CROSS-REFERENCES TO RELATED APPLICATIONS

|O0O1] This application claims priority to U.S. Provisional Patent Application No. 61/556,667, filed November ^" /, 201 1 and entitled "Analytical System and Method for Processing Samples." This appiication also claims priority to U.S. Provisional Patent Application No. 61/616,994, filed March 28, 2012 and entitled "Analytical System and Method for Processing Samples." This application also claims priority to U.S. Provisional Patent Application No. 61/680,066, filed August 6, 2012 and entitled "Analytical System and Method for Processing Samples." All of these applications are herein incorporated by reference in their entirety for all purposes. BACKGROUND

[0002} Conventional medical laboratory systems contain many segments for processing patient samples, some of which are automated and some of which require manual operation. Laboratory systems today have become more efficient due to those segments which have become automated. However, there are still several components of medical laboratory systems that can be automated in order to reduce the time It takes for an analysis of a sample, reduce the need for manual operation of the system, and reduce the space required by machinery.

[0003] Generally, the laboratory process can be organized into four phases: association, pre- analytical, analytical, and post-analytical. These four phases typically occur within any laboratory process. However, some conventional labs may have a process that uses standalone units throughout the lab while others may connect some of the units with a conveyance system to move the sample from unit to unit. These two styles have some com mon and some different processing needs. Additionally, some conventional labs may consistently process the same types of sample tubes (e.g., as in those from a kit) while others may have a wide range of tube types they must accommodate. Furthermore, many labs may have a preference for a particular manufacturer of an analyzer while others may use all of the analyzers from one manufacturer. [0804] Thus, there is a need for a more efficient system and method for processing patient samples that can accommodate both a process using standalone units and units connected with a conveyance system, a variety of sample tube types, and analyzers from any manufacturer.

(0005] One aspect of automated laboratory systems relates to tube identification. Automatic tube identification is needed in a laboratory system so that the laboratory system knows how to process samples in the sample tubes.

[0006] Conventional tube-in-rack detection typically utilizes image analysis tools on 2- dimensional images acquired by one camera or a plurality of cameras in order to determine objects in the field of view of the cameras. This technology is well known in various fields, including, e.g., the analysis of pathology samples by microscopes.

[0007] in other fields, this technology may be used to identify objects in moveable loading or unloading means of a system, including, e.g., identifying drawers of a workbench. See, e.g., WO/2010/017528. A series of images can be taken by each camera during the opening and closing of the drawer and stitched together to generate an overview image. Within this overview image, single objects can be detected by image analysis.

[0008] In the field of !aboratory automation systems, it is well known that single objects, such as a cap or closure of a sample tube, located in a holding rack can be identified by employing image analysis algorithms on top views of the hold racks. However, the image analysis algorithms are typically limited to the identification of only the single object and do not identify other details of the objects within the image.

[0009] Other tube identification mechanisms include the use of sample tube markers.

Conventional sample tube markers used to identify a sample tube requiring immediate analysis typically include self-adhering labels (e.g., colored labels indicating urgency), "urgent" stickers, or simply a handwritten note indicating urgency on already existing labels. These urgent sample tube markers are inefficient and non-automated, requiring a laboratory technician to apply and/or handwrite the indication of urgency.

[0010] Additionally, conventional sample tube markers used to identify a centrifuged sample may include g-force sensitive labels. These labels measure whether there was an impermissibly high shock daring transport. However, such labels are on the side of sample tubes, and as such cannot be easily reviewed or identified by overhead cameras and the like.

|O011] Embodiments of the invention address these and other problems, individually and collectively. BRIEF SUMMARY

[0012| Embodiments of the technology relate to systems and methods for efficiently processing patient samples.

[0013] One embodiment of the invention is directed to a system. The system includes at least one image acquisition device configured to obtain one or more images of a sample container holder or a sample container in the sample container holder when positioned above the sample container holder or the sample container in the sample container holder. The system also comprises an image analysis device coupled to the at least one image acquisition device and configured to analyze, by a processor, the one or more images of the sample container holder or sample containers in the sample container holder, to determine (a) a presence, absence, or characteristic of the sample container holder, wherein the characteristic of the sample container holder comprises a color or shape of the sample container holder, or a label or marker associated with the sample container holder, or (b) a presence, absence or characteristic of the sample container in the sample container holder, wherein the sample container characteristic includes one or more of a color or shape of the sample container, or a label or marker associated with the sample container.

[0014] Another embodiment of the invention is directed to a method. The method comprises acquiring, by the at least one image acquisition device, at least one image of the sarapl e container holder with the sample containers comprising samples, and analyzing, by an image analysis device, the at least one image. The a! least one image is analyzed to determine (a) a presence, absence, or a characteristic of the sample container holder, wherein the characteristic of sample container holder comprises a color or shape of the sample container holder, or a label or marker associated with the sample container holder, or (b) a presence, absenc e or a characteristic of the sample container in the sample container holder, wherein the sample container characteristic inckides one or more of a co!or or shape of the sample container holder, or a label or marker associated with the sample container.

[0015] Another embodiment of the invention is directed to a sample container cap comprising a cap body capable of covering a sample container body, and a movable element coupled to the cap body. The movable element is capable of indicating a status of the sample container for processing in a laboratory automation system.

[0016] Another embodiment of the invention is directed to a sample container cap comprising a sample cap body capable of covering an opersing of the sample container. A centnfugation status indicator device is in the sample cap body.

[0017] These and other embodiments of the technology are described in further detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018] FIG. 1 shows a block diagram of components associated with phases of a laboratory automation system.

[0039] FIG. 2 shows a block diagram of components associated with a pre-analyticai phase of a laboratory automation system.

[0020] FIG. 3 shows a system diagram according to an embodiment of the invention.

[0021] FIG. 4 shows a high-level block diagram of a tube and rack identification system showing elements of an analysis device according to an embodiment of the invention.

[0022] FIGS. 5(a)-5(c) show examples of camera units for sample tube or rack detection and analysis.

[0023] FIG. 6 show an example of an original image and a resulting analyzed image of a rack with sample tubes after a presence detection analysis.

[0024] FIG. 7 shows a sample tube with a sample tube body and a sample tube cap,

[0025] FIGS. 8(a)-8(b) depict one example of a top perspective view of a cap having an urgent sample indicator. [0026] FIGS. 9(a)~9(b) depict exemplary color indicators of centrifugation indicators.

[0027] FIGS. 10(a)- 10(b) show a non-centrifuged cap embodiment from a side cross-sectional view and a top plan view, respectively.

[0028] FIGS. 1 l (a)- l f (b) show a centrifuged cap embodiment from a side cross-sectional view and a top plan view, respectively.

[0029] FIG. 12 show a block diagram of an exemplary computer apparatus.

DETAILED DESCRIPTION

[0030] Embodiments of the invention relate to different ways to identify sample containers in an automated laboratory analysis system. One embodiment of the invention is directed to a system. The system includes at least one image acquisition device configured to obtain one or more images of a sample container holder or a sample container in the sample container holder when positioned above the sample container holder or the sample container in the sample container holder. The system also comprises an image analysis device coupled to the at least one image acquisition device and configured to analyze, by a processor, the one or more images of the sample container holder or sample containers in the sample container holder, to determine (a) a presence, absence, or characteristic of the sample container holder, wherein the characteristic of the sample container holder comprises a color or shape of the sample container holder, or a label or marker associated with the sample container holder, or (b) a presence, absence or characteristic of the sample container in the sample container holder, wherein the sample container characteristic includes one or more of a color or shape of the sample container, or labels and markers associated with the sample container.

[0031] In embodiments of the invention, a "sample container" may have any suitable shape or form. In some embodiments, the sample container may be in the form of a sample tube, which may have an aspect ratio of greater than about 3 : 1 . Such sample containers may be made or any suitable material including plastic, glass, etc. They may further include a sample tube body with a closed end and an open end, as well as a cap that is structured to cover and attach to the open end of the sample tube body. [0032] In embodiments of the invention, a "sample container holder" may be in any suitable shape or form, and may comprise any suitable material- I s some cases, the sample tube holder may be in the form of a sample tube rack. Sample container holders may include an array of recesses that can receive sample containers (e.g., sample tubes). They may also comprise any suitable material including plastic.

[0033] As discussed above, many conventional laboratory systems may have a process that uses standalone units throughout the lab, requiring that the samples be manually transported between each standalone unit, while others may connect some of the units with a conveyance system to move the samples from unit to unit. Additionally, as discussed above, sample tube sizes and equipment from different manufacturers may be constraints in conventional laboratory systems. Such conventional technology is slow and inaccurate. Embodiments of the present technology can be used in a modular laboratory system which is capable of accommodating different laboratory units and transport systems, sample tube sizes, and manufacturers by using more universal components and by grouping functions required by most laboratory systems into five basic functional units: (1 ) manager, (2) centrifuge, (3), aiiqtsotter, (4) output/sorter, and (5) storage units. These five basic functional un its will be described in more detail below.

[0034] in embodiments of the invention, the laboratory system operates a controlled process using a central controller or scheduler. By keeping the samples under the control of an intelligent scheduler, the system provides efficient usage of every instrument. The system can maintain a consistent minimal turnaround time and maximizes the throughput of the entire system by maintaining control of the process and only delivering samples to instruments when those instruments are ready and available.

[0035] The laboratory system according to an embodiment of the invention further utilizes one or more robotic gripper units mourned on robotic aims. Each robotic arm unit has a robotic gripper for gripping sample tubes and may be equipped with one or more means for detecting information about sample tubes. The terms "gripper" and "robotic gripper" are used interchangeably herein.

[0036] Use of a p!uraiity of robotic gripper units in the laboratory system also increases sample processing efficiency. For example, a first gripper, such as an input module gripper. identifies a sample tube and makes data measurements as described above. After the first gripper delivers the sample tube to a distribution area, a second gripper, such as a distribution area gripper, delivers a sample tube to a subsequent module such as a centrifuge module or conveyor. The use of multiple grippers allows an increase in processing efficiency over prior art systems that use only a single gripper to receive, identify, and toad all samples on a conveyor track.

I. Overall System

A. Phases of Laboratory System

[0037] FIG. 1 depicts one embodiment of a medical laboratory system for processing patient samples. The laboratory system includes components associated with the association phase 102, the pre-analytical phase 304, the analytical phase 106, and the post-analytical phase 108.

1. Association Phase

[0038] The association phase 102 is the first phase in the laboratory process. During this phase, the patient information, the requested tests for the patient sample, and a unique laboratory identifier (e.g., a barcode) are associated with one another. While the association phase 102 could be automated, in some embodiments, the association phase is handled manually. For example, in some embodiments, a laboratory technician (hereinafter reierred to as a "user") can assign a priority to the samples. The samples are loaded into racks or directly onto the system at specific entry points. Although grouping samples into a few basic priority levels (e.g., urgent or high priority, medium priority, low priority, etc.) may be desirable to provide a more consistent turnaround time, it is not necessary. Processing patient samples can be based on any priority defined by the user. However, if a priority is not specified, a priority can be assigned based on factors such as minimizing turnaround time, maximizing throughput, the availability of processes, etc.

2. Pre- A nalytical Phase [0039] The pre-analytical phase 104 includes preparing patient samples for analysis. During the pre-analytical phase 104, the patient and test information is deciphered, the process for analysis is planned, the quality checks are performed, the sample may be separated into its constituent components (e.g.. centrifuged), the sample may be d ivided for parallel analytical processes, and/or the sample can be delivered to one or more analyzers and/or racks. The pre- analytical phase 104 manages the flow of samples to different instruments and different analyzers within the lab system. This process management permits the system to operate efficiently and with minimal instruments. Additionally, the pre-analytical phase 104 ensures thai a backup of patient samples at different points within the lab system does not occur along the process, or if a backup does occur, the pre-analytical phase 104 ensures that the backup can be cleared quickly and without significant impact on the remainder of the system.

[0040] Embodiments of the system can identify the patient samples as quickly as possible and determine the best scheduling of each sample to provide a consistent minimal turnaround time and maximum throughput of the analytical processes. The steps and organization of those steps in the process are designed to avoid backups of patient samples. Modules of the lab system can operate at a throughput speed that ensures processing of samples at the maximum throughput of the upstream processes. However, in some embodiments, at the aliquotter unit, the throughput may be managed by the introduction of samples upstream and by small queues at each aliquotter station.

[0041] FIG. 2 is a more detailed depiction of the components associated with the pre-analytical phase 104. The components associated with the pre-analytical phase 104 include seven modules: input module 202, distribution area 204, centrifuge module 206, decapper 208, serum indices measurement device 210, aliquotter 212, and output sorter 214, Each of these modules may be physically and/or operationally coupled (directly or indirectly) to each other.

(a) In ut Module

[0042] The input module 202 shown in FIG. 2 can accommodate a variety of tubes, racks, prioritizations, etc. and is capable of receiving a specimen. Racks of tubes and/or individual tubes can be loaded onto one of several lanes 216, which may be manually operated drawers and/or automated devices. In FIG. 2, five lanes 216 are depicted. However, the lab system can have any number of lanes 21 . The lanes 216 are assigned priorities in accordance with those assigned by the user, in some embodiments, the highest priority lane (short turnaround time or "STAT") may have a fixed position for accepting a group of individual tubes from the user. Once tubes are loaded in the STAT lane, they become the next tubes processed. Other lanes can be assigned different priority levels in any manner. For example, when the drawers are manually operated, assigning one priority to at least two of the drawers and another priority to at least two other drawers may allow the system to operate continuously on one drawer wh i le the other drawer of the same priority is available to the user. [0043] In some embodiments, while the input module 202 is processing a drawer of samples, the user may be informed that the drawer should not be opened by using an indication such as a light on the drawer or a lock on the drawer. This may help maintain the process integrity and maximize throughput. When processing is complete on the first drawer, the drawer may be identified to the user as available, and the system may automatically begin processing another drawer. Additionally, the samples can be transferred to and from the drawers 216 of the input module 202 using an input module gripper 228.

(b) Distribution Area Module j()044j From the lanes (or drawers) 216 within the input module 202 of FIG. 2, one of at least two or more grippers 21 8 (discussed in more detail below) may select the highest priority tube and transport it to a fixed matrix called the distribution area 204. The distribution area 204 is capable of distributing a specimen to a desired component of the laboratory automation system. During the transfer to this module by the input module gripper 228, the levels of the sample's constituent components are measured and photographs of the sample tube arc taken. These photographs can be analyzed to determine the tube's manufacturer, diameter, height, cap color, etc. From this information, the volumes of the sample's components can be calculated, and an estimate of the total tube weight can be made. This weight can be later used to aid in balancing the centrifuge buckets in the centrifuge module 206, as will be discussed in more detail below.

[0045] To protect the distribution area 204 from filling with low priority tubes, a limit can be set on the number of tubes loaded into this area from the low priority input lanes. Moreover, the distribution area 204 may have a reserved area to ensure STAT samples have continuous access to the distribution area 204 from the STAT drawer in the input module 202.

[0046] The distribution area 204 can be the holding area which permits the system to access test information associated with the sample tube in the association phase 102 and plan the analysis process for the sample. This enables the system to schedule a sample tube's process with respect to the other sample tubes currently on the system. Scheduling enables the efficient processing of samples based upon priority without overloading any step in the overall system, permitting the optimization of turnaround time and throughput. Furthermore, the sample's schedule can be updated throughout the process as the system's activity or availability changes, providing real time active control of the sample.

J0047] Once the schedule is planned by the distribution area module 204, a gripper 21 8 then selects the sample tube that is the next tube to be transferred to the next module based on the priority of the tubes within the distribution area 204. The selected sample tube is transported from the distribution area 204 to the conveyance system 220, to the centrifuge module 206, or to an output drawer with an error area 222 based on the analysis performed by the distribution area module 204.

[0048] If the sample tube is being moved to the centrifuge module 206, the tube can be placed into the appropriate centrifuge adapter based upon the earlier weight estimation to ensure proper balance of the centrifuge rotor. The centrifuge adapter is the component which carries the tubes upon a shuttle from the distribution area 204 to the centrifuge whereupon a robotic gripper transfers the centrifuge adapter with the tubes to a bucket of the centrifuge.

[0049] If the distribution area module 204 determines that the sample tube does not require centrifugation, the grippers 218 places the sample into a carrier on the conveyance system 220 with the barcode label properly aligned to the carrier at the direction of the scheduler so as not to overload downstream processes. More details on the conveyance system 220 and the carriers will be discussed below. A carrier can refer to any suitable device, which can be present in a conveyance system and can carry or transport one or more sample containers or tubes.

Exemplary carriers may contain recesses which can hold the containers or tubes. If a problem exists with the sample (e.g., the volume is too low, the barcode is unreadable, no test information is downloaded, etc.), the sample tube is moved to the error area 222 and the user is notified of the issue.

{e} Centrifuge Module

[0050J The sample tube may be moved from the distribution area 204 of FIG. 2 to the centrifuge module 206 if the distribution area module 204 determines that the sample requires centrifugarion before analysis of the sample. When a sample tube is to be transported from the distribution area 204 to the centriiuge module 206, the sample tube is loaded by the distribution area robot gripper 218 into a centrifuge adapter from the distribution area 2.04. The adapters may locate and retain multiple tube sizes for centrifugation. The adapter sits in a shuttle 224 which moves between the distribution area 204 and the centrifuge module 206 once the adapter is filled with sample tubes. An adapter can be a device which holds sample containers and can be used in a centrifuge. Such adapters are commonly constructed of a polymeric material but not limited to and constructed as a single piece having a shape which allows retention of one or more containers in which a sample may be placed, !n some cases, an adapter is inserted into a device mounted on or in a centrifuge rotor. Lab Ware ^® (e.g., sample containers or tubes) holding the sample is inserted in the adapter.

[OOSij When the sample tubes in the adapters arrive at the centrifuge module 206 from the distribution area 204 via the shuttle 224, the adapters are loaded into an available centrifuge bucket. The configuration of the adapters allows for simplification of delivery to and removal from the centrifugation buckets. Once loaded into a centrifuge bucket, the samples can be centrifuged. The centrifuge module 206 may include one or more centrifuges that are refrigerated to maintain the temperature of the sample. In FIG. 2, two centrifuges 206-1 and 206-2 are depicted. The centrifuges use a swinging centrifuge bucket rotor which produces level sedimentation layers from which analyzers and pipettors can consistently aspirate the maximum volume of fluid. Once centrifugation is complete, the adapters can be removed from the centrifugation bucket and placed in an unloading area. The sample tubes are then removed from the adapters in the unloading area and placed in carriers on the conveyance system 220 for transport to the next module.

|0052] The timing for loading tubes into an adapter at the distribution module 204, sending the tubes in the adapter to the centrifuge module 206 via the shuttle 224, loading the adapter into a centrifuge bucket, centrifuging the samples, unloading the adapter from the centrifuge bucket, and unloading the tubes from the adapter is such that the process can be continuous, allowing for the continual centrifugation of samples as they arrive at the centrifuge module 206 from the distribution area 204. As the centrifuge completes a spin cycle, the last tube in the distribution area 204 is loaded by the distribution area gripper 2 i 8 into an adapter, and the shuttle 224 moves the adapter to a centrifuge in the centrifuge module 206. At the same time, an automated door on the centrifuge opens and provides access to a bucket as the rotor indexes into position at. the doorway. A centrifuge module gripper 226 in the centrifuge module 206 removes the adapter that is already in the bucket and moves that adapter to an area where the tubes will be unloaded to carriers on the conveyance system 220. Next, the centrifuge module gripper 226 selects an adapter that has been recently loaded with tubes from the distribution area 204 and deposits it into the empty bucket. While the rotor indexes to the next bucket, a previously emptied adapter is moved to the open position on the shuttle 224 for loading with tubes from the distribution area 204 when the shuttle 224 returns to the d istribution area 204. [0Θ53] After the final adapter is loaded into the centrifuge, the door closes and the spin cycle begins. The adapter shuttle 224 moves back to the distribution area 204, and a centrifuge module gripper 226 begins to unload tubes from the adapters removed from the buckets into carriers on the conveyance system 220. As the tubes are moved from the adapter to the carrier, the heights of the sedimentation layers are measured and the barcode on each tube is aligned with the carrier. If insufficient serum or plasma is present, the tube will be sent to an error area located in the output module 2 i 4.

[00541 I the scheduling algorithm pred icts the overloading of an analyzer with samples from the centrifuge module 206, the centrifuge module gripper 226 can unload the samples and distribute the samples from the adapters to the conveyance system. In some embodiments, the full cycle time of the centrifuges can be greater than or equal to, e.g., 360 seconds. In order to ensure optimal turnaround time (TAT) and throughput the centrifuges are kept, e.g.. I SO seconds out of phase for a 360 seconds cerrtrifugation cycle, in some embodiments, downstream processes do not prevent the unloading of samples from the centrifuge adapters. If all the remaining samples in an adapter are destined for unavailable process(es) and depending upon the unavailable process, sample tubes can either be moved to a buffer in the centrifuge instrument or moved to another buffer area elsewhere in the system.

[0055] The centrifuge module 206 may Include an automated centri fuge controlled by a centrifuge controller. The automated centrifuge can be loaded with multiple centrifuge buckets or receptacles, each bucket receiving multiple sample tubes. The centrifuge includes a motor coupled to a spindle, a rotor assembly, a controller, a lid, and optionally, a lid drive. The centrifuge controller indexes or stops the spindle at selected positions for automated placement and removal of either tubes, adapters, or buckets. The lid has a closed position and an open position, and the lid opens and closes in response to instructions from the centrifuge controller.

[0056] In some embodiments, before the loaded buckets are placed in the centrifuge, the buckets can be balanced in a balance system. The baiance system, which can be an included part of the centrifuge module 206, comprises a scale having sites for recei ving and holding a plurality of buckets, and a balance controller for selectively depositing sample tubes in cavities of the buckets while correlating incremental weight changes with the locations of each deposit for equalizing weight in pairs of the buckets. The balance controller can be implemented as a balance program within the central controller. The baiance program maintains a database of sample container weights. When a container's weight is combined with the sample's weight, the balance program can determine the optimum adapter cavity in which to place it thereby maintaining a balanced rotor within a tolerance. Sample weights are the product of density estimates and the sample volumes calculated from liquid level measurements and container geometry obtained during the initial pick-tip from the input. In some embodiments, baiance system may also include a supply of dummy loads in buckets for limiting weight variations between buckets. The dummy loads may be weighted for limiting the weight variations to not greater than, e.g., 10 grams between members of each pair of buckets.

[0057] in other embod iments, a scale need not be used. For example, in some embodiments, the weight of a sample container and a sample can be estimated, and the adapters can be automatically loaded to ensure a balanced rotor. In some cases, a picture of a sample tube may be taken, and the liquid level of a sample in the sample tube can be determined. Using information about the sample container (e.g., the sample container weight) and the determined liqu id level, the weight of the sample tube with the sample in it can be estimated. In such embodiments, a scale is advantageously not needed. Further dummy loads may also not be needed.

[0058] The centrifuge controller may operate to perform a number of functions, such, as receiving and storing a centrifuge spin profile incl uding a rotor spindle speed and duration, index ing the rotor's sample stations into an access position, spinning the rotor in accordance with the cycle profile, stopping the rotor with a predetermined sample station at the access position, etc.

(d) Decapper Module

[0 S9] The decapper module 208 of FIG. 2 is capable of decapping the cap from the sample tubes in carriers on the conveyance system 220 before they are analyzed. The decapper system may clamp a sample tube and remove the cap from a sample tube. The decapper module 208 follows the distribution module 204 and the centrifuge module 206. For sample tubes which do not require cap removal (e.g., for instances in which the samples may only require sorting), the carrier on the conveyance system 220 will bypass the decapper module 208. For sample tubes that require cap removal, the decapper module 208 may remove the cap from the sample tube and deposit the cap in a biohazardous waste disposal container below the deck of the decapper module 20S. The biohazardous waste disposal container is removable and replaceable to protect the user from biohazardous waste.

(e) Serum Indices Module

[0060] The serum indices module 210 of FIG. 2 is capable of measuring the serum index of a sample. Typically, this function is performed during the analytical phase 106. However, in some instances, certain laboratories may prefer to address any quality issues prior to delivering the samples to the analyzer. Thus, the serum indices module 210 provides this quality control option for samples that should be tested during the pre-anaiytical phase 104. For samples that do not require a serum index measurement, the sample may bypass the serum indices module 210.

[00611 The serum indices module 210 can be the next module after the decapper module 208 since a serum indices measurement typically requires access to the sample. Similar to the decapper module 208, the serum indices module 210 may have a biohazardous waste disposal container below the deck of this module. The container may be removable and replaceable to protect the user from biohazardous waste.

(f) AHqu otter Module

[0062] The aliquotter module 212 of FIG . 2 divides the sample in a primary tube into multiple secondary tubes depending on how many tubes are needed for analysis. This module may contain one or more pipettors for divid ing the sample into secondary samples. Further details regarding the a!iquotter module 212 can be found in U.S. Provisional Patent Application Nos. 61 /556,667, filed November 7, 201 1 , 61/616,994, filed March 28, 2012, and 61/680,066, filed August 6, 2012.

3. Analytical Phase

[0063] Referring again to FIGS, i and 2, the analytical phase 1 06 includes performing the actual measurements needed to process a sample and produce results. This phase is typically composed predominantly of one or more analysis instruments or analyzers. The analysis instruments or analyzers can be any analysis instruments or analyzers known in the art.

Typically, an analyzer may comprise a mechanism for selectively performing one or more types of analyses on a specimen. The analyzer's controller is in communication with the centra;

controller, so thai the central controller can instruct, the analyzer controller as to what analysis to perform for the specimen. Each analyzer's controller may also communicate analysis results to the memory of the central controller.

[0064] For a laboratory system that has the components associated with the pie-analytical 104, analytical 106, and post -analytical 108 phases connected together via a conveyance system 220, the samples may move past the output/sorter module 214 and onto analyzers. When the carrier reaches the destination analyzer for that particular sample, the carrier pulls off the main travel lane and forms a queue upstream of the analyzer's access point to the conveyance system 220. The queue length is minimal because of the planning done by the scheduler while the tube was still in the distribution area 204 and because of the controlled release of tubes by the distribution 204 and centrifuge 206 modules.

B. Tube or Rack Presence Detection Unit

[0065] The laboratory automated system may use a tube or rack presence detection apparatus for detecting the presence of a sample tube or rack and its characteristics. Analysis tools or an image analysis device can be used to analyze or process one or more images acquired by one or more cameras and determine objects in the field of view of the cameras. The image analysis device can determine the presence and characteristics of each rack and of each sample tube in the rack and identify each sample tube in the rack using the determined characteristics. [0066] The embodiments of the invention that relate to the tube or rack identification systems and methods can be used in any suitable part of the above-described system. For example, they may be used in the above-described input module 202, output module 214, or any other part of the system that uses racks and tubes. [0067] In embodiments of the invention, as noted above, an "image acquisition device" may be used to capture images such as 2-D images of sample containers or sample container holders. Examples of image acquisition devices comprise cameras as well as detectors that can detect any suitable type of electromagnetic energy.

[0068| In embodiments of the invention, "sample container characteristics" may comprise any suitable characteristics about a sample container. Such characteristics may relate to a physical characteristic of a container such as a tube body and/or tube cap. Examples of sample tube characteristics include cap color, cap shape, labels and markers.

[0069] In embodiments of the invention, "sample container holder characteristics" may comprise any suitable characteristics of a sample holder. A sample container holder may include a number of recesses to hold an array of sample containers. Exemplary sample container holders characteristics may comprise any suitable characteristics including at least one of a size, shape, or color, as well as labels and/or markers that are associated with (e.g., on) the sample container holders.

I . Sample Tube or Rack Identification 10070] FIG. 3 shows a high-level block diagram of some components in a sample tube and rack identification system according to an embodiment of the invention. FIG. 3 shows a camera 1802 coupled to an image analysis device 1808. The image analysis device 1808 can also be coupled to a gripper 228 and can provide instructions to it. The gripper 228 can then secure a specific sample tube in a rack with sample tubes 1806(a). [00 1] Although the instructions provided by the image analysis device are provided to a gripper 228 in this example, embodiments of the invention are not limited thereto. For example, embodiments of the invention can provide instructions to a central controller in the laboratory automation system to inform other downstream instruments or subsystems that a particular tube and/or rack has been identified. For example, once a particular sample tube in a sample rack has been identified, a scheduler in a central controller will know where that particular sample tube is in the system and can plan ahead for any subsequent processing. Thus, the instructions and/or analysis data provided by the image analysis device 1808 may be provided to any suitable downstream instrument or subsystem.

[0072] FIG. 4 shows a block diagram of an image analysis device 1808, It may ineiude a data input interface 1808(b) to receive data from the one or more cameras (e.g. camera 1802), and a processor 1808(a) coupled to the input interface 1808(b). The processor 1 808(a) may also be coupled to a data output interface 1808(c) which provides data to suitable devices which can manipulate and/or transport a sample tube. The central processor 1 808(a) may further be coupled to a memory 1808(d) which may comprise shape determination module 1808(d) -! , a color determination module 1 808(d)-2, a marker and label determination module 1808(d)-3, a tube presence deiection module 1808(d)-4, and an instruction module i 808(d)~5. The shape determination module 1808(d)- 1 may comprises computer code, executable by the processor 1808(a), to determine the shape of a sample tube or rack. The color determination module 1 S0S(dV2 may comprise computer code, executable by the processor 1808(a) to determine a color of a sample tube cap or rack. The marker and label determination module 1808(d)-3 may comprise computer code, executable by the processor 1808(a) to determine marker or label associated with a cap, tube body, or rack. The tube presence deiection module Ϊ 808(d)-4 may comprise code, executable by the processor, to determine the absence or presence of a sample tube at a particular rack location within a rack. The sample tube instruction module 3808(d)- 5 may comprise code, executable by the processor 1 808(a) to provide instructions to an externa; device via the data output interface 1808(c). The instructions that are provided may include instructions to a gripper unit, which cause the gripper unit to locate and grip a particular sample tube or tubes in one or more racks, Note that any of the previously described software modules may function independently or together. For instance, the shape determination module 1808(d)- 1 may operate with the color determination module 1 808(d)-2 to identify both the shape of a particular cap as well as its color, in order to identify the sample tube associated with the cap.

10073J In methods according to embodiments of the invention, at least one camera acquires at least one image of the rack with sample tubes comprising samples, The method further comprises analyzing, by the image analysis device, the at least one image to identify

37 characteristics of the sample tubes and/or rack. If the sample tubes comprise different samples, then These samples may be in different sample tubes with different characteristics, and the samples may be processed differently, after they have been identified. For example, after receiving instructions from the analysis device, a first sample tube with a first characteristic and a first sample could be sent to a storage unit by a gripper (coupled to a robotic arm) that is capable of moving in three directions (X, Y, and Z), while a second sample tube with a second characteristic and a second sample may be sent to a centrifuge, prior to being analyzed.

[0074] The processor 3808(a) may comprise any suitable data processor for processing data. For example, the processor may comprise one or more microprocessors that function separately or together to cause various components of the system to operate.

[0075] The memory 1 808(d) may comprise any suitable type of memory device, i n any suitable combination. The memory 1.808(d) may comprise one or more volatile or non-volatile memory devices, which operate using any suitable electrical, magnetic, and/or optical data storage technology. [0076] FIG. 5(a) shows a system 1 800 comprising a camera unit ( e.g., 2-D arrays or line scanners) comprising a camera 1 802 and i llumination elements 1 804 (e.g., lights). The camera 1 802 acquires a 2-D image for a target object can be used in the laboratory automation system to detect the presence of and identify the target object. T he camera 1 802 and the illumination elements 1804 may be movable or stationary and may be mounted to a frame (not shown) in a processing module above racks with sample tubes. In this example, the target objects are multiple sample tubes 1806(a) being provided in a 6x6 rack 1806(b). The 2-D image can then be further processed by image analysis software in the image analysis device and ca detect the presence and to derive characteristics of the target object (e.g., sample tubes or racks), such as tube cap indicators, rack markers, circular barcode labels, cap or rack color and shape, etc. The 2-D image can also be analyzed to determ ine the presence or absence of a sample tube in various sample tube locations in the rack 1 806. By analyzing the tube characteristics and by analyzing the presence of the sample tubes in a rack, a gripper or other transport device knows which samples to select for further processing, and also knows whether or not additional samples can be placed in the rack for further processing. [0077] FIG. 5(b) depicts another embodiment of a system for sample tube or rack detection and analysis. The image analysis device 1808 (e.g., camera unit, 2-D arrays or line scanners) comprises a plurality of cameras 1810(a), 1810(b), 1810(c) and illumination elements 1832 to acquire one or more 2-D images of the target objects can be used in the laboratory automation system to detect the presence of and identify the target objects. The image analysis device I 808 comprising the plurality of cameras 1810(a), I S 10(b), 1810(c) is arranged on top of an input module 202 facing the input area including the target objects. In this example, the target objects comprise sample tubes being provided in racks 1806 provided on a plurality of parallel drawers 216 of the input module 202. As shown, the plurality of cameras 1810(a), 1810(b). 1830(c) can capture different images 1820(a), 1820(b), 1820(c). Adjacent images 1820(a), 1 820(b) and 1820(b). 3820(c) can overlap so a larger image can be stitched together if desired.

[0078] The 2-D images obtained by the plurali ty of cameras 1810(a), 1810(b), 1810(c) can then be further processed by image analysis software to detect the presence of and to derive characteristic features of the. target objects (e.g., sample tubes and racks), such as tube cap indicators, rack markers, circular barcode labels, cap or rack color and shape, etc. Either a series of images can be acquired by the image analysis device 1808 during the movement of the drawers 216, or an overview image of the input area can be made in a closed state for the drawers 216.

[0079] FIG. 5(c) depicts another embodiment of a camera unit for sample tube or rack detection and analysis. A camera unit 1814 (e.g., 2-D arrays or line scanners) having a camera 3 816 and illumination elements 1818 to acquire 2-D images for target objects can be used in the laboratory automation system to detect the presence of and identify the target objects.

[0080] The camera unit 1814 is coupled to a lower end of a gripper 228 facing the input area. The gripper 228 comprises a gripper body 228(a) and gripper fingers 228(b), which can grip a sample tube 1840. The gripper 228 may also be attached to an X-Y gantry 1817 so that the gripper 228 can move in an X, Y, or Z direction. A series of images is acquired by the camera 1 816 during the movement of the input gripper 228.

[0081] In this example, the target objects are one or more sample tubes being provided in one or more racks 1806 provided on the drawers 216 of the input unit 202. The 2-D image can then be further processed by image analysis software to derive characteristic features of the target object (e.g., sample tubes and racks), such as lube cap indicators, rack markers, circular barcode labels, cap or rack coior and shape, etc.

[0082] When the camera unit 1814 takes a series of images, the images cam be stitched together by the analysis tool to generate an overview image. Within this overview image, single objects can be detected by image analysis performed by the analysis tool. For example, single objects such as markers on the holding racks or a cap or closure of a sample tube located in a holding rack can be detected using image analysts. 0083] The embodiment in FIG. 5(c) has advantages, For example, using this embodiment, a image can be taken of a sample tube rack with samples, and the image can be analyzed, and the grippcr can be instructed to select the appropriate sample tube from the sample tube rack and/or place a tube in a vacant sample tube location in the rack. The gripper and its robotic arm and process information while it Is moving, thereby resulti ng in a very efficient process.

10084] FIG. 6 depicts an example overlay image of an original image and the highlighted analyzed image of the sample tube identification in a sample rack based on a top-view image. Detected potential positions for a sample tube are highlighted with circles 1902, while a detected sample tube is indicated by a cross 1 904. Shape recognition software can recognize outlines of potential locations for sample tubes by recognition of particular shapes for the recesses that can receive the sample tubes. In some cases, the recesses in the rack may be colored to assist in the recognition of the empty recesses. Other rack locations with sample tubes cover the empty recesses, and may therefore be considered to be filled with sample tubes. A map of circles and crosses can be formed as shown in FIG. 6. and this can be overlaid on a top plan view image of the rack with the tubes. In some cases, the particular characteristics of the rack and the locations for sample tube placement (e.g., recesses) can be previously mapped and stored in a memory in the system. Thus, embodiments of the invention may determine the presence and/or absence of a sample tube at a particular rack location in a rack.

[0085] The analysis tool according to an embodiment of the invention is also capable of deriving details such as cap color, cap shape, markers or labels on the cap for a single sample tube in a holding rack, etc. The derived details may then be used to optimize the subsequent process steps for the laboratory automated system.

2, Sample Tube Marker

(a) Urgent Sample Indicator

[0086] The laboratory automation system can utilize a sample status indicator device, which can provide an easy way to mark a sample tube as an emergency or urgent tube requiring immediate analysis, without the application of additional material on the sample tube. Currently, sample tubes may be marked with self-adhering labels (e.g., colored labels indicating urgency), "urgent" stickers, or just by using a handwritten note indicating urgency on already existing labels, The urgent sample indicator mechanism of the present technology can indicate urgency or status of (he sample without the need to label or handwrite the indication.

[0087] The sample status indicator device includes a manually moveable element of the sample tube cap, wherein the moveable element can be moved to at least a first position and a second position. When the moveable element is moved to a first position, a window may display a first status of the sample tube (e.g., norma! or non-urgent). When the moveable element is moved to a second position, the window may display a second status of the sample tube (e.g., a mark indicating an urgent status). The indicator or marker can be read by operators as well as by an automated system. The indicator or marker can be a particular color, characters, numbers, icons, etc. [0088] For example, as soon as tubes with d ifferent priorities get collected In a multiple-tube rack, the conventional labels may get covered by the rack itself of by neighbor tubes, thus making it difficult to recognize such labels or stickers as an emergency mark for automated processes. In conventional situations, presorting must typically be performed. The urgent sample indicator of the present technology can provide the visual marker on the top of the tube so thai the urgent tubes can be recognized immediately by users as well as by an automated process via image processing. This allows the user to mix emergency samples together with lower priority samples in a rack or bag for transport. Undetected emergency samples become unlikely, and additional presorting may not be required. {0089] The indicators in embodiments of the invention can be status indicators. Examples of particular tube statuses include, but are not limited to, the particular priority associated with a tube (e.g.. urgent, not urgent, STAT, etc.), the particular processing desired for a tube (e.g. centrifuge, aliquot, etc.). etc. [0090] In one embodiment, the markers are not limited to emergency or prioritization marking, and can alternatively allow for several visual predefined marks, such as container content material, additives, reagents, etc., without the need for different parts. The moveable element can be moved (e.g., a first direction or second direction) to a certain position so that the window displays a particular indicator. [0091] In one embodiment, the positions to which the moveable element can be moved may have a mechanical latch function or a limitation device to switch between two or more positions. This prevents the moveable part from being accidentally moved to an incorrect position.

[0092] FIG. 7 shows a view of a sample tube 2002 comprising a sample tube body 2004 and a cap 2000 on the sample tube body. A sample such as a biological sample can be present in the sample tube 2002. The sample tube body 2004 may comprise a transparent or translucent material comprising plastic or glass. The sample cap 2000 may also comprise a materia! such as plastic.

[0093] FIGS. 8(a)-8(b) depict one example of a cap 2,000 having a movable element that expose or not expose an urgent sample indicator. [0094] In FIG. 8(a). the cap 2000 comprises a cylindrical cap body 2000(a) and a movable element 2000(b) at a top region of the cylindrical cap body 2000(a). The movable element 2000(b) may rotate so that a window 2000(b)- ! exposes a non-urgent indicator 2004. The nonurgent indicator 2004 may be a color such as green to indicate that the sample is to be processed in a non-urgent manner. Handles 2000(b)-2 in the form of protrusions may be present in the movable element 2000(b) to allow a human, a gripper or other element to move the movable element 2000(b) change the status of the sample tub. Whi le handles are described in detail, embodiments of the invention can include other types of handling features such as holes. [009S] in FIG. 8(b), the movable element 2000(b) is rotated an emergency or urgent position to expose an urgent sample indicator 2005. The urgent sample indicator 2005 may be red to indicate that the sample tube is to be processed as soon as possible.

|0096] While the indicators in FIGS. 8(a) and 8(b) are non-urgent 2004 and urgent 2005, respectively, it is understood that the sample tube cap 2000 shown in FIGS. 8(a) and 8(b) could have other types of indicators. For example, the indicators may indicate thai a sample is to be processed by a particular machine, by a particular process, in a particular order, etc.

[0097] The cap 2000 and its indication of sample tube status can be viewed by the camera units shown in FIGS. 5(a)-5(c) and can be identified and processed as described above. (b) Centrifugation Indicator

[0098] The laboratory automation system can utilize a centrifugation status indicator dev ice, which can indicate whether a sample has been centrifuged. Generally, the majority of sample tubes in a lab require centrifugation since only their serum is used for analysis. When a sample tube sits for long period of time, there is sedimentation of the specimen so that the specimen appears visually to have been spun. Additionally, it could become less apparent that a pre-spun sample was actually already spun if the specimen were shaken (e.g., during transport). If sample tubes that have been sitting for a period of time and pre-spun sample tubes are mixed, a user may not be able to discern which samples tubes were actually already spun. Furthermore, it may be difficult for a user to visually determine the quality of the centrifugation (e.g., whether or not the spin time and force (minutes*g) was sufficient or not).

[0099] The centrifugation status indicator device of the present technology provides a way to visualize the centrifugation status of a sample tube. The centrifugation status can be read by users or by a lab automation device independent from the actual appearance of the biood or other specimen in the sample tube. The centrifugation indicator prevents user error which could result in incorrect test results. The centrifugation indicator provides a visual mark which changes its appearance during centrifugation according to the centrifugation time and force, but keeps its state under normal tube transport conditions.

I0100J The visual marker of the centrifugation indicator may be on the top of the sample tube so that it can be recognized Immediately by users as well as by an automated process via image processing, it allows pre-spun samples to be mixed with un-spun samples in a rack and avoids the manual presorting of samples prior to automation entry. In one embodiment, the centrifuge indicator can be part of the sample tube cap for covering the sample tube.

[0101] Additionally, the centrifugation quality can be determ ined automatically and subsequent processes in the laboratory automation system can be controlled according to the result. One embodiment of a centrifugation indicator is shown in FIG. 9(a), The centrifugation indicator depicted includes a small container (which may be in the form of a cap housing) with a transparent top containing a colored gel 2302 (e.g. white) and particles 2304 of a different (e.g., higher) density and with a different color (e.g., blue). In an unspun state 2104, the particles 2304 and the colored get 2302 are distinct from each other. Using the example of white gel 2302 and blue particles 2304, the initial appearance of the container may be light blue when the two components are initially mixed, or the appearance may be blue in case the particles are on top of the gel 2302. During centrifugation, the blue particles move to the bottom of the container due to the higher density 2308, and the top appearance changes to white due to the lack of particles 231 0. The combination of the chosen materials provides the possibil ity to gain different appearances according to the applied centri ugation force and time. Additionally, more than one type of particles can be used to get a finer resolution of the applied spin time and force.

[01.02] In one embodiment, the centrifugation indicator is a transparent cylinder that is pressed onto a pressure sensitive device (e.g., pressure indicating film) which changes its appearance according to the applied centrifugation force. FIG. 9(b) depicts an example of this type of centrifugation indicator. The centrifugation indicator includes the pressure sensitive device 2312 (e.g.. foil) in a transparent cylinder 2314, which may comprise a transparent material such as a. transparent gel. The transparent cylinder 2314 allows the pressure sensitive device 2312 to be displayed. When the sample is not spun 231 6, the pressure sensitive device 2312 may have a transparent appearance. During centrifugation 2 18. the pressure sensitive device 2332 on the centrifugation indicator may have an appearance of one particular color. Once the sample tube has been spun 2320. the pressure sensitive device 2312 on the centrifugation indicator may have another appearance of another particular color. One example of a pressure sensitive device 2312 may be Prescale™ film by Fujifilm* [0103] FIG, 10(a) shows a side, cross-sectional view of a cap with a pressure sensitive ^, device 2336 in the form of a foil. The cap is shown in a non-centrifuged state. As shown, the cap can include a body with a cylindrical cap thread portion 2338 and a cylindrical cap top portion 2334 separated by a perpendicular circular horizontal portion 2340. A pressure sensitive device 2336 is on the horizontal portion 2340. A plurality of transparent posts 2332 may be on the pressure sensitive device 2336, and the top surfaces of the posts 2332 may be covered with an optically transparent cover 2330 (e.g., made of transparent plastic).

[0104] FIG 10(b) shows a top plan view of the cap in FIG. 10(a). in FIGS. 10(a) and 10(b), like reference numbers designated like elements. As shown, the pressure sensitive device 2336 may be a first color when no pressure is applied to it.

[0105] The same cap is shown in FIGS. 1 1 (a) and 1 1 (b). However, this cap is shown after centrifugation. As shown, the posts 2332 applied downward pressure on the pressure sensitive device 2336 causing a color change in the pressure sensitive device 2336 at areas under the posts 2332. When viewed from the top in FIG . 1 1 (b), a distinct pattern of three dots (of a second color) is shown against a background of a different color (e.g., the first color). This pattern can be viewed by a camera looking down on the cap, and an analysis device coupled to the camera can determine that the sample tube with the cap contains a centrifuged sample (as described above with respect to FIGS. 5(a)-5(c).

(e) Circiilar Barcode

[0106] The laboratory automation system can utilize a circular barcode identification device on top of a sample lube cap. A circular barcode can provide for an easy and fast way to identify the sample tubes before they get handled by the input gripper for the first time.

[0107] The various participants and elements described herein with reference to the figures may operate one or more computer apparatuses to facilitate the functions described herein. Any of the elements in the above description, including any servers, processors, or databases, may use any suitable number of subsystems TO facilitate the functions described herein, such as, e.g., functions for operating and/or controlling the functional units and modules of the laboratory automation system, transportation systems, the scheduler, the central controller, local controllers, [0108] Examples of such subsystems or components are shown in FIG. 12. The subsystems shown in FIG. 12 are interconnected via a system bus 4445, Additional subsystems such as a printer 4444, keyboard 4448, fixed disk 4449 (or other memory comprising computer readable media), monitor 4446, which is coupled to display adapter 4482, and others are shown, Peripherals and input/output (I/O) devices, which couple to I/O controller 4441 (which can be a processor or other suitable controller), can be connected to the computer system by any number of means known in the art, such as serial port 4484. For example, serial port 4484 or external interface 4481 can be used to connect the computer apparatus to a wide area network such as the Internet, a mouse, input device, or a scanner. The interconnection via system bus allows the central processor 4443 to communicate with each subsystem and to control the execution of instructions from system memory 4442 or the fixed disk 4449, as well as the exchange of information between subsystems. The system memory 4442 and/or the fixed disk 4449 may embody a computer readable medium.

[0109] Embodiments of the technology are not l imited to the above-described embodiments. Specific details regarding some of the above-described aspects are provided above. The specific details of the specific aspects may be combined in any suitable, manner without departing from the spirit and scope of embodiments of the iechnology. For example, back end processing, data analysis, data collection, and other processes may ail be combined in some embodiments of the technology. However, other embodiments of the technology may be directed to specific embodiments relating to each individual aspect, or specific combinations of these individual aspects.

[0110] it should be understood that the present technology as described above can be implemented in the form of control logic using computer software (stored in a tangible physical medium) in a modular or integrated manner. Furthermore, the present technology may be implemented in the form and/or combination of any image processing. Based on the disclosure and teachings provided herein, a person of ordinary skill in the art will know and appreciate other ways and/or methods to implement the present technology using hardware and a combination of hardware and software,

[0111] Any of the software components or functions described in this application, may be implemented as software code to be executed by a processor using any suitable computer language such as, for example, Java, C++ or Perl using, for example, conventional or object- oriented techniques. The software code may be stored as a series of instructions, or commands on a computer readable medium, such as a random access memory (RAM), a read only memory (ROM), a magnetic medium such as a hard-drive or a floppy disk, or an optica! medium such as a CD-ROM, Any such computer readable medium may reside on or within a single computational apparatus, and may be present on or within different computational apparatuses within a system or network.

[0112] The above description is illustrative and is not restrictive. Many variations of the technology will become apparent to those skilled in the art upon review of the disclosure. The scope of the technology should, therefore, be determined not with reference to the above description, but instead should be detennined with reference to the pending claims along with their ful l scope or equivalents.

[0113] One or more features from any embodiment may be combined with one or more features of any other embodiment without departing from the scope of the technology. [0114] A recitation of "a", "an" or "the" is intended to mean "one or more" unless speci fically indicaied to the contrary.

[0115] All patents, patent applications, publications, and descriptions mentioned above are herein incorporated by reference in their entirety for all purposes. None is admitted to be prior art.