Automated analytical system for processing biological samples

Abstract

To provide an automated analytical system.SOLUTION: A method is carried out by manually moving a sample rack from a loading position towards a processing position along a lane in a receiving bay. The movement is paused when the rack reaches a focusing position between the two above-mentioned terminal positions, where a proximal stopping element provides sufficient resistance for the movement of the rack to be hindered. In this position, a reader is moved so as to focus on the sample rack being inserted into the lane. With the reader so focused, the reader detects features of sample receptacles. The processing position is defined by a distal stopping element, marking the endpoint of the insertional movement of the sample rack. In this terminal position, the rack is positioned, detected in this position, and then locked for alignment with regard to the following processing of the content of the sample receptacles.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] FIELD OF THE INVENTION The present invention is in the field of systems and methods for performing biological or biochemical assays, and in this field, the invention relates to analytical systems for processing biological samples, which are processed in an automated manner after being introduced into the system. [Background technology]

[0002] background The processing of biological samples is of great importance for analytical and diagnostic purposes. In particular, the field of in vitro diagnostics (IVD) requires consistent, reliable, and accurate handling of sample specimens in a controlled environment. Given the often large throughput of clinical samples, ease of use and minimal time commitment are desirable, as they provide considerable relief to clinical technicians and other medical professionals.

[0003] In this regard, although a high degree of automation is often desirable, in some cases a balanced approach, at least with regard to the option of manual intervention, may be advantageous. The balance between integration and maximizing throughput, on the one hand, and flexibility and customization, on the other, is crucial in the medium-throughput sector of clinical diagnostics. For example, it may be advantageous to be able to process a large number of samples of a particular type in a batch, while preserving the possibility to process different sample types in mixed batches, prioritize processes requiring a short turnaround time (STAT), etc.

[0004] For example, analytical systems such as the cobas® 6800 / 8800 from Roche Diagnostics GmbH are primarily intended for use in the high-throughput sector, while point-of-care (PoC) solutions such as the cobas® LIAT from the same company address the low-throughput sector with the possibility of personalized analysis.

[0005] As outlined above, there is a need in the art to provide a balanced system for medium throughput purposes that provides a thoughtful mix between throughput and flexibility. Summary of the Invention

[0006] overview The present disclosure describes various aspects of an automated analysis system that meets the needs stated above.

[0007] In a first aspect described herein, a method for introducing a sample rack holding multiple sample containers into a sample receiving bay in a housing of an automated analysis system is provided. The method is performed by manually moving the sample rack along lanes in the receiving bay from a loading position toward a processing position. The movement is stopped when the rack reaches a focus position between the two end positions, where a proximal stop element provides sufficient resistance to prevent the rack from moving. At this position, a reading device in substantially the same horizontal plane as the lanes is moved to focus on each lane in the receiving bay and thus on the sample rack being inserted into the lane. With the reading device thus focused, movement of the sample rack toward the processing position is resumed past the proximal stop element and all the way to the processing position while the reading device detects characteristics of the sample rack and / or the multiple sample containers. The processing position is defined by a distal stop element that indicates the end of the sample rack's insertion movement. At this end position, the rack is positioned, detected, and then locked for subsequent processing of the contents of the sample containers.

[0008] In another aspect, the present disclosure relates to a system for processing biological samples, the system comprising a sample rack for a plurality of sample containers, a housing enclosing a receiving bay having a plurality of substantially parallel lanes for the sample rack, an optional platform that can be moved in and out of the housing to extend the lanes and position the sample rack in an inspection position, and an indicator system for indicating the status of biological samples in containers in dedicated positions on the sample rack.

[0009] A further aspect described herein is a system for providing binding particles for isolating biological material, the system comprising: a container for containing a suspension of binding particles; and a shaker for shaking the container to suspend the binding particles, the shaker comprising a bayonet lock configured to lock the container in a shaking position.

[0010] Also described herein is a method for shaking a container containing a suspension of binding particles. In a first step, the container is secured to a shaker equipped with a bayonet lock by pressing the container against the shaker at a predetermined horizontal displacement angle and rotating the container horizontally in the direction opposite to the displacement, thereby aligning and locking the container in a shaking position. In a second step, the container is shaken by the shaker, thereby suspending the binding particles.

[0011] Another aspect described herein is a system for processing biological samples, the system comprising a housing, an interface for observing and manipulating the processing within the housing, and a transparent sliding window that opens and closes the interface while being supported by a counterweight that stabilizes the window in its respective position.

[0012] Yet another aspect disclosed herein is a system for cooling reagents for performing a biological assay, the system comprising: a cooling chamber surrounded by a substantially insulated housing having a top lid with a closable opening; a reagent container within the cooling chamber having an open or penetrable top; a pipetter above the cooling chamber for aspirating the reagent from the container through the opening in the top lid; and a heating element below the lid configured to heat the lid above the dew point of air outside the cooling chamber.

[0013] Further disclosed herein is a thermal cycler for incubating biological samples, the thermal cycler comprising a mount for a microwell plate, a loading platform that rotates to reciprocate the microwell plate relative to the mount between a loading position and an incubation position, and a motor for rotating the loading platform between the above-mentioned positions.

[0014] Another aspect disclosed herein is a flexibly mounted pipette tip rack, where the rack is mounted on a work surface of an automated analysis system via one or more flexible elements positioned between the rack and the work surface.

[0015] In another aspect, the present disclosure describes a method for monitoring a valve system in an automated analyzer system, the method including: starting up the automated analyzer system by turning on a power source; during or immediately after the start-up process, performing a start-up valve check on the operational status of the valve using an electrical probe signal sent from a control unit to the valve and detecting a corresponding electrical response signal indicating that the valve is operational; operating the valve system in a full start-up mode of the automated analyzer system; repeatedly performing the above-mentioned probe signal check on an idle valve as an operational valve check; and generating an error message if the electrical response signal of the above-mentioned check is not present. [Brief explanation of the drawings]

[0016] [Figure 1A] 1 is a schematic diagram of an automated analysis system as described herein. [Figure 1B] 1 is a schematic diagram of an automated analysis system as described herein. [Figure 1C] 1 is a schematic diagram of an automated analysis system as described herein.

[0017] [Figure 2A] 1 shows a schematic representation of a receiving bay of the automated analysis system disclosed herein. [Figure 2B] 1 shows a schematic representation of a receiving bay of the automated analysis system disclosed herein. [Figure 2C] 1 shows a schematic representation of a receiving bay of the automated analysis system disclosed herein. [Figure 2D] 1 shows a schematic representation of a receiving bay of the automated analysis system disclosed herein. [Figure 2E] 1 shows a schematic representation of a receiving bay of the automated analysis system disclosed herein. [Figure 2F] 1 shows a schematic representation of a receiving bay of the automated analysis system disclosed herein.

[0018] [Figure 3A] 1A-1D show various views of the indicator system disclosed herein. [Figure 3B] 1A-1D show various views of the indicator system disclosed herein. [Figure 3C] 1A-1D show various views of the indicator system disclosed herein. [Figure 3D] 1A-1D show various views of the indicator system disclosed herein. [Figure 3E] 1A-1D show various views of the indicator system disclosed herein.

[0019] [Figure 4A]1 shows a perspective view of a system and method for providing binding particles for isolating biological material as described herein. [Figure 4B] 1 shows a perspective view of a system and method for providing binding particles for isolating biological material as described herein. [Figure 4C] 1 shows a perspective view of a system and method for providing binding particles for isolating biological material as described herein.

[0020] [Figure 5] 1 shows a diagram of a transparent window of the automated analysis system disclosed herein.

[0021] [Figure 6A] 1 shows a system for cooling reagents for performing biological assays as disclosed herein. [Figure 6B] 1 shows a system for cooling reagents for performing biological assays as disclosed herein. [Figure 6C] 1 shows a system for cooling reagents for performing biological assays as disclosed herein. [Figure 6D] 1 shows a system for cooling reagents for performing biological assays as disclosed herein. [Figure 6E] 1 shows a system for cooling reagents for performing biological assays as disclosed herein.

[0022] [Figure 7A] FIG. 1 is a schematic diagram of a thermal cycler set up for incubating biological samples as disclosed herein. [Figure 7B] FIG. 1 is a schematic diagram of a thermal cycler set up for incubating biological samples as disclosed herein.

[0023] [Figure 8]1A and 1B illustrate schematic diagrams of a flexibly mounted pipette tip rack as described herein.

[0024] [Figure 9] 1 shows a flow chart illustrating steps of a method for monitoring a valve system of an automated analyzer system as described herein. DETAILED DESCRIPTION OF THE INVENTION

[0025] Detailed Description The present disclosure describes embodiments of automated analytical systems, also referred to as automated analytical instruments, analytical devices, or analytical devices. Such instruments can perform assays on biological samples, particularly liquid biological samples, for example in the field of clinical diagnostics. For example, in the context of a clinical laboratory, the analytical device can be configured to perform multi-step analytical processes, such as nucleic acid testing, that involve adding and / or removing substances, such as samples, solid supports, buffers, oils, primers, polymerases, nucleotides, labels, probes, or other reaction fluids, to and / or from containers; shaking the container to mix the contents; maintaining and / or altering the temperature of the container's contents; heating or cooling the container's contents; altering the concentration of one or more components in the container's contents; separating or isolating components in the container's contents; detecting electromagnetic signal emissions (e.g., light) from the container's contents; inactivating or terminating an ongoing reaction; or any combination of two or more of such processes.

[0026] The analytical device is at least partially automated to perform the desired analytical or pre-analytical process. Thus, an automated analytical system can automatically identify the contents of a sample container and the assay to be performed. For example, the analytical device can read a label, such as a barcode or RFID tag, on a sample container to identify the type of sample in the container and the assay to be performed.

[0027] In the context of the analytical device described herein, in order to process the sample, the sample container must be introduced into the housing of the automated analytical system. For this purpose, several manual and / or automated measures can be implemented.

[0028] Accordingly, a first aspect described herein is a method for introducing a sample rack holding a plurality of sample containers with biological samples into a sample receiving bay in a housing of an automated analytical system, the method comprising: a) manually moving a sample rack along a lane within a sample receiving bay from a loading position toward a processing position; b) pausing the movement when the sample rack reaches a focus position defined by a proximal stop element between the loading position and the processing position; c) moving the reader in substantially the same horizontal plane as the lane and focusing the reader on the lane; d) resuming movement of the sample rack past the proximal stop element and detecting characteristics of the sample rack and / or the plurality of sample containers with the reader during movement until the sample rack reaches a processing position defined by the distal stop element; e) positioning, detecting and locking the sample rack in a processing position; f) processing the biological sample in the sample container; The method includes:

[0029] The methods described herein provide various advantages, for example, the introduction of sample racks into the sample receiving bay of an automated analytical system is ensured by multiple checkpoints.

[0030] Manually moving sample racks along lanes has proven preferable to automated transport in many situations. For example, when a user places a rack in a lane at the loading position, automated loading of the rack at a predetermined (typically relatively slow) speed is often perceived as more cumbersome than useful. Furthermore, manual intervention (voluntary, impatient, or inadvertent) during automated movement can lead to damage to the motor driving the movement. On the other hand, manually inserting a rack into a sample receiving bay can introduce potential sources of error. For example, a user may move the rack at an excessively high speed, preventing the barcode reader or camera from focusing on the correct lane, and thus the sample rack and / or sample container, leading to reading errors. Solutions found in the art include rigid configurations with tight-fitting guide rails and the like, but require the user to apply greater force to overcome the resulting friction. Such solutions are not only slow, but also impose additional strain on the user.

[0031] Pausing the movement according to the disclosed method with the aid of a proximal stop element combines the advantages of manual and automatic insertion: on the one hand, it allows the rack to be inserted quickly before and after reaching the focus position, while on the other hand it gives the reading device enough time to focus on the rack in the loaded lane when the rack is in the focus position, thus minimizing the risk of reading errors.

[0032] As used herein, "sample rack" refers to a sample vessel holder. In the field of in vitro diagnostics, dimensions and shapes are typically standardized. In some embodiments, the sample rack holds multiple sample vessels arranged consecutively in a row within corresponding dedicated sample vessel slots.

[0033] The "loading position" is the initial position where the sample rack is located at the beginning of insertion into the sample bay. For example, in the case of a sample rack with linearly arranged slots for sample containers as described above, a user can hold one end of the rack, e.g., by a handle, and position the other end at the beginning of a corresponding lane that forms part of the sample receiving bay. Starting from this loading position, movement begins toward the focus position and ultimately toward the processing position.

[0034] The "focus position" is an intermediate position between the loading and processing positions. Defined by the proximal stop element, this intermediate or transitional position allows the reader to focus on the loaded lane and, therefore, the corresponding sample rack and / or sample vessel within the sample rack.

[0035] As used herein, a "proximal stop element" can comprise or consist of a variety of elements, such as a baffle, a depression or protrusion on the bottom of a lane, a stop lug, a spherical piece, an injection-molded part, a bolt, a magnet, a catch pin, a catch plate, or a hook. Because the proximal stop element relates to the focus position, which is an intermediate or transitional position, it does not provide a binding or locking effect as described herein with respect to the processing position. Because its purpose is to cause a temporary suspension of the movement of the sample rack, it is sometimes referred to herein as a "delay element." In this context, if the element is a magnet, it is preferably a non-permanent magnet, such as an electromagnet that can be switched on and off. Similarly, if it is a bolt, it is preferably retractable from the path of the rack on the lane, and so on. In some embodiments, the proximal stop element is a baffle on the lane surface, the physical resistance of which signals that the rack has reached the focus position, thus prompting the user to stop movement at this point. In some embodiments, the proximal stop element is an injection-molded part, such as an injection-molded baffle.

[0036] When the sample rack reaches the focus position, in some embodiments this position is detected and a signal is sent to the reader or to a control unit that controls the reader.

[0037] The detection can be performed, for example, by a sensor. In such an embodiment, the sensor detects that the sample rack is in the focus position and triggers the transmission of a signal to the reading device. In some embodiments, such a sensor is an inductive sensor, a pressure sensor, an acceleration sensor, or a light barrier. For example, the sensor can detect a dedicated detection element included in the sample rack when the focus position is reached. The detection element can be a conductive element, such as a flag or platelet, that can be detected by a proximity sensor in the form of an inductive sensor.

[0038] Once the reader is properly focused, movement of the rack toward the processing position can be resumed. In some embodiments, proper focus is detected and indicated to the user by a signal, e.g., to prompt the user to resume movement. Detection may be by indication via the reader's control unit, an optical signal, e.g., an LED or other lamp, or an acoustic signal, e.g., a chime. As described above, resumption of movement can be accompanied by or followed by removing the proximal stop element from the path of the sample rack on the lane or overcoming the resistance of the proximal stop element by, e.g., manually applying more force or performing a specific movement, e.g., tilting or lifting the sample rack. During forward movement, the reader records information about the sample rack and / or sample vessels and / or their contents. For example, the sample rack can include sample vessels with identifiers, such as one-dimensional or two-dimensional barcodes. Thus, in some embodiments, the reader reads identifiers on the sample vessels and / or sample rack in step d). In some embodiments, the reader includes a light source, e.g., an LED. The light source can be axially aligned with the optical path of the reader, particularly when the reader is a barcode scanner, such as a laser barcode scanner, or a camera that reads barcodes and / or detects other characteristics of the sample rack and / or sample container. In some embodiments, a processing and / or control unit obtains information by decoding the read barcode and associates the information with the corresponding sample container. The information can then be used to perform assays on the biological sample material, identify the contents of the sample container, or identify patient information such as a patient identification number. Alternatively, or in addition, the reader can detect physical characteristics of the sample container and / or sample rack. In some embodiments, the reader measures physical parameters of the sample container and / or the biological sample in the sample container.In some embodiments, the physical parameter is the diameter of the sample vessel. For example, by measuring the diameter of a sample vessel, such as a long, thin sample tube, at its top end, it is possible to determine whether a cap is present on top of the sample vessel. This correlation can be used when a specialized cap has a diameter different from the diameter of the sample vessel itself. In many cases, the diameter of the cap exceeds the diameter of the sample vessel. However, embodiments are also contemplated in which the diameter of the specialized cap is smaller than the diameter of the corresponding sample tube. Alternatively, or in addition, the reading device can be a camera having a processor for processing the collected visual data. The processor can determine the presence or absence of a cap or the like on a sample vessel by recognizing features such as caps by characteristics other than diameter.

[0039] Upon reaching the processing position defined by the distal stop element, several actions are performed that are important to ensure the reliability of the method and to provide a robust starting point for downstream processing.

[0040] Positioning a sample rack in a processing position refers to aligning the rack with respect to its surroundings. In particular, downstream processing of biological samples contained in one or more sample containers, e.g., in a sample receiving bay of an automated analytical system described herein, may include dedicated elements or modules within the housing of the analytical device that interact with the sample rack, the sample containers, and / or the contents of the sample containers. For example, an uncapping device can remove caps from sample containers. Such caps may be screw caps or any other suitable caps known in the art. The uncapping device may be a robotic arm configured to perform a rotational movement, e.g., to loosen a screw cap. In some embodiments, a capping or re-capping device is also present within the housing of an automated analytical system disclosed herein. In some embodiments, the uncapping device and the (re-)capping device are the same module or device. Proper positioning of the sample rack in the processing position plays a crucial role, since the capping or uncapping device relies on precise spatial alignment with the corresponding cap and, therefore, the sample container covered by the corresponding cap. Furthermore, a pipettor or pipetting module can interact with the sample in the container in the case of a liquid biological sample. For the pipettor to operate smoothly, careful alignment between the sample container and the pipettor must be ensured. For example, if an elongated sample container is tilted so that its top opening is oriented horizontally, there is a risk that the pipettor, e.g., with a pipetting needle or a disposable pipette tip, will collide with the inner sidewall of the sample container far from the bottom, thus compromising the smooth and complete aspiration of the liquid sample by the pipettor. Furthermore, such a collision can lead to system errors, interruptions to operation, and even clogging or damage to the pipettor.Additionally, in some embodiments, liquid level detection (LLD), such as capacitive liquid level detection (cLLD), ultrasonic LLD, or electrical LLD, is performed by the pipettor at the processing location. LLD can also be hindered by misalignment of the sample rack and sample containers relative to the LLD device, which in some embodiments is integrated into the pipettor.

[0041] In this context, careful positioning of the sample rack at the processing location allows components such as cappers and / or decappers, pipettors, etc. to be properly aligned with the sample vessels, which is particularly important in embodiments where the sample vessels are tightly held in place within dedicated slots in the sample rack.

[0042] A "pipettor" is a device that allows for the automated drawing and / or delivery of fluids, for example, to transfer or mix fluids by inlet and outlet. In the context described herein, these fluids include liquid biological samples, reagents used to process liquid biological samples, wash solutions, dilution buffers, processed liquids, processed analyte-containing liquids, etc. Liquids can be drawn from and delivered to any of the following locations / containers: sample tubes, intermediate processing tubes, reagent containers, waste containers or locations, tip wash stations, output containers, reaction tubes, etc. In particular, pipettes can be used to aspirate fluid biological samples from sample containers described herein and deliver them to containers for downstream processing, such as isolation and / or analysis. Furthermore, pipettors can be used to aspirate and deliver reagents, such as sample preparation reagents, suspensions of binding particles for binding biological target materials, reagents for analyte amplification and / or detection, etc. Pipettors, in some embodiments, are driven by air or liquid pressure systems. As the pressurized liquid, the pipettor can, in some embodiments, use water or a commonly used reagent as known to those skilled in the art.

[0043] The pipettor can be equipped with one or more reusable, washable needles, such as steel needles, or can use disposable pipette tips. The pipettor can be attached to a transfer head, also called a pipetting head, that can move in one or two directions of movement in a plane, e.g., by guide rails, and in a third direction orthogonal to the plane, e.g., by a spindle drive. For example, the pipettor can be moved horizontally between a primary sample container, such as a tube, and a multiwell plate or another target location, and can be moved vertically to draw in or deliver a liquid biological sample or other liquid. The pipettor can be integrated into, or incorporated into, a work cell or can be a module of a system operably connected to the work cell. The position and operation of the pipettor (including parameters such as volume, flow rate, and flow direction) can be controlled by a control unit, as described below.

[0044] A "control unit" controls an automated system, such as the automated analytical systems described herein, in such a way that the steps required for a processing protocol are performed by the automated system. That is, the control unit can, for example, instruct the automated system to perform a specific pipetting step with a pipettor to mix a liquid biological sample with a reagent, or the control unit can control the automated system to incubate a biological sample or a reagent, or a mixture of both, at a specific temperature for a specific time, or the control unit controls the gripper, a reading device disclosed herein, including focusing on a sample rack in the correct lane, a positioning element described herein, a detection element described herein, a locking element described herein, an indicator system described herein, a shaker described herein, a transparent window described herein, a movable platform described herein, a loading platform described herein, a heating element described herein, a valve system described herein, and / or the precise operation of a pipettor described herein, or other operational or related parameters of the automated analytical systems described herein. The control unit can receive information regarding which steps need to be performed on a particular sample from a data management unit (DMU). In some embodiments, the control unit can be integral with the data management unit or embodied by common hardware. The control unit may be embodied, for example, as a programmable logic controller that executes a computer-readable program with instructions for performing operations according to a process operation plan. In particular, the control unit may include a scheduler for executing a sequence of steps, such as the movements described above, within a predetermined time period. Furthermore, the control unit may determine the order of processing of samples according to assay type, urgency, etc. The control unit may also receive data from the detection unit regarding measurements of parameters of the samples.

[0045] A "data management unit" is a computing unit for storing and managing data. This can include data about liquid samples processed by the automated system or about steps performed by specific modules of the automated system. The data management unit can be connected to an LIS (Laboratory Information System) and / or an HIS (Hospital Information System). The data management unit (DMU) can be a unit within the automated system with which it interacts or a unit co-located with such an automated system. It can also be part of the control unit. Alternatively, the DMU can be a unit located remotely from the automated system. For example, it can be embodied in a computer connected to the automated system, e.g., connected to the control unit of the automated analysis system described herein.

[0046] In addition to the importance of ascertaining the correct coordinates of the sample rack, and therefore the sample containers, as outlined above, it is also advantageous to provide for their proper orientation. For example, if the sample rack is correctly positioned with respect to its coordinates on the x-, y-, and z-axes, but is tilted at this particular location, other components, such as capping devices, pipettors, grippers, etc., may not be able to smoothly interact with the sample containers. The lane along which the sample rack is positioned and moves preferably contributes to positioning by being a flat, uniform, and smooth surface substantially perpendicular to the axis of gravity. In some embodiments, positioning the sample rack at the processing position includes aligning the sample rack with respect to all six spatial degrees of freedom.

[0047] In some embodiments, the sample rack is positioned in the analysis position by one or more positioning elements selected from the group consisting of fins, ribs, trapezoids, guide rails, catches, spring catches, latches, rotary latches, or brackets such as U-shaped brackets. In some embodiments, the positioning element is a guide rail integrated into the lane. In some embodiments, the positioning element is a combination of two or more of these elements. In some embodiments, the combination is a combination of a guide rail, a rotary latch, and a spring catch. In some embodiments, the combination is a combination of a guide rail and a distal stop element. In more specific embodiments, the distal stop element is a bracket. The bracket may be embodied, for example, as a U-shape.

[0048] Upon reaching the processing position, the presence of the sample rack is further detected at this position. Such detection can be achieved, for example, by a detection element such as a sensor or multiple sensors. In some embodiments, detection of the sample rack at the processing position is performed by one or more detection elements selected from the group consisting of a light barrier, such as a forked light barrier, an inductive sensor, or a touch sensor. As in the focus position, a dedicated element included in the sample rack can interact with a counterpart portion of the sample receiving bay. In some embodiments, a conductive element included in the sample rack induces a current that can be detected in an inductive sensor located on or near each lane of the processing position. Also, in some embodiments, a mechanical element included in the sample rack interrupts a light barrier, such as a forked light barrier, upon rotation when positioning the sample rack. In some embodiments, the mechanical element is a protrusion, such as a latch or knob. In some embodiments, the positioning element and the detection element are combined into a single structure. In the above embodiments in which the positioning element is a bracket, such as a U-shaped bracket, the side piece of the bracket is, in some embodiments, the end of the forked light barrier. More precisely, one side piece of the U-shape comprises a light source, such as a laser, and the opposite side piece of the U-shape comprises a detector. In such an embodiment, the forked light barrier serves as a positioning bracket to align the rack in the processing position and also performs detection by means of the light beam.

[0049] Locking the sample rack into a processing position is just as important as positioning itself, because if not locked, careful positioning can become unstable and can even be disrupted or completely destroyed by mechanical influences such as interactions with grippers or pipettors. Thus, lockstep constrains the sample rack into properly positioned alignment. In some embodiments, positioning is fixed with respect to all six spatial degrees of freedom.

[0050] In some embodiments, the locking is performed by one or more locking elements selected from the group consisting of a locking bolt, a locking pin, a cam lock, a magnet, a solenoid lock, a bar, a bracket, or a catch.

[0051] For example, the locking bolts can restrain the sample rack in a processing position by engaging corresponding recesses or through-holes in the sample rack.

[0052] In some embodiments, the sample rack is locked in the processing position by a solenoid lock. In such embodiments, the solenoid lock can be activated when the rack is detected in the processing position, and the solenoid can transition to a locked state. In some of these embodiments, the solenoid lock can be pushed vertically through the hole in the sample rack, e.g., from below the lane, upward into the hole in the sample rack, and possibly through the hole in the sample rack, to engage the sample rack and thus lock the sample rack in place. In other embodiments, the solenoid lock is positioned below and substantially parallel to the lane. In such embodiments, the solenoid lock is configured to perform a horizontal movement to lift the vertical locking bolt through the hole in the sample rack via a wedge mechanism. Thus, in some embodiments, the locking element is a combination of a horizontal solenoid lock and a vertical locking bolt.

[0053] Also, in some embodiments, the locking element interacts directly with the positioning element and / or the detection element. For example, in embodiments where a rotating latch positions a sample rack in a processing position, a locking element, such as a solenoid lock, can lock the rotating latch in the processing position. In embodiments where a rotating latch for positioning a sample rack rotates to block a light barrier, such as a fork-shaped light barrier, when positioning the sample rack, a locking element, such as a solenoid lock, can lock the rotating latch in the processing position such that the rotating latch is locked in a position blocking the light barrier.

[0054] Because users often want to remove sample racks from the analyzer after processing samples, the lock is reversible in some embodiments. For example, in the embodiments described above that include a solenoid lock, the solenoid can be reset to an open state to allow a user to remove the sample rack from the sample receiving bay.

[0055] Processing of a biological sample in a sample container can include a variety of procedures. Typically, in the case of biological samples, such as clinical sample material, among others, the sample is subjected to a preparation process that enriches or isolates specific types of analytes. The sample material may be suspected of containing a biological target material.

[0056] "Biological target material" or "biological material," in the sense of the present disclosure, includes any type of biological molecule, such as a protein or nucleic acid, but also other molecules that are naturally occurring or derivatives, or synthetic analogs or variants thereof. Furthermore, the term "biological material" includes viruses and eukaryotic and prokaryotic cells. In some embodiments, the biological target material is a nucleic acid, such as DNA, RNA, or PNA. DNA can be, for example, viral DNA, genomic DNA, or plasmid DNA. Biological target materials can be natural or modified. Natural biological materials are those that have not been irreversibly altered compared to the respective naturally occurring biological material, such as DNA or RNA, isolated from an organism. Modified biological materials include, for example, biotinylated molecules, such as nucleic acids or proteins.

[0057] As used herein, the term "biological sample" refers to a material that may contain an analyte of interest. The same applies to "liquid biological samples," which may be derived from any biological source, such as physiological fluids, including blood, saliva, ocular lens fluid, cerebrospinal fluid, sweat, urine, stool, semen, vaginal fluid, breast milk, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cultured cells, and the like. Test samples may be pre-treated prior to use, such as by preparing plasma from blood, diluting or generally diluting viscous fluids, or by lysis. Processing methods may include filtration, distillation, concentration, inactivation of interfering components, and addition of reagents. Biological samples may be used directly as obtained from their source or after pre-treatment to alter the sample's properties. In some embodiments, initially solid or semi-solid biological material is rendered liquid by dissolving or suspending it in an appropriate liquid medium. In further embodiments, the sample may be pre-treated, for example, with a wash buffer. In some embodiments, the biological sample is suspected of containing a specific antigen or nucleic acid.

[0058] In the context of this disclosure, the terms "isolation," "purification," or "extraction" of a biological target material refer to the following: Biological target materials, such as nucleic acids, must be purified, isolated, or extracted from biological samples, which typically contain a complex mixture of components, before they can be analyzed in a diagnostic assay, such as by amplification. Biological target materials, such as cells (human or exogenous) or viruses, contain a wide variety of different biomolecules, and often only a subgroup of these molecules is of interest in a given type of analysis. For example, nucleic acids that will be analyzed by PCR in a downstream process may need to be separated from other biomolecules.

[0059] Typically, one of the first steps involves releasing the contents of cells or virus particles, for example, by using enzymes and / or chemical reagents. This process is commonly referred to as lysis. One useful procedure for binding nucleic acids to concentrate the analyte of interest in the lysate involves selective binding of nucleic acids to a glass or silica surface on binding particles, such as magnetic particles, in a chaotropic salt solution, and separation of the nucleic acid from contaminants such as agarose, proteins, or cellular debris. Such compositions can be particularly useful for binding nucleic acids to glass surfaces, as they already contain the chaotropic agents normally required for such binding.

[0060] Furthermore, in some embodiments, the biological material purified in this manner can be subjected to biological or biochemical analysis. Such downstream analysis of the biological target material can include polymerase chain reaction (PCR) or nucleic acid sequencing, or antibody-mediated assays for proteins such as ELISA, etc. In some embodiments of the methods described herein, the analysis includes qualitative and / or quantitative detection of nucleic acids by amplification. In some embodiments, the amplification technique is PCR. In such embodiments, the automated analysis system described herein can include a thermal cycler. Other amplification techniques, such as isothermal amplification (LAMP, TMA, etc.), LCR, etc., can also be applied to analyze the target nucleic acid. In some embodiments, the analysis includes nucleic acid sequencing.

[0061] A corresponding automated analytical system is also described herein in the context of performing a method for introducing a sample rack holding a plurality of sample vessels into a sample receiving bay within a housing of the automated analytical system.

[0062] Accordingly, one aspect disclosed herein is an automated analytical system for processing a biological sample, comprising: -Housing; a sample rack configured to hold a plurality of sample vessels; a sample receiving bay within the housing, the sample receiving bay having a plurality of lanes arranged substantially parallel to one another and configured to accommodate the sample rack configured to hold a plurality of sample vessels; a proximal stop element for determining the focus position on the lane; - a reading device in substantially the same horizontal plane as the lane; a distal stop element defining a processing position on the lane; a positioning element configured to position the sample rack in a processing position; a detection element configured to detect the sample rack at the processing position; a locking element configured to lock the sample rack in a processing position; a processing module configured to process the biological sample in the sample container; The automatic analysis system includes:

[0063] The conditions and embodiments of the automated analytical system for processing biological samples are the same as those described in the context of the method disclosed herein for introducing a sample rack holding a plurality of sample containers into a sample receiving bay within the housing of the automated analytical system.

[0064] Another aspect described herein is an automated analytical system for processing a biological sample, comprising: -Housing; a sample rack configured to hold a plurality of sample vessels; a sample receiving bay within the housing, the sample receiving bay having a plurality of lanes arranged substantially parallel to one another and configured to accommodate a sample rack holding a plurality of sample vessels; an indicator system positioned along each of the lanes in alignment with a dedicated sample vessel slot of the sample rack when the sample rack is in the testing position, and configured to indicate the status of the sample vessel in the respective sample vessel slot; a processing module configured to process the biological sample in the sample container; The automatic analysis system includes:

[0065] This automated analysis system is particularly advantageous in that it provides users with the ability to perform manual processing on sample vessels containing samples requiring corrective action. For example, biological sample matrices, such as whole blood, tend to form clots, which can prevent smooth processing of the problematic sample and, in some embodiments, can prevent analysis. In order for the user to apply the appropriate corrective action, such as dissolving the clot in this example, the system must indicate which one or more sample vessels among multiple sample vessels held in a given sample rack contain such a sample that poses a problem for the processing module.

[0066] Common approaches in the art include, for example, displaying the location of the affected sample vessel within a sample rack on an external display. Such solutions are tedious and error-prone because the user must switch their gaze between the display and the rack to identify the affected sample vessel within the rack as shown on the screen.

[0067] The indicator system of the automated analysis system disclosed herein provides an elegant and uncomplicated remedy to such problems by flagging in situ the slot in the sample rack holding the affected sample vessel, whereby the user can directly identify such slot in the sample rack in situ by a signal in the immediate vicinity of the affected sample vessel.

[0068] In this context, a "test position" is a position of a sample rack on the surface of a sample receiving bay where a user can access the rack with sample containers through an interface such as an openable window of an automated analysis system.

[0069] In some embodiments, the indicator system comprises a light source on or within a surface of the sample receiving bay, the light source optically coupled via an optical light guide system to a light emission window located adjacent to a dedicated sample container position in the sample rack.

[0070] The optical signal is extremely convenient for the user to locate the problematic sample. The user can directly perform manual intervention at that location, for example, removing clots in the sample of the affected sample container while the affected sample container is held in a dedicated sample slot in the sample rack. Throughout this process, in some embodiments, the optical signal indicating each sample container remains activated, thus greatly reducing the risk that the user will process the wrong sample in a different container.

[0071] Physically separating the light source from the sample rack offers the advantage of keeping the complexity of the sample rack relatively low. Integrating the light source into the sample rack would require a power source, such as a battery. This not only makes each sample rack more expensive and complex, but also makes it more susceptible to external influences. For example, cleaning sample racks, especially in clinical environments, often involves subjecting the sample rack to harsh conditions to remove potentially harmful contaminants, such as pathogens, that may be present in the sample material. For example, immersing the sample rack in a solution containing bleach can damage the light source and batteries incorporated in the sample rack. The optical light guide system described herein can overcome such limitations.

[0072] The optical light guide system can include various components suitable for directing light from the light sources to the respective emission windows. For example, in the case of a single light source on or within the movable platform, an optical fiber arrangement can be used to direct the light to a dedicated output location. In such an embodiment, the light emitted by the single light source is split into multiple individual optical fibers, each connecting the light source to a dedicated light emission window. Such fibers can include a material that confers flexibility, such as a polymer. Corresponding optical fiber cables can be arranged throughout the sample rack, with their outputs directed toward the light emission windows and their inputs positioned in close proximity to the light sources.

[0073] In some embodiments, the light source comprises a plurality of individual light sources, such as LEDs, each optically coupled to the light emission window via an optical light guide system.

[0074] A fiber optic solution is equally conceivable for such a plurality of individual light sources, the number of light sources being equal to or less than the number of corresponding light emission windows.

[0075] In some embodiments, the number of individual light sources along a lane corresponds to the number of dedicated sample rack positions and / or light emission windows in the sample rack.

[0076] In particular, when the number of individual light sources is equal to the number of corresponding light emission windows, the optical light guide system can comprise a rigid light guide element. In some embodiments, the individual light sources are positioned substantially directly below dedicated sample container slots and corresponding light emission windows of the sample rack at the testing position.

[0077] In such embodiments, the light guiding rods can be positioned substantially parallel to the sample vessel slots in the sample rack. Furthermore, in some embodiments, the optical light guiding system is comprised of a tunnel positioned substantially parallel to the sample vessel slots in the sample rack. This simpler solution may reduce the light output at the emission window, but may further reduce the complexity of the sample rack. For example, with respect to the sample rack cleaning methods described herein, a tunnel is an extremely robust solution.

[0078] In some embodiments, the light-emitting window is configured to emit light of an indicated color. In a simple case, the light-emitting window can include a filter, such as a transparent screen made of a colored material. In more complex embodiments, multiple light sources emit light at different wavelengths in the visible spectrum, for example to generate different colored light beams. The different colors can indicate various states of the sample in the indicated sample container. For example, the sample may have solidified as described above and require mixing or re-pipetting by the user. The sample rack slot holding the sample container in question can be indicated, for example, by a red light. Sample containers that do not require user intervention can be indicated by a green light. A slot holding an incorrectly capped sample container can be indicated by an orange light, and so on.

[0079] In this context, a method for processing a biological sample is described herein, the method comprising: a) introducing a sample rack holding a plurality of sample vessels into the automated analysis system; b) indicating by an indicator system a sample in a sample container in a dedicated slot of the sample rack that requires testing; c) inspecting the corresponding samples and implementing corrective actions on the samples as necessary; Includes:

[0080] In certain situations, it is desirable to create additional workspace, such as an additional work surface, outside the housing of an automated analytical system. For example, if samples are to be manipulated outside the housing, a user would appreciate a convenient, easily accessible platform for receiving sample containers, for example, in a sample rack, and reintroducing them into the housing after performing manual steps.

[0081] Accordingly, a related aspect described herein is an automated analytical system for processing a biological sample, comprising: -Housing; a sample rack configured to hold a plurality of sample vessels; a sample receiving bay within the housing, the sample receiving bay having a plurality of lanes arranged substantially parallel to one another and configured to accommodate a sample rack holding a plurality of sample vessels; a movable platform configured to extend horizontally from the housing to form an extension of the plurality of lanes external to the housing, the platform having a positioning element configured to position a sample rack on the platform in an exposed testing position; an indicator system disposed along each of the elongated lanes aligned with a dedicated sample container slot of the sample rack when the sample rack is in the exposed inspection position, the indicator system being configured to indicate the status of the sample container in the respective sample container slot; a processing module configured to process the biological sample in the sample container; The automatic analysis system includes:

[0082] Because the movable platform can be extended outside the housing, the "exposed inspection position" is, in some embodiments, a position where the rack is not covered by the housing. In effect, a user can pull the movable platform toward themselves until a mechanical stop is reached, e.g., the platform is fully extended but still attached to the sample receiving bay of the automated analysis system. The user can then remove the sample rack from the sample receiving bay by sliding it along the lane onto the extended movable platform and pulling it out of the housing. The sample rack can then reach a mechanical stop, such as a baffle or hook, once it reaches the exposed inspection position where it is easily accessible to the user. As an additional advantage, the user also benefits from unobstructed visibility of the indicator system's signal outside the housing of the automated analysis system.

[0083] The "movable platform" may be retractable like a drawer, as described above. In some embodiments, the platform can be extended in a linear motion substantially parallel to the lanes. In such embodiments, the platform can be slidably suspended between guide rails. In other embodiments, the platform can be extended in a rotational motion that involves pulling the platform toward the user in front of the analyzer on either the left or right side of the platform until it reaches a substantially 90° angle, and then restraining the platform in the respective position. In some embodiments, the platform is positioned below the lanes in the sample receiving bay in its retracted state. When extended, the movable platform can extend beyond the lanes in the sample receiving bay, and in this fully extended state, can be restrained by an upward movement to form a uniform extension relative to the lanes in the sample receiving bay.

[0084] In this context, a method for processing a biological sample is described herein, the method comprising: a) introducing a sample rack holding a plurality of sample containers into a sample receiving bay of the automated analysis system; b) extending the movable platform outside the sample receiving bay and therefore outside the housing; c) extending the sample rack to an exposed inspection position; d) indicating by an indicator system which sample in the sample container in the dedicated slot of the sample rack requires testing; e) inspecting corresponding samples and implementing corrective actions on the samples as necessary; f) returning the rack to the sample receiving bay in the housing; g) returning the mobile platform to the stowed position; Includes:

[0085] The advantages of the various automated analysis systems described above can be combined by integrating their features.

[0086] Accordingly, another aspect described herein is an automated analytical system for processing a biological sample, comprising: -Housing; a sample rack configured to hold a plurality of sample vessels; a sample receiving bay within the housing, the sample receiving bay having a plurality of lanes arranged substantially parallel to one another and configured to accommodate the sample rack configured to hold a plurality of sample vessels; a proximal stop element for determining the focus position on the lane; - a reading device in substantially the same horizontal plane as the lane; a distal stop element defining a processing position on the lane; a positioning element configured to position the sample rack in a processing position; a detection element configured to detect the sample rack at the processing position; a locking element configured to lock the sample rack in a processing position; an indicator system positioned along each of the lanes in alignment with a dedicated sample vessel slot of the sample rack when the sample rack is in the testing position, and configured to indicate the status of the sample vessel in the respective sample vessel slot; a processing module configured to process the biological sample in the sample container; The automatic analysis system includes:

[0087] As noted above, additional convenient workspace can be advantageous, and therefore another aspect described herein is an automated analytical system for processing biological samples, comprising: -Housing; a sample rack configured to hold a plurality of sample vessels; a sample receiving bay within the housing, the sample receiving bay having a plurality of lanes arranged substantially parallel to one another and configured to accommodate the sample rack configured to hold a plurality of sample vessels; a proximal stop element for determining the focus position on the lane; - a reading device in substantially the same horizontal plane as the lane; a distal stop element defining a processing position on the lane; a positioning element configured to position the sample rack in a processing position; a detection element configured to detect the sample rack at the processing position; a locking element configured to lock the sample rack in a processing position; a movable platform configured to extend horizontally from the housing to form an extension of the plurality of lanes external to the housing, the platform having a positioning element configured to position a sample rack on the platform in an exposed testing position; an indicator system disposed along each of the elongated lanes aligned with a dedicated sample container slot of the sample rack when the sample rack is in the exposed inspection position, the indicator system being configured to indicate the status of the sample container in the respective sample container slot; a processing module configured to process the biological sample in the sample container; The automatic analysis system includes:

[0088] As mentioned above, processing of biological samples in sample vessels can include purification of target analytes, and binding particles can be utilized for this purpose. For example, suitable binding particles include or consist of particulate materials such as beads, including nanobeads. In some embodiments, they are analyte-binding particles for binding specific biological targets, which can be molecules, cells, or viruses. In these embodiments, the particles can have surfaces coated with specific or nonspecific binding molecules, such as nucleic acid capture probes, oligo or poly(dT) chains for binding mRNA, protein A for binding the Fc portion of immunoglobulins, Fab fragments of antibodies for binding specific proteins, nickel for binding histidine tags, streptavidin or biotin, integrins, adhesins, or other cell surface molecules. In some embodiments, the biological target molecules are cell surface molecules that enable specific cells to be captured by the analyte-binding particles. In one embodiment, the size difference between the monodisperse silanized ferrimagnetic iron oxide particles is less than 5% on average. In certain embodiments, the particle has a size or diameter of n, where n is a value between 20 nm and 600 nm, and in even more specific embodiments, the particle has a size or diameter of n, where n is 100 nm.

[0089] In some embodiments, binding particles, such as magnetic glass particles, are stored and used as a suspension. A container containing a suspension of binding particles for the isolation of biological materials is shaken, for example, on a shaker or mixed with an agitator. While the agitator can be another source of contamination, shaking poses the problem of losing the suspension due to spillage. On the other hand, in an automated solution, placing a cover on the container leads to the problem of making it possible to remove the suspension as easily as possible. For example, removing the cover before each removal requires an additional step in the method for providing a suspension of binding particles, and opening the container also increases the risk of contamination.

[0090] One aspect described herein is a system for providing binding particles for isolating biological material, comprising: a container containing a suspension of binding particles for binding biological material; a shaker configured to shake the container and suspend the binding particles, the shaker comprising a bayonet lock configured to lock the container in a shaking position; The system comprises:

[0091] The bayonet lock of the system for providing bound particles as described above provides an advantageous way of engaging the suspension container with a dedicated shaker. Particularly in embodiments where this step is performed manually, the bayonet lock allows the user to achieve a tight lock between the container and the shaker without having to apply excessively large force. As is known in the art, the bayonet lock is based on the principle of rotating components into a locked state.

[0092] In more specific embodiments, the system includes multiple pipettes or pipette tips, such as multi-channel pipettes, which provide both flexibility and increased throughput.

[0093] Accordingly, another aspect described herein is a system for providing binding particles for isolating biological material, comprising: - a linear arrangement of multiple pipettes or pipette tips; a container containing a suspension of binding particles for binding biological material and having a cover, said cover having openings and / or being penetrable for the linear arrangement of a plurality of pipettes or pipette tips; a shaker configured to shake the container and suspend the binding particles, the shaker comprising a bayonet lock configured to lock the container in a shaking position; The system comprises:

[0094] One advantage of the suspension container described above is that the cover has openings and / or is pierceable to allow for the linear arrangement of multiple pipettes or pipette tips. In this way, the risk of both spillage and contamination is significantly reduced, while the cover does not need to be removed to remove the suspension of binding particles. The suspension container can be used to provide suspension until empty without needing to be opened.

[0095] The cover may be apertured and / or pierceable for linear placement of multiple pipettes or pipette tips, and thus may be advantageously used for parallel delivery of the binding particle suspension. Using multiple pipettes allows the user to simultaneously deliver the binding particle suspension to multiple vessels, increasing both efficiency and flexibility when the pipettes can be controlled individually.

[0096] In the case of the above system, the corresponding method for providing binding particles for isolating biological material comprises the following steps: a) securing a container containing a suspension of binding particles for binding biological material, optionally with a cover, the cover having openings and / or being penetrable for linear placement of multiple pipettes or pipette tips, to a shaker equipped with a bayonet lock by pressing the container against the shaker at a predetermined horizontal displacement angle and rotating the container horizontally in the direction opposite to the displacement to align and lock the container in a shaking position; b) shaking the container in the shaking position with a shaker to suspend the binding particles; Includes.

[0097] In some embodiments, the predetermined horizontal displacement angle is 90° or less, and in some embodiments is between 1° and 60°, or between 5° and 45°, or about 20°.

[0098] Additionally, the automated analysis systems described herein can have an interface for a user to access the interior of the housing.

[0099] Accordingly, another aspect described herein is an automated analytical system for processing a biological sample, comprising: a) a housing; b) an interface for observing and manipulating the processes within the housing of the system; c) a transparent window for opening and closing the interface, the transparent window being slidable between an open position and a closed position and including a counterweight configured to hold the window in the open position, the closed position, or a position between the open position and the closed position; The automatic analysis system includes:

[0100] While the transparent window conveniently provides user visibility of processes within the analytical device, it may be necessary for the window to be opened to allow the user to physically interact with components within the housing. For example, components may need to be cleaned or replaced, or other maintenance procedures may need to be performed. Also, interaction with sample containers, for example, within a sample rack, may be desired or necessary.

[0101] Common approaches in the art include windows that can swing or slide open while being stabilized by traditional hinges, mechanical springs, gas springs, etc. For example, a window held in an open position above an analyzer by a gas spring poses the risk of falling downward, potentially onto the head or back of a user while examining the interior of the housing. This is especially true when a stabilizing element such as a gas spring approaches the end of its life and gradually loses pressure. The counterweight used with the above-mentioned windows provides a stable and durable solution that minimizes the risk of such an accident.

[0102] Additionally, the automated analyzer systems disclosed herein can include a storage unit for reagent containers. Such a storage unit may be included, for example, in a drawer that allows reagents to be removed from the analyzer and fresh reagents to be supplied. In some embodiments, the storage unit is a refrigerated chamber, since certain reagents routinely used in clinical diagnostics tend to deteriorate even when stored at elevated temperatures or at room temperature for extended periods of time. However, refrigerating the reagent storage unit can result in significant temperature differences between the refrigerated interior and the ambient environment, particularly when the analyzer is located in a warm or hot climate. Condensation can form on the exterior surfaces of the refrigerated compartment, causing problems as described below.

[0103] It is further advantageous in an automated analytical system to allow access to reagent containers and their contents by an operational module, such as a pipettor, as described above. Because pipettors typically operate from above the corresponding containers due to gravity alone, a window or simply a slit can be opened in the top of the refrigerated storage chamber to allow the pipettor to enter the storage and transfer reagents to or from designated containers within the chamber. When an opening is created, droplets of condensed water that may have formed on the top surface of the chamber can drip into the reagent containers below. This not only creates a risk of diluting the reagents in the containers, but also introduces contaminants into the reagents. Cross-contamination is a serious problem, particularly in clinical diagnostics, because it can affect results and even damage or render sample materials unusable. For example, a patient sample tested for a pathogenic nucleic acid sequence may be falsely deemed positive due to the presence of cross-contaminating nucleic acids.

[0104] In this regard, another aspect disclosed herein is a system for cooling reagents for performing a biological assay, comprising: a) a cooling chamber surrounded by a substantially insulated housing having a bottom and a top, the top being covered by a lid having an opening switchable between an open state and a closed state; b) a reagent container positioned within the cooling chamber and having an openable or pierceable top; c) a pipettor positioned above the cooling chamber and configured to aspirate reagent from the reagent container through an opening in a lid covering the cooling chamber; d) a heating element disposed beneath and in thermal contact with a lid covering the cooling chamber and configured to heat the lid such that the temperature of an upper surface of the lid is greater than the dew point of air outside the cooling chamber; The system comprises:

[0105] A "heating element" in the context of the present disclosure may be fabricated from materials such as, for example, aluminum and its alloys, copper, steel, silver, alumina ceramic, and / or silicon carbide. In embodiments in which the heating element is substantially fabricated from metal, a further advantage is achieved by facilitating water level detection, for example, by capacitive water level detection methods commonly used in automated liquid handling systems.

[0106] "Thermal contact" means either direct physical contact or proximity and / or contact mediated by a heat-conducting medium, such that substantially unimpeded heat transfer between the heating element and the surface is possible. The heating element, in some embodiments, is placed in direct physical contact or proximity with the surface on which external condensation is to be avoided.

[0107] In some embodiments of the systems disclosed herein, the heating device further comprises a temperature sensor. It may be desirable to monitor the temperature of the heating element and / or the surface of the cooling chamber lid and / or the temperature of the reagent container or reagent. In some cases, it may be beneficial to monitor the temperature and have its accuracy checked by a temperature sensor to ensure that the surface temperature is always above the dew point of the surrounding ambient air. For example, it may be advantageous to adjust the temperature of the heating element to a specifically desired value or range by adjusting the power supplied to the heating element in the event of a deviation above a predetermined threshold. Such controlled supply may be operated by a control unit or part thereof. The temperature of the heating element may be controlled by a temperature controller that compares the effective temperature with a target temperature. The controller may, for example, use a PID (proportional-integral-derivative) algorithm to reduce the deviation between the effective temperature and the target temperature, as known to those skilled in the art.

[0108] Thus, in some embodiments, outside and inside air conditions are monitored by one or more thermal sensors, and a temperature controller controls the power, and therefore the temperature output, of the heating element to maintain designated surfaces above the dew point of the outside air.

[0109] The heating element can be realized, for example, by applying an electrical resistance heating element to the inner surface of the cooling chamber lid. This can be achieved by applying a suitably shaped heating material to the surface of the heating element, for example, using a heat-resistant adhesive. Such a heating element can be fabricated from a carrier material such as polyimide (Kapton®) or a silicone polymer that contains a conductive material that generates heat under electric current. The heating material can include a heat sensor. The manufacture and application of such adhesive heating materials are known to those skilled in the art.

[0110] Alternatively, a conductive resistive heating material can be printed onto the inner surface of the cooling chamber lid using so-called "thick film" technology. To avoid electrical shorts, the heating elements, especially if they are conductive, are coated with an electrically insulating layer in some embodiments. Such an electrically insulating layer may be made of an oxide, such as aluminum oxide, for example. The resistive heating material may also be applied to the heating elements using screen printing. Such printable resistive heating materials typically include a conductive powder, such as silver, copper, or carbon, and a binder, such as a curable epoxy resin. The manufacture and application of such thick film heaters is also known to those skilled in the art.

[0111] Furthermore, so-called "thick film" techniques can be used to sputter or vacuum-deposit an electrically conductive resistive heating material onto the inner surface of the cooling chamber lid. Suitable materials for this purpose include gold or platinum. As with thick film techniques, an electrically insulating layer can be applied to avoid electrical short circuits. The heater geometry can be defined, for example, by a mask process or laser ablation. The manufacture and application of such thin film heaters is well established in the art.

[0112] As a further option, the heating element can be fitted with an electrically resistive wire, which can be made of, for example, constantan. Alternatively, the heating element can have one or more fluid paths for transporting a heat transport medium.

[0113] "Heat transport medium," as understood in the context of this disclosure, means a fluid of sufficient thermal conductivity to transfer thermal energy throughout the heating material of the heating element. Suitable fluids are known to those skilled in the art.

[0114] In some embodiments, outside and inside air conditions are monitored by one or more thermal sensors, and a control unit controls the power, and therefore temperature output, of the heating element to maintain designated surfaces above the dew point of the outside air.

[0115] The pipettor, as described herein, in some embodiments comprises a pipetting needle, such as a washable pipetting needle, or multiple pipetting needles arranged as a multi-channel pipettor. In some embodiments, the pipettor comprises a disposable pipette tip made of plastic or other suitable material known in the art. The pipettor, as well as other components such as switchable orifices and / or heating elements, may be controlled by a control unit as disclosed herein. In embodiments in which a temperature controller controls the heating element, the temperature controller may be embodied as an extension of or an integral part of a superordinate control unit that controls and coordinates substantially all of the numerous automated modules and / or processes of the automated analytical system described herein. Also, in some embodiments, the temperature controller may be a separate unit, although it is connected to the control unit via data transfer.

[0116] The reagent container may be any suitable container known in the art. In some embodiments, the reagent container is a flask, a plastic bottle, a canister, etc. In some embodiments, the reagent container is opened at the top prior to introduction into the cooling chamber. In some embodiments, the reagent container has a frangible top cover, such as a sealing membrane, that is pierced by a pipettor upon first use.

[0117] As described above, in some embodiments, the automated analysis system includes a thermal cycler. As known in the art, the operating principle of a thermal cycler is based on a specific profile of alternating heating and cooling steps. In some embodiments, the thermal cycler is a PCR cycler. The latter "cycles" a nucleic acid-containing sample through multiple iterations of denaturation, annealing, and extension catalyzed by a thermostable DNA polymerase, which in some embodiments is preceded by a step at a temperature suitable for reverse transcription of ribonucleic acid (RNA), which may be present in a viral sample, for example, into deoxyribonucleic acid (DNA). Samples, which may have been purified in the separation station in some embodiments of the automated analysis system disclosed herein, can be transferred to a multiwell plate, for example, for amplification and detection purposes. In some embodiments, the biological sample to be processed, as well as intermediate and final sample products, are transported between various modules of the automated analysis system described herein by one or more pipettors described herein.

[0118] The thermal cycler, in some embodiments, comprises a thermal assembly including a mount for holding sample containers, such as a multiwell plate, hi some embodiments, the mount is a block or plate with recesses configured to engage wells of the multiwell plate.

[0119] In this context, one aspect disclosed herein is a thermal cycler for incubating biological samples, comprising: a) a mount configured to receive and hold a multiwell plate; b) a loading platform configured to transport the multiwell plate to and from the mount and rotatable between a loading position and an incubation position; c) a motor configured to rotate the loading platform between a loading position and an incubation position; A thermal cycler comprising:

[0120] The thermal cyclers described herein conveniently load multiwell plates, such as microwell plates, via a rotatable platform. In some embodiments, the loading position has a displacement angle between the mount and the loading platform of 45° to 135°, or approximately 90°. In the loading position, the loading platform is accessible to a user or a robotic transfer module, such as a gripper. In this position, a multiwell plate can be placed on the loading platform, which may include fastening elements, such as clamps or latches. By rotating the loading platform toward the mount to the incubation position, the multiwell plate is finally positioned on the mount so that thermal contact is established between the mount and the multiwell plate for cyclic thermal incubation. In some embodiments, the motor driving the platform's rotational movement is a stepper motor. The rotational configuration is particularly advantageous when space is limited, as it eliminates the need for extending linear drawers, which would likely occupy more space. Furthermore, in some embodiments, the multiwell plate is transferred from a previous module, such as a separation station described herein, in an orientation incorrect for the thermal cycler. For example, when transferred from the separation station by a robotic gripper or the like, the multiwell plate may be displaced at an angle, such as about 90°, relative to the orientation of the mount, and the rotational movement of the drawer may thus advantageously contribute to placing the multiwell plate in the correct position for thermal cycling.

[0121] In some embodiments, one or more pipettors of the automated analyzer systems described herein can use disposable pipette tips. These can be conveniently supplied by automated movement of robotic elements within the housing of the automated analyzer systems described herein. For example, pipette tips can be supplied in a dedicated pipette tip rack, which can be introduced into the analyzer by a user through a dedicated interface, such as a consumables drawer. The pipette tip rack can be positioned on a mount within the analyzer housing, for example, for the pipetting head of the pipettor to pick up pipette tips from the rack. In some embodiments, multiple pipettes of the pipettor simultaneously engage multiple pipette tips. For example, pipette tips can be arranged in a dedicated rack in a two-dimensional pattern, such as an 8 x 12 pattern. The pipettor can be embodied as a multichannel pipettor, such as a linear 8-channel pipettor, capable of picking up eight pipette tips with a single vertical engagement movement relative to the pipette tips in the rack. Such robotic movements can be sensitive to tolerances in alignment between the pipettes and the pipette tips, particularly horizontal alignment. For example, horizontal misalignment between the coordinates of the pipette and the coordinates of its designated tip can lead to poor engagement, and in severe cases, can even snag the pipetting head hanging from the robot arm and damage the pipette.

[0122] Accordingly, another aspect disclosed herein is a flexibly mounted pipette tip rack, where the rack is mounted on a work surface of an automated analysis system via one or more flexible elements positioned between the rack and the work surface.

[0123] Suitable compliance elements, in some embodiments, are selected from the group consisting of a spring, a rubber or foam plastic layer, an O-ring, or a magnetic field.

[0124] The rack follows the movement by tilting in the biased direction, thereby compensating for small misalignments between the pipette and the pipette tip.

[0125] The automated analytical systems described herein may further include a fluidic network. Such a "fluidic network" is a system for supplying and transporting liquids. In some embodiments, the fluidic network comprises or is composed of a piping system including pumps, pipetters, reagent interfaces such as inlets or outlets, waste interfaces such as inlets or outlets, and / or valves. In some embodiments, the fluidic network is controlled by a control unit described herein. For example, the control unit may control the fluidic network to perform aspiration of reagents by a pipetter from sample containers in a sample rack in a processing position described herein. Furthermore, sample transfer by pumping and / or pipetting throughout the fluidic network to separate modules of the automated analytical systems described herein may be coordinated. For example, a sample aspirated from a primary sample container present in a sample rack may be pipetted into a secondary container and subjected to a purification process in a separation station. From there, a liquid containing the concentrated or isolated analyte may be transferred, for example, by pipetting, to a tertiary sample container and subjected to an amplification and detection process in a thermal cycler described herein. For example, tubing connecting pipettors to reagent containers etc. may be opened and closed by a valve system which may be controlled by a control unit. It may be advantageous to ensure that the valves of such a valve system are operable. For example, the electrical connection of a valve to a power source may be broken. In some cases, this may occur due to the inadvertent removal of an electrical plug which supplies power to an individual valve.

[0126] In this regard, yet another aspect of the present disclosure is a method for monitoring a valve system in an automated analyzer system, comprising the steps of: a) starting the automated analysis system by turning on the power; b) performing a start-up valve check on the operational status of the valve during or immediately after the start-up process, the check including sending an electrical probe signal from the control unit to the valve and detecting the presence or absence of an electrical response signal by the control unit, the presence of the response signal indicating that the valve is operational; c) operating the valve system in a full startup mode of the automated analyzer system and repeatedly performing the check of step b) on the idle valves as an operational valve check; d) generating an error message if a lack of electrical response signal is detected in step b) or step c); A method including:

[0127] The combination of an initial check of the operational status of the analyzer when it is powered up on the one hand, and continuous checks during normal operation of the analyzer on the other, provides a means for closely monitoring and ensuring the functionality of the valves in the valve system.

[0128] In some embodiments, the electrical probe signal is a voltage applied to a circuit associated with an individual valve, which in some embodiments is a printed circuit board (PCB).

[0129] A "printed circuit board" or "PCB" is a laminated sandwich structure of conductive and insulating layers. PCBs have two complementary functions: first, to attach electronic components to designated locations on the outer layers by soldering; and second, to provide reliable electrical connections (and also reliable open circuits) between the terminals of the components in a controlled manner, often referred to as PCB design. Each conductive layer is designed with a graphical pattern of conductors (similar to wires on a flat surface) that make the electrical connections on that conductive layer.

[0130] When the control unit applies a voltage to a circuit associated with an individual valve, a measurable current is induced in that circuit if the circuit is operational, i.e., connected to a power source controlled by the control unit and / or to the control unit itself if the control unit also functions as a power source. In some embodiments, the voltage is applied to the same circuit that is responsible for switching, i.e., opening and closing, the valve. In such embodiments, the voltage applied for purposes of performing the check is lower than the threshold required to switch the valve. In effect, the process performed during the check mimics switching the valve, albeit at a lower voltage so as not to result in opening or closing.

[0131] As used herein, an "idle state" of a valve means a state in which the valve is not switching between an open state and a closed state. In some embodiments, the control unit flags a valve as "idle" if it has not switched for a specified period of time, which may be between 1 second and 10 seconds, or between 2 seconds and 5 seconds, or about 3 seconds. Thus, the above-described method provides a means for continuous monitoring of the valve system without interfering with the switching of valves that are currently in an active, non-idle state.

[0132] However, in some embodiments, valves that are being switched are also included in the operational valve check. In some embodiments, the method further includes, in step c), performing the check of step b) for valves that are in an active state. The "active" state means that the respective valve is switching or about to be switched. In some embodiments, "active" means that the valve is a specific time away from switching, such as 10 seconds, 5 seconds, 2 seconds, 1 second, 500 ms, or 100 ms before switching.

[0133] In the operation of the automated analyzer systems described herein, various valves of the valve system may have different impacts on the results generated by the analyzer. The impact may depend on factors such as the position of the valve, which modules of the analyzer the valve operates between, etc. For example, any step within the automated analyzer system that may directly or indirectly affect the liquid biological sample being analyzed may have a greater impact on the results generated than, for example, steps related to the disposal of waste liquids.

[0134] In this regard, in some embodiments of the above-described method, step d) further includes suspending operation of the automated analysis system in the absence of an electrical response signal from at least a subset of the valves in the valve system. In some of these embodiments, the subset consists of any valves upstream of the sample interaction element in the fluidic network. A "sample interaction element" is a portion of the fluidic network that at some point contains a biological sample or provides some type of liquid to the biological sample, such as a pipettor that aspirates a biological sample from a sample container or a tube designated to provide reagents to an amplification and detection module. In the event of a failure of such an upstream valve, the sample, or at least its processing in the automated analysis system, may be compromised. For example, if a valve does not open, reagents may not be added to the sample, and analytical biochemical reactions may not be performed successfully. Because such errors can lead to false-positive diagnostic results and ultimately to incorrect or no treatment for a patient, operation of the automated system, e.g., a "run" in which a particular set of samples is being processed and analyzed, is halted in the above-described embodiments so that the respective valves can be repaired before operation resumes.

[0135] On the other hand, in such embodiments, there may also be a subset of valves in the valve system downstream of the sample-interacting element in the fluidic network. These latter valves do not affect the biological sample and therefore require less rigorous intervention, or no intervention at all, other than the generation of an error message. Such downstream valves include any valves in the fluidic network designated for waste disposal, etc., as described above.

[0136] Illustrative Embodiments The following examples are intended to illustrate certain embodiments of the systems and methods of the present disclosure, but they are not intended to be limiting.

[0137] The schematic diagram in Figure 1 shows an embodiment of the automated analysis system (1) described herein.

[0138] The perspective view of Figure 1A shows the analytical device (1) from a slightly upward perspective front view. The device is surrounded by a housing (100) that protects the interior from external influences and vice versa. For example, the interior is protected from external sources of contamination, while users outside the housing (100) are shielded from biological agents, such as pathogens, that may be processed inside.

[0139] However, the interior is observable through a transparent window 500. In this embodiment, the window 500 includes a handle 501, which may be a recess or hole. In other embodiments, the handle 501 may be embodied as a protrusion, such as a knob. Integrated within the transparent window 500 is a display 502, which may be embodied, for example, as a touchscreen. The display 502 serves as an interface for the user and can inform the user, for example, about the status of a particular sample within the analyzer 1, the temperature within the housing 100 or a particular module, the fill status of a reagent or waste container, the remaining number of consumables, the estimated time remaining for an experiment, etc. In some embodiments, the display 502 is an interactive device. In this context, the display can include a keyboard, a microphone including a voice processor, a touchscreen, or other suitable input device. By entering commands via the display 502, the user can affect operations performed by and within the analyzer 1. For example, a user may instruct the control unit to prioritize a particular sample among other samples present in the automated analysis system (1) at a given time. In other cases, a user may schedule a particular processing step or adjust a particular parameter of the system (1), such as temperature. In some embodiments, the display (502) is connected to a control unit as described herein, and a user may manipulate the above-mentioned processes and parameters via the control unit.

[0140] To improve visibility of the modules and processes within the housing (100), the analytical device (1) in the illustrated embodiment has additional transparent windows on the top (120) and sides (110) of the instrument.

[0141] The ventilation openings (140, 141) contribute to maintaining a preferred temperature within the housing (100) for sample and reagent stability, and ensure that incubation steps in modules such as separation stations can be carried out at specific required temperatures.

[0142] The illustrated automated analysis system (1) further comprises a connection interface (150) including a holder (151) for accessories such as a handheld barcode reader and a communication port (152) such as a USB port or other suitable port for data transfer.

[0143] Additionally, one can see the lower loading front (160) with several dedicated drawers, such as a reagent drawer (161) and a waste drawer (162), designated primarily for larger components such as bulk reagent containers and waste canisters. The upper loading front (170) in the illustrated embodiment is equipped with several flaps or drawers, such as a sample receiving bay cover flap (171). As can be inferred by inspecting the drawing, the upper loading front (170) is designated for the loading and retrieval of less bulky components than is the case with the lower loading front (160).

[0144] 1A also shows a signal lamp (180) mounted on top of the instrument (1). Such a lamp can indicate a warning, for example, by emitting various coded colors. Its placement on top of the automated analysis system (1) improves visibility from virtually any direction, as opposed to placement at the front or rear of the system (1).

[0145] At the bottom of the automated analyzer system (1) in the illustrated embodiment is a leveling mechanism (190) comprising a gravity sensor-based level indicator (191), such as an inclinometer, including a display or other type of indicator, such as a signal light like an LED, and an adjustable base (192) for leveling the instrument (1). Maintaining the analyzer in a position parallel to the floor and thus aligned with gravity is often important to avoid spillage of liquids within the housing (100), for example, due to tipping of sample vessels or opening of reagent containers.

[0146] Turning to the perspective rear view of the automated analysis system (1) shown in Figure 1B, various elements seen in Figure 1A can also be seen here. Additionally, in this view, the rear wall (101) of the analysis device (1) can be seen.

[0147] To illustrate one embodiment of the upper interior space of the automated analysis system (1), the perspective front view of FIG. 1C shows the automated analysis system (1) with the front window (500) open. The window (500) is transparent and therefore opens primarily to access internal components, allowing visual inspection even when the window (500) is closed. The window (500) is vertically slidable along guide rails (510, not visible in this view), and it can be assumed that the lower position is closed and the upper position is open. The display (502) is omitted from this view, and its location can be seen as a corresponding cutout in the window (500). As seen in FIGS. 1A and 1B, a side window (130) corresponding to the opposite side window (110) contributes to enabling visual monitoring of the internal process from the outside.

[0148] Various devices and modules can be seen within the housing 100. For example, on the right side, the sample receiving bay 200 can be seen from above, its dedicated interface covered by the sample receiving bay cover flap 171. A reading device 220, such as a camera or barcode reader, is shown within the sample receiving bay 200. The sample receiving bay 200 is shown with a sample rack 210 (not visible in this view) that holds a number of sample containers 215, which in this embodiment are sample tubes.

[0149] A pipettor (630, not visible in this view) is positioned substantially above the reagent storage unit (610, not visible in this view) located behind the reagent drawer (161), and therefore in this embodiment can be referred to as the reagent pipettor (630). Also visible is a drive belt (611) belonging to a drive mechanism for moving the reagent pipettor (630).

[0150] Some of the components within housing (100) that can be seen generally in this view are described below.

[0151] The individual drawings in Figure 2 illustrate various embodiments of the sample receiving bay (200) disclosed herein.

[0152] FIG. 2A can be understood as essentially an enlarged, separate perspective front view of the sample receiving bay (200) seen on the right side of FIG. 1C. In this embodiment, the bay (200) has eight lanes (230) arranged substantially parallel to one another and configured to receive and guide sample racks (210) that hold multiple sample containers (215, not shown) in dedicated sample container slots (212). In this view, only one of the lanes (230), the leftmost lane, is loaded with a sample rack (210). The sample rack (210) shown here includes a handle (211) for convenient manual loading and unloading by the user. Each lane (230) includes a protruding guide piece (231) that helps center the sample rack (210) during loading and unloading. This allows each lane to act as a short guide rail. Another part of each illustrated lane (230) is a proximal stop element (240) as described herein, represented in this embodiment by an injection-molded part, i.e., an injection-molded baffle. The proximal stop element (240) is configured to create friction with a corresponding protrusion (not shown) on the bottom of the sample rack (210), thereby prompting the user to pause the manual insertion operation and indicating that a focus position has been reached. In the latter position, the reader (220) focuses on the lane (230) holding the sample rack (210), for example, to read characteristics of the sample rack (210) or the sample containers (215) held therein. The reader (220) shown in this figure is embodied as a multi-component unit. It includes a camera or, in the case of a one-dimensional or two-dimensional barcode reader, a receiver (221) that collects electromagnetic waves, such as a light beam. The reader (220) in this embodiment further comprises a mount (222) movably attached to a guide rail (223). When driven by a motor (225), such as a stepper motor, the reader (220) is movable along the guide rail (223) to adjust the focus of the reader to the sample rack (210) in lane 1.Other embodiments are also possible in which the reader (220) is stationary, such as in the case of an autofocus camera. The reader (220) in this embodiment has an integrated light source (224) embodied as an LED ring around the edge of the receiver (221). The light source (224) is thus axially aligned with the optical path of the receiver (221) of the reader (220). In the illustrated embodiment, it can be assumed that the optical path between the reader (220) and the sample rack (210) containing the vessels (215, not shown) is not linear. The sample vessel slots (212) of the sample rack (210) have openings facing the side of the rack (210), so that identifiers, such as barcodes, on the sample vessels (215) can be accessible to the reader (220). In the embodiment shown in Figure 2A, the light beam following the optical path is bent at an angle of approximately 90° by a mirror (225) placed in the optical path of a reader (220) having a light source (224) and a receiver (221). This arrangement allows the reader (220) to move along the same axis as the sample racks (210) on their respective lanes (230), saving space, which is often limited in laboratories, as it does not require an increase in the width of the automated analysis system (1), as can be inferred from the diagram in Figure 1C.

[0153] The distal stop element (250) of the sample receiving bay (200) of the embodiment shown in Figure 2A includes or consists of part or all of the rear wall of the sample receiving bay (200). A user inserting a sample rack (210) into the receiving bay (200) along a dedicated lane (230) reaches the processing position by stopping the insertion movement when the resistance of this distal stop element (250) is encountered.

[0154] Positioning in this embodiment is provided by guide rails 260 as positioning elements 260 forming part of the lanes 230. Skirts projecting from the bottom of the sample racks 210 towards the sides of the racks 210 are guided in brackets on the guide rails 260.

[0155] A detection element (270), embodied in this view as a forked light barrier (270) located at the distal end of lane (230) fixed to rear wall (250) of sample receiving bay (200) and thus to distal stop element (250), further contributes to positioning sample rack (210) in the processing position. In its additional role as a positioning element, forked light barrier (270) functions as a mechanical bracket for a protrusion (not shown in this view) protruding from the distal end of sample rack (210). Furthermore, this protrusion blocks light barrier (270) in its role as a detection element.

[0156] Detection of the sample rack (210) in the processing position through this light barrier (270) triggers a mechanism that causes the upward extension of a vertically arranged locking bolt (280) that acts as a locking element through a hole in the sample rack (210), which, with the help of the positioning element (260) and the detection element (270), locks the sample rack (210) in an aligned processing position with respect to all six degrees of freedom.

[0157] FIG. 2B shows a horizontal cross section of the sample receiving bay (200) along lane (230) with the sample rack (210) inserted in the processing position.

[0158] Some of the elements introduced in Figure 2A are also visible in this cross-sectional view, such as the rack handle (211), the receptacle slots (212), the rear wall (250) of the sample receiving bay (200) acting as a distal stop element, and the guide rail (260) acting as a positioning element. This view provides a more detailed view of the proximal stop element (240), which is embodied as an injection-molded baffle.

[0159] Further shown is a locking mechanism for restraining the sample rack 210 in the processing position. When the sample rack 210 in the processing position is detected by the fork-shaped light barrier 270, which acts as a detection element, the horizontally disposed solenoid lock 281 is actuated by the control unit in some embodiments to extend to an extended position. This causes the horizontal wedge 282 to be pushed upward into a corresponding hole in the sample lock 210, thereby pressing against and sliding along a vertical wedge 283 that forms part of the vertical lock bolt 280, a locking element that immediately interacts with the hole and locks the sample rack 210 in the processing position.

[0160] A more detailed view of this locking mechanism is shown in Figure 2C, in which the sample rack (210) is not present to provide a clearer view of the locking elements. The reset force is applied to the solenoid lock (281) by horizontal spring (284) and to the locking bolt (280) by vertical spring (285). Screw (232) that fastens the locking mechanism to the bottom of lane (230) can also be seen.

[0161] Another embodiment of the locking mechanism is shown in the schematic cross-sectional views of Figures 2D-2F, which show various stages of insertion and removal of the sample rack (210).

[0162] In Figure 2D, the sample rack is moving from right to left toward the distal stop element (294) and thus the processing position (the movement of each element is indicated by an arrow). A spring catch (290) positioned below and projecting upward from the lane (230) is pushed down into the space below the lane (230) by the moving rack (210). A knob (216) projecting laterally from the rack (210) engages with a rotary latch (292) and rotates it counterclockwise. At this stage, the solenoid lock (291) is in a retracted, i.e., open, state. The light barrier (293), which extends toward the reader and thus perpendicular to the lane (230), is unobstructed and therefore in a non-detecting state.

[0163] Next, Figure 2E shows the sample rack (210) fully inserted and locked in the processing position. The knob (216) of the sample rack (210) engages the rotary latch (292) and pushes it into a substantially fully vertical position against the distal stop element (294). In this position, the spring catch (290) engages a corresponding recess (295) in the sample rack, locking the sample rack in place. Simultaneously, the rotary latch (292) achieves detection of the sample rack (210) in the processing position by interrupting the light barrier (293) with its dedicated tongue (2921). The rotary latch (292) itself is locked in place by the solenoid lock (291), which now extends to a closed state and engages the raised portion (2922) of the rotary latch (291). In this embodiment, positioning, detection, and locking are provided synergistically by multiple cooperating elements. The rotary latch (292) plays a role in positioning (by engaging the knob (216) of the sample rack (210)), detection (by blocking the light barrier (293) with its tongue (2921)), and locking (by being blocked by the solenoid lock (291) via its ridge (2922)).

[0164] Removal of the sample rack (210) in this embodiment is shown in Figure 2F. It is initiated by pulling the solenoid (291) back to the open position again, allowing the sample (210) to be extracted from left to right (see arrows) and the rotary latch (292) to be rotated again to the diagonal position, while the knob (216) disengages and the tongue (2921) moves out of the path of the light barrier (293) to end detection, disengaging the spring catch (290) and being pushed down by the moving sample rack (210).

[0165] The basic principles of the process shown in Figures 2D-2F also apply to other possible embodiments, including the embodiment shown in Figure 2C, which has a wedge mechanism for locking the sample rack (210) in a locked position.

[0166] An embodiment of an indicator system 300 of the automated analysis system 1 is shown in the drawing of FIG.

[0167] In this context, FIG. 3A shows a perspective schematic view of a sample receiving bay (200) according to one embodiment of the automated analysis system (1) disclosed herein.

[0168] The sample receiving bay (200) is depicted in an open state where access to the interior is possible for a user standing in front of the automated analysis system (1).

[0169] In this embodiment, the sample receiving bay (200) comprises a movable platform (350). The indicator system (300) is integrated into the movable platform (350), and the indicator system (300) interfaces with the upper surface, or work surface (351), of the platform (350). A display (502) integrated into a transparent window (500) is visible above the sample receiving bay (200).

[0170] The movable platform (350) is configured to extend horizontally from the housing (100) to form an extension of the plurality of lanes (230) outside the housing (100), and the platform (350) has positioning elements (352, not shown in this view) configured to position the sample rack (210) in an exposed inspection position. Figure 3A shows the movable platform (350) in a fully extended state, allowing the sample rack (210) to be extended and positioned on the platform for improved visual inspection or direct physical manipulation by a user.

[0171] The indicator system (300) of the illustrated embodiment comprises a plurality of individual light sources (3011), such as LEDs, aligned with the vessel slots (212) of a sample rack (210) configured to hold a plurality of sample vessels (215).

[0172] The interaction between the indicator system (300) and the sample rack (210) is shown in FIG. 3B. As in FIG. 3A, the movable platform (350) is shown in a fully extended position, but in this view the sample rack (210) is in an exposed inspection position on the working surface (351) of the platform (350). The sample rack (210) is positioned in the inspection position with the aid of a positioning element (352), which in this embodiment is located at the proximal end of the working surface (351) of the movable platform (350). The positioning element (352) may be, for example, a hook, a latch, a pin, a skirt, or any other conceivable mechanical solution. In some embodiments, the positioning element (352) comprises or consists of a magnet.

[0173] A schematic diagram of one embodiment of optical coupling between the light source (3011) and the light emission window (302) can be seen in the cross-sectional view of Figure 3C. In principle, the same arrangement as in Figure 3B can be seen. The sample rack (210) is in the exposed inspection position, and the indicator system (300), arranged along the extension lane (230) on the work surface (351) of the movable platform (350), is aligned with the dedicated sample container positions (212) of the sample rack (210). More precisely, in the illustrated embodiment, the individual light sources (3011) of the indicator system (300) are aligned with the sample container slots (212) of the sample rack (210) in the exposed inspection position, thereby positioning the individual light sources (3011) below and optically coupling with each of the light emission windows (302) adjacent to each of the sample container slots (212). In the embodiment shown here, the optical light guide system (303) optically coupling the light source (3011) and the light emission window (302) may be a vertically aligned light guide rod, a fiber, or simply a tunnel extending vertically through the sample rack (210).

[0174] In an alternative embodiment of the optical light guide system (303) shown in Figure 3D, a single light source (301) is positioned on or within the work surface (351) of the movable platform (350) below the sample rack (210) in the testing position. The optical light guide system (303) in this embodiment includes multiple optical fibers (3031), each of which couples the light source (301) to a corresponding light emission window (302) associated with a dedicated sample vessel slot (212).

[0175] FIG. 3E illustrates a two-dimensional top view of the individual light sources 3011 of the indicator system 300 according to the embodiment of FIGS. 3A-3C. The individual light sources 3011 in this embodiment have different colors and are configured to optically couple to their corresponding light emission windows 302. The sample rack 210 is omitted from this view to focus on the information display principle of the indicator system 300. Each of the individual light sources 3011 aligns with a corresponding sample container slot 212 of the sample rack 210 in the inspection or exposed inspection position, and the particular color of the light source 3011 indicates the particular status of the corresponding sample container 215 and its biological sample in the respective sample container slot 212. For example, a red color (represented by a circle with an x) can indicate a sample container slot 212 holding a sample container 215 with a coagulated biological sample that requires manual intervention by the user. A green light (represented by a solid black circle) may indicate a good sample, while a blue light (represented by an empty circle) may indicate an empty container slot (212). An orange color (represented by a filled circle with a +) may indicate an incorrectly capped sample container, etc. With the help of these easily decipherable visual signals, the user can easily identify problematic samples as well as the type of underlying problem based on the color code of the indicator system (300).

[0176] As described herein, the indicator system 300 disclosed herein may be positioned along a lane 230 within the housing 100 in the sample receiving bay 200 of the automated analysis system 1. While the movable platform 350 provides improved sample accessibility, embodiments having the indicator system 300 within the housing 100 can reduce user burden by eliminating the need to remove the sample rack 210 from the housing 100.

[0177] Once a biological sample is introduced into the analyzer (1) at the processing position sample rack (210), a dedicated module can begin performing processing steps on the sample. As mentioned above, one typical step prior to the analysis of a biological sample is an isolation or purification process.

[0178] In some embodiments of the automated analysis system (1) disclosed herein, the separation station performs the analyte isolation process using specialized binding particles for binding biological target materials. Because the binding particles, such as magnetic glass particles for binding nucleic acids, are often provided as a suspension in a specialized container, maintaining a uniform distribution of the binding particles throughout the suspension can be important. Particles that sink to the bottom of a stationary container typically alter the distribution, resulting in a lower particle density in the upper region of the container and a higher particle density at the bottom. Therefore, when aspirating a fixed volume of suspension, the amount of binding particles retrieved in different aspiration events may vary, even though the amount of suspension aspirated in every event is consistent. Particularly in clinical diagnostics, such variations can affect nucleic acid yield and potentially compromise the success of downstream biological sample analysis.

[0179] A convenient technique for maintaining the homogeneity of such suspensions involves shaking the vessel with the aid of a robotic shaker. For example, between two pipetting events, the shaker can shake the vessel, and therefore the suspension therein, for a specified period of time.

[0180] The diagrams in Figure 4 illustrate various stages of a convenient process for securing a container (410) containing a suspension of binding particles to a shaker (420) in a specialized system (400) for providing binding particles for isolating biological materials. Each of the individual Figures 4A-4C consists of an upper diagram showing a perspective view and a lower diagram showing the same configuration as the upper diagram but in a plan view from above of the suspension container (410).

[0181] Figure 4A shows the open state in which the suspension container (410) is displaced at a displacement angle that in this view is approximately 20° relative to the closed shaking position. The container (410) is positioned above the shaker (420).

[0182] In FIG. 4B, the container (410) is still placed on the shaker (420) at the same angle of displacement as in FIG. 4A and is pressed against the shaker from above.

[0183] The shaking position is shown in Figure 4C, where the container (410) containing the suspension of bound particles is secured to the shaker (420). Compared to the previous state from Figure 4B, the suspension container (410) has now been rotated 20° in a clockwise direction, thereby securing the container (410) to the shaker (420) via the bayonet lock (430).

[0184] Turning to another embodiment of the automated analytical system (1) described herein, FIG. 5 shows the transparent window (500) of the analytical device (1).

[0185] As described herein, in some embodiments, a user can access the interior space of the housing 100 through an interface that can be opened or closed by a transparent window 500. The transparent window 500 for opening and closing the interface is slidable between an open position and a closed position, and the window 500 includes a counterweight 530 configured to hold the window 500 in the open position, the closed position, or a position therebetween.

[0186] The transparent window (500) in this embodiment is slidable along a guide rail (510) and is connected to a counterweight (530) via a pulley (520).

[0187] The drawing in Figure 6 relates to the above-described system (600) for cooling reagents for performing biological assays in the automated analytical system (1) described herein.

[0188] Figure 6A shows a perspective view of an automated analytical system (1) described herein according to an embodiment substantially similar to that shown in Figure 1. The reagent drawer (161) is opened in this view to reveal portions of a cooling system (600) comprising a cooling chamber (610) surrounded by a substantially insulated housing (615) having a bottom and a top, the top being covered by a lid (620) comprising an opening (621) switchable between an open and a closed state. A pipettor (630) belonging to the cooling system (600) is inside the housing (100) of the analytical device (1) and therefore is not visible in this view.

[0189] In Figure 6B, lid 620 is shown in a partially exploded view separated from cooling chamber 610, which is normally covered by lid 620. Also visible removed from housing 615 is side door 616, which is integral with housing 615 when closed. Side door 616 may be useful for replacing or inspecting reagent containers or other components inside substantially insulated housing 615.

[0190] 6C shows a more detailed view of the cooling chamber (610) separate from the automated analysis system (1), again in a similar partially exploded view. Beneath the removed lid (620) are located reagent containers (640) within the cooling chamber (610) on the pipetting deck (612), each having a plurality of top openings (641) for receiving the needles or tips of a pipettor (630, not shown). Behind the removed side door (616) is visible the reagent reservoir (650), which in this embodiment comprises three distinct levels (651, 652, 653) at any of which a control unit can rearrange the separate reagent containers depending on which reagent containers are needed in a given situation. For example, reagent containers required for the immediate task can be placed near the top of the cooling chamber (610), such as on the third level (653), or directly on the pipette deck (612).

[0191] 6D shows a detailed view of the exploded lid (620). The upper portion shows the lid (620) with the opening (621), but also shows a heating element (625) embodied as an inlay positioned proximate to the underside of the lid (620) covering the cooling chamber (610), the heating element (625) configured to heat the lid (620) so that the temperature of the top surface of the lid (625) exceeds the dew point of the air outside the cooling chamber (610). The heating element (625) has openings (626) corresponding to the openings (621) in the lid (620), which are aligned with the openings in the lid, so that, for example, a pipetting needle can pass through the aligned openings (621, 626) in both the lid (620) and the heating element (625). In the assembled state, the heating element (625) in this embodiment is positioned in direct physical contact with the underside of the lid (620), thereby efficiently transferring thermal energy to the lid (620) and preventing condensation from forming on the outside of the lid. The heating element (625) is powered via a power connector (627) that is connected to a power source, such as that integral with a control unit or temperature controller.

[0192] Figure 6E shows the entire cooling system 600, including a pipettor 630 positioned above the cooling chamber 610, configured to aspirate reagent from a reagent container 640 through an opening 621 in a lid 620 covering the cooling chamber 610. The pipettor 630 in this embodiment includes a head 631 to which a pipetting needle 632 is attached. The right-hand view of Figure 6E shows an enlarged view of the circled area in the left-hand view. It will be appreciated that in this detailed view, corresponding portions of the lid 620 and the reagent container 640 have been omitted to allow an unobstructed view of the pipetting needle 632 inserted into a designated opening 641 in the top of the reagent container 640.

[0193] A further embodiment of the automated analysis system (1) disclosed herein, namely, a thermal cycler (700) for incubating biological samples, is shown in the diagram of FIG. 7. Easily isolated biological target materials, such as nucleic acids, can be transferred from a separation station to an amplification and detection module, which comprises the thermal cycler (700) including a mount (710) configured to receive and hold a microwell plate and a loading platform (720) configured to transport the microwell plate to and from the mount (710), the loading platform (720) being rotatable between a loading position and an incubation position. Furthermore, the thermal cycler (700) includes a motor, such as a stepper motor, configured to rotate the loading platform (720) between the loading position and the incubation position.

[0194] FIG. 7A shows a general view of the thermal cycler (700) with the loading platform (720) in the loading position, ie, rotated away from the mount and therefore accessible to the multiwell plate.

[0195] 7B, there is shown a more detailed view of the loading mechanism of the same embodiment, including mount 710 of thermal cycler 700. Still in the loading position, loading platform 720 includes a receiving tray 721 for receiving and holding a multiwell plate (not shown), which, once inserted by a gripper or other suitable transfer means, can be rotated to an incubation position that engages the multiwell plate with mount 710 for proper thermal contact.

[0196] 8 shows a diagram of a flexibly mounted pipette tip rack 800, which is mounted on a work surface 820 of an automated analysis system 1 via one or more flexible elements 810 positioned between the rack 800 and the work surface 820. The flexible elements 810 are springs attached to the bottom of the rectangular pipette tip rack 800 at its four corners, providing flexibility to the rack 800 in the vertical direction, for example to compensate for uneven forces exerted by a pipetting head.

[0197] FIG. 9 illustrates by a flow chart the steps of the method for monitoring the valve system of the automated analysis system (1) described herein.

[0198] The steps are described as follows:

[0199] First, the automated analysis system is started by turning on the power (910).

[0200] Second, during or immediately after the start-up process, a start-up valve check (920) is performed on the operational status of the valve, the check including sending an electrical probe signal from the control unit to the valve and detecting the presence or absence of an electrical response signal (930) by the control unit, if there is no electrical response signal it indicates that the valve is not operational and an error message (935) is generated, if there is a response signal it indicates that the valve is operational and the method can continue.

[0201] Third, a working valve check (940) is performed in full startup mode of the automated analysis system (1) to repeatedly perform checks on idle valves based on electrical probe signals.

[0202] Fourth, based on an assessment of whether a check was performed on an upstream valve and therefore potentially affecting the sample (950), if the valve is a downstream valve and therefore would not affect the sample, an error message is generated (955), and then operation of the valve system continues, performing further iterations of the operational valve check (940), and if the valve is an upstream valve, an error message is generated and the current operation is also aborted (960). In this way, sample material can be salvaged by aborting the ongoing experiment if a valve is identified as faulty.

[0203] In general, modifications and variations of all disclosed embodiments are possible in light of the above description, and it is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described in the above examples.

[0204] Throughout the foregoing specification, references to "one embodiment," "embodiment," "one example," or "example" mean that a particular feature, structure, or characteristic described with respect to that embodiment or example is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment," "in an embodiment," "one example," or "an example" in various places throughout this specification do not necessarily all refer to the same embodiment or example.

[0205] Furthermore, the particular features, structures or characteristics may be combined in any suitable combinations and / or subcombinations in one or more embodiments or examples.

Claims

[Claim 1] 1. A method for introducing a sample rack (210) holding a plurality of sample containers (215) into a sample receiving bay (200) in a housing (100) of an automated analysis system (1), comprising: a) manually moving the sample rack (210) along a lane (230) within the sample receiving bay (200) from a loading position towards a processing position; b) pausing the movement when the sample rack (210) reaches a focus position defined by a proximal stop element (240) between the loading position and the processing position; c) moving a reader (220) in substantially the same horizontal plane as the lane (230) and focusing the reader (220) on the lane (230); d) resuming the movement of the sample rack (210) past the proximal stop element (240) and detecting characteristics of the sample rack (210) and / or the plurality of sample vessels (215) with the reader (220) during the movement until the sample rack (210) reaches the processing position defined by the distal stop element (250); e) positioning, detecting and locking the sample rack (210) in the processing position; f) processing the contents of said sample vessel (215); A method comprising:

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