Adaptive scheduling system and method for operating a biological sample analyzer with variable rinsing

An improved biological sample analyzer for conducting assays of samples loaded therein, and a method and system for operation thereof, that schedules operations by instrument systems on each biological sample and schedules a conditional cleaning operation prior to a scheduled instrument system operation. The analyzer conducts the assays of the biological samples by performing the scheduled instrument system operations and performs a cleaning operation prior to any scheduled instrument system operation conditioned upon the instrument system operation scheduled prior to the cleaning operation. The biological analyzer can perform a warming operation prior to a scheduled instrument system operation determined upon the lapse of time between the scheduled instrument system operation and the instrument system operation scheduled prior thereto.

MICROFICHE APPENDIX 
Included are two microfiche of 139 total frames. 
REFERENCE TO RELATED APPLICATIONS 
The disclosures of the following copending applications assigned to the 
assignee of the present application and filed concurrently herewith are 
specifically incorporated by reference: 
"Adaptive Scheduling System and Method For Operating a Biological Sample 
Analyzer With Variable Interval Periods", by Kathy Burns, Ilya Ratner, 
Jeanine T. Douglas, Erica Kline, and Cass J. Grandone Ser. No. 07/709,723, 
filed Jun. 3, 1991; 
"Adaptive Scheduling System and Method For a Biological Analyzer With 
Reproducible Operation Time Periods", by Cass J. Grandone, Mark Pierce, 
Ilya Ratner, and Jeanine T. Douglas Ser. No. 07/709,721, filed Jun. 3, 
1991; 
"Retrofit Kit For Changing Single Immunoassay Instrument to Flexible 
Multiple Immunoassay Instrument", by Chadwick M. Dunn, Cass J. Grandone, 
Stephen L. Herchenback, Robert J. Nelson, Robert Perry, James T. Tyranski 
and Gary Lee Zuck Ser. No. 07/709,730, filed Jun. 3, 1991; 
"Carousel For Assay Specimen Carrier", by Cass J. Grandone, Steven L. 
Herchenback, Robert Perry, James T. Tyranski and Gary Lee Zuck Ser. No. 
07/709,726, filed Jun. 3, 1991; 
"Heat and Air Flow Control For Assay Carrier", by Chadwick M. Dunn, Cass J. 
Grandone, James T. Tyranski and Kris T. Luddington Ser. No. 07/709,728, 
filed Jun. 3, 1991; 
"Reagent Bottle and Cap", by James T. Tyranski Ser. No. 07/709,725, filed 
Jun. 3, 1991; and 
"Reagent Pack For Immunoassays", by Steven Herchenback, Robert Nelson, 
James T. Tyranski and Gary Lee Zuck Ser. No. 07/709,726, filed Jun. 3, 
1991. 
BACKGROUND OF THE INVENTION 
The present invention relates generally to biological sample analyzers used 
to perform assays of patient specimen samples. More particularly, the 
present invention relates to a method and system for the scheduling an 
adaptive rinse operation as part of the operating steps for performing 
assays of biological samples in an automatic analyzer. 
Biological sample analyzers, of the type considered herein, are automated 
instruments that may be used in hospitals, clinics, laboratories, or other 
locations, to run routine tests (assays) on samples of patient specimens 
such as blood, spinal fluid, urine, serum, plasma, and so on. An automated 
analyzer of the type discussed herein includes an analyzer unit that runs 
tests on a number of patient specimen samples that are loaded into the 
unit. An operator-user prepares the samples by placing portions of the 
patients' specimen samples into a number of like-sized sample containers. 
These samples may be diluted or otherwise treated, depending upon the type 
of analyzer used, the type of assay being performed, and other factors. 
The containers are then placed in the analyzer unit. The containers may 
first be placed in a rack or carousel that is then placed in the analyzing 
unit. The rack may accommodate a number of sample containers, e.g. 24. In 
addition, one or more appropriate chemical reagents, needed to perform the 
assays, are also placed in the analyzer unit. In order to mix reagents 
with the samples, the analyzer unit may also include a fluid moving 
system, such as a robotic probe mounted on a boom, which is adapted to 
draw up portions of the reagents and/or samples and expel them into 
appropriate locations, e.g. additional cells such as reaction cells 
provided in the sample containers, where a reaction can take place. The 
analyzer unit also may include a means for detecting a reaction in the 
reaction cells. This may include an optical detector to observe 
fluorescence reactions and make optical measurements to obtain a result 
for each sample. The analyzer unit may also typically include other 
mechanical systems to move the sample containers and the probe. The 
analyzer unit may also provide for cleaning the probe between certain 
tasks in order to avoid contamination between samples. For this purpose, 
the analyzer unit may also include a washing station and a waste 
dispensing container to hold the used rinse solution. (For purposes of 
this specification and claims, the terms "rinse" and "cleaning solution" 
are used interchangeably). 
After the operator-user loads the specimen samples, enters appropriate 
instructions, and starts the unit, the analyzer runs unattended. When 
placed in operation, the analyzer unit, using the appropriate chemical 
reagent, runs the same test on each of the samples in the sample 
containers and will perform identical operations on each of the samples 
loaded in the rack. When it is finished, the analyzer prints out or 
otherwise reports on the results of its testing. 
Biological analyzers utilize different chemistries for performing assays of 
specimen samples. One type of assays used in biological analyzers includes 
immunoassays and solid phase procedures. Analyzers for performing 
immunoassays in general and enzyme immunoassays in particular are known in 
the art. 
A biological analyzer that utilizes immunoassay chemistry to perform assays 
of specimen samples loaded therein is the IMx.RTM. analyzer introduced in 
1988 by Abbott Laboratories, of North Chicago, Ill. (A description of the 
IMx analyzer is included in "The Abbott IMx Automated Benchtop 
Immunochemistry Analyzer System", by Fiore, M. et al., Clinical Chemistry, 
Vol. 34, No. 9, 1988, which is specifically incorporated herein by 
reference in its entirety). The IMx analyzer is a biological sample 
analyzer that has been developed for use in conjunction with solid phase 
immunoassay procedures to perform a variety of assays (such as sandwich 
and competitive assays). The IMx analyzer uses a technology referred to as 
microparticle capture enzyme immunoassay (MEIA) and fluorescence 
polarization immunoassay (FPIA). The IMx analyzer includes a 
microprocessor used to control a robotic arm with 2 degrees of freedom and 
a rotating carousel to process the samples for assay. One assay can be 
done on each of 24 specimen samples in 30-40 minutes or more unattended 
after loading (i.e. with "walk away" automation). Assay results are output 
to a printer or a computer interface. 
A biological sample analyzer, such as the IMx analyzer described above, can 
execute the steps required for performing assays of up to 24 specimen 
samples, including the steps of counting the samples, identifying which 
assay to run, warming the reagents and reaction cells to appropriate 
temperatures, pipetting the reagents and samples, diluting samples if 
required, timing critical assay steps such as incubations, washing unbound 
conjugate, quantifying the fluorescence signal and performing data 
reduction to yield a useful result. 
The container used for holding each of the specimen samples for a 
biological sample analyzer, such as the IMx analyzer, may be a disposable 
assay cartridge having a plurality of wells, with at least one reaction 
well and one separation well. The separation well may contain a fibrous 
matrix positioned across its entrance and an absorbent material positioned 
below the fibrous matrix. Microparticles react with an analyte containing 
sample and one or more reagents to form a complex. This complex is 
immobilized on the matrix of the separation cell. The excess sample and 
reagent are washed through the matrix and captured in the absorbent 
material below. 
The results of the reactions may be read using known optical detection 
techniques. For example, using conventional solid phase procedures, an 
analyte can be labeled or tagged with an enzyme which in the presence of 
its substrate fluoresces and emits light at a known wave length. The rate 
at which the fluorescent product is produced is indicative of the 
concentration of the analyte in the biological sample. A conventional 
fluorometer is suitable for illuminating the fibrous matrix with a beam of 
light having the appropriate excitation wave length. The fluorometer also 
detects the intensity of the light at the emission wave length assays. 
Using this type of solid phase technology has been found to provide a high 
degree of sensitivity. 
A biological sample analyzer, such as the IMx analyzer, provides for 
performing assays of patients' specimen samples and reading the results of 
such assays in a mass production type manner. This allows such assays to 
be made available quickly and conveniently. 
The steps that the instrument systems follow to perform the assay in the 
biological analyzer are included in a program called a protocol. The 
protocol is written by an assay developer and may be included on the 
module. The protocol is a series of steps or instructions for the 
instrument systems to perform including time constraints on when the steps 
are to be performed. These steps could include mixing the sample with one 
or more reagents in a mixing cell, providing an incubation time, and 
measuring a reaction. Often, certain steps for each sample have to be 
separated by an incubation time to allow for a reaction to take place. 
Instrument systems, such as the probe, may perform some of the steps for 
one specimen sample until an incubation time is needed and then the probe 
performs a similar series of operations on another of the specimens, and 
so forth. When moving from one sample to the next, the probe may have to 
be decontaminated to prevent carryover by inserting it into a rinse 
solution. Commands to perform a rinse operation are included in the 
protocol. With this type of operation, the assay developer would typically 
write an instruction in the assay protocol to clean the probe after a 
series of operations to prevent contaminating the next sample. Because the 
types of samples and reagents is known to the assay developer, the assay 
developer could instruct the analyzer to perform a cleaning operation 
appropriate to clean the probe to prevent carry over. Different cleaning 
operations are necessary depending upon the type of specimens and reagents 
being handled. For example, it might be determined that the probe would be 
sufficiently cleaned by drawing into it a certain number of ml of the 
rinse solution and expelling the rinse. For other specimens and reagents, 
it may be necessary to perform the cleaning operation twice. 
Alternatively, it may be necessary to draw the rinse into the probe and 
hold it for a certain number of seconds. In a biological analyzer, such as 
the IMx analyzer, dozens of different types of rinses may be used 
depending upon the needs of assay. 
Even though such analyzers can provide significant advantages by performing 
assays quickly and conveniently, further advantages for the user could be 
obtained if the overall through put of the analyzer could be increased. 
One way to provide even more advantages and convenience for users of 
biological analyzers would be to provide the capability to perform more 
than one assay on the specimen samples in an unattended run. Although a 
biological analyzer such as the IMx analyzer can perform different types 
of assays and can perform assays on a number of specimen samples 
unattended, the analyzer can run only one type of assay at a time. If a 
different type of assay is to be performed, the analyzer would have to be 
reloaded with different reagents. Also, because different types of assays 
may require different amounts of the sample specimen, different amounts of 
reagents, different processing steps, different incubation times, etc., 
the analyzer would also be reset at the beginning of the run to perform 
the new assay. In the case of the IMx analyzer, a different memory module 
may have to be inserted containing the instructions for the analyzer unit 
for performing the different assay. Thus, even if only a few of several 
different types of assays need to be run, the operator-user has to load 
and run the analyzer for the first type of assay for only a few samples 
and then reload the analyzer to run the second type of assay on another 
batch of samples using perhaps different reagents. It is recognized that 
for many users of the IMx analyzer, or other biological sample analyzers, 
it would be convenient and advantageous to be able to perform more than 
one type of assay during an unattended run. 
Although analyzers having the capability to perform more than one assay in 
an unattended run have the potential to provide further advantages and 
convenience for the operator-user, when the operator-user is given the 
capability to choose which type of assays to perform in an unattended run, 
providing this feature presents several obstacles relating to the analyzer 
operation. One obstacle associated with operating an analyzer to perform 
more than one assay in a run relates to carryover. In the prior analyzers 
that perform only one assay in an unattended run, the developer could 
readily determine the sequence of operating steps and provide the 
appropriate instruction in the protocol for the type of cleaning 
operation, such as rinse, needed to prevent carryover. However, in an 
analyzer in which more than one assay is being performed, there is a large 
number of possible permutations of load list combinations available. For 
example, if there are 24 specimen samples in the carousel rack and the 
operator-user is permitted to select any one of three different assays to 
be performed on the samples, there are almost 2500 different permutations 
of possible combinations of assays and samples that the user can select. 
If the operator-user is permitted to select any one of four different 
assays to be performed on the 24 samples, there are approximately 10,000 
different permutations of possible combinations. Thus, the assay developer 
is no longer able to know with certainty which samples will be handled by 
sequential operations of the analyzer instrument systems, such as the 
probe or which reagents will be used for subsequent operations or even 
which operations will be performed sequentially. For example, the 
potential exists for an analyte to be present in a sample upon which an 
assay not specific to that analyte is performed to be carried over to a 
sample upon which an assay specific to that analyte is being performed 
thereby causing a false positive. Whereas in single assay runs, the assay 
developer could predict with a certainty the type of rinse needed to avoid 
contamination, with the load list combinations present with more-than-one 
assay runs, the number of permutations of possible operating sequences is 
high enough that it becomes difficult to predict the type of rinse 
operation is required. 
One way to address this concern is to establish a rinsing safety factor 
high enough to always effectively clean the probe regardless of the 
sequence of operations. Thus, the assay developer would use a strong rinse 
or a large quantity or duration of rinse between all operating steps. This 
rinse would be based upon the worst case contamination concern. If the 
worst case contamination were always provided for, the analyzer would use 
a considerable amount of rinse and would likely be using more rinse than 
is needed between instrument system operations for many load list 
permutations. 
Using more rinse than is necessary is inconvenient and requires the 
refilling the cleaning solution container frequently. Using more rinse 
than is necessary requires disposing of the large quantity of rinse waste 
generated. Moreover, excess rinse can lead to problems. For example, if 
too much of a certain rinse is used and some of it carries over to another 
sample for another assay that is sensitive to that rinse, it may interfere 
with the chemical reactions in performing the assay for the latter sample. 
Another problem related to operating an analyzer to perform more than one 
assay in a run relates to warming the probe. As mentioned above, assays 
and particularly immunoassays are sensitive to the temperature. For that 
reason, provision is made to stabilize the temperature as much as 
possible. When operating an analyzer with more than one assay type and the 
high number of possible combinations of operations, it is possible that 
the probe may be idled for a period of time and possibly cool off. one way 
to ensure that this does not happen is by inserting the probe into the 
rinse which is maintained at a preferred temperature. This operation is 
referred to as "pre-warming". In an analyzer that performs more than one 
assay and that has a high number of possible combinations of operating 
steps, it cannot readily be determined when such a pre-warming step should 
be performed if at all. 
Accordingly, it is an object of the present invention to provide a 
biological sample analyzer, and a method and system for operation thereof, 
that provides for a cleaning operation to prevent carryover and a 
pre-warming operation when needed, especially when more than one type of 
assay is performed on patient specimen samples loaded therein. 
It is a further object of the present invention to provide for a variable 
cleaning operation sufficient to prevent contamination of the fluid 
handling systems and which reduces excessive waste and improves through 
put. 
SUMMARY OF THE INVENTION 
The present invention provides for an improved biological sample analyzer 
for conducting assays of samples loaded therein, and a method and system 
for operation thereof, that schedules operations by instrument systems on 
each biological sample and schedules a conditional cleaning operation 
prior to a scheduled instrument system operation. The improved analyzer 
conducts the assays of the biological samples by performing the scheduled 
instrument system operations and performs a cleaning operation prior to 
any scheduled instrument system operation conditioned upon the instrument 
system operation scheduled prior to the cleaning operation. The biological 
analyzer can perform a warming operation prior to a scheduled instrument 
system operation determined upon the lapse of time between the scheduled 
instrument system operation and the instrument system operation scheduled 
prior thereto. 
For purposes of this specification and claims, it is understood that a 
cleaning operation in an analyzer of the type considered herein is 
typically performed by rinsing the probe of the analyzer in a cleaning 
solution or by aspirating a portion of cleaning solution with the probe or 
by other by operations. Reference to a cleaning operation shall be 
considered to include any of these types of rinsing operations. Rinsing 
operations may also be considered to include other types of cleaning 
operations. 
For purposes of this specification and claims, a "run" is considered to 
refer to the operation of the analyzer in performing the assays after the 
operator-user has loaded into the analyzer the specimen samples, reagents, 
rinse, or other accessory material and also entered any necessary 
information pertaining to the assays to be performed on the samples. The 
"run" concludes when the assays have been performed on all the samples and 
may include data analysis performed in generating an assay test result or 
printing or otherwise outputting the results of the assays. In automatic 
analyzers of the type considered herein, the run may proceed unattended.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS 
Referring to FIG. 1, there is depicted a schematic block diagram of a 
biological sample analyzer 10 of a first embodiment of the present 
invention. The biological system analyzer 10 includes an analyzer unit 12, 
in which is included a CPU 14. The CPU 14 operates analyzer unit 
instrument systems in accordance with means well known to those skilled in 
the art. The analyzer unit instrument systems include a fluid moving 
system 16, a carousel moving system 18, and a detection system 20. 
Additional systems may also be included. One or more modules 22 include 
programming, stored for example in a PROM, used for the operation of the 
analyzer unit 12 and the analyzer unit systems. The programming on these 
modules 22 may include separate programs (called protocols, described in 
more detail below) specifically adapted for performing specific different 
types of assays. These modules 22 may be removable to provide for 
additional different assays to be performed as well as to readily provide 
for updates and improvements to the system operation to be implemented. 
The analyzer unit instrument systems 16, 18 and 20 operate through an 
appropriate controller-interface 24. In this embodiment, the CPU 14 used 
is an Intel Model 80286 microprocessor. 
The carousel moving system 18 is adapted to move a carousel or rack 26 upon 
which is positioned a plurality of patient specimen sample containers 28. 
The carousel 26 is preferably removable in order to facilitate loading and 
unloading of the patient specimen sample containers 28 into the analyzer 
unit 12. The carousel 26 may also hold a first set of one or more reagents 
30 for performing a particular assay. A second set of one or more reagents 
may also be included in the analyzer unit 12 in a location off of the 
carousel 26. These reagents may be in reagent packs and may include 
reagents for performing MEIA and/or FPIA types of assay tests, as 
described above. 
The fluid moving system 16 includes one or more robotic pipette-booms 
adapted to move fluid from one location to another in the analyzer unit 
12, e.g. from one container to another, under the control of the CPU 14. 
The CPU 14 operates the carousel moving system 18 to move the carousel 26 
and the fluid moving system 16 to move the pipette-boom to mix the 
appropriate reagents with the specimen samples in the containers 28. The 
CPU 14 also operates the carousel moving system 18 to move the carousel 26 
and thereby the containers 28 into position to observe reactions at the 
detection system 20. The CPU 14 controls the detection system 20 which may 
include means for detecting florescence in a manner that is well known in 
the art. In a preferred embodiment, the detection system 20 includes a low 
pressure mercury lamp used in a fluorometer. The CPU 14 receives the 
information about the reactions from the detection system 20 and performs 
the appropriate data analysis, and outputs results to either a printer 34 
or to a data storage 36. A cleaning station 38 may also be provided in the 
analyzer unit 12. The cleaning station 38 includes a rinsing solution 40A 
and a waste container 42 into which waste fluid can be dispelled. 
FIG. 2 depicts a perspective view of the biological sample analyzer 10, 
partially disassembled, incorporating aspects of the first embodiment of 
the present invention. The analyzer unit 12 holds the circular carousel 
rack 26 into which are placed a plurality of assay container cartridges 
28. These cartridges 28 are preferably disposable. The assay container 
cartridges 28 are placed in a plurality of openings 40 (also referred to 
as "wedges") arranged around a central core of the carousel rack 26 which 
is specially formed to hold the cartridges. All the cartridge containers 
28 have individual alignment features that insure their accurate alignment 
within the rack 26. 
The carousel rack 26 containing the cartridge containers 28 can be 
circularly indexed to accurately position each assay cartridge container 
relative to the detection system 20 containing an optical reading 
apparatus. Because the reading positioning is highly accurate, the assay 
is properly positioned for reading at a reading station. 
The fluid moving system 16 includes a pipette/probe assembly that include 
syringes 48 (e.g. a 250 microliter sample syringe and a 2500 microliter 
diluent syringe may be provided) driven by stepper motors. The 
pipette/probe assembly can be positioned over the reagents 30, the 
individual cells of the containers 28, or the wash station 38. Stepper 
motors move the pipette system up and down as well as radially. The fluid 
moving system 16 transfers fluid from reagent bottles to separation wells 
and from well to well. The pipette itself is a drawn stainless steel tube, 
teflon coated to minimize carryover. Fluid levels may be sensed by 
measuring electrical conductivity between the pipette probe tip and an 
electrode. 
Carryover between samples and reagents is minimized by washing the 
pipette/probe over a wash station. 
Because enzyme immunoassays require precise temperature control to achieve 
repeatable performance, heating elements (not shown) are provided in the 
analyzer unit 12. 
The biological analyzer 10 illustrated in FIG. 2 is similar to the prior 
analyzer (the IMx analyzer) sold by Abbott Laboratories, Inc. Compared to 
the prior analyzer, this embodiment of the analyzer includes additional 
reagents 30 that are stored in the carousel 26 in the analyzer and are 
used to perform the greater-than-one assays during a run. The description 
of the details of construction of the analyzer are disclosed to help 
define the environment of the present invention and such details do not 
form part of the invention. This embodiment of the analyzer also includes 
additional programming to perform the greater-than-one assays during a 
run. 
As shown in FIG. 3, a first set of reagents 30 is included on the carousel 
26. In a preferred embodiment, these reagents 30 are included on a portion 
of the carousel 26 and located centrally of the sample wedges 40. 
An operator-user prepares for an assay run sequence by loading containers 
containing patient specimen samples (sometimes referred to as 
"disposables") into the carousel 26. In this embodiment, approximately 150 
microliters of sample, controls, or calibrators is added to a sample well 
of each of the reaction cells of the container. The carousel rack is then 
placed in the analyzer unit 12 and the appropriate reagent pack or packs 
are loaded into the unit or the carousel. 
In this embodiment of the analyzer 10, the operator-user also includes a 
calibration sample for each assay type being run. Thus, if three different 
types of assays are being run, three separate calibration samples are also 
run. The calibration samples have a known amount of the substance being 
tested for, and accordingly, are used as a basis for determining the 
amounts of the tested for substance in the unknown specimen samples by 
comparison of the reactions. This use of calibration samples is similar to 
what has been performed in the prior IMx analyzer. Typically, the 
calibration samples occupy specific positions (i.e. wedges) in the 
carousel rack 26. 
The operator-user enters a load list. This may be done by means of the 
input panel 54 (of FIG. 1). The entry of the load list may be prompted by 
a menu on the display 55. The load list identifies the wedges of the 
carousel in which patient specimen samples are located and which assay is 
to be run on each of the specimen samples. Not all of the wedges of the 
carousel have to be used. The operator-user has the option of selecting 
several different assays to be performed automatically in a single run and 
also has the option of selecting the number of specimen samples to be used 
for each different assay. In a preferred embodiment up to four different 
assays may be available, however, the present invention could be extended 
to even a greater number. In a preferred embodiment, the samples upon 
which the same assay is to be performed are grouped together, i.e. in 
adjacent wedges of the carousel. This facilitates input of the load list 
by allowing the operator-user to indicate at which wedge position the 
specimen samples for a specific assay begin. 
For purposes of efficiency, certain types of assays will be typically 
grouped together. For example, the assays for Prolactin, LH and FSH will 
be typically grouped together and the tests for CEA, AFP, and CA 19-9 will 
be grouped together. Other grouping of assays can be provided. These 
grouping are based, in part, upon the likelihood that an operator-user 
would want to run these assays at the same time. These combinations could 
be changed to include other assays or delete assays if different 
combinations would be preferred. If a different combination of assays were 
included, the appropriate reagents for those assays would be loaded in the 
analyzer unit. 
Although in a preferred embodiment, the user-operator enters a load list by 
inputting information into the input panel 54, the load list for a run may 
be entered by other means. For example, the load list could be entered via 
a computer or communications interface. Alternatively, the load list may 
be determined automatically by scanning information attached or otherwise 
associated with each specimen sample container. 
After closing a door or otherwise performing any other steps for preparing 
the analyzer unit, the operator-user actuates a run button on the input 
panel 54 of the analyzer unit. From this point, the analyzer can operate 
automatically and unattended until all the assays are finished. 
Under the control of a program run on the CPU 14, the analyzer unit 12 
begins a preparation process in which the following actions typically are 
taken: all stepper motors (fluids, syringe pumps, carousel motor, pipette 
system motors) are "home" (adjusted to times 0), the carousel rack is 
scanned to identify the type of carousel installed and its "lock" status. 
The reagent pack types may be read by a bar code scanner located on the 
pipette system to identify or confirm the assays to be run. The carousel 
heating systems warm the reagents and reaction cells to the appropriate 
temperatures by directing heated air throughout the carousel as described 
in the copending application referred to above. The program also calls a 
scheduling program that schedules the operations to be performed by the 
instrument systems on the specimen samples. 
FIG. 4 is a flow chart illustrating the program operation for the scheduler 
program 60 used to schedule the operations to be performed by the analyzer 
unit to perform the assays on the load list in accordance with one 
embodiment of the present invention. The scheduler program allows for 
scheduling the tasks performed by the analyzer in order to assure that 
certain tasks are performed within allowable time frames and with 
favorable through put. STAGE 1 includes procedures for creating a list of 
time blocks and block descriptors for each time block, estimating the 
running time for each block, and sorting the load list. STAGE 2 includes 
procedures that establish the schedule of time blocks for each specimen 
sample so that the operations of a time block of a sample being scheduled 
do not conflict with any time blocks of any samples that have already been 
scheduled and that incubation limits between time blocks are not exceeded. 
STAGE 3 includes procedures for scheduling the cleaning or warming 
operations in, between, or before time blocks. 
FIG. 5 is a flow chart illustrating the program routines for operating the 
analyzer and calling the scheduler routines. A first routine RUNSVZ begins 
the operation and performs certain initialization procedures. RUNSVZ calls 
the SCHEDULE program that includes the STAGE 1 procedures. Time 
estimations for performing the "blocks" of commands are developed in the 
TMCMDS routine and output to the SCHEDULE program. The SCHEDULE program 
calls the SCHED2 program that includes STAGE 2 and STAGE 3 procedures. 
TMCMDS.LST, SCHEDULE.LST, and SCHED2.LST, are included in Appendix 1 of 
this specification. 
FIG. 6 is a diagram showing correspondence between the load list 60 and 
lists of block descriptors associated with each specimen sample as 
developed by the STAGE 1 procedures of FIG. 4. Based upon the entered load 
list, the STAGE 1 procedures develop time allowances for the operations to 
the performed by the analyzer unit instrument systems upon each specimen 
sample. The load list 60 indicates the sample specimen, e.g. Samples 1-24. 
The time allowances are organized into "time blocks", 1, 2, 3, associated 
with each of the samples. The time blocks represent one or more operations 
or activities to be performed by the analyzer systems upon or for that 
sample. Each specimen sample typically has associated with it several time 
blocks. For example, Sample 1 (as well as Samples 2 and 3) has three time 
blocks associated with it, Sample 4 has four time blocks associated with 
it, and Sample 24 has five time blocks associated with it. According to 
this embodiment of the invention, the time blocks establish when an 
analyzer unit resource (e.g. an instrument system) is occupied with a task 
associated with a sample. Accordingly, only one time block can take place 
(i.e. be performed) at a time. 
As mentioned above, in the STAGE 1 procedures in which the time blocks are 
developed, each of the time blocks of each specimen sample has "block 
descriptors" associated with it. The block descriptors contain information 
such as which sample the block is associated with, how much time will be 
allowed to perform the steps in this time block, and importantly, whether 
this block must be performed within a specific time limit or a specific 
range of time limits of other blocks associated with this sample. 
After the STAGE 1 procedures are completed, the scheduler program calls the 
STAGE 2 scheduler procedures. The STAGE 2 procedures actually develop the 
schedule of time blocks generated by STAGE 1. The sample having the 
highest assigned priority sequence number is scheduled first. As mentioned 
above, the sequence number does not necessarily correspond to which assays 
are started first, but rather to which samples are scheduled first. It is 
evident however that the assay for the sample with the highest priority 
will begin first because it will be scheduled first and there will be no 
constraints on scheduling the time blocks of the assay for that sample. It 
is also likely that other assays for samples with high priorities will 
also tend to be begun sooner. 
Referring again to FIG. 4, after the STAGE 2 procedures are completed, 
including the determination of the minimum intervals between time blocks 
and the scheduling of the time blocks, STAGE 3 procedures are performed. 
STAGE 3 procedures include the scheduling of necessary and appropriate 
rinse operations between time blocks, as explained in more detail below. 
Referring to FIG. 7, there is depicted a diagram illustrating an example of 
a portion of the sequence of time blocks scheduled by the scheduler 
program, above. Note that a start time has been assigned to each time 
block. The analyzer can then use the schedule to perform the assays of the 
specimen samples. 
As mentioned above, the cleaning operation is scheduled in the STAGE 3 
procedures. It is a feature of this embodiment of the invention that 
instrument system steps (other than the cleaning operation steps) are 
scheduled and fixed (in STAGE 2) before the cleaning operation steps are 
fixed (in STAGE 3). Thus, the determination of the appropriate type of 
cleaning operation can be made in STAGE 3 based upon instrument system 
operations that precede as well as follow the cleaning operation. 
As mentioned above, in an analyzer of the type considered herein, a time 
block represents instrument system operations associated with only one 
specimen. The time blocks are scheduled to perform the assay for each 
sample and to utilize the time interval between time blocks of one sample 
to perform time blocks of assays associated with other samples. Therefore, 
cleaning operations may be considered appropriate at the transition 
between time blocks because it is at this time that the instrument systems 
are likely to stop handling one sample and start handling another. 
However, the type of cleaning operation considered appropriate may depend 
upon whether different samples are being handled with the same assay or 
different samples are being handled with different assays. This is because 
of the greater concern over carryover when going from different 
sample/different assay than when going from different sample/same assay. 
Therefore, if the cleaning operations are not fixed until the time blocks 
for other instrument operations are fixed, then a cleaning operation 
appropriate for the type of transition between time blocks can be made. 
Therefore, the schedule of the time blocks that include all the instrument 
system operations (other than cleaning operations) is first fixed so that 
it can then be determined from the sequence of scheduled time blocks which 
type of transition occurs between adjacent time blocks. Then, the 
appropriate cleaning operation can be scheduled. 
In the STAGE 3 procedures, the cleaning operations are fixed. Even though 
the cleaning operations scheduled are not fixed until STAGE 3, the 
cleaning operations are based upon the cleaning operation options provided 
by the protocol written by the assay developer. In preparing a protocol 
for an assay to be run on an analyzer in which more than one assay can be 
performed in a run, the assay developer may specify optional cleaning 
operations one of which will be scheduled and performed depending upon the 
operations that are scheduled before that cleaning operation. As mentioned 
above, because of the various schedule permutations, the assay developer 
does not know specifically which specimens or which assays will be handled 
before and after the cleaning operation. However, the assay developer does 
know that it will be one combination out of a number of combinations. 
Therefore, the assay developer specifies more than one cleaning operation. 
Then, after the scheduler portion of the program fixes all the time blocks 
and the assay types and specimens being handled by adjacent time blocks 
are fixed, the STAGE 3 procedures select the appropriate cleaning 
operation out of the alternative options provided by the protocol prepared 
by the assay developer to insert into a final schedule that is performed 
by the analyzer instrument systems. (Note that in the schedule developed 
for performing the time blocks in STAGE 2, the rinse execution time must 
be accounted for in the scheduling process. When there is a conditional 
rinse to be performed between adjacent time blocks or at the beginning or 
end of a time block, an appropriate amount of time should be reserved for 
the rinse operation and this amount of time should be sufficient to 
perform the alternative rinse operation that required the greatest amount 
of time. 
The principle of operation of this embodiment is demonstrated by reference 
to the protocol example included in Appendix 2 to this specification. This 
protocol example provides the instructions for performing the LH assay. 
The protocol is written in CLI (command line interpreter) which is a high 
level programming language specifically designed for assay developers for 
operating the analyzer. By using a high level programming language 
specifically tailored to operate the analyzer, the assay developer is 
relieved of the burden of learning to program the detailed analyzer 
instrument system operations. Instead, the CLI language permits the assay 
developer to concentrate on the chemistry of the assay. For example, in 
the protocol example shown in Appendix 2, "MB dilu" means to move the boom 
to the diluent. "AS" means to aspirate. 
In the protocol example of Appendix 2, the commands for performing the 
instrument system operations are contained within "blocks". Each block 
begins with the command "B 0" and ends with the command "E". In the 
preferred embodiment of this invention, all commands for instrument 
systems operations related to a specimen samples should be included in a 
time block so that the transition from handling one sample and then 
another will always correspond to a transition between time blocks and 
therefore be accounted for. A command for performing a cleaning operation 
may be specified at or close to the beginning of each block. In practice, 
a cleaning operation at the beginning of a block is almost always 
specified. In addition to specifying cleaning operations at the beginning 
or transition of blocks, the assay developer may also include instructions 
to perform cleaning operations within blocks, as appropriate. 
In the protocol language used, the command "KUSS" is a instruction to 
perform a cleaning operation. The parameters following the KUSS command 
specify further information about the cleaning operation. The first 
parameter is the condition, the second parameter is the type of cleaning 
operation to be performed and the third parameter is how many times the 
operation is to be performed. These parameters will be explained in more 
detail below. 
The second parameter of the KUSS command indicates the cleaning operation 
type. There are various types of cleaning operations that use, for 
example, different total volumes of rinse, different rinse dispensing 
speed, different volume/increment and different dispensing heights. In an 
analyzer of the type considered herein, about 60 different rinse 
operations are defined and are stored in memory. Each of these different 
rinse types is given a number. Thus, referring to the example of Appendix 
2 at line 2, the cleaning command for the first block is "KUSS 0 24 1". 
The second parameter, 24, refers to the type of rinse type designated by 
the number 24 and stored in memory. 
The third parameter of the KUSS command indicates the number of repetitions 
of the specified rinse type to perform. In the example, the third 
parameter following the KUSS command is "1" which indicates that the 
specified rinse, i.e. number "24", should be performed one time. 
The first parameter following the KUSS command is the conditional trigger. 
In this embodiment, the numbers "0", "1", and "2" are may be specified. 
"0" means that the rinse specified in this command should be performed 
regardless of the block preceding this block in the fixed schedule. "1" 
means that the rinse specified in this command should be performed if the 
block preceding this block in the fixed schedule is the same block/same 
assay only. "2" means that the rinse specified in this command should be 
used if the block preceding this block is a different block only. Note 
that if a "1" is specified, "2" must be located immediately after. In this 
scenario one rinse type is executed in IF THEN ELSE fashion; however, "2" 
can be specified without "1". 
For purposes of the conditions set forth in the conditional rinse commands, 
"Same Assay/Same Block, or Different Block" means that a Different Block 
can be the same assay/different block or different assay block. 
In a further aspect of the present embodiment, a default rinse is 
specified. The default rinse is scheduled by the scheduler program but is 
not listed as a command in the protocol written by the assay developer. 
This default rinse is used to address the problem of pre-warming the 
probe. As mentioned above, it is possible that depending upon the 
combination of assays provided on the load list, that there may be a 
substantial time between scheduled time blocks when the instrument 
systems, such as when the probe may be idle. In such a case, it is 
possible that the probe might cool off while it is idle. Then, when it is 
used again for the instrument operations of the next scheduled block, it 
may cool off the reagent or sample being handled thereby affecting the 
assay. The default rinse accounts for this potential problem by scheduling 
a default rinse prior to any block when the amount of time after the end 
of the previous block and before the start of the block exceeds a 
predetermined time. This time between blocks can be determined after the 
STAGE 2 procedures schedule all the time blocks. The default rinse in 
scheduled in STAGE 3 with the other rinse operations. If a rinse operation 
is specified by the protocol for the block anyway, the default rinse is 
not scheduled because the probe will be warmed sufficiently by the 
scheduled rinse operation. The default rinse is scheduled when no rinse 
operation is otherwise scheduled and a specified probe idle time elapses. 
In preferred embodiment, the pre-warm rinse type (600 microliters) is 
executed by default. 
FIG. 8 is a diagram illustrating the operation of the portion of the 
scheduler program used to determine the type of rinse and/or pre-warm 
operation to be scheduled at the start of the block in accordance with the 
description set forth above. The portions of the program code 
corresponding to the flow chart of FIG. 8 for performing the determination 
of the minimum interval can be found in Appendix 1 in SCHED2.LST starting 
at line 1176. 
The method of the present embodiment described above, eliminates carryover 
of unknown analyte by commanding the performing of between block rinsing 
as part of the commands at the beginning of a block before the first 
aspirate or dispense steps in the block. The current block (not the 
previous block-different assay) determines the worse case carryover rinse 
appropriate for that block. This approach safeguards against unknown 
analyte carryover across one or more blocks. 
The above method provides for reducing the amount of rinse solution used. 
When a block transition does not indicate a significant carryover concern, 
a lesser amount of rinse solution is used. Therefore, less rinse may be 
used overall thereby requiring that the rinse be replaced less frequently. 
Also, by using less rinse, less waste is generated. 
With this aspect of the invention, the scheduling routine dynamically and 
adaptively determines the appropriate type of cleaning operation based 
upon the actual sequence of activities selected by the scheduler. 
In alternative embodiments, the conditional cleaning command may be located 
at the end of a time block and be conditioned on the time block that 
succeeds the time block having the conditional rinse information. In a 
further embodiment, there may be conditional rinse information at both the 
beginning and the end of a time block and the rinse performed may be 
conditioned on one or the other rinse command, depending upon a priority, 
or on both. 
In a further embodiment of the present invention, a "paneling" feature 
could be provided. With "paneling", separate patient samples would not 
have to be prepared when it is desired to run several different assays on 
the same patient's sample. To provide this feature, one or more disposable 
cartridges not containing any patient specimen sample could be loaded into 
the carousel rack in addition to the cartridge containers having patient 
specimen sample. The fluid moving system of the analyzer would then move 
portions of the patient's specimen sample from the one disposable in which 
it had been provided, and pipette it to the disposables not containing the 
patient's sample. Thus, the analyzer unit can relieve the operator or 
others from the need for preparing separate containers. 
Although the present invention has been described in terms of a biological 
analyzer that operates automatically and unattended (e.g. in a "walk-away" 
mode in which the operator-user does not add or remove specimen during a 
run), it is understood that the present invention can readily be adapted 
to an "interruptable" mode analyzer in which the processing of the samples 
during a run can be interrupted so that an additional sample may be added. 
In such an analyzer, the processing program would modify the interrupted 
schedule so that the desired assay could be performed on the added 
specimen sample in a similar manner as if it were part of the original 
load list. 
It is intended that the foregoing detailed description be regarded as 
illustrated rather than limiting and that it is understood that the 
following claims including all equivalents are intended to define the 
scope of the invention.