WO2002037078A2

WO2002037078A2 - Automated immunoassay analyzer and method of using the same

Info

Publication number: WO2002037078A2
Application number: PCT/US2001/030341
Authority: WO
Inventors: Douglas R. Olson; Arthur L. Babson
Original assignee: Dpc Cirrus, Inc.
Priority date: 2000-10-31
Filing date: 2001-10-01
Publication date: 2002-05-10
Also published as: WO2002037078A3; AU2001294832A1

Abstract

An automated immunoassay analyzer which utilizes a magnetic field in combination with hydrodynamic forces generated by centrifugal action to efficiently separate a reaction mixture from a test sample. The automated immunoassay analyzer has a tube wash system. The tube wash system includes a drive shaft and a chuck coupled to the drive shaft. A waste chamber surrounds the chuck and includes an opening for accommodating a reaction tube. An elevating means is positioned below the waste chamber and is capable of lifting and lowering the reaction tube into the waste chamber. A housing for accommodating a magnet is also lifted and lowered by the elevating means. The method of use includes spinning the reaction tube while providing a magnetic attraction between an analyte bound magnetic support material and a magnet housed within the housing in order to retrain the analyte bound magnetic support material within the reaction tube during washing.

Description

AUTOMATED IMMUNOASSAY ANALYZER AND METHOD OF USING THE SAME

DESCRIPTION

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention generally relates to an automated immunoassay analyzer and, more particularly, to an automated immunoassay analyzer which utilizes a magnetic field in combination with hydrodynamic forces generated by centrifugal action to efficiently separate a label bound to a magnetic support material from an unbound label.

Background Description

An immunoassay is a well known laboratory method used to determine the amount of an analyte in a sample such as plasma or urine. This laboratory method is based on the interaction of antibodies with antigens, and because of the degree of selectivity for the analyte (either antigen or antibody), an immunoassay can be used to quantitatively determine very low concentrations of drugs, hormones, polypeptides, or other analyte compounds found in a test sample.

For many years, immunoassays were performed by hand by trained laboratory technicians. However, many companies have begun producing automated immunoassay analyzers to perform these immunoassays procedures.

Automating the immunoassay procedures can be onerous due to the large number of steps needed to be executed in order to complete these tests. By way of illustrative example used in a conventional scheme, a sample is first mixed with a reagent and a solid support having a bound antigen or antibody. The sample is then incubated so that the corresponding antigen or antibody in the sample and a labeled antigen or antibody provided in the reagent can be bound to the antigen or antibody on the solid support. Then, the solid support is thoroughly washed and the label (fluorescent, radioactive, chemiluminescent, or the like) is detected by an appropriate mechanism. Finally, the analyte of interest (antigen or antibody) is quantified from the detected label.

Most of today's automated immunoassay analyzers are designed for "walk away" operation, where the technician loads sample containing tubes onto a carousel and presses a start button. Thereafter, the automated immunoassay analyzer mixes appropriate reagents (often stored aboard the analyzer) with the sample, performs incubating and washing operations, detects the label, and computes the quantity of analyte in the sample from the detected label and stored calibration curves. The entire operation is typically done under computer control, and in some automated immunoassay analyzers, bar coding is used to identify the sample under test. The results of the immunoassays are typically output onto computer paper for inspection by the technician, or they can be monitored and displayed in real time as described in U.S. Pat. No. 5,316,726 to Babson et al. The immunoassay instrument described in U.S. Pat. No. 5,316,726 employs assay tubes that are preloaded with the immunoassay beads before the tubes are placed on the instrument.

Another automated immunoassay instrument is described in a trade brochure published by Olympus (Biomedical Products Division), Wendenstrasse 14-16, 2 Hamburg 1, Germany, describing an automated enzyme immunoassay analyzer under model no. "PK310", which is a sequential batch-processing system using a reaction disc containing U-shaped reaction tubes. A bead storage unit is included on-board the instrument for loading of assay tubes on the instrument comprising a plurality of bead cassettes mounted on a carousel. Each bead cassette stores a plurality of solid support beads as a column on a spiral track, where the beads exit the bottom of the spiral track into an open-air holding holder adjoining the outside of the base of the bead pack. The dispensed beads are picked up by a vacuum-operated bead transport for feeding into a U-shaped reaction tube.

Another recent advance in automated immunoassay instruments is disclosed in U.S. patent No. 5,885,530 to Babson et al., incorporated herein by reference in its entirety. This system can perform high volume testing on a broad range of analytes while selecting from among a diverse set of immunoassays for any given sample. This immuno analyzer instrument is capable of storing a wide variety of different types of reagents and heterogenous immunoassay beads, and further allows for reduced user interface (e.g., tests are performed automatically from computer input). This most recent immunoassay instrument includes a carousel which is capable of supporting a plurality of bead packs and dispensing the beads into a reaction tube. The reaction tube can be transported to a pipetting station where reagent and sample can be introduced. After an incubation interval, the reaction tube is then transported to a spin and wash station which uses centrifugal forces to expel the reaction mixture from the tube. The bound antigen or antibody (bound to the beads) of the test sample can then be detected and quantified.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an improved automated immunoassay analyzer.

It is another object of the present invention to provide an automated immunoassay analyzer having a wash and spin mechanism which utilizes a magnetic field in combination with centrifugal forces to separate waste fluid from a test sample (suspended medium).

According to the invention, an improved automated immunoassay analyzer is provided. The inventive automated immunoassay analyzer allows for loading and specimen extraction from the original sample tubes loaded directly on-board the instrument, wherein a wide variety of different types of tests can be performed on any given sample by the provision of a support material pack carousel and a reagent carousel. The automated immunoassay analyzer is computer controlled to allow automated picking, choosing and combining among the various support medium (e.g., magnetized beads, micro, particles or ferro-fluids) and reagents with a sample on-board the instrument to conduct the test(s) desired for each sample. The automated immunoassay analyzer has several computer controlled stations for performing many tasks such as, for example, mixing, washing and incubating and detection of test samples. In the washing operations, a washing station includes a spinning mechanism used in conjunction with a magnetic field for effectively separating and extracting waste fluids from the sample test.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, aspects and advantages will be better understood from the following detailed description of a preferred embodiment of the invention with reference to the drawings, in which: Figure 1 is a generalized block diagram of the automated immunoassay analyzer;

Figure 2A is a plan view diagram of the flow path of samples and assays through the automated immunoassay analyzer;

Figure 2B is a partial schematic view diagram of the flow path of samples and assays through the automated immunoassay analyzer;

Figure 3 is a flow chart of the processing steps performed on the assay tubes in the automated immunoassay analyzer;

Figure 4 is a cross sectional view of a holder for housing a ring magnet or magnetic array used in a tube wash system of the automated immunoassay analyzer;

Figure 5 A is a fragmentary cross-sectional side view of a reagent container with re-sealable lid used with the automated immunoassay analyzer;

Figure 5B is a top view of the reagent container with re-sealable lid of Figure 5A; Figure 5C is a rear view of the reagent container and re-sealable lid along the direction 5—5 indicated in Figure 5B;

Figure 5D is a fragmentary top view of the lid means;

Figure 5E is a fragmentary side view along direction 5'— 5' of Figure 5B of the of the self-sealing horizontal arm of the lid means and ramp guide means system;

Figure 5F is a fragmentary end view of along direction 5"— 5" of Figure 5B showing an interlocking ramp guide means and horizontal arm system for the lid means;

Figure 5G is a side exterior view of a reagent container with a re-sealable lid in a closed position;

Figure 5H is a side exterior view of a reagent container with a re-sealable lid in an open position;

Figure 51 is an isometric plan view of a reagent chamber for insertion into the reagent container;

Figure 5J is a top view of the reagent chamber of Figure 51;

Figure 5K is a cut-away view of the reagent chamber along line 5"'-5'" of 5J;

Figure 6 is a cross-sectional view of a sample dilution well system; Figure 7 A is an enlarged fragmentary cross-sectional side view of the assay tube (reaction tube) used in the tube wash system of Figure 8 A;

Figure 7B is a top view of the assay tube of Figure 7 A;

Figure 7C is an enlarged view of encircled area R in Figure 7 A;

Figure 7D is a side view of an alternative assay tube; Figure 8 A is a cross-sectional side view of a tube wash system of the invention in a nonengaged status with an assay tube;

Figure 8B is a cross-sectional side view of a tube wash system of the invention in an engaged status with an assay tube;

Figure 8C is an enlarged bottom view of a drive chuck used in a high speed spinning station of a tube washing station of the invention;

Figure 8D is a top perspective view of the drive chuck of Figure 8C; and

Figure 8E is a top perspective view of a tube holder used to support the bottom of an assay tube during washing in a tube washing station of the invention.

DETAD ED DESCRD?TION OF A PREFERRED EMBODIMENT OF THE INVENTION

The present invention is directed to an analytical instrument capable of producing reportable assay results through the processing of specimens and various other components of the chemistry system. This analytic instrument involves the control and timing of various internal operations as well as the acquisition and processing of data generated internally or through interaction with an external computer system (such as LIS). The analytic instrument of the present invention is an integrated electromechanical apparatus which processes specimens in order to generate test results. It should be well understood by those of ordinary skill that many different constituents in the sample can be tested by immunoassay by the present invention, depending on the selection of the biomaterial bound to the inert support (e.g., support material) in the assay tube.

Figure 1 shows a generalized block diagram of the automated immunoassay analyzer of the present invention. The automated immunoassay analyzer includes an instrument 10 capable of performing immunoassays on multiple samples. The instrument 10 is connected to a computer 12 via data communication lines 14. The data communication lines 14 are used to supply information from the instrument 10 to the computer 12. This information may include, for example, bar coded information on sample tubes, reagent supply packs, and support material supply packs on-board the instrument 10 as well as photon counts measured by a photomultiplier tube. The instrument 10 is preferably operated under the direction of on-board microprocessors (not shown). The computer 12 is connected to a display 16 which presents the operator with a status report on all tests ordered and operations occurring within the instrument 10. The display 16 is also capable of displaying operator commands and data collected from the instrument 10. A keyboard 18 or other user interface is connected to the computer 12, and is used to input patient information, desired tests and a host of other relevant information. Figure 2 A shows a top view of the instrument 10 of the present invention. Specifically, a reaction tube, feeder/dispenser 201 is shown in communication with a reaction tube load chain 202. The reaction feeder/dispenser 201 is capable of (i) accepting reaction tubes in bulk in a hopper, (ii) orienting the reaction tubes and (iii) individually delivering the reaction tubes to the reaction tube load chain 202 via an elevator ladder means (not shown). The reaction tubes are disposable unit dose devices used by the instrument 10 to contain support material such as, beads or preferably, magnetized support material or other magnetized micro-particles or ferro-fluids (referred generally as "support material"), and reagents during processing operations. The reactions tubes also contain sample/reagent mixtures during sample pre-treatment operations. As such, all transportation, incubation, separation and signal generation steps for all tests are carried out in these reaction tubes .

Still referring to Figure 2A, the reaction tube loader chain 202 is a chain having arcuate, horizontally oriented arms 202a that accept the reaction tubes from the reaction tube dispenser 201. The reaction tubes are supported on the oriented arms 202a by flanges 746 integrally formed at the top of the reaction tubes (see, Figure 7A). The reaction tube load chain 202 transports the reaction tubes first under a tube outlet where support material dropped by gravity after being dispensed from a support material dispenser and carousel 203 (bead carousel).

The bead carousel 203 supports a plurality of support material (bead) packs 203a, 203b, 203c, each capable of holding a large number of beads. The bead packs are capable of dispensing a single bead at a time, and an individual bead pack typically will contain a single type of bead which is suitable for use with a variety of different reagents. More than one bead pack of a given type of support material can be resident on the instrument 10, simultaneously. This allows for selection among the different types of stored beads. The support material involves a biomaterial used to quantitate analytes in solution that is bound to an inert support body. The biomaterial generally is selected from an antigen or an antibody. Generally, either one bead or a single known type of support material is consumed for each test conducted, and a particular type of bead or other support material may be used for any number of different assay types. However, a plurality of micro beads, each with bound binding agent could also be used with the present invention. The support material may also be a magnetized micro- particle (on the order from 1 micron to 10 microns) or magnetic ferro-fluids (150 nanometers or smaller). (Hereinafter, support material will be generally used to represent beads, magnetic beads, magnetic micro-particles or magnetic ferro-fluids and the like.) The magnetic micro-particles are dispensed by the reagent pipettor 205. Vertically oriented bar codes may be provided on the outer periphery of all bead packs which will be accessible for reading by a dedicated CCD bar code reader 212 for the bead carousel 203. The entire bead carousel 203 is housed within a dehumidified chamber maintained at about 10% relative humidity. Thus, the support material is originally separate from the reaction tubes, not pre- assembled, and the support material is selectively added to the reaction tubes , depending upon which test is ordered for a sample. After a single type of support material is fed to the reaction tube , the reaction tube load chain 202 advances the reaction tube to a position a reaction tube pipetting station 204. At the reaction tube pipetting station 204, reagent and (diluted) sample can be introduced via a reagent pipettor 205 and sample pipettor 206, respectively, to be combined with the dispensed support material at the bottom of the reaction tube . The positioning of the reaction tube at reaction tube pipetting station 204 is accomplished by pushing the reaction tube into a reaction tube processing side chain 213b of a reaction tube processor 213 via a reciprocal plunger. Figure 2 A further shows a rotatable sample carousel 207 which accommodates a plurality of easily removable tube racks 208. The removable tube racks 208 are each capable of holding a plurality of sample or diluent test tubes 208a. Deionized water or a protein diluent can be used as the sample diluent. Vertically oriented bar codes can be provided on the outer sidewalls of all sample tubes 208a which are accessible for reading by bar code reader 210 during a rotation of the sample carousel 207. The bar codes on the sample tubes 208a are manually rotated by an operator so as to be exposed to and read by the bar code reader 210 before operation of the instrument 10 in the automated mode. This procedure inventories the samples and locations thereof on the sample carousel 207. The bar code reader is preferably a scanning laser bar code reader which can read specimen and diluent bar codes on the sample carousel 207 and reagent bar codes on the reagent carousel 209.

The individual arcuate sample racks 208 are loaded upon a sample carousel platform 207a to effectively position the sample tubes 208a. This positioning of the sample tubes 208a effectively permits an unobstructed optical line between the bar codes and the bar code reader 210. The sample tube holders 208b, e.g., hollow sleeves having resiliently-biased tube gripping means, also have a slit in the sleeve wall to expose the bar code on the sample tube 208a. The sample carousel 207 includes a gap 207b through which the bar code reader 210 can scan the reagent carousel 209 located within the sample carousel 207.

The sample (and its diluent) pipettor 206 has a downward projecting pipette tip (not shown) positioned at the end of a pipette arm which can be actuated to travel both vertically (i.e., perpendicular to the plane of the paper) and circularly in arcuate swaths (i.e., along the plane of the paper) (see, Figure 2B). The amount of Z-axis translation of the sample pipettor 206 is closely controlled by a level sensing scheme (not shown) so that the sample pipettor 206 can be assured of dipping enough into the sample or diluent to siphon up the correct amount of fluid, but shallow enough not to damage the operations of the sample pipettor 206 or corrupt the sample pipettor 206 with fluid which may be carried over to the next tube. The sample pipettor 206 has an arc of motion which permits the sample pipettor 206 to intersect and travel to and from (i) the sample tubes and diluent tubes when located at the sample pipetting station 206b on the sample carousel 207, (ii) the sample dilution well 211, (iii) the reaction tube pipetting station 204 where reagent and (diluted) sample are introduced via the reagent pipettor 205 and sample pipettor 206, respectively, and (iv) the probe wash station 206a where water can be pumped through the inside of the sample pipette 206 to flush out the pipette interior and water also is rinsed over the exterior surfaces of the pipette tip after execution of any or each of operations (i), (ii) and/or (iii). Sample tube elevation sensors 206c preferably can be provided as indicated in Figure 2A, and can be photoelectric sensors used to detect the height of the sample tube at the sample pipetting station 206b. Also at the sample pipetting station 206b, clot detection can optionally be performed on the sample by the sample pipettor 206 using a pressure transducer and an analog-to-digital signal conversion scheme such as those generally known in the field. If the sample fails the clot detection test, the sample can be defaulted and its test discontinued by the computer control.

The sample dilution well 211 is a device in which a mixing tube is set in rotation and which rapidly mixes quantities of sample, diluent and water to form a homogenous mixture. These materials are added to the dilution well 211 by the sample pipettor 206, and mixing is accomplished by agitation of the dilution well

211. In turn, disposal of excess mixture from the dilution well 211 is accomplished by rotating the well 211 at high speeds.

Still referring to Figures 2A and 2B, the reagent carousel 209 is a rotatable carousel which accommodates a plurality of wedge-shaped reagent packs 209a, 209b, 209c, and so forth, each capable of holding a plurality of different reagents in separate compartments formed in each pack. The immunological reagents are in liquid form and consist of compounds which recognize specific analytes coupled to one of the labels bound to the support material. Three compartment wedges are shown in Figure 2A. The packs have self-sealing covers, as well as vertical bar codes on the outer periphery of the reagent packs which are accessible for scanning by the sample and diluent bar code reader 210 through the sample carousel gap 207b. The entire reagent carousel 209 is housed within a stationary refrigerated chamber (not shown) maintained at about 4°C. The chamber will include a sidewall opening, such as filled with a window, on the outer peripheral side of the reagent carousel 209 which permits the bar code reader 210 to read the bar codes presented on the outer peripheral sides of the reagent wedges as the bar code beam passes through the gap 207b in the sample carousel 207 (held stationary during inventory on the reagent carousel) and the window on the reagent carousel 209. The reagent chamber housing also will have a cover with holes which can be aligned with openings in underlying reagent wedge compartments to permit access by the reagent pipettor 205 through the reagent chamber cover. The reagent carousel 209 and sample carousel 207 each have a rotary drive. This arrangement allows either the reagent carousel 209 or sample carousel 207 to be individually rotated, for example, while the other is held stationary. This procedure allows inventory to be taken of either carousel, or to sequentially advance sample tubes around the sample carousel 207 to sample pipetting station 206b during automated assay mode, or to advance reagent wedges around the reagent carousel 209.

Referring still to Figures 2A and 2B, the reagent pipettor 205 also has a downward projecting pipette tip (not shown) positioned at the end of a pipette arm which can be actuated to travel both vertically (perpendicular to the plane of the paper) and circularly in arcuate swaths (along the plane of the paper). The reagent pipettor 205 has access to the reagent carousel 209, a reagent probe wash station 205a and reaction tube pipetting station 204 where the reagent is combined with the bead and sample in the reaction tube . The software of the computer 12 controls the sample pipettor 206 and reagent pipettor 205 to co-ordinate sequential deposits of fluids into the reaction tube at the reaction tube pipetting station 204. That is, if one pipette is detected as being situated over the reaction tube being fed at the reaction tube pipetting station 204, the other pipette will wait for the other pipette to clear the reaction tube before swiveling over the mouth of the reaction tube to deposit a contribution to the reaction tube .

After introducing the appropriate combination of sample and reagent into the reaction tube at the reagent pipetting station 204, the reaction tube is indexed once, i.e., moved 90 degrees, where the reaction tube is picked up and advanced by reaction tube processing main chain 213a of the tube processor 213. The reaction tube processor 213 comprises a serpentine channel 213' having a depth which permits flanges 746 of the reaction tubes 740 to rest on the top of the channel, and main chain 213a is a top track chain overlying and following the serpentine channel 213'. The main chain 213a has baffles (projections) (not shown) extending downward to contact and incrementally advance the reaction tubes through the serpentine channel 213'. In this way, the tube processor 213 transports the reaction tubes along a serpentine path for incubation of the tube contents and ultimately transfers the reaction tubes back to a side track chain 213b also located within the housing for tube processor 213. The side main chain 213b then conveys the reaction tubes to the wash station 214 or returns the reaction tubes to the beginning of the serpentine channel 213' for supplemental incubation. The side track chain 213b in the tube processor 213 is a track chain with arcuate arms that support the reaction tubes at flanges integrally formed at the top of the reaction tubes, similar to chain 202. The residence time for the reaction tubes in the tube processor 213 for a single pass is preferably about 30 minutes and tube processor 213 is heated to 37°C.

In one preferred arrangement, a plurality of reciprocating bars are used as reaction tube shaker bars (not shown), which are located on the bottom of the tube pathways in the tube processor 213. The reciprocating bars are oriented at a direction parallel to the direction of travel of the reaction tubes in the tube processor 213. These reciprocating (shaker) bars can bump the bottom portions of the reaction tubes and thereby continuously agitate the reaction tube contents to promote the immunological reactions.

After leaving the serpentine channel 213', the side chain 213b picks up the reaction tube at the end of the serpentine channel 213'. The main chain 213a circles back to a starting point 90° from the reaction tube pipetting station 204 (see Figure 2B) having chain movement direction arrows provided. If additional incubation is desired for a sample, the chain 213b is used to circle the reaction tube back to the beginning of the serpentine channel 213'. On the other hand, if the reaction tube needs to be advanced to wash and photometric analysis, the reaction tubes are shuttled out of the tube processor 213 and are picked up by a circular chain and moved to a high speed spin wash station 214. As discussed in more detail with reference to Figures 8A-8E, the wash station is capable of washing beads (such as 1/4 inch beads) as well as micro-particles and ferro-fluids. The wash station includes an angled, splined chuck surrounded by a holder and a tube elevating device. A ring magnet or an array of magnets is housed in the tube elevating device and a reaction tube is placed proximate to the ring magnet or array of magnets. The reaction tubes are first elevated onto the chuck and after several seconds of delay to allow the particles to collect on the inner wall of the tube, then rotated about the longitudinal (vertical) axes at high speed, whereby the ring magnet or array of magnets will create a magnetic field which will retain the magnetized beads or magnetized micro-particles or ferro-fluids in the reaction tube while the remaining waste fluids climb up outwardly tapered inside walls of the reaction tubes under centrifugal forces thereby expelling the waste fluids along the grooved chuck. In this manner, the immunoreactive bead(s) or magnetized micro-particles or ferro-fluids (support material) are retained within the reaction tube. The waste fluids drain into the liquid waste holder. Washing is accomplished by the addition of water into the tube one or more times to the reaction tube during, or followed by, high speed centrifugation. After washing the support material at the wash station 214 and expelling fluid contents of the reaction tube, the reaction tubes are either (i) shuttled out of the wash station onto a luminometer chain 215a of a detection station 215 where a substrate is added and quantification made of the analyte of interest or (ii) returned to the reaction pipetting station 204 by the side chain 213b where more reagent(s) is added, if necessary for the assay, before the steps of incubation and wash are repeated. The luminometer chain 215a transports the reaction tubes from the wash station 214 to a photo-multiplier tube (PMT) 216a at a reaction tube reading station 216 of detection station 215 for photometric reading. The chain 215a then moves the now assayed tube and the contained contents to waste. In the detection station 215, the luminometer chain 215a is a side link chain including lower reciprocating shaker bars, similar to those used in the tube processor 213. The detection station 215 includes an incubator and luminometer block heaters for heating the tube contents after addition of substrate.

In the preferred embodiment, chemiluminescent techniques are used to quantify the analyte. Signal generating chemistries for chemiluminescent techniques include one of either of two formats, each of which cause emission of light from the surface of the processed analytical elements (support material) to produce varying light intensities in response to the concentration of a sample analyte to be quantified. These two different chemistries require the following signal generating reagents stored aboard the instrument 10: (i) chemiluminescent enzyme substrate stored in reservoir 215b for the first chemistry, and (ii) first and second trigger reagents stored in reservoirs 218a and 218b for the second type of chemistry. Thus, depending on the chemistry employed by a particular bead (or micro-particles or ferro-fluids), appropriate signal reagents will be added to its reaction tube. For instance, the three signal reagents can be used with each being pumped by a separate, independently controlled solenoid pump at pumping station 220. Each pump is connected to one of three spigots (not shown) which reside over various sites on the luminometer chain 215a.

In the first chemiluminescent technique, alkaline phosphatase substrate is used by the present invention. Where the support material employs the alkaline phosphatase label, it will receive chemiluminescent substrate in the first luminometer chain position proximal to the tube wash station 214. The second type of test involves use of acridinium ester with injection of trigger reagents into the reaction tube at the reading station 216 and making an unattenuated count. Of these two chemistries, it is preferred to label the assay specific antigen or antibody in the reagent with alkaline phosphatase which will cleave a phosphate ester stabilized dioxetane. Decomposition of the dioxetane results in the emission of light photons which can be quantified at detection station 215 and are proportional to the quantity of analyte present. The light signal emitted from the bound labeled analyte on the inert support material in the reaction tube is measured and the quantity or analyte determined by the computer 12 by reference to an appropriate standard curve. However, it should be understood by those of skill in the art that other detection schemes such as fluorescence or radioactive ion emission could be used and appropriate labeling of reagent is required. The reaction tube, as containing the washed support material and substrate solution (e.g., chemiluminescent alkaline phosphatase substrate), is incubated on the luminometer chain 215a for about 5 minutes at 37°C and advanced to a position in front of the photomultiplier tube 216a where photon counts are measured. The PMT 216a is part of the reaction tube reading station 216 which also includes a luminometer shutter and attenuator wheel of the types as disclosed in U.S. Pat. No. 5,316,726, which description is incorporated herein by reference. Again, the reaction tube reading station 215 employs the PMT 216a to take light emission measurements on reaction tubes as they pass. A shutter (not shown) is employed to prevent crosstalk between adjacent tubes at the PMT station. This shutter device physically isolates the tube at the PMT 216a from those surrounding the PMT 216a. A rotatable filter (attenuator) wheel (not shown) is mounted between the PMT 216a and the reaction tube position in reaction tube reading station 216 when being read for photon counts. This wheel has three positions including (i) dark (PMT 216a receives no light), (ii) unattenuated (PMT 216a receives full light output of the reaction tube), and (iii) attenuated (a neutral density filter that is positioned between the PMT 216a and reaction tube to make attenuated counts). The features of such shutters and filter wheels are fully disclosed in U.S. Pat. No. 5,316,726. For example, a filter wheel can have three sections including (i) an open section for making unattenuated counts, (ii) one or more neutral density filter sections for making attenuated counts, and (iii) an opaque section for making dark count measurements to calibrate "noise" in the PMT 216a. Photometric data can be gathered by measuring the PMT dark counts and taking an attenuated count (known as the precount), and determining whether the precount value is above or below a preset cutoff value to determine whether an unattenuated measurement may be needed if the precount is below a cutoff value.

The average photon counts per second are converted to analyte concentration by the computer 12 using standard curves which mathematically relate photon counts to concentration. The photon count and concentration information for each reaction tube is archived to a magnetic storage device for. later analysis. The concentration for the reaction tube is also sent to display 16 of the computer 12. Periodic calibration with known calibrating solutions maintains the mathematical relationship for a particular instrument 10 and lot of reagents. Calibration of the standard curves may be performed according to protocol such as described in U.S. Pat. No. 5,316,726, which description is incorporated herein by reference.

Fluidic systems are provided throughout the instrument 10 as a system of pumps, valves, tubing and reservoirs adequate to provide for the transfer and disposal of fluids, as needed, throughout the instrument 10. Among these, the pumps include several positive displacement pumps 217a, 217b used in conjunction with the reagent and sample pipettes to permit withdrawing and feeding of precise amounts of sample and reagent. By way of example, the substrate reservoir 215b stores the chemiluminescent substrate which is pumped via injector pump 219 to the first chain position on luminometer chain 215a at detection station 215 via tubing lines (not shown). Liquid waste drained from the dilution well 211 and wash station 214 are collected on-board the instrument 10 in a liquid waste reservoir stored aboard the instrument 10 for appropriate disposal, and the reaction tube and the contents thereof including the support material and any liquid are collected from detection station 215 after completion of the photon count in a solid waste reservoir aboard the instrument 10 for appropriate disposal.

Other supporting fluid management equipment such as tubing lines, and so forth, is not shown for purposes of simplifying the illustration of the present invention. The computer control 12 allows the operator to pick the tests desired for each sample, and, if desired, to prioritize the sample if "stat" or unstable. A technician informs the computer 12 via keyboard input or other input means 18 of the relevant patient information and tests desired for each sample before placement of the sample tubes on the sample carousel 207. The location of the sample tube can then be tracked on the sample carousel 207 by the bar code of each sample tube. Similarly, the contents of each reagent wedge and bead pack are loaded into the computer's memory and the locations thereof can then be tracked about the respective carousels by the respective bar codes. The computer 12 can then instruct the instrument 10 to pick the appropriate support material and appropriate reagent, and place the support material in a reaction tube with a particular sample for assay. A system of logic circuitry, cabling, user input/output devices and software is provided for the computer 12, which accepts user commands and displays the results of those commands. Devices directly accessible to the user for managing the computer 12 can include a high resolution color monitor, keyboard, trackball, floppy disk drive, CD-ROM drive and speaker. A NDT can be included for the computer 12 that tracks the location and status of each sample (e.g., untested/test underway/ tested) intermittently, e.g., about every

18 seconds.

In preparing the instrument 10 for use, an operator first loads all required bulk materials into appropriate on-board storage areas including the reaction tubes, bead packs, reagent packs, bulk fluids including water, probe wash and bead wash solutions, and signal reagents including substrate and trigger reagents. Liquid and solid waste containers should be checked to determine if the containers need emptying. A work list is created either manually of through LIS download. The sample, diluent, and any control or adjustor containing test tubes are loaded onto the sample racks that are placed on the tube carousel, and all tubes are manually rotated so that their bar codes face outwards. Samples which require a known dilution are identified in advance, any samples requiring "STAT" priority handling are identified.

Inventory is automatically conducted on the test tubes in the sample rack, the reagent packs on the reagent carousel, and on the bead packs on the bead pack carousel, by rotating each respective carousel by its respective bar code reader to interrogate the contents aboard each of the sample, reagent and bead back carousels. The information from the bar code reader is sent to the computer 12 which tracks the position of all sample tubes 208a, reagent pack 209a, 209b, 209c, and so forth, and bead packs 203a, 203b, 203c, and so forth, within the instrument 12. Not all spaces on each carousel need to be filled since the bar code readers will simply identify an empty space on any of the sample carousel, reagent carousel, or bead pack carousel, to the computer 12. This will allow the computer 12 to track the empty space.

Position information can be derived and tracked with use of a shaft encoder (not shown) provided on the motor drive to counts steps of the motor such that the position of each sample tube, reagent pack, and bead pack is known by the instrument 10. In conjunction therewith, an internal optical sensor (not shown) formed of an emitter and detector pairing can be built into each carousel to reacquire and recognize, each time the instrument is started up, a fixed metallic reference point or "flag" in the device provided as a home or reference point from which motor steps can be counted from which to get to any position. In this way, the steps of the motor needed to move a sample tube to the sample pipetting station 206, or a reagent or diluent to the reagent pipetting station 204, or a bead pack to the bead dispensing position, can be managed by the instrument 10. Samples, reagents or bead packs can be replaced as needed during instrument operation.

After any interruption of the operation of the instrument, inventory is automatically taken again of the various sample rack, reagent pack, and bead pack carousels before testing is resumed. For example, whenever a pause command is hit by the operator at the computer control, or a seal is disrupted in the system, e.g., by opening the housing on the reagent carousel or bead carousel, the instrument 10, when placed back on-line, first re-inventories each of the bead carousel, reagent carousel, and sample carousel with the bar code readers to learn any changes possibly made. In this way, the location of each sample tube, or absence thereof (an empty space on the sample carousel 207a), is known by the system, and the reagent and bead packs present on the system are also known. This allows the computer 12 to know what and where items are on the instrument. The sample tubes are then assayed methodically in sequence around the carousel unless prioritization, e.g., for "STAT" or unstable samples, has been requested at the computer control by the operator.

Figure 3 illustrates the basic process steps performed by the instrument 10 of the automated immunoassay analyzer. First, at step 310, the sample (and any diluent tubes) is loaded into sample tube holder racks which are positioned on the sample carousel. Second, at step 312, the contents and carousel location of each the sample tubes, reagent packs, and bead packs are determined by bar code readers. At step 314, a portion of sample is withdrawn from a sample tube and mixed with diluent in the dilution well to form a homogenous mixture. The dilute sample is then combined with reagent and a support material such as the magnetized bead or magnetized micro-particles or ferro-fluids at the reaction tube pipetting station in step 316. At step 318, the reaction tubes in which sample and reagent have been combined with the support material are incubated. The time of incubation is determined by the dimensions of the incubation processor and time for incremental advancements in the analyzer. At step 320, the reaction tubes which have been incubated for the requisite period of time are transferred to a high speed washing station. Washing is achieved by rotating the reaction tubes about the longitudinal axes and by pipetting each water into the reaction tubes. High speed rotation of the tubes causes wash fluid to be rapidly removed from the inert support carrying the bound biomaterial which has the bound reagent label. The support material remains in the reaction tube due to a magnetic attraction between the magnetic ring or array of magnets and the magnetized support material. After completing washing in step 320, the reaction tube and inert bead support are free of unbound labeled reagent so that only bound labeled reagent will be detected. At step 322, a chemiluminescent substrate (e.g., phosphate ester dioxetane) is added to the assay tube, and the reaction tube is again incubated for a short time. During incubation, alkaline phosphatase from the reagent which is bound to the inert support cleaves the phosphate ester of the chemiluminescent substrate. Decomposition of the dioxetane releases photon energy, noting that the emitted light photons are proportional to the quantity of analyte present. After decomposition of the dioxetane, the photon emissions are counted at step 324 by a photomultiplier tube (PMT). At step 326, photon count information is sent to the computer for quantitative determination of the analyte.

While a sandwich type assay has been exemplified herein, the instrument 10 is amenable to different immunological chemistries for processing by the system, including any of the formats of sandwich assays, competition assays, or liquid phase capture assays. The system will support many different test categories, such as thyroid function, sex hormones, growth hormones, tumor markers, infectious diseases, allergy testing, immunoglobulin and related proteins and peptides, steroids and other small molecules, therapeutic drugs, drugs of abuse, and vitamins. The system will analyze samples of serum, plasma, or urine, and specific chemistry kits may also handle clarified cerebrospinal fluid or saliva.

The manner of handling certain conceivable errors in the practice of the assay on the inventive instrument is as follows. If there is a lack of required information, such as unreadable bar codes or the absence of information about which tests to run or how to run them, the analyzer can be programmed to verify the availability of all required information whenever the specimen carousel is accessed. If any information is found lacking, the operator may be alerted immediately by audible alarm or via on-screen display. As such, operators can expect the analyzer to process all on-board specimens before requiring further attention. Also, sample- specific fluidics problems could be encountered. These errors could involve insufficient sample or the presence of a clot in the sample.

Operators can be alerted immediately of such problems via both on-screen and audible alarms. However, the analyzer will continue to process other specimens while awaiting operator intervention. If there are hardware problems, such as fluidic component failures, clogged inlet filters, and so forth, operators can be alerted immediately of such via both on-screen and audible alarms. Until an operator intervenes, sampling operations should be suspended, but tube processor operations can continue.

The sample container rack of the invention allows the sample containers, as received, including sample containers received in nonuniform sizes, to be loaded directly into an automated analyzer without the need to devote time and effort to assessing the size of the original sample container or transferring the sample contents into a prescribed size of sample tube. To remove aliquots of sample from a sample container held in a holder of the rack, a downward projecting pipette (not shown) can be positioned at the free end of a translatable pipetting arm. To perform pipetting operations, the pipette tip must be inserted into and out of the sample tubes (and reagent containers) by moving the pipetting arm vertically down and then back up, respectively. The amount of vertical translation of the pipetting arm is closely controlled by a level sensing scheme (not shown) so that the pipetter can be assured of dipping into a sample container (or reagent container on a reagent carousel) far enough to siphon up the correct amount of sample or reagent, but shallow enough not to damage the operations of the pipetting station or corrupt the pipetter with sample or reagent which may be carried over to the next assay tube. A pair of precision syringe pumps can be connected to the pipetting station, where, preferably, one of the syringe pumps is calibrated for large volumes while the other is calibrated for small volumes. A probe wash station can be provided having separate wash wells for simultaneously flushing the inside and outside of the pipette tip. Extensive probe flushing on every pipetting cycle eliminates detectable sample carryover. The probe wash station should also have a fresh water supply. In a preferred embodiment, the pipetter may pick up one or more small air bubbles separated by water to aid in transfer of sample and reagent to an assay tube.

Vessels may be inserted manually into the racks which can accept a wide range of specimen containers. The vessels are then manually rotated until the bar codes on the vessels are visible through slots provided in each rack, and the rack is installed onto the sample carousel. Each rack can accept up to 15 specimens or more, and a plurality of racks, such as a total of up to six racks or more, may reside on the sample carousel at any time, depending on the relative sizing of the racks and carousel. As such, a total of up to 90 or even more specimens may be simultaneously resident on the analyzer using the rack system of the present invention. An operator may remove a rack from the analyzer at any time to supplement or replace the supply of specimens. For tracking purposes, each rack position should be designated, for example, as position A, B, and so forth, in both human and instrument readable forms. This information will be readily visible while looking at the sample rack carousel, and, preferably, will also be displayed graphically on a computer display screen. The display screen can also be programmed to include other details about specimen sampling in the software description documents, including, for example, which racks are present on the instrument; the location of these racks in relation to each other; the location on these racks of specimens and diluents; the locations of specimens which have been processed are thus no longer needed; the locations of specimens which cannot be used due to some error condition; and the operating status (whether racks may be accessed by the operator).

The analyzer instrument 10 can be provided with means to identify specimens either automatically via bar code or through operator input. In the former case, specimens will be identified by an accession number or other unique identification imprinted on a label in bar code format. To allow automated identification, the operator will need to first attach this label along a linear axis of the specimen tube and then insert the tube into a rack such that the label is visible. An on-board bar code reader can then be used to automatically associate the specimen with its location in a given rack. If bar codes are not available, the operator may install specimens into racks and then inform the computer controls of the analyzer of the appropriate accession numbers via keyboard and/or pointing device input.

Once specimens have been loaded in the sample container racks, and identified, the sampling process will entail the following steps: a) rotation of the sample carousel to position the selected specimen at the sampling position; b) identification of the specimen tube size; c) positioning of the sample probe at the specimen surface via level detection; d) withdrawal of an appropriate aliquot (e.g., about 5 to 100 μL); e) detection of probe clogging due to particulates or clots in the specimen; f) detection of other fluidic problems which might invalidate the current test; g) transfer of the aliquot to either a reaction tube or a sample dilution well as required; and h) washing of the sample probe in preparation for processing of the next specimen.

Operators may specify the order in which samples are processed. STAT specimens will always be processed first, while remaining samples may be handled in any of the following orders: a) sort by rack and by position within rack (default); b) process user designated priority tests first; c) sort by specimen accession number; or d) sort by test type.

In one mode of usage, the automated analyzer is programmed to prompt the operator to select a primary or secondary default tube type. In the former case, the tube length will determine the maximum depth at which the specimen surface should be located. If the fluid surface is not detected at or above this level, sampling of the specimen will be aborted. This will prevent contamination of the probe by either solids or RBC separation gel in the specimen tube. Where secondary is the chosen default tube type, the probe will travel all the way to the tube bottom in search of a fluid surface. Operators will be allowed to designate individual tubes as primary or secondary.

Also, it may be desirable to dilute specimens prior to assay at the request of the operator or automatically. This is accomplished via mixing of a specimen aliquot, water and quantity of a concentrated diluent in the sample dilution well described herein. Diluents, if so desired, can be supplied in screw-cap tubes accepted by the on-board specimen racks.

Figure 4 is a cross sectional view of a holder for housing a ring magnet or a magnetic array used in the tube wash system of the automated immunoassay analyzer. (The tube wash system is discussed in more detail with reference to Figures 8A-8E.) The holder is generally depicted as reference numeral 400 and includes a housing 402 which has a centrally located aperture 404 sized to fit a reaction tube (shown in Figures 7A-7D). A ring magnet 406 is fitted within the housing and preferably surrounds the centrally located aperture 404, although an array of magnets can equally be used by the housing 402. As discussed with reference to at least Figures 8A and 8B, the ring magnet 406 will surround a bottom portion of the reaction tube. (As discussed further in reference to Figures 8A and 8B, the magnets are powerful enough to hold magnetized support beads near a bottom portion of the tube during the washing stage). Rare earth elements such as neodimium-iron-boron or samarium-cobalt are preferred. Spacers 408 may be positioned within the housing 402 and are preferably used to adjust the height of the ring magnet 406. The spacers 408 may not be required if the ring magnet or array of magnets 406 are designed and positioned for a specific reaction tube or amount of support material placed within the reaction tube. A collar 410 is coupled to an upper portion pf the housing 402 above the ring magnet 406 for retaining the ring magnet 406 within the holder 400. A shoulder 412 is provided at a bottom portion of the housing 400 within the centrally located aperture 404. Referring to Figure 5 A, there is shown a reagent container 500 of the invention with a self-sealing lid mechanism 503 attached thereto. The container

500 itself has a reagent vessel 501 comprised of a plurality of separate reagent storing compartments or wells, indicated as three compartments in this example of 501a, 501b, and 501c. These compartments share a common cover 514, which provides compartment openings 508a, 508b, and 508c, respectively. The openings 508a-c have a size adequate to permit a reagent extracting pipette (not shown) to be introduced into and retracted from the compartment in an unencumbered manner. The reagent container can have any convenient geometric shape; however, the reagent container 500 preferably is provided in an overall wedge-like shape as shown in the top view of Figure 5 A. This shape of the reagent container shown in Figure 5 A allows a plurality of such reagent "wedges" to be situated side-by-side in a pie-like configuration on a carousel, thereby permitting a wide variety of reagents types to be accessible for immunoassay operations. Alternatively, the reagent compartments can be positioned in a linear array to provide a box-shaped reagent container. The reagent vessel 501 can be prepackaged with the compartments pre- filled with selected reagents deposited in the various compartments. The openings can be optionally pre-sealed with a detachable adhesive-coated metallic foil. The reagent container can be loaded on a reagent carousel (sealing foil removed (if any)), and then the lid means 503 attached to the exterior of vessel 501, in a manner described in greater detail below.

Importantly, the self-sealing lid means 503 automatically reseals the reagent container 500 between any intermittent reagent extractions from the container without the need for external force to be applied to effect re-closure. The lid means 503 is a molded plastic member with spring-like biasing force generated by a bend 516 located below the hinge 507. This arrangement compels the lid means to release any bias force by movement of the horizontal arm 506 along the x-direction towards projection 510 until caps 509a-c cover openings 508a-c to move lid means 503 (back) to a "closed" position (see Figure 5G).

When external force is supplied to the projection 510 in the x-direction adequate to overcome the normal bias force acting in the opposite direction, the arm 506 displaces rearward in the direction of hinge 507 until caps 509a-c are pushed far enough to horizontally clear the underlying compartment openings 508a-c. As can be more easily seen in Figure 5D, the lid caps 509a-c alternate with openings 515a-c. Depending on the location of arm 506, either the caps 509a-c or openings 515a-c can be aligned with the underlying openings 508a-c in the cover 514 of the reagent vessels. The caps 509a-c are sized slightly larger in diameter than openings 508a-c, respectively, such that the caps cover the openings when the lid means is in its normal position, versus its active position (described in greater detail below). As best seen in Figure 5D, a second hinge 513 is also provided at a location approximately midway between the opening 515a and the hinge 507. The hinges 507 and 513 can be formed as thinned portions in the lid means 503 during molding. The hinges 507 and 513 extend side edge-to-side edge and run perpendicular to the major length direction of the lid means 503. The first hinge 507 allows the arm 506 to generally slide forwards and backwards, and the second hinge 513 relieves stress created in the arm 506 when it is pushed backwards while traversing and restrained by the ramp guide means 551a, 551b (Figure 5E). This latter feature allows the arm 506 to retract along a horizontal line without tending to significantly arc (Figure 5H). Both of the hinges 507 and 513 are formed as thinned plastic regions in the arm molding which form flexure points along the arm 511 and arm 506, respectively. However, the thickness of the hinge(s) must be left sufficiently thick to prevent failure of the crimped or thinned hinge-like portion after only limited numbers of flexures.

The lid means 503 also is attached to the side wall 512 of the reagent vessel 501 at a lower end thereof. The lid means 503 can be preassembled with the reagent vessel or attached on site when used by the present invention. For example, when a fresh reagent wedge 500 is provided to a carousel of an immunoassay analyzer, the protective foil can be stripped from the upper surfaces of the openings 508a-c to expose the openings 508a-c, and the lid means 503 can be attached to the container before or after these steps.

Another aspect of the reagent container sealing system 503 is that the alternating caps 509a-c and the openings 515a-c in the horizontal arm 506 of the lid means 503 are maintained in translational alignment over the underlying openings 508a-c of the reagent vessel compartments by use of guide means (not shown in Figure 5 A for sake of clarity as to other above-discussed features). This arrangement restricts sideways movement of the horizontal arm 506 during its movement over the upper surface of cover 514.

As seen in Figure 5E, ramp guide means 551a and 551b are provided on the upper surface of cover 514. The ramps 551a and 551b, and corresponding lid projections 552a and 552b, are inclined at the same relatively small acute angle relative to the horizontal plane P extending coplanar with the upper flat surface portion of cover 514, such as inclined from the horizontal direction (i.e., the x- direction) at angle ranging from about 5° to 15°, and preferably about 10°. The direction of inclination of the ramp guide means 551a, 551b steeps up from the front F of cover 514 towards the rear RR of cover 514.

The acute angle established for the ramps 551a and 551b (and projections 552a and 552b) must be large enough such that as soon as the lid means 503 is pushed rightward along the x-direction via force applied at projection 510 (in the perspective of Figure 5), that the caps 509a-c of lid means 503 are contemporaneously translated upward up the ramps 551a and 551b and out of contact with the surfaces of the cap openings 508a-c of the cover 514. Thus, sliding friction between the cover 514 and the lid means 503 is avoided without resorting to a loose interfit of the lid means 503 and the cover 514. On the other hand, the acute angle α of the ramps 551a and 551b must not be set too large so as to make access difficult to the openings 509a-c of the cover 514 when the lid means 503 is pushed rightward along the x-direction via force applied at projection 510. That is, with an ever steeper angle for the ramps 551a and 551b, the horizontal profile of the openings 515a-c in the lid means 503 is diminished. The ratio of the vertical height H of the ramps 551a, 551b, relative to overall gap T between the arm 506 and the cover 514 (ratio H/T) is about 40-50%> for the highest point of each ramp and about 5.15% at the lowest end of each ramp. The arm 506, when horizontally displaced over the upper surface of the cover 514, is mechanically guided by ramp means 551a, 551b via downward projections 552a, 552b on the arm 505 having means to interconnect with the ramp means 551a, 551b while permitting inter-sliding movement along a single line of direction. For example, as shown in Figure 5F, interlockable hooks can be integrally formed on the ends of the projections 552a, 552b and the ramps 551a and 551b to allow slidable interfitting of these components. In more detail, the projection 552a actually is comprised of a pair of projections 152a and 152b located on opposite sides of the related cap 509a on arm 506. Similarly, the ramp guide means 551a, is comprised of a pair of upstanding members 151a and 151b extending from the cover 514 on either side of the cover opening 508a. The projection 152b, like the companion projection 152a, terminates in a downward projecting hook 521 which mechanically interfits with an upstanding hook or rail 511 formed in ramp guide portion 151b.

Therefore, when force is applied to the projection 510 in the x-direction by an operator or electromechanical actuator, the projections 552a and 552b will slide up ramp guide means 551a and 551b, respectively, avoiding sliding friction without resorting to loose interfit between the lid 503 and cover 514. Preferably, when access to the reagent compartments is desired, the projection 510 is horizontally pushed with adequate force to overcome the normal opposing bias force in the lid means 503 caused by the spring-arm 511 until the caps 509a-c in the arm 506 clear compartment openings 508a-c and openings 515a-c instead align over the compartment openings 508a-c. The lower end of arm 511 of the lid means 503 can be attached to the sidewall 512 of the reagent vessel by any convenient means. As one technique to attach the arm 511 of the lid means 503 to the inner vertical sidewall 512 of the reagent container 500 (Figure 5C) the inner vertical wall 512 of the reagent vessel 501 can have a sleeve 505 comprised of two upstanding walls 505a and 505b, which define an opening sized to receive tongue member 504 of arm 511 of lid

503, and a cover side 505c integral with side walls 505a, 505b which prevents movement of the arm off the sidewall 512. The tongue member 504 has a pair of prongs 504a and 504b that are normally biased outward in the y-direction, but which can be displaced inward in the y-direction by operator handling. Figure 5D is a fragmentary view of the lid means 503, where the labeled elements have the descriptions set forth herein. The prongs 504a and 504b of tongue 504 of the lid means 503, are inserted into the sleeve 505 through opening 513 to grip the respective walls 505a and 505b due to the outward spring-like bias of the prongs 504a and 504b, to thus attach the lid means 503 to the reagent vessel 501. Ribs or flanges (not shown) also can be formed on the inner sides of walls

505a and 505b of sleeve 505 to mechanically enhance the interlock between the tongue 504 and sleeve 505.

Figure 51 is an isometric plan view of a reagent chamber which can be inserted into reagent storing compartment or well 501a of the reagent vessel 501. The reagent chamber, depicted as reference numeral 530, is preferably insertable into the well 501a when micro-particles are used with the present invention. The reagent chamber 530 includes a rounded bottom portion 532 and baffles 534. The baffles 534 are preferably vertical baffles. The support material and more specifically the micro-particles are kept in suspension by rotating the entire carousel of the analyzer in preferably alternate directions in approximately 5° to

10° arcs of rotation every few seconds. The baffles 534 provide extra agitation for the suspension.

Figure 5J is a top view of the reagent chamber of Figure 51. As seen in this figure, the baffles 534 preferable extend from opposing inner surfaces 536 of the reagent chamber 530. Those of ordinary skill in the art can appreciate that other baffle arrangements may also be contemplated by the present invention such that additional agitation of the suspension may be accomplished.

Figure 5K is a cut-away view of the reagent chamber 530 along line 5"'-5'" of 5 J. In this view, it is noted that the baffles 534 may slope toward one another towards a bottom 538 of the reagent chamber 530. The baffles 534 may also be other shapes (which would provide a molding draft), and should thus not be limited to the shape as shown in Figure 5K. In one embodiment, the profile of the baffles should be higher than 5ml of volume of suspension; however, other heights are also contemplated for use with the present invention. The reagent wedges, i.e., "reagent packs", will simultaneously support a relatively large number of assay types, e.g., up to 24 or more, each requiring up to 3 or even more liquid reagents, without reduction of the on-board assay capacity of an automated chemical/bio chemical analyzer. The reagent packs of the invention also provide the ability to store and preserve reagents on-board an immunoanalyzer, for example, for relatively extended periods of time, e.g. one month, without detectable degradation. The reagent packs of the invention also permit reagents to be positively identified via an attached bar code. Also, the rotating carousel accommodates a plurality of wedge-shaped reagent packs, each reagent pack capable of holding a plurality of different reagents in different compartments thereof. These packs include instrument actuated covers as well as vertical bar codes which are accessible to the specimen and diluent bar code reader. The entire carousel is housed within a refrigerator chamber maintained at about 4°C.

By way of illustration, in immunoassay analysis, the reagents are supplied in liquid form, and are used to generate a detectable signal proportional or inversely proportional to the concentration of analyte in a specimen. During processing, they are deposited into individual reaction tubes associated with a bead having an appropriate biomaterial coated on its surface for the test needed on the sample. Reagents are contained within disposable packs, each bearing a plurality, e.g., up to three or more, different reagents in separate respective compartments.

These packs protect the contents therein from the environment by virtue of their instrument actuated lids and their construction from colored transparent materials. The packs are also constructed of a material, such as plastic, that is sufficiently translucent to permit operators to visually observe from the outside the fluid levels within the pack.

A plurality, e.g., up to 24 or more, of different reagent packs can be simultaneously resident on the analyzer instrument, and the operator may replace or supplement the supply of packs at any time. A quantity of reagent may be consumed from one or more of the chambers of a reagent pack for each test conducted. A particular reagent pack may be used for several different test types, but reagent/bead lot matching is required for each test type the reagent pack supports. A given test must use reagents from one type of reagent pack. More than one pack of a given type may be resident on the analyzer instrument simultaneously. Reagent packs serve the following functions:

a) to protect the reagents they contain from evaporation; b) to protect the reagents they contain from contamination; c) to package the reagents in a manner convenient for operator access and handling; d) to facilitate the dispensing of reagents into each reaction tube as needed; e) to provide the necessary space for attachment of labeling; and f) to enable visual estimation of reagent inventory by the operator. Reagent packs can be bar code labeled with all the information needed to identify them to both an analyzer instrument and the operator.

Figure 6 shows a high performance sample dilution system is also provided in the inventive instrument. In the sample dilution system of this invention, there is a unique combination including a dilution well waste chamber, a dilution well spinning means located in the base of the chamber, and a re-useable dilution well removably nested in the spinning means that is used to mix and dilute liquid samples by rotary motion imparted by the spinning means. Referring to Figure 6, there generally is shown a sample dilution system

610 of the present invention. Specimens may be diluted prior to assay either at the request of the user or automatically. This is accomplished via mixing of a specimen aliquot and a quantity of a diluent, such as a protein diluent or deionized water, in the sample dilution system 610. The dilution well waste chamber 611 is an enclosure defined by chamber walls 620 of chamber body 615 and a removable dilution well cover 613. As illustrated, the waste chamber 611 can be conveniently formed at least partly recessed in a work station table top 612, such as of an immunoassay instrument. The removable dilution well cover 613 has a central opening 614 for pipette access. Concentric projections 614' and 614" extending from the lower side 613' of the cover 613 help direct a pipette into the mouth 631 of the dilution well 625 and channel waste fluids during well cleaning, respectively. The chamber body 615 includes flange 617 retaining O-ring 616 which forms a seal with the rim 618 of the cover 613.

The chamber body 615 is stationary and defines inner sidewalls 620. The chamber body 615 also includes a bottom 621 having a drainage port 636 and a centrally located opening 619. The central opening 619 houses a rotatable dilution well spindle 622. Bearings 624 are provided between the stationary chamber body 615 and the rotatable spindle means 622. The spindle 622 includes a hollow sleeve

622' defining a recess 623 sized to allow the dilution well 625 to be nested and frictionally interfit inside the spindle 622 such that the dilution well 625 will travel in rotation with the spindle 622. The spindle can be driven in rotation by an adjustable motor 628 having a drive shaft 629 mechanically connected to the spindle 622 via a coupling 630. Teflon seals 626 are also preferably provided between the chamber body 615 and the spindle 622 to provide a water-tight system that seals the bearings 624 and motor 628/drive 629 from contact with fluids. The spindle 622 can be stainless steel or another material that is corrosion resistant in the presence of water. The dilution well 625, shown as a test tube-like insert configuration in

Figure 6, is nested in the rotatable spindle 622 during a dilution and mixing mode and a cleaning high speed spinning mode, but it is a separate removable piece from the system in a preferred embodiment. As shown in the Figure 6, the spindle 622 and nested dilution well 625 are centered in the chamber 611 relative to imaginary longitudinal axis γ. Preferably, the dilution well 625 is a non-wettable material, such as polypropylene, to facilitate water removal from the dilution well 625. In an alternate arrangement, the dilution well 625 can be formed integrally with the spindle 622.

The dilution well 625 includes an elongate tapered, hollow cylindrical section 625' having an opening 631 at its upper end 632 and terminating in a closed lower end 633. The tapering or draft angle of the inner surface 625" of the dilution well tube preferably is about 2° such that the inner walls 625" of the tube slope slightly outward away from axis γ. The taper facilitates creep of the waste fluids out of the bottom of the tube up to the opening 631 during a high speed cleaning mode. A distal tip 634 axially extends from the lower tube end 633 and the tip 634 conformably fits within the gripping recess 624 formed in the spindle 622. This arrangement effectively forms a grip by the spindle 622 on the dilution well 625. The upper end 632 of the dilution well 625 also has an integral flange 637 which extends radially outward in all directions and which serves as a splash guard that covers and helps protect the spindle 622 and the motor 628/drive 629 system from fluid contact during the execution of the cleaning mode of the dilution system 610. The dilution well 625 also includes a plurality of fins or baffles 635 integrally attached to the inner walls 625" of the dilution well 625 which project inward and effectively act as agitators during fluid mixing and dilution. For example, about 3-5 equidistantly spaced fins 635 can be used with the dilution well 625. The sample and diluent can be filled in the dilution well 625 to a depth that exceeds the height of the fins 635. The dilution well tube having these features can be formed of plastic material by use of conventional plastic molding techniques. The spindle drive system preferably is capable of adjustment between intermittent and continuous operation modes, the intermittent mode being useful during mixing of the contents in the dilution well. By intermittently energizing the motor 628 in pulses, the fluid contents of the tube are vigorously inter-mixed as encouraged by the fins or baffles 635 provided on the inner sidewalls 625" of the dilution well. On the other hand, the continuous high speed spinning mode is used to clean out the remaining excess fluid contents from the tube after the mixed sample has been withdrawn and transferred to an assay tube for beginning the actual sample analysis. During high speed rotation, left-over fluids in the tube creep up the interior walls of the tube until they reach the mouth of the tube at which point the waste fluids are flung out of the tube and against the inside walls of the dilution well waste chamber. The expelled fluids drain by gravity into the lower basin of the waste chamber and out of a drainage port into waste. Further tube cleaning can be accomplished by the repetitive additions of wash water to the tube during, or followed by, spinning out the wash fluids. An adjustable spin motor 628 preferably is used that is capable of precision control as to the motor speed and/or capability for relatively brief and instantaneous energization periods. For instance, to effect mixing and dilution of a sample and specimen in the nested dilution well 625, the motor preferably is "pulsed" to achieve rapid mixing, i.e., the motor is energized for about 100 milliseconds to place the spindle 622 (and dilution well 625) in rotation, and then de-energized for about 400 milliseconds such that the spindle de-accelerates and stops rapidly due to friction, and then repeating the energization/de-energization cycle at least several times. The dilution well contents are generally pulsed in this manner about 6-8 times, although 3-4 pulses typically has been found adequate for homogenous mixing to be achieved. This scheme effectively causes alternating acceleration/de-acceleration of the dilution well 625 in rotation at low average rpms such that the fluid contents are well agitated without causing the fluids to creep up the inner walls 625" of the dilution well 625 and be prematurely flung out and spilled from the dilution well 625. The pulsed (stop-and-go) tube rotations together with the agitator-like action of the sample tube fins or baffles 635 effectively mixes the sample and diluent held in the dilution well 625 into a homogenous mixture.

A sample pipette, which interacts with but does not form part of the dilution well system per se, can then be used to extract dilute sample from the dilution well 625 and transfer a fraction of the diluted sample to a reaction tube

(not shown) for assay. Once the dilute sample is extracted, the dilution well tube is driven in continuous rotation at high speed to cause any residual waste fluids to creep up the inner walls 625" of the dilution well 625 to opening 631 where the fluids are flung out of the tube as indicated by the arrows. The contents of the dilution well tube are captured within the dilution well waste chamber 611 and drained out of drainage port 636 at the base 621 of waste chamber 611. Wash water can be pipetted into the dilution well 625 through aperture 631 and spun out, once or several times in succession, to further clean the dilution well before introduction, dilution, and mixing of the next sample therein. For most high speed spin removal operations, the tube spin rate will generally range from about 3,000 to about 10,000 rpm. The expelled sample, diluent or other waste fluids drain by gravity into the lower reaches of the chamber 611 and are withdrawn for disposal via drainage port 631.

The sample dilution system is used as a subsystem of the immunoanalyzer used to perform immuno analysis on a sample of interest in which the sample can be diluted with diluent or water and mixed into a homogenous solution in the dilution well system. Then, a fraction of the mixed sample is withdrawn via a pipette, and then deposited in a reaction tube (already containing the coated support material) in which a liquid reagent is also added. (A discussion of the reaction tubes contemplated for use with the present invention is discussed with reference to Figures 7A-7D.) The mixture of reagent and diluted sample can then be processed according to conventional techniques such as by incubating and agitating the mixture, washing the bead, and then having a substrate (e.g., chemiluminescent) added and incubated for quantization of analyte (e.g., by reaction tube light output measurement). When the dilution well system is used in an immunoanalyzer instrument, it is possible to provide user defined dilution factors for the sample prior to analysis and to allow adjustment of the amount of sample dilution in response to prior results where samples give results exceeding the valid measurement limits. To provide the ability to perform a wide variety of different types of immunoassays on board a common immunoassay analyzer, a bead dispenser device is effectively used in combination with a plurality of like bead dispensers useful for supplying support material for heterogenous immunoassay to a common location for addition to reaction tubes. Each such bead dispenser device should be loaded with support material all having the same biomaterial coated thereupon, with the proviso that at least one or more of the bead dispensers stores a different type of biomaterial as coated on the support material as compared to a cohort bead dispenser. It should be understood by those of ordinary skill in the art, that the bead dispensers may dispense one bead at a time. It should further be recognized by those of skill in the art that each bead dispenser is capable of holding large numbers of beads. For instance, the bead dispensers may be loaded with about 200 coated beads.

The rotatable bead carousel 203, such as a rotatable platform, is used to accommodate a large number of bead dispensers, e.g., up to about 24 or even more. The entire carousel preferably is housed within a dehumidified chamber maintained at about 10% relative humidity. The bead carousel platform holding the bead dispensers can be rotated 360° to allow any given bead dispenser to be moved by an identifying and selecting means to a bead loading station where the carousel passes over and intersects (in a top view) the track of a reaction tube loading chain.

As disclosed above, it is useful and practical to provide means for identifying each of the plurality of bead dispensers, such as by a readable bar code associated with each bead dispenser, and the system further comprising a selecting means, such as including a bar code reader, for identifying and selecting from among the plurality of bead dispensers. For example, vertically oriented bar codes can be applied to each bead dispenser making such accessible to reading by a dedicated CCD bar code reader. The system also includes means electromechanically activatable for displacing a plunger of a selected bead dispenser as positioned at the bead loading station over a reaction tube to cause one bead to drop from the exit opening into the mouth of the reaction tube.

In conjunction therewith, there will also be means provided for identifying a reaction tube and its intended analyte contents and relating the reaction tube back to the related dispenser device having a given biomaterial bound to a surface of the support material. Such system can include a tube transport means capable of moving the identifiable reaction tube to a bead (support material) loading station, relating the identified reaction tube to a related bead dispenser device having a given biomaterial bound to a surface of the support material as needed to conduct the assay desired for the sample of interest subsequently to be added to the reaction tube. Once the related bead dispenser device and reaction tube are aligned at the bead loading station, then a bead is ejected from the related bead dispenser into the reaction tube. The reaction tube is then conveyed with the support material of the bead loading station to additional stations to conduct the immunoassay itself (e.g., sample and reagent addition, incubation, washing, quantization, and so forth). The next reaction tube is then brought to the bead loading station and the operation repeated for all reaction tubes to be analyzed.

In a preferred mode of using the bead dispensing system, when the analyzer 10 first encounters a bead dispenser of a particular test type and serial number, the computer 12 will initialize an internal database to reflect the initial number of beads in that particular bead dispenser. Then, each time a bead is dispensed from the bead dispenser, this internal counter will be decremented.

Whenever a new run is initiated, the computer 12 will verify that sufficient fresh (unexpired) beads for each test ordered are available on-board. If not, the operator will be advised via VDT display or audible warning, and so forth, to add another suitable bead dispenser before leaving the instrument 10 unattended. Further, when the bead carousel 203 is accessed, the analyzer preferably should have support software to verify the availability of all required information. If any information is lacking, e.g., the bar code is unreadable or there is an absence of information about which tests to run or how to run them, the operator will be alerted immediately. As such, the analyzer can be programmed to proceed to process all on-board specimens before requiring further attention. Regarding possible test specific problems, if no support material was dispensed, an additional attempt will be made to dispense such support material. In the case of dispensing bead, if two beads are dispensed then the bead count of the bead dispenser will be decremented by two, a new reaction tube drawn and an additional attempt made to dispense a bead. If the second attempt fails, operators are alerted immediately of the problem via both on-screen and audible alarms. Meanwhile, the analyzer can be programmed to continue to process other test types while waiting operator intervention. As to possible hardware problems, such as bead carousel component failures, jams, excessive humidity in the chamber, and so forth, operators are alerted immediately of such problems via both on-screen and audible alarms. Until the operator intervenes, sampling operations will be suspended; however, the tube processor operations can programmed to continue.

According to another aspect of the invention, there is an improved tube washing system 214 provided with a high speed spinning station having a ring magnet or an array of magnets and a chuck housed within and surrounded by a waste chamber. The waste chamber serves as a holder for collecting and draining wash water fluid spun out of a tube.

Referring to Figures 7A-7D, a discussion of the reactions tubes used with the improved washing system 214 will first be discussed. In Figure 7A, an enlarged fragmentary cross-sectional side view of the reaction tube used in the tube wash system of Figures 8 A and 8B is shown. The reaction tube 740 has at least one projection or ridge 743 upstanding from the inner surface 744 of the tube reaction 740. This ridge feature is shown as an enlarged view in Figure 7C. Preferably, the ridge 743 gradually tapers in height and width downward from the upper rim 758 of mouth 745 of the reaction tube 740 and disappears on the inner surface 744 as it approaches the inner bottom of the reaction tube 740. The ridge(s) 743, at the rim area 758, is sized in inward projection and width dimensions as described in detail with reference to Figures 8A-8E. Figure 7B shows an example of three ridges 743 on the inner surface 744 of the reaction tube 740. Preferably a plurality of ridges 743, e.g. three or more, are formed on the inner side 744 of the reaction tube 740 as equidistantly spaced around the inner circumference of the reaction tube 740. The ridges 743 preferably will have a draft angle of about 0.5 °, while the tube surface 744 has a draft angle of about 2° to prevent nesting of the tube in a bulk hopper. At a bottom end of the reaction tube 740 is preferably provided with a continuous circular sleeve 747 extending downward and defining a recess 746 in a bottom surface. This permits handling by a lifting means holder. At a top end of the reaction tube 740 is preferably a continuous flange means 746 provided on the outer side wall. To form the ridges 743 and the continuous flange 746 integral with the reaction tube 740, the reaction tube 740 can be injection molded with styrene-butadiene copolymer, such as "KRO3", commercially available from Phillips 66 Co, Bartlesville, Okla. 74004.

Figure 7D shows an alternate tube design. In this design, the reaction tube 740 has a negative chamfer of approximately 6°. As seen in Figure 7D, the reaction tube 740 includes several shoulders or steps 750 which form the negative chamfer. The negative chamfer of the reaction tube 740 of this embodiment assists in retaining the support material within the reaction tube during the^' spinning of the wash cycle (discussed with reference to Figures 8 A and 8B). Referring to Figure 8A, there generally is shown a novel tube washing system 810 provided with a high speed spinning station 820. The wash station may be used to wash beads (preferably 1/4 inch beads) as well as micro-particles and ferro-fluids) In Figure 8A, the high speed spinning station 820 is shown in a nonengaged position relative to the reaction tube 740. The high speed spinning station 820 includes an angled chuck 822 having grooves 822a. The chuck 822 is housed within and surrounded by a waste chamber 823. The waste chamber 823 is an enclosure defined by an upper surface 824, side wall 825, and a bottom surface 826 having an arcuate shape curving inward and upward near its center to define an opening 828 bounded by upward projection 821. The opening 828 has a size selected to permit entry of the reaction tube 740; that is, the flanges 746 of the reaction tube 740 have an outer profile diameter that is less than the diameter of the opening 828 defined by the bottom surface 826 of the waste chamber 823 such that the reaction tube 740 can be fitted within the opening 828.

A port 827 communicates with a lower end of the chamber 823 to provide a means of drainage of wash water and other fluids expelled from the reaction tube 740 during centrifugation and captured in waste chamber 823. Wash fluid that is expelled from the reaction tube 740 during spinning will strike the chamber walls 824 and 825 and then drain by gravity through the port 827 without being able to climb up and over projections 821 at the bottom surface of the chamber 823. Therefore, wash fluid will not seep out of a small gap provided between the reaction tube 740 and the closely confronting, but noncontacting, inward surfaces

821a of projections 821.

Figure 8 A further shows a pipette 833 which extends through a drive shaft 829 and the center of the chuck 822. A dispensing tip 834 of the pipette 833 emerges from the bottom of the chuck 822, a distance sufficient to permit the tip 834 to enter the reaction tube 740 (once lifted into chamber 823 as seen in Figure

8B) without closely approaching or contacting the support material. A solenoid wash pump (not shown) controllably delivers wash water volumes to the pipette 833. With this said, the pipette 833 does not spin with the chuck 822 due to the provision of bushing 857 around the pipette 833. The bushing 857 can spin while maintaining the pipette 833 in a centered non-spinning position. The chuck 822 is mounted in the drive shaft 829 for rotation and distends through the top surface 824 to reside inside the waste chamber 823. The drive shaft 829 is sealed with an O-ring 830, and the bearings 832 are provided between drive shaft 829 and a support frame 831. The drive shaft 829 is driven to rotate about axis z— z by a spin motor (not shown).

Still referring to Figure 8A, the high speed spinning station 820 further includes a elevating means 850 which includes a shoulder 856 and a tube holder 851. The continuous tube flange 746 rests on the shoulder 856 prior to the elevating means 850 being elevated and the reaction tube 740 engaging the chuck 822. In the non-elevated state of Figure 8A, the continuous circular sleeve 747 of the reaction tube 740 does not engage the tube holder 851; however, in the elevated position (of Figure 8) the continuous circular sleeve 747 of the reaction tube 740 engages the tube holder 851 and may further rest on the shoulder 412 of the housing 400. The continuous tube flange 746 also engages with the chuck groove(s) 822 of the chuck 822 such that the continuous tube flange 746 no longer rests on the shoulder 856 (Figure 8B). The tube holder 851 (i) is positioned partly within the aperture 404 of the holder 400 and (ii) is designed to hold and retain the reaction tube 740 during the lifting of the reaction tube 740 into the waste chamber 823. The tube holder 851 is further designed to hold the reaction tube 740 during the disengagement (lowering) of the reaction tube 740 from the chuck

822 during the downward movement of the elevating means 850. This ensures that the reaction tube 740 will properly disengage from the chuck 822. The tube holder 851 also includes a means for resting on the shoulder 412 of the housing 400 (in the engaged and non-engaged position of Figures 8A and 8B). The elevating means 850 further includes a reciprocal shaft 855, which is vertically moveable in the z— z axis direction. The shaft 855 is connected to a lift motor (not shown) which, when actuated, will drive the shaft 855 vertically upward to interfit the tube holder 851 with the bottom of the reaction tube 740, as supported and oriented by a slot in shoulder 856 having been shuttled thereto from a chain link of a tube conveyor 848, and continue to lift the reaction tube 740 to a height until it enters the waste chamber 823. The lift motor will also continue to lift the reaction tube 740 to a height which allows the reaction tube to enter the waste chamber 823 and the tube ridge(s) 743 to slide into and mate with the chuck groove(s) 822a (see, Figure 8D). In a preferred embodiment, the tube will be shuttled out from the chain prior to the lifting of the tube so that the washing will not interfere with chain motion during any cycle. The magnet holder 400 is also housed within the elevating means 851 and is supported on the shaft 855. The tube elevating means 850 includes bearings 854 permitting free rotation of the tube holder 851 relative to the elevating means 850. As seen in Figure 8B, once the reaction tube 740 is elevated into the chamber 823 effective to mechanically interlock with the chuck 822 via mating of tube ridge(s) 743 and the chuck groove(s) 822a of the chuck 822, the reaction tube 740 is rotated on its vertical axes z— z by driving the chuck 822 in rotation while the reaction tube 740 is supported at the bottom of the tube (747, 746) via the rotatable holder 851 which rotates the chuck 822. In this position, the continuous circular sleeve 747 of the reaction tube 740 may further rest on the shoulder 412 of the housing 400. The opening 828 defined by chamber projections 821 is sized to provide a small circumferential gap "G", e.g., about 12/1000 inch clearance, between the inner surfaces of projections 821 and the continuous tube flange 746. The magnets 406 are positioned about a bottom of the reaction tube 740.

During rotation, waste fluids are expelled from the reaction tube 740 into the waste chamber 823 through the grooves 822a in the chuck 822 due to centrifugal force. The magnetized immunoreceptive support material 741 (micro- particles or ferro-particles) is retained in the reaction tube 740 by the magnetic attraction imposed between the magnetic ring or array of magnets 406 positioned near the bottom of the reaction tube 740 and the magnetized support material 741. In the preferred embodiment, the magnets 406 are powerful enough to retain the magnetized support material near a bottom of the reaction tube 740 during the rotation thereof. For most applications, the tube spin rate will generally range from about 3,000 to about 10,000 rpm.

When rotation ceases, the expelled waste fluids drain by gravity into the lower basin 826a of the waste chamber 823 and are withdrawn for disposal via drainage port 827. Washing can be accomplished by the addition of water to the reaction tube 740 during, or followed by, centrifugation. Wash water is added to the reaction tube 740 via a solenoid wash pump (not shown) delivering volumes of wash water to pipette 833 which pipettes the volumes of water straight down into the reaction tube 740. Although not particularly limited to such, in a preferred operation, multiple 400 μL volumes of water (e.g. four) are pipetted into the reaction tube 740. After each addition, the wash water is almost instantaneously removed after washing the inert support 741 with the bound biomaterial by high speed rotation of the reaction tube 740.

Once the washing and centrifugation are completed for a given reaction tube 740, the reaction tube 740 can be lowered via the tube elevating means 850 by retracting the shaft 855 with the tube ridge(s) 743 sliding back out of the chuck groove(s) 822a and the reaction tube 740 eventually clearing the waste chamber 823. After washing, the reaction (or assay) tube 740 and inert support 741 will be free of unbound labeled reagent so that only bound labeled reagent will be detected. After completion of the washing operation, the washed tubes are transferred to a detection station for quantification of the analyte of interest, such as by chemiluminescent techniques described in U.S. Pat. No. 5,316,726, which is incorporated herein by reference.

Figures 8C and 8D show a detailed view of the chuck 822. The chuck 822 is preferably a bevel gear which has a body portion defined by an upper surface 822b of a generally hemispherical-shape merging into an upright stem 822d, and a grooved bottom surface 822c. As best seen in Figure 8C, the bevel gear 822 has alternating grooves or slots 822a and teeth 822e disposed around the entire circumference of bottom surface 822c. As seen in Figure 8D, the series of spaced apart teeth 822e and intervening grooves 822a angle up to hemispherical portion 822b at an angle, preferably an angle of about 45°. In the engaged state with the reaction tube 740 (Figure 8B), the ridge(s) 743 of the reaction tube 740 are sized in inward projection and width dimensions sufficient to permit sliding of the ridge(s) 743 into the groove(s) 822a of the chuck 822 so as to allow a nesting between two adjoining chuck teeth 822e. The inter-fit of the ridge(s) 743 and the chuck groove 822a preferably should be provided with close clearances since loose fits may cause wear on the ridges 743 or chuck teeth 822e. In one example, the three ridges 743 shown in Figure 7A are designed to be nested between three pairs of teeth in the chuck 822. This provides a means of temporarily physically and mechanically interlocking the reaction tube 740 and chuck 822 when the reaction tube 740 is engaged (lifted into) chamber 823 such as shown in Figure 8B. The total number of grooves 822a provided in chuck 822 will be more than the number of ridges 743 so that at least one and preferably a plurality of the grooves 822a will remain unobstructed by any ridge 743 of the reaction tube 740 during tube spinning. This will allow escape paths to exist thus allowing for wash fluids to be expelled from the reaction tube 740 during spinning within the waste chamber 823. As further seen in Figures 8D and 8E, the chuck 822 also has a central throughhole "c" capable of receiving and allowing the pipette to be passed through the chuck 822. The chuck 822 also is formed of a rigid material, such as metal.

As shown in Figure 8E, the tube holder 851 is a hollow metal tube 852 divided at a upper half by four slots "s" extending from the top end "t" to about halfway down the length of tube 852. This defines four 90° quadrants at the top end "t" of the tube 852. The tube 852 is flanged or hooked by bending outward at top end "t". The tube 852 preferably is beryllium-copper alloy, which provides good spring-like flexure properties. The flanged portion "t" of tube 852 is slightly oversized relative to the recess 746 in the reaction tube 740 for positive retraction.

Also, the flanged top "t" of the tube 852 interfrts the recess 746 of the bottom of the reaction tube 740, such that the circular sleeve 747 of the reaction tube 740 can slide over the outer flanged periphery at the top "t" of the tube 852 (with the continuous circular tube holder sleeve sliding in opposition over the outer sides of the circular sleeve 747).

The use of the tube washing system as thus described greatly facilitates the washing operation required in performing an immunoassay and represents a significant improvement over the use of aspiration equipment in an automated immunoassay analyzer environment. In particular, removal of the sample and wash fluid in the above-described manner allows the wash operation to be performed rapidly and facilely.

While the invention has been described in terms of its preferred embodiments, those skilled in the art will recognize that the invention can be practiced with modification within the spirit and scope of the appended claims.

Claims

Having thus described our invention, what we claim as new and desire to secure by Letters Patent is as follows:

L A tube wash system of an automated immunoassay analyzer, comprising: a drive shaft; a chuck coupled to the drive shaft; a waste chamber surrounding the chuck, the waste chamber having an opening for accommodating a reaction tube; an elevating means positioned below the waste chamber, the elevating means lifting and lowering the reaction tube into the waste chamber; and a housing for accommodating a magnet and partially surrounding the reaction tube, the elevating means lifting and lowering the housing relative to the waste chamber.

2. The tube wash system of claim 1, wherein the waste chamber is an enclosure defined by an upper surface, side wall and a bottom surface having an arcuate shape curving inward and upward surface which defines the opening.

3. The tube wash system of claim 2, wherein the waste chamber comprises a port communicating with a lower end of the waste chamber to provide a means of drainage of wash water and other fluids expelled from the reaction tube captured in the waste chamber during centrifugation of the reaction tube.

4. The tube wash system of claim 1, wherein the magnetic housing comprises an opening sized to accommodate the reaction tube.

5. The tube wash system of claim 4, further comprising at least one spacer positioned about the housing opening and below the magnet, the at least one spacer adjusting a height of the magnet.

6. The tube wash system of claim 4, wherein the magnet is a ring magnet or an array of magnets positioned about the housing opening.

7. The tube wash system of claim 6, further comprising a cap positioned on a top of the housing, the cap retaining the ring magnet or the array of magnets within the housing.

8. The tube wash system of claim 4, further comprising a tube holder positioned below the housing, the reaction tube extending through the housing opening and engaging the tube holder holding during portions of the lifting and lowering of the tube elevating means.

9. The tube wash system of claim 1, wherein the drive shaft is hollow and the chuck is fitted within the hollow drive shaft.

10. The tube wash system of claim 1, further comprising bearings surrounding the drive shaft.

11. The tube wash system of claim 1, further comprising a reciprocal shaft, the reciprocal shaft positioning the elevating means and the housing with respect to the waste chamber.

12. The tube wash system of claim 11, including shaft bearings which allow free rotation of the reaction tube relative to the elevating means.

13. A wash system for an automated immunoassay analyzer, comprising: means for rotating a vessel about a vertical axis, said vessel having one or more magnetic support materials therein; means for adding fluid to said vessel; means for applying a magnetic field on said one or more magnetic support materials.

14. The wash system of claim 13, wherein said means for applying the magnetic field is positioned external to said vessel positioned in said means for rotating.

15. The wash system of claim 14, wherein said means for applying the magnetic field is one of an electromagnet, a magnetic array and a ring magnet.

16. A method of washing a test sample used in an automated immunoassay analyzer, comprising the steps of: binding an analyte to a magnetized support material in a reaction tube; washing the anlayte bound magnetized support material; and maintaining a magnetic field about the anlayte bound magnetized support material during the washing.

17. The method of claim 16, wherein the washing step includes rotating the reaction tube.

18. The method of claim 16, wherein the washing step includes expelling waste fluid from the reaction tube.

19. The method of claim 18, wherein the washing step includes retaining the anlayte bound magnetized support material within the reaction tube by magnetic attraction between the anlayte bound magnetized support material and a magnet or array of magnets positioned outside of the reaction tube.

20. The method of claim 16, wherein the magnetized support material is one of a bead having magnetic particles interspersed therein, magnetized micro-particles and magnetized ferro-fluids.

21. The method of claim 16, wherein the washing step includes spinning the reaction tube in the range from approximately 3,000 to about 10,000 rpm.