Bioanalytical systems and methods

Abstract

A biological analysis system for performing assays or experiments includes one or more of a stage, a base, or a tray. The stage, base, or tray is configured to interchangeably receive (1) a first block and a corresponding first lid placed on the first block, or (2) a second block and a corresponding second lid placed on the second block. The system also includes a computer-readable memory containing instructions for detecting when the second lid is placed on the first block and / or detecting when the first lid is placed on the second block based on a lack of electrical continuity along an electrical path containing one of the blocks and one of the lids.

Description

Technical Field

[0001] This disclosure relates broadly, but not exclusively, to bioanalytical systems and related methods, including polymerase chain reaction (PCR) systems. Background Technology

[0002] Bioanalytical systems, such as PCR systems, are useful tools for diagnostics and research in biological or biochemical samples. PCR systems typically feature a thermal cycler, which heats and cools the sample in multiple cycles to achieve the desired amplification of one or more target molecules. Real-time PCR systems, also known as qualitative PCR (qPCR) systems, allow monitoring of PCR assays during each thermal cycle of the process.

[0003] There is a growing need to simplify the installation and setup of bioanalytical systems, enabling operators to use them more quickly and efficiently for their intended purposes. However, existing systems often require manual operation or intervention, which can lead to inefficiencies and inconsistencies.

[0004] Therefore, it is desirable to provide a bioanalytical system that can solve at least one of the above problems. Attached Figure Description

[0005] Embodiments of this disclosure will be better understood, and will be apparent to those skilled in the art, from the following written description, by way of example only, and in conjunction with the accompanying drawings, wherein: Figure 1 A block diagram illustrating an embodiment of a PCR instrument on which this teaching can be implemented is shown.

[0006] Figure 2 A block diagram illustrating a computer system that can be used to perform processing functions according to some exemplary embodiments of the present disclosure is shown.

[0007] Figures 3A to 3B Exploded and assembled diagrams of the block components according to the example embodiment are shown respectively.

[0008] Figures 3C to 3D A perspective view of a sample block and a sample holder according to an example embodiment is shown.

[0009] Figures 4A to 4B Each of the example embodiments is shown separately. Figures 3A to 3B The retracted and extended positions of the block components.

[0010] Figures 5A to 5B The images show the disengaged and engaged states, respectively. Figures 3A to 3B A sample block of a block assembly having a base according to an example embodiment.

[0011] Figures 6A to 6B It shows Figures 3A to 3BA magnified view of a portion of the block component.

[0012] Figure 7 A perspective view of an optical assembly having a cover stage attached thereto, according to an example embodiment, is shown.

[0013] Figures 8A to 8D A cross-sectional view illustrating the operation of the cover stage according to an example embodiment is shown.

[0014] Figures 9A to 9H Figures 9J-9K show different views of the cover platform according to the example embodiment.

[0015] Figures 10A to 10B Exploded and assembled diagrams of a bioanalytical system and a reagent with RFID tags according to an example embodiment are shown respectively.

[0016] Figures 11A to 11B An example embodiment is shown. Figures 10A to 10B A close-up cross-sectional view of the interior of the assembly system.

[0017] Figure 12 An example embodiment is shown. Figures 10A to 10B A partial cross-sectional view of the assembly system.

[0018] Figure 13 A flowchart of a method according to an example embodiment is shown.

[0019] Figure 14 A flowchart of a method according to an example embodiment is shown.

[0020] Figure 15 A flowchart of a method according to an example embodiment is shown.

[0021] Figure 16 This is a bottom view of the cover according to an embodiment of the present disclosure.

[0022] Figure 17 This is a top view of a sample block according to an embodiment of the present disclosure.

[0023] Figure 17A , 17B 17C shows Figure 17 An enlarged view of the components of the sample block shown.

[0024] Figure 18 It shows Figure 16 The perspective view of the lid is shown.

[0025] Figure 19 It shows Figure 17 A perspective view of the sample block shown.

[0026] Figure 20 It shows Figure 17 and 19 The image shows a perspective view of the sample block, with the sample holder placed on the sample block.

[0027] Figure 21 It shows Figure 17 and 19 The cross-section of the sample block with a sample holder is shown.

[0028] Figure 22 This is a perspective view of the second cover according to an embodiment of the present disclosure.

[0029] Figures 22A to 22B It shows Figure 22 An enlarged view of the elements of the cover shown in the figure.

[0030] Figure 23 This is a perspective view of a second sample block according to an embodiment of the present disclosure.

[0031] Figure 24 A first combination of connectors for a sample block and a cover according to an embodiment of the present disclosure is shown, wherein there is a lack of electrical continuity between the connectors.

[0032] Figure 25 A second combination of connectors for a sample block and a cover, according to an embodiment of the present disclosure, is shown, wherein there is a lack of electrical continuity between the connectors.

[0033] Figures 26A to 26B A view showing an embodiment where the cap is placed on a non-corresponding sample block.

[0034] Figure 27 A perspective view of another embodiment of the lid located above the sample block corresponding to the lid is shown.

[0035] Figure 28 It shows Figure 27 The diagram shows the plan view of the lid and sample block.

[0036] Figure 29 It shows Figure 27 Another perspective view of the cover and sample block shown.

[0037] Figure 30 and 31 A plan view of the electrical connectors for different caps is shown, which are configured to accommodate different types of sample holders.

[0038] Figure 32 It shows Figures 27 to 29 The image shows a perspective view of the sample block, with a calibration or alignment fixture placed on the sample block.

[0039] Figures 33 to 35 It shows Figure 32The cross-sectional view of the calibration or alignment fixture shown.

[0040] Figure 36 It shows the configuration with Figures 27 to 29 The diagram shows a view of the pill box or orifice of a sample holder used with the sample blocks, illustrating the positions of the irradiation beam and the bubble at the edge of the pill box or orifice.

[0041] Figure 37 It shows Figures 27 to 29 The cross-section of the sample block shown illustrates the features of a sample block used to move the sample block to calibrate or align the optical system of an instrument or system, where the sample block can be placed.

[0042] Figure 38 It is used to Figures 27 to 29 The flowchart shown illustrates a method for calibrating or aligning the optical system of an instrument or system with a sample block, which may be placed within the instrument or system.

[0043] Figures 39 to 41 yes Figures 32 to 35 The scanned image shows the hole of the calibration or alignment fixture. Detailed Implementation

[0044] To provide a more thorough understanding of this disclosure, the following description sets forth numerous specific details, such as specific configurations, parameters, and examples. However, it should be understood that such description is not intended to be a limitation of the scope of the invention, but rather to provide a better description of exemplary embodiments.

[0045] It should also be recognized that the methods and systems described herein can be implemented in various types of systems, instruments, and machines, such as bioanalytical systems. For example, various embodiments can be implemented in instruments, systems, or machines that perform polymerase chain reactions (PCR) on multiple samples. While generally applicable to quantitative polymerase chain reactions (qPCR) in which large numbers of samples are processed, it should be recognized that any suitable PCR method can be used according to the various embodiments described herein. Suitable PCR methods include, but are not limited to, digital PCR, allele-specific PCR, asymmetric PCR, ligation-mediated PCR, multiplex PCR, nested PCR, qPCR, genome walking, and bridging PCR. Furthermore, as used herein, thermal cycling can include the use of a thermal cycler, isothermal amplification, thermal convection, infrared-mediated thermal cycling, or helicase-dependent amplification.

[0046] As used herein, the terms “radio frequency identifier,” “radio frequency identifier tag,” or “RFID tag” can refer to a chip containing an integrated circuit and an antenna. The integrated circuit can store data that can be transmitted via radio frequency emitted by the antenna. The integrated circuit and antenna circuitry can be printed on the chip. An RFID “tag” or “transponder” can be read by an RFID reader using the transmitted radio frequency to query the transponder’s antenna. “Passive RFID” does not have its own power source but transmits signals in response to signals from a reader. “Active RFID” includes a battery as a power source. Some examples of RFID tags can be found in U.S. Patent Nos. 6,147,662; 6,917,291; 5,949,049; 6,652,812; 6,112,152; and U.S. Patent Application No. 2003 / 0183683, all of which are incorporated herein by reference in their entirety, including disclosures of RFID tags, chips, markers or devices, RFID readers and RFID systems, their design and use. A "writable radio frequency identifier" or "writable RFID" is an RFID tag with storage space that can be written to by an RFID writer.

[0047] As used herein, the term "sample holder" can refer to a structure used to directly or indirectly support one or more reaction sites, each configured to contain a biological sample and any associated reagents, dyes, probes, detergents, enzymes, master mixtures, etc. Examples of sample holders include, but are not limited to, microtiter plates, reaction plates, tubes, tube stages, surface plasmon resonance arrays, glass slides, conical low-capacity tubes, microfluidic cards, microarray chips, plates or boxes, through-hole arrays, sample preparation devices, assay preparation devices, electrophoresis devices, electroosmosis devices, immunoassays, combinatorial libraries, molecular libraries, phage display libraries, DNA libraries, DNA fingerprinting devices, SNP detection devices, vacuum containers, and other types of containers used to support biological reagents or assays. A sample holder may contain multiple reaction regions, reaction sites, or sample holding regions. Reaction regions may take the form of pores, through-holes, chambers, or surface indentations or spots (e.g., hydrophilic spots on a surface). Sample holders can be well-drained discs or microtiter plates, including, for example, 4, 12, 24, 48, 96, 192, 384, 768, 1536, 3072, 6144, 12288 or more wells or other types of sample retention areas. If the sample holder can be used to deliver, contain, surround, or otherwise permanently or temporarily retain a fluid, then the sample holder can retain the fluid. Sample holder materials can comprise any materials used in chemical and biochemical synthesis. Sample holder materials can comprise polymeric materials compatible with chemical and biochemical synthesis and assays, and include glass, silicates, cellulose, polystyrene, polysaccharides, sand, and synthetic resins, as well as polymers, including acrylamide, particularly cross-linked polymers, cotton, and other such materials. Sample holder materials can be in granular form or can be of a continuous design, such as test tubes or microtiter plates.

[0048] As used herein, the terms “communication,” “electrical communication,” or “electronic communication” generally refer to communication between two or more electronic components (e.g., electronic devices or electronic systems). Communication can be achieved via a physical connection to two electronic components (e.g., wires, cables, fiber optic cables, etc.) or via a third electronic component (e.g., a network system such as a local area network (LAN) or a wide area network (WAN)) to which both a first and a second communication component are connected. Additionally or alternatively, electrical communication can be configured via transmitter / receiver, such as direct wireless communication between devices (e.g., between antennas in two communication components, Bluetooth connection, etc.), or via a wireless network (e.g., a wireless router system, Wi-Fi connection, or a wireless data communication system such as that provided by a telecommunications provider). Additionally or alternatively, electrical communication can be provided via communication from a device to a public database such as a cloud database.

[0049] System Overview As described above, the instruments according to embodiments of this teaching can be used to perform various types of bioassays, experiments, tests, etc. In this disclosure, embodiments of instruments for performing polymerase chain reaction (PCR) assays are illustrated using microtiter plates. However, embodiments of this teaching extend to other types of instruments (e.g., capillary electrophoresis instruments, sequencing instruments such as next-generation sequencing (NGS) instruments, microarray systems, flow cytometers, etc.), sample holders (e.g., as discussed above), and assays of these types (e.g., capillary electrophoresis, genetic sequencing, genotyping, etc.).

[0050] Figure 1 A block diagram illustrating the components of an instrument, such as a real-time PCR instrument 100, on which embodiments of the present teachings may be implemented. The real-time PCR instrument 100 may include a lid or heated lid 110 placed on a plurality of samples 112 contained in a substrate, plate, or sample holder (not shown here). In various embodiments, the sample holder may be a glass or plastic slide having a plurality of sample regions with a lid between the sample regions and the heated lid 110. In various embodiments, the sample holder may include one or more reaction sites, which may include indentations, holes, through-holes, dimples, surface discontinuities, ridges, and combinations thereof, which may be patterned in a regular or irregular array formed on the surface of the sample holder. The PCR instrument also includes a sample block 114 for holding or maintaining the plurality of samples and a heated block 116 for heating and / or cooling the sample block 114 and the samples contained therein. Blocks 114 and 116 may be coupled or connected together to form a monolithic block or sample block assembly 114.

[0051] The real-time PCR instrument 100 has an optical system 124. Figure 1 In this system, the optical system 124 may include an irradiation source (not shown) that emits electromagnetic energy, an optical sensor, detector, or imager (not shown) for receiving electromagnetic energy from the sample 112 in the sample holder, and optical devices for guiding electromagnetic energy from each DNA sample to the imager. For Figure 1 In an embodiment of the PCR instrument / real-time PCR instrument 100, the control system 120 can be used to control the functions of the detection system, the heated lid, and the heated block. End users can... Figure 1 The user interface 122 of the PCR instrument / real-time PCR instrument 100 accesses the control system 120. Additionally, such as... Figure 2 The described computer system can be used to provide access to Figure 1 The functions of the PCR instrument and the control of the user interface. Additionally, Figure 2 The computer system 200 can provide data processing, display, and report preparation functions. All such instrument control functions can be used locally for the PCR instrument, or... Figure 2The computer system 200 can provide some or all of the remote control functions for control, analysis and reporting, which will be discussed in more detail later.

[0052] Computer-implemented systems The methods described in the embodiments herein can be implemented using a computer system.

[0053] Those skilled in the art will recognize that the operation of the various embodiments can be implemented as needed using hardware, software, firmware, or a combination thereof. For example, some processes can be performed using a processor or other digital circuitry under the control of software, firmware, or hardwired logic. (The term "logic" as used herein refers to fixed hardware, programmable logic, and / or suitable combinations thereof, as will be recognized by those skilled in the art, to perform the stated functions.) Software and firmware can be stored on a non-transitory computer-readable medium. As is well known to those skilled in the art, some other processes can be implemented using analog circuitry. Additionally, memory or other storage devices and communication components may be employed in embodiments of the invention.

[0054] Figure 2 A block diagram of a computer system 200, which can be used to perform processing functions according to various embodiments, is shown. Instruments for performing experiments can be connected to the exemplary computing system 200. The computing system 200 may include one or more processors, such as processor 204. Processor 204 may be implemented using a general-purpose or special-purpose processing engine, such as a microprocessor, controller, or other control logic. In this example, processor 204 is connected to bus 202 or other communication media.

[0055] Furthermore, it should be understood that Figure 2The computing system 200 can be implemented in any of a variety of forms, such as rack-mount computers, mainframes, supercomputers, servers, clients, desktop computers, laptop computers, tablet computers, handheld computing devices (e.g., PDAs, cellular phones, smartphones, PDAs, etc.), clustered grids, netbooks, embedded systems, or any other type of dedicated or general-purpose computing device that may be desired or appropriate for a given application or environment. Additionally, the computing system 200 can include conventional network systems comprising client / server environments and one or more database servers, or integrated with LIS / LIMS infrastructure. Various conventional network systems comprising local area networks (LANs) or wide area networks (WANs) and including wireless and / or wired components are known in the art. Furthermore, client / server environments, database servers, and networks are well-documented in the art. According to the various embodiments described herein, the computing system 200 can be configured to connect to one or more servers in a distributed network. The computing system 200 can receive information or updates from the distributed network. The computing system 200 can also transmit information to be stored within the distributed network, which can be accessed by other clients connected to the distributed network.

[0056] The computer system 200 may include a bus 202 or other communication mechanism for transmitting information, and a processor 204 coupled to the bus 202 for processing information.

[0057] Computer system 200 also includes memory 206 coupled to bus 202, which may be random access memory (RAM) or other dynamic memory for storing instructions executed by processor 204. Memory 206 can also be used to store temporary variables or other intermediate information during the execution of instructions to be executed by processor 204. Computer system 200 further includes read-only memory (ROM) 208 or other static storage device coupled to bus 202 for storing static information and instructions for processor 204.

[0058] The computing system 200 may also include a storage device 210, such as a hard disk, optical disk, or solid-state drive (SSD), which is provided and coupled to bus 202 for storing information and instructions. Storage device 210 may include a media drive and a removable storage interface. The media drive may include a drive or other mechanism for supporting fixed or removable storage media, such as a hard disk drive, floppy disk drive, magnetic tape drive, optical disk drive, CD or DVD drive (R or RW), flash drive, or other removable or fixed media drive. As illustrated in these examples, the storage media may include computer-readable storage media in which specific computer software, instructions, or data are stored.

[0059] In an alternative embodiment, storage device 210 may include other similar tools for allowing computer programs or other instructions or data to be loaded into computing system 200. Such tools may include, for example, removable storage units and interfaces (e.g., program cassettes and cassette interfaces), removable memory (e.g., flash memory or other removable memory modules), and memory slots, as well as other removable storage units and interfaces that allow software and data to be transferred from storage device 210 to computing system 200.

[0060] The computing system 200 may also include a communication interface 218. The communication interface 218 can be used to allow software and data to be transferred between the computing system 200 and external devices. Examples of the communication interface 218 may include a modem, a network interface (such as Ethernet or other NIC cards), a communication port (such as, for example, a USB port, an RS-232C serial port), a PCMCIA slot and card, Bluetooth, etc. The software and data transmitted via the communication interface 218 may be in the form of signals that can be received by the communication interface 218, including electronic, electromagnetic, optical, or other signals. These signals may be transmitted and received via a channel through the communication interface 218, such as a wireless medium, wires or cables, optical fibers, or other communication media. Some examples of channels include telephone lines, cellular telephone links, RF links, network interfaces, local area networks or wide area networks, and other communication channels.

[0061] The computing system 200 may be coupled to a display 212, such as a cathode ray tube (CRT) or liquid crystal display (LCD), via a bus 202 for displaying information to a computer user. An input device 214, including alphanumeric and other keypads, is coupled to the bus 202 for transmitting information and command selections to the processor 204, for example. The input device may also be a display configured with touchscreen input capabilities, such as an LCD. Another type of user input device is a cursor controller 216, such as a mouse, trackball, or arrow keys, for transmitting directional information and command selections to the processor 204 and for controlling cursor movement on the display 212. This input device typically has two degrees of freedom on two axes, a first axis (e.g., the x-axis) and a second axis (e.g., the y-axis), allowing the device to specify a position in a plane. The computing system 200 provides data processing and provides confidence levels for such data. Consistent with certain embodiments of the teachings of this invention, the computing system 200 provides data processing and confidence values ​​in response to the processor 204 executing one or more sequences of one or more instructions contained in memory 206. Such instructions can be read into memory 206 from another computer-readable medium (e.g., storage device 210). Execution of the instruction sequence contained in memory 206 enables processor 204 to perform the processing state described herein. Alternatively, hard-wired circuitry can be used in place of or in combination with software instructions to implement the embodiments taught in this invention. Therefore, implementations of the embodiments taught in this invention are not limited to any particular combination of hardware circuitry and software.

[0062] As used herein, the terms "computer-readable medium" and "computer program product" generally refer to any medium relating to providing processor 204 with one or more sequences or instructions for execution. Such instructions, generally referred to as "computer program code" (which may be grouped as a computer program or other groupings), when executed, cause computing system 200 to perform features or functions of embodiments of the present invention. These and other forms of non-transitory computer-readable media can take many forms, including, but not limited to, non-volatile media, volatile media, and transmission media. Non-volatile media include, for example, solid-state drives, optical disks, or magnetic disks, such as storage device 210. Volatile media include dynamic memory, such as memory 206. Transmission media include coaxial cables, copper wires, and optical fibers, including conductors including bus 202.

[0063] Common forms of computer-readable media include, for example, floppy disks, floppy disks, hard disks, magnetic tapes or any other magnetic media, CD-ROMs, any other optical media, punched cards, paper tapes, any other physical media with a perforated pattern, RAM, PROMs and EPROMs, FLASH-EEPROMs, any other memory chips or cassettes, carrier waves as described below, or any other media from which a computer may read.

[0064] Various forms of computer-readable media can be used to load one or more sequences of one or more instructions to processor 204 for execution. For example, the instructions may first be carried on the disk of a remote computer. The remote computer may load the instructions into its dynamic memory and transmit the instructions over a telephone line using a modem. A modem local to computing system 200 may receive data over the telephone line and convert the data into an infrared signal using an infrared transmitter. An infrared detector coupled to bus 202 may receive the data carried in the infrared signal and place the data on bus 202. Bus 202 loads the data into memory 206, from which processor 204 retrieves and executes the instructions. The instructions received by memory 206 may optionally be stored on storage device 210 before or after execution by processor 204.

[0065] It should be understood that, for clarity, embodiments of the invention have been described above with reference to different functional units and processors. However, it will be apparent that any suitable distribution of functionality across different functional units, processors, or domains can be used without departing from the invention. For example, illustrated functions that would be performed by a separate processor or controller can be performed by the same processor or controller. Therefore, references to specific functional units are to be regarded only as references to suitable means for providing the described functionality, and not as indications of a strict logical or physical structure or organization.

[0066] Figure 10A An exploded perspective view of a bioanalytical system or instrument 1000 according to an example embodiment is shown. Figure 10B It shows Figure 10A An assembled perspective view of system 1000. System 1000 may include a base plate, frame or support structure 301, and a housing, enclosure or chassis 1001 for housing, isolating and / or protecting various parts, components and sub-components of system 1000. System 1000 may further include a frame 704 that may be attached, secured, coupled to and / or supported by support structure 301. As discussed herein, system or instrument 1000 includes elements and systems relating to a qPCR system or instrument. However, the scope of the various embodiments disclosed herein may cover other types of systems or instruments, such as other types of bioanalytical systems or instruments, such as those listed above herein.

[0067] refer to Figure 3A and 3B System 1000 may contain block component 300. Figure 3A An exploded perspective view of block component 300 according to an example embodiment is shown. Figure 3B It shows Figure 3A An assembly perspective view of block component 300. See also: Figure 3C and 3D The block assembly 300 includes a sample block 302 or block containing an upper surface 303 and a plurality of containers or sample wells or receiving elements 304. For example, when the sample block 302 is configured to receive a standard 96-well or 384-well microtiter plate, the receiving elements may be disposed within a rectangular area having a long side of dimension “L” and a short side of dimension “S” smaller than dimension L. The sample block 302 may include a heated block 305 mounted to and in thermal contact with the upper part of the sample block 302, the heated block being configured to receive a sample holder or stage. The heated block 305 may include one or more elements (not shown) for heating and / or cooling, such as thermoelectric elements, one or more heat sinks or radiators, one or more heat exchangers or heat sinks, and / or one or more fans. The sample block 302 can be placed in or on a movable support or base 308, which may include a stage, base, or tray 306 configured to support, hold, or lock the sample block 302. The stage 306 may be a separate component attached to the movable base 308 or may be integrally formed with the movable base 308.

[0068] Still referencing Figures 3A to 3D And refer to other sources. Figure 4A and 4BSample block 302 can be configured to receive sample holder 316. Sample holder 316 may include multiple reaction sites or reaction regions 317. In the illustrated embodiment, sample holder 316 includes a microtiter plate comprising 96 reaction sites 317 in the form of 96 wells. Alternatively, sample holder may include a microtiter plate comprising 4, 12, 24, 48, 96, 192, 384, 768, 1536, 3072, 6144, 12288 or more wells or other types of sample retention regions. In some embodiments, sample holder 316 includes a card comprising 384 chambers or wells, which is loaded into the chambers or wells via multiple channels, for example, a TaqMan array card (TAC) manufactured by Thermo Fisher Scientific. Additionally or alternatively, the sample holder 316 includes a reaction region 317, which may take the form of multiple reaction volumes in a fluidic card, vias in a plate or chip, surface indentations, or other discontinuities or surfaces. In other embodiments, the sample holder 316 may include one or more linear reaction site strips, multiple individual vials, sample cards, microfluidic cards, via arrays, etc. The reaction sites 317 may alternatively include multiple vias or other forms discussed herein. In some embodiments, the block assembly 300 may also include a cap 800, which may be configured to cover the sample holder 316 and / or protect and / or provide optical access to the reaction sites 317. In the illustrated embodiment, the cap 800 is a thermal cap, configured to heat the top of the sample holder 316, the top of the block, and / or the volume above the sample holder 316 and / or the block. Alternatively, the cover 800 may be a non-thermal cover, such as a cover plate for protecting the contents of the sample holder 316, a plate with openings to provide optical access to the reaction site 317, and / or an array of small lenses configured to focus light into or onto the reaction site 317.

[0069] In some embodiments, the sample block 302 may be located on or within a movable base 308 configured to move or transport the sample block 302 from a position inside the housing 1001 to a suitable position, for example along... Figure 4B The horizontal axis is indicated by the double-arrow line in the diagram. The movable base 308 can be configured to move or transport the sample block 302 together with the sample holder 316, when present, from a location inside the housing 1001 to a location wholly or partially outside the housing 1001, for example, to replace the sample block 302 with a different sample block 302 (e.g., with a different format and / or reaction site density) and / or to replace the sample holder 316 with a different sample holder 316 (e.g., with a different number of sample or reaction sites).

[0070] For further reference Figure 6A and 6B The sample block 302 may include at least one locking member 310, and the stage, base, or tray 306 may include at least one corresponding locking member 312. The locking members 310 and 312 are preferably configured to engage with each other to prevent removal from the stage 306. Additionally or alternatively, the locking members 310 and 312 may be configured to align the sample block 302 with and / or fit it to the stage 306. In the illustrated embodiment, the locking member 310 includes a track member and a pair of latching members attached to or integral with the track member. Alternatively, the locking member 310 may include a single latching member or three or more latching members. In the illustrated embodiment, the locking member 312 includes a track member and a pair of latching members attached to or integral with the track member, wherein each latching member is configured to slide on and / or interlock with a corresponding latching member. Alternatively, the locking member 312 may include a single latching member or three or more latching members. As seen in the illustrated embodiments, sample block 302 preferably includes two locking members 310 located on opposite sides of sample block 302, while stage 306 includes two corresponding locking members 312 located on opposite sides of stage 306. In some embodiments, sample block 302 includes a single locking member 310 located on one side of sample block 302, while stage 306 includes a corresponding locking member 312 located on the same side of stage 306. As further discussed herein, locking members 310, 312 can be controlled by a controller to be in a locked configuration, such as when sample holder 316 is being exchanged, or in an unlocked configuration, such as when sample block 302 and / or mating hot caps (e.g., cap 800) are being exchanged. The sample holder 316 may additionally include a sample holder radio frequency identification (RFID) tag 318 containing information or data about the sample holder 316, reagents, dyes, or other chemicals contained in or on the sample holder 316, the history of the sample holder's use, measurement parameters, or instructions, etc. In some embodiments, the sample block 302 and / or the sample holder 316 include sensors 320 and / or 320' that communicate with the sample holder RFID tag 318. Additionally or alternatively, the sensor 320' may be located on the hot block 305.

[0071] As in Figure 10B As seen in some embodiments, system 1000 may optionally include at least one reagent container 1030 containing a reagent container RFID tag 1032. The contents of reagent container 1030 may be added to at least some reaction sites 317 in preparation for assay.

[0072] Figure 4A The illustration shows a closed position or configuration (e.g., retracted or engaged) according to an example embodiment. Figures 3A to 3B A cross-sectional view of the block assembly 300. When the block assembly 300 is in the closed position, the sample block 302 and the cap or heated cap are in a position for performing measurements on the sample holder 316. Figure 4B A cross-sectional view of the block assembly 300 in an open position or configuration (e.g., extended or retracted) is shown. In some embodiments, when the block assembly 300 is in the open position, the sample holder 316 can be replaced with a different sample holder 316; however, the sample block 302 remains locked to the stage 306, and the cover 800 is held by the cover stage 710 and retained inside the housing 1001 of the system 1000. In an alternative embodiment, when the block assembly 300 is in the open position, the sample block 302 and the hot cover are detached from their respective stages, and therefore, the sample holder 316, the sample block 302, and the hot cover are all available for replacement. In one embodiment, a driver, actuator, or drive mechanism 402, such as a stepper motor and worm gear, is operable to drive the movable base 308 and the stage, base or tray 306, and the sample block 302 mounted thereon, to slide back and forth between an open position and a closed position one or more predetermined distances relative to the support structure 301. A controller can be used to automate the operation of the drive mechanism. At least one sensor can be used to detect the position of the block assembly 300 to provide feedback to the drive mechanism 402. In the open position, the sample block 302 can be placed on or removed from the stage 306, thereby allowing a sample block to be replaced or replaced with another sample block having a different construction and / or configured to accommodate different types of sample holders while the system 1000 is still powered (e.g., while power is still being supplied to the current sample block 302 and / or the heated cap). In the closed position, normal operations involving the sample block 302 can be performed.

[0073] Figure 5A An example embodiment is shown. Figures 3A to 3B A cross-sectional view of a block assembly 300 having a sample block 302 detached from a movable base 308. Figure 5B A cross-sectional view of a block assembly 300 having a sample block 302 engaging with a movable base 308 is shown. For example, a driver, actuator, or drive mechanism 502, such as in the form of a can-stacking linear actuator, can drive a first connector member 504 (e.g., a concave connector) linked to the movable base 308 to engage / disengage horizontally with a second connector member 506 linked to the sample block 302. When the first connector member 504 and the second connector member 506 are engaged with each other, movement of the sample block 302 relative to the movable base 308 is prevented or minimized.

[0074] To further position and fix the sample block 302 relative to the base and prevent the sample block 302 from shifting during operation, as referenced above... Figure 3A As described in D and also Figure 6A Additional locking features are provided in the example embodiments shown in section B. In one embodiment, when the drive mechanism 502 (see section B) Figures 5A to 5B The first connector component 504 (see...) Figures 5A to 5B Oriented toward the second connector component 506 (see Figures 5A to 5B When moved, locking members 310 and 312 engage with each other. Locking members 310 and 312, together with connector members 504 and 506, help to hold the sample block 302 in place.

[0075] Figure 7 A perspective view of an optical module or component 700 and a cover stage 710 according to an example embodiment is shown. The cover stage 710 and / or optical component 700 may be attached to and / or supported by a frame 704. An extendable bellows 708 is disposed between the optical component 700 and the cover stage 710. For example, the bellows 708 is connected at one end to the optical component 700 and at the other end to the cover stage 710. A driver, actuator, or drive mechanism 712 is configured to vertically move the cover stage 710 up and down, as will be referred to below. Figures 8A to 8D Further detailed description.

[0076] When the cover stage 710 is lowered, the bellows 708 extends, and when the cover stage 710 is raised, the bellows 708 collapses. The bellows 708 provides a housing between the top of the cover stage 710 and the optical module 700, such that when the cover stage is in the extended, lowered position, the bellows 708 provides optical isolation from retained light from external sources that could otherwise introduce noise at the optical sensor during measurement. Advantageously, the bellows 708 facilitates the disclosed configuration that allows the heavier sample block 302 to be translated along the horizontal axis to place or replace the sample holder and / or sample block, while the lighter heated cover can be translated along the orthogonal axis to engage during preparation for operation or measurement using the system 1000 and during operation or measurement using the system 1000. Figure 10A As seen in the image, the frame 704, including the optical assembly 700 and the cover stage 710, can be attached or mounted to the support structure 301 for holding and transporting the hot block assembly. This provides two separate uniaxial translation systems (one for transporting the hot block assembly, and another for placing the cover 800 onto the hot block assembly). It has been found that this arrangement provides more precise alignment of the cover 800 to the reaction site 317 of the sample holder 316 compared to more complex systems involving a biaxial arrangement.

[0077] Figures 8A to 8DA cross-sectional view of the operation of the cover platform 710 according to an example embodiment is shown. Figures 8A to 8B An alternative cross-sectional view is shown when the cover stage 710 is lowered onto a heated cover mounted on a block assembly (not shown), such as block assembly 300 discussed above. In one embodiment, the cover stage 710 includes a plurality of alignment pins 802a, 802b (typically at least two such alignment pins) to align or approximately align the cover stage 710 with the heated cover. Specifically, the alignment pins 802a, 802b help ensure alignment between a third connector member 804 on the cover stage 710 and a fourth connector member 806 on the heated cover. Additionally or alternatively, the alignment pins 802a, 802b are used to align or fit the sample block 302 onto the cover stage 710. In some embodiments, the upper portions of the alignment pins 802a, 802b are inserted into corresponding through-holes or cylinders in the system 1000 to align or fit the cover stage 710 and the sample block 302 onto or fit the system 1000 (e.g., align the optical assembly 700). The third connector component 804 and the fourth connector component 806 may include electrical contacts to provide electrical communication and / or power to the heated cover. The cover platform 710 also includes a clamping mechanism comprising clamping arms 808a, 808b driven by a driver, actuator, or drive mechanism 810. The clamping arms 808a, 808b open as the cover platform 710 moves downward toward the heated cover. Figure 9B As seen in the illustration, there are two clamping arms 808a and two clamping arms 808b in the illustrated embodiment. In other embodiments, there may be one, three, or more clamping arms 808a, 808b.

[0078] Figure 8C A cross-sectional view is shown when the cover platform 710 contacts the heated cover. At this time, the third connector component and the fourth connector component ( Figure 8C (Not shown in the image) engagement. Furthermore, clamping arms 808a and 808b are actuated to close and generate an active clamping force on the hot cover to securely hold it. Thus, the hot cover is fully engaged with the cover platform 710 via the third connector member 804, the fourth connector member 806, and the clamping arms 808a and 808b. From this state, the drive mechanism 712 can move the cover platform 710 and the engaged hot cover upwards as shown in the image. Figure 8D The indicated elevation position.

[0079] Figures 9A to 9K Various views of the cover platform 710, drive mechanism 810, and clamping arms 808a and 808b are shown. (Reference) Figures 9A to 9C The cover platform 710 includes a carrier plate 900 that engages with the top surface of the hot cover and a drive mechanism 810 configured to rotate the clamping arm 808 via a link 905. Figure 9AA partial cross-sectional view of the drive mechanism 810 according to an example embodiment is shown. The drive mechanism 810 can control the movement of clamping arms 808a, 808b via corresponding links 905 shown in FIG. 9. Additionally, the drive mechanism can actuate a push rod to apply a downward force to a corresponding portion 915. Portion 915 is connected to a fourth connector member 806. Thus, the drive mechanism 810 can disengage the third connector member 804 and the fourth connector member 806 while opening the clamping arms 808a, 808b, thereby disengaging the heat cover from the cover platform 710. In some embodiments, the carrier plate 900 includes a push rod that can be coupled to the carrier plate 900 (e.g., using adhesives, bolts, fasteners, etc.), and this push rod is part of the integral structure of the carrier plate 900. Additionally or alternatively, the third connector component 804 and the fourth connector component 806 can be disengaged using a drive mechanism 712, for example, by separating the cover platform 710 from the hot cover, which can be achieved by lifting the cover platform 710 away from the hot cover.

[0080] Figures 9E to 9H A preferred embodiment of the operation of the drive mechanism 810 is illustrated. For simplicity, the mating heat cover is not shown. Figure 9E A first configuration of the drive mechanism 810 and the cover stage 710 is shown, wherein the clamping arms 808a, 808b are in a closed position suitable for, for example, holding the hot cover during measurement or biological testing. Figure 9F A second configuration of the drive mechanism 810 and the cover stage 710 is shown, wherein the drive mechanism 810 is lower relative to the rotation axis of the clamping arms 808a, 808b. As a result of this relative movement, the clamping arms 808a, 808b are now in an open position suitable for releasing the hot cover, for example, in preparation for replacing the hot cover and / or sample block 302 with a different hot cover and / or sample block 302 (e.g., replacing the 96-well format hot cover and sample block 302 with a 384-well or 384 array card format hot cover and sample block 302). Figure 9G A third configuration of the drive mechanism 810 and the cover platform 710 is shown, wherein the drive mechanism 810 is further lowered relative to the axis of rotation of the clamping arms 808a, 808b. As a result of this relative movement, the clamping arms 808a, 808b can now extend beyond the open position in the second configuration. Movement between the second and third configurations actuates the push rod to apply a downward force, thereby disengaging the third connector member 804 and the fourth connector member 806, as described above.

[0081] Further reference Figure 9H It has been found that, through proper design of the interface between the heat cap and the clamping arm 808, the heat cap can be more accurately aligned with the optical assembly 700. For example, it has been found that the tilt angle of the interface can be selected. This is to provide the desired lateral accuracy or repeatability in positions along the X and Y axes of a plane parallel to the upper surface 303. That is, the sample block 302 can be removed from the system 1000 and then returned to the system 1000 with accuracy or repeatability within a predetermined range. For example, in a preferred embodiment, tilted interface angles from 30 degrees to 50 degrees have been found. It provides lateral accuracy or repeatability of 200 micrometers or less. For an optical system scaled down by 20 times, this is equivalent to the accuracy or repeatability of an imaging sensor with a 10-micrometer sensor size. In another preferred embodiment, tilt interface angles from 30 to 50 degrees have been found. Provides lateral accuracy or repeatability of less than or equal to 100 micrometers.

[0082] Further reference Figure 9J Up to K, it has been found that the initial alignment of the cover stage 710 with the optical assembly 700 and the block assembly 300 is critical. For example, in some embodiments, the cover 800 includes an array of microlenses that focuses excitation light or electromagnetic radiation from an excitation source into each reaction site 317 of the sample holder 316. The lateral positioning of the microlens array on two axes in the horizontal plane determines the location of the focal point of each microlens within the corresponding reaction region 317. To facilitate the initial alignment of the microlens array with the block assembly 300 and / or the sample block, the cover stage 710 may include an upper plate or assembly 920 and a lower plate or assembly 925. During the mounting and / or alignment of the cover stage 710 into the system 1000, the upper plate 920 may be mounted or secured to the frame of the system 1000 (e.g., mounted or secured to the optical assembly 700). The lower plate 925, to which a heat-sealed cover is mounted or engaged during use, is movably mounted or attached to the upper plate 920. Then, for example, when the heated cover or its alternative is used, the lower plate 925 can be moved horizontally along one or both axes to position the lower plate in a position such that light or radiation from the excitation source is properly positioned within the aperture or reaction site 317 of the sample holder 316. Once the microlens array of the heated cover is aligned with the aperture or reaction site 317, the lower plate can be locked or secured to the upper plate.

[0083] In some embodiments, the lower plate 925 includes at least two alignment pins 930 for aligning or fitting the heat-sealed cap to the lower plate. As discussed above, the upper portions of the alignment pins 802a, 802b are inserted into corresponding through-holes or cylinders in the system 1000 to align or fit the cover stage 710 (more specifically, the upper plate 920) to the system 1000 (e.g., to align the optical assembly 700). Additionally or alternatively, the alignment pins 802a, 802b are used to align or fit the upper plate 920 of the sample block 302, and thus align or fit the system 1000. The lower plate 925 is used to adjust the alignment microlens array of the heat-sealed cap to the aperture or reaction region of the sample block 302, as discussed above. Thus, the pins 802a, 802b are used to approximately align the microlens array with the aperture or reaction region of the sample block 302, and the adjustable lower plate is used to provide a more accurate or precise alignment of the microlens array with the aperture or reaction region of the sample block 302.

[0084] The system based on this teaching can perform automated operations to install and replace / remove sample block 302 and the heat cap as needed. Some examples are now described with reference to Figures 3 through 9.

[0085] In one example of installing sample block 302 and the hot cap, block assembly 300 is initially in the open position when the user initiates the installation sequence. Depending on this configuration, the hot cap may have been pre-placed on sample block 302, or they may be placed together in situ. Alignment features help to correctly position the hot cap relative to sample block 302. One or more sensors may also be used to determine the presence and / or orientation of the hot cap on top of sample block 302. Sample block 302, along with the hot cap, is then placed into the stage, base, or tray 306 of block assembly 300.

[0086] Understandably, the above steps can be performed by an operator or, alternatively, by the articulated arm. In the latter case, the articulated arm can be remotely controlled by an operator or can be programmed to perform tasks autonomously.

[0087] Once the system can confirm the presence of sample block 302 and the heated cap, the remaining steps of the installation sequence can be executed automatically. For example, the drive mechanism 402 (see...) Figure 4A The block assembly 300 is pulled to the closed position. There, the drive mechanism 712 (see...) Figure 7 Move the cover platform 710 downwards (see below) Figure 7 The sample block 302 is effectively secured when the clamping arms 808a and 808b close onto the hot cover and the cover stage 710 applies clamping force to the hot cover mounted on the sample block 302.

[0088] When sample block 302 is held in the appropriate position, drive mechanism 502 (see...) Figure 5AThe first connector member 504 is moved to engage with the second connector member 506. The same movement causes locking members 310, 312 to engage with each other. As a result, the sample block 302 is secured to the movable base 308.

[0089] After engagement is complete, the drive mechanism 712 moves the cover plate 710, which is engaged with the heat-sealed cover, to an elevated position, ready for deployment. For example, an operator can begin a PCR experiment, and before the cover plate 710 descends to begin thermal cycling, the block assembly 300 can extend to an open position to load the sample holder, and then be pulled to a closed position.

[0090] In another example of removing sample block 302 and the hot cap, when the operator initiates the removal sequence, block assembly 300 may initially be in the closed position while the hot cap is in the raised position. The system can automatically operate drive mechanism 712 to lower the hot cap onto sample block 302. Once the hot cap is detected to be on top of sample block 302, clamping arms 808a, 808b open to release the hot cap. Furthermore, drive mechanism 810 (see Figure 8) causes push rods to apply a downward force to disengage the third connector member 804 and the fourth connector member 806 from each other. The cap stage 710 can be pulled to the raised position after separation from the hot cap.

[0091] Individually, the drive mechanism 502 automatically disengages the first connector member 504 and the second connector member 506 from each other, and disengages the locking members 310, 312 from each other. Thus, the sample block 302 with the heat-sealed cap on top is disengaged from the movable base 308, and the drive mechanism 402 can move the sample block 302 to an open position, where the sample block 302 and the heat-sealed cap can be retrieved / removed, for example, by an operator or articulated arm.

[0092] As in Figure 3A As seen in the diagram, system 1000 may also include electronic components 314, which may include one or more controllers or part of one or more controllers configured to control the movement and / or engagement of different components of system 1000. For example, at least some of the electronic components 314 may be configured individually or in combination with electronics of a system outside the housing 1001 communicating with system 1000 to control the movement or engagement of any or all of the following: sample block 302, stage 306, movable base 308, connector members 504 and / or 506, cover 800, third connector member 804 and / or fourth connector member 806, locking member 310 and / or 312, clamping arm 808a, clamping arm 808b, cover stage 710, bellows 708. For example, as... Figure 4A and 4BAs illustrated, at least some of the electronic components 314 may be configured, individually or in conjunction with electronics of a system external to the housing 1001 communicating with the system 1000, to control the movement of the sample block 302 and / or the movable base 308 relative to the support structure 301. Additionally or alternatively, the electronic components 314 may be configured to move the cover 800 and / or the cover stage 710 relative to the sample holder 316 and / or the sample block 302. In some embodiments, the electronic components 314 may be configured to operate the locking member 312 to engage the locking member 310 of the sample block 302, for example, to secure or lock the sample block 302 to the movable base 308 or the stage 306. In some embodiments, the electronic component 314 may be configured to, for example, secure or lock the cover 800 to the cover stage 710 using clamping arms 808a and / or 808b, wherein the cover stage 710 may be used to lift the cover 800 from the sample block 302 before moving the sample block outside the housing 1001 to replace or adjust the sample holder 316. Alternatively, the electronic component 314 may be configured to detach.

[0093] System Integration In addition to the block assembly 300, optical assembly 700, and canopy 710 as described above, system 1000 also includes a rear chassis assembly 1002 that can provide electrical and thermal management for system 1000. Figure 10A and 10B As illustrated, housing 1001 may enclose any or all of the block assembly 300, optical assembly 700, cover platform 710, and / or rear chassis assembly 1002. Housing 1001 may be formed from various components attached to each other, such as Figure 10B The components 1004, 1006, 1008, and 1010 shown are together with the front housing 1012.

[0094] The front housing 1012 also includes a drawer front 1014 and a door positioned above the drawer front. During operation, the drawer front moves forward as the block assembly moves from the closed position to the open position. If only the sample holder 316 is inserted or replaced, the door remains stationary. If the sample block 302 and / or the hot cap is replaced, the drawer front 1014 moves forward, and the door flips open from the top to allow the hot cap to pass through. Alternatively, during this operation, the door may be raised and / or retracted into the system 1000 to allow the hot cap to pass through. As a safety or preventative feature, the door may be configured to move to the open position (e.g., flip or raise) during system 1000 startup. This eliminates the possibility of damage to the system 1000 if, for example, the block assembly 300 was in the open position during a recent power outage (intentionally or accidentally, e.g., due to a power failure). In this case, no damage will occur to the door during or after system startup when the block assembly 300 is retracted into the housing 1001 to the closed position, as the door will be opened or retracted.

[0095] The front housing 1012 includes several input / output features. A display screen 1016 capable of receiving touch input is mounted on the front housing 1012. In one embodiment, the front housing 1012 includes an imaging system comprising one or more cameras that can be configured to detect or recognize the face of a see-through user of the system 1000. The imaging system can be configured to provide or generate one or more outputs if one or more predetermined criteria are met, for example, if the face of the see-through user matches stored data of an individual authorized to use the system 1000 and / or entitled to access certain capabilities of the instrument or information stored in the system 1000 or in a database that the system 1000 has access to. In some embodiments, the imaging system may include a 3D camera module. The 3D camera module is capable of detecting facial expressions and body postures and may be equipped with facial recognition software to automatically recognize the face of a registered user. Additionally or alternatively, the imaging system may be located in other locations, such as in the top or side panels of the system 1000, or one of them.

[0096] Alternatively or additionally, system 1000 may include a voice system 1018, which includes one or more microphones, for example, mounted on the front housing 1012. The voice system 1018 may be equipped with voice recognition software to automatically recognize voice commands from registered users.

[0097] System 1000 and / or front housing 1012 may also include a proximity sensor 1020 to detect an object or individual, such as a user, at a predetermined distance to activate the 3D camera module and the microphone. The proximity sensor can be any proximity sensor, probe, or device known in the art. Thus, in some example embodiments, the hands-free operating system 100 may be operated, for example, via voice commands or body gestures. In some embodiments, the output from the proximity sensor may be used to enable the imaging system and / or voice system 1018. The proximity sensor may be used in environments where two or more instruments 1000 are located in the same laboratory or room. Additionally or alternatively, the output from the proximity sensor 1020 may be used to determine whether the output from the imaging system and / or voice system 1018 will be used to start, power on, or activate system 1000 and / or allow access to certain capabilities of the instruments or information stored in system 1000 or in a database that system 1000 has access to.

[0098] In this way, it is possible to determine whether a user authorized to access two or more instruments 1000 is responding to a voice command or facial recognition signal. For example, if a user provides a voice command to activate or start one of the instruments 1000, or to implement certain functions of the system 1000, only the system 1000 closest to the user will respond. In some embodiments, several authorized users may be in the same laboratory or room, and each system 1000 will respond to each user based on their proximity to one of the corresponding instruments. It is contemplated that such capabilities can be used in other types of bioanalytical or non-bioanalytical instruments that have different capabilities and features than those disclosed herein, but have a proximity sensor 1020 used in the manner just described according to the embodiments discussed herein.

[0099] A pair of speakers 1022 can also be mounted on the front housing 1012 to provide audio updates, warnings, etc., so that the operator does not need to look at the display screen 1016 periodically.

[0100] System 1000 may also include several features to further enhance performance. (See reference) Figure 3C , 3DIn addition to 6A, block assembly 300 further includes at least one pusher member 600 configured to, when in the open position, at least partially elevate the sample holder 316 away from the sample block 302. This prevents the sample holder from sticking to the sample block 302 (as is the case in some existing systems) and facilitates removal of the sample holder from the sample block 302 after experiments, especially when removal is performed by an articulated arm (i.e., a robot). The inventors have found that manual and / or mechanical removal of the sample holder 316 is easier when the pusher member 600 is positioned along the long side of the sample holder 316 corresponding to the L dimension in FIG. 3, rather than on the short side corresponding to the S dimension. For example, after PCR assays using system 1000, the edges of the sample holder 316 bend downward toward the center. It has been found that the bending depth of the long side of the sample holder 316 is greater than the bending depth of its short side. By moving along the long side of the sample holder 316, the bending depth of the short side is greater than that of the long side. Figure 3C The pusher member 600 is placed on the long side corresponding to the L dimension in the sample holder 316, and the gap between the edge of the sample holder 316 and the surface 303 of the sample block 302 is greater than when the pusher member 600 is placed on the long side corresponding to the L dimension in the sample holder 316. Figure 3C The gap corresponds to the S dimension on the short side. This may be because the bending depth along the short side of the sample holder 316 is smaller, and it may also be because the larger bending on the long side will tend to make the sample holder 316 protrude further away from the surface 303.

[0101] Figure 11A A cross-sectional view is shown, illustrating an improved seal in the form of a double-lip seal 1100 attached to the lower surface of the heat cap. Figure 11B An enlarged view of seal 1100 is shown. The double-lip design of seal 1100 avoids the flaring problem and corresponding poor sealing problems that occur in existing systems using prior art single-edge or single-blade seals. These prior art single-blade designs have been found to cause higher pressure at the four corners of the seal during compression when the hot cap is in the downward position. Therefore, the sealing performance decreases with time and repeated use. The disclosed double-lip seal 1100 is configured to provide uniform contact with surface 303 of sample block 302, thereby reducing or minimizing heat loss / interference to or from the external environment. In addition to providing excellent sealing at surface 303, the bellows formed by the double-lip seal also provides additional insulating properties to the seal itself, as the air between the inner and outer walls of the seal provides additional insulation.

[0102] The system 1000 according to this teaching is also capable of detecting the presence of a sample holder on the sample block 302 and reading relevant information about the sample holder. For example, when the cover stage 710 is lowered onto the sample block 302 along with the hot cover before an experimental run, the actual height of the hot cover is monitored via feedback from one or more encoders. Due to the thickness of the sample holder, the height of the hot cover is greater when the sample holder is present than when the sample holder is absent. Therefore, it can then be determined whether the sample holder is present or absent. In some embodiments, one or more such encoders may be used to distinguish different types and / or brands of sample holders already located within the sample block 302 based on thickness differences between different types or brands. Similarly, encoders may be used to determine whether the correct or preferred sample holder is located within the sample block 302.

[0103] refer to Figure 3C , 3D System 1000 may include a first RFID antenna 1200a and a second RFID antenna 1200b communicating with corresponding first devices 1202a and second devices 1202b. Devices 1202a and 1202b may be RFID readers, RFID writers, or a combination of RFID readers / writers. In some embodiments, devices 1202a and 1202b may be combined into a single device communicating with both antennas 1200a and 1202b. Devices 1202a and 1202b, individually or in combination with another system communicating with system 1000, may be configured to read RFID tags 318. The RFID tag 318 and the data contained therein can be used to confirm the presence of RFID, confirm that the correct sample holder is being used, perform a pre-run check before performing a measurement using the system 1000, control the system 1000, and / or run a measurement on the system 1000 (e.g., by providing information about the sample holder 316 and / or reaction site 317 to generate a protocol for use by the system 1000 to run a measurement, experiment, or test on the sample holder 316). In some embodiments, devices 1202a and / or 1202b can be configured to write data generated during a measurement on the system 1000. Additionally, data recorded on the RFID tag 318 during the measurement and / or data already contained on the RFID tag before placement in the system 1000 can be used to process the data generated during the measurement.

[0104] After operation, RFID writers / readers 1202a and 1202b can write information to the sample holder's RFID tag to mark the sample holder in use, preventing the sample holder from being restarted. This information can also be transmitted to remote locations, for example, for inventory control and procurement purposes. These two readers also allow for the detection of the sample holder's orientation. If the user location does not place the sample holder in the correct orientation, the system software can account for angular offsets for display and analysis.

[0105] refer to Figure 13 In some embodiments, method 1300 is used to automatically perform a bioanalysis without user intervention or any further input after an initial instruction has been sent to begin the assay. The inventors have discovered that method 1300 offers unexpected advantages over current practices, in which users must manually input assay protocol information / instructions into the system used to run the assay (e.g., by cross-referencing the sample holder ID to view a database) and / or obtain the assay protocol information / instructions via a network such as a LAN or cloud database. These current practices are not only time-consuming but also less secure because proprietary information resides and / or is sent to a location remote from the instrument performing the assay. In many applications, it is crucial to maintain assay-related input and / or output data in a secure environment to prevent unauthorized access to such data. Using embodiments of the current teachings, all inputs required to configure the assay protocol are kept locally with the sample holder and the sample holder RFID tag. Furthermore, the sample holder RFID tag according to embodiments of this teaching can be configured to receive information related to the outputs from the assay run, such as operating parameters and conditions and / or data generated during the assay run.

[0106] Method 1300 can be used in conjunction with sample holder RFID tags and / or reagent container RFID tags, such as sample holder RFID tag 318 and / or reagent container RFID tag 1032. When a reagent container RFID tag is not present or is used, method 1300 includes elements 1310 and 1320, element 1310 comprising placing a sample holder (e.g., sample holder 316) into or on a bioanalytical system (e.g., system 1000), and element 1320 comprising receiving initial user input from a user to initiate a assay. In some embodiments, the initial user input may also initiate transport and / or positioning of the sample holder, as discussed above herein with respect to the movement of sample block 302 / heat block 305 after the sample holder has been placed into a stage, base, or tray 306.

[0107] Method 1300 further includes element 1330, which includes using one or more antennas associated with the sample holder RFID tag, such as one or two RFID antennas 1200a, 1200b, to read at least some RFID data. Method 1300 further includes element 1340, which includes generating instructions to perform a measurement at least in part based on the read RFID data. After receiving initial user input, method 1300 also includes element 1350, which includes performing a set of steps to perform a measurement on the sample holder without any further input or intervention from the user until the measurement is complete. This set of steps may be included or provided by a protocol that can be configured at least in part based on data contained on the sample holder RFID tag. Optionally, additional input may be made to the measurement protocol after the initial user input, for example, to further customize the protocol.

[0108] In some embodiments of method 1300, system 1000 may include one or more reagent containers, each having its own RFID tag (e.g., reagent container 1030 and reagent container RFID tag 1032). In such embodiments, method 1300 may also include element 1360, which contains information read from the reagent container RFID tag of one or more reagent containers. Method 1300 then includes any or all of elements 1310 to 1350.

[0109] refer to Figure 14 In some embodiments, the method 1400 for performing bioanalysis is used to determine the orientation of a sample holder within the system or instrument, for example, the orientation of a sample holder 316 within sample block 302. Advantageously, this allows, in some embodiments, the sample holder to be loaded without necessarily oriented to match a key. Additionally or alternatively, this can allow the same sample block (e.g., sample block 302) to be compatible with different types of sample holders, such as different types of plates, or with various plates having different form characteristics (e.g., compatible with both 96-well microtiter plates and 4, 8, or 12-well strips).

[0110] Using system 1000 as an example, method 1400 includes element 1410, which includes placing sample holder 316 in or on sample block 302. Method 1400 also includes elements 1420 and 1430, which include determining whether RFID data from RFID tag 318 of sample holder is being detected from one or both of RFID antennas 1200a and 1200b. If neither antenna 1200a nor 1200b receives RFID data, method 1400 includes element 1440 that generates (1) a signal indicating that sample holder 316 does not contain an RFID tag or (2) a signal indicating that sample holder is not present. If other active or passive means are used to determine the presence of sample holder 316, the system is configured to utilize the second option. Additionally or alternatively, the system may be configured to generate or produce an indeterminate signal if the possibility of a faulty RFID tag is suspected (e.g., based on a fuzzy antenna signal, or if other means exist to confirm the presence of an RFID tag on the sample holder).

[0111] Optionally, method 1400 may include element 1450, which includes generating at least one of the following if RFID data is received by one of the RFID antennas: (1) a signal indicating that the sample holder contains sample holder RFID 318 or (2) a signal indicating the orientation of sample holder 316. In some embodiments, the inventors have found that orientation detection is achieved by configuring antennas 1200a, 1200b, sample holder 316 and RFID tag 318 such that when sample holder 316 is received as Figure 3C , 3D In the indicated orientation, the signal from RFID tag 318 is strong enough to be received by antenna 1200a, but the signal to antenna 1200b is too weak to be received. Conversely, if sample holder 316 from... Figure 3C , 3D As shown, if the RFID tag 318 is rotated 180 degrees, the signal from the RFID tag 318 is strong enough to be received by the antenna 1200b, but the signal to the antenna 1200a is too weak to be received. In this way, the orientation of the sample holder 316 can be detected based on the signal or the lack of signal in the antennas 1200a and 1200b. Additionally or alternatively, a single RFID device 1202a or b and / or a single RFID antenna 1200a or b can be used to determine the orientation of the sample holder 316 based on the signal strength received from the RFID tag 318.

[0112] The inventors have discovered that it is advantageous to separate antennas 1200a, 1200b from RFID devices 1202a, 1202b. In some embodiments, communication between antennas 1200a, 1200b and RFID devices 1202a, 1202b is provided by a wire between each antenna and the corresponding RFID device. By separating them in this way, the inventors have discovered that the relatively smaller antennas 1200a, 1200b (compared to devices 1202a, 1202b) can be positioned above the sample holder 316 and / or sample block 302, allowing signals from a relatively small area of ​​the RFID tag to be received by the antenna closer to the RFID tag.

[0113] Optionally, method 1400 may include element 1460, which includes: if RFID data is received by both RFID antennas 1200a and 1200b, then generating (1) a signal indicating that sample holder 316 contains two sample holder RFID tags 318 or (2) a signal indicating the presence of two sample holders 316 with sample holder RFID tags 318.

[0114] In some embodiments, method 1500 using an instrument or system (e.g., system 1000) includes element 1510, which includes querying an activation and / or recognition system to produce a first output, the activation and / or recognition system including one or more of a voice activation and / or recognition system or a face activation and / or recognition system. For example, the activation and / or recognition system may include the image system and / or voice system 1018 discussed above herein.

[0115] Method 1500 further includes element 1520, which includes determining whether the first output meets one or more first predetermined criteria.

[0116] Method 1500 further includes element 1530, which includes querying a proximity sensor to generate a second output. For example, the proximity sensor may include the proximity sensor 1020 discussed herein.

[0117] Method 1500 further includes element 1540, which includes determining whether the second output meets one or more second predetermined criteria.

[0118] Method 1500 further includes element 1550, which includes the ability or data to start, power on, activate or otherwise use the instrument if (1) the first output satisfies one or more first predetermined criteria and (2) the second output satisfies one or more second predetermined criteria.

[0119] In some embodiments, the method 1500 of using the instrument includes methods of starting, powering on, or activating the instrument and / or utilizing or activating certain capabilities of the instrument or utilizing or consenting to access information stored in the system or in a database that the instrument has access to.

[0120] In some embodiments, system 1000 is configured to receive and use any one of two or more pairs of sample blocks and their associated caps to perform bioassays, wherein each pair of sample blocks and its associated cap is configured to receive, support, and / or retain different types of sample holders or sample stages (e.g., different sample volumes, different numbers of samples per sample holder, different sample volume geometries, etc.). For example, refer to... Figure 30 The system 1000 can be configured to accommodate a first sample block and associated cap (e.g., sample block 302 and associated cap 800) for holding a 96-well microtiter plate, and a second sample block and associated cap for holding a 384-well microtiter plate.

[0121] For example, continue to refer to Figure 30 System 1000 can be configured to receive a first sample block (e.g., sample block 1900, which will be discussed in more detail below) and an associated first cap (e.g., cap 1800, which will be discussed in more detail below), and to receive a second sample block (e.g., sample block 2300, which will be discussed in more detail below) and an associated second cap (e.g., cap 2200, which will be discussed in more detail below). In such embodiments, each sample block and associated cap can be configured to provide or allow the generation of a continuity signal or other such signal to or by system 1000. System 1000 can use this signal to confirm that an appropriate or correct pair of sample blocks and associated caps has been provided to system 1000. In the illustrated embodiment, cap 1800 includes a connector 1810 configured to mate with a corresponding connector 1910 of sample block 1900 (e.g., as shown in...). Figure 18 , 19 (As seen in [the diagram]). As discussed in further detail below, connectors 1810, 1910 can be configured to provide electrical continuity between connections when the cap 1800 is placed on the sample block 1900. Detection of this electrical continuity can be used to determine whether the sample block and the associated cap are compatible for use in system 1000. In a similar manner, the cap 2200 in the illustrated embodiment includes a connector 2210 configured to mate with a corresponding connector 2310 of the sample block 2300 (e.g., as seen in [the diagram]). Figure 22 , 23(As seen in the image). As discussed in further detail below, connectors 2210, 2310 can also be configured to provide electrical continuity between connections when the cap 2200 is placed on the sample block 2300. Similarly, detection of this electrical continuity can be used to determine whether the sample blocks and the associated cap are compatible for use in system 1000.

[0122] In some embodiments, the geometry, construction, and / or component connectors in the first and second pairs of sample blocks and caps are configured such that if, for example, the first cap is incorrectly placed on the second sample block and / or the second cap is incorrectly placed on the first sample block, continuity is not generated or provided between the corresponding connectors. In some embodiments, this can be achieved by changing the geometry and / or components of the first and second sample block connectors and / or the geometry and / or components of the first and second cap connectors. In such embodiments, the connectors may be positioned identically in a plane parallel to the opposing surfaces. The inventors have discovered that by configuring the connectors in this way, many of the same parts or components used in manufacturing the first and second sample blocks and / or the first and second caps can be used. Advantageously, this improves manufacturing efficiency and reduces inventory requirements and manufacturing costs because it reduces the number of different parts between the first and second sample block / cap pairs. For example, the housings or shells of caps 1800, 2200 and / or sample blocks 1900, 2300 may be identical. For example, the housings containing connectors 1810, 2210 and / or connectors 1910, 2310 can be identical, and only different connector components or component geometries need to be combined to prevent or avoid electrical discontinuity, etc., when the cover 1800 is not properly positioned on the sample block 2200 or when the cover 1800 is not properly positioned on the sample block 2300. See, for example, Figure 24 and 25 For example, in Figure 24 As seen in the image, when the cover 1800 is placed on the sample block 2300, an air gap 2400 exists between pins 1812 and 2312, thereby preventing or avoiding electrical continuity between the connectors. Similarly, as in... Figure 25 As seen in the image, when the cover 2200 is placed on the sample block 1900, there is an air gap 2500 between pin 1912 and pin 2212, thereby preventing or avoiding electrical continuity between the connectors.

[0123] In the embodiments illustrated above, the first set of sample blocks 1900 / caps 1800 and the second set of sample blocks 2300 / caps 2200 are configured to hold a standard 96-well microtiter plate with wells containing 0.1 mL and a standard 96-well microtiter plate with wells containing 0.2 mL, respectively. Other sample holder types are anticipated.

[0124] In other embodiments, a mismatch between a cover for one type of sample holder or sample stage and a sample block for another type of sample holder or sample stage can be achieved by positioning the connector in a plane parallel to the opposite surface of the cover / sample block of the first matching group, at a different location than the opposite surface of the cover / sample block of the second matching group for different types of sample holders or sample stages. For example, system 1000 can be configured to accommodate a third set of sample block / cover pairs configured to accommodate sample holders or stages different from the first and second sets discussed above. For example, refer again... Figure 30 The third cover of the set may include a third connector 3010, which, as shown, is displaced from the connectors of the first connector 1810 and the second connector 2210 of the first and second covers (e.g., covers 1800, 2200). Because the third connector is in different positions when placed on the first sample block 1900 or the second sample block 2300, there is no continuity between connector 3010 and the connectors of the first sample block 1900 or the second sample block 2300. In this way, the system can detect when any of the three sample blocks is mismatched with the covers configured for use in the system.

[0125] System 1000 can be configured to accommodate a fourth set of sample block / cap pairs, which is configured to accommodate sample holders or stages different from those of the first, second, or third sets discussed above. For example, refer to... Figure 31 The third cover of the group may include a third connector, which, as shown, is displaced from the connectors of the first connector 1810 of the first cover, the second connector 2210 of the second cover, and the third connector 3010 of the third cover. Because the fourth connector is located in different positions when placed on the first, second, and third sample blocks, there is no continuity between connector 3010 and the connectors of the first, second, and third sample blocks. In this way, the system can detect when any of the four sample blocks is mismatched with the cover configured for use in the system.

[0126] In the embodiments illustrated above, the third and fourth sets of sample blocks 2800 / caps 2700 are configured to hold a standard 384-well microtiter plate and a standard 384-well sample card, such as a TaqMan array card manufactured by Thermo Fisher Scientific. In other embodiments, the third set of sample blocks / caps is configured to hold a standard 384-well sample card. Other types of sample holders or stages are anticipated.

[0127] refer to Figures 16 to 21In some embodiments, system 1000 is configured to receive and use with a cover 1800 (e.g., a heated cover), which is configured to be placed on top of sample block 1900. (See also...) Figure 20 As seen in the diagram, sample block 1900 can be configured to drill holes in sample holder 2000 or sample stage. Cover 1800 includes a first connector 1810 and a second connector 1820, the first connector including a first connector element or pin 1812, and the second connector including a second connector element or pin 1822. Sample block 1900 includes a first connector 1910 and a second connector 1920, the first connector including a first connector element or pin 1912, and the second connector including a second connector element or pin 1922. When cover 1800 is placed or fitted onto sample block 1900, first connector 1810 is configured to align and / or engage with first connector 1910, and second connector 1820 is configured to align and / or engage with second connector 1920. Each of the pins or connector elements 1812, 1822, 1912, and / or 1922 can be or is capable of being in electrical communication with an electrical conductor (not shown), such as a wire, cable, or at least a portion of a circuit. In the illustrated embodiment, connectors 1810, 1820, 1910, and 1920 are electrical connectors, and elements 1812, 1822, 1912, and 1922 are conductive elements that make electrical contact with corresponding portions of the circuit.

[0128] The first connector 1910 includes a first connector element or pin 1912 configured to contact a mating member of connector 1820, wherein when the cover 1800 is placed on the sample block 1900, the element or pin 1912 and the mating member of connector 1820 (e.g., a mating connector element or pin, not shown) create a continuous and / or closed circuit. The second connector 1920 includes a second connector element or pin 1924 configured to contact a mating member of connector 1920, wherein when the cover 1800 is placed on the sample block 1900, the connector element or pin 1924 and the mating member of connector 1920 create a continuous and / or closed circuit.

[0129] refer to Figure 17A and 17BThe first connector 1910 further includes a transverse member 1914 configured to engage with a cutout, notch, or groove in the connector 1810 of the cover 1800 when the cover 1800 is placed on the sample block 1900. Similarly, the second connector 1920 further includes a transverse member configured to engage with a cutout, notch, or groove 1824 in the connector 1810 of the cover 1800 when the cover 1800 is placed on the sample block 1900. In some embodiments, the transverse member 1914 and the cutout, notch, or groove are aligned along an axis at a different angle (e.g., perpendicular to the axis) to the transverse member and the cutout, notch, or groove 1824. In this way, the orientation of the cover 1800 to the sample block 1900 can be ensured, because a misalignment of the cover 1800 will not provide electrical continuity.

[0130] like Figure 17 and 17C As shown, the sample block 1900 may further include one or more wave-shaped or corrugated springs 1930, which can be used to push the sample holder 2000 away from the sample block 1900 when the cover 1800 is not placed on the sample block 1900. This configuration contrasts with the push member 600, in which the sample holder 2000 has a different construction and dimensions. Figure 3C and 3D The sample holder 316 is shown in its construction and dimensions. For example, the sample holder 316 can be configured to provide a plurality of sample wells (e.g., 8 or 96 sample wells), each well being configured to have a nominal volume of 0.2 mL, while the sample holder 2000 is configured as a plurality of sample wells (e.g., 8 or 96 sample wells) of a microtiter plate, each well being configured to have a nominal volume of 0.1 mL. The inventors have discovered that the corrugated spring 1930 provides excellent performance in ejecting commercially available 0.1 mL microtiter plates due to the relatively thin edge of the 0.1 mL plate compared to the 0.2 mL plate.

[0131] Figure 18 and 19 This is a perspective view of the cover 1800 and the sample holder. The two dashed lines show the correspondence between connectors 1820, 1920 and connectors 1810, 1910 when the cover 1800 is flipped from the position shown in the figure and placed on top of the sample block 1900. Figure 20 This is a perspective view of sample block 1900, in which a 96-well microtiter plate is placed on the wells of sample block 1900. In some embodiments, sample holder 2000 is configured to hold one or more strips of 4, 8, or 12 wells or vials, such as 8-well sample strip 2010. Figure 21A cross-section of the sample holder 2000 in the sample block 1900 is shown. The corrugated spring 1930 is considered to be in a compressed configuration due to its contact with the bottom edge surface of the sample holder 2000.

[0132] refer to Figures 22 to 23 In some embodiments, system 1000 is configured to receive and use with a cover 2200 (e.g., a heated cover), which is configured to be placed on top of sample block 2300. For example, cover 2200 may comprise cover 800 as shown in Figures 8-D, 9B, C, and H. Reference Figure 22A , 22B Cover 2200 may include a first connector 2210 and a second connector 2220, the first connector including a first connector element or pin 2212, and the second connector including a first connector element or pin 2222. Sample block 2300 includes respective first connectors 2310 and second connectors 2320, the first and second connectors including first connector elements or pins 2312 and second connector elements or pins. Each of the pins or connector elements may be or can be in electrical communication with an electrical conductor (not shown), such as at least a portion of a wire, cable, or circuit. In some embodiments, connectors 2210, 2220, 2310, and 2320 do not include the lateral members and / or cutouts, notches, or grooves discussed above for connectors 1810, 1820, 1910, and 1920.

[0133] refer to Figures 24 to 2 6. As can be seen, the difference between the connector for cap 1800 / sample block 1900 and the connector for cap 2200 / sample block 2300 can be used to prevent cap 1800 from being accidentally placed on sample block 2300, or cap 2200 from being accidentally placed on sample block 1900, because the different construction of the connectors and / or connector elements or pins prevents continuity when the wrong cap is placed on the wrong sample block. The system may include a processor and / or memory containing instructions to inform the user when a mismatch occurs and / or prevent the instrument from receiving sample blocks and caps unless they are correctly paired. The various blocks and caps discussed herein can be used in conjunction with methods for performing biological experiments, tests, or assays.

[0134] In the various embodiments illustrated above, caps 800, 1800, 2200 and sample blocks 302, 1900, 2300 are configured for use with a 96-well microtiter plate. In some embodiments, system 1000 and block assembly 300 may be configured for a sample holder comprising 384 wells and / or 384 array cards, such as the TaqMan array card (TAC) manufactured by Thermo Fisher Scientific. For example, cap 800 and sample block 302 may be configured to receive a microtiter plate comprising 384 sample wells, wherein sample block 302 comprises 384 sample wells or receiving elements 304, and cap 800 comprises 384 corresponding openings for irradiating the 384 wells of the microtiter plate.

[0135] refer to Figures 27 to 29 In some embodiments, system 1000 is configured for use with a cover 2700 (e.g., a heated cover) configured to be placed above or on top of sample block 2800. Cover 2700 and sample block 2800 are configured to receive a TAC comprising 384 sample sites. In the illustrated embodiment, the cover includes 384 openings for allowing optical access to each of the 384 reaction sites of the TAC. In some embodiments, the sample block includes a smooth or flat surface 2830 in thermal contact with the TAC and may be configured to perform thermal cycling of the sample in the TAC or otherwise control the temperature of the sample. In other embodiments, the flat surface 2830 is replaced by a structure comprising 384 sample aperture receiving elements (not shown) configured to receive the 384 reaction sites of the TAC or a similar sample holder.

[0136] In some embodiments, cover 2700 includes a first connector 2710 and a second connector 2720, the first connector including a first connector element or pin 2712 and the second connector including a first connector element or pin 2722. Sample block 2800 includes respective first connectors 2810 and second connectors 2820, the first and second connectors including first connector elements or pins 2812 and second connector elements or pins 2822. In the illustrated embodiment, connectors 2710, 2720, 2810, and 2820 are electrical connectors, and elements 2712, 2722, 2812, and 2822 are elements that make electrical contact with corresponding portions of the circuit.

[0137] refer to Figure 30 In some embodiments, the connector of sample block 1900 for the 384-well microtiter plate is further offset upwards relative to connectors 1910 and 2310 of sample blocks 1900 and 2300 along the vertical axis of the drawing page. (Reference) Figure 31The connector 2810 of sample block 2800 is relative to the connectors 1810, 1910, and 2210 of sample blocks 1900 and 2300, and is also relative to the above. Figure 31 The connector of sample block 1900, referenced in the drawing, is offset further upwards along the vertical axis of the drawing page. Figure 31 It can also be seen that the corresponding connectors for the caps and sample blocks configured for the 384-well microtiter plate are located in the middle between the connectors of cap 2700 / block 2800 and the connectors of caps 1800, 2200 / sample blocks 1900, 2300. Therefore, the connectors for all four sample stage formats are configured to prevent unintentional use of any of the four caps with any of the remaining three sample blocks.

[0138] refer to Figure 32 In some embodiments, the calibration or alignment fixture 3200 is configured to align the sample block 2800 with the optical system of the system 1000. As shown in the illustrated embodiment, the alignment fixture 3200 may include one or more openings or holes 3210 in its top surface, for example, 384 openings corresponding to the 384 openings 2730 in the cover 2700. Further reference Figures 33 to 35 One or more holes 3210 of the alignment fixture 3200 may include a smaller opening 3220 located at the bottom of the hole. In some embodiments, one or more holes 3210 further include a reflective or optically active material (e.g., fluorescent or phosphorescent material) within or at the bottom of the opening. In the illustrated embodiment, the opening 3220 includes an elongated opening or slit that is the location where the sample block 2800 is to be aligned. The opening 3220 may have other shapes, such as circular. The opening 3220 may be centered within the hole 3210 or positioned at different alignment locations.

[0139] In the illustrated embodiment, the opening is offset by 300 micrometers (0.3 millimeters) from the center of the aperture 3210 to compensate for possible air bubbles that could form at the sample entry point into the aperture of the reaction region or in the aperture of the sample holder (e.g., a TaqMan array card). Reference Figure 36 This shows the position and offset alignment of such bubbles. (Reference) Figure 37 The sample block 2800 may include a movable portion 2850 that can detach and move relative to a fixed portion 2860, which can be secured to, for example, a tray 306. In the illustrated embodiment, the movable portion 2850 is aligned or in contact with an adjuster 2870 via a compression spring 2875. During alignment of the movable portion with the system 1000, the adjuster 2870 can be used to change the position of the sample block 2800 relative to the system 1000.

[0140] refer to Figure 38A method 3800 for aligning a sample block 2800 is shown. Method 3800 includes element 3810, which includes releasing a movable portion of the sample block from a fixed portion of the sample block. Method 3800 further includes element 3820, which includes placing an alignment fixture on the sample block. Method 3800 further includes element 3830, which includes positioning the sample block in an instrument (e.g., instrument 1000). Method 3800 also includes element 3840, which includes performing a scan at at least one reactive position of the fixture. Method 3800 further includes element 3850, which includes positioning the movable portion to an alignment position based on the scan. Method 3800 further includes element 3860, which includes securing the movable portion to the fixed portion. Method 3800 also includes element 3870, which includes confirming alignment by scanning at least one reactive position of the fixture. Method 3800 further includes element 3880, which includes removing the fixture from the sample block.

[0141] Method 3800 can be used to align sample block 2800 based on signals received at a detector (e.g., an imaging detector used in system 1000 during measurement). Alternatively, method 3800 can be performed using an instrument specifically configured to perform method 3800. Alignment of sample block 2800 can be based on signals generated during scanning of one or more wells 3210, for example, based on the average location of peak signals from a plurality of wells 3210 (e.g., all 384 wells 3210). In other embodiments, alignment of sample block 2800 can be based on signals generated during scanning of several wells 3210 or a single well 3210, for example, one or more wells 3210 located at or near the center of the array of wells 3210 and / or wells at one or more corners of the array of wells 3210. Reference Figure 40 The image shows the signal from a representative aperture 3210. It can be seen that the peak signal is generated 300 micrometers from the aperture center, which corresponds to the location of the smaller aperture 3220.

[0142] refer to Figure 39 A typical scan 3910 is shown. The peak signal 3920 of scan 3910 indicates a central portion of one of the sample volumes of bore 3210, and the minimum value on either side of the peak signal 3920 can indicate a portion of the alignment fixture 3200 between adjacent bores 3210. Figure 39As indicated, once a local maximum value is determined, the clamp 3200 can be offset or translated by a predetermined amount of 300 micrometers (0.3 millimeters). The offset amount may differ from 300 micrometers, depending on the specific application or a quantity determined by the user. The offset amount may be determined based on the peak signal 3920 from a single aperture 3210, or by the peak signals from two or more apertures 3210, for example, based on the average interval between the peak signals 3920 of multiple apertures.

[0143] refer to Figure 40 The diagram illustrates a typical scan using method 3800, which employs an alignment fixture 3200 with a sample block 2800. Each data point in the graph shows the average signal from 384 openings or holes 3210 of the fixture 3200 at each of 14 data points (0 to 13), corresponding to a gradually increasing offset across the hole 3210 as the movable portion 2850 is moved using the adjuster 2870. A peak signal is recorded at data point 10. The data from positions 11 to 14 can be used to confirm that data point 10 corresponds to the maximum signal resulting from alignment with the smaller opening 3220, and thus corresponds to the desired or predetermined alignment of the sample block 2800. For the illustrated embodiment, the desired or predetermined position is a position offset from the center of the hole or opening 3210. In the illustrated embodiment, the maximum signal corresponds to an offset of 0.3 mm from the center of the hole or opening 3210.

[0144] refer to Figure 41 The diagram illustrates a typical scan using method 3800, which employs an alignment fixture 3200 with a sample block 2800. Scans at positions 0 to 10 are performed in accordance with the above... Figure 40 The same method is used. For positions 11 to 14, the movable part 2850 moves in the direction opposite to data points 0 to 10. In this way, the alignment position is determined based on data points 0 to 10, and then the sample block moves back to the appropriate position where the signal is again maximum at data point 14.

[0145] Those skilled in the art will understand that many variations and / or modifications can be made to the present disclosure as illustrated in the specific embodiments without departing from the scope of the disclosure as broadly described herein. Therefore, the embodiments of the invention are to be considered illustrative rather than restrictive in all respects.

[0146] The following is a list of illustrative embodiments and / or implementations of this disclosure: 1. A bioanalytical system comprising: A sample block configured to hold a biological sample, and a base configured to hold the sample block, the sample block including a first connector; A first driver, the first driver including a second connector; A cover, the cover being positioned to cover the sample block, and a cover stage, the cover stage being configured to hold the cover, the cover including a third connector; A second driver, the second driver including a fourth connector; A controller, communicatively coupled to the first driver and the second driver, is configured to: Use the second driver to align the cap and / or the sample block with the cap stage; The second driver is used to engage the third connector with the fourth connector; The first connector is engaged with the second connector using the first driver; and The sample block is secured and / or locked to the base using the first driver.

[0147] 2. The system according to Embodiment 1, wherein the connector is an electrical connector configured to provide power and / or communication between the system and the sample block and between the system and the cover.

[0148] 3. The system according to embodiment 1 or 2, further comprising: A third driver, to which the controller is communicatively coupled; The controller is configured to use the third actuator to secure and / or lock the cover to the cover platform.

[0149] 4. The system according to embodiment 3, wherein the controller is configured to: The third actuator is used to disengage the cover from the cover platform; and The second driver is used to disengage the third electrical connector from the fourth electrical connector to separate the cover platform from the cover.

[0150] 5. The system according to any one of embodiments 1 to 4, wherein the controller is configured to use the third actuator to disengage the third electrical connector from the fourth electrical connector by moving the linkage from a first position that releases the cover from the cover platform to a second position that separates the third electrical connector from the fourth electrical connector.

[0151] 6. A bioanalytical system comprising: A sample block configured to hold a biological sample, and a base configured to hold the sample block, the sample block including a first connector; A first driver, the first driver including a second connector; A controller, communicatively coupled to the first driver, is configured to: The first connector is engaged with the second connector using the first driver; and The sample block is secured and / or locked to the base using the first driver.

[0152] 7. The system according to Example 6, wherein the connector is an electrical connector configured to provide power and / or communication between the system and the sample block.

[0153] 8. A bioanalytical system comprising: A sample block, the sample block being configured to hold a biological sample; A cover, the cover being positioned to cover the sample block, and a cover stage, the cover stage being configured to hold the cover, the cover including a first connector; A first driver, the first driver including a second connector; A controller, communicatively coupled to the first driver, is configured to: Use the first actuator to align the cap and / or the sample block with the cap stage; and The first driver is used to engage the first connector with the second connector.

[0154] 9. The system according to embodiment 8, wherein the connector is an electrical connector configured to provide power and / or communication between the system and the cover.

[0155] 10. The system according to embodiment 8 or 9, further comprising: A second driver, to which the controller is communicatively coupled; The controller is configured to use the second driver to secure and / or lock the cover to the cover platform.

[0156] 11. The system according to embodiment 10, wherein the controller is configured to: The second actuator is used to disengage the cover from the cover platform; and The first driver is used to disengage the first electrical connector from the second electrical connector to separate the cover platform from the cover.

[0157] 12. The system according to any one of embodiments 8 to 11, wherein the controller is configured to use the third actuator to disengage the third electrical connector from the fourth electrical connector by moving the linkage from a first position that releases the cover from the cover platform to a second position that separates the third electrical connector from the fourth electrical connector.

[0158] 13. The system according to any one of embodiments 1 to 12, wherein the cover is a heat cover.

[0159] 14. A bioanalytical system comprising: A sample block and a base, the base being configured to hold the sample block; A hot cap and a cover platform, the cover platform being configured to hold the hot cap; A first drive mechanism, configured to engage the sample block; A second drive mechanism, configured to engage the heat cover; and A controller, communicatively coupled to the first drive mechanism and the second drive mechanism, The controller is configured to automatically operate the first drive mechanism based on a first command to releasably engage the sample block with the base, and to automatically operate the second drive mechanism to releasably engage the heated cap with the cover stage.

[0160] 15. The system according to embodiment 14, wherein the controller is configured to automatically operate the first drive mechanism based on a second command to disengage the sample block from the base, and to automatically operate the second drive mechanism to disengage the hot cap from the cover stage.

[0161] 16. The system according to embodiment 14 further includes a third drive mechanism and a fourth drive mechanism, wherein, based on the first command, the third drive mechanism is configured to move the base and sample block to an open position, and the fourth drive mechanism is configured to move the hot cover and cover stage to a raised position.

[0162] 17. The system according to embodiment 15, wherein, based on the second command, a third drive mechanism is configured to move the base and sample block to an open position, and a fourth drive mechanism is configured to move the hot cap and cover stage to a lowered position.

[0163] 18. The system according to Example 17, wherein the hot cap is disposed on top of the sample block, between a closed position and an open position.

[0164] 19. The system according to Example 18 further includes at least one sensor configured to determine the presence of the hot cap on the top of the sample block.

[0165] 20. The system according to embodiment 16 further includes at least one first locking member connected to the sample block and at least one second locking member connected to the base, wherein the first locking member and the second locking member are configured to engage with each other to position and fix the sample block when the sample block is engaged with the base.

[0166] 21. The system according to Embodiment 16 further includes a plurality of alignment pins configured to align the cover stage with the sample block in the closed position.

[0167] 22. The system according to embodiment 14 further includes an optical component and an extendable bellows, wherein the bellows is disposed between the optical component and the cover stage.

[0168] 23. The system according to Embodiment 17, wherein: The sample block includes a top surface comprising a two-dimensional array of reaction regions, the two-dimensional array of reaction regions defining a periphery around the reaction regions at the top surface, the periphery comprising a pair of opposing long edges having a first length and a pair of opposing short edges having a second length shorter than the first length; The sample block includes a pair of pushing members that are adjacent to and substantially parallel to the respective long edge of the long edge; The sample block is configured to receive a sample holder; The pusher is configured to at least partially raise the sample holder relative to the sample block when the sample block is in the open position.

[0169] 24. The system according to embodiment 23 further includes an RFID reader configured to read a sample holder RFID tag attached to the sample holder.

[0170] 25. The system according to embodiment 23 further includes a detector configured to detect the presence of the sample holder on the sample block.

[0171] 26. The system according to embodiment 23 further includes a double-lip seal attached to the lower surface of the heat-sealed cap, wherein, in use, the double-lip seal is configured to contact the sample block and sealably surround the sample holder.

[0172] 27. The system according to Embodiment 15, wherein the first command includes an installation command for installing the sample block and the hot cap, and the second command includes a removal command for removing the sample block and the hot cap.

[0173] 28. The system according to embodiment 15, wherein the first command or the second command comprises one of touch input, keyboard input, voice command or gesture.

[0174] 29. A method for mounting a sample block and a heated cap in a bioanalytical system, the method comprising: Place the sample block and the heated cap on the base; Positioning the cover platform to engage the heated cover; In response to confirmation of the presence of the sample block and the hot cap, the cover stage is automatically moved to engage the hot cap.

[0175] 30. The method according to Example 29 further comprises raising the cover stage together with the engaged hot cover to separate the hot cover from the sample block.

[0176] 31. The method according to Example 29, wherein engaging the hot cap with the sample block comprises simultaneously aligning the hot cap with the sample block.

[0177] 32. The method according to embodiment 29, wherein automatically engaging the hot cover with the cover platform comprises moving the cover platform toward the hot cover and simultaneously aligning the cover platform with the hot cover.

[0178] 33. A method for removing a sample block and a heated cap from a bioanalytical system, the sample block being supported by a base, the method comprising: Using a cover stage, the hot cover is automatically lowered onto the sample block simultaneously with the sample block; Disconnect the heated cap from the cover stage, such that the heated cap rests on top of the sample block; and The sample block, together with the heated cover, is automatically moved from the closed position to the open position; and Remove the sample block from the base of the block assembly.

[0179] 34. The method according to embodiment 33 further comprises retrieving the sample block in the open position together with the hot cap.

[0180] 35. The method according to Example 33, wherein automatically lowering the hot cap onto the sample block includes aligning the hot cap with the sample block.

[0181] 36. A bioanalytical system comprising: case; A sample block, which is housed within the housing and configured to receive a sample holder, the sample holder comprising a sample holder RFID tag; A first RFID antenna and a second RFID antenna, the RFID antennas being configured to receive RFID data from the RFID tag of the sample holder during use; At least one RFID reader, the at least one RFID reader being configured to receive the RFID data from the first RFID antenna and being configured to receive the RFID data from the second RFID antenna.

[0182] 37. The bioanalytical system according to Example 36 further includes at least one RFID writer configured to write data on the RFID tag of the sample holder.

[0183] 38. The bioanalytical system according to any one of Examples 36 to 37, wherein the RFID antenna is spatially separated from the at least one RFID reader.

[0184] 39. The bioanalytical system according to Example 38, wherein the RFID antenna communicates with the at least one RFID reader via a wire or cable.

[0185] 40. The bioanalytical system according to any one of Examples 38 to 39, wherein the first RFID antenna is disposed near one side of the sample block, and the second RFID antenna is disposed near a different side of the sample block.

[0186] 41. The bioanalytical system according to any one of Examples 38 to 40, wherein the first RFID antenna is disposed near one side of the sample block and the second RFID antenna is disposed near the opposite side of the sample block.

[0187] 42. The bioanalytical system according to any one of Examples 38 to 41, wherein the sample block has an uppermost surface, the at least one RFID reader is disposed below the uppermost surface, and the RFID antenna is disposed above the uppermost surface.

[0188] 43. The bioanalytical system according to any one of Examples 36 to 42, wherein the system comprises the sample holder and the sample holder RFID tag.

[0189] 44. The bioanalytical system according to Example 43, wherein: The sample holder includes a plurality of spatially separated reaction sites, each of which includes a plurality of features; The sample holder RFID tag includes RFID data, which contains data on the plurality of features for each of the reaction sites; The RFID data contained in the data was at least 8 kilobytes, at least 64 kilobytes, or at least 128 kilobytes.

[0190] 45. The bioanalytical system according to Example 44, wherein the plurality of spatially separated reaction sites comprises at least 96 reaction sites, at least 384 reaction sites, at least 1536 reaction sites, at least 3072 reaction sites, or at least 12,288 reaction sites.

[0191] 46. ​​The bioanalytical system according to any one of Examples 43 to 45, wherein the RFID writer is configured to write measurement information generated during the measurement to the RFID tag of the sample holder, and optionally, the system is configured to use the measurement information to analyze data obtained during the measurement.

[0192] 47. The bioanalytical system according to any one of Examples 43 to 46, wherein said plurality of features includes one or more of the following: Sample holder ID; Sample holder shelf life; Sample holder part number; Sample holder barcode; Sample holder batch number; Sample holder type; Storage temperature and / or storage temperature range; Sample concentration – recommended range; is an E1 pipette support provided? Sales order number; Name of the test and / or its location on the sample holder; Determine ID; Suggested solutions or required solutions; Sample Name Name of the main mixture; Changes to the main mixture; Dye name; Recommendations or requirements regarding the use of filters or filter arrays during measurements on the sample holder; EDT file format and / or EDF file format; Internet link or address; Passive reference dye; Reaction volume; Target name; Dye name; Sample name; Analysis settings; Flag settings; Sample type; Target type; The operating plan includes one or more of the following: hot cap temperature, reaction volume, temperature step size, and temperature stage value; or Hole information for one or more wells, the information including one or more of the target name, dye name, or sample name; reagent name.

[0193] 48. The bioanalytical system according to Example 47, wherein the plate type is characterized by 48, 96, 384, 1536 or 3072 wells or through-holes.

[0194] 49. The bioanalytical system according to any one of Examples 47 to 48, wherein the plate type is characterized in that the volume of the well is 0.1 ml or 0.2 ml.

[0195] 50. The bioanalytical system according to any one of Examples 47 to 49, wherein the RFID data on the sample holder RFID includes rewritable data, the rewritable data comprising one or more of the following: Passive reference dye; Reaction volume; Target name; Dye name; Sample name; Analysis settings; Flag settings; Sample type; Target type; The operating plan includes one or more of the following: hot cap temperature, reaction volume, temperature step size, and temperature stage value; or Hole information for one or more wells, the information including one or more of the target name, dye name, or sample name; reagent name.

[0196] 51. The bioanalytical system according to any one of Examples 36 to 50, further comprising a sensor disposed in or embedded in one or more of the sample holder RFID tag, the sample block, or a thermal block coupled to the sample block.

[0197] 52. The bioanalytical system according to Example 51, wherein the sensor communicates with the sample holder RFID tag.

[0198] 53. The bioanalytical system according to any one of Examples 51 to 52, wherein the sensor comprises one or more of a thermal sensor, an accelerometer, a vibration sensor, a light sensor, and a photodetector.

[0199] 54. The bioanalytical system according to any one of Examples 51 to 53, wherein information from the sensor is written to the sample holder RFID tag at least once during the lifetime of the sample holder.

[0200] 55. The bioanalytical system according to any one of Examples 51 to 54, wherein the sensor is a temperature sensor, the sample holder is configured for PCR assay, and the sample holder RFID tag is configured to record the temperature of the sample holder during one or more thermal cycles during the PCR assay.

[0201] 56. The bioanalytical system according to any one of embodiments 36 to 55, wherein the at least one RFID reader comprises a first RFID reader configured to receive the RFID data from the first RFID antenna and a second RFID reader configured to receive the RFID data from the second RFID antenna.

[0202] 57. The bioanalytical system according to any one of Examples 36 to 56, wherein the system is configured such that during use, when the sample holder is received by the sample block, only one of the RFID antennas is capable of receiving the RFID data.

[0203] 58. The bioanalytical system according to any one of Examples 36 to 57, further comprising a processor and a memory coupled to the processor.

[0204] 59. The bioanalytical system according to Example 58, wherein the memory contains instructions for the following: Verify whether at least one of the first RFID antenna or the second RFID antenna is receiving RFID data or signals; Perform at least one of the following: If no RFID data or signal is received by the first RFID antenna or the second RFID antenna, a signal (1) indicating that the sample holder does not contain an RFID tag and / or a signal (2) indicating that the sample holder does not exist is generated; If RFID data is received by at least one of the RFID antennas, then at least one of the following is generated: (1) a signal indicating that the sample holder contains a sample holder RFID tag and / or (2) a signal indicating the orientation of the sample holder; and If the RFID data is received by both of the RFID antennas, a signal is generated that (1) indicates that the sample holder contains two sample holder RFID tags and / or (2) indicates that there are two sample holders with sample holder RFID tags.

[0205] 60. The bioanalytical system according to Example 59, wherein the orientation of the sample holder is based on the strength of the data or signal from the RFID tag.

[0206] 61. The bioanalytical system according to any one of Examples 58 to 60, wherein the memory contains instructions for: Receive initial user input from a user, the initial user input including at least one of the following: (1) input to load or receive the sample holder in the system, or (2) input to start the measurement; Read at least some of the RFID data; The measurement plan is generated based at least in part on the RFID data read; Upon receiving the initial user input, either (1) the measurement protocol is executed to perform the measurement until the measurement is completed without any further input or intervention from the user, or (2) the measurement protocol is modified based on additional input, and then the modified measurement protocol is executed to perform the measurement until the measurement is completed without any further input or intervention from the user.

[0207] 62. The bioanalytical system according to Example 61 further includes a reagent container containing a reagent container RFID tag, wherein the memory contains instructions for reading information from the reagent container RFID tag and generating the assay protocol based at least in part on the information from the reagent container RFID tag.

[0208] 63. The bioanalytical system according to any one of Examples 58 to 62, wherein the memory contains instructions for the following: Before performing the measurement, an alternative data source is used to confirm or verify the measurement protocol, and if the alternative data source is different from the RFID data, then at least one of the following is performed: modifying the measurement protocol, sending an alarm, or suspending the measurement protocol.

[0209] 64. The bioanalytical system according to any one of Examples 58 to 63, wherein the memory contains one or more instructions for: At least a portion of the RFID data is rewritten using the at least one RFID writer; At least a portion of the RFID data is encrypted using the at least one RFID writer; At least a portion of the RFID data is erased using the at least one RFID writer; Generate a signal indicating the completion of the measurement or operation; Modify data generated during or after the measurement; or Data generated during or after the analysis and measurement.

[0210] 65. A method for performing a bioanalysis, comprising: Provide a bioanalytical system, the bioanalytical system comprising: case; A sample block, which is housed within the housing and configured to receive a sample holder, the sample holder comprising a sample holder RFID tag; A first RFID antenna, configured to receive RFID data from the sample holder RFID tag during use; and At least one RFID reader, the at least one RFID reader being configured to receive the RFID data from the first RFID antenna; Place the sample holder into the bioanalytical system or the bioanalytical system; Receive initial user input from the user to initiate the measurement; At least some of the RFID data are read using the first RFID antenna; Instructions for performing the measurement are generated, at least in part, based on the RFID data read. After receiving the initial user input, a set of steps is performed to perform a measurement on the sample holder until the measurement is completed without any further input or intervention from the user, or (2) additional input is received, and then a set of steps is performed to perform a measurement on the sample holder until the measurement is completed without any further input or intervention from the user.

[0211] 66. The method according to embodiment 65 further comprises: Provide reagent containers that include RFID tags for the reagent containers; Read information from the RFID tag of the reagent container; and The assay protocol is generated based at least in part on the information read from the RFID tag on the reagent container.

[0212] 67. A method for performing a bioanalysis, comprising: Provide a bioanalytical system, the bioanalytical system comprising: case; A sample block, wherein the sample block is disposed within the housing; First RFID antenna; Second RFID antenna; and At least one RFID reader, the at least one RFID reader being configured to receive RFID data from the first RFID antenna and from the second RFID antenna; The sample holder is placed in or on the sample block, and the sample holder may include a sample holder RFID tag; Verify whether at least one of the first RFID antenna or the second RFID antenna is receiving RFID data or signals from the sample holder; Perform at least one of the following: If no RFID data is received by the first RFID antenna or the second RFID antenna, a signal (1) indicating that the sample holder does not contain an RFID tag and / or a signal (2) indicating that the sample holder does not exist is generated; If RFID data is received by at least one of the RFID antennas, then at least one of the following is generated: (1) a signal indicating that the sample holder contains a sample holder RFID tag and / or (2) a signal indicating the orientation of the sample holder; and If the RFID data is received by both of the RFID antennas, a signal is generated that (1) indicates that the sample holder contains two sample holder RFID tags and / or (2) indicates that there are two sample holders with sample holder RFID tags.

[0213] 68. The method according to any one of embodiments 65 to 67, further comprising: Receive initial user input from a user, the initial user input including at least one of the following: (1) input to load or receive the sample holder in the system, or (2) input to start the measurement; Read at least some of the RFID data; Based on the read RFID data, a measurement plan is generated; Upon receiving the initial user input, either (1) the measurement protocol is executed to perform the measurement until the measurement is completed without any further input or intervention from the user, or (2) the measurement protocol is modified based on additional input, and then the modified measurement protocol is executed to perform the measurement until the measurement is completed without any further input or intervention from the user.

[0214] 69. The method according to any one of embodiments 65 to 68, further comprising: Before performing the measurement, an alternative data source is used to confirm or verify the measurement protocol, and if the alternative data source is different from the RFID data, then at least one of the following is performed: modifying the measurement protocol, sending an alarm, or suspending the measurement protocol.

[0215] 70. The method according to any one of embodiments 65 to 69, further comprising: At least a portion of the RFID data is rewritten using the at least one RFID writer; At least a portion of the RFID data is encrypted using the at least one RFID writer; At least a portion of the RFID data is erased using the at least one RFID writer; Generate a signal indicating the completion of the measurement or operation; Modify data generated during or after the measurement; or Data generated during or after the analysis and measurement.

[0216] 71. According to the method of any one of Examples 65 to 70, information generated during the first measurement is written to the RFID tag of the sample holder, and optionally the written information is used to analyze the data obtained during the first measurement.

[0217] 72. The method according to any one of Examples 65 to 71, wherein the first assay is a PCR assay.

[0218] 73. The method according to Example 72, wherein the sample holder includes a temperature sensor, and the method further includes recording the temperature of the sample holder during one or more thermal cycles of the PCR assay.

[0219] 74. A bioanalytical system comprising: case; A sample block, which is housed within the housing and configured to receive a sample holder, the sample holder comprising a sample holder RFID tag; An RFID antenna configured to receive RFID data from the RFID tag of the sample holder during use; An RFID reader configured to receive the RFID data from a first RFID antenna; The RFID antenna is spatially separate from the RFID reader.

[0220] 75. The bioanalytical system according to Example 74, wherein the RFID antenna communicates with at least one RFID reader via a wire or cable.

[0221] 76. The bioanalytical system according to any one of Examples 74 to 75, wherein the first RFID antenna is disposed near one side of the sample block, and the second RFID antenna is disposed near a different side of the sample block.

[0222] 77. The bioanalytical system according to any one of Examples 74 to 76, wherein the first RFID antenna is disposed near one side of the sample block and the second RFID antenna is disposed near the opposite side of the sample block.

[0223] 78. The bioanalytical system according to any one of Examples 74 to 76, wherein the sample block has an uppermost surface, the at least one RFID reader is disposed below the uppermost surface, and the RFID antenna is disposed above the uppermost surface.

[0224] 79. The bioanalytical system according to any one of Examples 74 to 77, wherein the memory contains instructions for: Verify whether the RFID antenna is receiving RFID data or signals; Perform at least one of the following: If no RFID data or signal is received by the RFID antenna, a signal (1) indicating that the sample holder does not contain an RFID tag and / or (2) indicating that the sample holder does not exist is generated; If RFID data is received by the RFID antenna, at least one of the following is generated: (1) a signal indicating that the sample holder contains a sample holder RFID tag and / or (2) a signal indicating the orientation of the sample holder; or If the RFID data is received by the RFID antenna, a signal is generated that (1) indicates that the sample holder contains two sample holder RFID tags or (2) indicates that there are two sample holders with sample holder RFID tags.

[0225] 80. The bioanalytical system according to Example 79, wherein the orientation of the sample holder is based on the strength of the data or signal from the RFID tag.

[0226] 81. A sample holder for biological analysis, comprising: A retainer comprising a plurality of spatially separated reaction sites, each of the plurality of spatially separated reaction sites comprising a plurality of features; A sample holder RFID tag, the sample holder RFID tag being disposed in or on the sample holder, the sample holder RFID tag including RFID data, the RFID data containing data for the plurality of features for each of the reaction locations; The RFID data contained in the data was at least 8 kilobytes, at least 64 kilobytes, or at least 128 kilobytes.

[0227] 82. The sample holder according to Example 81, wherein the plurality of spatially separated reaction sites comprise at least 96 reaction sites, at least 384 reaction sites, at least 1536 reaction sites, at least 3072 reaction sites, or at least 12,288 reaction sites.

[0228] 83. The sample holder according to any one of embodiments 81 to 82, wherein the RFID data on the sample holder RFID includes one or more of the following: Sample holder ID; Sample holder shelf life; Sample holder part number; Sample holder barcode; Sample holder batch number; Sample holder type; Storage temperature and / or storage temperature range; Sample concentration – recommended range; is an E1 pipette support provided? Sales order number; Name of the test and / or its location on the sample holder; Determine ID; Suggested solutions or required solutions; Sample Name Name of the main mixture; Changes to the main mixture; Dye name; Recommendations or requirements regarding the use of filters or filter arrays during measurements on the sample holder; EDT file format and / or EDF file format; Internet link or address; Passive reference dye; Reaction volume; Target name; Dye name; Sample name; Analysis settings; Flag settings; Sample type; Target type; Reagent name; The operating plan includes one or more of the following: hot cap temperature, reaction volume, temperature step value, and temperature stage value. Hole information for one or more wells, the information including one or more of the target name, dye name, or sample name.

[0229] 84. The sample holder according to any one of Examples 83, wherein the plate type is characterized by 48, 96, 384, 1536 or 3072 holes or through holes.

[0230] 85. The sample holder according to any one of Examples 83 to 84, wherein the plate type is characterized in that the volume of the orifice is 0.1 ml or 0.2 ml.

[0231] 86. The sample holder according to any one of embodiments 83 to 85, wherein the RFID data on the sample holder RFID includes rewritable data, the rewritable data comprising one or more of the following: Passive reference dye; Reaction volume; Target name; Dye name; Sample name; Analysis settings; Flag settings; Sample type; Target type; Reagent name; The operating plan includes one or more of the following: hot cap temperature, reaction volume, temperature step value, and temperature stage value. Hole information for one or more wells, the information including one or more of the target name, dye name, or sample name.

[0232] 87. The sample holder according to any one of Examples 81 to 86, wherein the sample holder includes a sensor.

[0233] 88. The sample holder according to Example 87, wherein the sensor communicates with the sample holder RFID tag.

[0234] 89. The sample holder according to any one of Examples 87 to 88, wherein the sensor comprises one or more of a thermal sensor, an accelerometer, a vibration sensor, a light sensor, and a light detector.

[0235] 90. The sample holder according to any one of Examples 87 to 89, wherein information from the sensor is written to the sample holder RFID tag at least once during the lifetime of the sample holder.

[0236] 91. A sample holder according to any one of Examples 87 to 90, wherein the sensor is a temperature sensor, the sample holder is configured for PCR assay, and the sample holder RFID tag is configured to record the temperature of the sample holder during one or more thermal cycles during the PCR assay.

[0237] 92. A bioanalytical system comprising: case; A sample block, wherein the sample block is disposed within the housing; According to any one of Examples 81 to 91, the sample holder is disposed in the sample block or on the sample pack; An RFID antenna configured to receive RFID data from the RFID tag of the sample holder during use; An RFID reader configured to receive the RFID data from a first RFID antenna.

[0238] 93. The bioanalytical system according to Example 92, wherein an RFID writer is configured to write measurement information generated during the measurement to the RFID tag of the sample holder, and optionally, the system is configured to use the measurement information to analyze data obtained during the measurement.

[0239] 94. A bioanalytical system comprising: case; A block assembly comprising a sample block and a base, the base being configured to receive the sample block; A first drive mechanism is configured to generate relative movement between the sample block and the housing along a first axis between a closed position and an open position; A lock, configured to lock the sample block to the base; A processor and memory coupled to the processor, the memory including instructions for: Based on the first command, the lock is operated to provide a locked position in which the sample block is locked to the tray; Based on the second command, the lock is operated to provide an unlocked position in which the sample block is not locked to the tray; The sample block and the base are moved from the closed position to the open position, while the lock is in the locked position or the unlocked position.

[0240] 95. The bioanalytical system according to Example 79, wherein at least one of the commands is provided by a user of the bioanalytical system.

[0241] 96. A method for bioanalysis, comprising: A system is provided, the system comprising: Sample block; A base configured to receive the sample block; A heated cap, configured to be placed on the sample block; A platform configured to receive the heated cover; A processor and a memory coupled to the processor, the memory including instructions for moving the sample block and the base between an open position and a closed position; Attach the heat cap to the platform; The hot cap is separated from the sample block by lifting the stage; The sample block and the base are moved from the closed position to the open position using a drive mechanism; Place the sample plate in the sample block; Using the drive mechanism, the sample block is moved from the open position to the closed position; The heated cap is placed onto the sample block by lowering the stage.

[0242] 97. A method for bioanalysis, comprising: A system is provided, the system comprising: Sample block; A base configured to receive the sample block; A heated cap, configured to be placed on the sample block; A platform configured to engage the heat cap using a joining device; A processor and a memory coupled to the processor, the memory including instructions for moving the sample block and the base between an open position and a closed position; Disconnect the platform from the first hot cover; gripper The first hot cover is separated from the platform by lifting the platform; The first sample block and the first hot cover are moved from the closed position to the open position using a drive mechanism. The second block configuration is provided by at least one of the following: replacing the first sample block with a second sample block or replacing the first heat cap with a second heat cap.

[0243] 98. The method according to embodiment 82, wherein the engagement device includes one or more clamping arms disposed on opposite sides of the stage.

[0244] 99. The method according to any one of embodiments 82 to 83, further comprising: Optionally, the sample plate is placed in the sample block; Using the drive mechanism, the sample block is moved from the open position to the closed position; Lower the platform; The clamping arm is used to lock the stage to the hot cover; Perform qPCR assay; The hot cap is retracted from the sample block by raising the stage.

[0245] 100. A bioanalytical instrument comprising: A proximity sensor, configured to determine the presence or distance of the instrument to a user; An activation and / or recognition system, wherein the activation and / or recognition system comprises at least one of a voice activation and / or recognition system or a facial activation and / or recognition system; A processor and memory coupled to the processor, the memory including instructions for: The activation and / or identification system is queried to generate a first output; Determine whether the first output meets one or more first predetermined criteria; The proximity sensor is queried to generate a second output; Determine whether the second output meets one or more second predetermined criteria; If (1) the first output satisfies one or more first predetermined criteria and (2) the second output satisfies one or more second predetermined criteria, then the instrument is started, powered on, or activated.

[0246] 101. A method for starting, powering on, or activating a bioanalytical instrument, comprising: The system is queried to activate and / or recognize a system to produce a first output, the activation and / or recognition system comprising one or more of a voice activation and / or recognition system or a face activation and / or recognition system; Determine whether the first output meets one or more first predetermined criteria; Query the proximity sensor to generate a second output; Determine whether the second output meets one or more second predetermined criteria; If (1) the first output satisfies one or more first predetermined criteria and (2) the second output satisfies one or more second predetermined criteria, then the instrument is started, powered on, or activated.

[0247] 102. A method for starting, powering on, or activating a bioanalytical instrument, comprising: The system is queried to activate and / or recognize a system to produce a first output, the activation and / or recognition system comprising one or more of a voice activation and / or recognition system or a face activation and / or recognition system; Determine whether the first output meets one or more first predetermined criteria; Query the proximity sensor to generate a second output; Determine whether the second output meets one or more second predetermined criteria; If (1) the first output satisfies one or more first predetermined criteria and (2) the second output satisfies one or more second predetermined criteria, then the instrument is started, powered on, or activated.

[0248] 103. A bioanalytical system comprising: One or more of a platform, base, or tray, the platform, base, or tray being configured to interchangeably receive (1) a first block and a corresponding first cover placed on the first block, or (2) a second block and a corresponding second cover placed on the second block; A computer-readable storage device containing instructions for detecting when a second cover is placed on a first block and / or detecting when a first cover is placed on a second block based on the lack of electrical continuity along an electrical path containing one of the blocks and one of the covers.

[0249] 104. The bioanalytical system according to Example 103, wherein the memory further comprises instructions for one or more of the following: Send a message or alarm when the second cover is placed on the first block and / or when the first cover is placed on the second block; To prevent the stage, base, or tray from being received by the analysis system; To prevent the system from performing bioassays.

[0250] 105. The bioanalytical system according to Example 104, wherein: The first block is configured to receive a sample holder containing a biological sample and includes a first connector, the first connector including a first connector element that is in electrical communication with a first electrical conductor; The first cover includes a first cover connector, the first cover connector including a first cover connector element that is in electrical communication with the first cover electrical conductor; The second block is configured to receive a sample holder containing a biological sample and includes a second connector, the second connector including a second connector element that is in electrical communication with a second electrical conductor; The second cover includes a second cover connector, the second cover connector including a second cover connector element that is in electrical communication with the second cover electrical conductor; in: The first cover connector is configured to engage the first block connector to provide electrical continuity between the first block electrical conductor and the first cover electrical conductor; The second cover connector is configured to engage the second block connector to provide electrical continuity between the second block electrical conductor and the second cover electrical conductor; and At least one of the following: (1) the first connector is configured to engage the second cover connector to provide electrical isolation or lack of electrical continuity between the first electrical conductor and the second cover conductor, or (2) the second connector is configured to engage the first cover connector to provide electrical isolation or lack of electrical continuity between the second electrical conductor and the first cover conductor.

[0251] 106. A bioanalytical system comprising: The first block, configured to receive a sample holder containing a biological sample, includes a first connector, the first connector including a first connector element in electrical communication with a first electrical conductor; A first cover, configured to cover the first block, the first cover including a first cover connector, the first cover connector including a first cover connector element in electrical communication with a first cover electrical conductor; The second block, configured to receive a sample holder containing a biological sample, includes a second connector comprising a second connector element in electrical communication with a second electrical conductor. A second cover, configured to cover the second block, the second cover including a second cover connector, the second cover connector including a second cover connector element in electrical communication with the second cover electrical conductor; in: The first cover connector is configured to engage the first block connector to provide electrical continuity between the first block electrical conductor and the first cover electrical conductor; The second cover connector is configured to engage the second block connector to provide electrical continuity between the second block electrical conductor and the second cover electrical conductor; and At least one of the following: (1) the first connector is configured to engage the second cover connector to provide electrical isolation between the first electrical conductor and the second cover electrical conductor, or (2) the second connector is configured to engage the first cover connector to provide electrical isolation between the second electrical conductor and the first cover electrical conductor.

[0252] 107. The system according to any one of embodiments 105 to 106, further comprising a sample holder disposed on or in at least one of the blocks.

[0253] 108. The system according to any one of embodiments 105 to 107, wherein at least one of the blocks includes a wave spring disposed on a surface of at least one of the blocks and configured to apply a force to the sample holder in a direction away from at least one of the blocks.

[0254] 109. The system according to any one of embodiments 105 to 108, wherein one or more of the connector elements are conductive pins, conductive bosses, conductive wire or cable ends, or connector elements.

[0255] 110. The system according to any one of embodiments 105 to 109, wherein one or more of the electrical conductors comprise at least one of at least a portion of a wire, cable, or circuit.

[0256] 111. The system according to any one of embodiments 105 to 110, wherein at least one of the following: The first connector includes a first cavity, and the first cover connector includes a first protrusion configured to at least partially fit inside the first cavity; or The second connector includes a second cavity, and the second cover connector includes a second protrusion configured to fit inside the second cavity.

[0257] 112. The system according to embodiment 111, wherein at least one of the protruding portions is a boss.

[0258] 113. The system according to any one of embodiments 111 to 112, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first cover connector element; The first cavity contains the first connector element; The second protruding portion includes a second annular member, the second annular member including slotted, recessed and / or cut-out wall portions and a second internal volume containing the second cover connector element; The second cavity includes a transverse member configured to fit within the slotted, recessed, and / or cut-out portion and the second connector element.

[0259] 114. The system according to embodiment 113, wherein the transverse member and the second connector element form a single piece.

[0260] 115. The system according to any one of embodiments 113 to 114, wherein the second annular member comprises two slotted, grooved, and / or cut-out wall portions positioned approximately 180 degrees apart around the second annular member.

[0261] 116. The system according to any one of embodiments 113 to 115, wherein: The first cover connector element is recessed a first distance within the first annular part of the first protruding portion; The second connector element protrudes a second distance away from the lateral member, and the second distance is smaller than the first distance.

[0262] 117. The system according to any one of embodiments 113 to 116, wherein: The second cover connector element is recessed a third distance within the second annular part of the first protruding portion; The first connector element protrudes a fourth distance from the base plate of the first cavity, and the fourth distance is smaller than the third distance.

[0263] 118. The system according to any one of embodiments 105 to 110, further comprising: The first block includes a first auxiliary block connector, the first auxiliary block connector including a first auxiliary block connector element that is in electrical communication with the electrical conductor of the first auxiliary block; The first cover includes a first cover auxiliary connector, the first cover auxiliary connector including a first cover auxiliary connector element that is in electrical communication with the first cover auxiliary electrical conductor; The second block includes a second auxiliary connector, the second auxiliary connector including a second auxiliary connector element that is in electrical communication with the second auxiliary conductor; The second cover includes a second cover auxiliary connector, the second cover auxiliary connector including a second cover auxiliary connector element that is in electrical communication with a second cover auxiliary electrical conductor; in: The first cover auxiliary connector is configured to engage the first block auxiliary connector to provide electrical continuity between the first block auxiliary conductor and the first cover auxiliary conductor; The second cover auxiliary connector is configured to engage the second block auxiliary connector to provide electrical continuity between the second block auxiliary conductor and the second cover auxiliary conductor; and Optionally, at least one of the following: (1) the first auxiliary connector is configured to engage the second cover auxiliary connector to provide electrical isolation between the first auxiliary conductor and the second auxiliary cover conductor, or (2) the second auxiliary connector is configured to engage the first cover auxiliary connector to provide electrical isolation between the second auxiliary conductor and the first cover auxiliary conductor.

[0264] 119. The system according to embodiment 118, wherein at least one of the following: The first connector includes a first cavity, and the first cover connector includes a first protrusion configured to at least partially fit inside the first cavity. The second connector includes a second cavity, and the second cover connector includes a second protrusion configured to fit inside the second cavity; The first auxiliary connector includes a first auxiliary cavity, and the first cover auxiliary connector includes a first auxiliary protrusion configured to at least partially fit inside the first auxiliary cavity; or The second auxiliary connector includes a second auxiliary cavity, and the second cover auxiliary connector includes a second auxiliary protrusion configured to fit inside the second auxiliary cavity.

[0265] 120. The system according to embodiment 119, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first cover connector element; The first cavity contains the first connector element; The second protruding portion includes a second annular member, the second annular member including slotted, recessed and / or cut-out wall portions and a second internal volume containing the second cover connector element; The second cavity includes a transverse member configured to fit into the slotted, recessed, and / or cut-out portion and the interior of the second connector element; The first auxiliary protrusion includes a first auxiliary annular member, the first auxiliary annular member having a first auxiliary internal volume containing the first cover auxiliary connector element; The first auxiliary cavity contains the first auxiliary connector element; The second auxiliary protrusion includes a second auxiliary annular member, which includes an auxiliary slotted, recessed, and / or cut-out wall portion and a second auxiliary internal volume containing a second cover auxiliary connector element. The second cavity includes an auxiliary transverse member configured to fit inside the auxiliary slotted, recessed, and / or cut-out portion and the second auxiliary connector element.

[0266] 121. The system according to embodiment 120, wherein when the orientation of the second cover relative to the second block does not match a predetermined or expected orientation of the second cover relative to the second block, the second block cavity and the second auxiliary protrusion of the second cover create electrical isolation or lack of electrical continuity between the second block electrical conductor and the second cover auxiliary electrical conductor.

[0267] 122. The system according to embodiment 121, wherein the orientation of the second cover relative to the second block is rotated 180 degrees from the predetermined or intended orientation of the second cover relative to the second block.

[0268] 123. The system according to any one of embodiments 120 to 122, wherein: The transverse member of the second cavity is positioned along the first axis; The auxiliary transverse member of the second auxiliary cavity is positioned along a second axis, which is oriented at a different angle from the first axis; The grooved, recessed, and / or cut-out wall portions of the annular part of the second protruding member are arranged around the ring of the annular part along the first axis; The auxiliary grooved, recessed, and / or slitted wall portion of the auxiliary annular member of the second auxiliary protruding member is arranged around the ring of the annular member along the second axis.

[0269] 124. The system according to embodiment 123, wherein the second axis is orthogonal or approximately orthogonal to the first axis.

[0270] 125. The system according to any one of embodiments 113 to 124, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member.

[0271] 126. The system according to any one of embodiments 120 to 124, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member. The first auxiliary annular component includes auxiliary grooved, recessed, and / or cut-out wall portions; The first cavity includes an auxiliary transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member.

[0272] 127. The system according to embodiment 126, wherein: The transverse member of the first cavity is positioned along the third axis; The auxiliary transverse member of the first auxiliary cavity is positioned along a fourth axis, which is oriented at a different angle from the third axis; The grooved, recessed, and / or cut-out wall portions of the annular part of the first protruding member are arranged around the ring of the annular part along the third axis; The auxiliary grooved, recessed, and / or cut-out wall portion of the auxiliary annular member of the first auxiliary protruding member is arranged around the ring of the annular member along the fourth axis.

[0273] 128. The system according to embodiment 127, wherein the fourth axis is orthogonal or approximately orthogonal to the third axis.

[0274] 129. The system according to any one of embodiments 105 to 110, wherein at least one of the following: The first cover connector includes a first cover cavity, and the first block connector includes a first protrusion configured to at least partially fit inside the first cover cavity; or The second cover connector includes a second cover cavity, and the second block connector includes a second protrusion configured to fit inside the second cover cavity.

[0275] 130. The system according to embodiment 129, wherein at least one of the protrusions is a boss.

[0276] 131. The system according to any one of embodiments 129 to 130, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first connector element; The first cover cavity includes the first cover connecting element; The second protruding portion includes a second annular member, the second annular member including slotted, recessed and / or cut-out wall portions and a second internal volume containing the second connector element; The second cover cavity includes a transverse member configured to fit within the slotted, recessed, and / or cut-out portion and the second cover connector element.

[0277] 132. The system according to embodiment 131, wherein the transverse member and the second cover connector element form a single piece.

[0278] 133. The system according to any one of embodiments 113 to 132, wherein the second annular member comprises two slotted, grooved, and / or cut-out wall portions positioned approximately 180 degrees apart around the second annular member.

[0279] 134. The system according to any one of embodiments 113 to 133, wherein: The first connector element is recessed a first distance within the first annular part of the first protruding portion; The second cover connector element protrudes a second distance away from the lateral member, the second distance being smaller than the first distance.

[0280] 135. The system according to any one of embodiments 113 to 134, wherein: The second connector element is recessed a third distance within the second annular part of the first protruding portion; The first cover connector element protrudes a fourth distance from the bottom plate of the first cover cavity, and the fourth distance is smaller than the third distance.

[0281] 136. The system according to any one of embodiments 105 to 110, further comprising: The first cover includes a first auxiliary cover connector, the first auxiliary cover connector including a first auxiliary cover connector element that is in electrical communication with the first auxiliary cover electrical conductor; The first block includes a first auxiliary connector, the first auxiliary connector including a first auxiliary connector element that is in electrical communication with the first auxiliary conductor; The second cover includes a second cover auxiliary connector, the second cover auxiliary connector including a second cover auxiliary connector element that is in electrical communication with a second cover auxiliary electrical conductor; The second block includes a second auxiliary connector, the second auxiliary connector including a second auxiliary connector element that is in electrical communication with the second auxiliary conductor; in: The first auxiliary connector is configured to engage the first cover auxiliary connector to provide electrical continuity between the first cover auxiliary conductor and the first auxiliary conductor; The second auxiliary connector is configured to engage the second cover auxiliary connector to provide electrical continuity between the second cover auxiliary conductor and the second auxiliary conductor; and Optionally, at least one of the following: (1) the first cover auxiliary connector is configured to engage the second block auxiliary connector to provide electrical isolation between the first cover auxiliary conductor and the second auxiliary conductor, or (2) the second cover auxiliary connector is configured to engage the first block auxiliary connector to provide electrical isolation between the second auxiliary cover auxiliary conductor and the first auxiliary conductor.

[0282] 137. The system according to embodiment 136, wherein at least one of the following: The first cover connector includes a first cover cavity, and the first block connector includes a first protrusion configured to at least partially fit inside the first cover cavity; The second cover connector includes a second cover cavity, and the second block connector includes a second protrusion configured to fit inside the second cover cavity; The first cover auxiliary connector includes a first cover auxiliary cavity, and the first auxiliary connector includes a first auxiliary protrusion configured to at least partially fit inside the first cover auxiliary cavity; or The second cover auxiliary connector includes a second cover auxiliary cavity, and the second block auxiliary connector includes a second auxiliary protrusion configured to fit inside the second cover auxiliary cavity.

[0283] 138. The system according to embodiment 137, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first connector element; The first cover cavity includes the first cover connecting element; The second protruding portion includes the second annular member, which includes slotted, recessed, and / or cut-out wall portions and a second internal volume containing a second connector element; The second cover cavity includes a transverse member configured to fit inside the slotted, recessed, and / or cut-out portion and the second cover connector element. The first auxiliary protrusion includes a first auxiliary ring, the first auxiliary ring having a first auxiliary internal volume containing the first auxiliary connector element; The first cover auxiliary cavity includes the first cover auxiliary connector element; The second auxiliary protrusion includes a second auxiliary annular member, which includes an auxiliary slotted, recessed, and / or cut-out wall portion and a second auxiliary internal volume containing the second auxiliary connector element; The second cover cavity includes an auxiliary transverse member configured to fit within the auxiliary slotted, recessed, and / or cut-out portion and the second cover auxiliary connector element.

[0284] 139. The system according to embodiment 138, wherein when the orientation of the second block relative to the second cover does not match the predetermined or expected orientation of the second block relative to the second cover, the second cover cavity and the second auxiliary protrusion of the second block create electrical isolation or lack of electrical continuity between the second cover electrical conductor and the second block auxiliary electrical conductor.

[0285] 140. The system according to embodiment 139, wherein the orientation of the second block relative to the second cover is rotated 180 degrees from the predetermined or intended orientation of the second block relative to the second cover.

[0286] 141. The system according to any one of embodiments 138 to 140, wherein: The transverse member of the second cover cavity is positioned along the first axis; The auxiliary transverse member of the second cover auxiliary cavity is arranged along a second axis, which is oriented at a different angle from the first axis; The grooved, recessed, and / or cut-out wall portions of the annular part of the second protruding member are arranged around the ring of the annular part along the first axis; The auxiliary grooved, recessed, and / or slitted wall portion of the auxiliary annular member of the second auxiliary protruding member is arranged around the ring of the annular member along the second axis.

[0287] 142. The system according to embodiment 123, wherein the second axis is orthogonal or approximately orthogonal to the first axis.

[0288] 143. The system according to any one of embodiments 113 to 141, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cover cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member.

[0289] 144. The system according to any one of embodiments 138 to 141, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cover cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member; The first auxiliary annular component includes auxiliary grooved, recessed, and / or cut-out wall portions; The first cover cavity includes an auxiliary transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member.

[0290] 145. The system according to embodiment 144, wherein: The transverse member of the first cover cavity is positioned along the third axis; The auxiliary transverse member of the first cover auxiliary cavity is positioned along a fourth axis, which is oriented at a different angle from the third axis; The grooved, recessed, and / or cut-out wall portions of the annular part of the first protruding member are arranged around the ring of the annular part along the third axis; The auxiliary grooved, recessed, and / or cut-out wall portion of the auxiliary annular member of the first auxiliary protruding member is arranged around the ring of the annular member along the fourth axis.

[0291] 146. The system according to embodiment 145, wherein the fourth axis is orthogonal or approximately orthogonal to the third axis.

[0292] 147. The system according to any one of Examples 103 to 146, wherein the system comprises a system configured to perform one or more of the following: polymerase chain reaction (PCR) assay, experiment or test; real-time PCR assay, experiment or test; digital PCR assay, experiment or test; DNA amplification assay, experiment or test; sequencing assay, experiment or test; flow cytometry assay, experiment or test; or capillary electrophoresis assay, experiment or test.

[0293] 148. A method for performing bioassays using a bioanalytical system, the method comprising: Place one of the first or second pieces in or on a platform, base or tray; Optionally, a sample holder containing a biological sample may be placed in or on the stage, base, or tray; Place the running cover on the received first or second block, wherein at least one of the following is true: The first block includes a first connector, the first connector including a first connector element in electrical communication with a first electrical conductor, and the first cover includes a first cover connector, the first cover connector including a first cover connector element in electrical communication with a first cover electrical conductor; and / or The second block includes a first connector, the first connector including a first connector element that is in electrical communication with the second electrical conductor, and the second cover includes a second cover connector, the second cover connector including a second cover connector element that is in electrical communication with the second cover electrical conductor; Perform a continuity check; Based on the continuity check, at least one of the following is confirmed: (a) If the first base is in or on the platform, base or tray, then the operating cover is the first cover; (b) If the second base is in or on the platform, base, or tray, then the operating cover is the second cover; (c) If the first base is in or on the platform, base or tray, then the operating cover is not the first cover; (d) If the second base is in or on the platform, base, or tray, then the operating cover is not the second cover; If (a) or (b) is confirmed, then at least one of the following: Load or transport the placed blocks and trays into or to the bioanalytical system; The base and cover are provided to facilitate the operation of signals or messages for biological analysis or determination; Use the bioanalytical system to perform bioanalysis or assays; If (c) or (d) is confirmed, then at least one of the following: Abort the method; Provide a message, signal, or alarm indicating that the base and cover are not in good condition; Provide messages, signals, or alarms to change at least one of the cover or the block; The placed blocks and trays are loaded or transported to or onto the bioanalytical system, but the bioanalysis or assay is not performed.

[0294] 149. The method according to Example 148, wherein the bioanalytical system comprises polymerase chain reaction (PCR) assay, experiment or test; real-time PCR assay, experiment or test; digital PCR assay, experiment or test; DNA amplification assay, experiment or test; sequencing assay, experiment or test; flow cytometry assay, experiment or test; or capillary electrophoresis assay, experiment or test.

[0295] 150. A method for aligning a sample block of a bioanalytical system, comprising: Release the movable part of the block from the fixed part; Place the alignment fixture on the block; Position the block within the instrument; At least one reaction position of the fixture is scanned; The movable part is positioned in the alignment location based on scanning; Optionally, the movable part is fixed to the fixed part; Alignment is confirmed by scanning at least one of the reaction positions of the clamp: Optionally, the clamp may be removed from the block.

[0296] 151. The method according to Example 150, wherein: The alignment fixture includes one or more openings or holes in the top surface of the alignment fixture, which correspond to one or more openings in the cover. One or more of the holes include a smaller opening located at the bottom of the hole.

[0297] 152. The method according to embodiment 150 or 151, wherein the one or more holes further comprise a reflective or optically active material within the opening or at the bottom of the opening.

[0298] 152 The method according to any one of Examples 150 to 152, wherein the opening comprises an elongated opening or slit located at the position where the sample block is to be aligned.

[0299] 152 The method according to any one of embodiments 150 to 153, wherein the opening is centered in the hole or positioned in different alignment positions.

[0300] Those skilled in the art will understand that many variations and / or modifications can be made to the present disclosure as illustrated in the specific embodiments without departing from the scope of the disclosure as broadly described herein. Therefore, the embodiments of the invention are to be considered illustrative rather than restrictive in all respects.

Claims

1. A bioanalytical system comprising: The first block, configured to receive a sample holder containing a biological sample, includes a first connector, the first connector including a first connector element in electrical communication with a first electrical conductor; A first cover, configured to cover the first block, the first cover including a first cover connector, the first cover connector including a first cover connector element in electrical communication with a first cover electrical conductor; The second block, configured to receive a sample holder containing a biological sample, includes a second connector comprising a second connector element in electrical communication with a second electrical conductor. A second cover, configured to cover the second block, the second cover including a second cover connector, the second cover connector including a second cover connector element in electrical communication with the electrical conductors of the second cover; in: The first cover connector is configured to engage the first block connector to provide electrical continuity between the first block electrical conductor and the first cover electrical conductor; The second cover connector is configured to engage the second block connector to provide electrical continuity between the second block electrical conductor and the second cover electrical conductor; as well as At least one of the following: (1) the first connector is configured to prevent electrical continuity between the first electrical conductor and the second cover electrical conductor, or (2) the second connector is configured to prevent electrical continuity between the second electrical conductor and the first cover electrical conductor.

2. The system of claim 1, further comprising a sample holder disposed on or in at least one of the blocks.

3. The system according to claim 1, wherein, At least one of the blocks includes a wave spring disposed on the surface of at least one of the blocks and configured to apply force to the sample holder in a direction away from at least one of the blocks.

4. The system of claim 1, wherein one or more of the connector elements are conductive pins, conductive bosses, conductive wire or cable ends, or connector elements.

5. The system of claim 1, wherein one or more of the electrical conductors comprise at least one of at least a portion of a wire, cable, or circuit.

6. The system according to any one of claims 1-5, wherein at least one of the following: The first connector includes a first cavity, and the first cover connector includes a first protrusion configured to at least partially fit inside the first cavity; or The second connector includes a second cavity, and the second cover connector includes a second protrusion configured to fit inside the second cavity.

7. The system of claim 6, wherein at least one of the protruding portions is a boss.

8. The system according to claim 6, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first cover connector element; The first cavity contains the first connector element; The second protruding portion includes a second annular member, the second annular member including slotted, recessed and / or cut-out wall portions and a second internal volume containing the second cover connector element; The second cavity includes a transverse member configured to fit within the slotted, recessed, and / or cut-out portion and the second connector element.

9. The system of claim 8, wherein the transverse member and the second connector element form a single piece.

10. The system of claim 8, wherein the second annular member comprises two slotted, grooved, and / or cut-out wall portions positioned approximately 180 degrees apart around the second annular member.

11. The system according to claim 8, wherein: The first cover connector element is recessed a first distance within the first annular part of the first protruding portion; The second connector element protrudes a second distance away from the lateral member, and the second distance is smaller than the first distance.

12. The system according to claim 8, wherein: The second cover connector element is recessed a third distance within the second annular part of the second protrusion; The first connector element protrudes a fourth distance from the base plate of the first cavity, and the fourth distance is smaller than the third distance.

13. The system of claim 1, further comprising: The first block includes a first auxiliary connector, the first auxiliary connector including a first auxiliary connector element that is in electrical communication with the first auxiliary conductor; The first cover includes a first cover auxiliary connector, the first cover auxiliary connector including a first cover auxiliary connector element that is in electrical communication with the first cover auxiliary electrical conductor; The second block includes a second auxiliary connector, the second auxiliary connector including a second auxiliary connector element that is in electrical communication with the second auxiliary conductor; The second cover includes a second cover auxiliary connector, the second cover auxiliary connector including a second cover auxiliary connector element that is in electrical communication with a second cover auxiliary electrical conductor; in: The first cover auxiliary connector is configured to engage the first block auxiliary connector to provide electrical continuity between the first block auxiliary conductor and the first cover auxiliary conductor; The second cover auxiliary connector is configured to engage the second block auxiliary connector to provide electrical continuity between the second block auxiliary conductor and the second cover auxiliary conductor; and At least one of the following: (1) the first auxiliary connector is configured to prevent electrical continuity between the first auxiliary conductor and the second cover auxiliary conductor, or (2) the second auxiliary connector is configured to prevent electrical continuity between the second auxiliary conductor and the first cover auxiliary conductor.

14. The system of claim 13, wherein at least one of the following: The first connector includes a first cavity, and the first cover connector includes a first protrusion configured to at least partially fit inside the first cavity. The second connector includes a second cavity, and the second cover connector includes a second protrusion configured to fit inside the second cavity; The first auxiliary connector includes a first auxiliary cavity, and the first cover auxiliary connector includes a first auxiliary protrusion configured to at least partially fit inside the first auxiliary cavity; or The second auxiliary connector includes a second auxiliary cavity, and the second cover auxiliary connector includes a second auxiliary protrusion configured to fit inside the second auxiliary cavity.

15. The system according to claim 14, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first cover connector element; The first cavity contains the first connector element; The second protruding portion includes a second annular member, the second annular member including slotted, recessed and / or cut-out wall portions and a second internal volume containing the second cover connector element; The second cavity includes a transverse member configured to fit into the slotted, recessed, and / or cut-out portion and the interior of the second connector element; The first auxiliary protrusion includes a first auxiliary annular member, the first auxiliary annular member having a first auxiliary internal volume containing the first cover auxiliary connector element; The first auxiliary cavity contains the first auxiliary connector element; The second auxiliary protrusion includes a second auxiliary annular member, which includes an auxiliary slotted, recessed, and / or cut-out wall portion and a second auxiliary internal volume containing a second cover auxiliary connector element; The second cavity includes an auxiliary transverse member configured to fit inside the auxiliary slotted, recessed, and / or cut-out portion and the second auxiliary connector element.

16. The system of claim 15, wherein when the orientation of the second cover relative to the second block does not match a predetermined or expected orientation of the second cover relative to the second block, the second block cavity and the second auxiliary protrusion of the second cover prevent electrical continuity between the second block electrical conductor and the second cover auxiliary electrical conductor.

17. The system of claim 16, wherein the orientation of the second cover relative to the second block is rotated 180 degrees from the predetermined or intended orientation of the second cover relative to the second block.

18. The system according to claim 15, wherein: The transverse member of the second cavity is positioned along the first axis; The auxiliary transverse member of the second auxiliary cavity is positioned along a second axis, which is oriented at a different angle from the first axis; The grooved, recessed, and / or cut-out wall portions of the annular member of the second protruding member are arranged around the ring of the annular member along the first axis. The auxiliary annular portion of the second auxiliary protruding member, having a grooved, recessed, and / or cut-out wall portion, is arranged around the ring of the annular member along the second axis.

19. The system of claim 18, wherein the second axis is orthogonal or approximately orthogonal to the first axis.

20. The system according to claim 8, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member.

21. The system according to claim 15, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member. The first auxiliary annular component includes auxiliary grooved, recessed, and / or cut-out wall portions; The first cavity includes an auxiliary transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member.

22. The system according to claim 21, wherein: The transverse member of the first cavity is positioned along the third axis; The auxiliary transverse member of the first auxiliary cavity is positioned along a fourth axis, which is oriented at a different angle from the third axis; The grooved, recessed, and / or cut-out wall portions of the annular member of the first protruding member are arranged around the ring of the annular member along the third axis; The auxiliary annular portion of the first auxiliary protruding member, having a slotted, grooved, and / or cut-out wall portion, is positioned around the ring of the annular member along the fourth axis.

23. The system of claim 22, wherein the fourth axis is orthogonal or approximately orthogonal to the third axis.

24. The system of claim 1, wherein at least one of the following: The first cover connector includes a first cover cavity, and the first block connector includes a first protrusion configured to at least partially fit inside the first cover cavity; or The second cover connector includes a second cover cavity, and the second block connector includes a second protrusion configured to fit inside the second cover cavity.

25. The system of claim 24, wherein at least one of the protruding portions is a boss.

26. The system according to claim 24, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first connector element; The first cover cavity includes the first cover connector element; The second protruding portion includes a second annular member, the second annular member including slotted, recessed and / or cut-out wall portions and a second internal volume containing the second connector element; The second cover cavity includes a transverse member configured to fit within the slotted, recessed, and / or cut-out portion and the second cover connector element.

27. The system of claim 26, wherein the transverse member and the second cover connector element form a single piece.

28. The system of claim 26, wherein the second annular member comprises two slotted, grooved, and / or cut-out wall portions positioned approximately 180 degrees apart around the second annular member.

29. The system according to claim 26, wherein: The first connector element is recessed a first distance within the first annular part of the first protruding portion; The second cover connector element protrudes a second distance away from the lateral member, the second distance being smaller than the first distance.

30. The system according to claim 26, wherein: The second connector element is recessed a third distance within the second annular part of the second protrusion; The first cover connector element protrudes a fourth distance from the bottom plate of the first cover cavity, and the fourth distance is smaller than the third distance.

31. The system of claim 1, further comprising: The first cover includes a first auxiliary cover connector, the first auxiliary cover connector including a first auxiliary cover connector element that is in electrical communication with the first auxiliary cover electrical conductor; The first block includes a first auxiliary connector, the first auxiliary connector including a first auxiliary connector element that is in electrical communication with the first auxiliary conductor; The second cover includes a second cover auxiliary connector, the second cover auxiliary connector including a second cover auxiliary connector element that is in electrical communication with a second cover auxiliary electrical conductor; The second block includes a second auxiliary connector, the second auxiliary connector including a second auxiliary connector element that is in electrical communication with the second auxiliary conductor; in: The first auxiliary connector is configured to engage the first cover auxiliary connector to provide electrical continuity between the first cover auxiliary conductor and the first auxiliary conductor; The second auxiliary connector is configured to engage the second cover auxiliary connector to provide electrical continuity between the second cover auxiliary conductor and the second auxiliary conductor; and At least one of the following: (1) the first cover auxiliary connector is configured to prevent electrical continuity between the first cover auxiliary conductor and the second auxiliary conductor, or (2) the second cover auxiliary connector is configured to prevent electrical continuity between the second cover auxiliary conductor and the first auxiliary conductor.

32. The system of claim 31, wherein at least one of the following: The first cover connector includes a first cover cavity, and the first block connector includes a first protrusion configured to at least partially fit inside the first cover cavity; The second cover connector includes a second cover cavity, and the second block connector includes a second protrusion configured to fit inside the second cover cavity; The first cover auxiliary connector includes a first cover auxiliary cavity, and the first block auxiliary connector includes a first auxiliary protrusion configured to at least partially fit inside the first cover auxiliary cavity; or The second cover auxiliary connector includes a second cover auxiliary cavity, and the second block auxiliary connector includes a second auxiliary protrusion configured to fit inside the second cover auxiliary cavity.

33. The system according to claim 32, wherein: The first protruding portion includes a first annular member having a first internal volume containing the first connector element; The first cover cavity includes the first cover connector element; The second protruding portion includes a second annular member, the second annular member including slotted, recessed and / or cut-out wall portions and a second internal volume containing a second connector element; The second cover cavity includes a transverse member configured to fit inside the slotted, recessed, and / or cut-out portion and the second cover connector element. The first auxiliary protrusion includes a first auxiliary ring, the first auxiliary ring having a first auxiliary internal volume containing the first auxiliary connector element; The first cover auxiliary cavity includes the first cover auxiliary connector element; The second auxiliary protrusion includes a second auxiliary annular member, which includes an auxiliary slotted, recessed, and / or cut-out wall portion and a second auxiliary internal volume containing the second auxiliary connector element; The second cover cavity includes an auxiliary transverse member configured to fit within the auxiliary slotted, recessed, and / or cut-out portion and the second cover auxiliary connector element.

34. The system of claim 33, wherein when the orientation of the second block relative to the second cover does not match a predetermined or expected orientation of the second block relative to the second cover, the second cover cavity and the second auxiliary protrusion of the second block prevent electrical continuity between the second cover electrical conductor and the second block auxiliary electrical conductor.

35. The system of claim 34, wherein the orientation of the second block relative to the second cover is rotated 180 degrees from the predetermined or intended orientation of the second block relative to the second cover.

36. The system according to claim 33, wherein: The transverse member of the second cover cavity is positioned along the first axis; The auxiliary transverse member of the second cover auxiliary cavity is arranged along a second axis, which is oriented at a different angle from the first axis; The grooved, recessed, and / or cut-out wall portions of the annular member of the second protruding member are arranged around the ring of the annular member along the first axis. The auxiliary annular portion of the second auxiliary protruding member, having a grooved, recessed, and / or cut-out wall portion, is arranged around the ring of the annular member along the second axis.

37. The system of claim 36, wherein the second axis is orthogonal or approximately orthogonal to the first axis.

38. The system according to claim 26, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cover cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member.

39. The system according to claim 33, wherein: The first annular component includes slotted, grooved, and / or cut-out wall portions; The first cover cavity includes a transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first annular member; The first auxiliary annular component includes auxiliary grooved, recessed, and / or cut-out wall portions; The first cover cavity includes an auxiliary transverse member configured to fit inside the slotted, grooved, and / or cut-out portion of the first auxiliary annular member.

40. The system according to claim 39, wherein: The transverse member of the first cover cavity is positioned along the third axis; The auxiliary transverse member of the first cover auxiliary cavity is positioned along a fourth axis, which is oriented at a different angle from the third axis; The grooved, recessed, and / or cut-out wall portions of the annular member of the first protruding member are arranged around the ring of the annular member along the third axis; The auxiliary annular portion of the first auxiliary protruding member, having a slotted, grooved, and / or cut-out wall portion, is positioned around the ring of the annular member along the fourth axis.

41. The system of claim 40, wherein the fourth axis is orthogonal or approximately orthogonal to the third axis.

42. The system of claim 1, wherein the system is configured to perform one or more of the following: polymerase chain reaction (PCR) assay, experiment or test; real-time PCR assay, experiment or test; digital PCR assay, experiment or test; DNA amplification assay, experiment or test; sequencing assay, experiment or test; flow cytometry assay, experiment or test; or capillary electrophoresis assay, experiment or test.

43. The system according to claim 1, wherein, The system also includes a computer-readable storage device containing instructions for detecting when the second cover is placed on the first block and / or detecting when the first cover is placed on the second block based on the lack of electrical continuity along an electrical path containing one of the blocks and one of the covers.

44. The system according to claim 43, wherein, The memory further includes instructions for one or more of the following: Send a message or alarm when the second cover is placed on the first block and / or when the first cover is placed on the second block; To prevent the stage, base, or tray from being received by the analysis system; To prevent the system from performing bioassays.

45. A method for performing bioassays using a bioanalytical system, the method comprising: Place one of the first or second pieces in or on a platform, base or tray; Place the sample holder containing the biological sample in or on the first or second block; Place the running cover on the first or second block, wherein The first block includes a first connector, the first connector including a first connector element that is in electrical communication with the first block electrical conductor, and the first cover includes a first cover connector, the first cover connector including a first cover connector element that is in electrical communication with the first cover electrical conductor. and / or The second block includes a second connector, the second connector including a second connector element that is in electrical communication with the second block electrical conductor, and the second cover includes a second cover connector, the second cover connector including a second cover connector element that is in electrical communication with the second cover electrical conductor; Perform a continuity check; Based on the continuity check, at least one of the following is confirmed: (a) If the first block is in or on the platform, base or tray, and the continuity check results in electrical continuity, then the operating cover is confirmed to be the first cover; (b) If the second block is in or on the platform, base or tray, and the continuity check results in electrical continuity, then the operating cover is confirmed to be the second cover; (c) If the first block is in or on the platform, base or tray, and the continuity check result is a lack of electrical continuity, then the operating cover is confirmed to be not the first cover. (d) If the second block is in or on the platform, base or tray, and the continuity check result is a lack of electrical continuity, then the operating cover is confirmed to be the second cover; If (a) or (b) is confirmed, then at least one of the following shall be performed: Load or transport the placed blocks and trays into or to the bioanalytical system; The base and cover are provided to facilitate the operation of signals or messages for biological analysis or determination; Use the bioanalytical system to perform bioanalysis or assays; If (c) or (d) is confirmed, then at least one of the following shall be performed: Abort the method; Provide a message, signal, or alarm indicating that the base and cover are not in good condition; Provide messages, signals, or alarms to change at least one of the cover or the block; The placed blocks and trays are loaded or transported to or onto the bioanalytical system, but the bioanalysis or assay is not performed.

46. ​​The method of claim 45, wherein the bioanalytical system comprises polymerase chain reaction (PCR) assay, experiment or test; real-time PCR assay, experiment or test; digital PCR assay, experiment or test; DNA amplification assay, experiment or test; sequencing assay, experiment or test; flow cytometry assay, experiment or test; or capillary electrophoresis assay, experiment or test.

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