Multi-modal modular biological sample processing apparatus, system, and methods of use

Abstract

A biological sample processing apparatus having a plurality of bays configured interchangeably reactive any of a plurality of module types configured to independently receive and perform analysis on a sample cartridge assembly. Simultaneous access of one or more modules can be accomplished through different translation or pivoting of different portions of the front of the instrument. Advanced filter systems and servicing methods are also provided.

Description

CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1MULTI-MODAL MODULAR BIOLOGICAL SAMPLE PROCESSING APPARATUS,SYSTEM, AND METHODS OF USECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is being filed on December 29, 2025, as a PCT International application and claims the benefit of and priority to: U.S. Application No. 63 / 742,090 filed on January 6, 2025; U.S. Application No. 63 / 791,042, filed on April 18, 2025; and U.S. Application No. 63 / 846,754, filed on July 18, 2025, the disclosures of which are hereby incorporated by reference in their entireties.BACKGROUND

[0002] 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.

[0003] In the GeneXpert" sample analyzer by Cepheid®, 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. In order to increase sample throughput, such sample analyzers often include multiple such modules disposed within a common enclosure. However, to make the use of such systems feasible in the context of high-volume diagnostic testing, it is critical to develop systems and protocols that improve the efficiency and lifespan of the sample analyzer, increase time to result, simplify servicing, and ultimately limit down time and associated costs.SUMMARY

[0004] In general terms, the disclosure is related to lab on a chip calibration and feature extraction. In a non-limiting example, this disclosure is directed to a sample analyzer having one or more modules configured to receive a frame of analysis chip data from a biosensor array.

[0005] One aspect is a biological sample processing apparatus comprising: a chassis having an interior and an exterior; a rack secured within the interior of the chassis, the rack including a plurality of bays; and a plurality of sample processing modules configured to receive and perform analysis on a sample cartridge assembly, wherein each of the plurality ofCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1sample processing modules is independently operable and securable within the rack, wherein the plurality of sample processing modules is selected from two or more module types including: a first module type configured to perform nucleic acid amplification; a second module type configured to perform non-thermal cycling detection of an analyte; and a third module type configured to perform lab on a chip analysis, wherein each bay is configured to receive each type of sample processing module.

[0006] Another aspect is a system comprising: a biological sample processing apparatus including a chassis having an interior and an exterior, a rack secured within the interior of the chassis, the rack including a plurality of bays, and a barcode reader configured to read a first barcode directed to a first assay type, the first barcode being on or associated with a first sample cartridge assembly; a plurality of sample processing modules configured to receive and perform analysis on a sample cartridge assembly, wherein each sample processing module is independently operable and securable within the rack; and at least one processor configured to execute a set of instructions, wherein the at least one processor is configured to: receive a first signal from the barcode reader based on the first barcode, in response to the first signal, determine the first type of assay, and transmit instructions to run the first assay type to a first sample processing modules of the plurality of sample processing modules, wherein each bay is configured to receive each type of sample processing module.

[0007] Still another aspect is a biological sample processing apparatus having a fixed volumetric footprint, the apparatus comprising: a chassis having an interior and an exterior; and a rack secured within the interior of the chassis, the rack including a plurality of bays, each bay being configured to receive one of a plurality of sample processing modules, each sample processing module being configured to receive and perform analysis on a sample cartridge assembly, each sample processing module being independently operable and securable within the rack, wherein the plurality of sample processing modules are selected from two or more module types, wherein each bay is configured to receive each sample processing module type, and wherein the fixed volumetric footprint remains constant whether the rack is full or less than full.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 A is a front perspective view of an example sample analyzer.

[0009] FIG. IB is a back perspective view of an example sample analyzer.

[0010] FIG. 2 is a block diagram of an example sample analyzer.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0011] FIG. 3 is a perspective view of an example module.

[0012] FIG. 4 is perspective view of an example module configured to perform lab on a chip analysis.

[0013] FIG. 5 is a schematic diagram of an example sample cartridge assembly.

[0014] FIG. 6 is a perspective view of an example cartridge coupled to a reaction tube configured for lab on a chip analysis.

[0015] FIG. 7 is an exploded view of an example reaction tube configured for lab on a chip analysis.

[0016] FIG. 8 is a schematic of a cartridge configuration for configured for receiving and holding a fluid sample to be analyzed without an analysis chip.

[0017] FIG. 9 provides an embodied reaction tube configured for non-thermal cycling detection of an analyte.

[0018] FIG. 10 shows an example reaction tube configured for thermal convection analysis having x, y, and z dimensions defined as length (x), width (y), and height (z).

[0019] FIG. 11 is a perspective view of an example chassis of a sample analyzer.

[0020] FIG. 12 is a perspective view of an example rack for holding one or more module.

[0021] FIG. 13 is a perspective view of a sample analyzer having a hinged front access means.

[0022] FIG. 14 is a schematic diagram of a sample analyzer having a hinged front access means.

[0023] FIG. 15 is a schematic diagram of an example sample analyzer having a front panel attached to a chassis by a hinge.

[0024] FIG. 16 is a schematic diagram of an example sample analyzer having a front panel attached to a chassis by a long arm pivot hinge.

[0025] FIG. 17 is a top view of an example long arm pivot hinge in an open position.

[0026] FIG. 18 is a top view of an example long arm pivot hinge in a semi-closed position.

[0027] FIG. 19 is a top view of an example long arm pivot hinge in a closed position.

[0028] FIG. 20 is a perspective view of a sample analyzer with simplified toolless front access enabled by a long arm pivot hinge.

[0029] FIG. 21 is a top view of a sample analyzer with front access enabled by a retractable hinge assembly.

[0030] FIG. 22 is a side view of a retractable hinge assembly in an open position.

[0031] FIG. 23 is a side view of a retractable hinge assembly in a closed position.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0032] FIG. 24 is a perspective view of a sample analyzer with front access enabled by an extendable display panel.

[0033] FIG. 25 is a perspective view of a sample analyzer with front access enabled by a slidable display panel.

[0034] FIG. 26 is a perspective view of a different sample analyzer with front access enabled by a slidable display panel.

[0035] FIG. 27 is a front view an example sample analyzer.

[0036] FIG. 28 is a perspective view of the interior of an example chassis.

[0037] FIG. 29 is a perspective view of an example sample analyzer having a thermal management system.

[0038] FIG. 30 is a perspective view of an example sample analyzer having a thermal management system with side ventilation.

[0039] FIG. 31 is a top view of the interior of the chassis of the sample analyzer having a thermal management system.

[0040] FIG. 32 is a top schematic view of the interior of the chassis of the sample analyzer having a thermal management system.

[0041] FIG. 33 is a side view of an example baffle system.

[0042] FIG. 34 is a perspective view of an example baffle system.

[0043] FIG. 35 is a schematic view sample analyzer having a slidable fdter system.

[0044] FIG. 36 is a side view of an example filter housing affixed to an example sample analyzer.

[0045] FIG. 37 is a perspective view of an example filter housing.

[0046] FIG. 38 is a flow diagram illustrating an example system for manufacturing, testing, and using an analysis chip across different locations.

[0047] FIG. 39 is a block diagram illustrating an example analysis chip.

[0048] FIG. 40 is a schematic diagram illustrating an example analysis chip.

[0049] FIG. 41 is a block diagram illustrating a compensation system.

[0050] FIG. 42 is a flow chart illustrating an example method of compensating an analysis chip.

[0051] FIG. 43 is a block diagram illustrating an example testing system that includes a sample cartridge and a laboratory instrument.

[0052] FIG. 44 is a flow chart illustrating an example process for performing measurements using an analysis chip within an instrument.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0053] FIG. 45 is a diagram of an embodied method of the present disclosure as described in Example 1.

[0054] FIG. 46 is a diagram of an embodied method of the present disclosure as described in Example 2.

[0055] FIG. 47A presents a graph demonstrating performance of primers and probes having different melt temperatures (Tms).

[0056] FIG. 47B presents another graph demonstrating performance of primers and probes having different melt temperatures (Tms).

[0057] FIG. 48A is a graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the lower temperature value.

[0058] FIG. 48B is another graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the lower temperature value.

[0059] FIG. 48C is another graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the lower temperature value.

[0060] FIG. 48D is another graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the lower temperature value.

[0061] FIG. 49A is a graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the upper temperature value.

[0062] FIG. 49B is another graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the upper temperature value.

[0063] FIG. 49C is another graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the upper temperature value.

[0064] FIG. 49D is another graph demonstrating the output of the thermal convection assay across a range of temperatures varied by changing the upper temperature value.

[0065] FIG. 50A is a graph demonstrating the influence cycle temperature range has on assay signal output as a function of time. TTR was greatly improved with a wider temperature range of thermal convection cycling.

[0066] FIG. 50B is another graph demonstrating the influence cycle temperature range has on assay signal output as a function of time. TTR was greatly improved with a wider temperature range of thermal convection cycling.

[0067] FIG. 51 A is a graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Influenza A (Flu A), Influenza B (Flu B), SARS-CoV-2CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1(US CoV-2), Respiratory Syncytial Virus A (RSV A) and Respiratory Syncytial Virus B (RSV B) on the GeneXpert® revised cartridge C (RCC).

[0068] FIG. 5 IB is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Influenza A (Flu A), Influenza B (Flu B), SARS-CoV-2 (US CoV-2), Respiratory Syncytial Virus A (RSV A) and Respiratory' Syncytial Virus B (RSV B) on the GeneXpert® RCC.

[0069] FIG. 51C is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Influenza A (Flu A), Influenza B (Flu B), SARS-CoV-2 (US CoV-2), Respiratory' Syncytial Virus A (RSV A) and Respiratory' Syncytial Virus B (RSV B) on the GeneXpert® RCC.

[0070] FIG. 5 ID is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Influenza A (Flu A), Influenza B (Flu B), SARS-CoV-2 (US CoV-2), Respiratory' Syncytial Virus A (RSV A) and Respiratory Syncytial Virus B (RSV B) on the GeneXpert® RCC.

[0071] FIG. 5 IE is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Influenza A (Flu A), Influenza B (Flu B), SARS-CoV-2 (US CoV-2), Respiratory' Syncytial Virus A (RSV A) and Respiratory Syncy'tial Virus B (RSV B) on the GeneXpert® RCC.

[0072] FIG. 52A is a graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Flu A, FluB, US CoV-2, RSV A and RSV B on a prototype GeneXpert® cartridge (amine modified glass fiber filter cartridge).

[0073] FIG. 52B is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Flu A, Flu B, US CoV-2, RSV A and RSV B on a prototype GeneXpert® cartridge (amine modified glass fiber filter cartridge).

[0074] FIG. 52C is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Flu A, Flu B, US CoV-2, RSV A and RSV B on a prototype GeneXpert® cartridge (amine modified glass fiber filter cartridge).

[0075] FIG. 52D is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Flu A, Flu B, US CoV-2, RSV A and RSV B on a prototype GeneXpert® cartridge (amine modified glass fiber filter cartridge).

[0076] FIG. 52E is another graph demonstrating performance of the rapid qualitative, multiplex real-time PCR in vitro test to detect Flu A, Flu B, US CoV-2, RSV A and RSV B on a prototype GeneXpert® cartridge (amine modified glass fiber filter cartridge).CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0077] FIG. 53 shows the time-to-result (TTR) and endpoint probe fluorescence (EPF) for PCR tests of the SARS-CoV-2 N2 and E genes using embodied assays.

[0078] FIG. 54 shows the time-to-result (TTR) and endpoint probe fluorescence (EPF) for PCR tests of the SARS-CoV-2 E / RdRp genes using embodied assay methods and commercial multiplex test beads for SARS-CoV-2, Flu A, Flu B, RSV A and RSV B.

[0079] FIG. 55 is a graph of the temperature cycle over time for a thermal cycling event in the embodied reaction tubes. The average cycle time is 15 seconds or less with a temperature cycle range from 64°C to 98°C and excellent stability across greater than 20 cycles. The probe fluorescence shows that detectable signal was seen at approximately 25 cycles with a rapid rise in intensity.DETAILED DESCRIPTION

[0080] Various embodiments will be described in detail with reference to the drawings, wherein the reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the claims attached hereto. Additionally, any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the appended claims.

[0081] Though the disclosure is directed to a biological sample, the system is not intended to be so limited. The system can be used for any appropriate sample (e g., liquid, liquified solid, semi-solid, or the like) suspected of containing or to be tested for any target analyte (e.g., cell, nucleic acid, peptide, virus, bacteria, or the like).

[0082] FIG. 1 A is a front perspective view of an example sample analyzer 100. The sample analyzer 100 includes a module 102, a chassis 104, a front panel 106, a display 108, and a barcode reader 109. Also illustrated is a sample cartridge assembly 110. The sample cartridge assembly 110 includes a sample cartridge 112 and a reaction tube assembly 114. The reaction tube assembly 114 includes an analysis region 116.

[0083] The sample analyzer 100 measures properties of a biological sample. In some implementations, the biological sample can be a fluid sample. In some embodiments, the sample analyzer 100 is a laboratory instrument. In some embodiments, the sample analyzer includes more than one (e g., a plurality' of) modules 102. For example, the sample analyzer 100 can have a plurality' of modules 102 that can each independently perform analysis on a plurality of sample cartridge assemblies 110 in parallel. In some implementations, the sample analyzer 100 can include one or more different types of modules 102. In examples, the sampleCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1analyzer 100 can include up to 20 modules. For example, the sample analyzer can include between 3 and 20 modules, 4 and 20 modules. 6 and 20 modules, 8 and 20 modules, 10 and 20 modules, 12 and 20 modules, 14 and 20 modules, 16 and 20 modules, or 18 and 20 modules. In other examples, the sample analyzer can include up to 48 modules. For example, the sample analyzer can include between 4 and 48 modules, 8 and 48 modules, 10 and 48 modules, 12 and 48 modules, 14 and 48 modules, 16 and 48 modules, or 18 and48 modules. In further examples, the sample analyzer can include up to 80 modules. For example, the sample analyzer can include between 10 and 80 modules, 14 and 80 modules, 16 and 80 modules, 20 and 80 modules, 30 and 80 modules, 40 and 80 modules, or 50 and 80 modules.

[0084] As depicted in the example of FIG. 1A, the sample analyzer 100 can include between 1 and 20 modules 102. For example, the sample analyzer 100 can include an upper row 101 and a bottom row 103 of modules 102. For example, the upper row 101 and the bottom row 103 can each contain between 1 and 10 modules 102. Also shown in the example depicted in FIG. 1A, in some embodiments, the sample analyzer 100 includes a display 108. In some implementations, as shown in FIG. 1A, the display 108 can be integrated on the surface of the sample analyzer 100. For example, the display 108 can be mounted to the surface of the sample analyzer 100. In other implementations, the display 108 can be separate from the sample analyzer 100. As shown in the example illustrated in FIG. 1A, the sample analyzer 100 can include more than one display 108.

[0085] The module 102 is an analysis component of the sample analyzer 100. For example, the module 102 can be configured to receive the sample cartridge assembly 110 and the analysis region 116 therein. In examples, the module 102 can be independently operable and securable within the rack 200 of the sample analyzer 100. In examples, as further illustrated and described with respect to FIG. 12, a plurality’ of independently operable modules 102 can be configured to be received by any of a plurality of bays 201 within the rack 200 of the sample analyzer 100. In some implementations, as further illustrated in FIG. 3, each module 102 can include a module door 124 that can be opened to allow the sample cartridge 112 to be loaded into the module 102. In some examples, when the module 102 is inserted within the chassis 104 the module door 124 can be parallel to the front panel 106 of the sample analyzer 100. For example, when the module 102 is inserted within the chassis 104 the module door 124 can be flush with the front panel 106 of the sample analyzer 100. In other examples, when the module 102 is inserted within the chassis 104 the module door 124 can extend beyond the front panel 106 of the sample analyzer 100. In some embodiments, each module 102 can be configured to performCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1analysis on a sample cartridge assembly 110 independently. For example, the module 102 can be configured to operate separated from (e.g. outside ol) the sample analyzer 100.

[0086] In some examples, the module 102 can perform one or more of a variety of different assays on a sample. In some examples, each module 102 can be configured to perform a plurality7of different assays on a sample. In other examples, each module is configured to perform one type of assay (such as nucleic acid amplification or an immunoassay) and the sample analyzer comprises a plurality of different types of modules 102 to perform a variety of different assays on a sample. The type of assay tests performed may vary7and can be implemented using one or more modules including, for example, a qualitative or semi-quantitative assay, a quantitative assay, or a combined qualitative or semi-quantitative assay and a quantitative assay. In order to perform the assays, the module includes an optical sensor (e.g., light-based, fluorescence, luminescence, fiber optics, colorimetric) configured to process a signal from the qualitative or semiquantitative assay and / or an electrical or electrochemical connector (e.g., piezoelectric, amperometric, potentiometric, conductometric, impedimetric) configured to process a signal from the sample cartridge assembly. Other biosensors that can be included in the module to perform the assay can include a thermal biosensor, a magnetic biosensor, a gravimetric biosensor, or any other suitable biosensor for qualitative or semiquantitative assay, or a quantitative assay. In particular, the optical sensor includes an optical imager configured to image an assay of an optical test cartridge.

[0087] The module 102 can perform one or more of a variety of different assays on a sample, for example, the module 102 can perform an assay to detect a disease or presence of genetic material. The type of assay performed can vary7depending on the analyte being detected. Examples of analytes provided herein are for illustrative purposes and are not intended to limit the scope of the present disclosure. The module 102 disclosed herein is capable of detecting a pathogen, a protein, a cancer cell, a blood component, or a biomolecule. In some cases, the pathogen is, but not limited to, a virus, a bacterium, a fungus, or a protozoan. In some cases, the protein may be a prion protein that arise from a sporadic prion disease, a genetic prion disease, or an acquired prion disease. In some cases, the cancer cell may be a cancer cell from a tumor or a circulating tumor cell. In some cases, the blood component may be cell free nucleic acid, red blood cells, white blood cells, platelets, tissue, or proteins found in the blood. In some cases, a biomolecule may be a nucleic acid, an aptamer, a metabolite, a macromolecule, a proteins, lipids, or carbohydrates.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0088] In certain instances, the analyte may be hormones, antibodies, growth factors, cytokines, electrolytes (e.g., sodium, potassium, and chloride), enzymes (e.g., alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and amylase), receptors (e.g., neural, hormonal, nutrient, and cell surface receptors) or their ligands, cancer markers (e.g., PSA, TNF-alpha), markers of myocardial infarction (e.g., troponin, creatine kinase, and the like), toxins, drugs (e.g., therapeutic drugs, drugs of addiction), metabolic agents (e.g., including vitamins and minerals), metabolic products (e.g., glucose, urea nitrogen triglycendes, uric acid), nutrients, and the like. Non-limiting embodiments of protein analytes include peptides, polypeptides, protein fragments, protein complexes, fusion proteins, recombinant proteins, phosphoproteins, glycoproteins, lipoproteins, and the like. In certain embodiments, the analyte may be a post-translationally modified protein (e.g., phosphorylated, methylated, glycosylated protein). In certain embodiments, the analyte is a nucleic acid. In certain embodiments, the analyte is a protein or a small molecule.

[0089] A non-limiting list of analytes that may be analyzed by the module presented herein include A42 amyloid beta-protein, fetuin-A, tau, secretogranin II, prion protein, alpha-synuclein, tau protein, neurofilament light chain, parkin, PTEN induced putative kinase 1, DJ-1, leucine-rich repeat kinase 2, mutated ATP13A2, Apo H, ceruloplasmin, peroxisome proliferator- activated receptor gamma coactivator- 1 alpha (PGC-1), transthyretin, vitamin D-binding protein, proapoptotic kinase R (PKR) and its phosphory lated PKR (pPKR), CXCL13, IL-12p40, CXCL13, IL-8, Dkk-3 (semen). pl4 endocan fragment, serum. ACE2, autoantibody to CD25, hTERT, CAI25 (MUC 16), VEGF, sIL-2, osteopontin, human epididymis protein 4 (HE4), alpha-fetoprotein, albumin, albuminuria, microalbuminuria, neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule -1 (KIM-1), liver fatty acid binding protein (L-FABP), LMP1, BARF1, IL-8, carcinoembryonic antigen (CEA), BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and LZTS1, alpha-amylase, carcinoembryonic antigen, CA 125, IL8, thioredoxin, beta-2 microglobulin levels - monitor activity of the virus, tumor necrosis factor- alpha receptors - monitor activity' of the virus, CAI 5-3, follicle-stimulating hormone (FSH), luteinizing hormone (LH), T-cell lymphoma invasion and metastasis 1 (TIAM1), N-cadherin, EC39, amphiregulin, dUTPase, secretory gelsolin (pGSN), PSA (prostate specific antigen), thymosin 15, insulin, plasma C-peptide, glycosylated hemoglobin (HBAlc), C-reactive protein (CRP), interleukin-6 (IL-6), ARHGDIB (Rho GDP-dissociation inhibitor 2), CFL1 (Cofilin-l), PFN1 (profilin-1), GSTP1 (Glutathione S-transferase P), S100A11 (Protein SI 00- Al 1), PRDX6 (Peroxiredoxin-6). HSPE1 (lOkDaheatCEP Ref No. 2025-26316 | M&G Ref. No. 19582.0033WOU1shock protein, mitochondrial), LYZ (Lysozyme C precursor), GPI (Glucose-6-phosphate isomerase), HIST2H2AA (Histone H2A type 2-A), GAPDH (Glyceraldehyde-3- phosphate dehydrogenase), HSPG2 (Basement membrane-specific heparan sulfate proteoglycan core protein precursor), LGALS3BP (Galectin-3-binding protein precursor), CTSD (Cathepsin D precursor), APOE (Apolipoprotein E precursor), IQGAP1 (Ras GTPase-activating-like protein IQGAP1), CP (Ceruloplasmin precursor), and IGLC2 (IGLC1 protein), PCDGF / GP88, EGFR, HER2, MUC4. IGF-IR, p27(kipl), Akt, HER3. HER4. PTEN. PIK3CA, SHIP. Grb2, Gab2. PDK-1 (3-phosphoinositide dependent protein kinase-1), TSC1, TSC2, mTOR, MIG-6 (ERBB receptor feedback inhibitor 1), S6K, src, KRAS, MEK mitogen-activated protein kinase 1, cMYC, TOPO II topoisomerase (DNA) II alpha 170 kDa, FRAP1, NRG1, ESRI, ESR2, PGR, CDKN1B, MAP2K1, NEDD4-1, FOXO3A, PPP1R1B. PXN, ELA2. CTNNB1, AR, EPHB2, KLF6, ANXA7, NKX3-1, PITX2, MKI67, PHLPP, adiponectin (ADIPOQ), fibnnogen alpha chain (FGA), leptin (LEP), advanced glycosylation end product-specific receptor (AGER aka RAGE), alpha-2-HS-glycoprotein (AHSG), angiogenin (ANG), CD14 molecule (CD14), ferritin (FTH1), insulin-like growth factor binding protein 1 (IGFBP1). interleukin 2 receptor, alpha (IL2RA), vascular cell adhesion molecule 1 (VCAM1) and Von Willebrand factor (VWF), myeloperoxidase (MPO), ILL TNF, perinuclear anti- neutrophil cytoplasmic antibody (p-ANCA), lactoferrin, calprotectin, Wilm's Tumor- 1 protein, Aquaporin-1, MLL3, AMBP, VDAC1, E. coli enterotoxins (heat-labile exotoxin, heat-stable enterotoxin), influenza HA antigen, tetanus toxin, diphtheria toxin, botulinum toxins, Shiga toxin, Shiga-like toxin I, Shiga-like toxin II, Clostridium difficile toxins A and B, etc.

[0090] Exemplary' targets of nucleic acid aptamers that may be measured in a sample such as an environmental sample, a biological sample obtained from a patient or subject in need using the subject modules include: drugs of abuse (e.g. cocaine), protein biomarkers (including, but not limited to, nucleolin, nuclear factor-kB essential modulator (NEMO), CD-30, protein tyrosine kinase 7 (PTK7), vascular endothelial growth factor (VEGF), MUC1 glycoform, immunoglobulin p heavy chains (IGHM), immunoglobulin E, v3 integrin, -thrombin, HIV gpl20, NF-B, E2F transcription factor, HER3, Plasminogen activator inhibitor, Tenascin C,CXCL12 / SDF-1, prostate specific membrane antigen (PSMA), gastric cancer cells, HGC-27); cells (including, but not limited to, non-small cell lung cancer (NSCLC), colorectal cancer cells, (DLD-1), H23 lung adenocarcinoma cells, Ramos cells, T-cell acute lymphoblastic leukemia (T-ALL) cells, CCRF-CEM, acute myeloid leukemia (AML) cells (HL60), small-cell lung cancer (SCLC) cells, NCIH69, human glioblastoma cells, U118-MG, PC-3 cells, HER-2-CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1overexpressing human breast cancer cells, SK-BR-3, pancreatic cancer cell line (Mia-PaCa-2)); and infectious agents (including, but not limited to, Mycobacterium tuberculosis, Staphylococcus aureus, Shigella dysenteriae, Escherichia coli 0157:H7, Campylobacterjejuni, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella 08, Salmonella enteritidis). Exemplary targets of protein or peptide aptamers that may be measured in a sample obtained from a patient or subject in need using the subject modules include, but are not limited to: HBV core capsid protein, CDK2, E2F transcription factor, thymidylate synthase, Ras, EB1, and Receptor for Advanced Glycated End products (RAGE).

[0091] In certain cases, a biological sample (e.g., human blood sample) that contains or is suspected of containing a target nucleic acid may undergo preparation / processing prior to detection by a module of a sample analyzer of the present disclosure. In some embodiments, the preparation / processing may include the following steps: i) isolation of nucleic acid that contains a target nucleic acid from the sample, ii) optionally, enrichment of the target nucleic acid, iii) amplification of the target nucleic acid, and iv) processing of the amplified target nucleic acid. Each step can be performed manually, automatically, or by a combination thereof. In certain embodiments, the analyte is not amplified (i.e., the copy number of the analyte is not increased) prior to the measurement of the analyte. For example, in cases where the analyte is DNA or RNA, the analyte is not replicated to increase copy numbers of the analyte. In some cases, methods involve the use of one or more reference standards for quantifying an analyte. The reference standards may be employed to establish standard curves for interpolation and / or extrapolation of the analyte concentrations. In other embodiments, a system of the present disclosure may include reference standards that vary in terms of concentration level. Any combination of analytes may be measured by the assays of the modules. In some cases, assays of the present disclosure can be used to determine the presence or absence of an analyte in a sample or measure the amount of an analyte in a sample to identify or assess a disease or condition. Measurements of an analyte can be used, for example, but not by way of limitation, determine the likelihood of developing a disease or condition; diagnose, identify, or classify a disease or condition; estimate prognosis; determine the extent of a disease or condition; determine appropriate treatment; predict response of a disease or condition to treatment; monitor response of a disease or condition to treatment; determine treatment efficacy; and identify' recurrence of a disease or condition.

[0092] In various embodiments, an optical sensor is configured to convert light received from cells within a portion of the imaging chamber to an output signal, and a processorCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1connected to the optical sensor is configured to convert the output signal to a number count or percentage for each type of cell in the blood sample. In some embodiments, a differential blood cell count is a measurement of a number or percentage of each type of cell (e.g., white blood cells (WBCs)) that is in a whole blood sample.

[0093] In some embodiments, a plurality of sample processing modules 102 can include at least one module type selected from: a module that configured for PCR analysis; a module configured for isothermal analysis; a module configured for detection of at least one protein analyte; a module configured for assessing a chromosomal copy number of at least one gene of interest; a module configured for performing a multiplex detection of at least two nucleic acid analytes; a module configured for performing a multiplex detection of at least two protein analytes; a module configured for sequencing and detecting a nucleic acid molecule; a module that configured for preparation of a library for sequencing; a module that configured for nucleic acid analysis; a module configured for preparation of a sample prior to analysis; a module configured for detection of at least one enzyme of interest; a module configured for performing and detection of an immunoassay; a module configured for detection of an aptamer of interest; a module configured for detection of a whole cell or tissue; and a module configured for performing rapid PCR.

[0094] In some embodiments, the plurality of sample processing modules 102 can include at least one module configured for nucleic acid analysis. Nucleic acid analysis can include, but is not limited to, polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR), real time quantitative PCR (RT-qPCR), thermal convection PCR, isothermal PCR, thermocycle based PCR, hot-start PCR, loop-mediation isothermal amplification (LAMP), recombinase polymerase amplification (RPA), nucleic acid lateral flow immunoassay (NAFLIA), helicase dependent amplification (HAD), rolling circle amplification (RCA), nicking enzyme amplification reaction (NEAR), CRISPR-Cas detection methods (e.g., SHERLOCK (specific high-sensitivity' enzymatic reporter unlocking), DETECTR (DNA Endonuclease Targeted CRISPR Trans Reporter), and HOLMES (one-Hour Low-cost Multipurpose highly Efficient System), nucleic acid hybridization detection and probes (e.g., dot- blot, Southern blot, in situ hybridization, sequence specific probes (TaqMan probes), bead and microarray based oligonucleotide probes), fluorescence in situ hybridization (FISH), peptide nucleic acidfluorescence in situ hybridization (PNA-FISH), chromogenic in situ hybridization (CISH), nucleic acid sequencing, high-throughput sequencing, next-generation sequencing, deep sequencing, whole genome sequencing, whole exome sequencing, Northern blot, nucleaseCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1protection assays (NPA), oligo probes on chips, e.g., ViroChip, other detection methods such as fluorophore probes, enzyme or fluorescently labelled probes, turbidity, colorimetric, and the like. In certain embodiments, amplification is used for increasing the amount of nucleic acid for performing the assay and in the process of detecting and identifying nucleic acid sequences. For example, the amplification is performed in PCR and RT-PCR.

[0095] In examples, PCR analysis can be performed via thermal cycling, thermal convection, continuous flow PCR, thermal gradient, digital PCR, RT-PCR, and other PCR methods.

[0096] In examples, isothermal analysis can be performed via loop mediated isothermal amplification (LAMP), nucleic acid sequence based amplification (NASBA), self-sustained sequence replication (3 SR), rolling circle amplification (RCA), strand displacement amplification (SDA), Whole Genome Amplification (WGA), Helicase-Dependent Amplification (HD A), Recombinase Polymerase Amplification (RPA), and other isothermal amplification methods.

[0097] In some cases, analyzing the sample fluid comprises an immunoassay (IA). An immunoassay generally comprises contacting an antigen with an antibody specific for the antigen to form an antibody-antigen complex and detecting the antibody-antigen complex. In some embodiments, the antibody-antigen complex is an antibody-analyte complex. In other embodiments, the analyte is an antigen. In other embodiments, an antigen that may be bound by an antibody includes, but is not limited to, proteins, peptides, polysaccharides, lipids, or nucleic acids. Cartridges may be designed to perform various types of immunoassays. In some embodiments, the immunoassay may be a labelled immunoassay. In labelled immunoassays, the antibody-analyte complex may be detected using a detectably labeled antibody. Detectable labels may be selected from a variety of such labels known in the art, but normally are radioisotopes, fluorophores, enzymes (e.g., horseradish peroxidase), or other moieties or compounds which either emit a detectable signal (e.g., radioactivity, fluorescence, color) or emit a detectable signal after exposure of the label to its substrate. Additional labels can include, but are not limited to. DNA probes and reporters, electrochemiluminescent tags, and magnetic particles. Various detectable label / substrate pairs (e.g., horseradish peroxidase / diaminobenzidine, avidin / streptavidin, luciferase / luciferin), methods for labelling antibodies, and methods for using labeled antibodies to detect an antigen are well known in the art. In other embodiments, the immunoassay may be an unlabeled immunoassay. Unlabeled immunoassays are performed without labels and include, but are not limited to, techniques suchCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1as immunodiffusion and nephelometry. In some embodiments, the immunoassay may be a heterogeneous immunoassay. Heterogeneous immunoassays require separation of the antibody-analyte complex from the other components of the immunoassay prior to analysis. In other embodiments, the immunoassay may be a homogeneous immunoassay. Homogeneous immunoassays do not require separation of the antibody-analyte complex from the other components of the immunoassay prior to analysis. In some embodiments, the immunoassay may be a competitive immunoassay. In competitive immunoassays, the analyte competes with a specific quantity of labeled antigen for the antibody. In other embodiments, the immunoassay may be a noncompetitive immunoassay. In noncompetitive immunoassays, excess labeled antibody is used to bind with the analyte. Antibodies and antigens of an immunoassay may be arranged in a variety of configurations. In some embodiments, the antibodies and antigens of the immunoassay are in solution. In other embodiments, either the antibody or the antigen is bound to a solid surface. In yet another embodiment, the antibody or the antigen from the sample is bound to a solid surface. In some embodiments, the antibody is labelled. In some embodiments, the antigen is labelled. In some embodiments, more than one antibody may be used to detect the analyte. In other embodiments, two or more antibodies may bind to the same antigen. In other embodiments, two or more antibodies may bind to different epitopes of the same antigen. In other embodiments, two or more antibodies may bind to different antigens of an analyte. In other embodiments, a first antibody binds to an antigen, and a second antibody binds to the first antibody. In other embodiments, two antibodies compete to bind an antigen. In some embodiments, a known amount of an identifiable antigen or analyte competes with the antigen or analyte for binding with an antibody. Any suitable immunoassay may be utilized. Examples of well-known immunoassay variations include, but are not limited to, immunoassay, such as sandwich immunoassay (e.g., monoclonal -poly clonal sandwich immunoassays), enzyme detection, such as enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) (e.g., direct, indirect, competitive, and sandwich ELISA), competitive inhibition immunoassay (e.g., forward and reverse), enzyme multiplied immunoassay technique (EMIT), a competitive binding assay, bioluminescence resonance energy transfer (BRET), one-step antibody detection assay, homogeneous assay, heterogeneous assay, capture on the fly assay, and the like. In some embodiments, immunoassays may be used to detect nucleic acid sequences. Once a desired degree of target nucleic acid sequence amplification is achieved, the amplification product can be detected using an immunoassay. Various formats of assay processing can be employed. For example,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1an immunoassay can be performed to capture target amplified nucleic acid sequences using the tag incorporated into the amplified target nucleic acid. Specifically, a capture object (such as, a bead, e.g., a magnetic bead) include a binding member of a specific binding pair and captures the amplified target nucleic acid via interaction of the member of the binding pair with the other member of the binding pair, which other member that has been introduced into the amplified target nucleic acid during amplification. The capture object is not coated with a nucleic acid that can bind to the amplified target nucleic acid. Immunoassays of the present methods and devices may be analyzed using various methods to detect the antibody-analyte complex. Such methods of detection may depend on the format of the immunoassay and can include, but are not limited to, detection of a radiation, detection of an enzy me product, detection of fluorescence, changes in color, changes in turbidity, changes in electrical impedance, changes in optical properties, agglutination, and the like. In still other embodiments, assays for measuring biomolecules or clinical chemistry’ panels in a sample include enzymatic methods by using enzymes to react with analyte, such as electrolytes, CO2, serum creatinine, blood urea nitrogen, and detect reaction product.

[0098] In yet other embodiments, the assays for measuring biomolecules or clinical chemistry panels in a sample include chemical reaction methods, which are similar to enzymatic methods but with chemical reagents and using spectrophotometry7. In yet other embodiments, the assays for measuring biomolecules or clinical chemistry panels in a sample include changes in pH level. In yet other embodiments, the assays for measuring biomolecules or clinical chemistry panels in a sample include the use of nephelometry. Nephelometry is used to measure the amount of turbidity' or cloudiness by measuring scattered light and can be used in combination with immunoassays. In yet other embodiments, the assays for measuring biomolecules or clinical chemistry panels in a sample include the use of photometry, which measures absorbed light (UV, visible, IR) to determine amount of an analyte in a solution or liquid. In other embodiments, the assays for measuring biomolecules or clinical chemistry panels in a sample include coagulation assays.

[0099] In examples, as further described with respect to FIG. 12, each type of module 102 can have similar dimensions such that a given module 102 can be interchangeably received by any' bay of the sample analyzer 100. In other examples, each type of module 102 can be configured with interfacing members that allow a module 102 of any given ty pe to be received by any bay of the sample analyzer 100. In this manner, the sample analyzer 100 can beCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1customizable to a given laboratory's unique requirements such as turnaround requirements, analytes of interest, cost considerations, and the like.

[0100] In one example, the module 102 can be a first module type and a second module type. In one other example, the module 102 can be a first module type, a second module type, a third module type, or a combination thereof. In other examples, the module 102 can be a first module type, a second module type, a third module type, a fourth module type, or a combination thereof. In examples, the sample analyzer 100 can receive a plurality of sample processing modules 102 configured to perform either PCR analysis, lab on a chip analysis, or both. For example, a sample processing module 102 that is only configured to perform PCR analysis can be interchangeable with a sample processing module 102 that is only configured to perform lab on a chip analysis.

[0101] In examples, a plurality of sample processing modules can include at least one module of a first type that is configured to perform PCR analysis, at least one module of a second type that is configured to perform non-thermal cycling detection of an analyte, and at least one module of a third type that is configured for lab on a chip analysis. In other examples, a plurality of sample processing modules can include at least one module of a first type that is configured to perform PCR analysis and at least one module of a second type that is configured to perform non-thermal cycling detection of an analyte.

[0102] For example, a first module type can be configured to perform nucleic acid amplification. A wide variety of nucleic acid amplification methods may be performed. For example, nucleic acid amplification may include multiple cycles of sequential procedures in order to generate enough of the sample to be detectable. Nucleic acid amplification may include thermal convection, using heat differentials to drive a reagent between different regions of the reaction tube for spatially separate melting, annealing, and extending, in order to generate enough of the sample to be detectable. In other examples, amplification can comprise thermocycling or can be performed isothermally. Isothermal amplification typically requires the use of a nucleic acid polymerase that has strand displacement activity7and / or some other means to effect strand separation. Thermocycling is standardly carried out by subjecting a PCR reaction mixture to three temperatures per cycle in the following sequence: denaturation, usually at about 95°C; annealing, usually at about 5°C below the Tm of the primers; and extension (e.g., at about 72°C). Some methods simplify this temperature / time course to two temperatures per cycle. In yet another example, the first module is configured to perform active cooling. For example, active cooling facilitates nucleic acid amplification.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1In some embodiments, active cooling can be used in combination with or in replacement of other thermocycling methods. Nucleic acid amplification may include amplification at a constant temperature without thermal cycling, such as isothermal amplification. In embodiments, the first module type can be configured to perform nucleic acid amplification by thermal convention, thermal cycling, and isothermal amplification, among other means for nucleic acid amplification.

[0103] In another example, a second module type can be configured to perform nonthermal cycling detection of an analyte. For example, a second module type can be configured to perform non -thermal cycling detection of an analyte. For example, a second module type can be configured to amplify nucleic acids via ultrafast thermal convection as will be further illustrated and discussed with respect to FIG. 10 and 46-56. In other examples, the second module can perform thermally-dependent, non-thermal cycling detection via isothermal nucleic acid amplification. In further examples, the second module can perform non-thermally-dependent detection, such as immunofluorescence assay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, antigen assay, nucleic acid hybridization, metagenomic sequencing, CRISPR, turbidity, colorimetry, or combinations thereof.

[0104] In some embodiments, the first module ty pe can be configured to perform nucleic acid amplification and the second module type can be configured to perform non-thermal cycling detection are configured to detect the presence of an analyte within 30 minutes of initiation of sample processing. For example, the first and second module types are configured to detect the presence of an analyte in less than 20 minutes, less than 19 minutes, less than 18 minutes, less than 17 minutes, less than 16 minutes, less than 15 minutes, less than 14 minutes, less than 13 minutes, less than 12 minutes, less than 11 minutes, less than 10 minutes, less than 9 minutes, less than 8 minutes, less than 7 minutes, less than 6 minutes, or less than 5 minutes.

[0105] In still another example, the module 102 can be a third module ty pe configured to perform lab on a chip analysis. In examples, a third module ty pe can be configured to perform lab on a chip analysis on an analysis chip secured within the sample cartridge assembly^ 110. As further described with respect to FIGS. 39-40, an analysis chip can include a biosensor configured to detect target analytes, a temperature sensor configured to provide temperature data for compensating the biosensor, a processing unit configured to process signals from the biosensor and the temperature sensor, and a memory configured to storeCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1calibration data, trim coefficients, or a combination thereof. In some examples, the third module type can include a control unit further configured to receive and process data from the analysis chip. For example, as further described with respect to FIG. 3, the third module type can include a control unit 126 having an anomaly detection system, a chip calibration system, a feature calibration system, or a combination thereof. The third module type configured to perform lab on a chip analysis can detect one or more of the target analytes disclosed herein. In examples, the third module type configured to perform lab on a chip analysis is capable of various measurements and detection including analyzing nucleic acid (e.g., amplification, SNP detection, insertion or deletion determination, chromosome translocation), immunoassays, clinical chemistry assays, enzyme-linked immunosorbent assay, antigen assay, nucleic acid hybridization. CRISPR. turbidity, colorimetry, or combinations thereof.

[0106] In yet another example, the module 102 can be a fourth module type configured to perform sample preparation, next-generation sequencing, nucleic acid library preparation, or a combination thereof. In some examples, the fourth module type can be configured to perform nucleic acid amplification and lab on a chip analysis. In other examples, a fourth module type can be configured to perform non-thermal cycling detection of an analyte and lab on a chip analysis. In further examples, a fourth module type can be sized and shaped to occupy two receiving bays 201.

[0107] In some implementations, the module 102 can be slidably secured within the interior of the chassis 104. For example, once secured within the chassis 104, the exterior of each module 102 can be flush with the front panel 106. In some embodiments, the module 102 can be removably secured within the interior of the chassis 104. In some examples, one or more modules 102 may periodically require maintenance or replacing. For example, over time, components of the modules 102 may be replaced or become obsolete. Currently, replacing or repairing modules requires specific tools and careful removal of one or more parts of the sample analyzer 100 which can be time-consuming and require significant down time especially when needing to access several modules. Advantageously, the sample analyzer 100 discussed herein facilitate toolless, removal, repair or replacement of modules 102 with improved speed and accessibility. Examples of solutions for enabling simplified toolless access of modules 102 from the front of the sample analyzer are discussed herein with respect to FIGS. 11-26. Furthermore, any of the various solutions and embodiments for enabling toolless access to theCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1modules 102 from the front of the sample analyzer 100 as discussed herein can include more, fewer, or different combinations of components from one another.

[0108] The chassis 104 is the main structural frame of the sample analyzer 100. For example, the chassis 104 can include an interior and an exterior. For example, each module 102 can be removably secured within the interior of the chassis 104. In some examples, each module 102 can be secured within the interior of the chassis 104 such that the module door 124 of each module 102 is accessible from the exterior of the chassis 104. In some examples, the sample analyzer 100 further includes one or more module rack 200 secured within the interior of the chassis. An example module rack 200 is illustrated and described with reference to FIG.12.

[0109] The front panel 106 forms the front of the sample analyzer 100. In some examples, as discussed herein, the front panel 106 is configured to allow toolless access to the modules 102. For example, the front panel 106 can be hingedly secured to the chassis 104 such that a plurality7of modules 102 can be simultaneously accessed. Examples implementations of a front panel 106 secured to the chassis 104 by along arm pivot hinge 302 are illustrated and discussed with reference to FIGS 13-20. The front panel is further illustrated and described with reference to FIG. 27.

[0110] The display 108 is configured to display information to a user. For example, the display 108 can be a liquid-crystal display (LCD), a light-emitting diode (LED) display , or the like. In some examples, the display 108 can be a touch screen display. In some embodiments, the information on the display 108 can also be communicated to external monitors. In some examples, the display 108 can be configured to output information, receive user input, or both. The display 108 can be configured to output information to a user in the form of a user interface. The display 108 can be configured to receive information or instructions from a user via the user interface. An example user interface will be further illustrated and described with respect to FIG. 27.

[0111] Any convenient technique may be utilized in order to identify the presence and / or the type of sample cartridge, fluid sample, user, or a combination thereof. For example, mechanical techniques (e.g., keying or a unique pin structure associated with different types of cartridges) or electronic techniques (e.g., digital encodings stored on a non-volatile memory, RFID techniques or other wireless identifiers, magnetic encodings, etc.) or optical techniques, such as barcodes, 2D bar codes or other optical identifiers capable of being read by a camera present on the sample cartridge, or combinations thereof. In embodiments, a barcode readerCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1109 is configured to facilitate the identification of a sample cartridge assembly 110, a fluid sample, a user, or a combination thereof. For example, the barcode reader 109 can be configured to scan a sample cartridge assembly identifier, a fluid sample identifier, a user identification badge, or a combination thereof. In examples, an identifier can be a digital label, a printed label, an RFID tag, and the like. In some embodiments, based on the information received via the barcode reader 109. the sample analyzer can identify the type of module 102 configured to process the sample cartridge assembly 110, the fluid sample therein, or the type of analysis to be performed on the fluid sample. For example, based on the information received via the barcode reader 109, the sample analyzer 100 can be configured to unlock a door of one or more module 102 to allow the loading or unloading of a sample cartridge assembly 110. In some embodiments, the sample analyzer 100 can be configured to unlock a door of one or more module of a module type based on the information received via the barcode reader 109. In some examples, all or a portion of the information received via the barcode scanner can be output to the display 108. In other examples, the sample analyzer can be configured to identify to a user, via the display 108, one or more indicator light(s), or a combination thereof, one or more module to which the sample cartridge assembly can be inserted. For example, based on the information received via the barcode reader 109, the sample analyzer 100 can be configured to identify' to a user one or more module(s) to which a given sample cartridge can be inserted, based in part on the respective one or more module(s) being of one or more module type(s) appropriate to process the given sample cartridge assembly 110, the fluid sample currently or to be received therein, the sample analysis to be executed on the fluid sample, or a combination thereof.

[0112] In some implementations, the processor 121 of the sample analyzer 100 can receive one or more signal(s) from the barcode reader 109. based on a given barcode scanned by the barcode reader 109. In some embodiments, based on the one or more signal(s) received from the barcode reader 109, the processor 121 can execute a set of instructions, such as those stored within a memory 123. For example, the set of instructions can include unlocking one module of a given module type, one module of any module type, a plurality of module of a given module type, a plurality of modules of a subset of module types, or a plurality of modules of any module type. In some implementations, based on the one or more signal received from the barcode reader 109, the processor 121 can execute a set of instructions to identify to a user which module(s) the sample cartridge assembly can be inserted into. For example, the processor 121 can execute a set of instructions to identify to a user one or more module toCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1which a given sample cartridge assembly may be inserted into via the user interface, one or more indicator light, or both.

[0113] In some examples, the barcode reader 109 is configured to read a first barcode directed to a first assay type, the first barcode being on or associated with a first sample cartridge assembly. For example, a unique assay type may be associated with a unique identifier in a lookup table. For example, a first assay type may be associated with a first unique identifier in a lookup table. In another example, a second assay type may be associated with a second unique identifier in a lookup table. In other embodiments, a unique assay type may be associated with a unique set of instructions executable by the sample analyzer 100. For example, a unique set of instructions may relate to sample processing steps and analysis required to execute a unique assay type. For example, a first assay type can be associated with a first set of instructions executable by the sample analyzer 100, one or more of module 102, or both. In other examples, a second assay type can be associated with a second set of instructions executable by the sample analyzer 100, one or more module type, or both.

[0114] In some embodiments, the processor 121 of the sample analyzer 100 can be configured to execute a set of instructions including receiving a first signal from the barcode reader based on the first barcode and, in response to the first signal, determine the first type of assay. In further examples, the processor 121 can be configured to transmit instructions to run the first assay type on a first sample processing module type of the plurality of sample processing modules. For example, the processor 121 can be configured to transmit instructions to the sample analyzer 100 to unlock only modules of a first module type, based on the first signal. Similarly, based on a second signal, the processor 121 can be configured to transmit instructions to the sample analyzer 100 to unlock one or more module of a second module type. In further examples, based on a third signal, the processor 121 can be configured to transmit instructions to the sample analyzer to unlock one or more module of a third module type.

[0115] The sample cartridge assembly 110 includes components for receiving and processing a biological sample for analysis by the sample analyzer 100. The sample cartridge assembly 110 includes the sample cartridge 112 and the reaction tube assembly 114. An example sample cartridge assembly 110 is further illustrated and described with reference to FIG. 5.

[0116] The sample cartridge 112 is configured to receive a biological sample and secure the reaction tube assembly 114. The sample cartridge 112 can include one or more chambers configured to receive and process a biological sample. In some examples, the biological sampleCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1can be a fluid sample. Once a biological sample is added to the sample cartridge 112, the sample cartridge assembly 110 can be loaded into the module 102 for processing and analysis.

[0117] The reaction tube assembly 114 is configured to channel a processed sample to the analysis region 116. For example, the reaction tube assembly 114 can fluidically couple to the sample cartridge 112. For example, the reaction tube assembly 114 can include one or more fluidic channel configured to transport a biological sample from the sample cartridge 112 to an analysis region 116. In some examples, the reaction tube assembly 114 can secure an analysis chip and facilitate proper alignment of the analysis chip with electrical contacts or detection units housed within the module 102. An example reaction tube assembly 114 having an analysis chip is illustrated and described with respect to FIGS. 6 and 7. An example analysis chip 142 will be further illustrated and described with respect to FIGS. 39-40.

[0118] The analysis region 116 is configured to provide a sealed region to facilitate analysis of the biological sample. For example, the analysis region 116 can present a volume of processed biological sample for optical, electrical, electro-optical, or electrochemical interrogation (e.g., to a light excitation source, such as LED or light box and, detector) within the module 102 such that PCR detection can take place. For example, the analysis region 116 can include two flat faces, as described with respect to FIGS. 9 and 10, configured to present a volume of a processed biological sample to a light excitation source (e.g. one or more LED or light box) and a detector of a first module type or a second module type. In other examples, the analysis region 116 can present a volume of processed biological sample to a sensing region of an analysis chip therein. For example, the analysis region can present a volume of processed biological sample to a sensing region of an analysis chip therein configured to be received by a third module type.

[0119] In some examples, the internal power, computing components, and modules 102 of the sample analyzer 100 can generate significant heat. In some examples, the heat generated by one or more module 102 can vary depending on the type of analysis that the module 102 is conducting (e.g. PCR or lab on a chip). Advantageously, as introduced in FIG. IB and discussed in further detail herein, the sample analyzer 100 provides enhanced thermal management through directed air inflow and outflow.

[0120] FIG. IB is a back perspective view of an example sample analyzer 100. The sample analyzer includes a back panel 118. The sample analyzer 100 is configured with a thermal management system that includes an air intake vent 120 and an air outlet vent 122.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0121] The back panel 118 can form the back of the sample analyzer 100. The back panel can include one or more air vents, including the air intake vent 120 and the air outlet vent 122.

[0122] The air intake vent 120 is configured to direct cool air to one or more components of the sample analyzer 100. As illustrated in FIG. IB, the sample analyzer 100 can include more than one (e.g. a plurality) of air intake vents 120.

[0123] The air outlet vent 122 is configured to direct hot air away from the sample analyzer 100. As illustrated in FIG. IB, the sample analyzer 100 can include more than one (e.g. a plurality) of air outlet vents 122.

[0124] The thermal management system discussed herein can account for variations of heat generated within the sample analyzer 100. For example, air inflow and air outflow can be channeled based on the heat sensed at different modules 102 or the type of analysis that the respective modules 102 are conducting or capable of conducting (e.g. PCR or lab on a chip). For example, not every module 102 can conduct both PCR and lab on a chip analysis. As discussed herein, a module 102 that conducts PCR analysis must include thermal cycling units which generate significant heat. In some embodiments, the thermal management system can direct more cool airflow to modules 102 that can conduct only PCR analysis. Overall, this thermal management system reduces downtime and improves the overall lifespan of the sample analyzer 100 and modules 102 by providing more efficient cooling and prevention of hot spots or overheating. In some examples, introduction of cool airflow to the modules 102 can unintentionally introduce dust or other debris. Example thermal management systems and filtration methods are further illustrated and described with respect to FIGS. 29- 37.

[0125] FIG. 2 is a block diagram of an example sample analyzer. The sample analyzer includes a display 108, a barcode reader 109, a processor 121, a memory' 123, and a plurality of module receiving bays 201.

[0126] As described with respect to FIG. 1A, the display 108 is configured to display information to a user. For example, the display 108 can be a liquid-crystal display (LCD), a light-emitting diode (LED) display, or the like. In some examples, the display 108 can be a touch screen display. In some embodiments, the information on the display 108 can also be communicated to external monitors. In some examples, the display 108 can be configured to output information, receive user input, or both. The display 108 can be configured to output information to a user in the form of a user interface. The display 108 can be configured to receive information or instructions from a user via the user interface. An example user interface will be further illustrated and described with respect to FIG. 27.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0127] The processor 121 is configured to analyze and process data and signals acquired by one or more component of the sample analyzer. For example, the processor 121 can be configured to analyze and process data and signals acquired by the barcode reader 109. In some embodiments, the processor 121 can be configured to instructions stored in the memory 123. In some implementations, the processor 121 can be configured to communicate instructions to one or more module bay 201. module 102. or both. For example, the processor 121 can be configured to communicate instructions to one or more module bay 201, module 102, or both based on data and signals acquired by one or more component(s) of the sample analyzer.

[0128] In some embodiments, the processor 121 can be further configured to analyze and process data and signals acquired by the analysis chip 142. In some embodiments, the processor 121 analyzes and interprets the signals received from the analysis chip 142 to extract information. For example, the processor 121 can interpret data by applying algorithms or models for pattern recognition, statistical analysis, or diagnostic evaluations. In some embodiments, as further discussed herein, the processor 121 can calibrate and interpret data received from the analysis chip 142 to calculate clinically relevant results.

[0129] The memory 123 is configured to store data related to the operation of one or more component(s) of the sample analyzer. For example, the memory 123 can be configured to store data related to the operation of one or more module bay 201, module 102, display 108, barcode reader 109, or a combination thereof. In some implementations, the memory 123 can store instructions. In some implementations, the memory 123 can further store data generated by other components such as the processor 121 or the analysis chip 142.

[0130] As discussed with respect to FIG. 1A, the barcode reader 109 is configured to facilitate the identification of a sample cartridge assembly 110, a fluid sample, a user, or a combination thereof. In some implementations, the processor 121 of the sample analyzer 100 can receive one or more signals from the barcode reader 109, based on a given barcode scanned by the barcode reader 109. In some embodiments, based on the one or more signals received from the barcode reader 109, the processor 121 can execute a set of instructions.

[0131] As discussed with respect to FIG. 1A, the module receiving bays 201 (e.g. 201a-201n) are configured to receiving any of the plurality of module types described herein. In some implementations, the processor can send instructions to the one or more module receiving bays 201 based on data acquired by one or more component(s) of the sample analyzer 100.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0132] FIG. 3 is a perspective view of an example module. The module 102 includes a module door 124, a control unit 126. an optical unit 127, a syringe drive 128, and a valve drive 130. Also shown is an example sample cartridge assembly 110.

[0133] The module door 124 can move between open and closed positions. For example, the module door 124 can be opened to allow the sample cartridge 112 to be loaded into the module 102. In some embodiments, the module door 124 moves between open and closed positions, such as by pivoting or swinging on a hinge. In the example illustrated in FIG. 3, the module door 124 is in an open position that allows the sample cartridge 112 to be inserted into the module 102. In other instances, the module door 124 can be opened to allow a sample cartridge to be removed from the module 102. In some examples, the module door 124 is closed while a sample analysis protocol is performed.

[0134] The control unit 126 is the central processing unit of the module 102. In some embodiments, the control unit 126 manages the overall operation of the module 102. In some implementations, the control unit 126 can manage one or more steps of a sample processing protocol.

[0135] In a third type of module configured for lab on a chip analysis, the control unit 126 can further comprise an anomaly detection system, a frame processing system, a feature calibration system, or a combination thereof. For example, an anomaly detection system can be configured to identify and detect anomalies during sample processing. For example, the anomaly detection system can identify and detect anomalies within a chip carrier device 114 (which is an example of the reaction tube assembly 114) containing an analysis chip 142. In some implementations, the anomaly detection system can detect leaks within the chip carrier device 114. In other implementations, the anomaly detection system can detect bubbles within the chip carrier device. For example, the anomaly detection system can detect anomalies within the chip carrier device using data collected by the analysis chip 142. In some embodiments, instructions for the steps executed by the anomaly detection system can be stored within a memory of the control unit 126. In some examples, the steps executed by the anomaly detection system can be performed by a processor 121 of the control unit 126. In some implementations, results or alerts generated by the anomaly detection system can be displayed on the display 108. Examples of anomaly detection systems and methods are shown and described in commonly assigned U.S. Application No. 63 / 810,492, filed on May 22, 2025, entitled “ANOMALY DETECTION ON A LAB ON A CHIP,’' which is incorporated by reference.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0136] In examples, a frame processing system can be configured to process one or more frame of data received from the analysis chip. For example, the frame processing system can apply one or more normalization or calibration factor to improve the accuracy of downstream calculations. In other examples, the frame processing system can output data to a feature extraction system for further analysis. In some embodiments, a feature extraction system can be configured to receive data from the frame processing system. For example, the feature extraction system can analyze the analysis chip data to calculate one or more clinically relevant result. In examples, the feature extraction system can output results to the display 108. Examples of a lab on a chip calibration and feature extraction systems and methods are shown and described in commonly assigned U.S. Application No. 63 / 860,501, filed on August 08, 2025, entitled ' LAB ON A CHIP CALIBRATION AND FEATURE EXTRACTION. ” which is incorporated by reference.

[0137] The optical unit 127 is configured to detecting a target analyte in a fluid sample introduced to the reaction tube. Various detection of different target analytes may be performed by the optical unit using detectable labels including fluorophores, radioisotopes, enzymes (e.g., horseradish peroxidase), DNA probes and reporters, electrochemiluminescent tags, biochemiluminescent tags, magnetic particles, other moieties or compounds which either emit a detectable signal (e.g., radioactivity7, fluorescence, color) or emit a detectable signal after exposure of the label to its substrate, or optical sensors including complementary metal-oxide semiconductor (CMOS) sensors, N-type metal-oxide semiconductor (NMOS) sensors, photodiodes, active-pixel sensors (APSs), avalanche photodiodes, image sensors, charge-coupled devices (CCDs), intensified charge-coupled devices (ICCDs), light emitting diodes, photon counters, bolometers, pyroelectric detectors, photoresistors, photovoltaic cells, photodiodes, photomultiplier tubes (PMTs), phototransistors, quantum dot photoconductors or photodiodes, and combinations thereof. In some examples, the first module t pe, the second module type, the third module type, or all three, include an optical unit 127. In some examples, the third module type does not include an optical unit 127. In some examples, the optical unit 127 can include an optical excitation assembly configured to optically interrogate the sample contained in the reaction vessel. For example, the excitation assembly can include multiple light sources, such as LEDs, for exciting fluorescently-labeled analytes in the reaction vessel In one example, the excitation assembly can include red, green, blue, and yellow LEDs and / or UV light source, for exciting fluorescently-labeled analytes in the reaction vessel. For example, the optical unit 127 for the first sample processing module or the second sample processingCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1module can include red, green, blue, and yellow LEDs and / or UV light source. In other examples, the optical unit 127 for the third sample processing module that is configured for lab on a chip analysis can include blue and UV LED light source. In further examples, the excitation assembly can also include one or more lenses for collimating the light from the light sources, as well as filters for selecting the excitation wavelength ranges of interest. In some implementations, the optical unit can further include a detection assembly configured to detect the fluorescence and generate an output signal. For example, a detection assembly can include multiple detectors, such as photodiodes, for monitoring the light emitted from the reaction vessel. In some implementations, a detection assembly can also include one or more lenses for focusing and collimating the emitted light, as well as filters for selecting the emission wavelength ranges of interest.

[0138] In some examples, the optical unit 127 can be configured to detect a target analyte in a fluid sample retained in a reaction tube not configured to retain an analysis chip. In some embodiments, the optical unit comprises at least two light sources for transmitting one or more optical excitation beams to the reaction tube. In other embodiments, the optical unit comprises at least two light sources for transmitting two or more optical excitation beams to the reaction tube. In some embodiments, the biological sample processing apparatus includes an optical unit that comprises at least five light sources for transmitting one or more excitation beams to the reaction tube. In other embodiments, the optical unit comprises at least five light sources for transmitting one or more excitation beams to the reaction tube. In other examples, the optical unit comprises at least five light sources for transmitting five or more optical excitation beams. In some implementations, each light source is independently controlled. In some examples, the optical unit comprises at least two detectors configured to detect emission light from a processed sample in a plurality of wavelengths. In other examples, the optical unit is configured to simultaneously and differentially detect at least four emission wavelength ranges from the processed sample. In further examples, the optical unit is configured to simultaneously and differentially detect at least six emission wavelength ranges from the processed sample. In still other examples, the optical unit is configured to simultaneously and differentially detect at least ten emission wavelength ranges from the processed sample. For example, the optical unit can contain one or more light sources collectively configured to excite dyes and FRET pairs to cause the emission of at least ten wavelengths. In examples, the emission wavelengths can then be differentiated or deconvolved for detection purposes. In examples if the present disclosure, dyes having a large Stokes shift (LSS), such as a Stokes shift of about 50 nm or more, of aboutCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU160 nm or more, of about 70 nm or more, of about 80 nm or more, of about 90 nm or more, etc.) are used. The LSS dyes allow for facile tuning of their spectroscopic properties, such as their excitation and emission wavelengths.

[0139] In examples, the LSS dyes facilitate analysis of numerous targets in a single reaction tube. Fluorescence-based optical assemblies for polymerase chain reaction (PCR) can detect multiple targets in a single reaction vessel (multiplexing) by distinguishing light from differently colored fluorophores. The dyes are selected in a way to minimize their spectral overlap. Every fluorophore in the ensemble can be excited with light at or near the absorption maximum and the emitted light (fluorescence) is detected at or near the fluorescence maximum. By limiting the range of wavelengths (band) for excitation and emission with optical filters, individual fluorophores can be distinguished. The specific combination of an excitation band and a simultaneously detected emission band defines an optical channel, each allowing for the identification of one PCR target. The achievable maximum number of optical channels depends on numerous interrelated factors, such as available spectral range, excitation light intensity, fluorophore brightness, fluorophore spectral width, filter bandwidth, and detector sensitivity. The LSS labels allow the implementation of additional channels, such that the modules can use up to ten optical filters per excitation and emission pathway. Therefore, with LLS fluorophores, up to ten individual PCR targets can be distinguished in a single reaction tube.

[0140] In some embodiments, the analyte can be detected by electrochemical means. Electrochemical analysis can be performed by utilizing a working electrode that detects an electrical signal generated by an electroactive species generated by the presence of an analyte in the sample. The detected electrical signal may be quantitated to determine the presence or concentration of the analyte in the sample as the electrical signal is proportional to the amount of analyte present in the sample. Electrochemical detection may involve amperometry, coulometry, potentiometry, voltametery, impedance, or a combination thereof. In certain embodiments, the electrochemical species may be generated by action of an analyte-specific enzy me on the analyte. In other embodiments, the electrochemical species may be generated by action of an enzyme on a substrate. In such embodiments, the enzyme is not specific to the analyte. Rather, the enz me is conjugated to a binding member that specifically binds to the analyte. In certain embodiments, redox mediators may be included in order to amplify the electrical signal generated by the electrochemical species. Analyte specific enzymes and redox mediators are well known and may be selected based on the desired sensitivity and / orCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1specificity. In embodiments, cartridges additionally include an electrochemical sensor for determining one or more target analytes, e.g., as part of an electrochemical assay.

[0141] The syringe drive 128 is configured to interact with the sample cartridge 112 to facilitate preparation of a biological sample. In some examples, the syringe drive 128 can facilitate transport of a biological sample into the reaction tube assembly 114. In some implementations, the syringe drive 128 can include a lead screw assembly configured to drive a plunger that can interface with a corresponding plunger 160 of the sample cartridge 112 to facilitate preparation and transport of a biological sample.

[0142] The valve drive 130 is configured to interact with the sample cartridge 112 to facilitate preparation of a biological sample. In some examples, the valve drive 130 can facilitate transport of a biological sample into the reaction tube assembly 114. In other examples, the valve drive 130 can facilitate transport of a biological sample between multiple chambers disposed within the sample cartridge 112. In some implementations, the valve drive 130 can include a gear assembly configured to rotate a corresponding rotary valve 162 of the sample cartridge 112.

[0143] The module 102 may further include an ultrasonic horn assembly having an ultrasonic horn and a hom housing that engages with the sample cartridge through a movable mechanism that moves the ultrasonic hom between a disengaged or retracted position to facilitate loading, positioning, and / or ejection of the assay cartridge from the module. The hom assembly may also facilitate an engaged or advanced position of the sample cartridge to pressingly engage the hom against a sonication chamber of the sample cartridge to facilitate lysis of biological cells within a chamber. In some embodiments, the movable mechanism includes a spring or biasing mechanism and a cam that engages a wedge surface of the hom housing to effect movement of the hom between the lowered and raised positions. In some embodiments, movement of the hom assembly is effected by an actuator common to other movable components, such as a loading / ejection arm and a cartridge module door so as to provide efficient coordinated movements of components within the diagnostic device module. The hom assembly also includes circuitry, such as a printed circuit board, with interfaces adapted for electrical connection to corresponding circuitry within the system to facilitate operation of the ultrasonic hom by the system. In some implementations, each type of sample processing module includes an ultrasonic hom assembly. In other implementations, one or more type of sample processing module in the sample analyzer may not include an ultrasonic hom assembly, depending on the assay or sample being processed.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0144] In examples where the module 102 is configured for lab on a chip analysis, the module 102 can include electrical contacts to facilitate the powering and detection of an analysis chip. For example, the module 102 can include electrical contacts that engage with the analysis chip to allow the sample analyzer 100 to electrically power, control, and communicate with the analysis chip.

[0145] In examples where the module 102 is configured for PCR analysis, the module 102 can include thermal cycling units configured to thermally cycle a sample within the reaction tube assembly 114. As discussed herein, such thermal cycling units can generate significant heat and modules containing such thermal cycling units can require more thermal management than modules conducting only lab on a chip analysis.

[0146] FIG. 4 is a perspective view of a portion of an example module 132 configured to perform lab on a chip analysis. The example module 132 includes a module door 124, a temperature control system 134, and an instrument interface 136. In some embodiments, the instrument interface 136 includes a plurality of pogo pins 138. As shown in FIG. 4, a sample cartridge assembly 110 is also illustrated. In the example shown, the sample cartridge assembly 110 includes a sample cartridge 112 coupled to a reaction tube assembly 114, configured for lab on a chip analysis. An example reaction tube assembly 114 configured for lab on a chip analysis will be further illustrated and discussed with respect to FIGS. 6-7.

[0147] The module door 124 provides access to the sample cartridge assembly 110, as previously discussed. In some embodiments, the module door 124 moves between open and closed positions, such as by pivoting or swinging on a hinge. As an example, illustrated in FIG.4, the module door 124 is in an open position that allows the sample cartridge assembly 110 to be inserted in or moved away.

[0148] The temperature control system 134 is designed to regulate and maintain specific temperature conditions required for the testing process. In some embodiments, the temperature control system 134 ensures that temperature-sensitive reactions, measurements, or sample preparations occur under optimal thermal conditions. For example, the analysis chip of the reaction tube assembly 114 is maintained at a suitable temperature to facilitate proper biochemical reactions and readings, enhancing the accuracy of the results generated by the instrument. In some examples, the temperature control system 134 includes a combination of sensors, heating and cooling elements, a control unit, and insulation mechanisms, all working together to achieve and sustain the desired temperature range.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0149] The instrument interface 136 of the example module 132 is incorporated into the module 132 within a cartridge receiving opening where the sample cartridge assembly 110 is received. In some embodiments, the instrument interface 136 includes pogo pins 138 (e.g. bridge connector) that engage with corresponding contacts on the analysis chip. In some examples, the instrument interface 136 reads calibration data or trimming coefficients from the analysis chip. For example, the calibration data or trimming coefficients reading allows the instrument to automatically adjust its settings and algorithms according to the specific characteristics of the analysis chip.

[0150] The pogo pins 138 are electrical contacts. In some embodiments, the pogo pins 138 are configured for interacting with electrical contacts of the analysis chip. In some embodiments, when the reaction tube assembly 114 is inserted into the module 132. the pogo pins 138 engage with corresponding contacts of the analysis chip to allow the module 132 to control analysis of the biological sample within the analysis chip. An example analysis chip 142 will be further illustrated and described with respect to FIG. 7 and FIGS. 39-40.

[0151] FIG. 5 is a schematic diagram of an example sample cartridge assembly. In the example illustrated in FIG. 5, the sample cartridge assembly 110 includes a sample cartridge 112. In the example shown, the sample cartridge 112 is coupled to a reaction tube assembly 114 configured for lab on a chip analysis. An example reaction tube assembly 114 configured for lab on a chip analysis is further illustrated and described with respect to FIG. 7.

[0152] In alternative embodiments, the same sample cartridge 112 can be coupled to a reaction tube 180 (FIG. 9) configured for nucleic acid amplification without an analysis chip 142. In still other embodiments, the same sample cartridge 112 can be coupled to a reaction tube 180 configured for non-thermal cycling detection of an analyte. An example sample cartridge assembly 178 coupled to a reaction tube 180 configured for nucleic acid amplification without an analysis chip or non-thermal cycling detection of an analyte is further illustrated and described with respect to FIG. 8. An example reaction tube 180 configured for nucleic acid amplification without an analysis chip or non-thermal cycling detection of an analyte is further illustrated and described with respect to FIG. 9.

[0153] In the example illustrated in FIG. 5, the sample cartridge 112 includes a syringe tube 158, a plunger 160, a rotary valve 162, a prepared sample chamber 164, and one or more fluidic port 166. The reaction tube assembly 114 includes a frame 150. The frame 150 includes one or more fluidic channel 168 and an analysis region 116. In the example shown, the reactionCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1tube assembly 114 is securing an analysis chip having a biosensor array 170 (also referred to herein as biosensor 170) interfacing with the analysis region 116.

[0154] The sample cartridge 112 is a container that receives and processes a biological sample. In some examples, the sample cartridge 112 includes one or more processing chambers. For example, the processing chambers can include reagents, fdters, beads, and other technologies necessary’ to prepare the biological sample, such as to extract, purify, and / or amplify a target molecule. In some implementations, the sample cartridge 112 can also include a plunger 160 and a rotary valve 162 for providing selective fluid communication between the various processing chambers. In some implementations, the processing steps that take place within the sample cartridge 112 can be controlled by the module 102. For example, the plunger 160 and rotary valve 162 of the sample cartridge can be manipulated by one or more components of the module 102. In some implementations, the sample cartridge 112 is configured to receive the reaction tube assembly 114. For example, the sample cartridge 112 can have a fluidic interface configured for fluidically coupling with reaction tube assembly 114. In some implementations, the sample cartridge 112 can have a pair of fluid ports that couple with corresponding fluid ports of the reaction tube assembly 114 to form a fluidic interface between the sample cartridge 112 and the reaction tube assembly 114. For example, a fluidic interface between the sample cartridge 112 and the reaction tube assembly 114 can include a fluidic port 166. In some implementations the sample cartridge 112 can include a first fluidic port 166A and a second fluidic port 166B.

[0155] The analysis region 116 is configured to provide a sealed region to facilitate analysis of the biological sample. For example, the analysis region 116 can present a volume of processed biological sample to a light detector within the module 102 such that PCR detection can take place. In other examples, the analysis region 116 can present a volume of processed biological sample to a sensing region of an analysis chip therein. In the example shown the biosensor array 170 is positioned within the analysis region 116 such that prepared solution will interface with the surface of the biosensor array 170.

[0156] The frame 150 is configured to fluidically couple with the sample cartridge 112 and includes one or more fluidic channel 168 to direct a prepared sample to the analysis region 116. For example, the frame 150 can be a molded frame. In some implementations, the frame 150 can be molded by an injection molding system. In some embodiments, the frame 150 is formed of transparent material. For example, the frame 150 can include an exterior and an interior. In some examples, the frame 150 includes at least one access point for receiving aCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1fluid sample. In some embodiments, the frame 150 includes one or more fluidic channel 168. In some examples, the frame 150 includes an analysis region 116. In some implementations, the frame 150 can be configured for PCR analysis. In some embodiments, the frame 150 can be molded of transparent or substantially transparent material such that excitation light can be introduced from the module 102 to the analysis region 116. In some implementations, such as the example illustrated in FIG. 5, the frame 150 can be configured to secure an analysis chip 142 for lab on a chip analysis.

[0157] In the example illustrated in FIG. 5, the frame 150 is configured to secure an analysis chip 142 and includes additional features necessary for lab on a chip analysis. An analysis chip can be a sensing chip such as a silicon sensing chip. In one example, the analysis chip has an active surface such as a biosensor array 170. In some embodiments, the analysis chip is a semiconductor diagnostic chip.

[0158] The frame 150 can secure an analysis chip and facilitate proper alignment of the analysis chip with the electrical contacts or detection units housed within the module 102. For example, the frame 150 can include an access opening 152 such that the I / O pads 154 of the analysis chip can be accessed by the module 102. In some examples, the module 102 can include electrical contacts that engage with corresponding contacts on an analysis chip. In some implementations, the frame 150 is configured to secure the analysis chip such that the biosensor array 170 is positioned at the analysis region 116. In this manner, prepared sample can be introduced to the analysis region 116 and interface with the biosensor array 170 such that lab on a chip analysis can be conducted by the module 102. In some examples, the frame 150 can be further configured to receive one or more gaskets configured to seal the interface between the frame 150 and the analysis chip. For example, the frame 150 can include one or more geometries configured to receive and maintain alignment of a gasket provided to seal the fluidic interface between the biosensor array 170 and the analysis region 116.

[0159] The syringe tube 158 houses the plunger 160 such that the plunger 160 can move up and down. For example, upward motion of the plunger 160 within the syringe tube 158 can cause liquid to be drawn into the syringe tube 158. By contrast, downward motion of the plunger 160 within the syringe tube within the syringe tube 158 can cause liquid to be expelled from the syringe tube 158.

[0160] The plunger 160 is configured to draw fluid into the syringe tube 158. In some embodiments, the movement of the plunger 160 within the syringe tube 158 can be controlled by the module. For example, the plunger 160 can be controlled by the syringe drive 128 of theCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1module 102. In this manner, the “syringe” action of the plunger 160 within the syringe tube 158 can be controlled by the module 102 such that liquid material can be selectively drawn into or expelled from the syringe tube 158.

[0161] The rotary valve 162 is configured to fluidically interconnect a plurality of processing chambers within the sample cartridge 112. For example, once liquid material has been drawn into the syringe tube 158, rotation of the rotary valve 162 can provide selective fluid communication between various chambers within the sample cartridge 112. In some embodiments, the rotation of the rotary valve 162 can be controlled by the module. For example, the rotary valve 162 can be controlled by the valve drive 130 of the module 102. In this manner, by rotation of the rotary valve 162, fluid communication between various chambers of the sample cartridge 112 (e.g. reagent chambers, reaction chambers, mixing chambers, etc.) can be controlled in executing various sample processing steps necessary to produce a prepared sample.

[0162] The prepared sample chamber 164 is configured to receive a prepared biological sample. For example, a prepared sample may have undergone the preparation steps necessary for analysis. In some embodiments, the prepared sample may be transferred from the prepared sample chamber 164 and introduced to a reaction tube assembly 114 through a fluidic port 166.

[0163] The fluidic port 166 provides a fluidic interface through which a fluid sample can be transported into a reaction tube assembly 114 coupled to the sample cartridge 112. For example, the fluidic port 166 can be configured to extend through an exterior wall of the sample cartridge 112. In some implementations, the fluidic port 1 6 can interface with a corresponding access point of the frame 150. In some embodiments, the fluidic port 166 allows for controlled fluid transport through the frame 150. In some embodiments, the fluidic port 166 can be an inlet port such that a fluid sample can be introduced to one or more (e.g. a plurality of) fluidic channel 168 disposed within the frame 150. For example, the fluidic sample can be introduced through the fluidic port through one or more fluidic channel 168 configured to introduce the fluid sample to the analysis region 116.

[0164] In some embodiments, two or more fluidic ports 166 can be provided at an exterior wall of the sample cartridge 112. For example, a first fluidic port 166A and a second fluidic port 166B can be provided. In some embodiments, the first fluidic port 166A can interface with a first access point of the reaction tube assembly 114. In some embodiments, the second fluidic port 166B can interface with a second access point of the reaction tube assembly 114. In some implementations the first fluidic port 166A and the second fluidic port 166B canCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1interchangeably interface a first access point and a second access point of the reaction tube assembly 114. In some examples, the first fluidic port 166A can be an inlet port configured to introduce the fluid sample to the reaction tube assembly 114. In some examples, the second fluidic port 166B can be an outlet port such that the analysis region 116 can be emptied through the second fluidic port 166B. In other examples, the first fluidic port 166A can be an outlet port and the second fluidic port 166B can be an inlet port such that the fluid sample flows in the opposite direction. In some implementations a fluid sample can be introduced and evacuated from both or either of the first fluidic port 166A and the second fluidic port 166B. In some embodiments when a fluid sample is evacuated from the reaction tube assembly 114 through either the first fluidic port 166A or the second fluidic port 166B, it is emptied into a waste chamber of the sample cartridge 112.

[0165] The biosensor array 170 is configured to analyze and detect analytes present in a fluid sample. In some implementations, the biosensor array 170 includes at least one pixel. In some embodiments, the biosensor array 170 can include one or more (e.g. a plurality7of) pixels arranged in a two-dimensional array. In other embodiments, the biosensor array 170 can have one or more pixels arranged in other configurations or orientations. Each pixel in the biosensor array 170 is an individual detector configured to measure a signal at its individually addressable location. In some examples, each pixel can include a photodetector circuit configured to convert incoming photons of light into an electrical signal. An example of an electrical signal is current. In some embodiments, each pixel can include a photo-to-charge transducer configured to convert photons of light into an electrical signal. An example of a photo-to-charge transducer is a photodiode. In this manner, each pixel can be configured to detect incoming light and produce an electrical signal that can be transmitted to the module 102 for further processing and analysis. An example analysis chip 142 will be further illustrated and described with respect to FIG. 7 and FIGS. 39-40.

[0166] FIG. 6 is a perspective view of an example sample cartridge assembly 110 coupled to a reaction tube assembly 114 configured for lab on a chip analysis. The sample cartridge assembly 110 includes a sample cartridge 112. a reaction tube assembly 114, and a chip carrier receptacle 140. In the example shown, the reaction tube assembly 114 includes an analysis chip 142.

[0167] The sample cartridge assembly 110 includes components for receiving and processing a biological sample for analysis by the sample analyzer 100. In some embodiments, the sample cartridge assembly 110 is configured to facilitate the introduction, handling,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1preparation, and processing of a biological sample for analysis by the sample analyzer 100. The term 'sample preparation” as used herein refers to a process t pically 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, enzy matic, detergents, solvents, cell-bomb, etc., filtration, and / or concentration). For example, the sample cartridge assembly 110 interfaces with the sample analyzer 100 to ensure the sample reacts with reagents and is analyzed by the sample analyzer 100.

[0168] The sample cartridge 112 is configured to receive the biological sample and hold the chip carrier device 114 (which is an example of the reaction tube assembly 114). In some embodiments, the sample cartridge 112 includes one or more processing chambers for sample handling and processing. In some examples, the processing chambers are configured to facilitate biochemical, molecular, or analytical reactions for sample preparation and testing. For example, the biological sample is combined with reagents, buffers, or enzy mes in the processing chambers and is reacted to generate analytical results. In some embodiments, once the biological sample is added to the sample cartridge 112, the sample cartridge assembly 110 is loaded into the module 102 for processing and analysis. In examples, each type of sample processing module is configured with similar fluidic control and a processing system (e.g., sample cartridge) to permit sample handling and preparation of various sample types including, but not limited to, cells, spores, microorganisms, viruses. In other examples, each type of sample processing module is configured with customized fluidic control and a processing system (e.g., sample cartridge) to permit sample handling and preparation of specific sample types including, but not limited to, cells, spores, microorganisms, viruses. In some examples, the module 102 is configured to prepare a nucleic acid library for sequencing a sample. For example, the module 102 can be configured to prepare a nucleic acid library for sequencing a sample introduced to the module via the sample cartridge 112. In examples, preparing a nucleic acid library' for sequencing a sample can include amplifying a sample containing nucleic acid via the reaction tube assembly 114 such that the reaction tube assembly 114 can amplify the nucleic acid and detect the signals generated during amplification. In some examples, the sample cartridge assembly 110 can include one or more filter to isolate the nucleic acid from the sample, form a library prep reaction mixture comprising the nucleic acid and a library' prep reagent, cause the library' prep reaction mixture to flow into the reaction tube assembly 114, or a combination thereof. In examples, a nucleic acid library' can include tagged nucleic acid fragments, amplicons, adapter labeled nucleic acid, or a combination thereof. In some examplesCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1the tagged nucleic acid fragments, amplicons, or adapter labeled nucleic acid may be isolated via a filter within the sample cartridge assembly 110 before being eluted therefrom. In some examples, in preparing a nucleic acid library, the tagged nucleic acid fragments, amplicons, or adapter labeled nucleic acid may be selected, by size, via a filter within the sample cartridge assembly.

[0169] The chip carrier device 114 is configured to secure the analysis chip 142 while ensuring proper integration with the module 102. In some embodiments, the chip carrier device 114 facilitates alignment of the analysis chip 142 with the electrical contacts or the detection units within the module 102. In some examples, the chip carrier device 114 establish a fluidic connection between the analysis chip 142 and the sample cartridge 112. For example, the chip carrier device 114 includes one or more fluidic ports 166 (shown in FIGS. 5 and 7) that transport the biological sample from the sample cartridge 112 to the analysis chip 142 for processing and analysis.

[0170] The chip carrier receptacle 140 is a slot formed on a sidewall of the sample cartridge 112. In some embodiments, the chip carrier receptacle 140 receives and secures the chip carrier device 114. For example, the chip carrier receptacle 140 secures the chip carrier device, ensuring that the analysis chip 142 is fluidically connected to the sample cartridge 112. In some embodiments, the chip carrier receptacle 140 secures the chip carrier device 114 while keeping the analysis chip 142 accessible to the module 102. An example of the analysis chip 142 is illustrated and described in further detail with reference to FIG. 7 and FIGS. 39-40.

[0171] FIG. 7 is an exploded view of an example reaction tube configured for lab on a chip analysis. In this example, the chip carrier device 114 includes a gasket 144 and a frame 150. The frame 150 further includes a fluidic port 166, at least one fluidic channel 168, a chip receiving region 146, and an analysis region 116.

[0172] The gasket 144 is a mechanical seal that prevents leakage between two or more surfaces. In some embodiments, the gasket 144 provides a fluid-tight seal between the frame 150 and the analysis chip 142. In some examples, the gasket 144 is coupled to the frame 150 to maintain alignment and prevent leakage during operation. In some embodiments, the gasket 144 is a rectangular webbing structure designed to fit within the chip receiving region 146.

[0173] In some embodiments, the gasket 144 includes tabs to facilitate handling and placement, allowing a placement tool to position it within the frame 150. In some examples, the gasket 144 also incorporates a compression ring at its center, enhancing the seal between the analysis chip 142 and the frame 150 by applying uniform pressure across the interface.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0174] The frame 150 provides structural support and secures the analysis chip 142 in place. In some embodiments, the frame 150 is a frame formed using an injection molding process. In some examples, the frame 150 includes alignment features, such as guide rails, recesses cavities, or interlocking mechanisms, to ensure the analysis chip 142 is correctly positioned and secured. In some embodiments, the frame 150 incorporates the gasket 144 to prevent contamination and maintain fluid integrity’ during sample processing. In some examples, the frame 150 includes an integrated fluidic pathway, such as the fluidic channel 168 that directs the flow of biological samples, reagents, or buffer solutions to designated regions on the analysis chip 142.

[0175] The frame 150 includes a fluidic port 166 that is positioned at an end of the frame 150. In some embodiments, the frame 150 includes two fluidic ports 166 that are configured to input and output a biological sample. For example, the two fluidic ports 166 are fluidly connected to the sample cartridge 112. In some examples, one of the two fluidic ports 166 directs the biological sample to the fluidic channel 168, and one of the two fluidic ports 166 directs the biological sample from the fluidic channel 168 to the sample cartridge 112, forming a path through the chip earner device 114.

[0176] The fluidic channel 168 defines a fluidic pathway for transporting a biological sample. In some embodiments, the fluidic channel 168 is integrated into the frame 150, where one or more fluidic channels 168 can be formed to facilitate the biological sample movement. For example, the fluidic channel directs the biological sample from the fluidic port 166 to the analysis chip 142.

[0177] In some embodiments, multiple fluidic channels 168 are present to accommodate different processing steps, such as reagent mixing, washing, or waste disposal. In some examples, the fluidic channel 168 incorporates microfluidic design elements, such as capillary forces, valves, or pumps, to regulate sample flow and optimize interaction with the analysis chip 142.

[0178] The chip receiving region 146 is configured to receive the analysis chip 142. In some embodiments, the chip receiving region 146 aligns the analysis chip 142 with the fluidic channel 168. In some examples, the chip receiving region 146 is formed within the frame 150. For example, the chip receiving region 146 is a recessed area within the frame 150, designed to accommodate the analysis chip 142.

[0179] The analysis region 116 is a designated area of the chip carrier device 114. In some embodiments, the analysis region 116 is designed to facilitate the analysis of samples directlyCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1on the analysis chip 142. In some examples, the analysis region 116 acts as a transparent window that allows specific wavelengths of light to penetrate for activating fluorescent tags used in various assays. This targeted illumination enables the photodetectors of the analysis chip 142 to detect the presence of fluorescence, thereby allowing the instrument to accurately process and interpret the analytical data. Therefore, the analysis region 116 exposes the analysis chip 142 to the necessary’ light conditions required for the fluorescence-based tests.

[0180] FIG. 8 is a schematic of a sample cartridge assembly 178 including an exploded view of a sample cartridge 112 coupled to a reaction tube 180. Advantageously, as described with respect to FIG. 5, the same sample cartridge 112 can be coupled to a reaction tube assembly 114 configured for lab on a chip analysis. An example sample cartridge 112 coupled to a reaction tube assembly 114 configured for lab on a chip analysis is illustrated and described with respect to FIG. 6.

[0181] In the example shown, the sample cartridge assembly 178 includes a sample cartridge 112 coupled to a reaction tube 180. The reaction tube 180 is configured to receive and retain a sample for analysis without an analysis chip 142. For example, reaction tube 180 can be configured for nucleic acid amplification without an analysis chip. In other examples, the reaction tube 180 can be configured for non-thermal cycling detection of an analyte. For example, as illustrated in FIG. 8, the sample cartridge assembly 178 can be processed by a module enabled with thermal convection cycling capabilities. An example reaction tube 180 will be further illustrated and described with respect to FIG. 9. Examples of non-thermal cycling detection of an analyte (e.g. via thermal convection) will be further illustrated and discussed with respect to FIG. 10 and FIGS. 46-56.

[0182] FIG. 9 is a schematic diagram of an example reaction tube configured for receiving and processing a fluid sample to be analyzed without an analysis chip 142. An example of such a reaction tube is disclosed in Infl Pat. Appl. Publ. No. WO2022 / 155304. The reaction tube 180 comprises a fluid inlet port 182A for sample and solution introduction (dotted arrow denotes path into and out of the device), an inlet passage 184 A, and an analysis region entrance 186 that leads to the analysis region, 188. After the reaction has occurred, the materials can be removed via the outlet passage 184B and then out of the fluid outlet port, 182B. In some examples, the analysis region 188 can be heated via one or more external devices that are situated orthogonally to the major axis of the reaction tube and apply heat to the faces of the analysis region, 190A and 190B, to create a thermal cycling amplification process without an analysis chip. In some examples, the reaction tube 180 can be configured for non-thermalCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1cycling detection of an analyte. For example, as further described herein, the temperature difference within the analysis region 188 can create a thermal convection cycle. In some embodiments, the thermal convection cycle forms an ordered or regular fluid flow pattern that is roughly cyclical. In some embodiments, the thermal convection cycle forms an irregular or turbulent flow pattern. In some examples, the thermal convection cycle can form a regular flow pattern approximately spanning the entire analysis region 188. In other examples, the thermal convection cycle can include a plurality of thermal convection cycles forming a plurality of regular or irregular flow patterns throughout the analysis region 188 (e g. in one or more of the comers of the analysis region 188).

[0183] FIG. 10 shows an example analysis region of the reaction tube configured for thermal convection analysis having x, y. and z dimensions defined as length (x), width (y), and height (z). The analysis region of the reaction tube can be a walled structure having X, Y, and Z dimensions defined as length (X), width (Y), and height (Z). In some embodiments, as shown in FIG. 10, the analysis region (188) of the reaction tube 180 comprises a walled structure comprising two opposing major walls, 192A and 192B, along with two side walls, 194A and 194B. The example shown in FIG. 10, the opposing major walls 192A and 192B are of the same length, but in some embodiments, they may be of different lengths. Likewise, the example in FIG. 10 shows the side walls 194 A and 194B of the same length, but in some embodiments, they may be of different lengths and further, may comprise multiple wall elements such that the overall structure has more than four sides. For example, the reaction tube when viewed from the Z-axis can form a hexagon wherein the side walls 194A and 194B each comprise two side wall elements of the hexagon. In some embodiments the reaction tube, when viewed from the Z-axis comprises a regular or irregular polygon of 4-, 5-, 6- , 7- , 8-, 9, or 10-sides. In some examples, the 3D shape of the analysis region of the reaction tube is cylindrical, cube, spherical, rectangular, pyramidal, conical, or diamond. The angle between an opposing major wall and a side wall can be from 30° to 150°, 45° to 135°, 60° to 120°, 75° to 105°, or 90°±20°

[0184] In some embodiments, the two opposing major walls 192A and 192B are directly or indirectly heated. The heating of major walls 192 A and 192B are independent and can be done via known methods, such as via electricity (induction, resistance), acoustic, fluid (liquid, air), or light (infrared). The heating can be conductive, radiative, or convective or a combination thereof. The heating of the major walls 192 A and 192B defines a first region at a first temperature and a second region at a second temperature, respectively, in the reaction tube.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1The creation of a first region at a first temperature and a second region at a second temperature in the reaction tube 180 induces a heat differential in the sample in the reaction tube 180, which leads to athermal amplification process.

[0185] In addition to the thermal processes for amplification disclosed herein, it has unexpectedly been found that the dimensions of the analysis region of the reaction tube - alone or in combination with other aspects of the disclosure - can have an impact on the speed and efficiency of the reactions disclosed herein. In some embodiments, the length of the two opposing major walls is from 1 to 25 mm, 1.4 to 25 mm, 1.6 to 25 mm, 1.8 to 25 mm, 2 to 25 mm, 2.5 to 25 mm, 3 to 25 mm, 4 to 25 mm, 5 to 25 mm, 6 to 25 mm, 8 to 25 mm, 10 to 25 mm, 12 to 25 mm, 15 to 25 mm, 20 to 25 mm, 1 to 20 mm, 1.4 to 20 mm, 1.6 to 20 mm, 1.8 to 20 mm, 2 to 20 mm, 2.5 to 20 mm, 3 to 20 mm. 4 to 20 mm, 5 to 20 mm, 6 to 20 mm, 8 to 20 mm, 10 to 20 mm, 12 to 20 mm, 15 to 20 mm, 1 to 15 mm, 1.4 to 15 mm, 1.6 to 15 mm, 1.8 to 15 mm, 2 to 15 mm, 2.5 to 15 mm, 3 to 15 mm, 4 to 15 mm, 5 to 15 mm, 6 to 15 mm, 8 to 15 mm, 10 to 15 mm, 12 to 15 mm, 1 to 12 mm, 1.4 to 12 mm, 1.6 to 12 mm, 1.8 to 12 mm, 2 to 12 mm, 2.5 to 12 mm, 3 to 12 mm, 4 to 12 mm, 5 to 12 mm, 6 to 12 mm, 8 to 12 mm, 10 to 12 mm, 1 to 10 mm, 1.4 to 10 mm, 1.6 to 10 mm, 1.8 to 10 mm, 2 to 10 mm, 2.5 to 10 mm, 3 to 10 mm, 4 to 10 mm, 5 to 10 mm, 6 to 10 mm, 8 to 10 mm, 1 to 8 mm, 1.4 to 8 mm, 1.6 to 8 mm, 1.8 to 8 mm, 2 to 8 mm, 2.5 to 8 mm, 3 to 8 mm, 4 to 8 mm, 5 to 8 mm, 6 to 8 mm, 1 to 6 mm, 1.4 to 6 mm, 1.6 to 6 mm, 1.8 to 6 mm, 2 to 6 mm. 2.5 to 6 mm, 3 to 6 mm, 4 to 6 mm, 5 to 6 mm. 1 to 5 mm, 1.4 to 5 mm, 1.6 to 5 mm, 1.8 to 5 mm, 2 to 5 mm, 2.5 to 5 mm, 3 to 5 mm, 4 to 5 mm, 1 to 4 mm, 1.4 to 4 mm, 1.6 to 4 mm, 1.8 to 4 mm, 2 to 4 mm, 2.5 to 4 mm, 3 to 4 mm, 1 to 3 mm, 1.4 to 3 mm, 1.6 to 3 mm, 1.8 to 3 mm, 2 to 3 mm, 2.5 to 3 mm, 1 to 2.5 mm, 1.4 to 2.5 mm, 1.6 to 2.5 mm, 1.8 to 2.5 mm, 2 to 2.5 mm, 1 to 2 mm, 1.4 to 2 mm, 1.6 to 2 mm, 1.8 to 2 mm, 1 to 1.8 mm, 1.4 to 1.8 mm, or 1.6 to 1.8 mm.

[0186] In some embodiments, the height of the two opposing major walls is from 1 to 25 mm, 1.4 to 25 mm, 1.6 to 25 mm, 1.8 to 25 mm, 2 to 25 mm, 2.5 to 25 mm, 3 to 25 mm, 4 to 25 mm, 5 to 25 mm, 6 to 25 mm, 8 to 25 mm, 10 to 25 mm, 12 to 25 mm, 15 to 25 mm, 20 to 25 mm, 1 to 20 mm, 1.4 to 20 mm, 1.6 to 20 mm, 1.8 to 20 mm, 2 to 20 mm, 2.5 to 20 mm, 3 to 20 mm, 4 to 20 mm, 5 to 20 mm, 6 to 20 mm, 8 to 20 mm, 10 to 20 mm, 12 to 20 mm, 15 to 20 mm, 1 to 15 mm, 1.4 to 15 mm, 1.6 to 15 mm, 1.8 to 15 mm, 2 to 15 mm, 2.5 to 15 mm, 3 to 15 mm, 4 to 15 mm, 5 to 15 mm, 6 to 15 mm, 8 to 15 mm, 10 to 15 mm, 12 to 15 mm, 1 to 12 mm, 1.4 to 12 mm, 1.6 to 12 mm, 1.8 to 12 mm, 2 to 12 mm, 2.5 to 12 mm, 3 to 12 mm, 4 to 12 mm, 5 to 12 mm, 6 to 12 mm, 8 to 12 mm, 10 to 12 mm, 1 to 10 mm, 1.4 to 10 mm, 1.6CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1to 10 mm, 1.8 to 10 mm, 2 to 10 mm, 2.5 to 10 mm, 3 to 10 mm, 4 to 10 mm, 5 to 10 mm, 6 to 10 mm, 8 to 10 mm. 1 to 8 mm. 1.4 to 8 mm, 1.6 to 8 mm, 1.8 to 8 mm, 2 to 8 mm, 2.5 to 8 mm, 3 to 8 mm, 4 to 8 mm, 5 to 8 mm, 6 to 8 mm, 1 to 6 mm, 1.4 to 6 mm, 1.6 to 6 mm, 1.8 to 6 mm, 2 to 6 mm, 2.5 to 6 mm, 3 to 6 mm, 4 to 6 mm, 5 to 6 mm, 1 to 5 mm, 1.4 to 5 mm, 1.6 to 5 mm, 1.8 to 5 mm, 2 to 5 mm, 2.5 to 5 mm, 3 to 5 mm, 4 to 5 mm, 1 to 4 mm, 1.4 to 4 mm, 1.6 to 4 mm, 1.8 to 4 mm, 2 to 4 mm, 2.5 to 4 mm, 3 to 4 mm, 1 to 3 mm, 1.4 to 3 mm, 1.6 to 3 mm, 1.8 to 3 mm, 2 to 3 mm, 2.5 to 3 mm, 1 to 2.5 mm, 1.4 to 2.5 mm, 1.6 to 2.5 mm, 1.8 to 2.5 mm, 2 to 2.5 mm, 1 to 2 mm, 1.4 to 2 mm, 1.6 to 2 mm, 1.8 to 2 mm, 1 to 1.8 mm, 1.4 to 1.8 mm, or 1.6 to 1.8 mm.

[0187] In some embodiments, the average distance between the two opposing major walls is from 0.25 to 10 mm, 0.5 to 10 mm, 1 to 10 mm, 2 to 10 mm, 3 to 10 mm, 5 to 10 mm, 7 to 10 mm, 0.25 to 7 mm, 0.5 to 7 mm, 1 to 7 mm, 2 to 7 mm, 3 to 7 mm, 5 to 7 mm, 0.25 to 5 mm, 0.5 to 5 mm, 1 to 5 mm, 2 to 5 mm, 3 to 5 mm, 0.25 to 3 mm, 0.5 to 3 mm, 1 to 3 mm, 2 to 3 mm, 0.25 to 2 mm, 0.5 to 2 mm, 1 to 2 mm, 0.25 to 1 mm, 0.5 to 1 mm, or 0.25 to 0.5. The two opposing major walls and the side walls form a volume within the reaction tube. The volume of the analysis region of the reaction tube can be from 0.5 pL to 6500 pL, 1 pL to 5000 pL, 5 pL to 5000 pL, 10 pL to 5000 pL, 25 pL to 5000 pL, 50 pL to 5000 pL, 75 pL to 5000 pL, 180 pL to 5000 pL, 250 pL to 5000 pL, 500 pL to 5000 pL, 1800 pL to 5000 pL, 1 pL to 1800 pL, 5 pL to 1800 pL, 10 pL to 1800 pL, 25 pL to 1800 pL. 50 pL to 1800 pL, 75 pL to 1800 pL. 180 pL to 1800 pL, 250 pL to 1800 pL, 500 pL to 1800 pL. 1 pL to 500 pL. 5 pL to 500 pL, 10 pL to 500 pL, 25 pL to 500 pL, 50 pL to 500 pL, 75 pL to 500 pL, 180 pL to 500 pL, 250 pL to 500 pL, 1 pL to 250 pL, 5 pL to 250 pL, 10 pL to 250 pL, 25 pL to 250 pL, 50 pL to 250 pL, 75 pL to 250 pL, 180 pL to 250 pL, 1 pL to 180 pL, 5 pL to 180 pL, 10 pL to 180 pL, 10 pL to 65 pL, 25 pL to 180 pL, 25 pL to 65 pL, 50 pL to 180 pL, 50 pL to 65 pL, 75 pL to 180 pL.

[0188] In some embodiments, the major walls of the reaction tube have a ratio of height to length of from 0.5:1 to 1:2, 0.75:1 to 1:5, 1:1 to 1:1.75, 1:1 to 1:1.5 or 1:1 to 1: 1.25. In some embodiments, the ratio of the length to height of the reaction tube and / or the average distance between the two opposing major walls is such that an induced thermal convection cycle in a solution in the reaction tube has an average cycle time of 15 seconds or less when the temperature difference between the two opposing major walls is from 25-37°C.

[0189] As described with respect to FIG. 8, in some embodiments, the reaction tube 180 is part of a sample cartridge assembly 178. The sample cartridge 112 may be relatively small,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1such that it can be easily hand-held, portable, and / or disposable. The sample cartridge 112 can hold one or more reagents and / or chemicals that are used to process a sample, in order to ultimately detect some property of the sample. One example of such a process is PCR, which is used to amplify the presence of DNA. Additionally, in some embodiments, a filter may be disposed in the fluidic path between the sample cartridge 112 and the reaction tube 180. This filter can be used to isolate sample nucleic acids from the sample and may comprise an amine or other modification to maximize efficiency or effectiveness. As further described with respect to FIG. 5, the cartridge 112 may further include additional chambers or fluidic connections to allow for chemical processes. In some embodiments, the self-contained cartridge comprises a lysis chamber, wherein the lysis chamber can comprise one or more lysis reagents for releasing nucleic acid. In some embodiments, the self-contained cartridge comprises additional chambers optionally in fluid communication with the sample chamber or the reaction tube 180. For example, multiple reaction tubes 180 may be in communication with a single sample chamber to allow for amplification of different target nucleic acids.

[0190] During the amplification process, there comprises two regions within the reaction tube 180, a first and a second region. The first region is a sub-section of the volume of the reaction tube 180 wherein the solution is maintained at a first temperature, said first temperature in a range capable of denaturing a target nucleic acid sequence into a singlestranded nucleic acid template. In some embodiments, first temperature is from 90°C to 180°C, from 94°C to 180°C, or from 97°C to 99°C. In some embodiments, the first temperature is maintained at a certain level with a variance of less than 3°, 2°, or 1°C over the time of the amplification reaction.

[0191] The second region is a sub-section of the volume of the reaction tube 180 wherein the solution is maintained at a second temperature lower than the first temperature, said second temperature in a range capable of annealing a primer pair to a single-stranded nucleic acid template. In some embodiments, second temperature is from 60°C to 70°C, from 64°C to 68°C, or from 65°C to 67°C. In some embodiments, the second temperature is maintained at a certain level with a variance of less than 3°. 2°, or 1°C over the time of the amplification reaction. In some embodiments, the first temperature is from 97°C to 99°C and the second temperature is from 65°C to 67°C. In some embodiments, the difference in temperature between the first temperature and the second temperature is equal to or greater than 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, or 37°C or from 25-37°C, 25-35°C, 27-35°C, 28-34°C.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0192] The temperature difference between the first and second regions creates a thermal convection cycle. The phrase ‘“thermal convection cycle” or “thermal convection cycling” refers to the use of heat differentials to cyclically drive a reagent between different regions of the reaction tube for spatially separate melting, annealing, and extending in a reaction tube with constant heating temperatures at different locations. Convective PCR thermal cycling is implemented by inducing thermal convection inside the reaction tube, which stratifies the reaction into spatially separate and stable melting, annealing, and extension zones created by the temperature gradient. Techniques for Convective PCR thermal cycling are described in Miao et al. (2020) 1108 Anal. Chim. Acta 177-197. In some embodiments, the thermal convection cycle forms an ordered or regular fluid flow pattern that is roughly cyclical. In some embodiments, the thermal convection cycle forms an irregular or turbulent flow pattern. In some embodiments, the thermal convection cycle is a type of Rayleigh-Bernard convection.

[0193] Methods of controlling the temperature of the reaction tube 180 by a thermal control device are provided in, for example, U.S. Publ. Appl. Nos. 2022 / 0253079 Al and 2020 / 0116398 Al. As described above, the reaction tube 180 has opposing major faces and an active thermal element adjacent to at least one major face of the reaction-vessel. In some embodiments, there comprises more than one active element, for example, two active thermal elements applied bilaterally on major faces on opposite sides of the reaction-vessel. One or more sensors may be incorporated and configured to measure the temperature of a portion of the active element(s). The one or more sensors can further include a second temperature sensor positioned and configured to measure the ambient temperature indicative of the thermal operating environment around the reaction-vessel.

[0194] In some embodiments, the thermal control device is configured as a removable module that can be coupled with a reaction-vessel extending from a sample analysis cartridge configured for detection of a nucleic acid target in a nucleic acid amplification test (NAAT), e.g., Polymerase Chain Reaction (PCR) assay. Preparation of a fluid sample in such a cartridge generally involves a series of processing steps, which can include chemical, electrical, mechanical, thermal, optical or acoustical processing steps according to a specific protocol. Such steps can be used to perform various sample preparation functions, such as cell capture, cell lysis, purification, binding of analyte, and / or binding of unwanted material. Such a sample processing cartridge can include one or more chambers suited to perform the sample preparation steps. A sample cartridge suitable for use with the present disclosure is shown and described in U.S. Pat. No. 6.374,684 and U.S. Pat. No. 8,048.386.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0195] The number of amplification cycles in the reaction tube can be fixed or vary depending on the target nucleic acid and detection methods. In some embodiments, the number of amplification cycles is from 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 15, 1 to 10, 5 to 50, 5 to 40, 5 to 30, 5 to 20, 5 to 15, 5 to 10, 10 to 50, 10 to 40, 10 to 30, 10 to 20, 15 to 50, 15 to 40, 15 to 30, 15 to 20, 20 to 50, 20 to 40, or 20 to 30. In some embodiments, the number of amplification cycles is 1. 2, 3, 4. 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. 17. 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. The average cycle time is the averaged time it takes for a target nucleic acid to go through the thermal amplification process steps of denaturation, annealing, and extension. In convective PCR, a ‘cycle’ exists only in an averaged sense, as reagents continuously follow different local trajectories. Measurement of the average cycle time can be done via standard methods. The average cycle time for the amplification methods described herein are, in seconds, from 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 15, 1 to 10, 5 to 50, 5 to 40, 5 to 30, 5 to 20, 5 to 15, 5 to 10, 10 to 50, 10 to 40, 10 to 30, 10 to 20, 15 to 50, 15 to 40, 15 to 30, 15 to 20, 20 to 50, 20 to 40, or 20 to 30 (seconds). In some embodiments, the average cycle time for the amplification methods described herein is. in seconds, 1, 2, 3, 4, 5, 6, 7, 8. 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 (seconds).

[0196] In some embodiments, the amplification efficiency or time for the method to complete 20 amplification cycles is critical to performance. In some embodiments, the amplification efficiency is less than 20 minutes, less than 19 minutes, less than 18 minutes, less than 17 minutes, less than 1 minutes, less than 15 minutes, less than 14 minutes, less than 13 minutes, less than 12 minutes, less than 11 minutes, less than 10 minutes, less than 9 minutes, less than 8 minutes, less than 7 minutes, less than 6 minutes, or less than 5 minutes. In some embodiments, the amplification efficiency is from 5 minutes to 20 minutes. 5 minutes to 18 minutes, 5 minutes to 15 minutes, 5 minutes to 12 minutes, 5 minutes to 10 minutes, 8 minutes to 20 minutes, 8 minutes to 18 minutes, 8 minutes to 15 minutes, 8 minutes to 12 minutes, 8 minutes to 10 minutes, 10 minutes to 20 minutes, 10 minutes to 18 minutes, 10 minutes to 15 minutes, 10 minutes to 12 minutes, 12 minutes to 20 minutes, 12 minutes to 18 minutes. 12 minutes to 15 minutes, 15 minutes to 20 minutes, or 15 minutes to 18 minutes.

[0197] In some embodiments the module, reaction tube and / or cartridge that comprise the reaction tube is CLIA compliant. As used herein, “Clinical Laboratory' Improvement Amendments (CLIA)’’ refers to The Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations in effect as of the original filing date of the present application. The CLIACEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1regulations include federal standards applicable to all U.S. facilities or sites that test human specimens for health assessment or to diagnose, prevent, or treat disease. A “CLIA-compliant” test is one that complies with these regulations. “CLIA-waived” tests include tests that does not comply with all of these regulations. For example, CLIA-waived tests include test systems cleared by the U.S. Food and Drug Administration for home use and those tests approved for waiver under the CLIA criteria. In examples, the assays performed in the sample analyzers disclosed herein are performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Accordingly, the module and cartridge can be Clinical Laboratory Improvement Amendments (CLIA)-compliant, is operated in compliance with CLIA, is operated by a CLIA-compliant laboratory, or is operated in a CLIA-compliant location. The module and cartridge can be a Clinical Laboratory Improvement Amendments (CLIA)-certified device, is operated by a CLIA-certified laboratory, is operated in a CLIA-certified location, is operated under the oversight of a CLIA-compliant laboratory, or is operated under the oversight of a CLIA-certified laboratory7. Advantageously, detection can be effected without transporting the sample from the site where the sample is collected (e.g., a POC diagnosis is preferably a hospital, an urgent care center, an emergency room, a physician's office, a health clinic, or a home).

[0198] FIG. 11 is a perspective view of an example chassis 104 of a sample analyzer 100. At least one control panel 212 is secured within the chassis 104. In some embodiments, more than one (e.g. aplurality of) control panels 212 are secured within the chassis 104. The example illustrated in FIG. 11 shows four control panels 212 secured within the chassis 104.

[0199] The control panel 212 is configured to manage the overall operation of the module 102. For example, the control panel 212 can manage one or more steps of a sample processing protocol. For example, the control panel 212 can include a memory and instructions for controlling interactions between different internal components, regulating measurement cycles and executing one or more calibration processes. In some examples, the control panel 212 can be configured to power the module 102. In some embodiments, the control panel 212 can be configured to manage the operation of one module 102. In other embodiments, the control panel 212 can be configured to independently manage the operation of a plurality of modules 102. For example, the control panel 212 can include a plurality of communication ports 214, each communication port 214 being configured to interface with one of a plurality of modules. For example, each communication port 214 can be configured to independently manage theCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1operation of each of a plurality of modules 102. For example, each of a plurality' of modules can be assigned to one of a plurality of communication ports 214.

[0200] In the example illustrated in FIG. 11, the control panel 212 includes five communication ports 214. In this manner, a group of five modules 102 can be simultaneously managed by one control panel 212. In some configurations, each control panel 212 can be independently powered by a central communication unit 470 of the sample analyzer 100. For example, a central communication unit 470 of the sample analyzer 100 can independently power or shutoff one or more groups of modules, each group of modules being managed by one of a plurality' of control panels 212. In the example shown in FIG. 5, the sample analyzer 100 can have four independently operable control panels 212, each control panel 212 managing the overall operation of up to five modules 102. Advantageously, this configuration allows for one or more groups of modules 102 to independently remain in operation while power to at least one group of modules is independently shutoff. For example, if only one module 102 must be turned offline for removal (e.g. for repair or maintenance) a central communication unit 470 of the sample analyzer 100 can independently shutoff the control panel 212 that the offline module 102 is assigned to and continue to power the remaining control panels 212 such that at least one module 102 can remain online and thereby continue to process samples. An example central communication unit 470 is illustrated and described with respect to FIG. 28.

[0201] FIG. 12 is a perspective view of an example rack 200 for holding at least one module 102. The rack 200 includes a frame 202 with a top portion 204 and a bottom portion 206. The top portion 204 includes at least one upper spring 208. The bottom portion 206 includes at least one clip 210. In the example shown, the top portion 204 of the rack 200 includes at least one upper spring 208 configured to secure the at least one module 102 and the bottom portion 206 of the rack 200 includes at least one clip 210 configured to secure the at least one module 102. Also shown is at least one control panel 212 secured within the frame 202. The control panel 212 includes a plurality of power and communication connections 213. In examples, each power and communication connection 213 can be positioned at a respective bay 201 such that power and communication capabilities can be provided to any module 102 type when inserted into a receiving bay 201.

[0202] The rack 200 can be secured within the interior of the chassis 104. The rack 200 can be configured to receive at least one module 102. In some examples, the rack 200 can be configured to receive a plurality of modules 102. For example, the rack 200 can removably secure one or more modules 102. In some examples, the rack 200 can be configured to receiveCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1ten modules 102. In some examples, the rack 200 can secure an upper row 101 of modules 102. In other examples, the rack 200 can secure a bottom row 103 of modules 102. The rack 200 can have a frame 202 having a top portion 204 and a bottom portion 206. In examples, the rack 200 can include a plurality of receiving bays 201.

[0203] A module receiving bay 201 is configured to receiving any of the plurality of module types described herein. For example, each receiving bay 201 includes at least one upper spring 208 and at least one clip 210 configured to receiving any of the plurality of module types described herein. In some examples, each type of module 102 described herein can be fitted with an upper interfacing member suitable to be retained by the upper spring 208 and a lower interfacing member suitable to be retained by the clip 210. In other examples, each type of module can have suitable dimensions to be received by any of the plurality of receiving bays 201. In examples, each module 102 can include an edge connector configured to interface with any of a plurality’ of power and communication connections 213 within the control panel 212 of the rack 200. In some examples, each receiving bay 201 can further include one or more positioning members configured to guide a given module 102 to a power and communication connection 213 positioned within the respective receiving bay 201 that the module 102 is to be secured within. In some embodiments, the external structures or shells of each module type can be identical to enable interchangeability within any one of the receiving bays 201. For example, the external structures of the example module 102 depicted in FIG. 3 are identical to the external structures of the example module 132 configured to perform lab on a chip analysis depicted in FIG. 4. For example, despite the example module 132 having a different instrument interface 136 which includes a plurality of pogo pins 138, the external structures of example module 132 are substantially identical to the external structures of example module 102. That is to say, the external structures of a first type of module, a second type of module, and a third ty pe of module can be substantially identical, even though one or more module type can have different internal structures. For example, a third module ty pe can have a different instrument interface 136, yet still have an external structures identical to the external structure of the first module type and the external structure of the second module type.

[0204] The frame 202 can be formed of a lightweight material, to reduce added weight, yet sturdy enough to secure a plurality of modules 102. For example, the frame 202 can be formed of aluminum sheet metal. In some examples, the frame can include one or more rails or guides to accurately position each module 102 into a respective module receiving zone. As shown in FIG. 12, the frame 202 can also be configured to secure at least one control panelCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1212. In some embodiments, the frame can include one or more rails to accurately position each module 102 into a module receiving zone such that the module 102 interfaces with the at least one control panel 212.

[0205] The top portion 204 can include at least one upper spring 208. For example, the upper spring 208 can be configured to secure at least one module 102. For example, the upper spring 208 can be configured to removably secure at least one module 102. In some examples, the upper spring 208 can be formed of a strong, flexible material. For example, the upper spring 208 can be formed of a material strong enough to secure a module 102 yet flexible enough to allow quick, toolless removal. For example, the upper spring 208 can be formed of stainless steel. In some embodiments, the upper spring 208 can automatically engage in a locked position once the module 102 is fully inserted within the rack 200. In some implementations, the upper spring 208 can be manipulated by a user without tools into an unlocked position to release the module 102 from the rack 200. For example, the upper spring 208 can be lifted by a user to release the module 102 from the rack 200. In some embodiments, the top portion 204 can include a plurality of upper springs 208, each upper spring 208 configured to secure one module 102. For example, the top portion 204 can include ten upper springs 208.

[0206] The bottom portion 206 can include at least one clip 210. For example, the at last one clip 210 can be configured to secure at least one module 102. In some examples, the clip 210 can be configured to prevent the module 102 from sliding out of the rack 200. In some embodiments, the clip 210 can automatically engage in a locked position once the module 102 is fully inserted within the rack 200. In some implementations, the clip 210 can be manipulated by a user into an unlocked position such that the module 102 can be removed without tools. For example, the clip 210 can be pinched by a user to release the module 102. In some embodiments, the bottom portion 206 can include a plurality of clips 210, each clip 210 configured to secure one module 102. For example, the bottom portion 206 can include ten clips 210.

[0207] FIG. 13 is a perspective view of a sample analyzer 100 having a hinged front access means. The sample analyzer 100 includes a chassis 104. a front panel 106, at least one module 102, and a display 108. The display 108 is contained in a bezel frame 220.

[0208] The front panel 106 includes at least one display 108. For example, the display 108 can be contained in a bezel frame 220 integrated with the front panel 106. In the example depicted in FIG. 13, the two displays 108 are contained in a unified bezel frame 220. The front panel 106 is attached to the chassis 104 by a long arm pivot hinge 302. For example, the frontCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1panel 106 is attached to the chassis 104 by a long arm pivot hinge 302 such that the sample analyzer 100 has a hinged front access means. In this manner, each of the modules 102 can be simultaneously accessed from the front of the sample analyzer 100. For example, each of the modules 102 can be simultaneously accessed without rotating the sample analyzer 100 or pulling the sample analyzer 100 away from a wall. Example embodiments of the long arm pivot hinge 302 will be discussed with respect to FIGS. 14-20.

[0209] FIG. 14 is a schematic diagram of an example sample analyzer 100 having a hinged front access means. The sample analyzer 100 has a front panel 106 attached to a chassis 104. The front panel 106 has a proximal end P and a distal end D. In the example shown, the front panel 106 has a swing radius R and a swing angle A. In the example shown, the front panel 106 is attached to the chassis 104 at a central point C.

[0210] The swing radius R can be the distance between the central point C and the distal end D of the front panel 106 when the front panel 106 is in an open position.

[0211] The swing angle A can be the angle between the front panel 106 and the chassis 104 when the front panel 106 is in a fully opened position. In some embodiments, it can be necessary for the swing angle A to be approximately 90 degrees (e.g. less than 120 degrees) to avoid contact between the front panel 106 and adjacent structures. For example, the swing angle A may be approximately 90 degrees to avoid contact with an adjacent wall. In another example, the sample analyzer 100 may be one of a row of sample analyzers 100. In this example, the swing angle A must be approximately 90 degrees to avoid contact between the front panel 106 and an adjacent sample analyzer 100. In some embodiments, to allow a simultaneous access of a plurality of modules 102 through the front of a sample analyzer 100 a long arm pivot hinge 302 will be configured to attach the front panel 106 to the chassis 104 at the central point C. However, as will be illustrated with respect to FIG. 15, depending on the hinge employed, a portion of the front panel 106 proximal to the chassis 104 can interfere with access to one or more modules 102.

[0212] FIG. 15 is a schematic diagram of an example sample analyzer 100 having a front panel 106 attached to a chassis 104 by a hinge 300. In the example shown, at least one module 102 is secured within the chassis 104. In the example shown, when the front panel 106 is fully opened, the swing angle A is approximately 90 degrees. However, when the front panel 106 is in a fully open position at least one module 102 is unable to be fully accessed. In the example shown, at least a portion of the front panel 106 is obstructing the module 102 and thereby preventing the removal of the module 102, or both. For example, as indicated by the arrows inCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1FIG. 15, the module 102 cannot be removed for repair of replacement due to interference between the removal path of the module 102 and at least a portion of the front panel 106.

[0213] FIG. 16 is another schematic diagram of an example sample analyzer 100 having a front panel 106 attached to a chassis 104 by a hinge 302 such as a long arm pivot hinge. The front panel has a proximal end P and a distal end D. In the example depicted in FIG. 16, at least one module 102 is secured within the chassis 104. In the example shown, the front panel 106 has a swing angle A. In the example, when the front panel 106 is in a fully open position, the swing angle A is approximately 90 degrees (e.g. less than 120 degrees). In the example shown, when the front panel 106 is in a fully open position there is a distance L between the proximal end P of the front panel 106 and the chassis 104.

[0214] The long arm pivot hinge 302 illustrated in FIG. 16 is enables a distance L between the proximal end P of the front panel 106 and the chassis 104 when the front panel is in a fully open position. As shown in the example, all of the at least one modules 102 can be accessed from the front of the sample analyzer 100. Advantageously, as shown in the example, when the front panel 106 is in a fully open position, the swing angle A is still approximately 90 degrees thus avoiding contact with any neighboring obstructions. The hinge 302 is also referred to herein as a long arm pivot hinge. The long arm pivot hinge 302 is illustrated and described with further reference to FIGS. 17- 20.

[0215] FIG. 17 is a top view of an example long arm pivot hinge 302 in an open position. The long arm pivot hinge 302 is within a sample analyzer 100 having at least one module 102, a chassis 104, a front panel 106. Also shown is a clip 210 securing the module 102 within the chassis 104. As illustrated and discussed with respect to FIG. 16, all of the at least one modules 102 are fully accessible when the long arm pivot hinge 302 is in an open position. Similar to the example illustrated and discussed with respect to FIG. 16, the angle A between the front panel 106 and the chassis 104 is approximately 90 degrees when the long arm pivot hinge 302 is in a fully open position thereby avoiding any contact with neighboring sample analyzers 100 or other obstructions.

[0216] In the example illustrated in FIG. 17, the long arm pivot hinge 302 attaches the front panel 106 to the chassis 104. The long arm pivot hinge 302 is attached to the chassis 104 by a pivotable attachment means 320. For example, a pivotable attachment member 320 can be a solid material or rod such as a pin, a screw, or the like. The long arm pivot hinge is attached to the front panel 106 by a rigid attachment means 322. For example, a rigid attachment means 322 can be a screw, a bolt assembly, rigid plastics, solidified adhesive compounds, and the like.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0217] FIG. 18 is a top view of an example long arm pivot hinge 302 in a semi-closed position. The long arm pivot hinge 302 has a center of rotation 324. In some embodiments, the long arm pivot hinge 302 pivots about the center of rotation 324 as the front panel 106 moves between open and closed positions. For example, the long arm pivot hinge 302 pivots about the center of rotation 324 as the front panel 106 is opened. In another example, the long arm pivot hinge 302 pivots about the center of rotation 324 as the front panel 106 is closed. In some examples the long arm pivot hinge 302 is attached to the chassis 104 by an attachment member at the center of rotation 324. For example, the long arm pivot hinge 302 may be attached to chassis 104 by the pivotable attachment member 330 at the center of rotation 324.

[0218] FIG. 19 is a top view of an example long arm pivot hinge 302 in a closed position. The long arm pivot hinge 302 has a center of rotation 324. In some examples, the long arm pivot hinge 302 can be formed of a single piece of material which can significantly improve ease of manufacturability, decrease assembly time, and lower costs. For example, the long arm pivot hinge 302 can have a hinge body. For example, the long arm pivot hinge 302 can have a unitary hinge body. For example, the long arm pivot hinge 302 can be formed of a single piece of rigid metal such as steel. In the example shown, the long arm pivot hinge 302 has a hinge body with a first segment 340, an angled segment 342, and a second segment 344.

[0219] In the example shown the first segment 340 and the second segment 344 are connected by the angled segment 342. In some implementations the angled segment 342 can have a first end 346 and a second end 348. In some embodiments, the angle of the angled segment 342 can be selected to enable a desired swing angle of the front panel 106. In some embodiments the first segment 340 and the second segment 344 are connected by the angled segment 342 such that the angle between the first segment and the second segment 344 is approximately 90 degrees.

[0220] In the example show n, the first segment has a length 350 and the second segment has a length 352. For example, the length 350 can be the distance between the end of the first segment 340 and a first end 346 of the angled segment 342. In another example, the length 350 can be the distance between the center of rotation 324 and a first end 346 of the angled segment 342. In some embodiments the length 352 can be the distance between end of the second segment 344 and a second end 348 of the angled segment 342. In some implementations the length 350 of the first segment 340 is longer than the length 352 of the second segment 344. In some embodiments, the length 350 of the first segment can be selected to enable a minimumCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1distance L between the proximal end P of the front panel 106 and the chassis 104 when the front panel is in a fully open position.

[0221] In the example shown, the center of rotation 324 is arranged within the first segment 340. For example, the first segment can include a through-hole configured as the center of rotation of the long arm pivot hinge 302. In some embodiments, the hinge body can have a center of rotation and at least one through hole arranged at the center of rotation. In this manner the pivotable attachment member 330 can be efficiently and precisely secured at the center of rotation 324 with minimal parts and assembly steps.

[0222] FIG. 20 is a perspective view of a sample analyzer 100 with simplified toolless front access enabled by a long arm pivot hinge 302. In the example show n, any of the one or more modules 102 secured within the chassis 104 can be accessed when the front panel 106 is in an open position.

[0223] FIG. 21 is a top view of a sample analyzer with front access enabled by a retractable hinge assembly 400. For example, the retractable hinge assembly 400 can include a hinge 402 that extends to enable opening of the front panel 106.

[0224] FIG. 22 is a side view of the retractable hinge assembly 400 in an open position. For example, the retractable hinge assembly 400 can include a hinge conveyor 404 that can alternate between extended and retracted positions.

[0225] FIG. 23 is a side view of the retractable hinge assembly 400 in a closed position.

[0226] FIG. 24 is a perspective view of a sample analyzer 100 with front access enabled by an extendable display panel 430. In some examples, the sample analyzer 100 also has at least one front panel flap 432. In the example shown, the extendable display panel 430 is low ered such that an upper row' of modules 102 is accessible.

[0227] FIG. 25 is a perspective view of a sample analyzer with front access enabled by a slidable display panel 440. In some examples, the sample analyzer 100 also has at least one front access flap 442. In the example shown, the slidable display panel 440 is raised such that the bottom row of modules 102 is accessible.

[0228] FIG. 26 is a perspective view of a different sample analyzer with front access enabled by an extendable front panel 450. The extendable front panel 450 includes a slidable display panel 452. In some embodiments, the extendable front panel 450 includes one or more access flap 454. For example, the access flap 454 can be locked in an open position while accessing a module 102. In the example shown the slidable display panel 452 is low ered and the access flap 454 is opened such that an upper row of modules is accessible.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0229] FIG. 27 is a front view an example sample analyzer 100. The sample analyzer 100 includes at least one display 108 is contained in a bezel frame 220. In some implementations, the display 108 can be configured to display real-time processing information including the assay being performed and a completion status. For example, the display 108 can display a user interface indicating one or more steps of the sample processing protocol being performed, the type of assay being assay being performed, the type of sample cartridge therein (e.g. PCR or lab on a chip) and the like. In some embodiments, the display 108 can include a user interface configured to receive input from a user.

[0230] In the example shown, the sample analyzer 100 also includes at least one module status indicator 460. For example, the module status indicator 460 can be a light (e.g. LED light) that can change colors depending on a module status. For example, the module status indicator 460 can indicate when a module 102 is currently processing a sample, has finished processing a sample, is ready to process a new sample, has reached an error, and the like. For example, a plurality of module status indicators 460 can be provided such that the status of each of a plurality of modules 102 can be quickly and efficiently assessed by a user.

[0231] FIG. 28 is a perspective view of the interior of an example chassis 104. In the example shown, the central communication unit 470 is secured within the chassis 104. As previously discussed, the central communication unit 470 can be configured to control the operations of the sample analyzer 100. For example, as discussed with respect to FIG. 5, the central communication unit 470 can be configured to independently control one or more groups of modules, each group of modules being managed by one of a plurality of control panels 212. The central communication unit 470 can be sensitive to overheating from one or more components within the chassis 104. In some examples, the central communication unit 470 itself can be a source of significant heat within the chassis 104. In further implementations, the chassis 104 can further include an ethemet switch to enable and enhance connectivity to network resources to the components within the chassis 104. In still further implementations, the chassis 104 can include additional components to power the sample analyzer 100 such as batteries, power supply units and the like.

[0232] FIG. 29 is a perspective view of an example sample analyzer 500 having a thermal management system. In the example, the sample analyzer 500 has been configured to provide a directed airflow path through the module from an air intake and out through an air outlet. In the example shown, the thermal management system with air outflow parallel to air inflow. However, this configuration can have several drawbacks. For example, the air outflow flowingCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1parallel to the air inflow, at the back panel 118 of the sample analyzer 500, can cause the air outflow to mix with the air inflow such that warm is reintroduced to the sample analyzer 500. In addition, the air outflow can cause the back panel 118 of the sample analyzer 500 to become hot. For example, if the sample analyzer 500 is stationed such that the back panel 118 is adjacent to a wall, the air outflow can quickly cause the back panel 118 to become hot, which can be dangerous to a user accidentally or intentionally touching the back panel 118 (e.g. while moving a sample analyzer 500, changing fdters arranged at the back panel 118. or the like.) In addition, air inflow through one or more air intake vent 120 can introduce a considerable amount of dust and debris that can negatively impact the operation of the sample analyzer 500, reduce the lifespan of the modules therein, increase system failures and resulting maintenance operations, or a combination thereof. Example filter systems for effectively filtering the air intake while enabling efficiency of maintenance, time savings, and user convenience are illustrated and described with respect to FIGS 35-37. Furthermore, any of the various filter solutions and embodiments as discussed herein can include more, fewer, or different combinations of components from one another.

[0233] FIG. 30 is a perspective view of an example sample analyzer 100 having a thermal management system with side ventilation. In the example shown, the sample analyzer 100 has a back panel 118. The thermal management system includes at least one air intake vent 120 and at least one air outlet vent 122.

[0234] The air intake vent 120 is configured to direct cool air to one or more components of the sample analyzer 100. For example, the air intake vent 120 can include an air inlet configured to direct air inflow to the interior of the chassis 104. In some embodiments, the sample analyzer 100 can include more than one (e.g. a plurality) of air intake vents 120. In the example illustrated in FIG. 30, the sample analyzer includes eight air intake vents. In some examples, four upper air intake vents can direct air inflow to an upper row of modules 102 and four lower air intake vents can direct air inflow to a lower row of modules 102. In some embodiments, each of the air intake vents can direct air inflow to the chassis 104, in a plane perpendicular to the front panel 106.

[0235] The air outlet vent 122 is configured to direct hot air away from the sample analyzer 100. In some embodiments, the air outlet vent 122 is perpendicular to the air intake vent 120. For example, the air outlet vent 122 can include an air outlet configured to direct air outflow perpendicular to the air inflow. As illustrated in FIG. 30, the sample analyzer 100 can include more than one (e.g. a plurality of air outlet vents 122). For example, the sample analyzer 100CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1can include a plurality of air outlet vents 122 arranged in one or more direction, with each of the one or more direction being perpendicular to each of the one or more air intake vents 120. For example, air outlet vent 122A directs air outflow to the top of the back panel 118, perpendicular to the air inflow. For example, air outlet vent 122A directs air outflow to the top of the back panel 118, in a plane parallel to the front panel 106. As another example, air outlet vent 122B directs air outflow to the side of back panel 118, perpendicular to the air inflow. For example, air outlet vent 122B directs air outflow to the side of back panel 118, in a plane parallel to the front panel 106.

[0236] In some embodiments, the sample analyzer 100 includes a plurality of independently operable fans 502 arranged within the chassis 104. In other embodiments, the sample analyzer 100 includes a plurality of independently operable fans 502 arranged within the back panel 118. Each of the independently operable fans 502 can be configured to direct air inflow to the interior of the chassis 104. In some implementations, each of the independently operable fans 502 can be configured to pull air through one of the one or more air intake vents 120. In some examples, each of the independently operable fans 502 can be configured to direct air inflow to a subset of one or more (e.g. a plurality ol) modules 102 secured within the chassis 104. Advantageously, in this manner, the operation of each of the independently operable fans 502 can be adjusted to increase or decrease air inflow based on the heat sensed in different zones within the sample analyzer 100, the type of analysis that one or more modules 102 within a subset of modules 102 is conducting, capable of conducting (e.g. PCR or lab on a chip), or both. This both improves thermal management of the sample analyzer 100 and energy efficiency of the overall system. An example thermal management system having independently operable fans 502 is further illustrated and described with respect to FIG. 31.

[0237] FIG. 31 is a top view of the interior of the chassis 104 of the sample analyzer 100 having a thermal management system. In the example shown, the chassis 104 includes a back panel 118 having a plurality of air intake vents 120. Arranged interior to the back panel 118 are a plurality of independently operable fans 502 configured to direct air inflow to the interior of the chassis 104. In the example shown, each of the plurality of independently operable fans 502 is fluidically coupled to one of the plurality of air intake vents. In the example shown at least one baffle 504 is arranged within the interior of the chassis 104. In some examples, a plurality of baffles 504 can be arranged within the interior of the chassis 104. For example, each of a plurality of baffles can be configured to guide air inflow to one or more zone within the chassis 104 of the sample analyzer 100.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0238] FIG. 32 is a top schematic view of the interior of the chassis 104 of the sample analyzer 100 having a thermal management system. In the example shown, the chassis 104 includes a back panel 118 having a plurality of air intake vents 120. In the example shown, a plurality of baffles 504 are arranged within the interior of the chassis 104. For example, the plurality7of baffles 504 can be held within a baffle assembly 520, where the baffle assembly 520 is secured within the chassis 104. In the example shown, each of the plurality7of baffles 504 is configured to guide air inflow to one module 102. In some embodiments, each of the air intake vents 120 can direct air to one or more baffles 504. In some examples, the air intake vents 120 can direct air to the same number of baffles 504. In other examples, the air intake vents 120 can direct air to different numbers of baffles. For example, as illustrated in FIG. 32, air intake vent 120A directs air inflow to three modules via four baffles. Also illustrated in FIG.32, air intake vent 120B directs air inflow to two modules via three baffles. In addition, the baffles can have different geometries such that more or less air is directed to certain modules (e.g. depending on the module is configured to perform PCR analysis, lab on a chip analysis, or both). In this manner, the baffles can be tailored to direct air inflow to zones each of the one or more modules 102 based on the type of analysis that the module 102 is capable of conducting (e g. PCR or lab on a chip). This both improves thermal management of the sample analyzer 100 and lifespan of each of the modules 102.

[0239] FIG. 33 is a side view of an example chassis 104 having at least one baffle 504. As shown in the example, each of the baffles 504 can have geometries that enable directed air flow to regions within the chassis 104. For example, the air inflow may be directed into the chassis 104 in a plane perpendicular to the front panel 106, a baffle 504 can be configured to redirect the air inflow in a different direction within the chassis 104 such that it is targeted at one or more region within the chassis 104. For example, a baffle 504 can be configured to redirect the air inflow in a different direction within the chassis 104 such that it is targeted at a module 102 or group of modules 102.

[0240] FIG. 34 is a perspective view of an example baffle assembly 520. The baffle assembly 520 includes a plurality of baffles 504 and at least one opening configured to fluidically couple with a fan 502. In this example, each of the plurality of baffles 504 can be configured to rotate on an axis. In this manner, air can be directed to one or more region within the chassis 104 based on the temperature sensed therein, the type of analysis being performed by one or more module 102 (e g. PCR or lab on a chip), or both.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0241] FIG. 35 is a schematic view sample analyzer 100 having a slidable filter system. In the example shown the sample analyzer 100 has a back panel 118 arranged at the exterior of the chassis 104. Affixed to the back panel 118 is a filter housing 600.

[0242] The filter housing 600 can be a frame configured to interface with each of a plurality7of air intake vents 120. The filter housing 600 can support at least one filter 602. In some examples, the filter housing 600 can support one or more (e.g. a plurality of) filters 602.

[0243] The filter 602 can slidably secured within the filter housing 600. For example, the filter 602 can be removably slid into the filter housing 600. In some embodiments, the air inflow directed through each of a plurality7of air intake vents 120 can be simultaneously filtered by a single filter 602. For example, the filter 602 can filter each of a plurality of air intake vents 120 such thereby preventing the introduction of dust or other debris to any of the modules 102 while directing air inflow to the interior of the chassis 104.

[0244] In some examples, the filter 602 can be held within the filter housing 600 arranged at the exterior of the chassis 104 such that it is easily accessible for maintenance. In some embodiments, the filter 602 can be configured to have a handle such that it can be easily removed or replaced by a user in a single motion. As such, the filtration for each of a plurality of air intake vents 120 can be simultaneously replaced, without removal of any components other than the filter itself, thereby significantly improving efficiency of maintenance, time savings, and overall convenience to a user.

[0245] FIG. 36 is a side view of an example filter housing 600 affixed to an example sample analyzer. The filter housing 600 includes at least one channel 610 for slidably receiving a filter 602.

[0246] FIG. 37 is a perspective view of an example filter housing 600. The filter housing 600 can be a frame configured to interface with each of a plurality of air intake vents 120. In the example shown, the filter housing 600 includes at least one aperture 620 configured to interface with at least one air intake vent 120. The filter housing 600 can support at least one filter 602. In some examples, the filter housing 600 can support one or more (e.g. a plurality of) filters 602.

[0247] FIG. 38 is a flow diagram illustrating an example system 700 for manufacturing, testing, and using an analysis chip across different locations. The example process is divided into three main stages: a Wafer Manufacturing Facility7W, a Cartridge and Analysis chip Integrating Facility7I, and a Laboratory7L. The example Wafer Manufacturing Facility W performs operations 702, 704, 706, and 708. The example Cartridge and Analysis chipCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1Manufacturing Facility I performs operations 722 and 724. The example laboratory L performs operations 742, 744, 746, 748 and 750. Other embodiments include more, fewer, or different operations from the example illustrated in FIG. 38. Example systems and methods of manufacturing, testing, and using an analysis chip are further shown and described in commonly assigned U.S. Application No. 63 / 795,030, filed on April 25, 2025, entitled “BIOCHIP AND BIOCHIP COMPENSATION SYSTEM,” which is incorporated by reference.

[0248] An analysis chip 710 is fabricated in the Wafer Manufacturing Facility W before integration. As illustrated in FIG. 38, the operation 702 is performed to fabricate the analysis chip 710. In some embodiments, a temperature sensor is integrated into the analysis chip 710 to monitor and control thermal conditions, which affect the performance of the analysis chip 710. In some embodiments, a memory is integrated into the analysis chip 710 to store operational data and instructions necessary for its function. In some embodiments, multiple electrical contacts are deposited onto the analysis chip 710, configured to interface with an external electrical device.

[0249] Subsequently, the operation 704 tests the wafer to ensure quality and functionality. In some embodiments, the operation 704 is performed to analyze the overall performance of the wafer, such as evaluating its electrical characteristics, and structural integrity . For example, the defective or malfunctioning chips will be identified before cutting into individual chips.

[0250] Further, the operation 706 is performed to compensate the analysis chip at waferlevel. In some embodiments, the compensation includes calibrating the analysis chip, trimming the analysis chip, or a combination thereof, to ensure that the analysis chip 710 functions accurately under varying environmental conditions. The compensation process in operation 706 not only addresses temperature variations but also performs trimming to fine-tune circuit or sensor parameters, correct manufacturing variations and optimize performance for future measurements. Further, the calibration data or trim coefficients, including temperature compensation parameters and sensor calibration coefficients, are stored in a memory to facilitate real-time adjustments and maintain optimal performance during operation. An example of operation 706 is illustrated and descnbed in detail with reference to FIG. 42.

[0251] Finally, the operation 708 is performed to dice the wafer into individual chips, also known as a die. In some embodiment, the operation 704 is performed to separate the wafer into individual chips, each including a functional circuit. Further, the individual chips will be packaged before integrated into a system.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0252] The analysis chip-integrated cartridge 730 is manufactured for laboratory testing in the Cartridge and Analysis chip Manufacturing Facility I. As illustrated in FIG. 38, the operation 722 is performed to prepare the analysis chip 710 for integration into a cartridge (shown in FIG. 6). In some embodiments, quality control is performed at operation 722 to ensure the analysis chip 710 is functional before it is assembled into the cartridge.

[0253] Further, the operation 724 is performed to integrate the analysis chip 710 into a chip carrier device 114 (shown in FIG. 7). In some embodiments, the operation 724 ensures that the analysis chip 710 is mounted within the cartridge to establish alignment, electrical connectivity, and mechanical stability.

[0254] In Laboratory L, testing is conducted, and results are reported. As illustrated in FIG. 38, the operation 742 is performed to set up an instrument in preparation for testing. Subsequently, the operation 744 is performed to load the cartridge into the instrument that will be used for testing in the laboratory. In some embodiments, the operation 744 ensures that the cartridge is positioned within the instrument to establish electrical and mechanical connections required for testing.

[0255] Further, the operation 746 is performed to run the test of a biological sample that is analyzed by the analysis chip 710. As part of operation 746, a sub-step 748 is executed where trim coefficients are applied to ensure accurate and reliable test results. The parameters help compensate for variations in sensor performance, temperature fluctuations, and manufacturing tolerances, thereby enhancing the precision and reproducibility of the analysis chip’s analysis. An example of operation 746 is illustrated and described in further detail with reference to FIG.44.

[0256] Finally, the operation 750 is performed to process and report the results. An example of operation 750 is illustrated and described in further detail with reference to FIG.44.

[0257] Performing compensation of the temperature sensors in the analysis chips at the wafer level or inspection stage, prior to instrument loading, provides multiple advantages, including early defect detection that improves yield, reduces waste, and lowers production costs. In some embodiments, compensating the temperature sensor of the analysis chip includes calibrating the temperature sensors, trimming sensor parameters, or a combination thereof. Calibration ensures that the sensors meet specified accuracy requirements, while trimming corrects for manufacturing variations and enhances long-term stability. Conducting these compensation processes at an early manufacturing stage improves the reliability of the analysisCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1chips for critical applications and simplifies the final instrument design by reducing the need for complex system-level calibration. Further, integrating inspection and compensation into wafer-level manufacturing streamlines production, facilitates automation and scalability , and promotes consistent performance across devices and production batches.

[0258] FIG. 39 is a block diagram illustrating an example analysis chip 142. In the example illustrated in FIG. 39, the analysis chip 142 includes a biosensor 170, a temperature sensor 804. a processing device 806. and a memory 808.

[0259] The analysis chip 142 is a microelectronic device that analyzes and detects biological materials. The analysis chip 142 hosts biomedical reactions to screen biological analytes or test for biological analytes.

[0260] The biosensor 170 is a component that detects biological analytes. The biosensor 170 combines a biological sensing element with a transducer to detect and measure a biological, chemical, or physical processes. In some embodiments, the biosensor 170 includes a biosensor array.

[0261] The temperature sensor 804 is a component that monitors the operating temperature of the analysis chip 142. In some embodiments, the temperature sensor 804 is positioned adjacent to the biosensor 170 to provide temperature data to compensate the biosensor 170.

[0262] The processing device 806 manages and processes data received from other components of the analysis chip 142. In some embodiments, the processing device 806 is configured to process signals from the biosensor 170 and the temperature sensor 804. For example, the processing device 806 includes a digital core to digitize the analog signals.

[0263] The memory 808 is a component configured to store data related to the operation of the analysis chip 142. For example, the memory 808 stores the data generated by other components, such as the temperature sensor 804 and the biosensor 170. In some embodiments, the memory 808 stores calibration data or trimming coefficients or both, including temperaturebased correction factors.

[0264] In the example illustrated in FIG. 39, the biosensor 170, the temperature sensor 804, and the memory 808 are each connected to the processing device 806, forming an integrated system.

[0265] FIG. 40 is a schematic diagram illustrating another example of the analysis chip 142. In the example illustrated in FIG. 40, the analysis chip 142 includes a biosensor 170, a temperature sensor 804, a processing device 806 and a memory 808, which are the same orCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1similar to those illustrated and described with reference to FIG. 39. The example analysis chip 142 shown in FIG. 40 further includes a first data processing unit 812a, a second data processing unit 812b, a reference generator 814, a test control 816, a resistive heater 818, and a plurality of I / O pads 154. Other examples of the analysis chip 142 can include any one or more of the components illustrated in FIG. 40, and combinations thereof. In other words, other examples may have more or fewer components than shown in FIG. 40.

[0266] As previously discussed, the analysis chip 142 is a microelectronic device. In some embodiments, the microelectronic device is fabricated using semiconductor fabrication techniques, such as Complementary Metal-Oxide-Semiconductor (CMOS) technology' that integrates microelectronic components with biochemical functionalities. For example, the biosensor 170, the temperature sensor 804, the processing device 806. and the memory 808 are integrated to a single chip by using the CMOS technology. In some examples, the analysis chip 142 interfaces with lab instruments for signal detection and data acquisition. Further, the analysis chip 142 processes biological or chemical signals and transmits the processed data to the lab instrument.

[0267] The biosensor 170 includes a plurality' of individual sensor elements. In some embodiments, the plurality' of individual sensor elements is arranged in a matrix including a plurality' of rows and columns. In the illustrated example, the plurality7of individual sensor elements is arranged in a 32 x 32 matrix. In other embodiments, the biosensor 170 has other quantities of sensor elements, including more or fewer sensor elements. In other embodiments, the biosensor 170 has sensor elements that are arranged in other configurations or orientations (e.g., triangle, diamond, circle, or the like).

[0268] In some embodiments, the biosensor 170 is designed to detect specific biological interactions, such as utilizing techniques of Continuous Wave Fluorescence (CWF), Time-Gated Fluorescence (TGF), a combination of CWF and TGF, or other detection techniques. In some examples, the biosensor 170 seamlessly' interfaces with lab instruments to provide rapid and accurate analysis of biological samples. As shown in the example in FIG. 40, the biosensor 170 further converts the detected data into electrical signals and transmits the signals to the processing device 806 to be processed through algorithms to extract the needed information.

[0269] As previously discussed, the temperature sensor 804 monitors the operating temperature of the analysis chip 142. In some embodiments, the temperature sensor 804 is used for compensating the biosensor of the analysis chip to ensure reliable biochemical measurements. In some embodiments, the temperature sensor 804 includes an improvedCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1architecture with a one-point trim at room temperature, allowing for precise compensation at the wafer level or during inspection before instrument loading. In some embodiments, the temperature sensor 804 connects to the processing device 806, and the reading temperature is processed by the processing device 806. In some examples, the temperature sensor 804 is positioned proximal to the biosensor 170 to facilitate real-time adjustments and compensations to the readings of the biosensor 170. For example, by placing the temperature sensor 804 close to the biosensor 170, the lag time is minimized between detecting a temperature change and adjusting the response from the biosensor 170.

[0270] As previously discussed, the processing device 806 manages and processes data. In some embodiments, the processing device 806 includes a digital core that digitizes analog signals transmitted from other components, performs computations, and executes algorithms to interpretate the data from the biosensor 170 and the temperature sensor 804. In some examples, the processing device 806 also manages data storage.

[0271] As previously discussed, the memory7808 stores data related to the operation of the analysis chip 142. In some embodiments, the memory 808 is anon-volatile memory7that stores data permanently. For example, the memory 808 is a One-Time Programmable (OTP) memory that allows data to be written only once, after which the data is permanently stored and cannot be modified or erased. In some embodiments, the OTP memory7808 permanently stores calibration data or trimming coefficients or both, including temperature-based correction factors.

[0272] As shown in the example in FIG. 40, the memory7808 is a Triple Redundant OTP memory that surrounds the processing device 806. The triple scheme ensures robustness and reliability7by surviving any wafer-level or package-level processing damages. For example, even if the data in one or two OTP memories are corrupted or damaged during manufacturing, packaging, or operational stresses, the remaining OTP memory will retrieve the original data. The triple scheme is illustrated as an example, but the embodiment is not limited thereto. In other embodiments, the number of memories can be more or less than three, and the scheme can be different.

[0273] The data processing units 812a and 812b are signal processing components that reduce the high-frequency noise of the system and improve the signal quality. In some embodiments, the data processing units 812a and 812b reduce the high-frequency noise by downsampling the signal while preserving essential low-frequency components. For example, the first data processing unit 812a acts as a low-pass filter, removing high-frequency noise withCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1frequencies above a certain cutoff threshold, thereby preventing aliasing when higher frequency signals are misinterpreted as lower frequency signals during the sampling process.

[0274] Once the higher frequencies have been filtered out by the first data processing unit 812a, the signal is downsampled. For example, downsampling involves reducing the overall number of samples in the signal by a specific factor, which lowers the data rate and simplifies further processing. The signal is passed to the second data processing unit 812b after downsampling. In some embodiments, the second data processing unit 812b further smooths the signal and refines noise suppression to reduce the residual noise not filtered by the first data processing unit 812a.

[0275] As shown in the example in FIG. 40, the first data processing unit 812a is positioned on the first side of the biosensor 170 to receive raw data from the first half of the biosensor 170, and the second data processing unit 812b is positioned on the second side of the biosensor 170 to receive raw data from the second half of the biosensor 170. In some embodiments, the first data processing unit 812a and the second data processing unit 812b covert the high-frequency data into a lower frequency stream, which is more manageable for subsequent digital processing stages.

[0276] The reference generator 814 is a component that provides reference signal or voltage to ensure the consistency in signal measurements. In some examples, the reference generator 814 generates reference signals necessary for accurate sensor compensation. For example, the reference generator 814 adjusts the reference signals to compensate for environmental variations such as temperature fluctuations, ensuring consistent and precise compensation under various conditions.

[0277] The test control 816 is a dedicated area designed to monitor the performance of the assay, acting as an internal quality control. In some embodiments, the test control 816 provides a baseline signal to compare against the test result from the sample to ensure the validity and reliability of assay results. In some examples, the test control 816 detects errors or anomalies during the testing process.

[0278] The resistive heater 818 is a microscale heating element that generates heat when an electrical current passes through the resistive material. In some embodiments, the resistive heater 818 adjusts the temperature of the analysis chip 142 to accelerate biomedical reactions.

[0279] The I / O pads 154 are conductive elements designed to connect to an external circuit. In some embodiments, the I / O pads 154 connect to an electrical circuit to facilitateCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1signal amplification, processing, and transmission. In some examples, the electrical circuit converts the biochemical signals into readable electrical outputs that will be analyzed further.

[0280] Any of the memory described herein can be implemented as computer readable media. Computer readable media includes any available media that can be accessed by the processing device 806. By way of example, computer readable media include computer readable storage media and computer readable communication media.

[0281] Computer readable storage media includes volatile and nonvolatile, removable, and non-removable media implemented in any device configured to store information such as computer readable instructions, data structures, program modules or other data. Computer readable storage media includes, but is not limited to, random access memory, read only memory, electrically erasable programmable read only memory, flash memory or other memory technology, compact disc read only memory, digital versatile disks or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and that can be accessed by the processing device 806. Computer readable storage media does not include computer readable communication media.

[0282] Computer readable communication media typically embodies computer readable instructions, data structures, program modules or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media. The term “modulated data signal’7refers to a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, computer readable communication media includes wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, radio frequency, infrared, and other wireless media. Combinations of any of the above are also included within the scope of computer readable media.

[0283] FIG. 41 is a block diagram illustrating a compensation system 850. The example compensation system 850 includes a wafer tester 852, a heater 854, a chip interface 856 and a controller 858.

[0284] The compensation system 850 is designed to calibrate the analysis chip, trim the analysis chip, or a combination thereof during the manufacturing process. In some embodiments, the compensation system 850 interacts with the analysis chip to ensure that the fabricated analysis chip meets expected performance specifications by verifying and adjusting various parameters during production and testing.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0285] The wafer tester 852 is a component used to test the electrical properties of semiconductor wafers. In some embodiments, the wafer tester 852 is designed to interface with the wafer directly. For example, the wafer tester 852 interacts with the wafer to evaluate the functionality and quality of semiconductor devices by applying electrical signals to the chips on the wafer and measuring the output. In some examples, the wafer tester 852 is not only configured to execute the compensation process but also integrates the heater 854 to regulate the temperature of the wafer during compensation, ensuring that the temperature conditions are optimal for accurate testing.

[0286] The heater 854 is configured to maintain a controlled temperature environment for the wafer. In some embodiments, the heater 854 is integrated into the wafer tester 852 and designed to bring the wafer to a specific temperature during compensation process. For example, because the properties of the semiconductor materials are affected by the temperature, maintaining a controlled thermal environment ensures accurate and reliable electrical measurements.

[0287] The chip interface 856 establishes both the physical and electrical connection between the wafer tester 852 and the analysis chip on the wafer. In some embodiments, the chip interface 856 serves as a signal transmission interface, facilitating the exchange of test signals between the wafer tester 852 and the analysis chip. For example, this interface enables measurement and analysis of the electrical characteristics of the analysis chip, ensuring proper functionality and compensation. In some examples, depending on the testing requirements, the chip interface 856 may include probe contacts, microelectrode arrays, or other specialized connectors designed to minimize signal distortion and enhance test accuracy.

[0288] The controller 858 is the central unit that coordinates the activities of the compensation system 850. In some embodiments, the controller 858 manages the operation of the wafer tester 852, the heater 854, and the monitoring of the chip interface 856. For example, the controller executes software that processes input from these components and dynamically adjusts their operation to maintain precise compensation. In some examples, the controller 858 functions as the command center of the compensation system 850, overseeing the operation of the integrated heater 854. It utilizes real-time feedback from temperature sensors on the analysis chip to dynamically adjust the heater settings, ensuring that the wafer remains at optimal conditions for accurate compensation. This closed-loop temperature control minimizes fluctuations and enhances the reliability of the compensation process.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0289] In some embodiments, the controller 858 manages the operation of the heater, determines the temperature-based correction factor, and provides the temperature-based correction factor to the analysis chip. In some examples, the controller 858 adjusts the temperature-based correction factor based on a comparison between the temperature reading of the analysis chip and a reference temperature value.

[0290] FIG. 42 is a flow chart illustrating an example method 706 of a wafer-level compensation process for analysis chips. The example method 706 includes operations 862, 864, 866, 868, 870, 872, and 874. Other embodiments include more, fewer, or different operations from the example illustrated in FIG. 42.

[0291] The operation 862 is performed to prepare calibration instrument. In some embodiments, the calibration instrument is set up and verified for accuracy. In some examples, is configured to apply controlled temperature variations and record sensor readings. Further, necessary' software scripts or automated calibration procedures are loaded into the system of the calibration instrument.

[0292] The operation 864 is performed to set up wafer temperature. For example, the entire wafer is placed in a temperature-controlled chamber or on a heated chuck to simulate real-world operating conditions. In some embodiments, the temperature is precisely controlled within a tight tolerance (e.g., ±0.1°C) to ensure repeatable calibration. However, in other embodiments, the tolerance is not strictly constrained and may vary based on specific calibration requirements. In some examples, a reference temperature sensor in the operation 864 is applied to verify the actual temperature of the wafer.

[0293] The operation 866 is performed to probe all of the analysis chips on the wafer. In some embodiments, wafer probes are used to make electrical contact with each analysis chip on the wafer. For example, the wafer probes are fine-tipped probes that touch specific contact pads (e.g. I / O pads) of each analysis chip to supply power and read the temperature sensor outputs. In some embodiments, the I / O pads may be configured on the chip carrier device, the analysis chip, or both. In some examples, sensor readings from the temperature sensor are recorded at various temperatures to determine how each chip responds.

[0294] The operation 868 is performed to trim the temperature sensor. In some embodiments, the trimming process is to ensure to ensure that each sensor provides an accurate and consistent temperature reading across the wafer. For example, the temperature sensor trimming process compensates for variations in fabrication, material properties, and circuit characteristics. In some examples, the trimming process also includes compensation forCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1environmental factors. For example, multi-temperature trimming is performed to adjust the sensor response at different temperature points to ensure accuracy across a broad range. In some embodiments, the trimming process calculates correction values based on deviations between measured sensor output and the expected reference values.

[0295] The operation 870 is performed to store trim coefficients or calibration data in a memory. In some embodiments, once the appropriate corrections or data are determined, trim coefficients or calibration data are stored in the memory of each analysis chip. For example, the coefficients or calibration data are stored and will used in real-time by the analysis chip during normal operation to adjust raw sensor readings and improve accuracy. In some examples, multiple trim coefficients or calibration data are stored to correct for different temperature ranges.

[0296] The operation 872 is performed to complete the trimming and storage process for all of the analysis chips on the wafer. For example, the trimming and coefficient storage process is repeated for every analysis chip on the wafer. In some embodiment, the operation 872 is performed to ensure each analysis chip meets required performance specifications. In some examples, the defective analysis chips that fail calibration will be removed.

[0297] The operation 874 is performed to store the wafer for future use. In some embodiments, the wafer is stored under controlled conditions to maintain its accuracy and reliability after compensation. For example, the wafer is packaged in a protective enclosure to prevent contamination. In some examples, the wafer is sent for dicing where individual analysis chips are cut from the wafer and packaged.

[0298] FIG. 43 is a block diagram illustrating an example sample analyzer 100 that includes a sample cartridge 112 and a module 900 configured for lab on a chip analysis. In the example sample analyzer 100. the sample cartridge 112 includes an analysis chip 142 with a plurality of I / O pads 154. The example sample analyzer 100 also includes a module 900 configured for lab on a chip analysis. As illustrated in FIG. 43, the module 900 includes a control unit 902, an instrument interface 982, a data processing unit 984, a communication interface 986, an instrument interface 982. and a power supply unit 990.

[0299] The example sample analyzer 100 is configured to analyze a biological sample. In some embodiments, the module 900 configured for lab on a chip analysis is designed to interface with the sample cartridge 112 through an instrument interface, facilitating electrical and data communication.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0300] As previously discussed, the sample cartridge 112 is designed for receiving and processing a biological sample for analysis by the module 900 configured for lab on a chip analysis. In some embodiments, the sample cartridge 112 is inserted into the module 900 configured for lab on a chip analysis and interfaced with the instrument interface for analytical processing.

[0301] As previously discussed, the analysis chip 142 is a microelectronic device that includes sensors or detection elements for analyzing the biological sample. In some embodiments, the analysis chip 142 utilizes electrochemical, optical, or impedance-based sensing techniques to detect target analytes such as nucleic acids, biomarkers, proteins, metabolites, or other biologically significant molecules. These target analytes are obtained, isolated, collected, or captured from a sample, including, without limitation, blood, biological fluids, liquefied solids, or tissue. The process enables the analysis chip 142 to detect and analyze specific biological markers, facilitating diagnostic or research applications.

[0302] As previously discussed, the I / O pads 154 are conductive elements integrated into the analysis chip 142. In some embodiments, the I / O pads 154 functions as the sensing interface, facilitating electrochemical reactions, signal transduction, or impedance measurement to generate raw data for processing. In some examples, the I / O pads 154 connected to the instrument interface 982, allowing the sample cartridge 112 to interact with the module 900 for data acquisition and analysis.

[0303] The module 900 is configured for lab on a chip analysis. As further discussed herein, the module 900 is a processing and analysis device configured to receive the sample cartridge 112. In some embodiments, the module 900 interacts with the sample cartridge 112 to facilitate the sample data detection, measurement, and processing. In some examples, the module 900 analyzes the data received from the analysis chip 142 and provides test results to the user.

[0304] The control unit 902 is the central processing unit of the module 900. In some embodiments, the control unit 902 manages the overall operation of the module 900. For example, the control unit 902 controls interactions between different internal components and regulates measurement cycles, compensation processes, and data processing tasks. In some examples, the control unit 902 is implemented as a microcontroller, microprocessor, or embedded computing system with dedicated firmware. In some embodiments, the control unit 902 sends instructions to internal components of the module 900 or to external devices via signals transmitted through the communication interface 986.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0305] The instrument interface 982 serves as the primary connection between the module 900 and the sample cartridge 112. In some embodiments, the instrument interface 982 provides electrical connectivity to power the analysis chip 142 and I / O pads 154. In some examples, the pogo pins of the instrument interface 982 connect to the I / O pads 154 of the analysis chip, allowing the instrument interface 982 to receive raw signals from the analysis chip 142. In some embodiments, the signals received from the analysis chip 142 are transmitted to the data processing unit 984 through the instrument interface 982.

[0306] The data processing unit 984 is configured to analyze and process the acquired data and signals. In some embodiments, the data processing unit 984 analyzes and interprets the signals received from the analysis chip 142 to extract useful information. For example, the data processing unit 984 interprets data by applying algorithms for pattern recognition, statistical analysis, or diagnostic evaluation. Further, the data processing unit 984 converts the analog signals into digital data. In some examples, the data processing unit 984 performs signal amplification and filtering by enhancing weak signals and removing unwanted noise.

[0307] The communication interface 986 is media between the module 900 and external devices. In some embodiments, the communication interface 986 enables data exchange between the module 900 and external devices by wired communication (e g., USB, Ethernet, or serial data transfer) or wireless communication (e.g., Bluetooth, Wi-Fi, or NFC for remote data access).

[0308] The user interface 988 provides an interactive platform for users to operate and monitor the module 900. In some embodiments, the user interface 988 includes a touchscreen display or LCD screen to present real-time results and system status. In some examples, the user interface 988 includes physical or virtual buttons for navigation and command input. In some embodiments, the user interface 988 enables the user to interact with the module 900 to initiate tests, review analysis results, and configure system settings.

[0309] The pow er supply unit 990 provides the necessary electrical energy for all internal components of the module 900. In some embodiments, the pow er supply unit 990 connects to each component of the module 900 to supply the power to ensure stable operations.

[0310] FIG. 44 is a flow chart illustrating an example process 1000 for performing measurements using an analysis chip within an instrument. The example process 1000 performs the operations 1002, 1004, 1006, 1008, 1010, 1012, 1014, 1016, and 1020. Other embodiments include more, fewer, or different operations from the example illustrated in FIG. 44.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0311] The operation 1002 is performed to power on the instrument. In some embodiments, the instrument is powered on once the cartridge is loaded, initiating the internal processes required for measurement.

[0312] The operation 1004 is performed to load the cartridge into the instrument. In some embodiments, the user inserts the cartridge, which includes the analysis chip and necessary reagents, into the instrument.

[0313] The operation 1006 is performed to read trim coefficients from the memory. In some embodiments, the instrument retrieves pre-stored trim coefficients from the memory to compensate for variations in sensor readings. For example, the retrieved coefficients adjust measurements for temperature, voltage offsets, fabrication differences and other variations to improve accuracy.

[0314] The operation 1008 is performed to set up the analysis chip. In some embodiments, the analysis chip is initialized for operation. For example, the operation 1008 includes applying power and initializing its circuits, setting up internal parameters (e.g., voltage levels, reference currents), preparing fluidic pathways for interaction with the sample.

[0315] The operation 1110 is performed to run the test. In some embodiments, the testing process begins based on predefined protocols. For example, the analysis chip operates according to its designed function, which includes biochemical, electrical, optical, or other applicable measurements.

[0316] The first sub-step 1012 of the operation 1110 is performed to start the measurement process. In some embodiments, the instrument begins the measurement sequence at the first sub-step 1012, preparing to interact with the sample through the analysis chip.

[0317] The second sub-step 1014 of the operation 1110 is performed to interact the analysis chip with the sample under test. In some embodiments, the analysis chip is exposed to the sample at the second sub-step 1014, initiating a reaction or interaction that generates a measurable signal.

[0318] The operation 1016 is performed to collect and process data from the analysis chip. In some embodiments, the data processing unit collects and processes data produced by the analysis chip as it interacts with the sample at the operation 1016. In some examples, the collected data includes electrical, optical, or biochemical signals. Further, the data will be temporarily stored in the data processing unit for additional analysis.

[0319] The operation 1020 is performed to display the results to the user. In some embodiments, the final measurement results are displayed to the user in a reasonable format,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1providing diagnostic information. For example, the format includes graphical representations such as charts or graphs and numeric data displayed in tables. In some examples, color coding or other visual aids are used to highlight critical values or trends, making it easier for users to assess the diagnostic information provided quickly.EXAMPLES IMPLEMENTING PCR AMPLIFICATION VIA NON-THERMAL CYCLING DETECTION OF AN ANALYTE

[0320] The present disclosure can be better understood by reference to the following examples implementing non-thermal cycling detection of an analyte which are offered by way of illustration. All reagents, starting materials, and solvents used in the following examples were purchased from commercial suppliers (for example, Sigma Aldrich, St. Louis, MO) and were used without further purification unless otherwise indicated.Starting Solution

[0321] The starting solution comprises an aqueous solution of compounds necessary to initiate an amplification reaction with a target nucleic acid. The starting solution may initially be separated into one or more dry’ components and an aqueous solution comprising one or more components, where the dry component can comprise matenals that are sensitive to air, heat, light or have a limited lifetime in solution. The two components can be combined prior to entering the reaction vessel or one of the components may be initially present in the reaction vessel. In the case where the starting solution is a single aqueous solution, it can be present in the reaction vessel or added at some point before, after, or during the addition of the target nucleic acid.

[0322] In embodiments where the starting solution comprises a dry component, the nature, composition, and method of producing dried components is well-known to those of ordinary skill in the art as evidenced by the following references: U.S. Pat. Nos. 5,098,893. 5,102,788, 5,556,771, 5,763,157, 6,294,365, and 5,413,732, U.S. Pat. Appl. Publ. Nos. 2006 / 0068398 and 2006 / 0068399; and Pharm. Dev. Technol., 10: 151-173 (2005) and Pharm. Biotechnol., 14: 281-360 (2002). Dried components include, but are not limited to, solid and / or semi-solid particulates, powders, tablets, crystals, capsules, beads, spheres and the like, which are manufactured in a variety of ways.

[0323] In some embodiments, the starting solution comprises a thermostable polymerase, a primer pair that is optionally labeled, and optionally, one or more of: a probe, a reverse transcriptase, and additional reagents. In some embodiments, the starting solution comprises a reaction mixture including a thermostable polymerase, a primer pair, and optionally, a probe,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1a reverse transcriptase, and additional reagents. A “reaction mixture” means a solution containing all the necessary reactants for performing a reaction, which may include, but not be limited to, buffering agents to maintain pH at a selected level during a reaction, salts, co-factors, scavengers, and the like.

[0324] In some embodiments, the solution comprises at least four, at least six, at least eight, or at least ten sets of primer pairs. In such embodiments, the amplification reaction may comprise detecting at least four, at least six, at least eight, or at least ten target nucleic acids, respectively. In embodiments with multiple primer pair, the target nucleic acids may come from the same or different samples.Primers

[0325] Primers useful in the methods described herein are generally capable of selectively hybridizing to: genomic DNA, a target RNA (genomic or transcript), a cDNA reverse transcribed from the target RNA, and / or an amplicon that has been amplified from genomic DNA, a target RNA, or a cDNA (collectively referred to as “template”), and, in the presence of the template, a polymerase and suitable buffers and reagents, can be extended to form a pnmer extension product. Primers are generally of a sufficient length to ensure selective hybridization to their target nucleic acids. Generally, primers of at least 15 nucleotides in length hybridize specifically in most contexts, and this length can be reduced, e.g., by including of affinity-enhancing modifications, such as those discussed above. Primers can but need not be exactly complementary to their target nucleic acids. Primers can have any degree of complementarity described above for exemplary polynucleotides. In illustrative embodiments, primers can be 8 to 45 nucleotides in length and at least 90% complementary' to their target nucleic acids: 8 to 45 nucleotides in length and at least 95% complementary to their target nucleic acids: 8 to 45 nucleotides in length and at least 99% complementary to their target nucleic acids: 8 to 30 nucleotides in length and at least 90% complementary to their target nucleic acids: 8 to 30 nucleotides in length and at least 95% complementary' to their target nucleic acids: 8 to 30 nucleotides in length and at least 99% complementary to their target nucleic acids. In embodiments wherein a primer is less than 100% complementary to it target nucleic acid, having the 3' nucleotide in the primer be complementary to its target nucleic acid facilitates the production of an extension product.

[0326] In some embodiments, the primer is present at a concentration of at least 500 nM, 600 nM, 700 nM, or 800 nM. In some embodiments, the primer is present at a concentration of from 500 nM to 1000 nM. 500 nM to 900 nM, 500 nM to 800 nM, 600 nM to 1000 nM, 600CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1nM to 900 nM, 600 nM to 800 nM, 700 nM to 1000 nM, 700 nM to 900 nM, or 700 nM to 800 nM.

[0327] In some embodiments, a primer that selectively hybridizes to its target nucleic acid hybridizes to its target nucleic acid with at least 5-fold greater affinity than to non-target nucleic acid under the same assay conditions. In some embodiments, a primer that selectively hybridizes to its target nucleic acid hybridizes to its target nucleic acid with at least 10-fold greater affinity than to non-target nucleic acid under the same assay conditions.

[0328] In some embodiments, a primer pair is designed to produce an amplicon that is 50 to 1500 nucleotides long, 50 to 1000 nucleotides long, 50 to 750 nucleotides long, 50 to 500 nucleotides long, 50 to 400 nucleotides long, 50 to 300 nucleotides long, 50 to 200 nucleotides long, 50 to 150 nucleotides long, 100 to 300 nucleotides long, 100 to 200 nucleotides long, or 100 to 150 nucleotides long.

[0329] The primers have a melt temperature, Tm. In some embodiments, the primer melt temperature is 76-82°C, 77-81 °C, or 78-80°C. In some embodiments, the primer melt temperature is 13°C or less, 12°C or less, 11 °C or less, 10°C or less, 9°C or less, 8°C or less, or from 7-13°C or from 8-10°C below the first temperature in the reaction vessel.

[0330] The primers have an annealing temperature, Ta. In some embodiments, the primer annealing temperature is 60-80°C, 60-75°C, or 60-70°C. In some embodiments, the primer annealing temperature is 0°C or greater, 1°C or greater, 2°C or greater, 3°C or greater, 4°C or greater. 5°C or greater, 6°C or greater. 7°C or greater, 8°C or greater, 9°C or greater, or 10°C or greater, or from 0-10°C or from 0-6°C greater than the second temperature in the reaction vessel.

[0331] In some embodiments, the primer further comprises a stabilizing base. A stabilizing base refers to a greater tendency for the modified base to pair an unmodified complementary base, as compared to the tendency of canonical bases to form base pairs (e.g., A-T and G-C). The stabilizing base can be present at any location on the primer. However, in some embodiments, it is advantageous for at least one stabilizing base to be at the 2nd or 3rd position from the 3’ end of the primer. Stabilizing bases can exert their effects by differences in, e.g., hydrogen bonding in base pairing, in base stacking, and effects on the secondary structure of sequences in which they appear. Stabilizing bases are known; some are known to exist in nature (e.g., inosine), and some have been produced by synthetically modifying a canonical base. Example stabilizing bases include locked nucleic acids (LNAs), unlocked nucleic acids (UNAs), AP-dC (G-clamp), 2-aminoadenine, 5-methylcytosine. C(5)-CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1propynylcytosine, C(5)-propynyluracil, 2-aminoadenine, 2-thiothymine, deoxyinosine, 7-alkyl-7-deazaguanine, 2'-hypoxanthine, or 7-nitro-7-deazahypoxanthine. 3-(2'-deoxy-beta-D-ribofuranosyl)pyrrolo-[2,3-d]-pyrimidine-2-(3H)-one, N4-alkylcytosine, 2-thiocytosine, and combinations thereof.

[0332] In some embodiments, the primer is labeled with a detectable moiety. The detectable moiety may comprise a fluorescent dye and a quencher molecule. In some embodiments, the primer is not labeled.Probes

[0333] In some embodiments, the starting solution further comprises one or more probes. Probes useful in the methods described herein are generally capable of selectively hybridizing to: genomic DNA, a target RNA (genomic or transcript), a cDNA reverse transcribed from the target RNA, and / or an amplicon that has been amplified from genomic DNA, a target RNA, or a cDNA (collectively referred to as “template”). Generally, probes of at least 15 nucleotides in length hybridize specifically in most contexts, and this length can be reduced, e.g., by including of affinity-enhancing modifications, such as those discussed above. Probes can but need not be exactly complementary to their target nucleic acids. Probes can have any degree of complementarity described above for exemplar} polynucleotides. In illustrative embodiments, probes can be 8 to 45 nucleotides in length and at least 90% complementary' to their target nucleic acids: 8 to 45 nucleotides in length and at least 95% complementary to their target nucleic acids: 8 to 45 nucleotides in length and at least 99% complementary to their target nucleic acids: 8 to 30 nucleotides in length and at least 90% complementary to their target nucleic acids: 8 to 30 nucleotides in length and at least 95% complementary' to their target nucleic acids: 8 to 30 nucleotides in length and at least 99% complementary to their target nucleic acids. In embodiments wherein a primer is less than 100% complementary to a target nucleic acid, any points or regions of non-complementarity are typically located so as not to disrupt the ability of the probe to selectively hybridize to its target nucleic acid.

[0334] In some embodiments, the probe is present at a concentration of at least 500 nM, 600 nM, 700 nM, or 800 nM. In some embodiments, the primer is present at a concentration of from 500 nM to 1000 nM, 500 nM to 900 nM, 500 nM to 800 nM, 600 nM to 1000 nM, 600 nM to 900 nM, 600 nM to 800 nM, 700 nM to 1000 nM, 700 nM to 900 nM, or 700 nM to 800 nM.

[0335] In some embodiments, a probe that selectively hybridizes to its target nucleic acid hybridizes to its target nucleic acid with at least 5-fold greater affinity than to non-target nucleicCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1acid under the same assay conditions. In some embodiments, a probe that selectively hybridizes to its target nucleic acid hybridizes to its target nucleic acid with at least 10-fold greater affinity than to non-target nucleic acid under the same assay conditions.

[0336] The probes have a melt temperature, Tm. In some embodiments, the probe melt temperature is 76-82°C, 77-81°C, or 78-80°C. In some embodiments, the probe melt temperature is 13°C or less, 12°C or less, 11 °C or less, 10°C or less, 9°C or less, 8°C or less, or from 7-13°C or from 8-10°C below the first temperature in the reaction vessel.

[0337] The probes have an annealing temperature, Ta. In some embodiments, the probe annealing temperature is 60-80°C, 60-75°C, or 60-70°C. In some embodiments, the probe annealing temperature is 0°C or greater, 1°C or greater, 2°C or greater, 3°C or greater, 4°C or greater. 5°C or greater>6°C or greater. 7°C or greater, 8°C or greater, 9°C or greater, or 10°C or greater, or from 0-10°C or from 0-6°C greater than the second temperature in the reaction vessel.

[0338] In some embodiments, the probe further comprises a destabilizing base. A destabilizing base refers to a lesser tendency for the modified base to pair an unmodified complementary base, as compared to the tendency of canonical bases to form base pairs (e.g., A-T and G-C). The destabilizing base can be present at any location on the primer. In some embodiments, the destabilizing base decreases the melt temperature of the target nucleic acid. Destabilizing bases can exert their effects by differences in, e.g., hydrogen bonding in base pairing, in base stacking, and effects on the secondary structure of sequences in which they appear. Destabilizing bases are known to exist in nature and have been produced by synthetically. Example destabilizing bases include locked nucleic acids (LNAs), unlocked nucleic acids (UNAs), AP-dC (G-clamp), 2-aminoadenine, 5-methylcytosine, C(5)-propynylcytosine, C(5)-propynyluracil. 2-aminoadenine, 2-thiothymine, deoxyinosine, 7-alkyl-7-deazaguanine, 2'-hypoxanthine, or 7-nitro-7-deazahypoxanthine, 3-(2'-deoxy-beta-D-ribofuranosyl)pyrrolo-[2,3-d]-pyrimidine-2-(3H)-one, N4-alkyl cytosine, 2-thiocytosine, and combinations thereof.

[0339] In some embodiments, the probe is labeled with a detectable moiety or label. Detectable moieties include directly detectable moieties, such as fluorescent dyes, and indirectly detectable moieties, such as members of binding pairs. When the detectable moiety is a member of a binding pair, in some embodiments, the probe can be detectable by incubating the probe with a detectable label bound to the second member of the binding pair. In some embodiments, a primer or probe is not labeled, such as when a primer or probe is immobilized,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1e.g., on a microarray or bead. A labeled primer is extendable, e.g., by a polymerase. In some embodiments, a probe is extendable. In other embodiments, a probe is not extendable. The following discussion centers on probes, as these are more typically employed for detecting in the methods described here, but those of skill in the art appreciate that the polynucleotide labeling strategies described below apply equally to the labeling of primers.

[0340] In some embodiments, the probe is a Fluorescence Resonance Energy Transfer (FRET) probe that, in some embodiments, is labeled at the 5 '-end with a fluorescent dye (donor) and at the 3'-end with a quencher (acceptor), a chemical group that absorbs (i.e., suppresses) fluorescence emission from the dye when the groups are in close proximity (e.g., attached to the same probe). Thus, in some embodiments, the emission spectrum of the dye should overlap considerably with the absorption spectrum of the quencher. In other embodiments, the dye and quencher are not at the ends of the FRET probe.

[0341] Illustrative FRET probes, which include, but are not limited to, a TaqMan® probe, a Molecular Beacon probe and a Scorpion probe. A TaqMan® probe is a linear probe that typically has a fluorescent dye covalently bound at one end of the DNA and a quencher molecule covalently bound elsewhere, such as at the other end of the DNA. The FRET probe comprises a sequence that is complementary to a region of the cDNA or amplicon such that, when the FRET probe is hybridized to the cDNA or amplicon, the dye fluorescence is quenched, and when the probe is digested during amplification of the cDNA or amplicon, the dye is released from the probe and produces a fluorescence signal. In some embodiments, the amount of target nucleic in the sample is proportional to the amount of fluorescence measured during amplification.

[0342] Like TaqMan® probes, Molecular Beacons use FRET to detect a PCR product via a probe having a fluorescent dye and a quencher attached at the ends of the probe. Unlike TaqMan® probes. Molecular Beacons remain intact during the PCR cycles. Molecular Beacon probes form a stem-loop structure when free in solution, thereby allowing the dye and quencher to be in close enough proximity to cause fluorescence quenching. When the Molecular Beacon hybridizes to a target nucleic acid, the stem-loop structure is abolished so that the dye and the quencher become separated in space and the dye fluoresces. Molecular Beacons are available, e.g., from Gene Link™ (see www.genelink.com / newsite / products / mbintro.asp).

[0343] In some embodiments, Scorpion probes can be used as sequence-specific primers and for PCR product detection. Like Molecular Beacons, Scorpion probes form a stem-loop structure when not hybridized to a target nucleic acid. However, unlike Molecular Beacons, aCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1Scorpion probe achieves both sequence-specific priming and PCR product detection. A fluorescent dye molecule is attached to the 5'-end of the Scorpion probe, and a quencher is attached elsewhere, such as to the 3'-end. The 3' portion of the probe is complementary to the extension product of the PCR primer, and this complementary portion is linked to the 5'-end of the probe by a non-amplifiable moiety. After the Scorpion primer is extended, the targetspecific sequence of the probe binds to its complement within the extended amplicon, thus opening up the stem-loop structure and allowing the dye on the 5'-end to fluoresce and generate a signal. Scorpion probes are available from, e g., Premier Biosoft International (see www.premierbiosoft.com / tech_notes / Scorpion.html).

[0344] In some embodiments, labels that can be used on the FRET probes include colorimetric and fluorescent dyes, such as Alexa Fluor dyes: BODIPY dyes, such as BODIPY FL, Cascade Blue, and Cascade Yellow: coumarin and its derivatives, such as 7-amino-4-methyl coumarin, aminocoumarin and hydroxy coumarin: cyanine dyes, such as Cy3 and Cy5: eosins and erythrosins: fluorescein and its derivatives, such as fluorescein isothiocyanate: macrocyclic chelates of lanthanide ions, such as Quantum Dye™: Marina Blue: Oregon Green: rhodamine dyes, such as rhodamine red, tetramethylrhodamine and rhodamine 6G: Texas Red: fluorescent energy transfer dyes, such as thiazole orange-ethidium heterodimer; and TOT AB.

[0345] Specific examples of dyes include, but are not limited to, those identified above and the following: Alexa Fluor 350, Alexa Fluor 405, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 500. Alexa Fluor 514, Alexa Fluor 532. Alexa Fluor 546. Alexa Fluor 555, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 610, Alexa Fluor 633, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, and, Alexa Fluor 750; amine-reactive BODIPY dyes, such as BODIPY 493 / 503, BODIPY 530 / 550, BODIPY 558 / 568, BODIPY 564 / 570, BODIPY 576 / 589, BODIPY 581 / 591. BODIPY 630 / 650, BODIPY 650 / 655, BODIPY FL, BODIPY R6G, BODIPY TMR, and, BODIPY-TR: Cy3, Cy5, 6-FAM, Fluorescein Isothiocyanate, HEX, 6-JOE, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, REG, Rhodamine Green, Rhodamine Red, Renographin, ROX, SYPRO, TAMRA, 2', 4', 5 ',7'-Tetrabromosulfonefluorescein, and TET.

[0346] Examples of dye / quencher pairs (i.e., donor / acceptor pairs) include, but are not limited to, fluorescein / tetramethylrhodamine: lAEDANS / fluorescein: EDANS / dabcyl: fluorescein / fluorescein: BODIPY FL / BODIPY FL; and fluorescein / QSY 7 or QSY 9 dyes. When the donor and acceptor are the same, FRET may be detected, in some embodiments, by fluorescence depolarization. Certain specific examples of dye / quencher pairs (i.e.,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1donor / acceptor pairs) include, but are not limited to, Alexa Fluor 350 / Alexa Fluor 488: Alexa Fluor 488 / Alexa Fluor 546: Alexa Fluor 488 / Alexa Fluor 555: Alexa Fluor 488 / Alexa Fluor 568: Alexa Fluor 488 / Alexa Fluor 594: Alexa Fluor 488 / Alexa Fluor 647: Alexa Fluor 546 / Alexa Fluor 568: Alexa Fluor 546 / Alexa Fluor 594: Alexa Fluor 546 / Alexa Fluor 647: Alexa Fluor 555 / Alexa Fluor 594: Alexa Fluor 555 / Alexa Fluor 647: Alexa Fluor 568 / Alexa Fluor 647: Alexa Fluor 594 / Alexa Fluor 647: Alexa Fluor 350 / QSY35: Alexa Fluor 350 / dabcyl: Alexa Fluor 488 / QSY 35: Alexa Fluor 488 / dabcyl: Alexa Fluor 488 / QSY 7 or QSY 9; Alexa Fluor 555 / QSY 7 or QSY9: Alexa Fluor 568 / QSY 7 or QSY 9: Alexa Fluor 568 / QSY 21: Alexa Fluor 594 / QSY 21; and Alexa Fluor 647 / QSY 21. In some instances, the same quencher may be used for multiple dyes, for example, a broad-spectrum quencher, such as an Iowa Black® quencher (Integrated DNA Technologies, Coralville. IA) or a Black Hole Quencher™ (BHQ™: Sigma- Aldrich, St. Louis, MO).

[0347] Specific examples of fluorescently labeled ribonucleotides useful in the preparation of probes for use in some embodiments of the methods described herein are available from Molecular Probes (Invitrogen), and these include. Alexa Fluor 488-5-UTP, Fluorescein- 12-UTP, BODIPY FL-14-UTP. BODIPY TMR-14-UTP, Tetramethylrhodamine-6-UTP, Alexa Fluor 546-14-UTP, Texas Red-5-UTP, and BODIPY TR-14-UTP. Other fluorescent ribonucleotides are available from Amersham Biosciences (GE Healthcare), such as Cy3-UTP and Cy5-UTP.

[0348] Specific examples of fluorescently labeled deoxyribonucleotides useful in the preparation of probes for use in the methods described herein include Dinitrophenyl (DNP)-l '-dUTP, Cascade Blue-7-dUTP, Alexa Fluor 488-5-dUTP, Fluorescein- 12-dUTP, Oregon Green 488-5-dUTP, BODIPY FL-14-dUTP, Rhodamine Green-5-dUTP, Alexa Fluor 532-5-dUTP, BODIPY TMR-14-dUTP, Tetramethylrhodamine-6-dUTP, Alexa Fluor 546-14-dUTP, Alexa Fluor 568-5-dUTP, Texas Red-12-dUTP, Texas Red-5-dUTP, BODIPY TR-14-dUTP, Alexa Fluor 594-5-dUTP, BODIPY 630 / 650-14-dUTP, BODIPY 650 / 665-14-dUTP: Alexa Fluor 488-7-OBEA-dCTP, Alexa Fluor 546-16-OBEA-dCTP, Alexa Fluor 594-7-OBEA-dCTP, and Alexa Fluor 647-12-OBEA-dCTP. Fluorescently labeled nucleotides are commercially available and can be purchased from, e.g., Invitrogen.

[0349] As noted above, exemplary detectable moieties also include members of binding pairs. Exemplary binding pairs include, but are not limited to, biotin and streptavidin, antibodies and antigens, etc.Sample / Target Nucleic AcidCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0350] The target nucleic acid is obtained from a biological sample. The biological sample may be from one or more of a nasopharyngeal swab, a nasal swab, blood, plasma, serum, semen, spinal fluid, tissue biopsy, tear, urine, stool, saliva, smear preparation, bacterial culture, mammalian cell culture, viral culture, human cell, bacteria, extracellular fluid, or in vitro nucleic acid modification reaction mix. Illustrative biological samples include skin samples, lesion swabs, vesicular lesion fluid samples, pustular lesion fluid samples, rectal samples, and samples of bodily fluids, such as nasal aspirates, nasal washes, nasal swabs, nasopharyngeal swabs, saliva, oropharyngeal swabs, throat swabs, bronchoalveolar lavage samples, bronchial aspirates, bronchial washes, endotracheal aspirates, endotracheal washes, tracheal aspirates, nasal secretion samples, mucus samples, sputum samples, plasma samples, whole blood samples, etc.

[0351] The sample to be tested is, in some embodiments, fresh (i.e., never frozen). In other embodiments, the sample is a frozen specimen. In some embodiments, the sample is a tissue sample, such as a formalin-fixed paraffin embedded sample. In some embodiments, the sample is a liquid cytology sample.

[0352] In some embodiments, a sample to be tested is contacted with a buffer after collection. For example, in the case of skin sample, lesion swab, vesicular lesion fluid sample, pustular lesion fluid sample, or rectal samples, a buffer (including, e.g., a preservative) can be added to the sample. In embodiments where the sample is a swab sample, the swab can simply be placed in a buffer. In some embodiments, that sample is contacted with the buffer immediately: in the case of a swab, the swab is immediately placed in the buffer. In some embodiments, the sample (e.g., including the swab) is contacted with buffer within 5 minutes, within 10 minutes, within 30 minutes, within 1 hour, or within 2 hours of sample collection.

[0353] In some embodiments, less than 5 ml, less than 4 ml, less than 3 ml, less than 2 ml, less than 1 ml, or less than 0.75 ml of sample or buffered sample are used in the present methods. In some embodiments, the sample volume is 50, 75, 100, 125, 150, 175, 200, 250, or 300 pL or greater. In some embodiments, 0.01 ml to 1 ml of sample or buffered sample is used in the present methods.

[0354] In some embodiments, one or more additional steps are done to separate, purify, and / or isolate the target nucleic acid from the sample. Methods for separation, purification, and / or isolation techniques useful for the present disclosure and include, but are not limited to: filtration, organic (e.g.. phenol-chloroform method), inorganic (e.g., salting out and proteinase K treatment), adsorption (silica-gel membrane), spin column, and magnetic bead extraction. InCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1some embodiments, the purification step is done within immediately before amplification or as part of a cartridge-based method.

[0355] The target nucleic acid, as noted above, refers to nucleic acids to be detected and is generally used herein to refer to a segment of nucleic acid that is defined by a primer pair and that gives rise to an amplicon produced in an amplification reaction. In some embodiments, an assay can employ multiple target nucleic acids for one or more organisms and single target nucleic acids for one or more different organisms. In some embodiments, the target nucleic acid has a length equal to or less than 90, 88, 87, 86, 85, 83, 82, 81, or 80 nucleotides, or from 60-90, 60-87, 60-86, 60-85, 60-83, 60-80, 65-90, 65-87, 65-86, 65-85, 65-83, 65-80, 70-90, 70-87, 70-86, 70-85. 70-83, 70-80, 75-90, 75-87, 75-86, 75-85, 75-83, 75-80, 65-87, 67-87, or 69-86 nucleotides. In some embodiments, the target nucleic acid comprises a ratio of AT to GC content of greater than 1.

[0356] In some embodiments, the method, system, or cartridge includes at least four sets of primer and probes; alternatively, at least eight sets of primer and probes. In another aspect, the primer and probes are selected from a group consisting of: at least one primer pair and probe for detecting the presence of at least one influenza A gene in the sample selected from an influenza A PA gene, an influenza A PB2 gene, and an influenza A MP gene; at least one primer pair and probe for detecting the presence of at least one influenza B gene in the sample selected from an influenza B NS gene, an influenza B MP gene; at least one primer pair and probe for detecting the presence of an avian influenza gene in the sample selected from an avian influenza MP gene and an avian influenza HA gene; at least one primer pair and probe for detecting the presence of at least one SARS-CoV-2 gene in the sample selected from a SARS-Cov-2-E gene, a SARS-Cov-2-RdRp gene, and a SARS-Cov-2-N2 gene; and at least one primer pair for and probe detecting the presence of at least one respiratory syncytial virus (RSV) A gene in the sample and a respiratory syncytial virus (RSV) B gene.

[0357] The primers and probes used to detect the presence of target nucleic acids may bind to any number of genes in the disease vector. In some embodiments, the disease vector is one of: Influenza A PA, Influenza A MP, Influenza A PB2, Influenza B NS, Influenza B MP, SARS-Cov-2-E, SARS-Cov-2-N2, SARS-Cov-2-RdRp, RSV A, and RSV B.

[0358] In some embodiments, the primer and probe are selected from a group consisting of at least two primer pairs detecting the presence of influenza A PA gene, influenza A PB 2 gene, and influenza A MP gene; at least two primer pairs and probes for detecting the presence of influenza B NS gene and an influenza B MP gene; at least three primer pairs and probes forCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1detecting SARS-Cov-2-E gene, a SARS-Cov-2-RdRp gene, and a SARS-Cov-2-N2 gene; and a primer pair and probe for detecting the presence of at least one respiratory syncytial virus (RSV) A gene in the sample and a respiratory syncytial virus (RSV) B gene.

[0359] Any use of section headings is intended to aid reading of the document and is not to be interpreted as limiting. Further, information that is relevant to a section heading can occur within or outside of that particular section. Furthermore, all publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference should be considered supplementary to that of this document: for irreconcilable inconsistencies, the usage in this document controls.

[0360] In the methods described herein, the steps can be carried out in any order without departing from the principles of the present disclosure, except when a temporal or operational sequence is explicitly recited. Furthermore, specified steps can be carried out concurrently unless explicit claim language recites that they be carried out separately. For example, a claimed step of doing J and a claimed step of doing K can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process.

[0361] Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, and so forth used in the specification and claims are to be understood as being modified in all instances by the term '‘about.” As used herein, in connection with a measured quantity, the term “about” refers to that variation in the measured quantity as would be expected by the skilled artisan making the measurement and exercising a level of care commensurate with the objective of the measurement and the precision of the measuring equipment used. Accordingly, unless otherwise indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, and not as an attempt to limit the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0362] Those skilled in the art will appreciate that many modifications to the embodiments described herein are possible without departing from the spirit and scope of the present disclosure. Thus, the description is not intended and should not be construed to be limited toCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1the examples given but should be granted the full breadth of protection afforded by the appended claims and equivalents thereto. In addition, it is possible to use some of the features of the present disclosure without the corresponding use of other features. Accordingly, the foregoing description of or illustrative embodiments is provided for the purpose of illustrating the principles of the present disclosure and not in limitation thereof and can include modification thereto and permutations thereof. Each embodiment described herein is envisaged to be applicable in each combination with other embodiments described herein.

[0363] Example 1 - FIG. 45 is a diagram of an embodied method of the present disclosure. A biological Sample 1200 containing a target nucleic acid is obtained from a patient and added to a Sample Cartridge 1210. Sample Cartridge 1210 contains a number of spatial regions that allow for chemical processes to be done on the Sample 1200, including isolation and filtration. A Reaction tube 1220 containing a thermostable polymerase, a primer pair configured for amplification of the target nucleic acid, a reverse transcriptase and a fluorescent probe are added to the Sample Cartridge 1210. The combination of the Sample Cartridge 1210 and the Reaction tube 1220 is placed in a Fast PCR Instrument 1230.

[0364] The Fast PCR Instrument 1230 provides the electronic and mechanical control for the Reaction tube 1220. The Fast PCR Instrument 1230 controls the electronic heating of two heaters, Heater 1 1240 and Heater 2 1250, adjacent the Reaction tube 1220 on opposite faces. Heaters 1240 and 1250 may be part of Reaction tube 1220, part of Sample Cartridge 1210, or Fast PCR Instrument 1230. Heaters 1240 and 1250 are maintained at a first and second temperature, respectively, to create two regions with unique temperatures. Heater 1 1240 creates a First Heated Region, 1241, in the Reaction tube 1220 where the temperature is chosen to be from 94-180°C with a variance of 1°C over the amplification process time. Heater 2 1250 creates a Second Heated Region, 1251. in the Reaction tube 1220 where the temperature is chosen to be from 64-68°C with a variance of 1°C over the amplification process time. The heaters described herein can maintain a desired temperature at any ambient temperature.

[0365] The Sample 1200 is filtered in the Sample Cartridge 1210 to isolate the target nucleic acid. The isolated target nucleic acid enters the Reaction tube 1220 and the Amplification Reaction 1260 is initiated by heating the Reaction tube 1220. The temperature difference between the First Heated Region 1241 and Second Heated Region 1251, and, in some cases, the structure of the Reaction tube 1220 are such that the amplification rate is comparable to a regular thermal cycle time of 15 seconds or less. Twenty amplification cyclesCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1are completed in less than 15 minutes and the resulting amplified target nucleic acid is Detected 1270 by fluorescent probe.

[0366] Example 2 - FIG. 46 is a diagram of an embodied method of the present disclosure. A biological Sample 1300 containing a target nucleic acid is obtained from a patient and added to a Sample Cartridge 1310. Sample Cartridge 1310 contains a number of spatial regions that allow for chemical processes to be done on the Sample 1300, including isolation and filtration. A Reaction tube 1320 containing at least 4 U / pL of a thermostable polymerase, a primer pair configured for amplification of the target nucleic acid wherein each primer is at a concentration of at least 500 nM, a reverse transcriptase and a fluorescent probe are added to the Sample Cartridge 1310. The combination of the Sample Cartridge 1310 and the Reaction tube 1320 is placed in a Fast PCR Instrument 1330.

[0367] The Fast PCR Instrument 1330 provides the electronic and mechanical control for the Reaction tube 1320. The Fast PCR Instrument 1330 controls the electronic heating of two heaters, Heater 1 1340 and Heater 2 1350, adjacent the Reaction tube 1320 on opposite faces. Heaters 1340 and 1350 may be part of Reaction tube 1320, part of Sample Cartridge 1310, or Fast PCR Instrument 1330. Heaters 1340 and 1350 are maintained at a first and second temperature, respectively, to create two regions with unique temperatures. Heater 1 1340 creates a First Heated Region, 1341, in the Reaction tube 1320 where the temperature is chosen to be from 94-180°C with a variance of 1°C over the amplification process time. Heater 2 1350 creates a Second Heated Region, 1351. in the Reaction tube 1320 where the temperature is chosen to be from 64-68°C with a variance of 1 °C over the amplification process time.

[0368] The Sample 1300 is filtered in the Sample Cartridge 1310 to isolate the target nucleic acid. The isolated target nucleic acid enters the Reaction tube 1320 and the Amplification Reaction 1360 is initiated by heating the Reaction tube 1320. The temperature difference between the First Heated Region 1341 and Second Heated Region 1351, and, in some cases, the structure of the Reaction tube 1320 are such that the cycle time is 15 seconds or less. Twenty amplification cycles are completed in less than 15 minutes and the resulting amplified target nucleic acid is Detected 1370 by fluorescent probe.

[0369] Example 3 - Oligomers for an influenza B (Flu B) target were screened for the optimal Tm. Table 1 below shows the Tm of oligos tested. Some oligos included base modifications for Tm adjustment. Primers and probes having Tms between 78-80°C worked best, as shown in FIG. 47A. Oligos with Tms outside this narrow range showed reduced performance, as shown in FIG. 47B.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1Table 1: Flu B Oligomer Tm Testing

[0370] Example 4 - The effect of amplicon length and amplicon Tm on time to result (TTM) and effective positive fluorescence (EPF) was tested. Stronger targets generally have either low amplicon Tm (84-86°C), low amplicon length (~80nt) or both, as shown in Table 2, below. Sequence factors, such as folding and non-specific interactions, also contribute to performance. Results show that there is a need to balance primers Tm stabilization while keeping a low amplicon Tm.Table 2: Direct Detection of Target AnalytesCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0371] Example 5 - FIGS. 48A-48D shows the assay is robust across a range of cycle temperatures by comparing relative fluorescent units overtime as the assay is thermally cycled. FIG. 48A shows the RFU signal over time with the assay cycled across temperatures from 64°C to 98°C. FIG. 48B is cycled from 65°C to 98°C, FIG. 48C is cycled from 66°C to 98°C and FIG. 48D is cycled from 68°C to 98°C. As shown in FIGS. 49A-49D, tests done lowering the upper temperature also provide evidence of the robustness of the assay. FIG. 49A shows the RFU signal over time with the assay cycled across temperatures from 64°C to 98°C. FIG. 49B is cycled from 64°C to 97°C, FIG. 49C is cycled from 64°C to 95°C and FIG. 49D is cycled from 64°C to 94°C.

[0372] FIG. 50A and FIG. 50B compare RFU to time as a function of two different cycle temperature ranges. FIG. 50A shows the RFU vs time for an assay cycled between 69°C to 94°C, while FIG. SOB provides a graph of RFU for an assay cycled between 64°C to 98°C. The TTR for a Flu A target (PA) improved by 100 seconds with the wider temperature window shown in FIG. 50B. Narrow temperature ranges are major contributor to strict oligo design requirements. The wider cycle ranges greatly improve the assay. The 64-98°C temperature range is also operational at high ambient temperatures. A second Flu A target (MP1) is enabled with 64-98°C window and gives improved coverage and LoD compared to the narrower temperature window (not shown).

[0373] Example 6 - A rapid, qualitative, multiplex real-time PCR in vitro test using thermal convection cycling PCR technology was developed for de Cart AP+ and does not require PEG. Additionally, fewer on-board reagents requires fewer fluidic steps, hence, contributing to faster sample prep time by ~2 minutes testing Influenza A (Flu A), Influenza B (Flu B), SARS-CoV-2, Respirator}7Syncytial Virus A (RSV A) and Respiratory Syncytial Virus B (RSV B) and a control in individuals of all ages with signs and symptoms of respiratory tract infection (RTI). The sample type and sample collection process is a nasopharyngeal swab (NPS) and / or anterior nasal swab (NS) collected in universal transport medium (UTM) or viral transport medium (VTM). The TTR for the test was < 15 min, no EAT due to multiplexing. The test was run on a GeneXpert® system including the current GeneXpert® cartridge configuration (see FIG. 8) with thermal convection capabilities.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0374] Table 3 provides a summan' of the rapid, qualitative, multiplex real-time PCR in vitro test using thermal convection cycling PCR technology’ on the revised cartridge C (RCC) cartridge, referenced in W02021263101 Al and WO2015013676A1.Table 3: Target Summary for Fast PCR

[0375] FIGS. 51A-51E show performance of the rapid, qualitative, multiplex real-time PCR in vitro test using thermal convection cycling PCR technology on the GeneXpert® RCC. FIG. 51A compares the EPF over time for Flu A, FIG. 51B for Flu B, FIG. 51C for SARS-CoV-2, FIG. 51D for RSV A and FIG. 51E for RSV B. The assay was performed at 1 x LoD (referencing Xpert Xpress CoV-2 / Flu / RSV plus) on a nasophary ngeal swab (NPS) matrix. The assay showed a 100% hit rate (8 / 8) with a TTR of ~16 min on the GeneXpert® RCC with 65 pL reaction tube (also referenced herein as reaction vessel).

[0376] Similarly, FIGS. 52A-52D shows performance of the rapid, qualitative, multiplex real-time PCR in vitro test using thermal convection cycling PCR technology on a prototype GeneXpert® universal cartridge with amine modified glass fiber filter (as referenced in US20240035016A1). FIG. 52A compares the EPF over time for Flu A, FIG. 52B for Flu B, FIG. 52C for SARS-CoV-2. FIG. 52D for RSV A and FIG. 52E for RSV B. The assay was performed at 3 x LoD (referencing Xpert Xpress CoV-2 / Flu / RSV plus) on a nasopharyngeal swab (NPS) matrix. The prototype GeneXpert® universal cartridge with amine modified glass fiber filter does not require PEG. Additionally, fewer on-board reagents facilitate fewer fluidic steps, hence, contributing to faster sample prep time by ~2 minutes. Overall, the prototype GeneXpert® universal cartridge with amine modified glass fiber filter detected all five targets with the significant advantage of a fast sample prep time.

[0377] Example 7 - Solutions were created having 0, 1250, 6250, 12500, or 25000 copies per mL of intact SARS-CoV-2 virus as a target nucleic acid. A nasal matrix was created utilizing a nasal swab in 3 mL of collection buffer (20 mM Tris, pH 9, 0.1% Tween-20, 882 UCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1RNAse inhibitor (CRI)). Target nucleic acid samples and PCR reaction mixtures / reagents were pre-mixed and transferred into SmartCycler tubes (Cepheid) where the embodied fast thermal cycling processes described in Examples 1 and 2 were applied. The sample was heated to 55°C for 60 seconds and introduced into the reaction vessel where it was cycled through a thermal convection cycle having an average cycle time of 15 seconds. The upper cycle temperature was set to 98°C and the lower cycle temperature was set to 62°C. Samples were optically monitored. At least 20 amplification cycles were done for each concentration of target nucleic acid, and four replicates of each test were run.

[0378] FIG. 53 shows the time-to-result (TTR) and endpoint probe fluorescence (EPF) for PCR tests of the N2 and E genes of SARS-CoV-2. Four samples at each virus concentration were tested. A Cepheid Internal Control (CIC) was also measured to verify the effectiveness of on-board sample processing, integrity of extracted nucleic acids, favorable reaction conditions for PCR performance, and absence of excess PCR inhibitors. The CIC is an exogenous (non-sample, non-analyte) nucleic acid pre-loaded in the cartridge that coextracts and co-amplifies along with the sample nucleic acids.

[0379] As shown in FIG. 53, at 6,250 copies of virus per mL, both the SARS-CoV-2 N2 and E PCR tests had 100% detection rates with average EPFs of 264 and 470, respectively. At 12,500 copies of virus per mL, the N2 and E PCR tests again had 100% detection rates with average EPFs of 321 and 909, respectively. Relative to conventional rapid antigen tests, the 6,250 virus / mL detection limit represents a one to two order of magnitude improvement in the detection limit. Additionally, the TTRs for 6,500 virus per mL N2 and E PCR tests were only about two and a half minutes to three minutes (167 and 194 seconds, respectively). Including the 60 second RT phase at 55 °C and the 15 second cycle time, the total runtime to detection was still under 4.5 minutes. Additional data are shown below in Table 4.Table 4: Direct Detection of SARS-CoV-2 VirusCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0380] Example 8 - Solutions were created having 0, 1250, 6250, or 12500 copies per mL of intact SARS-CoV-2 virus as a target nucleic acid. Commercial multiplex test beads for SARS-CoV-2, Flu A, Flu B, RSV A and RSV B were used in direct detection assays of the viral solutions. The SARS-Cov-2-E gene and the SARS-Cov-2-RdRp gene were targeted in single channel tests.

[0381] Nasal swabs of the samples were inserted in 3 mL of collection buffer (20 mM Tris, pH 9, 0.1% Tween-20, 882 U RNAse inhibitor (CRI)). Target nucleic acid samples and PCR reaction mixtures / reagents were pre-mixed and transferred into SmartCycler tubes (Cepheid) where the embodied fast thermal cycling processes described in Examples 1 and 2 were applied. The sample was heated to 55°C for 60 seconds and introduced into the reaction vessel where it was cycled through a thermal convection cycle having an average cycle time of 15 seconds. The Tm was set to 98°C and the Ta was set to 62°C and the samples were optically monitored. At least 20 amplification cycles were done for each concentration of target nucleic acid, and four replicates of each test were run.

[0382] FIG. 54 shows the time-to-result (TTR) and endpoint probe fluorescence (EPF) for PCR tests of the E / RdRp genes of SARS-CoV-2. A Cepheid Internal Control (CIC) was also measured. At 6,250 copies of virus per mL, the E / RdRp test had a 100% detection rate with for the four sample replicates that were run and an average EPF of 618 and a TTR of just 180 seconds. Additional data are shown below in Table 5.Table 5: Direct Detection of SARS-CoV-2 Virus

[0383] Example 9 - FIG. 55 is a graph of the temperature cycle over time for a thermal cycling event in the embodied reaction vessels. The target in this case is a GFP gene with sequences of unmodified F / R PCR primers and an unmodified FAM TaqMan® probe. The average cycle time is 15 seconds or less with a temperature cycle from 64°C to 98°C and excellent stability across greater than 40 cycles. The probe fluorescence shows that detectable signal was seen at approximately 25 cycles with a rapid rise in intensity.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1Terms and Definitions

[0384] Terms used in the claims and specification are defined as set forth below unless otherwise specified.

[0385] The terms “polymerase chain reaction,” or “PCR,” refer to a reaction for the in vitro amplification of specific DNA sequences by the simultaneous primer extension of complementary’ strands of DNA. In other words, PCR is a reaction for making multiple copies or replicates of a target nucleic acid flanked by primer binding sites, such reaction comprising one or more repetitions of the following steps: (i) denaturing the target nucleic acid, (ii) annealing primers to the primer binding sites, and (iii) extending the primers by a nucleic acid polymerase in the presence of nucleoside triphosphates. Usually, the reaction is cycled through different temperatures optimized for each step in a thermal cycler instrument. Particular temperatures, durations at each step, and rates of change between steps depend on many factors well-know n to those of ordinary’ skill in the art (see, e.g., McPherson et al. eds (1995) PCR: A Practical Approach, 2nd Ed., IRL Press, Oxford; and the like). For example, in a conventional PCR using Taq DNA polymerase, a double stranded target nucleic acid may be denatured at a temperature greater than about 90°C, primers annealed at a temperature in the range of about 50°C to about 75°C, and primers extended at a temperature in the range of about 72°C to about 78°C. The term “PCR” encompasses derivative forms of the reaction, including but not limited to, RT-PCR, real-time PCR, nested PCR, quantitative PCR. multiplexed PCR, and the like. In various embodiments PCR reaction volumes can range from a few hundred nanoliters, e.g. 200 nL, to a few hundred pL, e.g. 200 pL.

[0386] The term “real-time PCR” refers to a PCR for which the amount of reaction product, i.e. amplicon, is monitored as the reaction proceeds. There are many forms of realtime PCR that differ mainly in the detection chemistries used for monitoring the reaction product (see, e.g., Gelfand et al. U.S. Pat. No. 5,210,015 (“TAQMAN™”); Wittwer et al. U.S. Pat. Nos. 6,174,670 and 6,569,627 (intercalating dyes); Tyagi et al. U.S. Pat. No. 5,925,517 (molecular beacons); and the like). Detection chemistries for real-time PCR are reviewed, inter aha in Mackay et al. (2002) Nucl. Acids Res. 30: 1292-1305.

[0387] The terms “quantitative PCR” or “qPCR” refer to a PCR designed to measure the abundance of one or more specific target sequences in a sample or specimen. Quantitative PCR includes both absolute quantitation and relative quantitation of such target sequences. Typically , quantitative measurements are made using one or more reference sequences that may be assayed separately or together with a target sequence. The reference sequence can beCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1endogenous or exogenous to a sample or specimen, and in the latter case, may comprise one or more competitor templates. Typical endogenous reference sequences include but are not limited to segments of transcripts of the following genes: [3-actin, GAPDH, 2-microglobulin, ribosomal RNA, and the like. Techniques for quantitative PCR are well-known to those of ordinary7skill in the art (see, e.g., Freeman et al. (1999) Biotechniques, 26: 112-126; Becker-Andre et al. (1989) Nucl. Acids Res. 17: 9437-9447; Zimmerman et al. (1996) Biotechniques, 21: 268-279; Diviacco et al. (1992) Gene, 122: 3013-3020; and the like).

[0388] The term '‘nucleic acid” includes any form of DNA or RNA, including, for example, genomic DNA; complementary7DNA (cDNA), which is a DNA representation of mRNA, usually obtained by reverse transcription of messenger RNA (mRNA) or viral RNA or by amplification; DNA molecules produced synthetically or by amplification; mRNA; and noncoding RNA. Nucleic acid encompasses double- or triple-stranded nucleic acid complexes, as well as single-stranded molecules. In double- or triple-stranded nucleic acid complexes, the nucleic acid strands need not be coextensive (i.e, a double-stranded nucleic acid need not be double-stranded along the entire length of both strands).

[0389] The term nucleic acid also encompasses any modifications thereof, such as by methylation and / or by capping. Nucleic acid modifications can include addition of chemical groups that incorporate additional charge, polarizability7, hydrogen bonding, electrostatic interaction, and functionality to the individual nucleic acid bases or to the nucleic acid as a whole. Such modifications may include base modifications such as 2’ - position sugar modifications, 5-position pyrimidine modifications, 8-position purine modifications, modifications at cytosine exocyclic amines, substitutions of 5-bromo-uracil, sugar-phosphate backbone modifications, unusual base pairing combinations such as the isobases isocytidine and isoguanidine, and the like.

[0390] More particularly, in some embodiments, nucleic acids, can include poly deoxyribonucleotides (containing 2-deoxy-D-ribose), polyribonucleotides (containing D-ribose), and any other type of nucleic acid that is an N- or C-glycoside of a purine or pyrimidine base, as well as other polymers containing nonnucleotidic backbones, for example, polyamide (e.g., peptide nucleic acids (PNAs)) and polymorpholino polymers (see, e.g., Summerton and Weller (1997) “Morpholino Antisense Oligomers: Design, Preparation, and Properties,” Antisense & Nucleic Acid Drug Dev. 7:1817-195; Okamoto et al. (2020) “Development of electrochemically gene-analyzing method using DNA- modified electrodes,” Nucleic Acids Res. Supplement No. 2: 171-172), and other synthetic sequence-specific nucleic acid polymersCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1providing that the polymers contain nucleobases in a configuration which allows for base pairing and base stacking, such as is found in DNA and RNA. The term nucleic acid also encompasses locked nucleic acids (LNAs), which are described in U.S. Patent Nos. 6,794,499, 6,670,461, 6,262,490, and 6,770,748.

[0391] The nucleic acid(s) can be derived from a completely chemical synthesis process, such as a solid phase-mediated chemical synthesis, from a biological source, such as through isolation from any species that produces nucleic acid, or from processes that involve the manipulation of nucleic acids by molecular biology tools, such as DNA replication, PCR amplification, reverse transcription, or from a combination of those processes.

[0392] The term “oligonucleotide” is used to refer to a nucleic acid that is relatively short, generally shorter than 200 nucleotides, more particularly, shorter than 100 nucleotides, most particularly, shorter than 50 nucleotides. Typically, oligonucleotides are single-stranded DNA molecules.

[0393] As used herein, the term “gene” encompasses coding sequences, introns, and any- associated control sequences that participate in the expression of the coding sequences.

[0394] The term “sequence identity,” in the context of two or more amino acid or nucleotide sequences, refers to two or more sequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection.

[0395] For sequence comparison to determine percent nucleotide or amino acid sequence identity-, typically one sequence acts as a “reference sequence,” to which a “test” sequence is compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence relative to the reference sequence, based on the designated program parameters. Alignment of sequences for comparison can be conducted using BLAST set to default parameters.

[0396] As used herein, the term “complementary” refers to the capacity for precise pairing between two nucleotides; i.e., if a nucleotide at a given position of a nucleic acid is capable of hydrogen bonding with a nucleotide of another nucleic acid to form a canonical base pair, then the two nucleic acids are considered to be complementary to one another at that position. Complementarity- between two single-stranded nucleic acid molecules may- be "partial,” inCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1which only some of the nucleotides bind, or it may be complete when total complementarity exists between the single-stranded molecules. The degree of complementarity between nucleic acid strands has significant effects on the efficiency and strength of hybridization between nucleic acid strands.

[0397] The term “analy te” refers to any moiety7that is to be detected and / or quantified. Analytes include, but are not limited to particular biomolecules (proteins, antibodies, nucleic acids (e.g., DNA and / or RNA), carbohydrates, lectins, etc.), bacteria or components thereof, bacterial toxins or components thereof, viruses or components thereof (e.g., coat proteins), fungi or components thereof, fungal toxins or components thereof, protozoa or components thereof, protozoal toxins or components thereof, drugs, other toxins, food pathogens, and the like.

[0398] “Selective hybridization” or “selective annealing” refers to the binding of a nucleic acid to a target nucleic acid in the absence of substantial binding to other nucleic acids present in the hybridization mixture under defined stringency conditions. Those of skill in the art recognize that relaxing the stringency of the hybridization conditions allows sequence mismatches to be tolerated.

[0399] As used herein, the Tm is the temperature at which a population of double-stranded nucleic acid molecules becomes half-dissociated into single strands. Methods for calculating the Tm of nucleic acids are well known in the art (see, e.g., Berger and Kimmel (1987) METHODS IN ENZYMOLOGY. VOL. 152: GUIDE TO MOLECULAR CLONING TECHNIQUES, San Diego: Academic Press, Inc. and Sambrook et al. (1989) MOLECULAR CLONING: A LABORATORY MANUAL, 2ND ED., VOLS. 1-3, Cold Spring Harbor Laboratory)). As indicated by standard references, a simple estimate of the Tm value may be calculated by the equation: Tm=81.5+0.41(% G+C), when anucleic acid is in aqueous solution at 1 M NaCl (see, e.g., Anderson and Young, Quantitative Filter Hybridization in NUCLEIC ACID HYBRIDIZATION (1985)).

[0400] The term “primer” refers to an oligonucleotide that is capable of hybridizing (also termed “annealing”) with a nucleic acid and serving as an initiation site for nucleotide (RNA or DNA) polymerization under appropriate conditions (i.e., in the presence of four different nucleoside triphosphates and an agent for polymerization, such as DNA or RNA polymerase or reverse transcriptase) in an appropriate buffer and at a suitable temperature. The appropriate length of a primer depends on the intended use of the primer, but primers are ty pically at least 7 nucleotides long and, in some embodiments, range from 10 to 30 nucleotides, or, in someCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1embodiments, from 10 to 60 nucleotides, in length. In some embodiments, primers can be, e.g., 15 to 50 nucleotides long. Short primer molecules generally require cooler temperatures to form sufficiently stable hybrid complexes with the template. A primer need not reflect the exact sequence of the template but must be sufficiently complementary to hybridize with a template.

[0401] A primer is said to “anneal to’' or “hybridize to” another nucleic acid if the primer, or a portion thereof, hybridizes to a nucleotide sequence within the nucleic acid. The statement that a primer hybridizes to a particular nucleotide sequence is not intended to imply that the primer hybridizes either completely or exclusively to that nucleotide sequence. For example, in some embodiments, amplification primers used herein are said to “anneal to” or be “specific for” a nucleotide sequence.” This description encompasses primers that anneal wholly to the nucleotide sequence, as well as primers that anneal partially to the nucleotide sequence.

[0402] The term “primer pair” refers to a set of primers including a 5’ “upstream primer” or “forward primer” that hybridizes with the complement of the 5’ end of the DNA sequence to be amplified and a 3’ “downstream primer” or “reverse primer” that hybridizes with the 3’ end of the sequence to be amplified. As will be recognized by those of skill in the art, the terms “upstream” and “downstream” or "forward” and “reverse” are not intended to be limiting but rather provide illustrative orientations in some embodiments.

[0403] A “probe” is a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, generally through complementary base pairing, usually through hydrogen bond formation, thus forming a duplex structure. The probe can be labeled with a detectable moiety to permit facile detection of the probe, particularly once the probe has hybridized to its complementary target. Alternatively, how ever, the probe may be unlabeled but may be detectable by specific binding with a ligand that is labeled, either directly or indirectly. Probes can vary significantly in size.

[0404] As used herein with reference to a portion of a primer or a nucleotide sequence within the primer, the term “specific for” a nucleic acid, refers to a primer or nucleotide sequence that can specifically anneal to the target nucleic acid under suitable annealing conditions.

[0405] The term “target nucleic acid” refers to nucleic acids to be detected and is generally used herein to refer to a segment of nucleic acid that is defined by a primer pair and that gives rise to an amplicon produced in an amplification reaction; the term “amplification target” is also used herein to refer to this type of target nucleic acid. Primers and probes are also said to “target” nucleic acid sequences, and so these sequences can also be understood as “targetCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1nucleic acids.” Additionally, primers and probes are said to “target” or “be specific for” genes. In this usage, the primers and probes can be used to detect the presence of a particular gene by specifically hybridizing to a portion of the gene that indicates its presence. The meaning of “target” and “target nucleic acids” will be clear to one of skill in the art from the context in which the term is employed.

[0406] In some embodiments, the target nucleic acid has a length equal to or less than 90, 88. 87, 86, 85, 83, 82, 81, or 80 nucleotides, or from 60-90, 60-87, 60-86. 60-85, 60-83, 60-80.65-90, 65-87, 65-86, 65-85, 65-83, 65-80, 70-90, 70-87, 70-86, 70-85, 70-83, 70-80, 75-90, 75-87, 75-86, 75-85, 75-83, 75-80, 65-87, 67-87, or 69-86 nucleotides. In some embodiments, the target nucleic acid comprises a ratio of AT to GC content of greater than 1.

[0407] The term “polymerase” refers to an enzyme that catalyze the synthesis of DNA or RNA polymers via the successive addition of nucleotides to a growing nascent nucleic acid strand (primer) by using the complementary template strand. “Thermostable polymerase” refers to polymerases that originate from a thermophile and are therefore thermostable, allowing for amplification via thermocycling.

[0408] The term “reverse transcriptase” refers to an RNA-dependent DNA polymerase enzyme that converts an RNA genome into DNA by creating a complementary strand of DNA based on the RNA sequence. Reverse transcriptase allows RNA templates to be amplified in the same manner as DNA. In some embodiments, the reverse transcriptase is present at concentrations of 6 U / pL or greater. 7 U / pL or greater, or 8 U / pL or greater, of reaction volume.

[0409] As used herein, the term “thermostable polymerase” or “thermophilic polymerase” refers to an enzyme that is relatively stable to heat when compared, for example, to nucleotide polymerases from E. coli, and which catalyzes the template-dependent polymerization of nucleoside triphosphates. A “thermostable polymerase,” will, e.g., retain enzymatic activity for polymerization and exonuclease activities when subjected to the repeated heating and cooling cycles used in PCR. Preferably, a “thermostable nucleic acid polymerase” has optimal activity at a temperature above 45°C, or at a temperature ranging from 40°C to 80°C and more preferably from 55°C to 75°C. A representative thermostable polymerase enzyme isolated from Thermus aquaticus (Taq) is described in U.S. Pat. No. 4,889,818 and a method for using it in conventional PCR is described in 239 Science 487 (1988). Other thermostable DNA polymerases include, but are not limited to, DNA polymerases from thennophilic Eubacteria or Archaebacteria, for example. T. thermophilus. T. bockianus, T. flavus, T. rubber,CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1Thermococcus litoralis, Pyroccocus furiousus, P. wosei, Pyrococcus spec. KGD, Thermatoga maritime, Thermoplasma acidophilus, and Sulfolobus spec. In some embodiments, the thermostable polymerase is present at concentrations of 6 U / pL or greater, 7 U / pL or greater, or 8 U / pL or greater, of reaction volume. In some embodiments, the thermostable polymerase is inactive during reverse transcription and / or the activity7of the thermostable polymerase is inhibited at temperatures 55°C and below.

[0410] Amplification according to the present teachings encompasses any means by which at least a part of at least one target nucleic acid is reproduced, typically in a template dependent manner, including without limitation, a broad range of techniques for amplifying nucleic acid sequences, either linearly or exponentially. Illustrative means for performing an amplifying step include PCR, nucleic acid strand-based amplification (NASBA), two- step multiplexed amplifications, rolling circle amplification (RCA), and the like, including multiplex versions and combinations thereof, for example but not limited to, OLA / PCR, PCR / OLA, LDR / PCR, PCR / PCR / LDR, PCR / LDR, LCR / PCR, PCR / LCR (also know n as combined chain reaction — CCR), helicase-dependent amplification (HD A), and the like. Descriptions of such techniques can be found in, among other sources, U.S. Pat. Nos. 5,830,711, 6.027,889, 5,686,243, 6,027,998, and 6,605,451, PCT Publ. Nos. WO97 / 31256, WOOl / 92579; WO0056927A3, and WO9803673A1; Ausubel et al., PCR Primer: A Laboratory7Manual, Diffenbach, Ed., Cold Spring Harbor Press (1995); The Electronic Protocol Book, Chang Bioscience (2002); 34 J. Clin. Micro. 501-07 (1996); The Nucleic Acid Protocols Handbook. R. Rapley, ed.. Humana Press, Totowa, N.J. (2002); 4 Curr. Opin. Biotechnol. 41-7 (1993), 29 Genomics 152-162 (1995); 252 Science 1643-50 (1991); Innis et al., PCR Protocols: A Guide to Methods and Applications, Academic Press (1990); 18 Nature Biotechnology7561-64 (2000); and 28 Infection 97-102 (2000); Belgrader, Barany, and LCR Kit Instruction Manual. Cat. #200520, Rev. #050002, Stratagene, 2002; 88 Proc. Natl. Acad. Sci. USA 188-93 (1991); 25 Nucl. Acids Res. 2924-2951 (1997); 27 Nucl. Acid Res. e40i-viii (1999); 99 Proc. Natl Acad. Sci. USA 5261-66 (2002); 109 Gene 1-11 (1991); 20 Nucl. Acid Res. 1691-96 (1992); 2 BMC Inf. Dis.18 (2002); 13 Genome Res. 294-307 (2003); 241 Science 1077-80 (1988); 2 Expert Rev Mol Diagn. 542-8 (2002); 53 J. Microbiol. Methods 165074 (2003); 12 Curr. Opin. Biotechnol. 21-7 (2001).

[0411] A “nucleic acid template” or “template,” as used herein is a single-stranded DNA nucleic acid that contains the target sequence for copying via amplification. A template forCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1replication can be from any DNA source, such as genomic DNA (gDNA), complementary DNA (cDNA), or plasmid DNA.

[0412] In some embodiments, amplification comprises at least one cycle, an “amplification cycle,” comprising the thermocycling procedure of: 1) denaturing dual-strand DNA into single-stranded DNA at elevated temperature which melts the hydrogen bonds between complementary bases to separate the strands; 2) annealing at a lower temperature of at least one primer with complementary or substantially complementary sequences in at least one target nucleic acid; and 3) extending or synthesizing at least one strand of nucleotides in a template-dependent manner using a polymerase. The cycle may or may not be repeated. If repeated, the amplification cycle is described as “X amplification cycles,” wherein X is a whole number defining said number of cycles.

[0413] As used herein, “in solution” means not immobilized on a substrate of any kind, for example, a bead or a surface in a cassette, such as a chamber wall.

[0414] A “multiplex amplification reaction” is one in which two or more nucleic acids distinguishable by sequence are amplified simultaneously.

[0415] A “reagent” refers broadly to any agent used in a reaction, other than the analyte (e g., nucleic acid being analyzed). Illustrative reagents for a nucleic acid amplification reaction include, but are not limited to, buffer, metal ions, polymerase, reverse transcriptase, primers, template nucleic acid, nucleotides, labels, dyes, nucleases, dNTPs, and the like. Reagents for enzyme reactions include, for example, substrates, cofactors, buffer, metal ions, inhibitors, and activators.

[0416] The term “label,” as used herein, refers to any atom or molecule that can be used to provide a detectable and / or quantifiable signal. In particular, the label can be attached, directly or indirectly, to a nucleic acid or protein. Suitable labels that can be attached to probes include, but are not limited to, radioisotopes, fluorophores, chromophores, mass labels, electron dense particles, magnetic particles, spin labels, molecules that emit chemiluminescence, electrochemically active molecules, enzy mes, cofactors, and enzy me substrates.

[0417] The term “dye,” as used herein, generally refers to any organic or inorganic molecule that absorbs electromagnetic radiation and produces a detectable signal (e.g., a fluorescent signal).

[0418] The term “quencher,” as used herein generally refers to any organic or inorganic molecule that reduces the level of a detectable signal.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0419] As used herein, the term “detecting’" refers to “determining the presence of an item. The terms “detect”, “detecting” or “detection” may describe either the general act of discovering or discerning or the specific observation of a detectably labeled composition. As used herein, the term “detectably different” or “spectrally distinguishable” refers to a set of labels (such as dyes / fluorophores) that can be detected and distinguished simultaneously.

[0420] As used herein, the terms “patient” and “subject” are typically used interchangeably to refer to a human. In some embodiments, the methods described herein may be used on samples from non-human animals, e g., a non -human primate, canine, equine, feline, porcine, bovine, lagomorph, and the like. Additionally, the term patient may be used for non-human animals in the veterinary context.

[0421] As used herein, “Clinical Laboratory Improvement Amendments (CLIA)” refers to The Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations in effect as of the original filing date of the present application. The CLIA regulations include federal standards applicable to all U.S. facilities or sites that test human specimens for health assessment or to diagnose, prevent, or treat disease. A “CLIA-compliant” test is one that complies with these regulations. “CLIA-waived” tests include tests that does not comply with all of these regulations. For example, CLIA-waived tests include test systems cleared by the U.S. Food and Drug Administration for home use and those tests approved for waiver under the CLIA criteria.

[0422] Aspects of the present disclosure are described in the following clauses, which are consistent with but may also add to the present disclosure. The features or combinations of features disclosed in the following clauses may also be included in or combined with any of the other embodiments disclosed elsewhere herein. Additionally , the clauses may be combined with any other clauses to form another combination according to the present disclosure.

[0423] Clause 1 is a biological sample processing apparatus comprising: a chassis having an interior and an exterior; a rack secured within the interior of the chassis, the rack including a plurality7of bays; and a plurality7of sample processing modules configured to receive and perform analysis on a sample cartridge assembly, wherein each of the plurality of sample processing modules is independently operable and securable within the rack, wherein the plurality of sample processing modules is selected from two or more module types including: a first module type configured to perform nucleic acid amplification; a second module t pe configured to perform non-thermal cycling detection of an analyte; and a third module typeCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1configured to perform lab on a chip analysis, wherein each bay is configured to receive each type of sample processing module.

[0424] Clause 2 is the biological sample processing apparatus of clause 1 , wherein the first or second module types are configured to detect the presence of an analyte within 15 minutes of initiation of sample processing.

[0425] Clause 3 is the biological sample processing apparatus of any one of clauses 1-2, wherein the first module type or the second module type is configured to perform PCR analysis via thermal convection.

[0426] Clause 4 is the biological sample processing apparatus of any one of clauses 1-3, wherein the first module type is configured to receive a sample cartridge assembly having a reaction tube and conduct polymerase chain reaction (PCR) or isothermal analysis.

[0427] Clause 5 is the biological sample processing apparatus of any one of clauses 1-4, wherein the second module type comprises a thermal convection unit and is configured to receive a sample cartridge assembly having a reaction tube.

[0428] Clause 6 is the biological sample processing apparatus of any one of clauses 1-5, wherein the third module type is configured to receive a sample cartridge assembly having a chip carrier device assembly configured to secure an analysis chip.

[0429] Clause 7 is the biological sample processing apparatus of any one of clauses 1-6, wherein the rack includes a plurality of module receiving zones configured to interchangeably secure any of the module types.

[0430] Clause 8 is the biological sample processing apparatus of any one of clauses 1-7, wherein the plurality of sample processing modules comprises at least three module types.

[0431] Clause 9 is the biological sample processing apparatus of any one of clauses 1-8, further comprising a fourth module type configured to perform nucleic acid sequencing on a sample.

[0432] Clause 10 is the biological sample processing apparatus of any one of clauses 1-9, wherein each of the module types are further configured to prepare a nucleic acid library for sequencing a sample introduced to the module via a sample cartridge.

[0433] Clause 11 is the biological sample processing apparatus of any one of clauses 1-10, wherein the plurality of sample processing modules include at least three modules being a subset of the two or more module types.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0434] Clause 12 is the biological sample processing apparatus of any one of clauses 1- 11, wherein each of the plurality of sample processing modules is configured to operate concurrently to one another.

[0435] Clause 13 is the biological sample processing apparatus of any one of clauses 1- 12, wherein the second or third module types is configured to perform isothermal nucleic acid amplification, immunoassay, electrochemical detection assay, immunofluorescence assay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, antigen assay, turbidity, or combinations thereof.

[0436] Clause 14 is the biological sample processing apparatus of any one of clauses 1- 13, wherein the first or second module type is configured to receive a sample cartridge assembly having a reaction tube secured therein, the reaction tube having a first side and a second side, wherein the second module type comprises a plurality of independently controlled heaters, the plurality of independently controlled heaters comprising: a first heater configured to maintain the first side of the reaction tube at a first temperature, and a second heater configured to maintain the second side of the reaction tube at a second temperature.

[0437] Clause 15 is the biological sample processing apparatus of clause 14, wherein the first or second module type further comprises an optical unit for detecting a target analyte in a fluid sample introduced to the reaction tube.

[0438] Clause 16 is the biological sample processing apparatus of claim 15, wherein the optical unit comprises at least two light sources for transmitting one or more optical excitation beams to the reaction tube.

[0439] Clause 17 is the biological sample processing apparatus of clause 15, wherein the optical unit comprises at least five light sources for transmitting one or more excitation beams to the reaction tube.

[0440] Clause 18 is the biological sample processing apparatus of clause 16 or 17, wherein each light source is independently controlled.

[0441] Clause 19 is the biological sample processing apparatus of any of clauses 15-18, wherein the optical unit comprises at least two detectors configured to detect emission light from a processed sample in a plurality of wavelengths.

[0442] Clause 20 is the biological sample processing apparatus of any of clauses 15-19, wherein the optical unit is configured to simultaneously and differentially detect at least four emission wavelength ranges from the processed sample.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0443] Clause 21 is the biological sample processing apparatus of any of clauses 15-20, wherein the optical unit is configured to simultaneously and differentially detect at least six emission wavelength ranges from the processed sample.

[0444] Clause 22 is the biological sample processing apparatus of any of clauses 15-21, wherein the optical unit is configured to simultaneously and differentially detect at least ten emission wavelength ranges from the processed sample.

[0445] Clause 23 is the biological sample processing apparatus of any clauses 14-22, wherein the plurality of independently controlled heaters are configured to enable melt analysis, amplification via one or more of thermal convection, thermal cycling, or isothermal amplification.

[0446] Clause 24 is the biological sample processing apparatus of any of clauses 14-23, wherein the 3D shape of the reaction tube is cylindrical, cube, spherical, rectangular, pyramidal, conical, or diamond.

[0447] Clause 25 is the biological sample processing apparatus of any of clauses 14-24, wherein the first temperature enables denaturing a target nucleic acid sequence into a singlestranded nucleic acid template.[044S] Clause 26 is the biological sample processing apparatus of any of clauses 14-25, wherein the second temperature enables annealing a primer pair to the single-stranded nucleic acid template.

[0449] Clause 27 is the biological sample processing apparatus of any of clauses 14-26, wherein the first temperature is about 90°C or greater, about 95°C or greater, about 97°C or greater, or about 98°C or greater.

[0450] Clause 28 is the biological sample processing apparatus of any of clauses 14-27, wherein the second temperature is about 70°C or less, about 68°C or less, about 67°C or less, about 65°C or less, or about 64°C or less.

[0451] Clause 29 is the biological sample processing apparatus of any of clauses 14-28, wherein the second temperature is from about 60°C to about 70°C, from about 64°C to about 68°C, or from about 65°C to about 67°C.

[0452] Clause 30 is the biological sample processing apparatus of any of clauses 14-29, wherein the difference between the first temperature and the second temperature is equal to or greater than about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, about 30°C, about 31°C, about 32°C, about 33°C, about 34°C, about 35°C, about 36°C, or about 37°C, from aboutCEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU125 to about 37°C, from about 25 to about 35°C, from about 27 to about 35°C, or from about 28 to about 34°C.

[0453] Clause 31 is the biological sample processing apparatus of any of clauses 14-30, wherein the first temperature is from about 97°C to about 99°C and the second temperature is from about 65°C to about 67°C.

[0454] Clause 32 is the biological sample processing apparatus of any of clauses 1-13, wherein the first module type further comprises: a loading bay configured to receive a reaction tube coupled to the sample cartridge assembly, the sample cartridge containing a sample; a plurality of heaters configured for thermal cycling the sample when introduced to the reaction tube, and an optical unit for detecting a target analyte in a processed sample, the sample having undergone processing.

[0455] Clause 33 is the biological sample processing apparatus of clause 32, wherein the plurality of heaters are independently controlled.

[0456] Clause 34 is the biological sample processing apparatus of clause 32 or 33, wherein the optical unit comprises at least two light sources for transmitting excitation beams to the reaction tube.

[0457] Clause 35 is the biological sample processing apparatus of any one of clauses 32-34, wherein the optical unit comprises at least five light sources for transmitting excitation beams to the reaction tube.

[0458] Clause 36 is the biological sample processing apparatus of clause 34 or 35, wherein the light sources are independently controlled.

[0459] Clause 37 is the biological sample processing apparatus of any of clauses 32-36, wherein the optical unit comprises at least two detectors configured to detect emission light from the fluid sample in a plurality of wavelengths.

[0460] Clause 38 is the biological sample processing apparatus of any of clauses 32-37, wherein the optical unit is configured to simultaneously and differentially detect at least four emission wavelength ranges from the processed sample.

[0461] Clause 39 is the biological sample processing apparatus of any of clauses 32-38, wherein the optical unit is configured to simultaneously and differentially detect at least six emission wavelength ranges from the processed sample.

[0462] Clause 40 is the biological sample processing apparatus of any of clauses 32-39, wherein the optical unit is configured to simultaneously and differentially detect at least ten emission wavelength ranges from the processed sample.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0463] Clause 41 is the biological sample processing apparatus of any one of clauses 32- 40, wherein the plurality of heaters are further configured to enable amplification via thermal convection, isothermal amplification, or nested PCR, melt analysis, or a combination thereof.

[0464] Clause 42 is the biological sample processing apparatus of any one of clauses 1- 41, wherein the third module ty pe comprises one or more of: a control unit configured to manage one or more steps of a sample processing protocol; and at least one pogo pin configured to interface with one or more I / O pad disposed on the analysis chip or chip carrier device.

[0465] Clause 43 is the biological sample processing apparatus of clause 42, wherein the analysis chip is configured to analyze and detect analytes present in a processed sample.

[0466] Clause 44 is the biological sample processing apparatus of clause 42 or 43, wherein the analysis chip further comprises a biosensor array, a memory, and a processing device.

[0467] Clause 45 is the biological sample processing apparatus of any of clauses 42-44, wherein the biosensor array further comprises a temperature sensor configured to measure the temperature across the biosensor array at a given timepoint.

[0468] Clause 46 is the biological sample processing apparatus of any of clauses 42-45, wherein the analysis chip is configured to perform a thermal cycling process.

[0469] Clause 47 is the biological sample processing apparatus of any of clauses 42-46, wherein the thermal cy cling process includes heating the active surface to an upper temperature or cooling the active face to a lower temperature.

[0470] Clause 48 is the biological sample processing apparatus of any of clauses 42-46, wherein the thermal cycling process includes heating the active surface to an upper temperature and cooling the active face to a lower temperature.

[0471] Clause 49 is the biological sample processing apparatus of clause 47 or 48, wherein the upper temperature is about 90°C or higher.

[0472] Clause 50 is the biological sample processing apparatus of any of clauses 47-49, wherein the lower temperature is between about 40°C to about 75°C.

[0473] Clause 51 is the biological sample processing apparatus of any of clauses 1-50, wherein each module type comprises a subset of light sources selected from a set of light sources, wherein each subset of light sources is configured to excite one or more dyes associated with one or more assays capable of being performed by the respective module type.

[0474] Clause 52 is the biological sample processing apparatus of clause 51 , wherein the third module ty pe comprises a blue light source and a UV light source.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0475] Clause 53 is the biological sample processing apparatus of clause 51, wherein the first or second module type comprises at least four light sources collectively configured to excite dyes and FRET pairs to cause the emission of at least ten wavelengths.

[0476] Clause 54 is the biological sample processing apparatus of any of clauses 1-53, wherein each of the sample processing modules comprises a sonication hom assembly configured to guide placement of the sample cartridge assembly within the sample processing module.

[0477] Clause 55 is the biological sample processing apparatus of any of clauses 1-54, wherein the rack comprises a top portion and a bottom portion.

[0478] Clause 56 is the biological sample processing apparatus of any of clauses 1-55, wherein a volumetric footprint of the apparatus remains constant whether the rack is full or less than full.

[0479] Clause 57 is the biological sample processing apparatus of any of clauses 1-56, wherein the first module type and second module type are configured to receive a sample cartridge assembly of a first type.

[0480] Clause 58 is the biological sample processing apparatus of clause 57, wherein the third module type is configured to receive a sample cartridge assembly of a second type.

[0481] Clause 59 is the biological sample processing apparatus of clause 57 or 58, wherein the cartridge assembly of the first type comprises a reaction tube and the sample cartridge assembly of the second type comprises a chip earner device assembly.

[0482] Clause 60 is a system comprising: a biological sample processing apparatus including a chassis having an interior and an exterior, a rack secured within the interior of the chassis, the rack including a plurality of bays, and a barcode reader configured to read a first barcode directed to a first assay type, the first barcode being on or associated with a first sample cartridge assembly; a plurality of sample processing modules configured to receive and perform analysis on a sample cartridge assembly, wherein each sample processing module is independently operable and securable within the rack; and at least one processor configured to execute a set of instructions, wherein the at least one processor is configured to: receive a first signal from the barcode reader based on the first barcode, in response to the first signal, determine the first ty pe of assay, and transmit instructions to run the first assay type to a first sample processing modules of the plurality of sample processing modules, wherein each bay is configured to receive each type of sample processing module.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0483] Clause 61 is the system of clause 60, wherein the barcode reader is further configured to: read a second barcode directed to a second assay type, the second barcode being on or associated with a second sample cartridge assembly, wherein the at least one processor being further configured to: receive a second signal from the barcode reader based on the second barcode, in response to the second signal, determine the second type of assay, and transmit instructions to run the second assay type to a second sample processing modules of the plurality of sample processing modules.

[0484] Clause 62 is the system of clause 61, wherein the first and second assay types are different.

[0485] Clause 63 is the system of clause 61, wherein the first and second assay types are the same.

[0486] Clause 64 is the system of any of clauses 60-63, wherein the first and second sample processing modules are the same type of module.

[0487] Clause 65 is the system of any of clauses 60-63, wherein the first and second sample processing modules are different types of modules.

[0488] Clause 66 is the system of any of clauses 60-65, wherein the first and second sample processing modules are selected from two or more module types including: a first module ty pe configured to perform nucleic acid amplification; second module type configured to perform non-thermal cycling detection of an analyte; and a third module type configured to perform lab on a chip analysis.

[0489] Clause 67 is the system of any one of clauses 60-66, wherein the first and second sample processing modules are configured to operate concurrently.

[0490] Clause 68 is the system of any one of clauses 60-67, wherein the barcode reader is integrated with the chassis.

[0491] Clause 69 is the system of any one of clauses 60-68, wherein the first and second assay types are at least two of low-plex, mid-plex, and high-pl ex.

[0492] Clause 70 is the system of any one of clauses 60-69, wherein the first assay type is associated with a first set of instructions executable by the biological sample processing apparatus, one or more of the plurality of sample processing modules, or both.

[0493] Clause 71 is the system of clause 70, wherein the second assay type is associated with a second set of instructions executable by the biological sample processing apparatus, one or more of the plurality of sample processing modules, or both.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0494] Clause 72 is the system of clause 71, wherein the first and second unique identifiers are distinct from each other.

[0495] Clause 73 is the system of clause 60, wherein the first assay type comprises polymerase chain reaction, isothermal nucleic acid amplification, nucleic acid hybridization, metagenomic sequencing, immunofluorescence assay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, antigen assay, biosensor, CRISPR, or clinical biochemical marker.

[0496] Clause 74 is the system of any of clauses 61-73, wherein the first and second assay types, being independent of each other, comprise polymerase chain reaction, isothermal nucleic acid amplification, nucleic acid hybridization, metagenomic sequencing, immunofluorescence assay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, antigen assay, biosensor, CRISPR, or clinical biochemical marker.

[0497] Clause 75 is a biological sample processing apparatus having a fixed volumetric footprint, the apparatus comprising: a chassis having an interior and an exterior; and a rack secured within the interior of the chassis, the rack including a plurality of bays, each bay being configured to receive one of a plurality of sample processing modules, each sample processing module being configured to receive and perform analysis on a sample cartridge assembly, each sample processing module being independently operable and securable within the rack, wherein the plurality of sample processing modules are selected from two or more module types, wherein each bay is configured to receive each sample processing module type, and wherein the fixed volumetric footprint remains constant whether the rack is full or less than full.

[0498] Clause 76 is the biological sample processing apparatus of clause 1, wherein the first cartridge assembly is configured to fit and be inserted one of the plurality of modules.

[0499] Clause 77 is the biological sample processing apparatus of clause 76, wherein the first cartridge assembly comprises a rotary valve assembly.

[0500] Clause 78 is the biological sample processing apparatus of clause 1, wherein the sample cartridge assembly is configured to fit and be inserted into any one of the plurality’ of sample processing modules.

[0501] Clause 79 is the biological sample processing apparatus of clause 78, wherein the sample cartridge assembly comprises a rotary valve assembly.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0502] Clause 80 is the biological sample processing apparatus of clause 4, wherein PCR comprises thermal cycling, thermal convection, continuous flow PCR, thermal gradient, digital PCR, or RT-PCR.

[0503] Clause 81 is the biological sample processing apparatus of clause 4, wherein isothermal analysis comprises loop mediated isothermal amplification (LAMP), nucleic acid sequence based amplification (NASBA), self-sustained sequence replication (3SR), rolling circle amplification (RCA), strand displacement amplification (SDA), Whole Genome Amplification (WGA), Helicase-Dependent Amplification (HDA), or Recombinase Polymerase Amplification (RPA).

[0504] Clause 82 is the biological sample processing apparatus of clause 1, wherein the analysis chip comprises a heater on a surface.

[0505] Clause 83 is the biological sample processing apparatus of clause 82, wherein the third module does not include a heater.

[0506] Although various clauses are described herein, those of ordinary skill in the art will understand that many modifications may be made thereto within the scope of the present disclosure. Accordingly, it is not intended that the scope of the disclosure in any way be limited by the examples provided.

[0507] In some instances, one or more components may be referred to herein as “configured to,’' “configurable to,’' “operable / operative to,’' “adapted / adaptable,” “able to,’' “conformable / conformed to.” etc. Those skilled in the art will recognize that such terms (e.g., “configured to”) can generally encompass active-state components and / or inactive-state components and / or standby-state components, unless context requires otherwise.

[0508] With respect to the appended claims, those skilled in the art will appreciate that recited operations therein may generally be performed in any order. Also, although various operational flows are presented in a sequence(s), it should be understood that the various operations may be performed in other orders than those which are illustrated, or may be performed concurrently. Examples of such alternate orderings may include overlapping, interleaved, interrupted, reordered, incremental, preparatory, supplemental, simultaneous, reverse, or other variant orderings, unless context dictates otherwise. Additional steps may also be performed, and disclosed steps can be excluded (and / or performed optionally) without departing from the present disclosure. Furthermore, terms like “responsive to,” “related to,” or other past-tense adjectives are generally not intended to exclude such variants, unless context dictates otherwise.CEP Ref. No. 2025-26316 | M&G Ref. No. 19582.0033WOU1

[0509] The present disclosure and claims sometimes utilize the words “first,"’ “second,” “third,” etc. as labels to particularly identify particular objects. Unless required by the context, such terms are used only as labels and do not require any particular order or arrangement with respect to each other or with respect to other objects.

[0510] The various embodiments described above are provided by way of illustration only and should not be construed to limit the claims attached hereto. While certain examples with certain combinations of features are illustrated and described herein, other combinations can be possible as well. Th...

Claims

WHAT IS CLAIMED IS:

1. A biological sample processing apparatus comprising:a chassis having an interior and an exterior;a rack secured within the interior of the chassis, the rack including a pl ural ity of bays; anda plurality of sample processing modules configured to receive and perform analysis on a sample cartridge assembly,wherein each of the plurality of sample processing modules is independently operable and securable within the rack,wherein the plurality of sample processing modules is selected from two or more module types including:a first module type configured to perform nucleic acid amplification;a second module type configured to perform non-thermal cycling detection of an analyte; anda third module type configured to perform lab on a chip analysis, wherein each bay is configured to receive each type of sample processing module.

2. The biological sample processing apparatus of claim 1, wherein the first or second module types are configured to detect the presence of an analyte within 15 minutes of initiation of sample processing.

3. The biological sample processing apparatus of any one of claims 1-2, wherein the first module type or the second module type is configured to perform PCR analysis via thermal convection.

4. The biological sample processing apparatus of any one of claims 1-3, wherein the first module type is configured to receive a sample cartridge assembly having a reaction tube and conduct polymerase chain reaction (PCR) or isothermal analysis.

5. The biological sample processing apparatus of any one of claims 1-4, wherein the second module t pe comprises a thermal convection unit and is configured to receive a sample cartridge assembly having a reaction tube.

6. The biological sample processing apparatus of any one of claims 1-5, wherein the third module type is configured to receive a sample cartridge assembly having a chip carrier device assembly configured to secure an analysis chip.

7. The biological sample processing apparatus of any one of claims 1-6, wherein the rack includes a plurality of module receiving zones configured to interchangeably secure any of the module types.

8. The biological sample processing apparatus of any one of claims 1-7, wherein the plurality7of sample processing modules comprises at least three module ty pes.

9. The biological sample processing apparatus of any one of claims 1-8, further comprising a fourth module type configured to perform nucleic acid sequencing on a sample.

10. The biological sample processing apparatus of any one of claims 1-9, wherein each of the module types are further configured to prepare a nucleic acid library for sequencing a sample introduced to the module via a sample cartridge.

11. The biological sample processing apparatus of any one of claims 1-10, wherein the plurality of sample processing modules includes at least three modules being a subset of the two or more module types.

12. The biological sample processing apparatus of any one of claims 1-11, wherein each of the plurality of sample processing modules is configured to operate concurrently to one another.

13. The biological sample processing apparatus of any one of claims 1-12, wherein the second or third module ty pes is configured to perform isothermal nucleic acid amplification,Illimmunoassay, electrochemical detection assay, immunofluorescence assay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, antigen assay, turbidity, or combinations thereof.

14. The biological sample processing apparatus of any one of claims 1-13, wherein the first or second module type is configured to receive a sample cartridge assembly having a reaction tube secured therein, the reaction tube having a first side and a second side, wherein the second module type comprises a plurality of independently controlled heaters, the plurality of independently controlled heaters comprising:a first heater configured to maintain the first side of the reaction tube at a first temperature, anda second heater configured to maintain the second side of the reaction tube at a second temperature.

15. The biological sample processing apparatus of claim 14, wherein the first or second module type further comprises an optical unit for detecting a target analyte in a fluid sample introduced to the reaction tube.

16. The biological sample processing apparatus of claim 15, wherein the optical unit comprises at least two light sources for transmitting one or more optical excitation beams to the reaction tube.

17. The biological sample processing apparatus of claim 15, wherein the optical unit comprises at least five light sources for transmitting one or more excitation beams to the reaction tube.

18. The biological sample processing apparatus of claim 16 or 17, wherein each light source is independently controlled.

19. The biological sample processing apparatus of any of claims 15-18, wherein the optical unit comprises at least two detectors configured to detect emission light from a processed sample in a plurality of wavelengths.

20. The biological sample processing apparatus of any of claims 15-19. wherein the optical unit is configured to simultaneously and differentially detect at least four emission wavelength ranges from the processed sample.

21. The biological sample processing apparatus of any of claims 15-20. wherein the optical unit is configured to simultaneously and differentially detect at least six emission wavelength ranges from the processed sample.

22. The biological sample processing apparatus of any of claims 15-21, wherein the optical unit is configured to simultaneously and differentially detect at least ten emission wavelength ranges from the processed sample.

23. The biological sample processing apparatus of any claims 14-22, wherein the plurality of independently controlled heaters are configured to enable melt analysis, amplification via one or more of thermal convection, thermal cycling, or isothermal amplification.

24. The biological sample processing apparatus of any of claims 14-23, wherein the 3D shape of the reaction tube is cylindrical, cube, spherical, rectangular, pyramidal, conical, or diamond.

25. The biological sample processing apparatus of any of claims 14-24, wherein the first temperature enables denaturing a target nucleic acid sequence into a single-stranded nucleic acid template.

26. The biological sample processing apparatus of any of claims 14-25, wherein the second temperature enables annealing a primer pair to the single-stranded nucleic acid template.

27. The biological sample processing apparatus of any of claims 14-26, wherein the first temperature is about 90°C or greater, about 95°C or greater, about 97°C or greater, or about 98°C or greater.

28. The biological sample processing apparatus of any of claims 14-27. wherein the second temperature is about 70°C or less, about 68°C or less, about 67°C or less, about 65°C or less, or about 64°C or less.

29. The biological sample processing apparatus of any of claims 14-28, wherein the second temperature is from about 60°C to about 70°C, from about 64°C to about 68°C, or from about 65°C to about 67°C.

30. The biological sample processing apparatus of any of claims 14-29, wherein the difference between the first temperature and the second temperature is equal to or greater than about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, about 30°C, about 31 °C, about 32°C, about 33°C, about 34°C, about 35°C, about 36°C, or about 37°C, from about 25 to about 37°C, from about 25 to about 35°C, from about 27 to about 35°C, or from about 28 to about 34°C.

31. The biological sample processing apparatus of any of claims 14-30, wherein the first temperature is from about 97°C to about 99°C and the second temperature is from about 65°C to about 67°C.

32. The biological sample processing apparatus of any of claims 1 -13, wherein the first module type further comprises:a loading bay configured to receive a reaction tube coupled to the sample cartridge assembly, the sample cartridge containing a sample:a plurality of heaters configured for thermal cycling the sample when introduced to the reaction tube, andan optical unit for detecting a target analyte in a processed sample, the sample having undergone processing.

33. The biological sample processing apparatus of claim 32, wherein the plurality of heaters are independently controlled.

34. The biological sample processing apparatus of claim 32 or 33, wherein the optical unit comprises at least two light sources for transmitting excitation beams to the reaction tube.

35. The biological sample processing apparatus of any one of claims 32-34, wherein the optical unit comprises at least five light sources for transmitting excitation beams to the reaction tube.

36. The biological sample processing apparatus of claim 34 or 35, wherein the light sources are independently controlled.

37. The biological sample processing apparatus of any of claims 32-36. wherein the optical unit comprises at least two detectors configured to detect emission light from the fluid sample in a plurality of wavelengths.

38. The biological sample processing apparatus of any of claims 32-37. wherein the optical unit is configured to simultaneously and differentially detect at least four emission wavelength ranges from the processed sample.

39. The biological sample processing apparatus of any of claims 32-38, wherein the optical unit is configured to simultaneously and differentially detect at least six emission wavelength ranges from the processed sample.

40. The biological sample processing apparatus of any of claims 32-39, wherein the optical unit is configured to simultaneously and differentially detect at least ten emission wavelength ranges from the processed sample.

41. The biological sample processing apparatus of any one of claims 32-40, wherein the plurality of heaters are further configured to enable amplification via thermal convection, isothermal amplification, or nested PCR, melt analysis, or a combination thereof.

42. The biological sample processing apparatus of any one of claims 1-41, wherein the third module ty pe comprises one or more of:a control unit configured to manage one or more steps of a sample processing protocol; andat least one pogo pin configured to interface with one or more I / O pad disposed on the analysis chip or chip carrier device.

43. The biological sample processing apparatus of claim 42, wherein the analysis chip is configured to analyze and detect analytes present in a processed sample.

44. The biological sample processing apparatus of claim 42 or 43, wherein the analysis chip further comprises a biosensor array, a memory, and a processing device.

45. The biological sample processing apparatus of any of claims 42-44, wherein the biosensor array further comprises a temperature sensor configured to measure the temperature across the biosensor array at a given timepoint.

46. The biological sample processing apparatus of any of claims 42-45, wherein the analysis chip is configured to perform athermal cycling process.

47. The biological sample processing apparatus of any of claims 42-46, wherein the thermal cycling process includes heating the active surface to an upper temperature or cooling the active face to a lower temperature.

48. The biological sample processing apparatus of any of claims 42-46, wherein the thermal cycling process includes heating the active surface to an upper temperature and cooling the active face to a lower temperature.

49. The biological sample processing apparatus of claim 47 or 48, wherein the upper temperature is about 90°C or higher.

50. The biological sample processing apparatus of any of claims 47-49, wherein the lower temperature is between about 40°C to about 75°C.

51. The biological sample processing apparatus of any of claims 1-50, wherein each module type comprises a subset of light sources selected from a set of light sources, wherein each subset of light sources is configured to excite one or more dyes associated with one or more assays capable of being performed by the respective module type.

52. The biological sample processing apparatus of claim 51, wherein the third module type comprises a blue light source and a UV light source.

53. The biological sample processing apparatus of claim 51, wherein the first or second module type comprises at least four light sources collectively configured to excite dyes and FRET pairs to cause the emission of at least ten wavelengths.

54. The biological sample processing apparatus of any of claims 1-53, wherein each of the sample processing modules comprises a sonication hom assembly configured to guide placement of the sample cartridge assembly within the sample processing module.

55. The biological sample processing apparatus of any of claims 1-54, wherein the rack comprises a top portion and a bottom portion.

56. The biological sample processing apparatus of any of claims 1-55, wherein a volumetric footprint of the apparatus remains constant whether the rack is full or less than full.

57. The biological sample processing apparatus of any of claims 1-56, wherein the first module type and second module ty pe are configured to receive a sample cartridge assembly of a first type.

58. The biological sample processing apparatus of claim 57, wherein the third module type is configured to receive a sample cartridge assembly of a second type.

59. The biological sample processing apparatus of claim 57 or 58, wherein the cartridge assembly of the first type comprises a reaction tube and the sample cartridge assembly of the second type comprises a chip carrier device assembly.

60. A system comprising:a biological sample processing apparatus including a chassis having an interior and an exterior, a rack secured within the interior of the chassis, the rack including a plurality of bays, and a barcode reader configured to read a first barcode directed to a first assay type, the first barcode being on or associated wi th a first sample cartridge assembly;a plurality' of sample processing modules configured to receive and perform analysis on a sample cartridge assembly, wherein each sample processing module is independently operable and securable within the rack; andat least one processor configured to execute a set of instructions, wherein the at least one processor is configured to:receive a first signal from the barcode reader based on the first barcode. in response to the first signal, determine the first type of assay, and transmit instructions to run the first assay type to a first sample processing modules of the plurality' of sample processing modules,wherein each bay is configured to receive each type of sample processing module.

61. The system of claim 60, wherein the barcode reader is further configured to:read a second barcode directed to a second assay type, the second barcode being on or associated with a second sample cartridge assembly,wherein the at least one processor being further configured to:receive a second signal from the barcode reader based on the second barcode, in response to the second signal, determine the second type of assay, and transmit instructions to run the second assay ty pe to a second sample processing modules of the plurality’ of sample processing modules.

62. The system of claim 61, wherein the first and second assay types are different.

63. The system of claim 61, wherein the first and second assay types are the same.

64. The system of any of claims 60-63, wherein the first and second sample processing modules are the same type of module.

65. The system of any of claims 60-63, wherein the first and second sample processing modules are different types of modules.

66. The system of any of claims 60-65, wherein the first and second sample processing modules are selected from two or more module types including:a first module type configured to perform nucleic acid amplification;second module type configured to perform non-thermal cycling detection of an analyte; anda third module type configured to perform lab on a chip analysis.

67. The system of any one of claims 60-66, wherein the first and second sample processing modules are configured to operate concurrently.

68. The system of any one of claims 60-67, wherein the barcode reader is integrated with the chassis.

69. The system of any one of claims 60-68, wherein the first and second assay types are at least two of low-pl ex, mid-pl ex, and high-plex.

70. The system of any one of claims 60-69, wherein the first assay type is associated with a first set of instructions executable by the biological sample processing apparatus, one or more of the plurality of sample processing modules, or both.

71. The system of claim 70, wherein the second assay type is associated with a second set of instructions executable by the biological sample processing apparatus, one or more of the plurality of sample processing modules, or both.

72. The system of claim 71, wherein the first and second unique identifiers are distinct from each other.

13. The system of claim 60, wherein the first assay type comprises polymerase chain reaction, isothermal nucleic acid amplification, nucleic acid hybridization, metagenomic sequencing, immunofluorescence assay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, antigen assay, biosensor, CRISPR, or clinical biochemical marker.

74. The system of any of claims 61-73, wherein the first and second assay types, being independent of each other, comprises polymerase chain reaction, isothermal nucleic acid amplification, nucleic acid hybridization, metagenomic sequencing, immunofluorescence assay, enzy me-linked immunosorbent assay, chemiluminescence immunoassay, antigen assay, biosensor, CRISPR, or clinical biochemical marker.

75. A biological sample processing apparatus having a fixed volumetnc footprint, the apparatus comprising:a chassis having an interior and an exterior; anda rack secured within the interior of the chassis, the rack including a plurality of bays, each bay being configured to receive one of a plurality of sample processing modules, each sample processing module being configured to receive and perform analysis on a sample cartridge assembly, each sample processing module being independently operable and securable within the rack,wherein the plurality of sample processing modules are selected from two or more module types,wherein each bay is configured to receive each sample processing module type, and wherein the fixed volumetric footprint remains constant whether the rack is full or less than full.

76. The biological sample processing apparatus of claim 1, wherein the first cartridge assembly is configured to fit and be inserted one of the plurality' of modules.

77. The biological sample processing apparatus of claim 76, wherein the first cartridge assembly comprises a rotary valve assembly.

78. The biological sample processing apparatus of claim 1, wherein the sample cartridge assembly is configured to fit and be inserted into any one of the plurality of sample processing modules.

79. The biological sample processing apparatus of claim 78, wherein the sample cartridge assembly comprises a rotary valve assembly.

80. The biological sample processing apparatus of claim 4, wherein PCR comprises thermal cycling, thermal convection, continuous flow PCR, thermal gradient, digital PCR, or RT-PCR.

81. The biological sample processing apparatus of claim 4, wherein isothermal analysis comprises loop mediated isothermal amplification (LAMP), nucleic acid sequence based amplification (NASBA), self-sustained sequence replication (3 SR), rolling circle amplification (RCA), strand displacement amplification (SDA), Whole Genome Amplification (WGA). Helicase-Dependent Amplification (HD A), or Recombinase Polymerase Amplification (RPA).

82. The biological sample processing apparatus of claim 1, wherein the analysis chip comprises a heater on a surface.

83. The biological sample processing apparatus of claim 82, wherein the third module does not include a heater.

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