WO2014074762A1

WO2014074762A1 - Method of increased throughput in an immunoassay analyzer

Info

Publication number: WO2014074762A1
Application number: PCT/US2013/069026
Authority: WO
Inventors: Beri Cohen
Original assignee: Siemens Healthcare Diagnostics Inc.
Priority date: 2012-11-12
Filing date: 2013-11-08
Publication date: 2014-05-15

Abstract

An immunoassay system with a theoretical number (Ρ_T) of stops required to achieve a longest single-pass includes a number of stops that is (2*Ρ_T+ 1). The system includes a closed-loop carrier with the same number of positions. In operation, the carrier will increment by two stops every cycle. All assays are placed in carrier positions corresponding to odd stops. Single-pass tests go around once and come out at the last stop. Two-pass tests go around a second time but are in the carrier positions corresponding to even stops on the second pass and do not interfere with the placement of new assays in the carrier positions corresponding to odd stops.

Description

Docket No: 2012P25897WO

METHOD OF INCREASED THROUGHPUT IN AN IMMUNOASSAY ANALYZER

BACKGROUND OF THE INVENTION

The throughput in an immunoassay (IA) analyzer is determined by the number of cycles or tests that can be completed in a given time period, usually expressed as tests/hr. There are, however, tradeoffs that must be made as between throughput and the mechanics of the system that affect such issues as size and cost.

Many immunoassay systems use a ring or another closed loop path such as a racetrack to carry the tests in cuvettes that move along the closed path to receive services such as cuvette loading, sample addition, reagent addition, washes, signal generation, cuvette unloading and so forth. In such systems, a single-pass assay is defined as an assay that completes all of its functions within one pass along, or around, the closed-loop path. A two-pass assay is defined as an assay that requires two trips along, or around, the closed-loop path to complete all of its needed operations.

In a known system, for example, the Siemens Centaur CP system, the cycle time is 20 seconds (180 tests/hr), and the reaction ring size has 80 positions. The optimal ring size in this system corresponds to the longest duration of a single-pass test in the assay menu. In this case it is the <test time>*<# of positions> and, therefore, 20*80=1600 seconds or about 26.7 minutes. If the throughput were reduced to about 90 tests/hr, the ring size required to maintain the longest single- pass test would be, therefore, 40 positions. In such a system, every cycle increments the ring by one position to allow a new test to be added and existing tests are discarded at the end of the single- pass providing an empty position for a new test.

When an assay requires two passes, however, the test occupies a position on the ring for the duration of the second pass, thus preventing that position from being used for a new test. A system that runs a worklist consisting entirely of two-pass assays will see a reduction of throughput to half of the theoretical value for single-pass assays.

What is needed is a way to reduce this inefficiency in a system where there may be a mix of single-pass and two-pass assays being implemented without increasing hardware complexity and cost.

BRIEF SUMMARY OF THE INVENTION

In a simpler, or lower-cost IA analyzer, the increased time it takes to complete analysis can be an acceptable trade-off for lesser complexity and fewer mechanisms. Thus, with a longer cycle time, a reaction ring can be made proportionally smaller. As an example, in a known system, as mentioned above, if a reaction ring for an instrument having a cycle time of 20 seconds has 80 positions, then only 40 positions are needed when the cycle time is 40 seconds. In one embodiment of the present invention, the reaction ring has 81 positions and increments by two positions every cycle, rather than by one position. Each new test will be added in an odd position. If an assay requires a second pass, the cuvette will occupy an even position in the second pass and will not prevent new assays from being added into the odd positions. Such an arrangement eliminates the throughput bottleneck that can be experienced in currently known systems, where throughput is half of the theoretical if all assays in a given run are two-pass assays.

In one embodiment, a method of operating an immunoassay system having a predetermined number PN of sequential stops, and a predetermined cycle time, wherein PN is an odd number, and a closed loop movable carrier comprising P sequential positions, wherein one of the stops is a carrier unloading stop, includes loading a first assay into a first carrier position corresponding to a first stop Ai; moving the carrier a net increment of two stops, within the cycle time, such that the first carrier position is corresponding to a second stop (Ai+2); and continually determining if a loaded carrier position with either a single-pass assay or a two-pass assay is presented at the carrier unloading stop. Further, if a single-pass assay is presented at the carrier unloading stop, then the presented single-pass assay is unloaded; and if a two-pass assay is presented at the carrier unloading stop and has completed two rotations, then the presented two-pass assay is unloaded.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Embodiments of the present invention may be better understood by referring to the following description in conjunction with the accompanying drawings in which:

Fig. 1 is a representation of an empty reaction ring;

Fig. 2 is a representation of the state of the ring after three single-pass assays in a single- pass worklist have been added;

Fig. 3 is a representation of the ring after a full set, with respect to the size of the ring, of single-pass assays has been added;

Fig. 4 is a representation of the ring where the first three two-pass assays of a worklist of two-pass assays have been added;

Fig. 5 is a representation of the ring with the worklist of Fig. 4 after 45 tests of the all-two- pass assays worklist have been added;

Fig. 6 is a representation of the ring with a steady state of two-pass assays being performed; Fig. 7 is a diagram of an instrument layout in a system according to an embodiment of the present invention; and

Fig. 8 is a block diagram of a system in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the present invention. It will be understood by those of ordinary skill in the art that these embodiments of the present invention may be practiced without some of these specific details. In other instances, well-known methods, procedures, components and structures may not have been described in detail so as not to obscure the embodiments of the present invention.

As will be described in more detail below, an immunoassay (IA) system with a theoretical number (Ρχ) required to achieve the longest single-pass has a number of stops equal to twice the theoretical number (Ρχ) plus one, i.e., <2*Ρχ+1>. The IA system also includes a closed-loop ring or carrier having the same number of positions. In operation, the ring will be incremented by two stops every cycle. Such a ring size is practical for a small analyzer and in a simpler, or lower-cost, IA system, the increased time it takes to complete analysis can be an acceptable trade-off for lesser complexity and fewer mechanisms.

Thus, with a longer cycle time, a reaction ring can be made proportionally smaller. As an example, if an instrument having a cycle time of 20 seconds has 80 stops, then only 40 stops are needed when the cycle time is 40 seconds. If, however, the system has 81 stops when the cycle time is 40 seconds, and increments by two stops every cycle, rather than by one stop per cycle, each new, i.e., subsequent, sample will, or can, be added at an odd stop. If an assay requires a second pass, the cuvette will be located at an even stop in the second pass and will not prevent new assays from being added at the odd stops.

In operation, new assays going through their first pass, whether they are single-pass or two- pass, will first occupy positions in the ring that correspond to odd-numbered stops in the system. With a ring having an odd number of total positions and incrementing two stops per cycle, each single-pass assay will be finished by the time it completes a full revolution and their positions on the ring will correspond to even stops on the analyzer as they enter the second revolution and will be traveling empty, the respective cuvettes having been removed at the completion of the first pass.

On the other hand, the two-pass assays will stay in the ring for the second pass or rotation and will be in, or correspond to, even stops, by virtue of the system, and ring, having an odd number of positions and having come around one rotation, and thus will not conflict with new assays that will occupy positions corresponding to odd stops, so the system will not slow down. At the end of the second pass, the two-pass assay will be removed from the ring before, or after, the final measurement and that position will correspond to an odd stop , available for a new test.

In the description to follow, various views of an analyzer with a closed-loop ring or carrier, according to embodiments of the present invention, at various stages of two hypothetical worklists of immunoassays, will be described. It should be noted that the ring can have various modes of moving and may pause during the cycle for sample delivery, reagent delivery, washing, adding signal-generating reagents, measuring signals, etc., as known to one of ordinary skill in the art. If disposable cuvettes are used, a cuvette load/unload operation may be necessary although it could be combined with other operations, otherwise, a cuvette wash station may be needed and the carrier loop length may be increased somewhat to provide for the additional time required to wash and dry the cuvette. As used herein, the terms "loading" and "unloading" can be construed as either loading a container and its reaction contents or adding sample and reagents to a fixed container and, therefore, are only meant to be examples of what may happen at a stop but not meant to be limiting.

Referring now to Fig 1, an immunoassay analyzer 10 includes a closed-loop reaction ring or carrier 100 with a plurality of ring positions 104 that, initially, are empty. The ring 100 is configured to rotate bi-directionally, i.e., either clockwise or counterclockwise. For discussion purposes only, there are 81 locations or stops 102 on the analyzer 10 which are sequentially numbered 1-81, as represented by the underlined numbers, with the odd locations specifically identified in Fig. 1 and the other figures. The analyzer stops 102 may be identified with a respective position number by a mark, i.e., the value, on a work surface adjacent the stop 102. Additionally, as an example only, the 75^th stop may be a wash station 108, the 77^th stop may be a signal-generating reagent addition station 112, the 79^th stop may be a signal reading station 116 and a cuvette unload station 120 may be provided at the 81^st stop.

The ring 100 also has 81 ring positions 104, i.e., the same amount as the stops 102 provided in the analyzer 10. In one embodiment, each ring position 104 is configured to receive a disposable cuvette but could also be a reusable cuvette with appropriate modifications. The use of one type of cuvette or the other, however, is not germane to the present invention. One of ordinary skill in the art will understand, from reading this disclosure, however, that any odd number 2*n+l, for n >2, could be chosen for the system.

To aid in an explanation of the various embodiments of the present invention, an index mark M is provided on the ring 100. Further, for ease of understanding, in the example the ring 100 is set such that the index mark M is initially aligned with the 1^st stop of the analyzer 10. In operation, a new cuvette is added to the ring position 104 adjacent the I^s stop 102 of the analyzer and a cuvette that has completed the assay is removed from the ring position 104 adjacent the 81^st stop 102. For each cycle of operation, the ring 100 is moved to have a net increment of two stops, e.g., the ring position adjacent the n* stop will move to the (n* + 2) stop in one cycle .

In one example, a first worklist is a series of identical single-pass assays that have the longest single-pass duration of 40 cycles from sample addition, i.e., at the 1^st stop, to cuvette unload at the 81^st stop. Referring now to Fig. 2, after three cycles the ring 100 has been loaded with three cuvettes, as represented by the solid circles, that are adjacent the 1^st, 3^rd and 5^th stops 102. Thus, the index mark M is now adjacent the 5^th stop with the first assay introduced also adjacent the 5^th stop, the second assay adjacent the 3^rd stop and the latest introduced assay at the 1^st stop, as shown in Fig. 2. One of ordinary skill will understand that the "snap-shot" shown in Fig. 2 is after the cuvette has been loaded at the 1^st stop but before the movement of the ring 100 two stops.

Assuming that new assays continue to be introduced at each consecutive cycle, the ring 100 is incremented, i.e., moved two positions, and after 40 cycles, as shown in Fig. 3, only positions of the ring 100 corresponding to odd-numbered stops on the analyzer 10 are filled, as represented by the solid circles. That is, each ring position 104 corresponding to an odd-numbered stop 102 has a cuvette in it. In addition, if the worklist was an endless list of single-pass assays, the ring 100 would appear as shown in Fig. 3, at any cycle. Thus, all of the odd positions 104 are occupied, completed tests are removed at the 81^st stop and new tests are inserted at the 1^st stop. The throughput is maintained at the rate of a new sample every cycle.

In an embodiment where a worklist of the longest two-pass assay is implemented, the state of the ring 100 where the first three assays have been inserted is shown in Fig. 4. In an operation similar to the single-pass embodiment described above, after three cycles, but before the two-step movement of the third cycle, the ring 100 has cuvettes in the 1^st, 3^rd and 5^th positions 104 as represented by the solid circles. Thus, the index mark M is now adjacent the 5^th stop with the first assay introduced adjacent the 5^th stop, the second assay adjacent the 3^rd stop and the latest introduced assay at the 1^st stop

Referring now to Fig. 5, after 45 cycles of the two-pass worklist, new assays continue to be introduced at the 1^st stop, and because of the two-stop increment, are loaded in the odd positions, i.e., the 1^st, 3^rd and 5^th as represented by the solid circles, and occupy those odd positions during the first pass. The first four assays of the two-pass worklist, however, have now entered a second revolution of the ring 100 and now occupy positions that are adjacent even-numbered stops of the analyzer. Thus, as shown by the locations marked with an X, the first assay (and the index mark M) is adjacent the 8^th stop, the second assay is adjacent the 6^th stop, the third assay is adjacent the 4 stop and the fourth assay is adjacent the 2ⁿ stop. The assays on their second trip around, advantageously, do not interfere with the introduction of new assays into the odd positions because they now occupy locations on the ring that are adjacent even-numbered stops of the analyzer due to the fact that the ring is moved two stops for each cycle.

In the present example, when the worklist is more than 80 tests long all ring positions 104 are occupied as shown in Fig 6. The "new" tests, i.e., those on their first rotation, are adjacent the odd stops 102, indicated by solid circles, and those on the second pass occupy the even stops 102, indicated by an X. Once an assay completes its second rotation, it is removed at the end of the rotation at the 81^st stop. It should be noted that the movement into the 81^st stop, as it is an odd number, necessitates a dedicated ring move during the cycle to provide for removal at this location, i.e., it is a net single position movement.

It should also be noted that there is nothing that prevents one from removing a cuvette at position 80 but doing so could necessitate a more complicated removal mechanism. Generally, a loading stop and an unloading stop do not have to be located at the beginning and the end, respectively, of the circle. They could be located, for example, at the 37^th and 58^th stops, and have a dedicated ring move within the cycle to bring the cuvettes needing these actions to these stops. The choice of stops 1 and 81 is provided for the simplicity of illustration and explanation. Also, as a result of this arrangement, with two adjacent cuvettes, where one is a single pass test and the other is a two-pass test, it is understood that it may be necessary for both to be removed in the same cycle and sufficient time, therefore, for both operations would then be allocated.

Advantageously, full throughput is maintained at the rate of a new sample every cycle, as opposed to known designs where such a worklist would result in stopping new sample processing for a period that is equivalent, in the worst case, to the number of cycles corresponding to the ring size, thus cutting throughput down to half of the maximum possible.

In the example above, when a test starts at the 1^st stop 102 and the cycle time is 40 seconds, it will take about 26.7 minutes to make a full trip around the ring 100. If shorter overall assay times are desired, the assay should start at a stop 102 closer to the wash station stop 108, in this example, the 77^th stop. For example, if the assay starts in the 41^st stop, it will take 20 cycles (at two stops per cycle) for it to arrive at the unload stop 120, i.e., the 81^st stop and, therefore, it will only take about 13.3 minutes.

The mathematical relationship for a single-pass assay is: <assay length in minutes> = (<ring size> - <starting position>)/2 * <cycle time in seconds> / 60 The length of a two-pass assay is the length of the single-pass plus the duration of a full trip around the ring, which is:

(<ring size> - <starting position>)/2 * <cycle time in seconds> / 60 + <ring size> 1 2 * <cycle time in seconds> / 60

Within this assay duration variability, more protocol flexibility is possible by varying the times at which reagents are added, number of reagents, wash sequence, etc. This variation provides for a wide variety of protocols to be achievable on a system that incorporates an embodiment of the present invention.

In a first approach, sample and reagent probes that can reach any location on the ring 100 are provided, or at least all locations required to achieve the desired assay protocol flexibility. In one non-limiting example, one or more X-Y-Z gantries that can reach every location on the ring 100 can carry the sample and reagent probes. In such a case, the ring 100 can increment every cycle and complex moves are not necessary. Any magnets that may be used at the wash station, i.e., for immunoassays using magnetic particles as carriers, can be fixed rare-earth or electromagnets. If a mixing action is necessary to homogenize the cuvette contents it can be done with a short- amplitude vibration (e.g. one cuvette position back and forth) so that cuvettes that are in the magnetic field of the wash station are not removed from it.

Where the mechanism for placing/moving sample and reagent probes may have limited reach, because of interference with other mechanisms or due to any other engineering considerations like timing, cost, complexity or reliability, a second approach may be used. In this case, the reaction ring can use the variable ring moves concept taught in US Patent Publication 20090308183, entitled "Assay Timing in a Clinical Analyzer Using a Cuvette Carrier," the entire contents of which are herein incorporated by reference. It should be noted, however, that a fixed magnet at the wash station may not be viable in this mode of operation because cuvettes will be going in and out of the magnetic field, thus reducing the effectiveness of the magnetic separation. A separate magnet ring that can be coupled to, and decoupled from, the incubation ring may be implemented, as described in the above-incorporated patent application.

In any event, one of ordinary skill in the art will understand that each approach may use a timing conflict management protocol when assays that have different timing requirements are run in a random-access mode. The above-incorporated patent application teaches a method of conflict management consisting of a reservation and lookahead system where assays that are already present on the ring have reserved the timing positions for all future operations and if a new assay has a conflict with any such reserved position, it will not be introduced. The system will check each subsequent test in the worklist for timing compatibility and the test will be introduced if no conflicts are found.

In an embodiment of the present invention, referring to Fig. 7, a system 700 has a layout of instruments that allows for an implementation of the embodiments of the present invention as described above. In the system 700, in order to save on space, fluidics and electronic components 704 are housed in the back of the system 700 and may be provided to hang over the ring 100 and, as a result, not all of the positions 104 may be accessible. Thus, the second flexible timing approach described above would be used in random access mode.

A single X-Y-Z gantry 708 supports a sample probe using disposable tips, a reagent probe using a fixed washable tip, and a gripper for loading cuvettes into the ring and unloading them and disposing into solid waste (not shown). Cuvettes and tips may be housed in manually loaded magazines. Samples and reagent may be loaded manually. The wash station, signal-generating reagent addition and signal measurement can be placed as a group at any desired location. One of ordinary skill in the art will understand that other configurations may be used and the one shown is merely a non- limiting example.

It should be noted that the movements of the carrier described herein represent overall increments per cycle. Thus, within the cycle there can be other moves to bring cuvettes to various service stations but the net increment per cycle is two positions.

Referring now to Fig. 8, in one embodiment, a system 800 includes the analyzer 10, as described above, in addition to a controller 804 coupled to the analyzer 10. The controller 804 includes a processor, memory, e.g., ROM and RAM, storage device, I/O device, and associated software, configured to control the analyzer 10 in accordance with that described above. Thus, the controller 804 is configured to at least receive an assay worklist and determine an appropriate order based on time or cycles needed. In addition, the controller 804 is coupled to the analyzer 10 in order to determine a configuration of the ring 100, i.e., which ring location is adjacent which stop, how long the ring 100 has been in the cycle, which ring positions are empty or occupied, etc. Accordingly, the controller 804 can identify empty locations on the ring 100 and determine if a scheduled assay can be accommodated in that location.

It should be noted that although a ring 100 is described, embodiments of the present invention are applicable to any closed-loop carrier, e.g., a "racetrack" as known to one of ordinary skill in the art. In addition, one of ordinary skill will understand that the new assays could be placed in "even" positions and the concepts of the present invention would still apply. The example using the odd positions was chosen simply for purposes of explanation and is not intended to be limiting.

Having thus described several features of at least one embodiment of the present invention, it is to be appreciated that various alterations, modifications, and improvements will readily occur to those skilled in the art. Such alterations, modifications, and improvements are intended to be part of this disclosure and are intended to be within the scope of the invention. Accordingly, the foregoing description and drawings are by way of example only, and the scope of the invention should be determined from proper construction of the appended claims, and their equivalents.

Claims

CLAIMS What is claimed is:

1. In an immunoassay (IA) system having a predetermined number P_N of sequential stops, wherein P_N is an odd number, and a closed loop movable carrier comprising P_N sequential positions, wherein one of the stops is a carrier unloading stop, a method of assay loading into and unloading from the carrier, comprising:

(a) loading a first assay into a first carrier position corresponding to a first stop Ai ;

(b) moving the carrier a net increment of two stops such that the first carrier position is corresponding to a second stop (Ai+2);

(c) continually determining if a loaded carrier position with either a single-pass assay or a two-pass assay is presented at the carrier unloading stop and:

(d) if a single-pass assay is presented at the carrier unloading stop, then unloading the presented single-pass assay; and

(e) if a two-pass assay is presented at the carrier unloading stop and has completed two rotations, then unloading the presented two-pass assay.

2. The method of claim 1, further comprising:

(f) continually determining if a second assay can be loaded into a second carrier position which is (2*y) positions away from the previously loaded assay, y being an integer;

(g) if it is determined in step (f) that a second assay can be loaded, then loading an assay into the second carrier position ; and

(h) moving the carrier a net increment of two stops.

3. The method of claim 2, further comprising:

repeating steps (f) - (h).

4. The method of claim 1, further comprising:

(f) loading a second assay into a second carrier position corresponding to the first stop Ai; and

(g) moving the carrier a net increment of two stops.

5. The method of claim 4, wherein the IA analyzer comprises a carrier loading stop at the first stop Ai.

6. The method of claim 4, further comprising:

repeating steps f) and g).

7. The method of claim 1, wherein step (b) comprises:

moving the carrier in a first direction.

8. The method of claim 1, wherein step (b) comprises:

moving the carrier in a first direction and in a second direction opposite the first direction.

9. The method of claim 1, wherein the carrier comprises one of:

a ring of assay positions; and

a racetrack of assay positions.

10. The method of claim 1 , wherein the IA analyzer comprises a carrier loading stop and wherein: the carrier loading stop is at stop Ai=l; and

the carrier unloading stop is at stop AI=P .

11. The method of claim 1 , wherein:

the carrier loading stop and the carrier unloading stop define a range less than the entire range of PN stops.

12. The method of claim 1 , wherein:

in step (a) Ai is chosen such that 1 < Ai< PN, wherein Ai is an odd number; and steps (b) - (e) are performed on stops from Ai to (Ai + X) where (Ai + X) < P .

13. The method of claim 1 , wherein the carrier unloading stop is at stop ¾=ΡΝ and:

in step (a) Ai is chosen such that 1 < Ai < PN, wherein Ai is an odd number; and steps (b) - (e) are performed on stops from Ai to PN.

14. The method of claim 1 , wherein in step (e), unloading comprises:

moving the carrier one stop, unloading the two-pass assay, then moving the carrier one additional stop.

15. The method of claim 1, wherein the closed loop movable carrier is configured to carry a disposable cuvette at each carrier location.

16. The method of claim 1, wherein the closed loop movable carrier is configured to carry a fixed and washable cuvette at each carrier location.

17. The method of claim 1 , further comprising:

(f) loading a second assay into a second carrier position corresponding to a second stop (Ai + X ,

wherein (Ai + X) is an odd number.

18. In an immunoassay (IA) system having a predetermined number PN of sequential stops, wherein PN is an odd number, and a closed loop movable carrier comprising P sequential carrier positions, the IA system further comprising a carrier loading stop and a carrier unloading stop, a method of assay loading into and unloading from the carrier, comprising:

(a) moving the carrier such that a first carrier position CLi is presented at the carrier loading stop;

(b) loading a first assay into the first carrier position CLi at the carrier loading stop;

(c) moving the carrier such that a second carrier position CLi+2 is presented at the carrier loading stop;

(d) loading a second assay into the second carrier position CLi+2 at the carrier loading stop; and

(e) continually determining, after each of steps (a) and (c), if a loaded carrier position with either a single-pass assay or a two-pass assay is presented at the carrier unloading stop and:

(f) if a single-pass assay is presented at the carrier unloading stop, then unloading the single-pass assay; and

(g) if a two-pass assay is presented at the carrier unloading stop and has completed two rotations, then unloading the two-pass assay.

19. The method of claim 18, wherein step (a) comprises:

moving the carrier in a first direction.

20. The method of claim 19, wherein step (c) comprises:

moving the carrier two stops in the first direction.

21. The method of claim 18, wherein step (c) comprises:

22. The method of claim 18, further comprising:

repeating steps a) - g).

23. The method of claim 18, wherein the carrier comprises one of:

a ring of assay positions; and

a racetrack of assay positions.

24. The method of claim 18, wherein:

the carrier loading stop defines a start of the carrier; and

the carrier unloading stop defines an end of the carrier.

25. The method of claim 18, wherein in step (g), unloading comprises:

moving the carrier one carrier position, unloading the two-pass assay, then moving the carrier one additional carrier position.

26. The method of claim 18, wherein the closed loop movable carrier is configured to carry a disposable cuvette at each carrier position.

27. The method of claim 18, wherein the closed loop movable carrier is configured to carry a fixed and washable cuvette at each carrier position.

28. The method of claim 1, wherein the IA system comprises a machine cycle time, wherein step (b) further comprises:

moving the carrier a net increment of two stops within the machine cycle time.

29. The method of claim 28, further comprising:

(g) if it is determined in step (f) that a second assay can be loaded, then loading an assay into the second carrier position ; and (h) moving the carrier a net increment of two stops within the machine cycle time.

30. The method of claim 28, further comprising:

(g) moving the carrier a net increment of two stops within the machine cycle time.

31 The method of claim 28, wherein step (b) comprises:

moving the carrier in a first direction and in a second direction opposite the first direction within the machine cycle time.

32. The method of claim 18, wherein the IA system comprises a machine cycle time, wherein step (c) further comprises:

moving the carrier such that the second carrier position CLi+2 is presented at the carrier loading stop within the machine cycle time.

33. The method of claim 32, wherein step (c) comprises:

moving the carrier two stops in a first direction within the machine cycle time.

34 The method of claim 32, wherein step (c) comprises: