level of a re-suspend liquid;

(b) liquid evacuating means for aspirating a liquid from said cuvette while said paramagnetic particles are held against the side wall of said cuvette;

(c) liquid dispensing means which are located downstream of said magnetic means for dispensing the re-suspend liquid into said cuvette for re-suspending said paramagnetic particles in said re-suspend liquid,

(d) second magnetic means disposed proximate said liquid dispensing means for assisting migration of said paramagnetic particles into said re-suspend liquid, and

(e) control means including a central processing unit for coordinating said liquid evacuating means, said liquid dispensing means and means for conveying said cuvette along said event path.

2. The analyzer as recited in claim 1, wherein said re-suspend liquid is an acid solution.

3. The analyzer as recited in claim 1, wherein said means for isolating said detectable product further comprises:

(a) wash apparatus for dispensing a wash solution into said cuvette after evacuation of said liquid while said paramagnetic particles are attracted against the side wall of the cuvette by said first magnetic means, and

(b) wash evacuating means for aspirating said wash solution while said paramagnetic particles are held against the side wall of said cuvette.

4. The analyzer as recited in claim 3, wherein the side of said cuvette has a first side wall portion and a second side wall portion which is opposite said first side wall portion and said paramagnetic particles are drawn by said first magnetic means against said first side wall portion, and, wherein said wash apparatus is a fixed nozzle which is positioned above the top opening of said cuvette for directing said wash solution against the second side wall portion of the cuvette.

5. The analyzer as recited in claim 3, wherein said wash apparatus comprises:

(a) a fixed support at one side of said event path,

(b) a carriage which is mounted on said fixed support for vertical movement between an upper position and a lower position,

(c) a vertically extending aspirating and dispensing probe which has a bottom free end and which is mounted on said carriage so that the bottom end of said probe is above said cuvette when said carriage is in its upper position and down to the bottom wall of said cuvette when said carriage is in its lower position, and

(d) drive means for selective moving said carriage vertically between said upper and lower positions for lowering said probe into said cuvette when the cuvette is positioned beneath said probe.

6. The analyzer as recited in claim 5, wherein said probe is mounted on said carriage for limited vertical movement relative to the carriage between a top position and a bottom position and is biased to said bottom position which enables said carriage to be lowered to bring the bottom end of the probe to the bottom wall of the cuvette and an additional motion which causes the probe to move upwardly relative to the carriage to insure that the bottom end of the probe always reaches the bottom wall of the cuvette and to insure complete aspiration of said wash solution.

7. The analyzer as recited in claim 1, wherein said liquid evacuating means comprises:

(a) a fixed support at one side of said event path,

(b) a carriage which is mounted on said fixed support for vertical movement between an upper position and a lower position,

(c) a vertically extending dispensing probe which has a bottom free end and which is mounted on said carriage so that the bottom end of said probe is above said cuvette when said carriage is in its upper position and down to the bottom wall of said cuvette when said carriage is in its lower position, and

(d) drive means for selective moving said carriage vertically between said upper and lower positions for lowering said probe into said cuvette when the cuvette is positioned beneath said probe.

8. The analyzer as recited in claim 1, wherein the side wall of said cuvette has a first side wall portion and a second side wall portion which is opposite said first side wall portion and said paramagnetic particles are drawn by said first magnetic means against said first side wall portion, and wherein said liquid dispensing means is a fixed nozzle which is positioned above the top opening of said cuvette for directing said re-suspend liquid against the second wall portion of the cuvette.

9. A method of evacuating liquid from a cuvette in an automated analyzer having a cuvette conveyed along an event path, said analyzer comprising a means for isolating a detectable product, wherein said detectable product is present in said cuvette having a bottom wall, a side wall and an open top said detectable product is formed by a reaction between a test sample, a labeled reagent and a solid-phase reagent which has paramagnetic particles, said method comprising:

(a) attracting the paramagnetic particles of said reagent against the first side wall of the cuvette by first magnetic means, said first magnetic means comprising a first upstream magnet for creating a first magnetic field at a first level along the side wall of the cuvette and a second downstream magnet for creating a second magnetic field at a second level along the side of the cuvette which is below said first level for positioning said paramagnetic particles below an upper level of a re-suspend liquid;

(b) evacuating the liquid from said cuvette while said paramagnetic particles are held against the first side wall of the cuvette,

(c) dispensing the re-suspend liquid into said cuvette after aspiration of the test sample, labeled reagent and solid phase reagent mixture for re-suspending said paramagnetic particles,

(d) assisting migration of said paramagnetic particles into said re-suspend liquid by second magnetic means disposed proximate said liquid dispensing means, and

(e) control means including a central processing unit for control means including a central processing unit for coordinating said evacuating means, said liquid dispensing means and means for conveying said cuvette along said event path.

10. The method as recited in claim 9, wherein said re-suspend liquid is an acid solution.

11. The method as recited in claim 9, wherein said method further comprises:

(a) dispensing a wash solution into said cuvette after evacuation of said liquid, and

(b) evacuating said wash solution from said cuvette while said paramagnetic particles are held against said first side wall by said first magnetic means.

12. The method as recited in claim 10, wherein said wash solution is directed against the second side wall of the cuvette.

13. The method as recited in claim 9, wherein said re-suspend liquid is directed against the first side wall of the cuvette for washing the paramagnetic particles from the first side wall of the cuvette.