Patent Application
20220134338
The analysis of samples such as clinical or environmental samples generally involves a series of processing steps, which may include separate chemical, optical, electrical, mechanical, thermal, or acoustical processing of the samples. Many conventional diagnostic assay systems shuttle a sample cartridge or container between various different processing locations at which various steps of sample processing and testing are performed. In some diagnostic apparatuses, such as the GeneXpert by Cepheid, a sample cartridge is processed while the sample remains within a sample cartridge or attached reaction vessel. In the GeneXpert apparatus, the sample cartridge is inserted within a sample processing module that performs the various sample processing steps, typically from sample preparation to analytical testing, after which the spent sample cartridge is removed from the module. Thus, the sample is processed and tested while the sample cartridge remains at a single location within the module. In order to increase sample throughput, such apparatus often include multiple such modules disposed within a common enclosure. The enclosure is equipped with an internal computer and power sources to power and communicate with the individual modules.
Due to the burden and wear-and-tear of sample processing, one or more modules may periodically require maintenance and replacing. Further, over time, components of the module may be replaced or become obsolete and require development of new modules. Accordingly, currently replacing modules requires disassembling the apparatus and individual modules to some extent, which can be time-consuming and require significant down time. Therefore, there is a need for an apparatus that facilitates periodic ready removal, repair and replacement of repaired or updated modules with improved ease of use. Further, performing multiple concurrent assays can be cumbersome and time-consuming such that there is need for improved configurations that improve ease of use.
Some embodiments of the invention relate to a biological sample processing apparatus having an enclosure with multiple processing modules therein.
In one aspect, the invention pertains to an apparatus having readily removable and replaceable processing modules. In some embodiments, the modules can be readily removed from the enclosure manually or with a single tool without requiring disassembly of the module or the enclosure. In some embodiments, replacement entails opening or removing one or more front access panels, while the enclosure itself and internal components therein remain intact. In some embodiments, the front access panel(s) can be removed by removal of less than four screws, typically, a single screw. In some embodiments, the invention pertains to a replacement module having new or improved components that is configured to be backwards-compatible for drop-in replacement in an existing apparatus, such as the GeneXpert systems. In another aspect, the invention pertains to modules configured so that one or more components are readily removable and replacement to allow replacement and improvement with next-generation components as they become available and older components become obsolete.
In some embodiments, the apparatus and modules are configured such that one or more modules, components or component assemblies are readily removable to facilitate repair, update and replacement as needed. In some embodiments, the apparatus components include any or all of: a CPU, including a communication unit and processing unit, and power supplies for individual modules within the enclosure. In some embodiments, the module components include any or all of: a valve drive, a syringe drive, a sonication horn, an instrument assembly, including a thermal cycling unit, or any combination thereof. In some embodiments, any of the above components can be configured to be readily removed and replaced to facilitate repair, update and replacement of the components as needed. In some embodiments, one or more of the components are constructed in a modular manner such that the components can be readily removed without requiring substantial or complete disassembly of the entire apparatus or module. In some embodiments, “without disassembly” means that front access panels can be removed, without disassembly of the enclosure and associated internal components. In some embodiments, the front access panel can be removed upon removal of less than four screws, two or less screws, typically by removal of a single screw. This approach inhibits removal of an unauthorized user without tools, while still allowing for ready removal and replacement of one or more modules.
In another aspect, the module includes additional components and/or functionality to facilitate sample processing that include any or all of: CPU connectivity, module servicing, system sample cartridge identification, a door mechanism for loading/unloading of the sample cartridge and thermocycling units. Sample cartridge identification can include barcode scanners, cameras, NFID or RFID detection, or any suitable identification means. In some embodiments, the module includes one or more features to facilitate and improve CPU connectivity. In some embodiments, the module includes one or more features to facilitate module servicing, including slidable tracks for inserting the module and one or more quick-release mechanisms to allow for ready removal of the module. In some embodiments, the module includes one or more features to facilitate and improve upon the module's thermal cycling ability, such as the use of gradient cooling by independently controlled heaters, or active cooling by a Peltier device. In some embodiments, the module includes one or more features to facilitate and improve upon cooling of the entire apparatus. The cooling features can include a directed airstream concept, including a filtered airstream, a closed/sealed system with non-PCR heating sources removed from the enclosure, and/or thermal conduction by a heat sink, which can include the enclosure housing. In some embodiments, the module includes one or more features to facilitate and improve upon identification of the sample cartridges, such as a barcode scanner within the cartridge receiving bay of the module. In some embodiments, the apparatus includes a central identifier to scan a sample, a cartridge or a user badge. In some embodiments, the system includes a barcode reader within each individual cartridge bay configured to read an inserted sample cartridge and a centralized external barcode reader that is configured to read a user badge, cartridge or sample such that a given user can use either scanner for a given sample cartridge. In some embodiments, the module includes one or more features to facilitate and improve upon the door mechanism for loading/unloading of the sample cartridges.
In another aspect, the module includes one or more features to provide backwards compatibility with earlier apparatuses to allow a user to use new module within an earlier generation apparatus. In another aspect, the modules are configured for forward compatibility with next generation apparatus utilizing next generation modules.
In one aspect, the invention pertains to a plurality of sample processing modules held by the enclosure. Each sample processing module is configured to hold a removable sample cartridge and to only perform sample processing on a sample within the corresponding removable sample cartridge. Each sample processing module can be configured to perform at least one of a plurality of testing processes on the sample within the removable sample cartridge and to perform nucleic acid amplification and detection. Typically, the respective modules are configured to perform sample preparation, nucleic acid amplification and detection. In some embodiments, at least one sample processing module can be configured for hybridizing a nucleic acid to an array on a solid support. In some embodiments at least one sample processing module can be configured for nucleic acid amplification and detection in a multiplex array of wells, wherein each separate well comprises a separate nucleic acid amplification reaction. In some embodiments, each of the separate wells of the multiplex array of wells is capable of carrying out a multiplex reaction (e.g. nested PCR). In some embodiments, at least one sample preparation module can be configured to prepare a sample to undergo a sample processing protocol for at least one nucleic acid. In some embodiments, at least one sample processing module can be configured for detection of at least one protein analyte. In some embodiments, at least one sample processing module can be configured to perform immunoassays. In some embodiments, at least one sample processing module can be configured for assessing a chromosomal copy number of at least one gene of interest. In some embodiments, at least one sample processing module can be configured for performing a multiplex detection of at least two nucleic acid analytes. In some embodiments, at least one sample processing module can be configured for performing a multiplex detection of at least two protein analytes. In some embodiments, at least one sample processing module can be configured for sequencing and detecting a nucleic acid molecule. In some embodiments, the plurality of sample processing modules can include at least one module for detecting at least one protein analyte contained within a biological sample within a test cartridge, at least one module for assessing chromosomal copy number of at least one gene of interest contained within a biological sample within a test cartridge; and at least one module for performing a sample processing protocol for at least one nucleic acid contained within a biological sample within a test cartridge. In some embodiments, the plurality of sample processing modules includes different modules configured for different types of sample processing.
In some embodiments, the plurality of sample processing modules can include at least one module that can be configured for hybridizing a nucleic acid to an array on a solid support and/or at least one module that can be configured for detection of at least one protein analyte and/or at least one module that can be configured for assessing a chromosomal copy number of at least one gene of interest and/or at least one module that can be configured for performing a multiplex detection of at least two nucleic acid analytes and/or at least one module that can be configured for performing a multiplex detection of at least two nucleic acid analytes and/or at least one module that can be configured for performing a multiplex detection of at least two protein analytes and/or at least one module that can be configured for sequencing and detecting a nucleic acid molecule and/or at least one module that can be configured for performing PCR and/or at least one sample processing module that can be configured for performing rapid PCR.
In some embodiments, the plurality of sample processing modules can be up to 16 sample processing modules made up of a combination of modules, which in some embodiments are different types of modules, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 modules (depending on whether other types of modules are included within the plurality). The modules all be of the same type and functionality or can be of differing types, including differing functionality, differing construction and same or similar functionality.
Some embodiments of the invention relate to a method for operating a sample processing apparatus that includes a housing having multiple processing modules therein. In the method, a sample cartridge holding an unprepared sample at one of a plurality of sample processing modules held by an enclosure can be received. As the cartridge is received, an identifier, such as a barcode scanner identifies the sample and sample cartridge. The user can interface with the apparatus by a central display on the enclosure housing and monitor status of the sample processing by the central display. The central display is configured to selectively display information of multiple parameters of the assay being performed, which can include identifying information of a module, a sample cartridge, a patient, an assay, or status information as to a particular assay being performed. The central display is configured to display information as to any of the one or more modules therein upon receiving a selection by a user via the touch display or automatically as needed (e.g. opening of the door, an error occurring, completion of the assay). While the sample is processing, another sample cartridge can be received within another module in the same manner, while the user interfaces with the apparatus via the central display.
Some embodiments of the invention relate to methods of removing and replacing modules within a sample processing apparatus that includes an enclosure housing having multiple processing modules therein. In the method, the user may tilt up a central display, remove any front access panels attached to the front of the enclosure, release one or more quick-release mechanisms and slidably remove one or more modules from the enclosure. A repaired or updated module can be replaced and inserted within the enclosure by sliding the module along one or more tracks and slidably connecting rear facing connectors on the module to plug-in type connectors in the rear of the enclosure.
In another aspect, the system can be configured such that the graphical user interface screen display selectable options that enable the user to remotely access a status, completion or result of the assay, or displays a unique on-screen identifier corresponding to a particular assay being run that, when scanned, enables the user to remotely access a website displaying the status, completion or result of the assay. In some embodiments, the selectable option communicates with a communication unit (e.g. by SMS) a link to the user's device to a website displaying information from a task record of the assay. The communication unit can utilize any of wired or wireless connections (e.g. NFC, Wifi, cellular) or any combination thereof. In some embodiments, the identifier is a URL-linked QR code found on the molecular diagnostic device's screen. The QR code can be scanned by a user's QR-recognizing mobile device, to enable the user to access, via the internet, real-time information from the task record of the assay being performed, thus creating walk-away capabilities to users so that the user can monitor a status and/or result of the assay remotely. In some embodiments, the test status/results may be linked to multiple mobile devices, such as smartphones or tablets. In an exemplary embodiment, the system generates and displays a unique QR code associated with a particular assay, the user captures an image of the QR code with the camera of their mobile device (e.g. smartphone), which allows the user to access a URL that shows the user a status of the test being run—remotely. In other embodiments, the display allows the user to select the option of texting (SMS) or emailing the user a link to the URL to one or more users by which the user(s) can also monitor the assay.
Embodiments of the invention pertain to an apparatus for performing multiple types of assays and related sample preparation. The apparatus can include multiple sample processing modules, typically having, or capable of having up to 15 different types of modules. The modules can be configured for different types of assays (e.g., immunoassay, PCR, rapid PCR, sequencing, chromosomal analysis, and flow cytometry, etc.) for detecting different types of target analytes (e.g., nucleic acid, whole cell, DNA, RNA, protein, virus, drugs, etc.). The apparatus can also include modules dedicated to sample preparation (e.g., lysis, chemical treatment, filtration, etc.). A cartridge-based sample holder is standardized for each type of module, so that in most cases each module can interface with the same cartridge. The modules, regardless of type, can all share the same chassis footprint and electronic interface, such that types of modules can be changed with little difficulty. The enclosure and modules are configured to allow for ready removal and replacement with updated modules or componentry.
As used herein, the term “biological sample” (interchangeable with “test sample” or “sample”) encompasses any material that may contain an analyte of interest (e.g., a particular protein or nucleic acid), often taken from or otherwise derived from a living organism. “Biological samples” may include, but are not limited to, samples of tissues such as biopsy and autopsy samples, and frozen or paraffin embedded sections taken for histological or pathology purposes. Such samples may include whole blood, serum, plasma, cerebrospinal fluid, sputum, tissue, cultured cells, e.g., primary cultures, explants, transformed cells, stool, urine, vesicle fluid, mucus, and other bodily secretion, or tissue that could be sampled with a swab device. Furthermore, in some cases, a “biological sample” can be material taken from an environment (e.g., water, air, soil, and the like) where the presence of a particular organism may be suspected.
As used herein, the term “configured” describes a particular arrangement of hardware components, such as chassis, heaters, fans, optical sensors, fluid couplings, fluid passages, microfluidics, piezoelectric components, processor, memory containing instructions, supporting circuitry, and/or connectors, etc.
As used herein, the term “sample processing module” (interchangeable with “processing module” and “module”) is defined as a modular sub-portion of the testing system, which has a particular physical form factor compatible with the system and includes hardware components (heaters, fans, optical sensors, fluid couplings, fluid passages, microfluidics, piezoelectric components, processor, memory containing instructions, supporting circuitry, and/or connectors, etc.) configured to perform a particular process for a sample, which can include any or all of a sample preparation and analytical testing process.
As used herein, the term “sample preparation” is defined as a process typically performed prior to one or more particular assays. The process changes a physical characteristic of a sample prior to the assay(s), for example, by physical, chemical, and/or enzymatic treatment (e.g., lysis by sonification, enzymatic, detergents, solvents, cell-bomb, etc., filtration, and/or concentration).
As used herein, the term “assay” (interchangeable with “testing process” and “biological testing process”) is defined to be an investigative procedure performed on a sample, including but not limited to, determining the presence/absence and/or the quantity/concentration of a particular analyte.
Non-limiting exemplary analytes can include any nucleic acids and/or proteins, analytes specific for bacterial pathogens (e.g. methicillin resistant Staphylococcus aureus, C. difficile, tuberculosis, group B strep., chlamydia, and gonorrhea), viral pathogens (e.g. influenza, Covid-2, RSV, HIV, HCV, and HBV), tumor cells (e.g., bladder cancer, lung cancer, breast cancer, colon cancer, and leukemia), biothreat analytes such as anthrax or ricin, chromosomal alterations, such as gene duplication, gene deletions or gene translocations, cells expressing specific cell surface markers such as CD4+ cells, detection of gene mutation/alterations such as single nucleotide polymorphisms (SNPs) and methylation status of genes.
As used herein, the term “removable sample cartridge” (interchangeable with “sample cartridge” and “cartridge”) refers to a specialized container for holding a sample that is configured to temporarily physically interface with a sample processing module such that control aspects (fluid connections, heaters, piezoelectric components, optical sensors, etc.) of the sample processing module can directly or indirectly perform a process on the sample within the container, after which the removable sample cartridge can be removed from the sample processing module to further analyze, process, or dispose of the sample. The removable sample cartridge couples and uncouples with the sample processing module without the need for using additional tools (e.g., screwdriver, hex-key, etc.) to fasten the removable sample cartridge to the sample processing module, akin to an electrical plug interfacing with an electrical wall outlet, except for cases of jamming or other malfunction, which may require such tools to help remove the cartridge. In some embodiments, the removable sample cartridge may contain, or has physical aspects for receiving, particular chemicals, such as primers and reagents (including reactants).
In this application, the term “nucleic acid” or “polynucleotide” refers to deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and polymers thereof in either single- or double-stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogs of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, mutations including point mutations, single nucleotide polymorphisms (SNPs), and complementary sequences as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); and Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). The term nucleic acid is used interchangeably with gene, cDNA, and mRNA encoded by a gene.
The term “gene” means the segment of DNA involved in producing a polypeptide chain; it includes regions preceding and following the coding region (leader and trailer) involved in the transcription/translation of the gene product and the regulation of the transcription/translation, as well as intervening sequences (introns) between individual coding segments (exons).
A “polynucleotide hybridization method” as used herein refers to a method for detecting the presence and/or quantity of a polynucleotide based on its ability to form Watson-Crick base-pairing, under appropriate hybridization conditions, with a polynucleotide probe of a known sequence.
In this application, the terms “polypeptide,” “peptide,” and “protein” are used interchangeably to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers. As used herein, these terms encompass amino acid chains of any length, including full-length proteins (i.e., antigens), wherein the amino acid residues are linked by covalent peptide bonds. The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine.
As used herein, the terms “multiplex” and “array” refer to an assay format that permits simultaneous detection and/or quantification of multiple analytes (e.g., dozens or more of the same or different molecules) in a single run/cycle of the assay.
As used herein, the term “solid support” refers to an inert solid material, which may be a natural material, such as glass and collagen, or a synthetic material, such as acrylamide, cellulose, nitrocellulose, silicone rubber, polystyrene, polyethylene vinyl acetate, polypropylene, polymethacrylate, polyethylene, polysilicates, polyethylene oxide, polycarbonates, teflon, fluorocarbons, nylon, polyanhydrides, polyglycolic acid, polylactic acid, polyorthoesters, polypropylfumarate, glycosaminoglycans, and polyamino acids. One example is silica gel preimpregnated with fluorogenic substrates. A “solid support” typically provides a supporting structure for performing an assay in various apparatus of this application.
Replaceable Sample Processing Modules and System
The apparatus and modules of the present invention can be further understood by referring to the detailed examples of
The sample processing modules are connected by a communications bus to a control unit having a controller (for example, see control unit module 150 in
Generally, each sample processing module 200 will share the same structural format and can be configured to electronically interface with the enclosure via a shared type of connector inside the enclosure. This arrangement allows for easy swapping of modules when different configuration needs arise for the user. Each sample processing modules 200 is configured to interface with a sample testing cartridge 10, for example, such as the vessel disclosed in
In some embodiments, the sample processing module 200 is configured as a sample preparation module to prepare a sample for later processing (e.g., lysis by ultrasonification). An example of such a configuration is shown in commonly assigned U.S. Pat. No. 6,739,537, entitled “APPARATUS AND METHOD FOR RAPID DISRUPTION OF CELLS OR VIRUSES”, which is incorporated by reference. Another example of such a configuration is shown in commonly assigned U.S. Pub. No. US 2010/0129827, entitled “METHOD AND DEVICE FOR SAMPLE PREPARATION CONTROL”, which is incorporated by reference.
In some embodiments, flow cytometry is one of the detection methods that can be used in one or more sample processing modules for detecting the presence of a predetermined target, such as a certain cell type or a population of cells that express a particular marker. Methods and instrumentation for practicing flow cytometry are known in the art, and can be used in the practice of the present invention. Flow cytometry in general resides in the passage of a suspension of cells or microparticles comprising a label (e.g. a fluorophore) as a stream past a laser beam and the detection of the label (e.g. fluorescent emission) from each particle by a detector, such as a photo multiplier tube. Detailed descriptions of instrumentation and methods for flow cytometry are found in the literature. Examples are McHugh, “Flow Microsphere Immunoassay for the Quantitative and Simultaneous Detection of Multiple Soluble Analytes,” Methods in Cell Biology 42, Part B (Academic Press, 1994); McHugh et al., “Microsphere-Based Fluorescence Immunoassays Using Flow Cytometry Instrumentation,” Clinical Flow Cytometry, Bauer, K. D., et al., eds. (Baltimore, Md., USA: Williams and Williams, 1993), pp. 535-544; Lindmo et al., “Immunometric Assay Using Mixtures of Two Particle Types of Different Affinity,” J. Immunol. Meth. 126: 183-189 (1990); McHugh, “Flow Cytometry and the Application of Microsphere-Based Fluorescence Immunoassays,” Immunochemica 5: 116 (1991); Horan et al., “Fluid Phase Particle Fluorescence Analysis: Rheumatoid Factor Specificity Evaluated by Laser Flow Cytophotometry,” Immunoassays in the Clinical Laboratory, 185-189 (Liss 1979); Wilson et al., “A New Microsphere-Based Immunofluorescence Assay Using Flow Cytometry,” J. Immunol. Meth. 107: 225-230 (1988); Fulwyler et al., “Flow Microsphere Immunoassay for the Quantitative and Simultaneous Detection of Multiple Soluble Analytes,” Meth. Cell Biol. 33: 613-629 (1990); Coulter Electronics Inc., United Kingdom Patent No. 1,561,042 (published Feb. 13, 1980); and Steinkamp et al., Review of Scientific Instruments 44(9): 1301-1310 (1973). These references are incorporated herein by reference.
In some embodiments, one or more of the sample processing modules can be configured for detection of nucleic acids and/or proteins. Basic texts disclosing general methods and techniques for detection of nucleic acids and proteins include Sambrook and Russell, Molecular Cloning, A Laboratory Manual (3rd ed. 2001); Kriegler, Gene Transfer and Expression: A Laboratory Manual (1990); and Ausubel et al., eds., Current Protocols in Molecular Biology (1994). These references are incorporated herein by reference. A variety of polynucleotide amplification methods are well established and frequently used in research. For instance, the general methods of polymerase chain reaction (PCR) for polynucleotide sequence amplification are well known in the art and are thus not described in detail herein. For a review of PCR methods, protocols, and principles in designing primers, see, e.g., Innis, et al., PCR Protocols: A Guide to Methods and Applications, Academic Press, Inc. N.Y., 1990, which is incorporated by reference herein. PCR reagents and protocols are also available from various commercial vendors.
The apparatus 100 has a main logic board with edge connectors for establishing electrical connections to the modules. The apparatus 100 also preferably includes a fan for cooling its electronic components. The apparatus 100 may be connected to the controller using any suitable data connection, such as a universal serial bus (USB), ethernet connection, or serial line. It is presently preferred to use a USB that connects to the serial port of controller. Alternatively, the controller may be built into the apparatus 100.
The processing modules 200 are preferably independently controllable so that different chemical reactions and sample preparations can be run simultaneously in the apparatus 100. The apparatus 100 is modular so that each processing module 200 can be individually removed from the apparatus 100 for servicing, repair, replacement or upgrade. Typically, each module is readily removable, for example by a quick-release connection, to facilitate quick and easy removal of a module. This modularity reduces downtime since all the processing modules are not off line to repair one, and the instrument 100 can be upgraded and enlarged to add more modules as needed.
Apparatus 100 further include a central display 110 for displaying status indicators or instructions regarding any of the modules 200. In addition, the display can be configured to display metrics, status information or instructions for all modules or any combination of modules. For example, the display may indicate remaining times for all modules, or for a subset of modules that are currently processing. In another example, the display may show a user instructions regarding a sample processing protocol or to remove spent sample cartridges from one or more modules in which sample processing is completed. In some embodiments, the display is a touch screen that allows a user to interface with or control the modules. For example, the user may initiate a sample testing by inputting commands and information through the display. In some embodiments, the central display 110 is tiltable so as to be more easily viewed by the user at multiple angles. As shown in
The apparatus 100 can also include a microprocessor or microcontroller containing firmware for controlling the operation of the apparatus and modules. The microcontroller communicates through a network interface 132 to the controller computer via, for example, a USB connector. In some embodiments, the apparatus 100 includes network interface inlet and outlet ports for receiving a data connection through inlet port and outputting data to another apparatus through outlet port. In other embodiments, the apparatus can be configured to send and receive data wirelessly by any suitable means. The apparatus 100 also includes a microprocessor or microcontroller containing firmware for controlling the operation of the apparatus 110 and modules 200. The microcontroller communicates through a network interface to the controller computer via, for example, a USB connector.
As can be seen in
In another aspect, the apparatus is configured to allow for easy removal of the individual modules for repair or replacement. Whereas previous apparatus required some level of disassembly of the apparatus and/or modules to facilitate removal, this apparatus is configured so that the modules can quickly be removed and replaced without disassembling the modules and without disconnecting or removing the remaining modules from the apparatus. In some embodiments, the apparatus uses quick-release mechanisms for various panels and for the modules themselves to allow the user to quickly remove and replace the modules manually without any tools, or with minimal tools, for example, by use of a single specialized removal tool. This latter aspect may be desirable as it prevents easy removal of the modules by unauthorized personnel and limits module removal to those in possession of the specialized removal tool.
As shown in
As shown in
In the embodiment shown in
In another aspect, the apparatus can include an improved identifier located within the cartridge receiving bay. The identifier is used to identify any of: a sample cartridge, a sample, and a user badge of personnel. Scanning from within the module bay enables new workflows, and tests to be initiated at the module. Cartridge scanning occurs passively within the module during loading, simplifying workflow and reducing errors. This approach allows an entire test to be performed interacting only with the GX instrument.
In another aspect, the apparatus can include an improved bay door design, such as that shown in
In another aspect, the apparatus can include an improved thermal cycling unit in the instrument assembly 240, such as that shown in
Examples of such new and/or replacement modules are depicted as Module 2 (M2), and include M2N, M2R and M2S. The M2N module is a “new module” that retains the core technologies of the M1 module for use in the new apparatus described herein. M2N is equipped with front-loading installation and quick-release features so as to be readily removable as described herein. The M2 module replaces “end-of-life” components in the M1 and may include one or more new components with functionality that may or may not be used by the conventional enclosure. The M2R module is designed as a “retrofit module” so as to retrofit the conventional apparatus with new functionality. M2R includes features that fit in non-front loading apparatus. For example, the M2R can include a cartridge identifier (e.g. barcode scanner) within the bay, whereas, the conventional M1 module relied on use of an external peripheral device (e.g. handheld barcode scanner), thereby improving functionality of existing conventional apparatus. M2S is a “sustaining module” that replaces only certain components (e.g. motherboard) that are required to maintain the same functionality as the original M1 module, which allows use of a conventional apparatus to be maintained without adding new functionality. The M2S module is equipped with the same mounts and connectors as the M1 to allow for in field replacement of old M1 modules. This option is advantageous for those users that desire only to extend use of their existing conventional device and operate in the same manner. Thus, M2S is designed as a drop-in replacement of the M1 module with a new motherboard that is used in in all M2 modules, yet still utilize connections and available components that are the same as the M1 module. Any of the M2 modules can be equipped with mountings (e.g. simple brackets along the top and/or bottom) so as to be compatible with earlier generations of apparatus enclosures.
As described, the new M2 modules are designed with certain components and/or modules that are the same, substantially the same, or substantially the same in functionality as the earlier M1 module, while certain other components are different and may be configured to provide the same or similar functionality or entirely new functionality from that of the M1 modules. It is appreciated that some of these updated components may not be utilized by the conventional apparatus of M1, while other components may actually allow updates in functionality of the conventional M1 apparatus.
Examples of designs that maintain certain components while replacing others are shown in
Alternatively, the power supply may comprise a battery. In some embodiments, the apparatus is powered with a specialized portable battery pack, which improves portability for use in remote locations (e.g. sub-Saharan regions) or temporary aid stations. For such embodiments, the apparatus can be equipped with a portable plug-in battery pack 400 that can be plugged into receptacle 140, as shown in
As shown in
In another aspect, the CPU unit of the apparatus is modular such that it can be easily removed and replaced as needed. As shown in
In yet another aspect, the apparatus 100 can include a display output 116 for an external display 600 in addition to the central display, as shown in
Remote Monitoring of Assay Status
In yet another aspect, the system can include a feature that allows a user to monitor the status and/or a result of an assay remotely. Such a feature is particularly advantageous given the nature of conducting assays with the respective sample processing modules, which often take half an hour or more. Many conventional diagnostic systems utilize a single-use, consumable test cartridge that is processed by a non-portable instrument on a laboratory bench top or floor. A user of the system is required to load cartridges into the instrument, and view status, alerts and results through the graphical user interface displayed on the instrument-mounted touchscreen of the instrument. As a test typically takes half an hour or more to run and show results, a user may walk away from the processor to attend to other matters, returning when they estimate the test will be done. Some users set one or more alarms, which can be become cumbersome, particularly when the user is running multiple differing assays concurrently. This remote monitoring feature allows the user to untether from the systems processor and receive continuous real-time information on the test(s) being run without having to estimate completion times or use multiple alarms. The instrument sends real-time test status and results to a server, which provides the information on a website accessible remotely by the user. In some embodiments, the instrument updates the information being displayed in response to any change in the status of the assay being performed (e.g. completion, error, stoppage, result, etc.). It is noted that the test results are not stored indefinitely on the server utilized in remote monitoring. In some embodiments, after a set period of time (e.g. hours, days, weeks) and/or confirmation by the user, the status and result information is no longer available or stored on the server associated with the remote monitoring website. The exact period of time can be set by a system administrator. This further enhances the security of the test result. The full test result can be stored longer or permanently in other systems/servers for access by the physician or the patient's electronic medical record. Additionally, in some embodiments, the testing apparatus only stores the test results for a pre-set period of time (e.g. hours, days), typically two days, which further reduces the possibility of test result information being improperly accessed or disseminated.
In some embodiments, this feature is achieved by use of a URL that is updated with status information by the system so that a user can view the URL from any internet-ready device. In some embodiments, this entails the user scanning a unique QR code generated by the system and displayed on the user interface by the user's mobile device (e.g. smartphone, tablet). The QR code directs the user's device to the URL, so that the user can continue to monitor the status of the assay from a remote location. In other embodiments, the system texts or emails the user a link to the URL so that the user can monitor the status of the assay from any internet-ready device (e.g. desktop device, tablet, smartphone).
In some embodiments, the running test screen and test result screen on the instrument have a QR code. The QR code contains a link (URL) to the server. To provide a basic level of security, the link contains a hash generated from the instrument ID and test ID which is used to look up the test information on the server. It is at least 256 bits and preferably more bits long. For example if the link uses A-Z,a-z,0-9×16 characters the result is 992 bits which results in 4.18×1098 possible combinations. Since the chance of finding any test let alone a specific test by searching the links would be infeasible, this approach provides a sufficient level of security for the information being displayed despite being accessible via the internet. In some embodiments, the server could increase this time further by limiting the number of searches from sources of too many searches to one per second or one per minute. In some embodiments, the link could also be an app URL that opens the test information in a custom test viewer app. In this manner, the system can allow for display of advanced data that may include more sensitive information, such as the patient ID or name, the test result, and technical details of the test. It is appreciated that various other approaches to authentication of the user can be utilized in order to provide more advanced data sets having more sensitive patient information.
In one aspect, the above noted features can be used for each of multiple assays being performed concurrently by multiple modules. The user can select the desired notification option and/or scan the unique QR code associated with each assay so as to show the status and/or test result on their device (e.g. mobile device). By providing a unique link/website for each assay being performed, the user can open each on a unique tab in their native web browser of their internet-ready device (e.g. smartphone, tablet), so that multiple tests can be monitored by multiple tabs in their browser. In some embodiments, the user can forward the link in an SMS to other users or can display the QR code on their device for scanning by other users to allow remote monitoring by multiple people.
In a first aspect, the system establishes a basic security 810 scheme for the task information as an obstacle to unauthorized access. In this embodiment, the system generates any suitable number of random characters (e.g. 16 characters, 24 characters, etc) for use in the online accessible http link address. For example, it is estimated that, by generating 16 random characters for use in the link, at one million attempts per second, it would take 15 trillion years to search all possible combinations of 16 characters. If more security is desired, larger sets of random numbers can be used, or alternative security means could be utilized. Moreover, even if a party were to somehow access the http link, only a basic data set 821 would be accessed, which still does not identify the patient or test result, such that the privacy of the patient's health information is maintained. Next, the task record 820 of task information (or a subset thereof) that is accessed remotely is defined. In this embodiment, the task record information includes a basic data set 821, which includes basic task information (e.g. ID, status, ETA, time attributes), user information (e.g. user ID, type, classification), instrument information (e.g. ID, module, software or firmware versions for instrument or module), and cartridge information (e.g. assay, version, lot expiration, serial number). In some embodiments, the task record 820 can further include an advanced data set 822 that includes additional data, which can include patient information (e.g. ID, name, location), test information (e.g., ID, type), and result information (e.g. summary, detail, raw data, error data). It is appreciated that each of the basic data set and advanced data sets could omit one or more of fields of this data or include one or more various other fields of data. In some embodiments, the advanced data set requires additional authorization by a user accessing the link (e.g. password protected, higher security protocol, etc.). Any suitable authorization scheme or specialized application could be used for this feature. The admin configuration determines which fields of data are sent without authorization. Next, the task record is sent securely to the server via HTTPS POST at the online-accessible access link 830 (e.g. https://example.com/save?field=value&field=value . . . ), which is also sent to the user by SMS or email or associated with the QR code. The https can securely transmit the path and the parameters and returns the task record result (see link 831), or the parameters can also be sent as a part of the path (see link 832).
Although the above description contains many specificities, these should not be construed as limitations on the scope of the invention, but merely as illustrations of some of the presently preferred embodiments. Many possible variations and modifications to the invention will be apparent to one skilled in the art upon consideration of this disclosure.
This application is a Non-Provisional of and claims the benefit of priority of Provisional Application No. 63/107,934 filed Oct. 30, 2020, which is incorporated herein by reference in its entirety. This application is generally related to U.S. Pat. No. 10,132,728 entitled “Apparatus with Heterogeneous Processing Modules,” issued on Nov. 20, 2018; U.S. Pat. No. 6,660,228, entitled “Apparatus for Performing Heat-Exchanging, Chemical Reactions,” issued Dec. 9, 2003; U.S. Pat. No. 6,391,541, entitled “Apparatus for Analyzing a Fluid Sample”, issued May 21, 2002; Int'l Pub. No. WO/2000/072970, entitled “Cartridge for Conducting a Chemical Reaction,” and Int'l Pub. No. WO/2000/073412, entitled “Apparatus and Method for Analyzing a Fluid Sample,” the entire contents of which are incorporated herein by reference for all purposes.
| Number | Date | Country | |
|---|---|---|---|
| 63107934 | Oct 2020 | US |
