Oven and gripper design for biological analysis instrument

Abstract

A biological analysis system for analyzing a biological sample is provided. The system includes a sample holder including a position identifier set, including a first, second, and third position identifier. The system further includes an oven, and a gripper arm system configured to move a sample holder between functional areas of the biological analysis system. The oven includes an outer housing, an inner housing, and an air gap between the outer housing and the inner housing. The oven further includes a heater configured to supply heat to the biological sample and a heat circulating assembly configured to circulate heated air within the housing around the biological samples. The gripper arm system includes an optical sensor configured to measure the position of each position identifier and a processor for determining an x, y, and z position of each position identifier to generate an adjusted coordinate system for controlling the gripper arm.

Description

Docket No. TP388680WO1OVEN AND GRIPPER DESIGN FOR BIOLOGICAL ANALYSIS INSTRUMENTCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application Nos. 63 / 689,106 and 63 / 689,474, both filed on August 30, 2024. All of which are incorporated herein by reference.BACKGROUND

[0002] Biological analysis instruments utilize biological and biochemical reactions to monitor, measure, and / or analyze such reactions. Such instruments are commonly used in sequencing, genotyping, polymerase chain reactions (PCR), and other biochemical reactions to monitor progress and provide quantitative data.

[0003] For example, some biological analysis instruments utilize DNA-DNA hybridization arrays using DNA-binding dyes or fluorescent probes to produce fluorescent signals indicative of the degree of similarity between sample and probe. In a hybridization analysis, arrays are set up with selected sets of DNA sequences of interest. If a sample has complementary sequences to the target DNA in the array, a fluorescent dye can be attached. When excitation light shines on the DNA array after hybridization, array spots fluoresce if a dye is attached.

[0004] The instrument to perform this biological analysis may also include fluidic reservoirs, pumps, wash stations, an optical system, ovens, and gripper arms or plate handling robots. Hybridization requires accurate temperature control and an oven is often used to perform the process. Gripper arms are used to automate the transfer the hybridization plates, or sample holder plates, within the biological analysis instrument to different functional areas according to sample processing protocols. These components allow an automated system to efficiently and quickly process biological samples.

[0005] Previously, ovens within the hybridization biological analysis instrument could not maintain proper and uniform heated air flow when processing the hybridization plates, especially when holding more than two hybridization plates. Further, the plate handling robot would previously be aligned and calibrated with a manual, time-consuming process.Docket No. TP388680WO1

[0006] Moreover, there are increasing demands to provide greater numbers of reactions per test or experiment, creating a need to quickly produce high quality results.

[0007] The combination of having large numbers of samples and the desire to perform experiments in a faster high-quality manner has created a need for improved performance of the oven and plate handling robots to test, and / or analyzing one or more biological samples.SUMMARY

[0008] In one exemplary embodiment, an apparatus for heating a biological sample is provided. The apparatus includes an outer housing and an inner housing. Between the outer housing and the inner housing is an air gap. The apparatus also includes a heater configured to supply heat to the biological sample within the housing. A heat circulating assembly is configured to circulate heated air within the housing, where the heat circulating assembly includes a fan and a heat deflector. The apparatus further includes a sample holder rack configured to hold a sample holder including the biological sample.

[0009] In another exemplary embodiment, a system for adjusting a gripper arm in a biological analysis instrument is provided. The system includes a gripper arm configured to move a sample holder between functional areas of the biological analysis instrument, a position identifier set on a sample holder rack, an optical sensor configured to measure the position of the first position identifier, and a processor. The position identifier set includes a first, second, and third position identifier. The processor is configured to determine an x-position, a y-position, and a z-position of each position identifier of the position identifier set using the optical sensor, where the x-position, the y-position, and the z-position are used to generate an adjusted coordinate system. The processor is further configured to control the movement of the gripper arm using the adjusted coordinate system.

[0010] In yet another exemplary embodiment, a biological analysis system for analyzing a biological sample is provided. The system includes a sample holder including a position identifier set, including a first, second, and third position identifier. The system further includes an oven, and a gripper arm system configured to move the sample holder between functional areas of the biological analysis system. The oven includes an outer housing, an inner housing,Docket No. TP388680WO1 and an air gap between the outer housing and the inner housing. The oven further includes a heater configured to supply heat to the biological sample and a heat circulating assembly configured to circulate heated air within the housing around the biological samples. The gripper arm system includes an optical sensor configured to measure the position of each position identifier and a processor. The processor is configured to determine an x, y, and z position of each position identifier using the optical sensor to generate an adjusted coordinate system for controlling the gripper arm.DESCRIPTION OF THE FIGURES

[0011] FIG. 1 illustrates a block diagram of a genotyping instrument upon which embodiments of the present teachings may be implemented.

[0012] FIG. 2 illustrates an exemplary biological analysis instrument according to embodiments described herein.

[0013] FIG. 3 illustrates an exemplary cutaway view of a biological analysis instrument according to various embodiments described herein.

[0014] FIG. 4 illustrates an exemplary oven according to various embodiments described herein.

[0015] FIG. 4B illustrates a front view of an oven according to various embodiments described herein.

[0016] FIG. 5 illustrates a cross-section view of an oven according to various embodiments described herein.

[0017] FIG. 6A illustrates another exemplary front view of an oven according to various embodiments described herein.

[0018] FIG. 6B illustrates a front view of an oven with a closed door according to various embodiments described herein.Docket No. TP388680WO1

[0019] FIG. 7 A illustrates an exemplary back view of an oven according to various embodiments described herein.

[0020] FIG. 7B illustrates an exemplary back view of an oven with a closed door according to various embodiments described herein.

[0021] FIG. 8 illustrates a simulated exemplary air flow diagram in an oven according to various embodiments described herein.

[0022] FIG. 9 illustrates an exemplary computing system for implementing various embodiments described herein.

[0023] FIG. 10 illustrates an exemplary distributed network system according to various embodiments described herein.

[0024] FIG. 11 depicts an exemplary gripper arm according to various embodiments described herein.

[0025] FIG. 12 illustrates a magnified view of an optical sensor of a gripper arm according to various embodiments described herein.

[0026] FIG. 13 illustrates a flowchart of a method of calibrating a gripper arm according to various embodiments described herein.

[0027] FIG. 14A illustrates an exemplary gripper arm determining a x-position according to various embodiments described herein.

[0028] FIG. 14B illustrates an exemplary gripper arm determining a y-position according to various embodiments described herein.

[0029] FIG. 14C illustrates an exemplary gripper arm determining a z-position according to various embodiments described herein.

[0030] FIG. 14D illustrates an exemplary gripper arm determining a z-position according to various embodiments described herein.Docket No. TP388680WO1

[0031] FIG. 15 illustrates an example of actual positions of position identifiers versus expected positions according to various embodiments described herein.

[0032] FIG. 16 illustrates an exemplary signal processing block diagram for calibrating an LED excitation source according to various embodiments described herein.DETAILED DESCRIPTION

[0033] To provide a more thorough understanding of the present invention, the following description sets forth numerous specific details, such as specific configurations, parameters, examples, and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present invention but is intended to provide a better description of the exemplary embodiments.

[0034] In various embodiments, the devices, instruments, systems, and methods described herein may be used to detect one or more types of biological components of interest. These biological components of interest may be any suitable biological target including, but are not limited to, DNA sequences (including cell-free DNA), RNA sequences, genes, oligonucleotides, molecules, proteins, biomarkers, cells (e.g., circulating tumor cells), or any other suitable target biomolecule.

[0035] Embodiments of the present disclosure are generally directed to devices, instruments, systems, and methods for monitoring or measuring a biological reaction for a large number of small volume samples. As used herein, samples may be referred to as sample volumes, or reactions volumes, for example.

[0036] Hybridization of the fluorescent dye to the specimen results in fluorescent emission light. Hybridization analyses are an inexpensive way to screen a large number of targets. As such, this method is a simple and useful in a way to screen for hereditary susceptibility to different problems, such as cancer, sickle cell disease, Alzheimer’s, thyroid disease, hereditary deafness or blindness, for example. It can also be used to promote health and productivity in agriculture by using it on animals and plants as part of good breeding (e.g. corn with high yield that is not susceptible to blight or mold).Docket No. TP388680WO1

[0037] In a hybridization analysis, there are millions of array spots featuring short strands of DNA on fused silica substrates. Arrays arc set up with selected sets of DNA sequences of interest. A fluid sample is prepared for a particular person, plant, or animal’s DNA. The array is then immersed in this sample and baked in a hybridization oven, where, if the subject’s DNA is complementary to the DNA targets on the array, they will bond (hybridize). When they hybridize, a ligation region is formed near the bond of the array DNA and the sample DNA. Thus, a fluorescent dye can be attached to this ligation region. When excitation light shines on the DNA array after hybridization, array spots light up (fluoresce) if dye is attached. This means that location (with its known DNA array content) was complementary with the sample’s DNA.

[0038] FIG. 1 illustrates a block diagram of a genotyping instrument upon which embodiments of the present teachings may be implemented.

[0039] Sequencing Instruments

[0040] In various embodiments, nucleic acid sequence data can be generated using various techniques, platforms or technologies, including, but not limited to: hybridization-based systems, capillary electrophoresis, microarrays, and / or ligation-based systems, polymerase-based systems, direct or indirect nucleotide identification systems, pyro sequencing, ion- or pH-based detection systems, electronic signature-based systems, fluorescent-based detection systems, single molecule methods, etc.

[0041] Various embodiments of genotyping platforms, such as a nucleic acid sequencer, can include components as displayed in the block diagram of FIG. 1. Various embodiments of biological analysis instrument 100 can provide for automated sequencing that can be used to gather sequence information from a plurality of sequences in parallel, such as substantially simultaneously. In various embodiments, biological analysis instrument 100 can determine the sequence of a nucleic acid, such as a polynucleotide or an oligonucleotide. The nucleic acid can include DNA or RNA, and can be single stranded, such as ssDNA and RNA, or double stranded, such as dsDNA or a RNA / cDNA pair. In various embodiments, the nucleic acid can include or be derived from a fragment library, a mate pair library, a ChIP fragment, or the like. In particular embodiments, biological analysis instrument 100 can obtain the sequence informationDocket No. TP388680WO1 from a single nucleic acid molecule or from a group of substantially identical nucleic acid molecules.

[0042] According to various embodiments, biological analysis instrument 100 can include a control system 102. Control system 102 controls fluidic delivery from fluidic systems 108 to samples 104. Fluidic systems 108 may include a reagent reservoir for storing reagents. The reagents can include RNA-based primers, forward / reverse DNA primers, oligonucleotide mixtures for ligation sequencing, nucleotide mixtures for sequencing-by-synthesis, optional ECC oligonucleotide mixtures, buffers, wash reagents, blocking reagent, stripping reagents, and the like. Fluidic systems 108 are used for hybridization and wash sequences. Further, heating and cooling elements 106 are used in the hybridization step of samples 104 according to various embodiments.

[0043] In various embodiments, samples 104 may be in reactions sites within a sample holder. A sample holder may be, according to various embodiments described herein, an array plate, a microarray, a flow cell, a substrate, a multi-well tray, such as a standard microtiter 96- well, a 384-well plate, a 24-well plate, or a microcard, or a substantially planar support, such as a glass or plastic slide or a silicon chip, or the like. Further, according to various embodiments described herein, reaction sites may include, but are not limited to, wells, through-holes, indentations, spots, cavities, sample retainment regions, and reaction chambers, for example. Samples 104 may be included in multiple lanes, multiple channels, multiple wells, or other means of processing multiple sample sets substantially simultaneously.

[0044] Optical system 110 scans each reaction site to generate an image that is analyzed for fluorescence. Optical system 110 includes an optical sensor, such as an imaging or detection sensor. For example, the imaging or detection sensor can include a CCD, a CMOS, an ion sensor, such as an ion sensitive layer overlying a CMOS, a current detector, or the like.

[0045] According to various embodiments, control system 102 controls various elements of biological analysis instrument 100. For example, control system 102 controls heat / cool elements 106 in conjunction with fluidic systems 108 to perform some processing steps of the biological analysis. Further, control system 102 controls optical system 110. Control system 102 may be accessible to an end user through user interface 112 of biological analysis instrument 100.Docket No. TP388680WO1According to various embodiments, control system 102 includes a computer system, as depicted in FIG. 9, which provides the control the function biological analysis instrument 100, as well as the user interface 112. Control system 102 may provide data processing, display and report preparation functions. All such instrument control functions may be dedicated locally to the biological analysis instrument 100, or control system 102 may be part of a more remote distributed system as depicted in FIG. 10 in various embodiments.

[0046] As mentioned above, user interface 112 may provide user access to control system 102. Further, user interface 112 displays data collected in useful and in an easily to digest manner according to embodiments of the present teachings. User interface 112 may be local to biological analysis instrument 100 in some embodiments. In other embodiments, user interface 112 may be remote to biological analysis instrument 100 and be connected to a distributed network.

[0047] FIG. 2 illustrates an exemplary biological analysis instrument 200 according to embodiments described herein. Biological analysis instrument 200 may include a housing 202 and a user interface 204. Automated stations within biological analysis instrument 200 to perform the biological analysis are included within housing 202. A user may interact with biological analysis instrument 200 with user interface 204. Other reagents and fluid that may need to be replaced may be accessible by the user.

[0048] Various stages of a biological analysis are viewable in a cutaway perspective view of a biological analysis instrument. FIG. 3 illustrates an exemplary cutaway view of a biological analysis instrument according to various embodiments described herein.

[0049] Oven 300 is used for hybridization of biological samples to a target (described above). Oven 300 includes oven shelves 306 for holding sample holders. In this example, four sample holders are shown on sample holder racks 306. In other examples, oven 300 may include one, two, three, four, five, or any number of sample holder racks the oven is configured for according to various embodiments of the present teachings.

[0050] Other stages that may be included are storage area 304 for sample holders, trash bin 312, wash station 308, and unclamp station 310.Docket No. TP388680WO1

[0051] To move sample holders from one stage to the next, a robotic gripper arm 302 may be included in a biological analysis instrument. Gripper arm 302 may move a sample holder from a storage location 304 to oven 300 to perform the hybridization step of the biological analysis, for example. Gripper arm 302 may also move sample holder to be scanned by optical sensor 314 to view fluorescent results as another example. According to various embodiments, to more accurately move gripper arm 302, gripper arm 302 has a sensor connected to read position identifiers 316 connected to areas in biological instrument. Examples of areas where teaching posts 316 for gripper aim calibration may be located are in storage area 304, oven 300, and scanning area. Various embodiments of a method and system for calibration of gripper arm 302 are described later in this document.

[0052] Oven

[0053] As mentioned above, an oven included in a biological analysis instrument performs a hybridization stage of various biological analyses. Various embodiments described herein provide an effective and efficient oven to maintain a consistent thermal uniformity throughout the internal space of the oven. FIGS. 4A and 4B illustrate front views of an exemplary oven according to various embodiments described herein.

[0054] Oven 400 includes sample holder racks 410 for holding sample holders. Sample holders include biological samples. Also mentioned above, in various embodiments, samples 104 may be in reactions sites within a sample holder. A sample holder may be, according to various embodiments described herein, an array plate, a microarray, a flow cell, a substrate, a multi-well tray, such as a standard microtiter 96-well, a 384-well plate, a 24-well plate, or a microcard, or a substantially planar support, such as a glass or plastic slide or a silicon chip, or the like. Further, according to various embodiments described herein, reaction sites may include, but are not limited to, wells, through-holes, indentations, spots, cavities, sample retainment regions, and reaction chambers, for example. Samples 104 may be included in multiple lanes, multiple channels, multiple wells, or other means of processing multiple sample sets substantially simultaneously.

[0055] An oven, according to various embodiments described herein, may be configured to increase the number of sample holders that can be included in the oven. Oven 400 is configuredDocket No. TP388680WO1 with four sample holder racks 410. However, in various embodiments, oven 400 may be configured to accommodate two, three, four, five, or any number of sample holder racks to increase the number of biological samples that can be processed at a time within the oven.

[0056] Improving thermal uniformity to improve the performance of the hybridization process is provided according to various embodiments of the present teachings. The heat flow of the oven has been optimized to maintain thermal uniformity of ± 1 °C throughout the internal space according to various embodiments described herein. Further, ease of manufacture and reducing overall cost may be provided according to various embodiments.

[0057] Oven 400 includes outer housing 402 and inner housing 416. With reference to FIG. 4B, outer housing 402 and inner housing 416 form air gap 420. Outer housing 402 and inner housing 416 may be composed of a metal, such as stainless- steel sheet metal.

[0058] A plastic support plate may be included to support and also insulate outer housing 402 and inner housing 416.

[0059] In an example, outer housing 402 and inner housing 416 are made from 304 stainless steel. Outer housing 402 and inner housing 416 may also be made of Anodized or Alodined Aluminum 5052-h32 or 6061 -t6. Conduction of the material and weight may be considered in choosing a material for outer and inner housings according to embodiments of the present teachings.

[0060] According to various embodiments, the dimensions of oven 400 may be chosen to fit in the space allocated within a biological analysis instrument. In one example, an oven may be approximately 270mm x 212mm x 180mmFurther, a sample holder may be approximately 130mm x 89mm. The distance between the sample holders may be 37mm. The dimensions of the sample holder rack and spacing are chosen to give the most clearance and heat flow around the sample holder rack as possible and fit within the door opening for the arm gripper to reach in according to various embodiments.

[0061] Air gap 420 provides insulation to improve thermal uniformity. Previously, insulation material, such as Aerogel, surrounded the oven. Aerogel is a costly material and requires labor intensive application. However, air gap 420 has been found to act as effectiveDocket No. TP388680WO1 insulation according to various embodiments described herein. In one example, the air gap can range from 10mm to 30mm.

[0062] A heater 404 is included in oven 400 according to various embodiments described herein. Heater 404 maybe a cartridge heater with heat sinks to supply heat to oven 400. In one example, the heater is made up of 4 Watlow cartridge heaters with dimensions of 6.35mm diameter x 50.4mm long. Each heater is 25 watts each for a total of 100 watts.

[0063] In an example, heater 404 is set into a block with a thermal sensor to protect them from overheating. Heat from heater 404 is distributed using extruded aluminum heat sink fins on both sides to give a larger area to heat the air going through the heat sink fins. Heater 404 is controlled by control board 412 to regulate the temperature to within + / - 1 °C according to various embodiments described herein.

[0064] In other embodiments, heater 404 may be strip heaters. However, cartridge heaters may be preferred because the form factor of the cartridges gives us the best heat coverage to size ratio. In some embodiments, heater 404 and fan 418 are placed in the remaining space to the side of sample holder racks 410 and mostly centered within oven 400 to give us the most airflow as possible. Further a heat circulating assembly comprising a fan 418 and heat deflector 406 may also be included in oven 400. Heat circulating assembly may also only comprise fan 418 in some embodiments. Fan 418 and heat deflector 406 arc placed to circulate the heated air from heater 404 within the confines of oven 400 to achieve thermal performance. The flow of air over heater 404 and the heat circulating assembly of fan 418 and heat deflector 406 allows for even and consistent convection heating of the oven air.

[0065] In one example, fan 418 is composed of two 12v 60mm square fans that can run up to 7,000 RPM. Fan 418 may be chosen to get the airflow required to move the heated air around and through all the sample holders. In this example, fan 418 have ceramic bearings to handle higher temperatures of around 48 °C. According to various embodiments described herein, the fan may also handle temperatures up to 70°C. Fan speed may be controlled by an electronic control board 412. Temperature and humidity may also be monitored in the oven. Fan 418 may be mounted to a metal plate in the middle between heater 404 and the bottom of the oven at a 30- degree angle. Fan 418 may be positioned at an angle within the range of 0 to 42 degreesDocket No. TP388680WO1 according to various embodiments described herein. In other embodiments, fan 418 may be positioned at an angle within the range of 38 to 42 degrees. This distance and angle allow the air flow to curve around the sample holder racks, and up and through all the sample holder racks to get a uniform heat pattern at all four sample holder rack locations according to various embodiments of the present teachings.

[0066] Heat deflector 406 may help direct the cooler air down and over the heat sink fins for a more uniform air flow. In various embodiments, heat deflector 406 spans the entire top corner of the oven from the front to the back surface to prevent air from leaking around it. Heat deflector 406 is positioned at an angle configured to match fan 418 position angle with a range of 0 to 42 degrees. In other embodiments, fan 418 may be positioned at an angle within the range of 38 to 42 degrees. The angles of the fan and heat deflector are chosen to optimize the air flow for temperature uniformity and heat transfer from the heater assembly to the air. Circuit board 420 includes an air temperature sensor and a humidity sensor in this example.

[0067] As mentioned above, sample holder racks 410 are included in oven 400 to hold sample holders including biological samples. Sample holder racks 410 may be configured to be removable for cleaning. Sample holder racks 410 may also be removed without the need for any tools (screw drivers or wrenches) according to some embodiments. The small slots in the side wall of sample holder racks 410 and a spring can allow a user to depress the spring and remove the sample holder rack.

[0068] A sample holder may be, according to various embodiments described herein, an array plate, a microarray, a flow cell, a substrate, a multi-well tray, such as a standard microtiter 96-well, a 384-well plate, or a microcard, or a substantially planar support, such as a glass or plastic slide or a silicon chip, or the like. In accordance with various embodiments described herein, reaction sites may include, but are not limited to, through-holes, wells, indentations, spots, cavities, sample retainment regions, and reaction chambers, for example.

[0069] FIG. 5 illustrates a cross-section view of an oven according to various embodiments described herein. In this view, front door 502 and back door 504 may be viewed. Gear box 414 may be used to open and close front door 502 and back door 504. Further, air gap 420 between outer housing 402 and inner housing 416 is depicted. In some embodiments, a temperatureDocket No. TP388680WO1 sensor 506 is used to measure internal oven temperature to verify function and accuracy of the oven during initial calibration or during a repair.

[0070] FIG. 6A illustrates another exemplary front view of an oven including front door 502 according to various embodiments described herein. FIG. 6B illustrates oven 400 with front door 502 closed.

[0071] Similarly, FIG. 7A illustrates an exemplary back view of an oven including back door 504 according to various embodiments described herein. FIG. 7B illustrates an exemplary back view of an oven with back door 504 closed according to various embodiments described herein.

[0072] Both front door 502 and rear door 504 include air gap 420 between the outer housing 402 and inner housing 416. Front door 502 and back door 504 may have an outer housing made of aluminum to reduce weight. The inner housing may include a plastic surface (Delrin) to resist the transfer of heat to the aluminum. In some embodiments, front door 502 is seldom removed and is mostly for service. Back door 504 is controlled by a stepper motor in gear box 414 and can be moved into any position. Gear box 414 may be controlled from control board 412. Back door 504 may typically be opened a small amount to load the top sample holder rack first, but the amount back door 504 is opened may depend on the workload and number of sample holders required for a particular biological analysis.

[0073] FIG. 8 illustrates an exemplary perspective view of simulated air flow within an oven according to various embodiments described herein. In an oven configuration according to various embodiments described herein, heated air is more uniform in temperature. FIG. 8 illustrates computational fluid dynamics (CFD) modeling of the heated airflow within an exemplary oven. Thermal modeling was used to confirm a more uniform heated airflow according to various embodiments described herein.

[0074] Heater 804 heats the air and fan 818 distributes the heated air within the oven and around sample holder racks 810. Additionally, heat deflector 806 affects the heated airflow within the oven.Docket No. TP388680WO1

[0075] Sample holder racks 810 also show less variation in temperature between each sample holder rack. Sample holder rack-to- sample holder rack and sample holder rack temperature deviations in the example of FIG. 8 have minimal temperature variation, as shown in Table 1.Table 1

[0076] However, in a simulation of a non-optimal oven configuration, the sample holder rack-to-sample holder rack and sample holder rack temperature deviations show more variation and non-uniformity in temperature, as shown in Table 2.Table 2

[0077] Uniform heating of samples within the sample holder racks improves the quality of results obtained from a biological analysis.

[0078] Computing System

[0079] Additionally, the described implementation includes software, but the present teachings may be implemented as a combination of hardware and software or in hardware alone. The present teachings may be implemented with both object-oriented and non-objcct-oricntcd programming systems.Docket No. TP388680WO1

[0080] FIG. 9 is a block diagram that illustrates a computer system 900 that may be employed to carry out processing functionality, according to various embodiments. Instruments to perform experiments may be connected to the exemplary computing system 900. Computing system 900 can include one or more processors, such as a processor 904. Processor 904 can be implemented using a general or special purpose processing engine such as, for example, a microprocessor, controller or other control logic. In this example, processor 904 is connected to a bus 902 or other communication medium.

[0081] Further, it should be appreciated that computing system 900 of FIG. 9 may be embodied in any of a number of forms, such as a rack-mounted computer, mainframe, supercomputer, server, client, a desktop computer, a laptop computer, a tablet computer, handheld computing device (e.g., PDA, cell phone, smart phone, palmtop, etc.), cluster grid, netbook, embedded systems, or any other type of special or general purpose computing device as may be desirable or appropriate for a given application or environment. Additionally, computing system 900 can include a conventional network system including a client / server environment and one or more database servers, or integration with LIS / LIMS infrastructure. A number of conventional network systems, including a local area network (LAN) or a wide area network (WAN), and including wireless and / or wired components, are known in the art. Additionally, client / server environments, database servers, and networks arc well documented in the art. According to various embodiments described herein, computing system 900 may be configured to connect to one or more servers in a distributed network. Computing system 900 may receive information or updates from the distributed network. Computing system 900 may also transmit information to be stored within the distributed network that may be accessed by other clients connected to the distributed network.

[0082] Computing system 900 may include bus 902 or other communication mechanism for communicating information, and processor 904 coupled with bus 902 for processing information.

[0083] Computing system 900 also includes a memory 906, which can be a random-access memory (RAM) or other dynamic memory, coupled to bus 902 for storing instructions to be executed by processor 904. Memory 906 also may be used for storing temporary variables or other intermediate information during execution of instructions to be executed by processor 904.Docket No. TP388680WO1Computing system 900 further includes a read only memory (ROM) 908 or other static storage device coupled to bus 902 for storing static information and instructions for processor 904.

[0084] Computing system 900 may also include a storage device 910, such as a magnetic disk, optical disk, or solid-state drive (SSD) is provided and coupled to bus 902 for storing information and instructions. Storage device 910 may include a media drive and a removable storage interface. A media drive may include a drive or other mechanism to support fixed or removable storage media, such as a hard disk drive, a floppy disk drive, a magnetic tape drive, an optical disk drive, a CD or DVD drive (R or RW), flash drive, or other removable or fixed media drive. As these examples illustrate, the storage media may include a computer-readable storage medium having stored therein particular computer software, instructions, or data.

[0085] In alternative embodiments, storage device 910 may include other similar instrumentalities for allowing computer programs or other instructions or data to be loaded into computing system 900. Such instrumentalities may include, for example, a removable storage unit and an interface, such as a program cartridge and cartridge interface, a removable memory (for example, a flash memory or other removable memory module) and memory slot, and other removable storage units and interfaces that allow software and data to be transferred from the storage device 910 to computing system 900.

[0086] Computing system 900 can also include a communications interface 918. Communications interface 918 can be used to allow software and data to be Iran si erred between computing system 900 and external devices. Examples of communications interface 918 can include a modem, a network interface (such as an Ethernet or other NIC card), a communications port (such as for example, a USB port, a RS-232C serial port), a PCMCIA slot and card, Bluetooth, etc. Software and data transferred via communications interface 918 are in the form of signals which can be electronic, electromagnetic, optical or other signals capable of being received by communications interface 918. These signals may be transmitted and received by communications interface 918 via a channel such as a wireless medium, wire or cable, fiber optics, or another communications medium. Some examples of a channel include a phone line, a cellular phone link, an RF link, a network interface, a local or wide area network, and other communications channels.Docket No. TP388680WO1

[0087] Computing system 900 may be coupled via bus 902 to a display 912, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user. An input device 914, including alphanumeric and other keys, is coupled to bus 902 for communicating information and command selections to processor 904, for example. An input device may also be a display, such as an LCD display, configured with touchscreen input capabilities. Another type of user input device is cursor control 916, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 904 and for controlling cursor movement on display 912. This input device typically has two degrees of freedom in two axes, a first axis (e.g., x) and a second axis (e.g., y), that allows the device to specify positions in a plane. Computing system 900 provides data processing and provides a level of confidence for such data. Consistent with certain implementations of embodiments of the present teachings, data processing and confidence values are provided by computing system 900 in response to processor 904 executing one or more sequences of one or more instructions contained in memory 906. Such instructions may be read into memory 906 from another computer-readable medium, such as storage device 910. Execution of the sequences of instructions contained in memory 906 causes processor 904 to perform the process states described herein. Alternatively, hard-wired circuitry may be used in place of or in combination with software instructions to implement embodiments of the present teachings. Thus, implementations of embodiments of the present teachings are not limited to any specific combination of hardware circuitry and software.

[0088] The term "computer-readable medium" and “computer program product” as used herein generally refers to any media that is involved in providing one or more sequences or one or more instructions to processor 904 for execution. Such instructions, generally referred to as “computer program code” (which may be grouped in the form of computer programs or other groupings), when executed, enable the computing system 900 to perform features or functions of embodiments of the present invention. These and other forms of non-transitory computer- readable media may take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Non-volatile media includes, for example, solid state, optical or magnetic disks, such as storage device 910. Volatile media includes dynamic memory, such as memory 906. Transmission media includes coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 902.Docket No. TP388680WO1

[0089] Common forms of computer-readable media include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CD-ROM, any other optical medium, punch cards, paper tape, any other physical medium with patterns of holes, a RAM, PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave as described hereinafter, or any other medium from which a computer can read.

[0090] Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to processor 904 for execution. For example, the instructions may initially be carried on magnetic disk of a remote computer. The remote computer can load the instructions into its dynamic memory and send the instructions over a telephone line using a modem. A modem local to computing system 900 can receive the data on the telephone line and use an infra-red transmitter to convert the data to an infra-red signal. An infra-red detector coupled to bus 902 can receive the data carried in the infra-red signal and place the data on bus 902. Bus 902 carries the data to memory 906, from which processor 904 retrieves and executes the instructions. The instructions received by memory 906 may optionally be stored on storage device 910 either before or after execution by processor 904.

[0091] It will be appreciated that, for clarity purposes, the above description has described embodiments of the invention with reference to different functional units and processors.However, it will be apparent that any suitable distribution of functionality between different functional units, processors or domains may be used without detracting from the invention. For example, functionality illustrated to be performed by separate processors or controllers may be performed by the same processor or controller. Hence, references to specific functional units are only to be seen as references to suitable means for providing the described functionality, rather than indicative of a strict logical or physical structure or organization.

[0092] Distributed System

[0093] Some of the elements of a typical Internet network configuration 1000 are shown in FIG. 10, where a number of client machines 1002 possibly in a remote local office, are shown connected to a gateway / hub / tunnel-server / etc. 1010 which is itself connected to the internet 1008 via some internet service provider (ISP) connection 1010. Also shown are other possible clients 1012 similarly connected to the internet 1008 via an ISP connection 1014, with these unitsDocket No. TP388680WO1 communicating to possibly a central lab or office, for example, via an TSP connection 1016 to a gateway / tunncl-scrvcr 1018 which is connected 1020 to various enterprise application servers 1022 which could be connected through another hub / router 1026 to various local clients 1030. Any of these servers 1022 could function as a development server for the analysis of potential content management and delivery design solutions as described in the present invention, as more fully described below.

[0094] Gripper Arm

[0095] As previously mentioned, gripper arms, or plate handling robot systems are utilized in biological analysis instruments to increase throughput and add accuracy and repeatability to biological analyses. In the field of laboratory automation instruments, it is common to utilize gripper arms for the purpose of moving sample holders from storage areas to functional areas of a biological analysis instrument. These gripper arms typically feature three or more axes of movement, enabling precise positioning, and are equipped with a sample holder gripper to facilitate the pick-up and drop-off of sample holders. The primary objective of these gripper arms is to automate the process of transferring sample holders within the instrument, thereby implementing the desired sample processing protocols.

[0096] One of the challenges in using gripper arms is the need for accurate and precise picking up and dropping off sample holders. This is due to tolerance stack- up of part variations and assembly variations, which can affect the alignment and positioning of the gripper arms. In previous biological analysis instruments, a manual process is used to teach the gripper arm of each instrument assembly to account for assembly variability, which involves using fixtures specific to different locations. However, this manual process is susceptible to operator variation and can be time-consuming. Other previous gripper systems may use machine vision to detect fiducials, or types of touch sensors to detect reference features. Using a through beam optical sensor according to various embodiments described herein may be more accurate and perform a calibration method more quickly than previous systems.

[0097] According to embodiments described herein, an improved method and system for calibrating a gripper arm system to be more precise with improved control to enhance accuracy and repeatability is provided. According to embodiments described herein, the effort and timeDocket No. TP388680WO1 required for training the gripper arm system is reduced increasing efficiency while using in performing analyses as well as in manufacturing and in field service.

[0098] Further, according to embodiments described herein, the need for external fixtures and tools is greatly reduced or even eliminated. Embodiments of the present teachings aim to eliminate the reliance on external fixtures and tools used in the legacy calibration process. This simplifies the overall system and reduces costs.

[0099] Additionally, data collected during the calibration process according to various embodiments can be utilized in manufacturing, providing valuable insight for quality control and process optimization. For example, data collected can provide guidance to the assembly process where certain variations cannot be compensated for through software adjustments alone. This guidance can include information for leveling the gripper arms, ensuring proper alignment, and facilitating smooth and accurate movements.

[0100] The calibration system according to various embodiments described herein utilizes multiple optical through-beam sensors on the gripper arms to measure the position of position identifiers as alignment features at various locations in the functional stages where the gripper arms interact. In various embodiments, position identifiers are cylindrical posts. The optical sensor of the gripper arm searches and records the positions of the edges of these position identifiers in the x, y, and z directions within its coordinate system. In various embodiments, there are at least three position identifiers that are accurately positioned relative to the specific location.

[0101] For instance, on each slot of a sample holder rack, the three position identifiers are positioned with precision according to the machined sample holder rack part configuration. They are not affected by additional tolerance stack-up. By measuring the positions of these three position identifiers, the system can correct any translational and rotational variations in three- dimensional space according to various embodiments described herein.

[0102] To establish consistency and independence from instrument variations, frames of references with local coordinate systems are defined for both the functional areas for sample holders and the gripper arm itself. With reference to FIG. 3, functional areas may includeDocket No. TP388680WO1 storage area 304 for sample holders, oven 300, optical scanner 31 , trash bin 312, wash station 308, and unclamp station 310. Transformations between these established frames of references are determined based on the measured positions of the position identifiers, which encapsulate the assembly variability.

[0103] Moreover, the optical sensors on the gripper arms may provide an additional functionality by directly detecting the type of sample holder being used according to various embodiments described herein. Through measuring the edges of the sample holder, the system can distinguish between different types of sample holders based on their dimensions. This capability not only enables the system to identify specific sample holders, but also allows it to determine the proper alignment and seating of the sample holder.

[0104] These functionalities contribute to improved error detection and handling, ultimately enhancing the reliability and usability of the system. By accurately detecting and aligning the sample holders, the calibration system ensures precise and efficient gripper arm operations, reducing errors and optimizing overall system performance.

[0105] Multiple position identifiers are utilized at each functional area of the biological analysis instrument to enable corrections of translation and rotation errors in three dimensions. Multiple position identifiers 316 are depicted in FIG. 3. The dimensions and positional accuracy of these position identifiers arc tightly controlled to meet the desired specifications.

[0106] FIG. 11 depicts an exemplary gripper arm according to various embodiments described herein. Left gripper arm 1112 and right gripper arm 1114 utilize multiple optical through beam sensors (1108 and 1110) are integrated at different locations on the gripper arms. In this example, optical sensors 1108 sense y and z positions while optical sensors 1110 sense x and z positions. The apertures of LED excitation sources 1104 and photo detectors 1106 are precisely machined features of the gripper arms. This design ensures accuracy within machining tolerances without not subjected to tolerance stack-up.

[0107] Circuit board 1102 includes excitation LEDs and photo detectors. The system may also incorporate sensor signal processing electronics (not shown) and algorithms that facilitateDocket No. TP388680WO1 automatic calibration of the detection threshold to half of the unobstructed signal. This calibration process according to various embodiments described herein eliminates the effects of sensor variation caused by component variability, alignment, temperature, and aging.

[0108] FIG. 12 illustrates a magnified view of an optical sensor of a gripper arm according to various embodiments described herein.

[0109] Optical sensor 1206 detects LED beams from LED excitation source 1204 within a gripper arm. Optical sensor 1206 and LED excitation source 1204 are surrounded in walls 1214 so that stray light does not interfere with the various optical sensors. The gripper arm includes an excitation aperture 1208 and a sensor aperture 1210 for the LED beam to travel between. When a position identifier blocks the LED beam sensor signal processing electronics 1202 can determine the precise position of a sample holder or sample rack of a functional area of the biological analysis instrument.

[0110] Control software and algorithms are implemented with a computing system (FIG. 9) to establish frames of references with associated local coordinate systems that remain independent of instrument variations. The transformations between these frames of references account for the assembly variation and are used to generate an adjusted coordinate system. An adjusted coordinate system is used to control the gripper arms more precisely and accurately. These transformations are calculated based on the automated measurement of position identifier positions using the gripper arm optical sensors.

[0111] FIG. 13 illustrates a flowchart of a method of calibrating a gripper arm 1300 according to various embodiments described herein. A position identifier set is included on a sample holder rack and used to calibrate a gripper arm according to various embodiments described herein. A position identifier set may also be included on the sample holder or on other functional areas where the gripper arm may interact according to various embodiments of the present teachings. In various embodiments, three position identifiers are needed to calibrate the gripper arm.

[0112] Method 1300 includes measuring the position of each position identifier of the position identifier set 1302. For example, for the first position identifier in the set, an opticalDocket No. TP388680WO1 through beam sensor measures the edge of the first position identifier in the x-direction. Similarly, an edge of the first position identifier is measured in the y-dircction. Further, the edge of the first position identifier is measured in the z-direction. The same measurements are taken for each of the position identifiers in the position identifier set. In one example, the x-, y-, and z- positions of the second and third position identifiers are measured. The x-, y-, and z- positions are determined using the measured edge positions and the known geometry of the position identifiers.

[0113] In other examples, the position identifiers may be included on a sample holder. Sample holder rack and sample holders may be in any one of the functional areas within the biological analysis instrument.

[0114] In step 1304, an x-position, a y-position, and a z-position is determined for each of the position identifiers. A predetermined coordinate system was generated by the biological instrument design and dimensions of the instrument and components. The x, y, and z positions are determined by optically sensing a position identifier. In step 1306, translational and rotational variations are determined by using the x, y, and z positions of each position identifier. In step 1308, an adjusted coordinate system is generated based on the determined translational and rotational variations to compensate for the determined translational and rotational variations.

[0115] To further illustrate detection of position identifiers, FIGS. 14A-D show an exemplary gripper arm with optical sensor 1408 detection position identifier 1404.

[0116] In FIG. 14A, sample holder rack 1402 includes position identifier 1404. Gripper arm 1406 includes optical sensor 1408. Gripper arm 1406 includes a LED excitation source to emit LED beam 1410 to optical sensor 1408. As gripper arm 1406 moves in a negative x-direction to an expected position of position identifier 1404, position identifier blocks LED beam 1410. Optical sensor 1408 determines the x-position when half of LED beam 1410 is blocked by position identifier 1404. As such, an x-position may be adjusted based on the measurement of position identifier 1404. In various embodiments, position identifier may be a post. In some embodiments, unused LED beams at the time may be turned off to prevent interference from any reflected stray light.Docket No. TP388680WO1

[0117] Similarly, FIG. 14B illustrates detection of position identifier 1404 to determine an adjusted y-position. In this example, gripper arm 1406 is moved in a negative y-dircction to an expected position of position identifier 1404 so that position identifier 1404 breaks LED beam 1412. When optical sensor 1414 detects half of LED beam 1412 is blocked by position identifier 1404, an adjusted y-position is determined.

[0118] Further, determining an adjusted z-position is depicted in FIGS. 14C and 14D according to various embodiments described herein. In FIG. 14C, gripper arm 1406 is moved to an expected position of position identifier 1404 in a negative z-direction. When optical sensor 1412 determines LED beam 1408 is blocked by position identifier 1404, an adjusted z-position is determined.

[0119] Similarly, in FIG. 14D, an adjusted z-position is determined by optical sensor 1414 when half of LED beam 1410 is blocked by position identifier 1404.

[0120] Adjusted x, y, and z positions are used to generate an adjusted coordinate system to refine expected positions. Expected positions are determined using the known dimensions of the biological analysis instrument and components. Using the adjusted coordinate system, a gripper arm is calibrated to move more precisely according to various embodiments described herein.

[0121] FIG. 15 depicts a storage area 1500 for sample holder racks and sample holder 1520. In this example, sample holder 1520 deviates from a nominal position, or expected position, due to assembly variances. As described above, the x, y, z positions of each position identifier in a position identifier set are detected using the optical sensors on the gripper arm. A position identifier set may include a first, second, and third position identifier. In the example, an actual position 1502 of a position identifier is illustrated. The nominal position 1504 of the position identifier is shown. Similarly, a second position identifier’s actual position 1506 is shown along a nominal position 1510. After an optical sensor measures the x, y, and z positions of the position identifiers, the deviation can be determined by a processor by comparing the actual positions (1502 and 1508) with the nominal positions (1504 and 1510).Docket No. TP388680WO1

[0122] As such, the nominal coordinate system 1514 may be adjusted based on the deviation and an adjusted coordinate system 1512 can be generated. A gripper arm controlled based on the adjusted coordinate system 1512 can more accurately move sample holders in the instrument.

[0123] FIG. 16 illustrates an exemplary signal processing block diagram for calibrating a LED excitation source according to various embodiments described herein. In a LED calibration method according to various embodiments of the present teachings, the gain setting of programmable gain transimpedance amplifier (PGA) 1608 is determined by setting LED current source 1606 to half of a desired operating current. Next, the gain of PGA 1608 is set to the lowest gain. If a sensor signal is less than the threshold of threshold comparator 1610, gain is increased until the threshold is crossed. The gain setting of PGA 1608 is then set at the gain the threshold is crossed.

[0124] Next, the LED current setting of the LED current source 1606 is determined. The LED current setting should be set every time the sensor is used. First, LED current source 1606 is set to zero. Then the current is increased at LED current source 1606 until the threshold of threshold comparator 1610 is crossed. LED current source 1606 is then set at double the current of when the threshold was crossed.

[0125] Examples

[0126] The following numbered examples are embodiments:1. An apparatus for heating a biological sample, the apparatus comprising: an outer housing; an inner housing; an air gap between the outer housing and the inner housing; a heater configured to supply heat to the biological sample within the housing; a heat circulating assembly configured to circulate heated air within the housing, wherein the heat circulating assembly comprises a fan and a heat deflector; andDocket No. TP388680WO1 a sample holder rack configured to hold a sample holder including the biological sample.2. The apparatus of example 1, wherein the sample holder rack is configured to hold four sample holders.3. The apparatus of examples 1 or 2, wherein the fan is connected to the inner housing below the heater.4. The system of any of the examples 1 to 3, wherein the fan is configured to direct air at an angle to allow air flow around the sample holder.5. The system of any of example 4, wherein the angle is 0 to 42 degrees.6. The system of example 4 or 5, wherein the angle is 30 degrees.7. The system of any of the examples 1 to 6, wherein the heat deflector is configured to direct cooler air down and over the heater.8. The system of any of the examples 1 to 7, wherein the heat deflector is located on top of the sample holder rack.9. The system of any one of the examples 1 to 8, wherein the heat deflector is configured to match the angle of the fan.10. The system of any one of the examples 1 to 9, wherein the sample holder is a hybridization tray.11. A system for adjusting a gripper arm in a biological analysis instrument, the system comprising: a gripper arm configured to move a sample holder between functional areas of the biological analysis instrument; a position identifier set on a sample holder rack, wherein the position identifier set includes a first position identifier, a second position identifier, and a third position identifier;Docket No. TP388680WO1 an optical sensor configured to measure the position of each position identifier of the position identifier set; a processor configured to: determine an x-position, a y-position, and a z-position of each position identifier of the position identifier set using the optical sensor, wherein the x-position, the y-position, and the z-position are used to generate an adjusted coordinate system, and control the movement of the gripper arm using the adjusted coordinate system.12. The system of example 11, wherein each position identifier of the position identifier set is a post.13. The system of examples 11 or 12, wherein the adjusted coordinate system adjusts predetermined coordinates of the storage area and functional areas of the biological analysis instrument.14. The system of any one of the examples 11 to 13, further comprising: a gripper arm control system, wherein the gripper arm control system uses the adjusted coordinate system to move the sample holder from one location to another location within the biological analysis instrument.15. The system of any one of the examples 11 to 14, wherein the processor is further configured to determine translational and rotational variations to generate the adjusted coordinate system.16. The system of any one of the examples 11 to 15, wherein the x-position of the first position identifier is based on when the first position identifier blocks half of a light beam detected by the optical sensor, the y-position is based on when the first position identifier blocks half of a light beam detected by the optical sensor, and the z-position is based on when the first position identifier blocks half of a light beam detected by the optical sensor.Docket No. TP388680WO117. The system of any one of the examples 11 to 16, wherein the x-position of the second position identifier is based on when the second position identifier blocks half of a light beam detected by the optical sensor, the y-position is based on when the second position identifier blocks half of a light beam detected by the optical sensor, and the z-position is based on when the second position identifier blocks half of a light beam detected by the optical sensor, and wherein the x-position of the third position identifier is based on when the third position identifier blocks half of a light beam detected by the optical sensor, the y-position is based on when the third position identifier blocks half of a light beam detected by the optical sensor, and the z-position is based on when the third position identifier blocks half of a light beam detected by the optical sensor.18. A biological analysis system for analyzing a biological sample, the system comprising: a sample holder including a position identifier set, wherein the position identifier set includes a first position identifier, a second position identifier, and a third position identifier; an oven, wherein the oven comprises: an outer housing; an inner housing an air gap between the outer housing and the inner housing; a heater configured to supply heat to the biological sample within the housing; a heat circulating assembly configured to circulate heated air within the housing; a sample holder rack configured to hold the sample holder including the biological sample; and a gripper arm system configured to move the sample holder between functional areas of the biological analysis system, wherein the gripper arm system comprises:Docket No. TP388680WO1 an optical sensor configured to measure the position of each position identifier of the position identifier set; a processor configured to: determine an x-position, a y-position, and a z-position of each position identifier of the position identifier set using the optical sensor, wherein the x-position, the y-position, and the z-position are used to generate an adjusted coordinate system, and control the movement of the gripper arm using the adjusted coordinate system.19. The system of example 18, wherein the fan is configured to direct air at an angle to allow air flow around the sample holder.20. The system of example 19, wherein the angle is 0 to 42 degrees.21. The system of example 18 or 19, wherein the angle is 30 degrees.22. The system of any one of the examples 18 to 21, wherein the adjusted coordinate system adjusts predetermined coordinates of the storage area and functional areas of the biological analysis instrument.23. The system of any one of the examples 18 to 22, wherein the processor is further configured to determine translational and rotational variations to generate the adjusted coordinate system.

[0127] Although the present invention has been described with respect to certain exemplary embodiments, examples, and applications, it will be apparent to those skilled in the art that various modifications and changes may be made without departing from the invention.

Claims

Docket No. TP388680WO1CLAIMSWhat is claimed is:

1. An apparatus for heating a biological sample, the apparatus comprising: an outer housing; an inner housing; an air gap between the outer housing and the inner housing; a heater configured to supply heat to the biological sample within the housing; a heat circulating assembly configured to circulate heated air within the housing, wherein the heat circulating assembly comprises a fan and a heat deflector; and a sample holder rack configured to hold a sample holder including the biological sample.

2. The apparatus of claim 1, wherein the sample holder rack is configured to hold four sample holders.

3. The apparatus of claims 1 or 2, wherein the fan is connected to the inner housing below the heater.

4. The system of any of the claims 1 to 3, wherein the fan is configured to direct air at an angle to allow air flow around the sample holder.

5. The system of any of claim 4, wherein the angle is 0 to 42 degrees.

6. The system of claim 4 or 5, wherein the angle is 30 degrees.

7. The system of any of the claims 1 to 6, wherein the heat deflector is configured to direct cooler air down and over the heater.

8. The system of any of the claims 1 to 7, wherein the heat deflector is located on top of the sample holder rack.Docket No. TP388680WO19. The system of any one of the claims 1 to 8, wherein the heat deflector is configured to match the angle of the fan.

10. The system of any one of the claims 1 to 9, wherein the sample holder is a hybridization tray.

11. A system for adjusting a gripper arm in a biological analysis instrument, the system comprising: a gripper arm configured to move a sample holder between functional areas of the biological analysis instrument; a position identifier set on a sample holder rack, wherein the position identifier set includes a first position identifier, a second position identifier, and a third position identifier; an optical sensor configured to measure the position of each position identifier of the position identifier set; a processor configured to: determine an x-position, a y-position, and a z-position of each position identifier of the position identifier set using the optical sensor, wherein the x-position, the y-position, and the z-position are used to generate an adjusted coordinate system, and control the movement of the gripper ami using the adjusted coordinate system.

12. The system of claim 11, wherein each position identifier of the position identifier set is a post.

13. The system of claims 11 or 12, wherein the adjusted coordinate system adjusts predetermined coordinates of the storage area and functional areas of the biological analysis instrument.

14. The system of any one of the claims 11 to 13, further comprising: a gripper arm control system, wherein the gripper arm control system uses the adjusted coordinate system to move the sample holder from one location to another location within the biological analysis instrument.Docket No. TP388680WO115. The system of any one of the claims 11 to 14, wherein the processor is further configured to determine translational and rotational variations to generate the adjusted coordinate system.

16. The system of any one of the claims 11 to 15, wherein the x-position of the first position identifier is based on when the first position identifier blocks half of a light beam detected by the optical sensor, the y-position is based on when the first position identifier blocks half of a light beam detected by the optical sensor, and the z-position is based on when the first position identifier blocks half of a light beam detected by the optical sensor.

17. The system of any one of the claims 11 to 16, wherein the x-position of the second position identifier is based on when the second position identifier blocks half of a light beam detected by the optical sensor, the y-position is based on when the second position identifier blocks half of a light beam detected by the optical sensor, and the z-position is based on when the second position identifier blocks half of a light beam detected by the optical sensor, and wherein the x-position of the third position identifier is based on when the third position identifier blocks half of a light beam detected by the optical sensor, the y-position is based on when the third position identifier blocks half of a light beam detected by the optical sensor, and the z-position is based on when the third position identifier blocks half of a light beam detected by the optical sensor.

18. A biological analysis system for analyzing a biological sample, the system comprising: a sample holder including a position identifier set, wherein the position identifier set includes a first position identifier, a second position identifier, and a third position identifier; an oven, wherein the oven comprises: an outer housing; an inner housing an air gap between the outer housing and the inner housing;Docket No. TP388680WO1 a heater configured to supply heat to the biological sample within the housing; a heat circulating assembly configured to circulate heated air within the housing; a sample holder rack configured to hold the sample holder including the biological sample; and a gripper arm system configured to move the sample holder between functional areas of the biological analysis system, wherein the gripper arm system comprises: an optical sensor configured to measure the position of each position identifier of the position identifier set; a processor configured to: determine an x-position, a y-position, and a z-position of each position identifier of the position identifier set using the optical sensor, wherein the x- position, the y-position, and the z-position of each position identifier are used to generate an adjusted coordinate system, and control the movement of the gripper arm using the adjusted coordinate system.

19. The system of claim 18, wherein the fan is configured to direct air at an angle to allow air flow around the sample holder.

20. The system of claim 19, wherein the angle is 0 to 42 degrees.

21. The system of claim 18 or 19, wherein the angle is 30 degrees.

22. The system of any one of the claims 18 to 21, wherein the adjusted coordinate system adjusts predetermined coordinates of the storage area and functional areas of the biological analysis instrument.Docket No. TP388680WO123. The system of any one of the claims 18 to 22, wherein the processor is further configured to determine translational and rotational variations to generate the adjusted coordinate system.

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