Molecular diagnostic assay system

Abstract

Provided herein are improved subassemblies and control methods for use in diagnostic assay systems adapted to receive assay cartridges. Such subassemblies include: a brushless DC motor, a door opening and closing mechanism and an assay cartridge loading mechanism, a syringe and valve drive mechanism assembly, an ultrasonic horn, a thermal control device, and an optical detection / excitation device. Such systems can further include a communication unit configured to wirelessly communicate with a user's mobile device to receive user input related to the functions of the system with respect to the assay cartridge housed therein and to relay diagnostic results related to the assay cartridge to the mobile device.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 196,845, filed July 24, 2015, entitled “Molecular Diagnostic Assay System,” the entire contents of which are incorporated herein by reference.

[0003] This application relates in general to: U.S. Patent Application No. 13 / 843,739, filed concurrently with this application, entitled "Thermal Control Device and Methods of Use"; U.S. Patent Application No. 13 / 828,741, filed March 14, 2013, entitled "Remote Monitoring of Medical Devices"; U.S. Patent Application No. 8,048,386, filed February 25, 2002, entitled "Fluid Processing and Control"; and U.S. Patent Application No. 8,048,386, filed August 25, 2000, entitled "Fluid Control and Processing". U.S. Patent No. 6,374,684, entitled "System (Fluid Control and Processing System); the entire patent application / patent is incorporated herein by reference for all purposes. Background Technology

[0004] Technological advancements have made today's world an increasingly interconnected environment. While air travel allows ordinary people to travel from one continent to another and around the world in a single day, it can also enable the rapid spread of infectious pathogens, exposing global populations to deadly diseases with potentially devastating consequences. Recent outbreaks of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Ebola hemorrhagic fever serve as examples of how public health events originating in one region can rapidly escalate into major global concerns. The high degree of mobility in today's world necessitates reliable diagnostic tools to provide real-time results and facilitate early detection and prompt response to any potential epidemics.

[0005] On the other hand, many remote and underdeveloped areas remain in the world where local residents do not have easy access to healthcare. Inadequate accessibility to healthcare institutions (such as hospitals and clinics) or even medical product / service retailers (such as pharmacies) severely hinders any efforts to achieve timely diagnosis and treatment for patients, especially those with infectious diseases, making it difficult to properly assess epidemic risks or effectively contain the rapid spread of epidemics. Therefore, there is an urgent need for new and improved diagnostic tools that are highly portable and capable of performing complex molecular tests to produce rapid, reliable, and accurate diagnostic results, regardless of location—whether in healthcare institutions, community clinics, retail service providers, or in resource-constrained environments where electricity, communications (e.g., the internet), traditional healthcare services, and / or healthcare professionals may not have regular access.

[0006] The inventors have developed a highly precise yet fully portable and very easy-to-use molecular diagnostic testing system that meets the above requirements. This system surpasses existing molecular diagnostic testing systems (e.g., Cepheid's GeneXpert). ® The novel molecular diagnostic testing system described herein, after improvements, comprises a medical diagnostic device that is optionally battery-powered, typically small and lightweight, thus allowing for fully portable use anywhere patients may be far from hospitals, laboratories, or even pharmacies. This diagnostic device can perform fully automated molecular diagnostic tests (optionally detecting multiple pathogens simultaneously), providing rapid and accurate results (typically within 1 or 2 hours, and sometimes as fast as 15-20 minutes). Its operation is simple, using one or more pre-manufactured test kits to quickly obtain test results indicating whether a patient carries a specific pathogen or has a specific disease state.

[0007] This newly designed molecular diagnostic testing system also includes components that provide secure cloud-based connectivity to transmit diagnostic results from portable testing devices to remote reporting systems or mobile devices, such as handheld devices used by doctors or patients to receive diagnostic reports. These remote reporting systems can be centralized data collection or processing centers. Utilizing this cloud-supported connectivity, data sharing can occur almost instantaneously, allowing doctors to begin treating patients without any delay and enabling large-scale monitoring and reporting of any potential epidemics.

[0008] These key features overcome current limitations that tend to prevent or hinder early diagnosis and effective treatment for patients in impoverished and remote areas with limited healthcare facilities and diagnostic testing capabilities. This newly designed molecular diagnostic testing system is the first truly point-of-care diagnostic tool, offering the advantages of rapid deployment and full operational capability in virtually any environment. It truly brings diagnostic testing to people wherever they are. Its combination of deployability, rapid and accurate diagnostic capabilities, sophisticated yet easy-to-operate technology, and cloud-based connectivity makes this new molecular diagnostic testing system the ultimate solution for emerging markets and a trendsetter defining the future of medical diagnostic testing. Summary of the Invention

[0009] In one aspect, the present invention provides an improved diagnostic testing system. Such a system may include improvements involving various sub-components, including: a gate actuation assembly, a syringe actuator and a valve actuator, an ultrasonic horn, a thermal and optical detection assembly, and a device management / communication system. It is understood that any of these sub-components may be included individually in such a diagnostic testing system or combined with any other sub-component to provide the improved performance aspects described herein.

[0010] In some embodiments, the present invention includes a diagnostic testing system adapted to receive a test kit (sometimes also referred to as a "sample kit" or "test kit"). Such a system may include any one or a combination of the various features and sub-components described herein.

[0011] In some implementations, the diagnostic testing system includes a brushless DC (BLDC) motor operatively coupled to, for example, a door opening / closing mechanism and a test kit loading system, a syringe driver and / or a valve driver.

[0012] In some implementations, the diagnostic testing system includes a door opening / closing mechanism that is cooperatively coupled to the test kit loading mechanism and driven by a reversibly driven transmission mechanism.

[0013] In some implementations, the diagnostic testing system includes a syringe driver operatively coupled to an n-phase BLDC motor and controlled at least in part based on the monitoring current draw of the BLDC motor.

[0014] In some implementations, the diagnostic testing system includes a valve actuation mechanism that is operatively coupled to an n-phase BLDC motor based at least in part on voltage signals provided by n voltage sensors of the BLDC motor, without using any encoder hardware or position sensors.

[0015] In some embodiments, the diagnostic testing system includes: an ultrasonic horn, which can be coupled to a test kit for dissolving biological material within the test kit, and is operatively coupled to a controller configured to control the ultrasonic processing at least in part based on a frequency that provides the highest output amplitude as a resonant frequency.

[0016] In some embodiments, the diagnostic testing system includes: a thermal control device having a first thermoelectric cooler thermally coupled to a reaction vessel (sometimes also referred to as a "reaction tube") of the test kit and at least one other thermal manipulation device thermally coupled to the first thermoelectric cooler, and being controlled to increase the efficiency of the first thermoelectric cooler to facilitate rapid thermal cycling of the reaction vessel between a first temperature and a second temperature using the first thermoelectric cooler.

[0017] In some embodiments, the diagnostic testing system includes an optical excitation / detection block that can be mounted relative to the reaction vessel to emit excitation energy into a fluid sample within the reaction vessel at a substantially orthogonal angle, and detect the excitation from that angle through one or more edges (sub-faces) and / or the main face of the reaction vessel.

[0018] In some embodiments, the diagnostic testing system includes a communication unit configured to wirelessly communicate with a user's mobile device to receive user input related to the functionality of the testing kit contained therein and to relay diagnostic results related to the testing kit to the mobile device.

[0019] Some embodiments of the present invention relate to a door operating system for a diagnostic laboratory system. The system may include a rack for the diagnostic laboratory system. A brushless direct current (BLDC) motor may be coupled to the rack of the diagnostic laboratory system. A reversible drive mechanism may be operated by the BLDC motor. A door may be moved relative to the rack of the diagnostic laboratory system from a closed position to an open position (and from an open position to a closed position). The BLDC motor may be configured to operate the reversible drive mechanism based on a current measurement of the BLDC motor associated with a reverse drive event of the reversible drive mechanism.

[0020] Some embodiments of the present invention relate to a method for operating a door opening / closing system for a diagnostic testing system. In this method, a command is received to open a test kit receiving door of the diagnostic testing system. A brushless DC (BLDC) motor coupled to a reversible drive mechanism operably coupled to the door is operated to open the door from a closed position (and vice versa). A first reverse drive event occurring on the reversible drive mechanism can be detected based on monitoring of the current. Based on the detection of the first reverse drive event, operation of the BLDC motor that positions the door in the open position can be stopped, and an aspect of the test kit loading mechanism can be positioned suitable for receiving test kits.

[0021] Some embodiments of the present invention relate to a system for operating a syringe for a diagnostic testing system. The system may include a rack for the diagnostic testing system. A brushless direct current (BLDC) motor may be coupled to the rack of the diagnostic testing system. A reversible lead screw may be operated by the BLDC motor. A plunger rod may be operated by the lead screw to engage a plunger head in a syringe channel of a removable test cartridge. The BLDC motor may be configured to operate the lead screw based on monitoring the current draw of the BLDC motor, the current being correlated with pressure changes within the removable test cartridge.

[0022] Some embodiments of the present invention relate to a method for operating a syringe for a diagnostic testing system. A command to power a brushless direct current (BLDC) motor can be received. The BLDC motor is operable to rotate a reversibly driven lead screw. A plunger rod is coupled to and movable by the lead screw. Power can be applied to the BLDC motor to move the plunger rod to engage a plunger head within a syringe channel of a removable test cartridge. At least one current associated with the operation of the BLDC motor can be monitored to determine the quality of the removable test cartridge. Changes in the current of the BLDC motor can be detected. Based on the detected change in current, the operation of the BLDC motor can be altered within the removable test cartridge.

[0023] Some embodiments of the present invention relate to a horn assembly having an ultrasonic horn and a horn housing, the horn assembly engaging with a disposable test kit via a movable mechanism that moves the ultrasonic horn between a disengaged or retracted position and an engaged or advanced position. The disengaged or retracted position facilitates loading and ejection of the test kit from a diagnostic device module. The engaged or advanced position presses the horn against the ultrasonic processing chamber of the test kit to promote the lysis of biological cells within the chamber as part of a diagnostic assay, which may include, but is not limited to, polymerase chain reaction (PCR) analysis. In some embodiments, the movable mechanism includes a spring or biasing mechanism and a cam that engages a wedge-shaped surface of the horn housing to move the horn between a lowered position and an raised position. In some embodiments, movement of the horn assembly is achieved via an actuator shared with other movable components, such as a loading / unloading arm and a test kit module door, to provide efficient coordinated movement of components within the diagnostic device module.

[0024] Some embodiments of the present invention relate to a horn having an ultrasonic horn and at least one piezoelectric actuator controlled under closed-loop feedback. In some embodiments, the horn includes control circuitry that utilizes sinusoidal control and phase matching to control the resonant frequency. These features ensure in-phase vibration between the piezoelectric actuators to provide a consistent and robust ultrasonic energy delivery, wherein the ultrasonic horn has smaller size and power requirements than other feasible approaches.

[0025] Some embodiments of the present invention relate to a method for operating a valve actuator. A command can be received to power a brushless direct current (BLDC) motor coupled to a rack to move a valve actuator to a specific position. The valve actuator can be configured to rotate the position of a valve body of a removable test cartridge. A drive mechanism can be coupled between the BLDC motor and the valve actuator. The BLDC motor does not include any position sensor or encoder hardware but may include multiple Hall effect sensors. Powering the BLDC motor can rotate its shaft a specific number of revolutions to move the valve actuator to the specific position based on a sinusoidal signal generated by the Hall effect sensors.

[0026] Some embodiments relate to a system for operating a valve actuation mechanism. The system may include a valve actuation mechanism frame. A brushless direct current (BLDC) motor may be coupled to the frame. The BLDC motor does not include any position sensor or encoder hardware but may include multiple Hall effect sensors. A drive unit may be coupled to the BLDC motor. A valve actuator may be coupled to the drive unit. The valve actuator may be configured to rotate the position of the valve body of a removable test cartridge. The position of the valve actuator output may be determined based on analysis of the sinusoidal signal generated by the Hall effect sensors.

[0027] Some embodiments of the present invention relate to a diagnostic device that may include a thermo-optical subassembly (“TOS”) comprising a thermal control device component and an optical excitation / detection component. In some embodiments, the thermal control device includes a thermoelectric cooler (“TEC”) component that performs thermal cycling of the reaction vessel. The optical excitation / detection component excites and optically detects the target analyte with improved control, speed, and efficiency. In some embodiments, the TOS includes a mounting component for interface connection between the thermal control device and the optical component, and defines a cavity for receiving a reaction vessel with a prepared fluid sample for performing assays of the target analyte. In some embodiments, the mounting component provides the thermal control device and the optical component near the reaction vessel to perform thermal cycling for amplification, excitation, and optical detection of the target analyte simultaneously or rapidly and continuously. In some embodiments, the reaction vessel includes a microarray or multiple individual reaction wells and / or a pre-amplification chamber within the reaction vessel. In some embodiments, the TOS includes one or more mechanisms that move the thermal control device to pressure-engage at least one surface of the reaction vessel when positioned within the diagnostic device, thereby improving the efficiency of the thermal cycling. In some implementations, the TOS is integrated with one or more printed circuit boards (PCBs), processors, and controllers to coordinate thermal cycling and optical excitation / detection according to a specific assay. In some implementations, the TOS includes sensors for detecting proximity to the reaction vessel or associated sample test kit to facilitate the positioning of thermal control devices and / or optical components relative to the reaction vessel or its operation.

[0028] Some embodiments of the present invention relate to a thermal control device that may include: a first TEC having a working surface and a reference surface; a second TEC having a working surface and a reference surface; and a thermal capacitor or thermal intervenor disposed between the first TEC and the second TEC such that the reference surface of the first TEC is thermally coupled to the working surface of the second TEC via the thermal capacitor. In some embodiments, the thermal intervenor is located between the first and second TEC devices. In some embodiments, the thermal intervenor acts as a thermal capacitor. In some embodiments, the thermal control device includes a controller operatively coupled to each of the first TEC and the second TEC, the controller being configured to operate the second TEC in parallel with the first TEC to increase the speed and efficiency of operating the first TEC as the temperature of the working surface of the first TEC changes from an initial temperature to a desired target temperature.

[0029] Some embodiments of the present invention relate to an optical component that may include an optical excitation block and an optical detection block located on an optical mount configured to receive a reaction vessel. In some embodiments, the reaction vessel includes two opposing primary planar walls spaced apart from each other by secondary planar walls, wherein at least two of the secondary planar walls are offset from each other by approximately 90 degrees. In some embodiments, the optical excitation block is positioned to transfer excitation energy into the reaction vessel through one of the secondary walls, and the optical detection block is positioned for detection along the primary plane of the reaction vessel. In some embodiments, excitation and detection occur via opposing secondary walls of the reaction vessel. In some embodiments, the optical excitation and optical detection components are orthogonal to each other. Compared to conventional systems, the optical component is suitable for having a relatively low numerical aperture (e.g., low angular divergence). This configuration provides a large detection volume with a small numerical angle, thereby providing improved optical sensitivity and facilitating optical alignment.

[0030] On the other hand, the TOS includes sensors for detecting the proximity and / or position of the test kit or reaction vessel relative to the TOS and for identification. In some embodiments, the sensors are near-field communication sensors adapted to detect when the test kit has been loaded into the diagnostic device (sometimes also called a "diagnostic module") of the diagnostic testing system, identify the test, and link the test kit to a sample identifier. In some embodiments, the TOS includes a controller for coordinating the operation of thermal control devices and optical modules in response to the sensors.

[0031] Some embodiments of the present invention relate to a method for managing a diagnostic testing system via a mobile device. User input for controlling the functions of a diagnostic device can be received at the mobile device. In response to receiving the user input, control information can be sent to the diagnostic testing device via the mobile device. Data (e.g., medical data) from the diagnostic testing device can be received at the mobile device. The data can be relayed to a server without storing or describing the data.

[0032] Some embodiments of the present invention relate to a diagnostic testing apparatus having a communication subsystem. The system may include diagnostic components. A processor is communicatively coupled to the communication subsystem and the diagnostic components. The processor is configured to enable the diagnostic testing apparatus to wirelessly receive device commands from a mobile device using the communication subsystem. The processor is also configured to wirelessly transmit device command responses to the mobile device using the communication subsystem. The processor is further configured to perform tests using the diagnostic components. The processor is also configured to wirelessly transmit encrypted diagnostic information (e.g., medical information) indicating the test results to a remote server using the communication subsystem. Attached Figure Description

[0033] Figure 1AThis is a perspective view of a diagnostic testing system according to some embodiments of the present invention.

[0034] Figure 1B This is an exploded view of a diagnostic testing system according to some embodiments of the present invention.

[0035] Figures 2A to 2C This is a perspective view of a brushless DC (BLDC) motor according to some embodiments of the present invention.

[0036] Figure 2D It is a graph of the sinusoidal variable voltage output pattern of a BLDC motor according to some embodiments of the present invention, with additional markings to illustrate the process for encoding the mechanical angular position of the motor rotor.

[0037] Figure 2E This is a circuit diagram for controlling a BLDC motor according to some embodiments of the present invention.

[0038] Figures 3A to 3C This is a diagram of a model for determining the torque output of a BLDC motor according to some embodiments of the present invention.

[0039] Figure 4A This is a perspective view of a door opening mechanism according to some embodiments of the present invention.

[0040] Figures 4B to 4E This is a cross-sectional view of a diagnostic testing system in use according to some embodiments of the present invention.

[0041] Figure 5A This is a cross-sectional view of a diagnostic testing system in use according to some embodiments of the present invention.

[0042] Figure 5B and Figure 5C This is a flowchart of a method for operating a diagnostic testing system according to some embodiments of the present invention.

[0043] Figure 6A and Figure 6B This is a perspective view of a valve drive mechanism according to some embodiments of the present invention.

[0044] Figure 6C This is a graph relating the output signal to the valve actuator position according to some embodiments of the present invention.

[0045] Figures 7A to 7B An ultrasonic horn assembly for a diagnostic testing system is shown according to some embodiments of the present invention.

[0046] Figures 8A to 8D Partial views of an ultrasonic horn assembly according to some embodiments of the present invention are shown.

[0047] Figures 9A to 9B Cross-sectional views of a diagnostic testing system during and after kit loading are shown according to some embodiments of the invention.

[0048] Figure 10A A cross-sectional view of the test kit is shown. Figure 10B A cross-sectional view is shown of a test kit mounted in a diagnostic testing system having an ultrasonic horn assembly, according to some embodiments of the present invention.

[0049] Figures 11A1-2 to 11B1-2 show side views and cross-sectional views of horn assemblies in separated and joined positions according to some embodiments of the present invention.

[0050] Figure 12A An exemplary ultrasonic horn is shown. Figure 12B A control diagram for the operation of an ultrasonic horn is shown according to some embodiments of the present invention.

[0051] Figure 13 The transfer function for controlling a horn assembly according to some embodiments of the present invention is shown.

[0052] Figure 14 A schematic diagram of the control of a horn assembly according to some embodiments of the present invention is shown.

[0053] Figures 15 to 17 A control diagram of a horn assembly according to some embodiments of the present invention is shown.

[0054] Figure 18 An exemplary TOS sub-component preceding the insertion assay module is shown according to some embodiments of the present invention.

[0055] Figures 19A to 19B The front and rear views of an exemplary TOS sub-component according to some embodiments of the present invention are shown.

[0056] Figures 20A to 20B An exploded view of an exemplary TOS according to some embodiments of the present invention is shown.

[0057] Figures 21A to 21B An exemplary TOS optical component and associated PCB are shown according to some embodiments of the present invention.

[0058] Figures 22A to 22B Exemplary thermal control device components and associated PCBs with robust flexible connections in an exemplary TOS are shown according to some embodiments of the present invention.

[0059] Figures 23A to 23BAn exemplary thermal control device component is shown, configured to engage with an optical mount of an exemplary TOS according to some embodiments of the present invention.

[0060] Figures 24A to 24B The illustration shows exemplary thermal control device components that are movably coupled to optical mounts in open and clamped configurations, respectively, according to some embodiments of the present invention.

[0061] Figure 25 An exemplary thermal control device component is shown that is movably coupled to an optical mount and a sliding base according to some embodiments of the present invention.

[0062] Figures 26A to 26B An exemplary thermal control device component according to some embodiments of the present invention is shown, which is movably coupled to a sliding base actuated by a gear rack of a module.

[0063] Figure 27 An exemplary block control diagram of a TOS component according to some embodiments of the present invention is shown.

[0064] Figure 28 An exemplary schematic diagram of the optical and thermal control components of a TOS according to some embodiments of the present invention is shown.

[0065] Figure 29 An exemplary TOS for a diagnostic testing system is shown according to some embodiments of the present invention.

[0066] Figures 30A to 30B Two exemplary optical component configurations for a reaction vessel in a diagnostic apparatus are shown according to some embodiments of the present invention, and Figure 30C A detailed schematic diagram of an exemplary optical component configuration according to some embodiments of the present invention is shown.

[0067] Figure 31 Exemplary detailed views of excitation block 310 and detection block 320 according to some embodiments of the present invention are shown.

[0068] Figure 32 Fluorescence detection using exemplary optical components for excitation and detection is illustrated according to some embodiments of the present invention.

[0069] Figure 33A A schematic diagram of a thermal control device according to some embodiments of the present invention is shown.

[0070] Figures 33B to 33C A model of an exemplary thermal control device according to some embodiments of the present invention is shown.

[0071] Figure 34A thermal cycle under closed-loop control according to some embodiments of the present invention is shown.

[0072] Figure 35 Ten consecutive thermal cycles in a full range of PCR thermal cycles are shown according to some embodiments of the present invention.

[0073] Figure 36A The thermal cycling performance of five cycles, starting at the beginning of the thermal cycle and after two days of continuous thermal cycling, is shown.

[0074] Figure 36B A control diagram of the setpoint used in a control loop according to some embodiments of the present invention is shown.

[0075] Figure 37 A diagram showing the setpoints used in a control loop according to some embodiments of the present invention is illustrated.

[0076] Figure 38 This is an exemplary illustration of the software architecture of a diagnostic testing system according to some embodiments of the present invention.

[0077] Figure 39 A logical view of software executed by a diagnostic device according to some embodiments of the present invention is provided.

[0078] Figure 40 This is a block diagram of a diagnostic testing system (Epsilon instrument core architecture) according to some embodiments of the present invention.

[0079] Figure 41 is a diagram showing various states of a hierarchical system machine (HSM) component according to some embodiments of the present invention.

[0080] Figure 42 This is a diagram illustrating the core internal components and interfaces of an instrument according to some embodiments of the present invention.

[0081] Figure 43 This is a block diagram illustrating software components executed on a mobile device according to some embodiments of the present invention.

[0082] Figure 44 This is a block diagram illustrating software components executed by a remote diagnostic reporting service according to some embodiments of the present invention.

[0083] Figure 45 This is a data flow diagram illustrating the top-level data flow in a diagnostic testing system according to some embodiments of the present invention.

[0084] Figure 46 It shows a ratio Figure 45 A more detailed data flow diagram of the implementation of the data flow, in which the components of the mobile device are depicted separately.

[0085] Figure 47 This is a data flow diagram illustrating the location configuration process of a diagnostic testing system according to some embodiments of the present invention.

[0086] Figure 48 This is a data flow diagram illustrating a process for providing operational updates to a mobile device in a diagnostic testing system according to some embodiments of the present invention.

[0087] Figure 49 This is a data flow diagram illustrating a process for providing operational updates to a diagnostic device in a diagnostic testing system according to some embodiments of the present invention.

[0088] Figure 50 This is a data flow diagram of such a process in a diagnostic testing system according to some embodiments of the present invention.

[0089] Figure 51 This is a data flow diagram illustrating a process for providing diagnostic device commands in a diagnostic testing system according to some embodiments of the present invention.

[0090] Figure 52 This is a data flow diagram illustrating a process for providing registration of medical diagnostic devices on a network of a diagnostic testing system according to some embodiments of the present invention.

[0091] Figure 53 These are illustrations of a computer system according to some embodiments of the present invention, which may be at least partially incorporated into the apparatus and components of the diagnostic testing system described herein.

[0092] Figure 54 This is a flowchart of a method for managing a diagnostic testing system using a mobile device according to some embodiments of the present invention. Detailed Implementation

[0093] 1. System Overview

[0094] Figure 1A A perspective view of a system 10 for testing biological samples according to an embodiment of the present invention is shown. The compact form factor of system 10 provides a portable sample testing device that can communicate wirelessly or directly (wired) with a local computer or a cloud-based network. Therefore, system 10 can be advantageously used in developing countries and in physician clinic laboratories for on-site care applications, including mobile diagnostic centers.

[0095] System 10 can be used with disposable test kits configured to accept biological samples and suitable for performing specific tests. The system and test kits are highly flexible and can be used to detect a wide variety of analytes, including nucleic acids and proteins. Non-limiting exemplary analytes that can be detected using the system and test kits include bacteria, viruses, and disease-specific markers for a variety of pathogenic disease states, including health-related infections (MRSA, Clostridium difficile, vancomycin-resistant enterococci (VRE), norovirus), major infectious diseases (MTB / RIF, influenza, RSV, EV), sexual health (CT / NG, GBS), oncology (e.g., breast cancer or bladder cancer), and genetics (FII / FV). In some embodiments, system 10 can identify the type of test kit through integrated near-field communication capabilities (e.g., RFID, laser scanning) and thus apply appropriate testing routines to the test kit. In some embodiments, test kit identification uses Bluetooth technology, RFID tags, barcodes, QR tags, etc.

[0096] Once the test kit is physically inserted into system 10 and initialized by system 10, the system will perform sample processing functions. In some embodiments, sample processing may include sample preparation, nucleic acid amplification, and analyte detection. The results of the detection process can be uploaded wirelessly or directly via a wired connection to a local computer or a cloud-based network. Advantageously, the local computer may be a wireless communication device, such as a tablet or cellular phone, with software applications specifically designed to control the system and communicate with the network.

[0097] System 10 can be powered by an external power source, but may have an uninterruptible power supply (UPS) to prevent power outages or field use. An UPS allows for field use of the system and, in some embodiments, can provide power for at least one day, preferably up to two days. In some embodiments, a UPS allows for continuous operation for up to four hours. As shown in this external view, system 10 may include a housing 12 and a door 14 for receiving test kits (not shown). Different types of housings 12 can be configured to meet the specific needs of a particular user. Typically, housing 12 is formed of a fundamentally rigid material (e.g., a hardened polymer or metal structure) to protect and support the components within. Although not shown here, in some embodiments, housing 12 may be heavily reinforced (armored) for field use, or, as shown here, decorated for use in a doctor's office.

[0098] Figure 1B An exploded view of system 10 (without enclosure) is shown, with the main subsystems shown outwards. An overview of the subsystems is provided below. The following sections describe further details of each subsystem.

[0099] Various subsystems utilizing brushless direct current (BLDC) motors are disclosed. Typically, each motor may have a stator assembly mounted to a printed circuit board (PCB) substrate and may include a reversibly driven drive mechanism, such as a lead screw. In some embodiments, such BLDC motors utilize analog sensors (e.g., Hall effect sensors) to determine angular positioning as a triggering tool and force-based current monitoring. Such BLDC motors may include a rotor having multiple magnets disposed thereon and mounted on a substrate having at least as many sensors as there are phases of the motor. Three sensors are positioned such that rotor displacement can be controlled based on linear portions of measurements from the sensors, providing improved resolution and granularity without the need for any position-based sensor or encoder hardware. Therefore, the BLDC motors described herein do not require encoder hardware, and their associated power transmission systems do not require position sensors. For example, the system may include a syringe drive mechanism 16 comprising a brushless BLDC motor having an output shaft that engages with a reversibly driven lead screw. A lead screw drives a plunger rod that engages with the plunger head of a removable test kit. Such a syringe drive mechanism 16 can share a PCB 30 with a door drive mechanism 18. The door drive mechanism also includes a BLDC motor with an output shaft that engages with a reversibly drive lead screw. The motors of the syringe drive mechanism 16 and the door drive mechanism 18 are shown mounted directly to opposite sides of the PCB; however, this is not critical, and both motors can be mounted on the same side. In some embodiments, each motor can be mounted to its own PCB. Utilizing such a BLDC motor is advantageous because the improved resolution and granularity allow for increased accuracy and efficiency, and also allow for further miniaturization of the mechanism driven by such a motor. However, it should be recognized that the use of such a BLDC motor is not necessary, and any mechanism described herein can also be driven by a conventional type of motor if desired, but for some embodiments, additional sensors and / or circuitry may be required.

[0100] As described above, the unique feature of a BLDC motor is the inclusion of multiple Hall effect sensors, but without any conventional encoder hardware. In some embodiments, the syringe drive mechanism and the door drive mechanism, along with their associated subsystems, do not include position sensors. In some embodiments, the angular position of the BLDC rotor and output shaft can be derived separately from circuitry on the PCB and the sinusoidal output of an analog sensor. Therefore, conventional position sensors (e.g., encoders, optical sensors, etc.) do not need to be used with the BLDC motor used in this invention. To enable the BLDC motor to provide smooth torque generation, motor control techniques such as sinusoidal commutation can be implemented. Furthermore, pulse width modulation can be used to center the drive voltage for high-speed operation.

[0101] Furthermore, since the lead screw of the mechanism is reversibly actuated, force-based end-of-stroke detection can be used to determine the start and stop points for driving the mechanism. Force-based end-of-stroke detection can be derived by monitoring the current of the BLDC motor (e.g., the current in the bridge circuit), which deviates from a standard (increases or decreases) when a force-based event occurs. Therefore, this deviation can be used as a trigger event for starting, stopping, reversing, decelerating, and / or accelerating the BLDC motor. For example, in the case of syringe drive mechanism 16, current sensing can be correlated with pressure and thus used to deliver consistent or deliberately altered pressure to the plunger rod by tuning the associated BLDC motor's RPM (rotational speed). This reduces the need for in-line pressure sensors to monitor test kit pressure.

[0102] The valve actuation mechanism 20 can similarly use the same type of BLDC motor. In some embodiments, the valve actuation mechanism 20 may include a worm gear train that ultimately outputs to a rotary valve actuator for rotating the valve of the removable test kit. In some embodiments, the worm gear mechanism is not reverse-driveable like the syringe actuation mechanism and door actuation mechanism described above. However, the valve actuation mechanism can use the same type of Hall effect position determination and force-based triggering (current monitoring). For example, if unexpectedly rotating the valve actuator requires substantially less or more current, such an event can indicate a blockage or malfunction of the test kit. Here, force-based triggering can be used to sense a failure in test kit integrity.

[0103] The ultrasonic horn mechanism 22 is partially integrated with the valve actuation mechanism 20. The ultrasonic horn mechanism 22 can apply programmable ultrasonic power to a test chamber for a programmable duration, for example, to lyse a target sample within the test chamber. In some embodiments, the ultrasonic horn mechanism 22 may employ a resonant piezoelectric actuator to apply vibrations at frequencies of approximately 30 kHz or higher, approximately 40 kHz or higher (such as approximately 50 kHz (e.g., 50.5 kHz)). The ultrasonic horn mechanism 22 includes control circuitry that uses the phase of a measured current associated with the voltage excitation to determine the resonant frequency. This frequency can be adjusted by the control circuitry to maintain a preset phase relationship. In some embodiments, the amplitude of the voltage excitation can be continuously adjusted to maintain a commanded power level. Based on these functions, the control circuitry can maximize the power output of the horn.

[0104] System 10 also includes a door drive and test kit loading system 24 powered by a door drive mechanism 18. The lead screw of the door drive mechanism 18 outputs power to the door drive and test kit loading system 24 to open and close the door 14 and engage and store the test kit 32.

[0105] The rear rack section 26 and the front rack section 28 provide structural support for system 10 and mounting arrangements for other subsystems. The rack sections are generally elongated to provide a smaller overall footprint for system 10 and to make system 10 portable. In some embodiments, the system may have a footprint of 9.1 inches × 3.0 inches × 4.2 inches and a weight of approximately 2.2 pounds. An elongated circuit board, or PCB 30, generally matches the footprint of the rack sections. PCB 30 includes most or all of the processors, subprocessors, memory, and control circuitry required to control system 10. However, the aforementioned BLDC motors may be integrated with their respective printed circuit boards, which have separate control circuitry connected to PCB 30. PCB 30 also includes communication circuitry (e.g., near-field communication circuitry, USB, wireless) and power supply circuitry.

[0106] System 10 is compatible with various types of test kits 32, which are typically configured to receive and retain material samples, such as bodily fluids (e.g., blood, urine, saliva) or liquid-soluble solids (e.g., soil, spores, chemical residues). Test kit 32 may be a wall structure having one or more fluid channels and connection ports. Test kit 32 may be relatively small, making it easily suitable for handheld, portable, and / or disposable use. Examples of such test kits (which can be used with System 10) are disclosed in U.S. Patent No. 6,660,228, International Publication No. WO 2014052671 A1, and U.S. Patent No. 6,374,684, all of which are incorporated herein by reference for all purposes.

[0107] The test kit 32 may include a reaction vessel 33 extending outward from the rear, which engages with a thermal cycling and detection module 34. The module 34 includes one or more devices configured to deliver energy to and remove energy from aspects of the test kit 32. Such devices may include dual thermoelectric coolers. The module 34 also includes one or more detection aspects, as discussed in further detail below.

[0108] 2. Brushless DC (BLDC) Motor Architecture

[0109] Figure 2AThis is a plan view illustrating elements of a brushless direct current (BLDC) motor 100 used in some embodiments of the present invention. Further details of the BLDC motor can be found in commonly assigned U.S. Provisional Application No. 62 / 195449, filed July 22, 2015, entitled “Simple Centroid Implementation of Commutation and Encoding for DC Motor,” the entire contents of which are incorporated herein by reference for all purposes.

[0110] In one aspect, a BLDC motor, comprising a rotor and a stator, is configured to generate smoothly varying Hall effect voltages without requiring any filtering or noise reduction. In some embodiments, this characteristic is provided by using permanent magnets extending within the rotor beyond the stator core. In some embodiments, the BLDC motor includes as many Hall effect sensors as phases of the motor, positioned such that the motor can be controlled substantially solely based on the linear portion of the measured voltage pattern received from the sensors. In some embodiments, this includes radially spaced sensors around the stator such that the linear portions of the measured voltage waveforms intersect. For example, a three-phase BLDC may include three Hall effect sensors radially spaced 40 degrees from each other, thereby allowing the system to control the sensor positions in increments of 40 degrees.

[0111] In some embodiments, the motor includes an inner stator assembly 101 with nine pole teeth extending radially from the center, each pole tooth terminating in a pole shoe 103, and each pole tooth having a winding providing an electromagnetic coil 102. The motor also includes an outer rotor 104 having an outer cylindrical skirt 105 and twelve permanent magnets 106 arranged in alternating polarities around the inner periphery of the skirt 105. The permanent magnets are shaped to provide a cylindrical inner surface to the rotor and an outer curved surface adjacent to the pole shoe. The BLDC motor in this example is a three-phase twelve-pole motor. A control device is provided, however... Figure 2A As not shown, as is known to those skilled in the art, the switching current in coil 102 provides electromagnetic interaction with permanent magnet 106 to drive the rotor.

[0112] It should be noted that the number of pole teeth and polarity, as well as the internal stator and external rotor actually disclosed, are exemplary and not limited in the present invention, which can be operated with motors of various different designs.

[0113] Figure 2B yes Figure 2AThe image shows a partial cross-sectional side view of the motor, cut open to show one of its nine pole teeth and a coil. The pole tooth terminates in a pole shoe 103, which is adjacent to one of twelve permanent magnets 106 arranged immediately around the inner circumference of a cylindrical skirt 105 surrounding the outer rotor 104. The pole teeth and pole shoes of the stator assembly 101 are part of the magnetic core and define the distal end of the core at the height of line 204. In this embodiment, the stator assembly 101 is supported on a substrate 201, which in some embodiments is a printed circuit board (PCB). The PCB may include control units and traces for managing the current switching of the coil 102 to provide an electromagnetic field that interacts with the magnetic field of the permanent magnets 106 to drive the rotor. The PCB substrate may also include control circuitry for encoding and commutation. The rotor 104 is physically engaged with the stator 101 via a drive shaft 107, which engages a bearing assembly in the stator to precisely guide the rotor's rotation. In this embodiment, the drive shaft 107 passes through an opening in the PCB 107 for a specific purpose and can be engaged to drive a mechanical device.

[0114] Figure 2B Three linear Hall effect sensors 202a, 202b, and 202c are shown, supported by a substrate 201 and strategically positioned according to some embodiments of the invention to generate a variable voltage pattern that can be used to encode the angular position of the rotor and provide commutation for the motor 100. Figure 2B In this design, the total height of the skirt 105 of rotor 104 is represented by dimension D. Dimension d1 represents the extension of the distal end of the rotor magnet at line 204 below the distal end of the magnetic core. In conventional motors, there is no reason or motivation to extend this edge below the distal end of the magnetic core, especially since this would increase the height of the motor and require increasing the gap between the rotor and the base plate. In fact, technicians would limit dimension D to prevent such an extension, as increasing the dimension would only add unnecessary cost and increase the size of the conventional motor. Furthermore, at the distal end of the rotor in a conventional motor, where it is at or above the distal end of the magnetic core, the switching of current in coil 102 produces a considerable field effect, and the signal detected by the Hall effect sensor arranged to sense the permanent magnet at that location will not produce a smoothly varying Hall effect voltage. More precisely, the Hall effect in conventional motors is essentially impaired by noise. The conventional method to address this problem is to introduce noise filtering or, more commonly, to utilize an encoder.

[0115] Extending the rotor magnet below the far end of the iron core avoids the damaging effect of the flipping magnetic field from the stator coils on the signal detected by the Hall effect sensor. The specific extension d1 will depend on several factors specific to the particular motor arrangement, and in some embodiments d1 will be 1 mm or more (e.g., 2 mm, 3 mm, 4 mm, 5 mm, 6 mm or greater), while in others the extension will be less than 1 mm. In some embodiments, this distance is a function of the size of the permanent magnet and / or the magnetic field strength. In some embodiments described in detail herein, an extension of 1 mm is sufficient to produce a varying voltage with a sinusoidal signal without noise or saturation. Placing the Hall effect sensor at a interval d2 to generate the Hall effect voltage produces a smooth, variable voltage without noise. In some embodiments, the Hall effect sensor produces a smooth, variable DC voltage in the range of about 2 volts to about 5 volts without noise or saturation. The size d2 can vary depending on the choice of sensor, the rotor design, the strength of the permanent magnet in the rotor, and other factors known to those skilled in the art. To avoid sensor saturation and produce a smooth, variable DC voltage with substantially no noise, feasible intervals can be readily found for any given situation.

[0116] Figure 2C It is along Figure 2B The image shows a plan view of a portion of the substrate 201 taken in the direction of arrow 3, illustrating the placement of Hall effect sensors 202a, 202b, and 202c relative to the distal edge of rotor 104, the distal edge of rotor 104 being... Figure 2B The image shows a dimension d1 extending below the far edge of the magnetic core. Figure 2C In the diagram, the rotational trajectory of a rotor 104 comprising twelve permanent magnets 106 is shown by dashed outline 302. Depending on the specific details of the commutation, the rotor rotates in either direction 303.

[0117] As shown in this non-limiting exemplary embodiment, each of the Hall effect sensors 202a, 202b, and 202c is radially positioned below the distal edge of the rotor magnet, directly inside the center trajectory of the rotating magnet. Hall effect sensor 202b is positioned at a 40-degree arc relative to Hall effect sensor 202a along the rotational trajectory of the rotor magnet. Similarly, Hall effect sensor 202c is positioned at another 40-degree arc relative to Hall effect sensor 202b around the rotor trajectory.

[0118] Figure 2DThree voltage patterns 401, 501, and 601 are shown, generated by the permanent magnet 106 of the rotor 104 above Hall effect sensors 202a, 202b, and 202c in a three-phase BLDC motor. The sinusoidal variable voltage pattern 401 is generated by the permanent magnet 106 of the rotor 104 above Hall effect sensor 202a. The starting point of 0 degrees is arbitrarily set as the point of maximum voltage. Three complete sinusoidal waveforms are generated during a full 360-degree rotation of the rotor. Voltage pattern 501 is generated by the permanent magnet 106 of the rotor 104 above Hall effect sensor 202b. Furthermore, the substantially noiseless sinusoidal variable voltage pattern 501 is generated by the permanent magnet 106 of the rotor 104 above Hall effect sensor 202b. Because Hall effect sensor 202b is positioned at an arc length of 40 degrees from Hall effect sensor 202a, the phase of sinusoidal pattern 501 is offset by 120 degrees relative to the phase of sinusoidal pattern 401. Furthermore, a substantially noiseless sinusoidal variable voltage pattern 601 is generated by the permanent magnet 106 of the rotor 104 above the Hall effect sensor 202c. Since the Hall effect sensor 202c is positioned at an arc length of 40 degrees from the Hall effect sensor 202b, the phase of the sinusoidal pattern 601 is offset by 120 degrees relative to the phase of the sinusoidal pattern 501. The pattern repeats once every 360 degrees of rotor rotation.

[0119] Since the Hall effect sensors are identical and sense the same edge magnetic field at the same distance, the three voltage patterns 401, 501, and 601 each have substantially the same maximum and minimum peak values. Furthermore, patterns 401, 501, and 601 intersect at multiple points (e.g., points 402, 502, and 602). Notably, the pattern segments between the intersections are essentially straight lines, and it can be seen that these straight line segments provide a continuous sequence of connected straight line segments. Additionally, the zero-crossing point of each straight line segment, as well as the maximum and minimum peak values ​​of each pattern, can be sensed and recorded.

[0120] Figure 2DTwo straight line segments between intersections 402, 502, and 602 are shown. As a non-limiting example, the line segment between intersections 402 and 502 is shown as divided into 20 equal-length segments, which can be conveniently accomplished by sensing the voltage at intersections 402 and 502 and simply dividing them. In this example, since the physical rotation of the rotor from one pattern intersection to another is a 20-degree rotation of the motor, the calculated amount for each voltage change represents 20 / 20, i.e., a rotor rotation of 1.00 degree. This is only a relatively rough example illustrating the method. In some embodiments of the invention, circuitry on PCB 201 senses the intersections and divides them between the intersections using an 11-bit analog-to-digital converter (ADC), providing 2048 counts. In this embodiment, the mechanical rotational movement of rotor 205 is approximately 0.0098 degrees per count. The system resolution can be increased (or decreased) by using an ADC with higher (or lower) bit resolution. For example, an 8-bit ADC can resolve each count to approximately 0.078 degrees, a 16-bit ADC to approximately 0.00031 degrees, and a 20-bit ADC to approximately 0.00002 degrees. Alternatively, increasing or decreasing the number of poles will correspondingly increase or decrease the system's resolution.

[0121] In some embodiments, the present invention provides a high degree of accuracy and precision for the mechanism driven by motor 100. In the non-limiting example described above using an 11-bit ADC, the motor position can be controlled to 0.0098 degrees mechanically. Combined with gear reduction, extremely fine control of the translation and rotation of the mechanism can be achieved. In some embodiments, motor 100 is coupled to a translation drive for an infusion pump unit to draw in and expel fluid during diagnostic procedures.

[0122] Figure 2E This is a diagram depicting a circuit in some embodiments of the invention, which controls motor 100 by using the output of Hall effect sensors and by using a unique method that analyzes only the linear portion of the phase separation curve generated by the sensors, the linear portion being divided into equal segments as described above. The outputs of Hall effect sensors 202a, 202b, and 202c are provided to a proportional-integral-derivative (PID) motion control circuit for commutation purposes, and the waveform generated by the interaction between the rotor magnet and the Hall effect sensors is provided to... Figure 2EThe multiplexer circuit shown is illustrated above. As described above, in a non-limiting exemplary embodiment, an ADC is used to generate a segmentation of the linear portion of the phase-separated waveform of motor 100, and motor 100 can be driven, for example, by a Texas Instruments DRV8313 motor drive circuit. Those skilled in the art will understand that this circuit is not necessarily unique, and will further understand that other circuit arrangements can be used, which also fall within the scope of this invention. In some embodiments, the circuitry for sensing the Hall effect sensor and providing motor encoding instructions can be implemented in a programmable system-on-a-chip (PSSoC) on the PCB. The circuitry may also include torque estimation circuitry, which can be configured to estimate the torque value generated by the motor based on current and voltage measurements acquired at the PSoC, thereby avoiding the need for additional force sensors throughout the larger system.

[0123] 3. Motor torque estimation

[0124] In some implementations, multiple aspects of the BLDC motor 100 and the control circuitry can be used to detect torque without requiring external sensors. This can be achieved in different ways, for example, by estimating the torque based on the principle that the electrical power supplied to the BLDC motor equals the mechanical power extracted from the motor plus the electrical power consumed by the motor (i.e., copper losses), such as... Figure 3A The model is shown. This principle is quantified by the following formula:

[0125]

[0126] The power consumed is calculated from the following formula. :

[0127]

[0128] or ,in

[0129] Referring to the power balance formula above, logically it follows:

[0130]

[0131] The substitution of power variables leads to the following equilibrium formula:

[0132]

[0133] Therefore, solving for the motor torque The results are as follows:

[0134]

[0135] Therefore, there are two possible solutions for calculating the motor torque here, one of which uses the bridge current. The most positive and most negative torque solutions generated by the above formulas are shown below:

[0136] as well as

[0137] Considering that torque can be calculated based on motor constants and other variables, motor constants can also be used. To calculate motor torque, such as Figure 3B and Figure 3C The motor model shown is illustrated.

[0138] ,in,

[0139] Therefore, the closest calculated (use ) calculation solution or The solution is assumed to be correct. The following table defines the variables mentioned above.

[0140]

[0141] The principles described above can be used to estimate torque values ​​based on readily available current and voltage measurements, which can be achieved using low-cost programmable system-on-chip integrated circuits (such as PSoC® circuits from Cypress Semiconductor). Additional variables (such as friction) and, for example, cogging effects caused by harmonic disturbance torques through the use of Kalman filters can be considered. As those skilled in the art will understand, the advantage of using low-cost and simple integrated circuits for torque estimation is a significant one compared to existing devices that rely on sensors (pressure sensors, encoders, etc.) to provide device feedback, thereby reducing the number of components required and the cost of the entire system. This advantage is greatly realized when torque sensing is used to trigger commands, as described below in the door opening and test kit loading, syringe driving, and valve driving subsystems.

[0142] 4. Door opening and test kit loading subsystem

[0143] On the other hand, the present invention provides an opening / closing door and test kit loading subsystem driven by a reversible drive mechanism to facilitate manual loading and unloading of test kits from and from a diagnostic testing system. In some embodiments, the opening / closing door mechanism and the test kit loading system are integrated to provide coordinated movement such that a reversible drive of the mechanism is typically detected when the user manually pushes the test kit into the system, thereby initiating the closing of the door when the test kit is manually loaded into the open compartment of the system. It will be understood that, as described herein, such a mechanism can be driven by a BLDC motor and can utilize motor torque estimation or various conventional motors and methods known to those skilled in the art. Examples of such a configuration are described in detail below.

[0144] Figure 4A A perspective view of the door opening and test kit loading subsystem 100 is shown. This system includes a brushless direct current (BLDC) motor 100 mounted to PCB 30' as described above. The BLDC motor 100 includes an output shaft (not shown) to which a lead screw 109 is attached. The lead screw 109 is a reversible drive aspect of the transmission mechanism that operates to open and close the door 14 and to power the test kit loading mechanism.

[0145] The lead screw 109 is threadedly engaged with the nut of the bridge 108. Therefore, when the lead screw 109 rotates, the bridge 108 moves upward or downward according to the direction of rotation of the lead screw 109 (e.g., ...). Figure 4A (The orientation of the device is shown in the diagram). The first rack portion 110 and the second rack portion 112 are fixed to the bridge 108. Both rack portions are elongated to include rack 114 and cam channel 116 forming an "L" shaped path.

[0146] A pair of pinions 118 mesh with a rack 114. The up-and-down movement of the rack 114 is caused by the movement of the bridge 108 and the lead screw 109, which causes the pinions 118 to rotate accordingly. The pinions 118 are connected to each other via a common shaft 120, which is supported by a subframe 122 fixed to a larger portion of the system 10 (e.g., the rear frame portion 26). Each pinion 118 includes fingers 124 for stopping the rotation of the pinion 118 at certain interfaces.

[0147] Each pinion 118 is integrated with a larger gate gear 126. Therefore, the pinions 118 and gate gear 126 rotate at the same RPM. The gate gear 126 engages with the rack 128 of the gate 14. Therefore, as the gate gear 126 rotates, the rack 128 and the gate 14 move up and down according to the direction of rotation of the gate gear 126.

[0148] Figures 4B to 4E The method of loading the test kit is depicted graphically. Figure 4BIn this process, a command is sent to the BLDC motor 102 to open the door 14, positioning the system to accept the insertion of the test kit 32. Upon receiving the command, the system 100 operates the BLDC motor 102 to rotate the lead screw 109. This action causes the bridge 108 and the fixed rack portions 110 / 112 to move upward, thus initiating the rotation of the pinion 118 and the gate gear 126. This movement causes the door 14 to move upward as the gate gear 126 rotates relative to the rack 128.

[0149] After door 14 is fully opened, pinion 118 disengages from rack 114 of the first rack portion 110 and the second rack portion 112, which continue to move upward. The upward movement of the first rack portion 110 and the second rack portion 112 also causes the test kit loading arm 130 to be actuated by pin 132, which is constrained to move along cam channels 116 of the first rack portion 110 and the second rack portion 112. This movement forces the test kit loading arm 130 to rotate about pivot 134, which positions the first arm portion 136 in the upward position.

[0150] The first rack portion 110 and the second rack portion 112 will move upward until a force-based event occurs that reverses the drive lead screw 109. Such an event could be, for example, the bridge 108 encountering a stop or the first rack portion 110 and the second rack portion 112 pulling the test kit loading arm 130. The reverse drive event can be detected as a change in current at the bridge circuit of the BLDC motor. Based on the reverse drive event, the BLDC motor is commanded to stop rotating and stop at the indicated position. Advantageously, this step is performed without the assistance of any position sensor.

[0151] exist Figure 4C In this process, the test kit 32 is inserted into the system 10 until a portion of the test kit 32 contacts the first arm portion 136. Slight movement against the first arm portion 136 causes another reverse drive event at the lead screw 109, which can be detected as a change in current at the bridge circuit of the BLDC motor. This event serves as a command for the BLDC motor to reverse the direction of the aforementioned door-opening step, in order to capture the test kit and close the door.

[0152] like Figure 4DAs shown, the upward movement of the first rack portion 110 and the second rack portion 112 causes the pin 132 to be guided along the length of the cam channel, which in turn causes the test kit loading arm 130 to rotate clockwise. This causes the second arm portion 138 of the test kit loading arm 130 to push the test kit inward into its original position. Additionally, the first rack portion 110 and the second rack portion 112 are raised until the fingers 124 of the pinion 118 rotate through the notches 140 of the first rack portion 110 and the second rack portion 112, causing the pinion 118 to move relative to the rack 114 and the gate gear 120 to move relative to the gate rack 128. In this way, the door 14 is moved downward to the closed position.

[0153] like Figure 4E As shown, the door 14 is moved downwards to fully close by the continued movement of the lead screw 109. The BLDC motor is powered to perform this operation until a force-based event occurs that reverses the drive of the lead screw 109. Such an event could be, for example, the bridge 108 encountering a stop or the first rack portion 110 and the second rack portion 112 pushing the test kit loading arm 130. The reverse drive event can be detected as a change in current at the bridge circuit of the BLDC motor. Based on the detection of the reverse drive event, the BLDC motor is commanded to stop rotating and stop at the position shown. Advantageously, this step is performed without the assistance of any position sensor.

[0154] 5. Syringe drive subsystem

[0155] As described above, embodiments of the present invention may include multiple aspects of the syringe driving mechanism 16. For example... Figure 5A As shown, the syringe drive mechanism 16 includes a BLDC motor 200 as described above. The BLDC motor 200 includes an output shaft connected to a reversibly driveable lead screw 209.

[0156] The lateral extension arm 206 includes a nut threadedly connected to the lead screw 209. The lateral extension arm 206 is also secured to the plunger rod 208. The lateral extension arm 206 and the plunger rod 208 can be driven downward and upward by commanding the BLDC motor 200 to rotate the lead screw 209 in the appropriate direction.

[0157] After the test cartridge 32 is secured and the door 14 is closed, the syringe drive mechanism 16 can be used to interface with the test cartridge 32. The test cartridge includes a syringe channel 210 that holds the plunger head 212. Moving the plunger rod 208 downward into the syringe channel 210 causes the head of the plunger rod 208 to engage the plunger head 212. In this way, the combined plunger head 212 and plunger rod 208, together with the syringe channel, function as a syringe to pressurize / depressurize the test cartridge 32. Programmed pumping of the test cartridge 32 allows fluid to flow into and out of the various chambers of the test cartridge 32 for testing.

[0158] After engagement with the plunger head 212, the plunger rod 208 can be actuated by the BLDC motor 200 to any desired position within the syringe channel 210, including for implementing various syringe pumping algorithms. The current of the BLDC motor 200 can be continuously monitored to provide consistent pressure to the plunger rod, thus reducing the need for an in-line pressure sensor to monitor the pressure of the test kit.

[0159] Therefore, because the lead screw 209 can be reverse-driven, a pressure decrease within the test chamber 32 can cause the stationary plunger rod 208 to be pulled downwards. The pressure decrease can be detected by monitoring the measuring current of the BLDC motor 200, detecting the relative change, and then accordingly changing the output of the BLDC motor 200. Similarly, a pressure decrease within the test chamber 32 can cause the stationary plunger rod 210 to be pushed upwards. An increase in pressure can be detected by monitoring the measuring current of the BLDC motor 200, detecting the relative change, and then accordingly changing the output of the BLDC motor 200. Advantageously, this can be performed without the aid of any pressure sensor.

[0160] In another example, the current associated with the moving plunger rod 208 can be monitored to detect changes indicating an increase or decrease in the pressure rate. Therefore, upon detecting a relative change, the output of the BLDC motor 200 can be altered to increase or decrease the pressure rate applied by the moving plunger rod 208. Advantageously, this can be performed without the aid of any pressure sensor.

[0161] Figure 5B The diagram illustrates an example of method 220 for determining the appropriate load for a test kit and testing its integrity using the aforementioned BLDC current monitoring principle. It is assumed that test kit 32 has already been... Figure 5A The physical loading is shown.

[0162] At operation 222, a command is sent to begin the loading process. As a result, an overforce limit is set at operation 224. The overforce limit is the maximum force that the BLDC motor 200 can apply to the plunger rod 208 for this operational purpose, which is associated with the plunger rod 208 abutting against the bottom of the syringe channel 210 to compress the plunger head 212. At operation 226, the BLDC motor 200 is operated to move the plunger rod 208 into the syringe channel 210, causing the head of the plunger rod 208 to engage the plunger head 212. At operation 228, using... Figure 2E Torque estimation circuit and Figures 3A to 3CThe method continuously monitors the torque of the BLDC motor 200 to determine whether the plunger rod 208 has traveled to the bottom of the syringe channel 210. If the over-force limit is not exceeded, the loading process is determined to have failed at operation 230. Sometimes, the plunger head 212 may be missing due to manufacturing errors or physical defects. In either case, the plunger rod 208 will meet at the end of the possible stroke within the syringe channel 210 without the bottom properly abutting against the plunger head 212, and therefore will not exceed the over-force limit.

[0163] If the overforce limit is exceeded, it is determined that the plunger rod 208 has pushed the plunger head 212 to the bottom of the syringe channel 210, and method 220 moves to operation 232, where an underforce limit is set. The underforce limit is the maximum force that the BLDC motor 200 can apply to the plunger rod 210 for this operational purpose, which is related to depressurizing the plunger head 212. At operation 234, the BLDC motor 200 is operated to move the plunger rod 210 upward within the syringe channel 210. At operation 236, the torque of the BLDC motor 200 is continuously monitored to determine if the underforce limit has been exceeded. As a result of operation 228, the plunger head 212 will be highly compressed. The underforce limit is the amount of force required to depressurize the plunger head, thereby zeroing the position of the plunger head 212 for subsequent operations. Once the underforce limit is exceeded, the BLDC motor 200 will stop operating, and the method will move to operation 238, where it is determined whether the syringe has been evacuated. In this operation, the valve of the test kit 32 is operated to seal the syringe passage 210 and isolate it from the atmosphere, which was not the case in the preceding steps. After this, the BLDC motor 200 is operated to pull the plunger rod 208 upward against the vacuum within the syringe passage 210. If the plunger rod 208 cannot move freely and a force is detected, it is determined at operation 240 that a vacuum has been established and therefore the integrity of the test kit 32 is undamaged. If the plunger rod 208 moves freely without a detected force, it is determined at operation 242 that a vacuum has not been established and therefore the integrity of the test kit 32 is compromised.

[0164] Figure 5C Another example of method 248 for determining the initialization of the syringe (i.e., plunger rod 208, syringe channel 210, and plunger head 212) of the test kit using the aforementioned BLDC current monitoring principle is shown. Assume the test kit 32 is as follows: Figure 5A As shown, it has been physically loaded, and the box is as follows: Figure 5B The image shown has been properly loaded.

[0165] At operation 250, a command is sent to begin the loading process. As a result, an upper limit force is set at operation 252. The upper limit force is the maximum force that the BLDC motor 200 can apply to the plunger rod 208 for this operational purpose, which is the maximum force that is applied when the plunger head 212 is positioned at the top of the syringe channel 210 (relative to...). Figure 5A (The orientation of the device shown is associated with this).

[0166] At operation 254, the BLDC motor 200 is operated to move the plunger rod 208 upward within the syringe channel 210, causing the plunger head 212 to reach its apex position within the syringe channel 210. At operation 256, using Figure 2E Torque estimation circuit and Figures 3A to 3C The methodology continuously monitors the torque of the BLDC motor 200.

[0167] Once the overforce limit is exceeded, it is determined that the plunger head 212 has reached its apex, and method 248 moves to operation 258, where a lower lower limit force is set. The lower limit force is the maximum force that the BLDC motor 200 can apply to the plunger rod 210 for this operational purpose, which relates to positioning the plunger head 212 against the bottom of the syringe channel 210 without excessively compressing the plunger head 212. At operation 260, the BLDC motor 200 is operated to move the plunger rod 210 downward within the syringe channel 210. At operation 262, the torque of the BLDC motor 200 is continuously monitored to determine if the lower limit force set at operation 258 has been exceeded. Once the lower limit force is exceeded, the BLDC motor 200 stops operating, and it is assumed that the plunger head 212 has been positioned at the bottom of the syringe channel 210. After this, method 248 moves to operation 238, where it is determined whether the syringe has moved a predetermined distance (e.g., 60 mm). This is performed by counting the revolutions of the lead screw 209 using a Hall effect sensor of the BLDC motor 200 and correlating that count with the linear travel of the syringe rod 208. In some cases, upper and lower limits may be triggered by obstructions or excessive friction within the syringe channel 210. Therefore, a stroke check step is performed to ensure that the syringe rod 208 can move freely without obstruction. If the syringe rod 208 has traveled at least the predetermined amount of stroke, initialization is determined to be successful at operation 266. However, if the syringe rod 208 has not traveled at least the predetermined amount of stroke, initialization is determined to be unsuccessful at operation 268.

[0168] 6. Valve Actuation Subsystem

[0169] As described above, embodiments of the present invention may include multiple aspects of the valve actuation mechanism 20. For example... Figure 6A and Figure 6BAs shown, the valve drive mechanism 20 includes the BLDC motor 300 as described above.

[0170] The BLDC motor 300 is mounted on a base frame 304, which has multiple reinforcing ribs 306 that contribute to its rigidity. The base frame 304 includes an elongated first portion 307 that serves as a mounting base for the stator 308 of the BLDC motor 300. An elongated shaft 310 extends from the BLDC motor 300 and holds a first worm gear 312. The first worm gear 312 engages with and rotates a first worm wheel 314, which rotates on a shaft 316 shared with a second worm gear 318.

[0171] The second worm gear 318 engages with and rotates the second worm wheel 320. The second worm wheel 320 is integrated with a rotary valve actuator 322, which is configured to cooperate with the rotary valve mechanism of the test kit 32. The valve actuator 322 is mounted to the elongated second portion 324 of the base frame 304. The elongated second portion 324 includes a channel 325 for cooperation with the ultrasonic horn mechanism 22.

[0172] In operation, the BLDC motor 300 is powered to rotate, which in turn rotates the valve actuator 322 via the aforementioned worm gear drive. The valve actuator 322 is essentially decelerated, which allows for high precision in positioning the valve actuator 322. The syringe drive mechanism 16 does not include any position sensor because the angular position of the stator 308 can be derived solely from the sine wave output of the Hall effect sensor and, by knowing the final drive gear ratio, from that position of the valve actuator.

[0173] Worm gear drives cannot be reverse-driven as in the syringe drive and door drive mechanisms described above. However, the same type of Hall effect position derivation and force-based triggering can be used for valve drive mechanisms. Here, force-based triggering can indicate a failure in the integrity of the test cartridge. For example, if unexpectedly turning the valve actuator requires substantially less or more power, such an event can indicate a blockage or malfunction in the test cartridge. While each of the syringe drive, door drive, and valve drive mechanisms is described using the improved BLDC motor described herein, it is understood that any or all of the actuators and drive mechanisms can also utilize conventional types of BLDC motors, servo motors, or other suitable motors as will be understood by those skilled in the art, although some features may require additional sensors or circuitry.

[0174] Furthermore, by executing a centering protocol based on a sinusoidal signal generated by a Hall effect sensor, the BLDC motor is configured to the original and center positions of the valve drive output. This compensates for gear backlash and gear wear over time. Figure 6CThe Hall voltage signal-valve actuation position diagram is shown below. As shown, the given position of valve actuator 322 can vary depending on gear backlash and wear.

[0175] 7. Speaker assembly

[0176] In some embodiments, an ultrasonic horn subassembly is provided for use in the diagnostic testing system described herein. In some embodiments, the ultrasonic horn assembly includes an ultrasonic horn, a horn housing, a spring, a base, and control circuitry configured to operate the horn. The horn housing is adapted to support and secure the ultrasonic horn and includes portions for retaining the spring coil to facilitate movement between horn-disengaged and horn-engaged positions, and wedges for interfacing with a cam mechanism of the system to actuate the horn between disengaged (lowered) and engaged (raised) positions. While a helical spring is described herein, it should be understood that various other types of springs or biasing mechanisms may be used. In the disengaged position, the tip of the ultrasonic horn is flush with or lower than the base surface where the test cartridge is located to facilitate loading and removal of the test cartridge from the system. In the engaged position, the tip of the ultrasonic horn extends above the base surface to engage the dome portion of the ultrasonication chamber of the test cartridge to facilitate ultrasonication of biological material in the fluid sample contained within the ultrasonication chamber during sample analysis preparation and / or processing. In some embodiments, horn movement is achieved by an actuator mechanism shared with one or more other movable parts of the system, such as doors of the system. The speaker assembly also includes circuitry (e.g., a printed circuit board) with an interface adapted to be electrically connected to a corresponding circuitry within the system to allow the system to operate the ultrasonic speaker.

[0177] In some implementations, the diagnostic testing system is placed upright during the testing process (e.g., Figures 9A to 9B As shown), the horn moves between a separated position (lowered below the test kit) and an engaged position (raised towards the test kit) to engage and contact the ultrasound processing chamber of the test kit. It is understood that in some embodiments, the design can be different, and thus, depending on the design of the test kit and the diagnostic testing system, the horn can be in various other orientations and / or positions relative to the test kit in the separated and engaged positions.

[0178] 7.A. Design and assembly of the horn component

[0179] Figure 7A An ultrasonic horn sub-assembly 700 configured for use in a diagnostic laboratory system is shown according to some embodiments of the present invention. Figure 7B Depicting Figure 7AAn exploded view of the horn assembly. In this embodiment, the horn sub-assembly includes an ultrasonic horn 710, a horn housing 720, a spring coil 730, a control circuit 740, and a base frame 750. The horn sub-assembly can be tested as a separate sub-assembly before being inserted into the system, and can also be removed or replaced as needed.

[0180] Figures 8A to 8D The components of the horn assembly are shown during the various stages of assembly. For example... Figure 8A As shown, the ultrasonic horn 710 is snapped into the horn housing 720 (the horn housing 720 is shown cut away to show the horn residing therein). The housing can be designed such that snapping the horn into the housing positions or locks the horn within a predetermined orientation and position relative to the housing. For example, the ultrasonic horn can be designed to include features that are not perfectly axisymmetric about the longitudinal axis of the horn, such that corresponding features or surfaces on the internal portion of the housing engage to secure the horn in the proper position within the housing and prevent the horn from rotating within the housing. Non-axisymmetric features may include, but are not limited to, flat portions on one or both sides of the horn, protrusions or tabs extending outward from the horn, or contacts through which the horn is electrically connected.

[0181] In some implementations, the horn 720 is integrated into a sub-assembly and controlled by control circuitry to provide an output suitable for lysing biological material required for a specific assay.

[0182] from Figure 8A As can be seen, the outer surface of the horn housing 720 includes a spring retaining portion 722 for retaining the spring coil 730 to allow movement of the housing 720 between a disengaged position and an engaged position. The retaining portion includes an upper retaining surface 722a and a lower retaining surface 722b, which engage with the spring when in a non-compressed state. The housing 720 may also include one or more wire retainers 723 to secure and / or guide wires electrically connected to the horn 710 during movement of the horn between the disengaged and engaged positions. The horn housing 720 includes a wedge-shaped portion 721 for engagement with a cam in the system.

[0183] like Figure 8CAs shown, a partially assembled speaker assembly can snap into a speaker base 750. The base includes a positioning feature 751 that engages a corresponding feature of the housing 720 to secure the position and orientation of the housing when snapped into place. The base also includes one or more features for securing the entire speaker assembly 700 within the diagnostic testing system; for example, the base may include a base portion having one or more holes through which the base can be mounted to a module. In some embodiments, the base is formed from a polymer material by injection molding; however, it is understood that it can be formed from a variety of other materials (e.g., polymers, ceramics, metals) using a variety of other manufacturing processes (e.g., pressing, machining, etc.). After the speaker assembly is placed in the base, circuit components 740 are attached to the base. The base may include one or more mounting features 752a through which circuit components (e.g., a PCB) can be secured via one or more fasteners or screws 752b. The circuit components may be electrically connected to the speaker before or after they are attached to the base. The completed speaker assembly 700 can then be tested and provided to the user individually or within the diagnostic testing system.

[0184] 7.B Ultrasonic horn positioning interface

[0185] In some embodiments, the ultrasonic horn is mounted on a movable mechanism, through which the ultrasonic horn is positioned relative to the ultrasonic processing chamber of a test cartridge disposed within the diagnostic testing system. In some implementations, the test cartridge includes a portion located at the bottom of the cartridge (e.g., Figure 10A The ultrasound processing chamber is a (centrally oriented) structure with a downward-facing dome (the outer surface of the dome is convex relative to the test chamber), such as... Figure 10AAs shown in the example, this corresponds to the circular tip 711A of the dome-shaped output portion 711 of the ultrasonic horn. Although the tip is circular in this embodiment, it is understood that the tip of the dome portion can be shaped in various ways as needed, including but not limited to flat, pointed, concave, convex, round, or dome-shaped. The dome-shaped portion of the ultrasonic processing chamber and the circular horn tip concentrates the ultrasonic energy transmitted from the horn to effectively achieve the desired ultrasonic levels required for lysing cellular material (e.g., enhanced cells, spores, etc.) and releasing DNA into fluid samples with minimal ultrasonic horn power and size requirements. For the circular tip 711a of the dome-shaped output portion 711 of the ultrasonic horn, it is preferable to press it against the dome 1211 of the ultrasonic processing chamber 1210 with sufficient force to ensure that the tip of the horn remains in contact with the dome-shaped surface of the ultrasonic processing chamber during the delivery of ultrasonic energy. In some embodiments, the movable mechanism is configured to move the ultrasonic horn upward (along the engagement direction) to press the dome of the ultrasonic processing chamber and the ultrasonic horn together with a force of at least 0.5 pounds. In some embodiments, the force applied to ensure engagement between the circular tip of the horn and the dome portion of the ultrasonic processing chamber is between approximately 1 pound and approximately 2 pounds. In some embodiments, the applied force is approximately 1.4 pounds. Although the interface connection cam and wedge are described herein, it should be understood that various other mechanisms, with or without biasing members, can be used to facilitate movement of the horn between a disengaged and engaged position. For example, in some embodiments, such a mechanism may include a lead screw, cable, etc.

[0186] In some implementations, the movable mechanism used to position the ultrasonic horn against the ultrasonic processing chamber is integrated within an interconnect network of actuators that enable movement of various other components of the diagnostic testing system, such as opening and closing system doors, loading and discharging test kits from the system, and movement of valve assemblies and syringe assemblies within the system. It is understood that the movable mechanism may be integrated with actuators of one or more other components, or it may be completely independent of other mechanisms and actuators.

[0187] Figures 9A to 9B The diagram shows a cross-sectional view of the diagnostic testing system during and after the loading of the test kit into the system, illustrating the mechanism for positioning the ultrasonic horn in conjunction with closing the system door and loading the test kit. Figure 9A A partially inserted test kit 32 is depicted, wherein the distally facing portion of the base of the test kit begins to engage with the discharge teeth of the discharge / loading cam 1120. In this position, the outer surface of the cam 1120 engages with the upper surface 721 of the wedge-shaped portion 721 of the horn housing, as can be seen... Figure 11A-1 and Figure 11A-2 This can be seen in more detail in the side view and cross-section.

[0188] As the test kit 32 is inserted more fully, the test kit presses against the discharge teeth, and the discharge / loading cam 1120 rotates clockwise, causing the loading teeth of the cam to engage with the lower surface of the test kit, pulling the test kit inward to the fully loaded position. As the discharge / loading cam 120 rotates, the outer surface 1121 of the cam slides along the wedge tip 721a of the wedge portion 721 of the horn housing slide member, pushing the horn housing away from the test kit to the disengaged position, thereby partially compressing the spring coil 730. When the test kit is fully inserted, the wedge tip 721a is received within the inwardly curved portion 1121a of the circular portion of the cam 1120, which allows the horn housing 720 to move upward a short distance, thereby allowing the coil to be at least partially decompressed, causing the circular tip 711a of the ultrasonic horn to protrude above the surface along which the test kit is loaded and press-fit into the dome-shaped portion of the ultrasonic processing chamber. This position can be achieved in... Figure 11B-1 and Figure 11B-2 This can be seen in more detail in the side views and cross-sectional views. For example, it can be seen from... Figure 9A and Figure 9B As can be seen, the rotation of cam 120 is actuated by the closing movement of the first rack portion 110 of the rack mechanism, which in this embodiment moves downward (in the direction of the arrow). Through an interconnected network of gears, this closing movement of the door after the test kit is inserted also simultaneously actuates the door 100 of system 1000 from... Figure 9A The open position of the test kit 32 is actuated to the closed position for easy insertion and loading, such as... Figure 9B As shown. The movement of the rack and pinion mechanism can be achieved by one or more motors, such as any of the motors described herein.

[0189] Figure 10AA cross-sectional view of a test cartridge for a diagnostic testing system according to some embodiments of the present invention is shown. As described above, the dome-shaped portion 1211 of the ultrasonic processing chamber 1210 is located on the bottom surface of the test cartridge. The ultrasonic processing chamber 1210 is in fluid communication with a network of channels in the test cartridge through which fluid is delivered via valves and the movement of a syringe to achieve pressure changes during the testing process. After sample preparation and / or processing, the prepared fluid sample is delivered to a chamber of a reaction vessel 33 while an excitation device and an optical detection device are used to optically sense the presence or absence of a target analyte of interest (e.g., nucleic acid) (e.g., bacteria, viruses, pathogens, toxins, or other target analytes). It will be understood that such a reaction vessel may include various different chambers, conduits, or micropore arrays for detecting the target analyte. Exemplary uses of such a reaction vessel for analyzing fluid samples are described in commonly assigned U.S. Patent No. 6,818,185, filed May 30, 2000, entitled “Cartridge for Conducting a Chemical Reaction,” the entire contents of which are incorporated herein by reference for all purposes.

[0190] 7.C Ultrasonic Speaker Control

[0191] In some embodiments, operation of the ultrasonic horn is performed using a horn control circuit configured to control the current amplitude and phase estimation in an optimized excitation manner according to the needs of a specific assay, and to provide a consistent and robust delivery of ultrasonic power proportional to the current at a fixed voltage. In some embodiments, the system provides fully digital control of the ultrasonic power delivery. In some embodiments, the system provides operation of the ultrasonic horn without conventional transformers and full-wave rectification analog circuitry, thereby allowing for reduced power consumption, smaller horn assembly size, and an overall reduction in system size. In some embodiments, power delivery and control are performed to control the active power (which is the total power) entering the ultrasonic horn (as opposed to reactive power). The control circuitry is configured to apply programmable ultrasonic power to the assay chamber for a programmable duration to lyse target cells according to the needs of a specific assay.

[0192] In some implementations (e.g., see reference) Figure 12AThe ultrasonic horn includes a mass block 713 (typically a solid metal core) adjacent to one or more piezoelectric actuators 714, which vibrates when connected to a power supply 716 via an electrical contact 715. The solid mass block includes a tapered portion 712' leading to an elongated portion 712 that focuses ultrasonic waves and terminates in a dome-shaped output portion 711, which further focuses the ultrasonic waves to output them at its tip 711a. Typically, multiple piezoelectric actuators can be used to provide a larger ultrasonic output with lower relative requirements (compared to a single actuator suitable for delivering higher ultrasonic energy).

[0193] In some implementations, the horn assembly may utilize an off-the-shelf horn with horn control circuitry that operates the horn using closed-loop or feedback control to provide consistent and robust ultrasonic energy at a desired level with a lower relative power requirement than the horn's likely power requirements. For example, such an off-the-shelf horn with multiple piezoelectric actuators, when operated to provide an ultrasonic energy level suitable for lysing cells in a diagnostic assay, may not be able to operate consistently by simply applying a set current level due to out-of-phase actuator operation. When current is applied, the piezoelectric actuators expand outward, and if this outward expansion occurs at even slightly different times (out of phase), the result is low-frequency coupling into the vibration, preventing the horn from delivering the appropriate level of ultrasonic energy. For this reason, such a horn may only operate at lower ultrasonic levels or may not be reliable for providing consistent energy delivery for the duration required in a particular diagnostic assay.

[0194] In some embodiments, the system employs an improved control scheme that allows for the consistent delivery of ultrasound energy levels suitable for lysing cells for a specific duration in diagnostic testing, using the horn as described above. In some embodiments, the horn assembly is configured to apply vibration at a frequency of approximately 50.5 kHz using a resonant piezoelectric actuator. In some embodiments, the horn assembly is configured to apply a vibration frequency in the range of approximately 20 kHz to approximately 50 kHz. For example, the vibration frequency may be approximately 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or approximately 50 kHz. In some embodiments, the vibration frequency is greater than 50 kHz. In some embodiments, the system utilizes a closed-loop control system to provide piezoelectric excitations that remain in phase with each other for the duration required for the sonication of biological materials.

[0195] In some implementations, the system applies current and / or voltage to the piezoelectric actuator by increasing the applied power to a desired level, thereby minimizing the occurrence of out-of-phase excitation. Examples of this approach include... Figure 10B As shown. In some implementations, power delivery and control are performed to control the active power (which is the total power) entering the ultrasonic horn (as opposed to reactive power). By essentially maintaining a specific phase relationship between voltage and current, reactive power is essentially eliminated. Reactive power occurs when the piezoelectric actuator is not in a locked phase and the horn is simply vibrating. By increasing the power, rather than simply turning on the power, increasing the power allows the system to maintain the phase relationship between current and voltage and prevents vibration from causing the horn to deliver the desired level of ultrasonic energy.

[0196] Figure 12B The simulated horn power transfer function is shown, which illustrates the phase relationship between the excitation current and voltage at the power resonance point.

[0197] In some implementations, the horn control circuit uses a closed control loop to operate the horn. In the internal control loop, frequency adjustment maintains the current phase relationship. In the external control loop, the amplitude of the voltage excitation is continuously adjusted to maintain the commanded power level. Examples of these internal and external control loops are provided in... Figure 14 As shown in the image.

[0198] Figure 13 A control schematic diagram of an ultrasonic horn assembly according to some embodiments of the present invention is shown. The ultrasonic processing interface is configured according to the power (watts) and duration (seconds) required for a specific assay. A typical power level of 5-10 watts is applied for 15 to 30 seconds to adequately lyse typical spore cells and release approximately 50% of the spore-bound DNA into the solution within sample chamber 1210, such as... Figure 10B As shown. However, it should be understood that the power, duration, and required sonication efficiency vary from assay to assay and may be greater or less than the levels described, depending on the assay requirements, design, and type of cells or materials being sonicated. In some embodiments, the PSoC DAC generates a sine wave from 0 to 4V. The DAC output passes through a TI audio amplifier. The TI amplifier multiplies the signal by 20dB. The TI-amplified signal passes through a step-up transformer before being sent to the speaker. Power is estimated using the voltage read from the sensor (DAC voltage amplified by the TI and transformer) and the current (P = V). I cos(Φ) (actual power). Therefore, the power delivered to the speaker is controlled by controlling the DAC voltage. The control loop drives the input voltage to maintain the power at the desired level. See, for example... Figure 15 .

[0199] In some implementations, the horn control circuit is configured such that the frequency from which the highest active power amplitude is obtained from the frequency scan is determined as the resonant frequency. The phase between the input and output voltages is measured at the resonant frequency. During ultrasonic processing, the control loop locks the measured phase between the input and output voltages by adjusting the input frequency. The current amplitude is the product of the sensor coefficient and the PSoC amplifier, which amplifies the signal before reading it. An exemplary relationship between power and input voltage can be obtained from... Figure 16 I saw it in [the context]. Figure 17 The diagram shows an exemplary relationship between the horn current amplitude and phase and frequency.

[0200] In some embodiments, the horn control circuit utilizes sinusoidal control to regulate the amplitude input to the horn driver. This circuit can employ phase matching for resonant frequency control to ensure that the voltage and current maintain a specific phase relationship, which can be used, for example, to eliminate reactive power. In some embodiments, the circuit utilizes a frequency sweep with a 1 Hz resolution; however, it is understood that this configuration can effectively provide virtually unlimited frequency resolution. This configuration allows for the delivery of consistent and robust ultrasonic energy levels using an ultrasonic horn with lower power and size requirements than is possible for such a device.

[0201] 8. Thermo-optical sub-assemblies

[0202] In some embodiments, the present invention provides a thermo-optical sub-assembly (TOS) for a diagnostic testing system. In some embodiments, the TOS includes a thermal control component and an optical excitation / detection component. The TOS can interface with other components of the diagnostic testing system, including ultrasonic horns, doors, syringes, and valves. In some embodiments, the TOS includes a thermal control instrument and an optical component instrument with excitation and optical detection components. The TOS unit is configured to define a cavity into which a reaction vessel can be inserted to perform nucleic acid amplification and / or detection of a target analyte using the thermal control component and to perform optical interrogation of the target analyte using the optical component instrument. The TOS is used in a system having one or more circuit boards (e.g., a motherboard) that control the operation and coordination between various components of the testing system. In some embodiments, the CellCore is mounted on the motherboard. In some embodiments, each hardware sub-assembly carries its own dedicated PSoC processor and associated electronics. In some embodiments, the diagnostic testing system includes communication devices (e.g., wireless, NFC, USB) that allow modification and / or updating of the control software or control parameters used by the system. The TOS may also include one or more sensors (e.g., an NFC reader) to determine the location or presence of the test kit or valve assembly to coordinate the operation of multiple components of the system. In some embodiments, the TOS includes a test kit position sensor (e.g., an NFC reader) physically located on the TOS to allow it to be physically close to the test kit when inserted into the diagnostic testing system. In some embodiments, the TOS can be cascaded with other electronic subsystems via USB and / or a wireless interface such as NFC or Bluetooth.

[0203] 8. A TOS Design

[0204] It should be understood that the thermal control device and optical detection device can be defined in various configurations as needed. In the embodiments described herein, the thermal control and optical detection devices are configured for use with a reaction vessel having two opposing main surfaces and two edges (auxiliary surfaces). The thermal control device can be configured for unilateral heating of one main surface of the reaction vessel or bilateral heating of both main surfaces. In the embodiments described herein, the thermal control device is configured to be positioned adjacent to one or both main surfaces of the reaction vessel. Similarly, the optical detection device can be configured according to various configurations, such as optical detection from the main surface of the reaction vessel or from one or more edges (auxiliary surfaces) of the reaction vessel. Typically, the optical detection configuration corresponds to the configuration of the thermal control device; for example, the optical detection device is positioned to detect optics through portions of the reaction vessel not covered by the thermal control device. In some embodiments, when using unilateral heating, the opposing unheated main surfaces can be covered with a transparent insulating material to control heat transfer while still allowing optical detection through the insulating material. In some embodiments, the system utilizes a thermal control device configured for unilateral heating and an optical detection device configured for excitation / detection from the main surface and / or one or more edges (auxiliary surfaces) of the reaction vessel. In other embodiments, the system utilizes a thermal control device configured for bilateral heating and an optical detection device configured for optical excitation / detection from one or more edges of the reaction vessel. Exemplary configurations are provided below.

[0205] Figure 18 An exemplary diagnostic testing system 1000 is shown for performing detection of a target analyte in a fluid sample prepared within a disposable test kit (not shown) when inserted into a disposable test kit system. As described herein, the diagnostic testing system 1000 includes multiple components and sub-assemblies, one of which is a TOS sub-assembly 1100. Figure 18 As shown, the TOS 1100 sub-assembly can be installed from the front of the system. The TOS can be inserted into the frame or housing of the system 1000 with door 14 open and secured with one or more screws (not shown) such that the front panel 1110 faces the receiving compartment of the system's test kit. The front panel 1110 defines a cavity opening or slot 1111 through which the planar reaction vessel of the test kit can be inserted. In some embodiments, the TOS can be tested as a separate sub-assembly before insertion into the diagnostic testing system. In some embodiments, the TOS can be removed or replaced as needed.

[0206] In some implementations, the diagnostic testing system uses disposable test kits. Exemplary test kits suitable for the systems described herein are described in U.S. Patent No. 6,818,185, filed May 30, 2000, entitled “Cartridge for Conducting a Chemical Reaction,” the entire contents of which are incorporated herein by reference for all purposes.

[0207] In some embodiments, the TOS slot 1111 and cavity are sized to accommodate the reaction vessel (typically within + / - 0.020 inches), and the optical mounts and associated components are adapted to position the optical components relative to the reaction vessel to facilitate the excitation and optical detection of the target analyte. In some embodiments, the TOS is spatially configured to position a thermal control device, such as a dual TEC device, relative to the reaction vessel to control and facilitate thermal circulation of the fluid sample within the reaction vessel of the assay kit. In some embodiments, the TOS moves the thermal control device, for example, retracting the dual TEC before insertion into the reaction vessel, and then engaging and clamping the dual TEC to the reaction vessel when it is in place.

[0208] Figures 19A to 19B A front view and a rear view of an exemplary TOS sub-component 1100 according to some embodiments of the present invention are shown. Figure 19A In the example, the reaction vessel 33 is shown inserted into the cavity opening 1111 of the front panel 1110, and the thermal control bracket / heat sink 820 and the cooling fan 822 can be seen (see [reference]). Figure 20B ).exist Figure 19B In the image, a robust flexible PCB configuration and a thermal contact mechanism 840 can be seen that allow the thermal control device to move laterally before clamping and engaging the reaction vessel 33. The thermal control device 800 and the optical component 900 are connected via their powered and controlled PCBs 830 and 831 through a robust flexible connector 832 that allows lateral movement. The thermal contact mechanism 840 includes an open configuration (see [link to image]). Figure 24B ) and clamping configuration (see Figure 24AA sliding component that translates between the optical component 900 and the reaction vessel 33 engages the side of the thermal control device's TEC surface 810 in a clamping configuration. In some embodiments, the thermal contact mechanism 840 includes a movable and / or adjustable bracket 842 that can slide up and down along a vertically extending mounting member 844 to ensure proper alignment with the optical component 900 and the reaction vessel, and can move laterally toward the thermal control device to ensure proper thermal contact with the reaction vessel 33 to facilitate effective thermal circulation. In some embodiments, the thermal contact mechanism 840 includes a bottom support or guide 846 to facilitate insertion of the reaction vessel into the thermal contact mechanism 840. And in some embodiments, this movement is achieved by the axial movement of the gate drive rack 110, such as... Figure 26A and Figure 26B As shown.

[0209] Figures 20A to 20B An exploded view of an exemplary TOS according to some embodiments of the present invention is shown. It can be seen that the TOS assembly includes an optical mount 930 with a window through which the excitation component 910 and the optical detection component 920 can be operated when assembled. The optical mount is attached to the front plate 1110 via a bracket 1113 and at least partially surrounds a flange 1112 around the reaction vessel opening 1111. A thermal control device 800 is coupled to the optical mount 930 via two pins 834 extending through a thermal contact mechanism 840 and through two holes in the optical mount 930. The assembly may also include a sensor for detecting the proximity or identification of a test kit within the system. In some embodiments, the sensor is a near-field communication (NFC) sensor 1190, but it should be understood that various other sensors may be used. It is understood that in some embodiments, NFC can be suitable for detecting a variety of different things, including but not limited to: the location / presence of the test kit, the type of test kit, a specific test, microfluidic processes unique to a specific test, the presence of a mobile device (e.g., a PDA), and various other specific parameters. In some implementations, NFC allows for workflows associated with specific systems / kits, thereby avoiding the need for diagnostic testing systems to otherwise have to access separate databases in the cloud. This feature is particularly useful in resource-constrained settings where internet access may be unavailable.

[0210] Figures 21A to 21B The optical components and associated PCB of an exemplary TOS according to some embodiments of the present invention are shown. The optical components include an excitation assembly 910, an optical detection assembly 920, and associated PCB components 830, 831, and circuitry 833. In some embodiments, the PCB is connected by a robust flexible connector 832 that allows the thermal control device to move laterally relative to the reaction vessel. Figures 22A to 22BAn associated PCB and thermal control device component with a robust flexible connector is shown in an exemplary TOS. Figures 23A to 23B A thermal control device 800 is shown prior to attachment to an optical mount 930 of an exemplary TOS. In some embodiments, the optical mount 930 includes alignment features 931 to ensure proper alignment between the optical component 900 and the reaction chamber portion of the reaction vessel 33. Alignment features may include one or more features that engage with corresponding features of the reaction vessel, such as a hole receiving a distal extension pin of a reaction tube, a bump or ridge engaging a corresponding recess of the reaction vessel, a pair of magnets, or any suitable feature facilitating alignment between the reaction vessel and the optical component 900.

[0211] Figures 24A to 24B and Figure 25 A thermal control device component movably coupled to an optical mount and a sliding base is shown according to some embodiments of the invention. In some embodiments, the thermal control mechanism 840 presses against the reaction vessel of the engagement test kit. In some embodiments, the force applied to engage the thermal control device with the reaction vessel is at least 1 pound. In some embodiments, the amount of force used is between 1 pound and 3 pounds, typically clamping at about 1.3 pounds to ensure that the TEC surface remains parallel and in full contact with the main surface of the reaction vessel 33. Figures 26A to 26B The operation of the gear rack 110, which enables the thermal control device to move laterally between the clamped and open positions, is shown (see respective diagrams). Figure 24A , Figure 24B ).

[0212] Figure 28 A schematic diagram of an optical module and thermal module assembly 810 of a TOS according to some embodiments of the present invention is shown. The optical module includes a detection block chip or detection component 920 and an excitation block chip or excitation component 910 disposed on a PCB carrier. Figure 28 An exemplary TOS is shown for use in the diagnostic testing system disclosed herein.

[0213] 8.B Optical Components

[0214] Figure 30A An exemplary optical component configuration for use with the diagnostic testing system disclosed herein is shown. Figure 30BDetailed schematic diagrams of exemplary optical component configurations according to some embodiments of the present invention are illustrated. In some embodiments, the optical excitation and detection device operates via a secondary face (edge) of the reaction vessel of the assay chamber, while a thermal control device engages one or more opposing primary faces of the reaction vessel. In some embodiments, the thermal control device component is thermally engaged on one side of the primary face of the reaction vessel. In some embodiments, the thermal control device component is thermally engaged on both sides of the primary faces of the reaction vessel. The latter configuration may be particularly useful for heating and cooling larger fluid sample volumes. Such a configuration may use a ceramic plate heater for heating and passive cooling (e.g., ambient air blown across the ceramic heater) to achieve thermal circulation of the fluid in the reaction vessel or may include any TEC configuration described herein.

[0215] According to some embodiments of the present invention, a miniaturized LED excitation chip can excite a fluid sample through the secondary edge of the reaction vessel, while a miniaturized detection chip collects fluorescence through the main surface of the reaction vessel 33, as if... Figure 30B The configuration shown. Additionally, the dual-TEC design provides controlled heating and cooling through opposing surfaces, offering improved temperature control compared to passive cooling used in some thermal cycling devices. In some reaction vessels, for example... Figure 30A The configuration in this case features a narrow edge viewing window (approximately 1.0mm × 4.5mm), and this small size makes traditional lens operation difficult. For example... Figure 30B As shown, collecting fluorescence from the main surface of the reaction vessel provides a larger detection window, allowing for the collection of more signal while still ensuring that excitation and detection are orthogonal to each other. In some embodiments, the size of the optical detection chip is designed to match the size of the reaction vessel. Figure 30C Detailed views of each of exemplary excitation and detection blocks according to some embodiments of the present invention are shown. As shown, excitation block 910 includes an LED light source 911 that guides light through a filter and lens 912, and then through a rod lens 913, thereby emitting light of a desired wavelength to a desired location in reaction vessel 33. Optical detection block 920 includes a photodiode detector 921 that detects light emitted from reaction vessel 33. Before being received by photodiode detector 921, the emitted light passes through rod lens 923 and filter and lens 922 to ensure detection of a specific wavelength that indicates the presence of a target analyte within reaction vessel 33.

[0216] In some embodiments, the optical component 900 includes an optical excitation component 910 and an optical detection component 920, positioned on an optical mount adapted to receive the planar reaction vessel 33. The optical excitation component 910 is positioned to emit excitation energy through an edge (subsurface) of the planar surface of the reaction vessel 33, and the optical detection component 920 is positioned along the main planar surface of the reaction vessel. In one aspect, the optical excitation component and the optical detection component are orthogonal to each other. In some embodiments, the optical component is configured to utilize a lens with a high numerical aperture. In some embodiments, the optical component is configured to operate at a low numerical aperture without the need for a lens. In such embodiments, the optical path can travel from the light source through a filter to the detection component without the need for a lens to focus the light generated by the excitation. Such embodiments can be configured such that the excitation optical path and the detection optical path are spatially opposite each other to improve the detection of light generated by excitation at low numerical apertures without the need for a lens. Using this spatial separation in the detection of excitation light allows for light detection without a lens, which allows for a reduction in system size.

[0217] In fluorescence detection systems, the amount of excitation light typically exceeds the amount of emitted fluorescence signal. To effectively detect the emitted signal, it is crucial to collect as much emitted light as possible. Therefore, most conventional systems employ a high numerical aperture (NAP) in their optical detection systems. A high NAP allows for the collection of more light, which in turn provides higher resolution, while a low NAP typically results in the collection of less light, leading to lower resolution. Most conventional fluorescence optical detection systems use a configuration including a lens and a bandpass filter in the optical path between the light source and the detector. The filter is typically placed between the lens and the detector, such that the lens provides collimated light that passes through the filter. Without a lens (and collimated light), the filter becomes much less efficient because the high angle of incidence light passing through the bandpass filter only passes through unfiltered light. A lens eliminates this problem because it collimates (reducing the high angle of incidence beam), resulting in more efficient filtering of the excitation wavelength.

[0218] In some embodiments of the invention, the optical system does not include a lens. Without a lens, a low numerical aperture configuration is employed, where the optical path consists only of a light source, a bandpass filter, and a detector. Using a low numerical aperture with this configuration reduces the high incident light angle (unlike when using a lens), thereby improving filtering efficiency and resulting in a strong signal of emitted light, where most of the excitation wavelength is filtered out.

[0219] In some embodiments, the optical module includes a UV LED, a blue LED, a green LED, a yellow LED, and a red LED, associated optical filters, coupling optical elements, and a protective glass. In some embodiments, the optical device is completely encapsulated in epoxy resin, which provides shock protection and prevents dust and moisture intrusion. In some embodiments, the optical excitation and detection chips have reduced dimensions, for example, each less than 10 mm, typically about 5 mm (length) x 4 mm (width) x 3 mm (height).

[0220] Figure 31 A detailed view of excitation block 910 and detection block 920 is shown, indicating the relative areas of adjacent reaction vessels through which light emitted from the excitation block and collected by the detection block passes.

[0221] Figure 32 Fluorescence detection utilizing optical components for excitation and detection components according to some embodiments of the present invention is illustrated. It can be seen that, according to some embodiments, Figure 32 The configuration matches the arrangement pattern of the excitation and detection blocks used in relation to the use of low numerical apertures.

[0222] 8.C Thermal control device

[0223] 8.C.1 Overview

[0224] Figure 27 A block control diagram of a thermal control device 800 in a TOS board according to some embodiments of the present invention is shown. In some embodiments, the thermal control device includes dual thermoelectric coolers (TECs) with a thermal capacitor disposed therebetween. In some embodiments, the thermal control device employs closed-loop control using two thermistors to control the operation of each TEC, thereby optimizing the heating and cooling of active surfaces coupled to the reaction vessel or vessel. Compared to conventional temperature control devices, this configuration provides lower noise, improved temperature stability, high gain, and high bandwidth. In some embodiments, a single thermal control device is used to heat / cool a fluid sample across the main surface of the reaction vessel. In some embodiments, thermal control devices are used on each main surface of the reaction vessel to heat / cool a fluid sample across both main surfaces of the reaction vessel.

[0225] In any of the described embodiments including first and second thermoelectric coolers, the second thermoelectric cooler can be replaced by a thermal control device. Such a thermal control device includes any of a heater (e.g., a resistance temperature detector), a cooler, or any device suitable for temperature regulation. In some embodiments, the thermal control device is included in a microenvironment shared with the first thermoelectric cooler, such that operation of the thermal control device alters the temperature of the microenvironment relative to the ambient temperature. In this respect, the device alters the surrounding environment to allow the first thermoelectric cooler to cycle between a first temperature (e.g., an amplification temperature of 60-70°C) and a second higher temperature (e.g., a denaturation temperature of about 95°C), cycling between these temperatures as quickly as possible. If both the first and second temperatures are higher than the actual ambient temperature, it would be more effective to raise the temperature within the microenvironment above the ambient temperature for a second heat source within the microenvironment (e.g., a thermoelectric cooler or heater). Alternatively, if the ambient temperature exceeds the second higher temperature, the thermal control device can cool the microenvironment to an ideal temperature to allow for more efficient and rapid cycling between the first and second temperatures.

[0226] In some embodiments, the thermal control device includes a first thermoelectric cooler having a working surface and a reference surface, a thermal control device, and a controller operatively coupled to each of the first thermoelectric cooler and the thermal control device. The controller may be configured to coordinate with the thermal control device to operate the first thermoelectric cooler in order to increase the efficiency of the first thermoelectric cooler as the temperature of its working surface changes from an initial temperature to a desired target temperature. The thermal control device may include a resistance temperature detector (RTD) heating element or a second thermoelectric cooler, or any suitable means for regulating temperature.

[0227] In some embodiments, the thermal control device further includes one or more temperature sensors coupled to the controller and arranged along or near the first thermoelectric cooler, the thermal control device, and / or a microenvironment shared by the first thermoelectric cooler and the thermal control device. The thermal control device can be thermally coupled to the first thermoelectric cooler through a microenvironment defined within a diagnostic testing system, wherein the thermal control device is configured such that the temperature of the microenvironment can be controlled and regulated from an ambient temperature outside the system.

[0228] In some embodiments, the thermal control device includes a controller coupled to each of the thermoelectric cooler and the thermal manipulation device, the controller being configured to control the temperature within the chamber of the reaction vessel in thermal communication with the thermal control device. In some embodiments, the controller is configured to operate the first thermoelectric cooler based on a thermal modeling of the in-situ reaction chamber temperature within the reaction vessel. The thermal modeling can be performed in real time and can utilize Kalman filtering depending on the accuracy of the model.

[0229] In some embodiments, a thermal control device is disposed within the device diagnostic testing system and positioned in thermal communication with the reaction vessel of the test kit disposed within the system. The controller can be configured to perform thermal cycling during the polymerase chain reaction within the chamber of the reaction vessel.

[0230] In some embodiments, the thermal control device includes a first thermoelectric cooler having a working surface and a reference surface, a thermal manipulation device, a thermal inserter disposed between the first thermoelectric cooler and the thermal manipulation device, and a first temperature sensor such that the reference surface of the first thermoelectric cooler is thermally coupled to the thermal manipulation device via the thermal inserter (which may be a thermal capacitor as disclosed herein), and the first temperature sensor is adapted to sense the temperature of the working surface of the first thermoelectric cooler. The device may also include a controller operatively coupled to each of the first thermoelectric cooler and the thermal manipulation device. The controller may be configured to operate the thermal manipulation device in coordination with the first thermoelectric cooler to increase the speed and efficiency of the first thermoelectric cooler when the temperature of the working surface of the first thermoelectric cooler changes from an initial temperature to a desired target temperature. In some embodiments, the controller is configured with a closed control loop having a feedback input of a predicted temperature based on a thermal model including input from the first temperature sensor.

[0231] Various aspects of this thermal control device are described in section [number] of the paper entitled "Thermal Control Device and Methods of Use" filed concurrently with this application. The entire contents of U.S. Nonprovisional Application No. [Application Number] are incorporated herein by reference for all purposes. It will be understood that thermal control devices used in TOS systems according to some embodiments of the invention may include any combination of the elements described therein.

[0232] 8.C.2TEC Design

[0233] In some embodiments, the thermal control device includes: a first thermoelectric cooler (TEC) having a working surface and a reference surface; a second TEC having a working surface and a reference surface; and a thermal inserter disposed between the first TEC and the second TEC such that the reference surface of the first TEC is thermally coupled to the working surface of the second TEC via the thermal inserter. In some embodiments, the thermal inserter functions as a thermoelectric capacitor. In some embodiments, the thermal control device includes a controller operatively coupled to each of the first TEC and the second TEC, the controller being configured to operate the second TEC in parallel with the first TEC to increase the speed and efficiency of operating the first TEC as the temperature of the working surface of the first TEC changes from an initial temperature to a desired target temperature. In some embodiments, the first thermoelectric cooler and the second thermoelectric cooler are thermally coupled via a thermoelectric capacitor having sufficient thermal conductivity and mass to transfer and store thermal energy, thereby reducing the time spent switching between heating and cooling, thus providing a faster and more efficient thermal cycle. In some embodiments, the device utilizes a thermocouple within the first thermoelectric cooler assembly and another thermocouple within the thermoelectric capacitor layer and operates using first and second closed control loops based on the temperatures of the first and second thermocouples, respectively. To utilize the thermal energy stored in the thermoelectric capacitor layer, the second control loop may be configured to lead or lag the first control loop. By using one or more of the aspects described herein, embodiments of the present invention provide faster and more robust thermal control devices for performing rapid thermal cycling, preferably in about two hours or less, even in the aforementioned problematic high-temperature environments.

[0234] In some embodiments, the thermal control device includes a thermal capacitor formed of a sufficiently large mass of thermally conductive material to adequately store thermal energy, thereby facilitating faster switching speeds between thermal cycles and improving the heating and cooling efficiency of the TEC. In some embodiments, the thermal capacitor comprises a material with a higher thermal mass than the working and reference surfaces of the first and second TECs, and may be formed of a ceramic material. In some embodiments, the thermal capacitor is formed of a copper layer with a thickness of approximately 10 mm or less (e.g., approximately 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 mm, or less). This configuration allows for a thermal control device with a relatively thin planar structure, making it suitable for reaction vessels in reduced-size nucleic acid analysis devices.

[0235] In some embodiments, the thermal control device includes: a first temperature sensor adapted to sense the temperature of the working surface of a first TEC; and a second temperature sensor adapted to sense the temperature of a thermal capacitor. In some embodiments, the first and second temperature sensors are coupled to a controller such that the operation of the first and second TECs is at least partially based on inputs from the first and second temperature sensors to the controller. In some embodiments, the second temperature sensor is embedded in or at least in thermal contact with the thermally conductive material of the thermal container. It should be understood that in any of the embodiments described herein, the temperature sensors can be positioned in various other locations, provided that the sensors are in sufficient thermal contact with the corresponding layers to sense the temperature of those layers.

[0236] In some embodiments, the thermal control device includes a controller configured with a main control loop and an auxiliary control loop, with an input from a first temperature sensor provided to the main control loop and an input from a second temperature sensor provided to the auxiliary control loop. The controller may be configured such that the bandwidth response of the main control loop is faster (or slower) than the bandwidth response time of the auxiliary control loop. Typically, both the main and auxiliary control loops are closed-loop loops. In some embodiments, the controller is configured to cycle between a heating cycle and a cooling cycle, in which the working surface of the first TEC is heated to an increased target temperature and in the cooling cycle, the working surface of the first TEC is cooled to a decreased target temperature. The controller may be configured such that the auxiliary control loop switches the second TEC between heating and cooling modes before the first control loop switches between heating and cooling to thermally load the hot container. In some embodiments, the temperature of the auxiliary control loop relative to the working surface of the first TEC maintains the temperature of the hot capacitor within approximately 40°C. In some embodiments, the temperature of the auxiliary control loop relative to the working surface of the first TEC maintains the temperature of the thermal capacitor within about 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 degrees Celsius. The controller can be configured to maintain the efficiency of the first TEC by operating the second TEC, such that heating and cooling through the working surface of the first TEC occurs at a rate of change of about 10°C / second. Non-limiting exemplary rates of change achievable by the invention include 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1°C / second. In some embodiments, the target temperature increase is about 90°C or higher, and the target temperature decrease is about 40°C or lower. In some embodiments, the target temperature increase is about 95°C, and the target temperature decrease is in the range from about 60°C to about 75°C, including all temperatures between the two ends of this range.

[0237] In some embodiments, the thermal control device further includes a heat sink coupled to a reference surface of the second TEC to prevent thermal runaway during cycling. The thermal control device may be configured in a generally planar configuration and its dimensions are designed to correspond to the planar reaction chamber portion of the reaction vessel of the assay kit. In some embodiments, the planar dimensions have a length of about 45 mm or less and a width of about 20 mm or less, or a length of about 40 mm by about 12.5 mm, such as about 11 mm by 13 mm, to accommodate the reaction vessel in a miniature PCR analysis device. The generally planar configuration may be configured and sized to have a thickness of about 20 mm or less from the working surface of the first TEC to the opposite side of the heat sink. Advantageously, in some embodiments, the thermal control device may be adapted to engage with the reaction vessel to thermally cycle the reaction vessel on one side, allowing optical detection of the target analyte from the opposite side of the reaction vessel during thermal cycling.

[0238] In some embodiments, methods for controlling temperature are provided herein. These methods include the steps of: operating a first thermoelectric cooler (TEC) having a working surface and a reference surface to heat and / or cool the working surface from an initial temperature to a target temperature; operating a second thermoelectric cooler (TEC) having a working surface and a reference surface to increase the efficiency of the first TEC as the temperature of the working surface of the first TEC changes from the initial temperature to the desired target temperature, the working surface of the second TEC being thermally coupled to the reference surface of the first TEC via a thermoelectric capacitor. Such methods may further include the steps of: operating the first TEC including operating a main control loop having a temperature input from a temperature sensor at the working surface of the first TEC, and operating the second TEC including operating an auxiliary control loop having a temperature input from a temperature sensor within the thermoelectric capacitor. In some embodiments, the method further includes: cycling between a heating mode in which the working surface of the first thermoelectric cooler is heated to an increased target temperature and a cooling mode in which the working surface is cooled to a decreased target temperature; storing thermal energy from thermal fluctuations between the heating and cooling modes in a thermoelectric capacitor, the thermoelectric capacitor including a layer having increased thermal conductivity compared to the working surface and reference surface of the first and second thermoelectric coolers, respectively.

[0239] In some embodiments, the method of controlling the temperature in a thermal cycle includes cycling between a heating mode and a cooling mode of a first thermoelectric device while simultaneously cycling between a heating mode and a cooling mode of a second thermoelectric device, thereby maintaining the efficiency of the first thermoelectric device during the cycle. In some embodiments, the controller is configured such that the bandwidth response of the main control loop is faster than that of the auxiliary control loop. The controller may also be configured such that the cycle is timed by the controller to switch the second thermoelectric device between modes before switching the first thermoelectric device between modes to thermally load the thermal capacitor. In some embodiments, the target temperature for raising is about 95°C or higher, and the target temperature for lowering is about 50°C or lower. In some embodiments, the method of controlling the temperature further includes maintaining the temperature of the thermal capacitor relative to the temperature of the operating surface of the first TEC within about 40°C by controlling the operation of the second TEC during the cycle of the first TEC, so as to maintain the efficiency of the first TEC during the cycle. In some embodiments, the efficiency of the first TEC is maintained by operating the second TEC such that heating and / or cooling through the operating surface of the first TEC occurs at a rate of change of 10°C / second or less. Such a method may also include: operating a heatsink connected to the reference plane of the second TEC during cycles with the first TEC and the second TEC to prevent thermal runaway.

[0240] In some embodiments, this document provides a thermal cycling method for a polymerase chain reaction (PCR) process. Such a method may include the steps of: engaging a thermal control device with a reaction vessel containing a fluid sample to perform a PCR for amplifying a target polynucleotide, such that the working face of a first TEC is thermally engaged with the reaction vessel; and thermally cycling the thermal control device according to a specific protocol for amplifying the target polynucleotide contained in the fluid sample. In some embodiments, engaging the thermal control device with the reaction vessel includes engaging the working face of the first TEC with one side of the reaction vessel, such that the opposite side remains uncovered by the thermal control device to allow optical detection from the opposite side. In some embodiments, each of the heating and cooling modes uses one or more operating parameters, wherein one or more operating parameters are asymmetric between the heating and cooling modes. For example, each of the heating and cooling modes has a bandwidth and loop gain, wherein the bandwidth and loop gain of the heating and cooling modes are different.

[0241] In some embodiments, a method for controlling temperature using a thermal control device is provided. This method includes the steps of: providing a thermal control device for first and second TECs, with a thermal capacitor between the first and second TECs, wherein each of the first and second TECs has a working surface and a reference surface; heating the working surface; cooling the working surface; heating the reference surface; and cooling the reference surface. In some embodiments, each of the heating and cooling working surfaces is controlled by one or more operating parameters. In some embodiments, the magnitude of one or more operating parameters is different during the heating of the working surface compared to the cooling of the working surface.

[0242] In some embodiments, the method includes reliability testing among multiple thermal control devices using alternating fixing devices. This method includes the steps of alternating thermal cycling between a thermal control device and a second or more thermal control devices to achieve thermal cycling of a second or more reaction vessels by operating fixing devices that alternately position the thermal control device and the second or more thermal control devices at a working position, and performing thermal cycling of the corresponding reaction vessel at the working position. In some embodiments, the fixing device is a rotatable hub, wherein the thermal control device and two or more thermal control devices are circumferentially distributed around the outer side of the hub, such that operating the fixing device includes rotating the hub.

[0243] 8.C.2.a Exemplary TEC Design Configuration

[0244] Figure 33A An exemplary thermal control device is shown, comprising a first TEC 811 (main TEC) and a second thermal control device (such as an auxiliary TEC 812 or a resistance temperature detector) thermally coupled via a thermal capacitor 813 (also referred to as a thermal inserter). The TECs are configured such that the working surface 811a of the first TEC 811 is thermally coupled to a reaction vessel 33 to facilitate control of thermal circulation therein. The device may optionally include a coupling fastener 819 for mounting the device onto a pipe. In some embodiments, the device may be secured to a fastener that positions the device near the pipe. The opposing reference surface 811b of the first TEC is thermally coupled to the working surface 812a of the second TEC 812 via the thermal capacitor layer. This configuration may also be described as having the reference surface 811b in direct thermal contact with one side of the thermal capacitor layer 813, and the working surface 812a in direct thermal contact with the opposing side of the thermal capacitor layer 813. In some embodiments, the reference surface 812b of the second TEC is thermally coupled to a heat sink 817 and / or a cooling fan 818, such as... Figure 33BAs shown in the embodiment. In this embodiment, the thermal control device 800 is configured such that it is thermally coupled along one side of the planar portion of the reaction vessel 33 to allow optical excitation from another direction (e.g., one side of the tube) via an optical excitation device 910 (such as a laser) and optical detection from another direction (e.g., the opposite side of the tube) using an optical detection device 920.

[0245] A thermocouple 816 is included in or near the working surface 811a of the first TEC 811 to allow precise control of the temperature of the reaction vessel. The temperature output of this thermocouple is used in a main control loop 814, which utilizes the working surface 811a to control heating and cooling. A second thermocouple 816' is included in or near a thermocapacitor layer and uses its associated temperature output in a second control loop 814', which controls heating and cooling via the working surface 812a of the second TEC. In one respect, the first control loop is faster than the second control loop (e.g., the second control loop lags behind the first control loop), taking into account the thermal energy transferred and stored within the thermocapacitor layer. By using these two control loops, the temperature difference between the working surface 811a and the reference surface 811b of the first TEC 811 can be controlled to optimize and improve the efficiency of the first TEC, allowing for faster and more consistent heating and cooling via the first TEC, while the thermocapacitor allows for faster switching between heating and cooling, as described herein and demonstrated in the experimental results presented below.

[0246] Instead of attaching a standard heat sink to a ceramic plate opposite the reaction vessel, an additional (auxiliary) TEC is used to maintain the operating surface of the main TEC at a temperature within approximately 40°C. In some embodiments, two PID (proportional-integral-derivative) control loops are used to maintain this operation. In some embodiments, a non-PID control loop is used to maintain the temperature of the operating surface of the main TEC. Typically, a fast PID control loop drives the main TEC to a predetermined temperature setpoint, monitored by a thermistor mounted on the underside of the ceramic plate in contact with the reaction vessel. This loop operates at maximum speed to ensure rapid and accurate attainment of the control temperature. In some embodiments, a slower second PID control loop maintains the temperature of the bottom surface of the main TEC to maximize thermal efficiency (experimentally determined to be within approximately 40°C of the operating surface temperature). As mentioned above, a non-PID control loop can also be used to maintain the TEC temperature to maximize thermal efficiency. In some embodiments, it is advantageous to suppress the interaction between the two control loops to eliminate one loop controlling the other. It is even more advantageous to use a thermal capacitor layer to absorb and store heat energy from the first and / or second TEC to facilitate rapid switching between heating and cooling.

[0247] This document describes in detail two non-limiting exemplary methods used in some embodiments of the invention for achieving rapid and efficient switching between heating and cooling. First, the bandwidth response of the auxiliary control loop is intentionally limited to be much lower than that of the fast main loop, a so-called "inertial loop." Second, a thermal capacitor is sandwiched between the two TECs. While it is desirable that the overall thermal control device be relatively thin to allow use on the reaction chamber portion of the reaction vessel, it should be understood that the thermal capacitor layer can be thicker, provided it provides sufficient mass and thermal conductivity to act as a thermal capacitor for either TEC. In some embodiments, the thermal capacitor layer is a thin copper plate with a thickness of about 1 mm or less. Copper is advantageous due to its extremely high thermal conductivity, and a 1 mm thickness has been experimentally determined to adequately accommodate both TECs while providing sufficient mass for the thin layer to act as a thermal capacitor for storing thermal energy. While copper is particularly useful due to its thermal conductivity and high mass, it is understood that various other metals or materials with similar thermal conductivity and high mass can be used, preferably materials with thermal conductivity (even less than either TEC) and a mass equal to or greater than either TEC, to allow the layer to function as a thermal capacitor while storing thermal energy. On the other hand, the heat container layer may include a second thermistor for monitoring the "back-side" temperature (e.g., reference plane) used by the auxiliary PID control loop. Both control loops can be digitally implemented in a single PSoC (System-on-Chip) chip, which can send control signals to two bipolar Peltier current sources. Those skilled in the art will understand that in some embodiments, non-PSOC chips can also be used for this control, such as field-programmable gate arrays (FPGAs) suitable for this invention. In some embodiments, the dual TEC module includes a heat sink to prevent thermal runaway, which can be bonded to the back side of the auxiliary TEC using, for example, thermally conductive silver epoxy resin. Alternative bonding methods and materials suitable for this invention are well known to those skilled in the art.

[0248] Figure 33B A schematic diagram of a dual-TEC design is shown. The temperature of the PCR reaction vessel (measured by a thermistor (816) (elliptical)) is managed by the main TEC and controlled by a loop in the PSoC firmware. Optimal thermal efficiency of the main TEC is maintained by a second thermistor (816') (elliptical) in thermal contact with the copper layer, which enters an auxiliary PSoC loop to control the second TEC.

[0249] 8.C.2.b Initial Dual TEC Manufacturing

[0250] Figure 33CAn exemplary dual-TEC heating / cooling module is shown, comprising a thermal control device 800 thermally bonded to one main surface of a reaction vessel, an optical excitation block adjacent to a secondary surface (e.g., an edge) of the reaction vessel, and an optical detection block 920 abutting against the opposite main surface of the reaction vessel 33. In some embodiments, both the main TEC and the auxiliary TEC (Laird, OptoTECHOT20,65,F2A,1312, datasheet below) measure 13 (width) x 13 (length) x 2.2 (thickness) mm and have a maximum thermal efficiency of 60%. In some embodiments, the planar region affected by the TEC module matches the GX reaction vessel. In some embodiments, it is configured to accommodate reaction vessels ranging from 25 µl to 100 µl.

[0251] Figure 33B An exemplary dual-TEC module for unilateral heating and cooling of a reaction vessel in a chemical analysis system is shown. It will be understood that in some embodiments, the design can be modified to provide dual TECs on both sides for bilateral heating. The heatsink includes a mini-fan for flushing heat and maintaining TEC efficiency. The temperature of the main TEC (top) circulates within the reaction vessel, monitored by a thermistor mounted on the underside of the ceramic in contact with the tubes. The "back-side" TEC maintains the temperature of the gap copper layer (using a thermistor) to ensure optimal thermal efficiency of the main TEC. The heatsink with the integrated mini-fan keeps the entire module in thermal equilibrium.

[0252] In some implementations, a small thermistor with a temperature tolerance of + / - 0.1°C is bonded to the underside of the top surface of the main TEC using silver epoxy resin. This thermistor detects the temperature applied to the reaction vessel and is an input to the main control loop in the PSoC, which controls the drive current of the main TEC. The bottom surface of the main TEC is bonded to a 1 mm thick copper plate with silver epoxy resin. A slot is formed in the copper plate containing a second TR136-170 thermistor, encapsulated in silver epoxy resin, to monitor the "backside temperature," the signal input to the auxiliary control loop in the PSoC. An auxiliary TEC, then controlled by the auxiliary control loop, is sandwiched between the copper plate and an aluminum heatsink. The heatsink is machined to an overall thickness of 6.5 mm, keeping the overall package thickness less than 13 mm, with planar dimensions of 40.0 (L) x 12.5 (W) mm, necessary for space constraints within the reduced-size instrument. A 12 x 12 mm Sunon Mighty mini fan (datasheet below) is bonded to an insert machined into the heatsink, where the TEC interacts with the heatsink. It should be noted that mini fans do not require direct cooling of the heatsink; quiet, durable, and inexpensive low-voltage (3.3V maximum) brushless motors are sufficient to maintain heatsink performance by removing hot surface air from the aluminum / air interface using shear flow, rather than direct air cooling (as in some conventional analytical apparatus).

[0253] The prototype unit can be tested to determine whether the heating / cooling rate, thermal stability, robustness to increased ambient temperature, and overall system reliability are sufficient to meet engineering requirements. The thermal performance has proven acceptable, thus meeting the design goals of the exemplary scale-down system: smaller size, robustness, and lower cost (requiring fewer components compared to dual-sided heating / cooling). Furthermore, single-sided heating / cooling enables more efficient optical inspection through the side of the reaction vessel.

[0254] Figure 33C A CAD drawing of the dual-TEC heating / cooling module, LED excitation and detection block, and reaction vessel within an exemplary system is shown. The reaction vessel undergoes thermal cycling on one side (the first main surface of the reaction vessel) and fluorescence detection is performed via the opposite side (the second main surface of the reaction vessel). LED illumination is maintained across the edge (sub-surface) of the reaction vessel.

[0255] 8.C.2.c Initial heating / cooling performance

[0256] The heating and cooling performance of an exemplary TEC assembly was measured using a custom-designed fixture that clamped the TEC assembly against one surface of the reaction vessel. The TEC assembly was thermally isolated from the fixture by making it a thermally insulating Delrin. To simulate the heat load of PCR, the reaction vessel was filled with a fluid sample that made firm contact with a fluorescent detection block on the tube surface opposite the TEC assembly. It should be noted that the temperature on the top TEC surface of the contact tube in this geometry was independently measured to be equal to or higher than the temperature measured on the main TEC thermistor. Therefore, it is reasonable to use the read temperature of the main TEC thermistor to initially characterize the thermal performance of the dual TEC heating / cooling system. Any mismatch between the thermistor and reaction vessel temperatures can be characterized and adjusted to utilize a feedback loop between the main TEC thermistor and the temperature of the fluid sample in the reaction vessel.

[0257] In some embodiments, clamping devices are used to secure the thermal control device to the reaction vessel used for thermal characterization. In one example, the reaction vessel may be filled with a fluid sample and secured to allow thermal contact between the heating / cooling module and one side of the reaction vessel. The other side of the tube may be clamped onto a fluorescence detection block. An LED excitation block illuminates the solution through the edge of the tube. In some embodiments, both excitation and detection are performed through the secondary side of the tube.

[0258] In some implementations, the PSoC control board employs PID control to maintain the temperature setpoint of the main TEC thermistor and provide a bipolar drive current (positive voltage during heating, negative voltage during cooling) to the TEC device, as well as power the mini-fan. This PID loop is tuned to maximize the performance of the main TEC. A script is written to cycle the tube's setpoint between the high and low temperature extremes of the PCR thermal cycle. Specifically, the low temperature setpoint is 50°C for 12 seconds, starting once the measured temperature remains within + / - 0.1°C for 1 second. Similarly, the high temperature setpoint is 95°C for 12 seconds, starting once the setpoint temperature remains within + / - 0.1°C for 1 second. The script loops infinitely between 50°C and 95°C.

[0259] The auxiliary control loop also remains within the same PSoC chip, read from the copper damping / thermal capacitor layer (see...). Figure 33A The temperature of the auxiliary thermistor, which is in thermal contact with and acts on the auxiliary TEC, is measured. By controlling the temperature of this copper layer, the so-called "back-side" temperature, a different set of PID control parameters was found to properly maintain the system's thermal performance. As expected, this control loop has a much lower bandwidth than the main TEC control loop. The PSoC and related programs also allow for multiple setpoints for the back-side temperature, which can be used to maximize the rate-of-change performance by keeping the main TEC operating under optimal effective thermal conditions.

[0260] Figure 34 An exemplary thermal cycle from the reaction vessel temperature is shown, with the thermal cycle measured at 50°C → 95°C → 50°C (main trace) under closed-loop control. The closed-loop heating and cooling rates are approximately 7°C / second. The main control is the desired temperature setpoint of the thermal cycle (a function of the square of the elapsed time between 0 and 20 seconds), and the main trace is the measured temperature of the tube. It can be seen that the actual thermal cycle lags behind the desired thermal cycle indicated by the main control function. The thermal efficiency of the main TEC is determined to be highest when the temperature difference between the tube and the back side is no more than 30°C, so the back side temperature is controlled at 65°C when heated to the maximum temperature (95°C for the tube) and at 45°C when the tube is cooled to 50°C (back side trace). Once the main TEC rises to a higher temperature, the back side temperature can be slowly and controllably driven to a lower temperature, thus anticipating the next thermal cycle (shown as starting from approximately 37 seconds elapsed). This approach is similar to using a back-side TEC to apply a "hot spring" effect to the main TEC, and is suitable for PCR systems because the heat distribution to be applied to a specific PCR assay is known to the assay designer. Note that the closed-loop rate of change for stable and repeatable heating and cooling is approximately 6.5 seconds over a range of 45°C, as shown in ten consecutive thermal cycles. Figure 35As shown, the actual closed-loop change rate corresponding to both heating and cooling is approximately 7°C / second. Performance remained constant across multiple cycles throughout the entire PCR thermal cycling range.

[0261] 8.C.2.d Early and near-term reliability tests

[0262] A typical PCR assay involves approximately 40 thermal cycles from the annealing temperature (~65°C) to the DNA denaturation temperature (~95°C) and back to the annealing temperature. To assess reliability, the exemplary thermal control module was cycled between 50°C (on the order of magnitude of the lowest temperature for PCR experiments) and 95°C, with 10 seconds allowed at each temperature for system thermal equilibrium to be reached.

[0263] Figure 36A A comparison of the first 5 and last 5 cycles of a 5000-cycle test is shown. Note that the time axis of the right-hand track comes from a small data sampling range; 5000 cycles takes approximately 2 days. This module has cycled over 10,000 times while maintaining performance. It can be seen that the thermal cycling performance of cycles 1-5 (left side) remains unchanged after 5000 cycles (4,995-5,000 cycles on the right side), and there is no change in thermal performance between the initial and final cycles. There are two encouraging reasons for this. First, the closed-loop parameters of rapid heating / cooling are remarkably stable during repeated thermal cycling. Even small thermal instabilities can cause drift in the measured temperatures of both the main TEC and the back-side TEC, rapidly escalating to thermal runaway (which would trigger an overcurrent shutdown fault in the firmware). A properly tuned system does not exhibit this behavior, demonstrating the system's robustness. Second, the module's thermal efficiency remains stable within 5000 cycles. In fact, this unit was subsequently cycled over 10,000 times without catastrophic or gradual performance degradation. Figure 36B The thermal cycling performance is shown at the start of thermal cycling and after five cycles following two days of continuous thermal cycling.

[0264] 8.D Thermal modeling methods for controlling thermal cycles

[0265] On the other hand, the thermal control device can be configured to control temperature based on thermal modeling. This aspect can be used to configure thermal control devices for unilateral or bilateral heating. In some embodiments, such a device includes a first thermoelectric cooler and another thermal manipulation device, each coupled to a controller that coordinates with the thermal manipulation device to control the first thermoelectric cooler to improve control, speed, and efficiency when heating and / or cooling using the first thermoelectric cooler. However, it should be recognized that this thermal modeling aspect can be incorporated into the control of any configuration described herein.

[0266] An example of this method is in Figure 37The state model diagram is shown below. This diagram illustrates a seven-state model used with a single-sided version of the thermal control device. The model applies electrical theory to model the temperature of a real-world thermal system, including the temperature of the thermoelectric cooler surface, the reaction vessel or container, and a sample of fluid within the reaction vessel. The diagram shows the seven states of the model and three measurement states used in the Kalman algorithm to obtain the best estimate of the contents within the reaction vessel, assuming it is water.

[0267] exist Figure 37 In the circuit model, capacitors represent the material's heat capacity, resistors represent the material's thermal conductivity, the voltage at each capacitor and power source represents the temperature, and the current source represents the thermal power input from the front thermoelectric cooler (TEC) adjacent to the pipe surface. In this embodiment, the model's input is the back-side TEC temperature, which can be predicted from models T1-T7, the heat input (watts) of the front-side TEC, and the temperature of the "block" adjacent to the opposite container or pipe surface. This completes the model part of the algorithm. As previously mentioned, the Kalman algorithm typically combines the model with measured sensor signals, which are also part of the model's output. Here, the measured thermistor signals converted to temperature are used for both the front and back-side TECs. For the back-side temperature measurement, it is not the model's output but is assumed to be the same. One reason for this assumption is that R1 is negligible in terms of overall thermal conductivity.

[0268] 8.C.2.e Replacement TEC Design

[0269] Variables in modular construction can lead to subtle differences in device performance. For example, the current module is hand-assembled with machined heat sinks and gapped copper layers, all components bonded together by hand using conductive epoxy resin. Variations in epoxy resin thickness or small angles created between components within the module's sandwich structure can result in different thermal properties. Crucially, the thermistors are also attached to the ceramic using thermal epoxy resin. Small gaps between the thermistors and the ceramic cause errors between the controlled temperature and the measured temperature. Finally, soldering small wires to create electrical contacts for the two TECs, two thermistors, and the fan power supply wires is extremely time-consuming.

[0270] In some embodiments, the thermal control device includes heating and cooling surfaces (e.g., a TEC device as described herein) on each primary (opposite) side of the reaction vessel. In such embodiments, optical detection can be performed along secondary surfaces (e.g., edges). In some embodiments, optical detection is performed along a first secondary surface, and optical excitation is performed along a second secondary surface orthogonal to the first secondary surface. Such embodiments can be particularly useful when heating and cooling of large volumes (100-500 μl fluid samples) is required.

[0271] In some implementations, the thermal control module uses a custom Peltier device comprising an integrated surface-mount thermistor mounted on the underside of a ceramic plate in contact with the reaction vessel. A tiny 0201 package thermistor (0.60 (L) x 0.30 (W) x 0.23 (H) mm) can be used to minimize convection within the Peltier device that causes temperature variations by limiting the component thickness. Furthermore, because the thermal contact and position of the surface-mount thermistor can be precisely controlled, these components exhibit a very consistent characteristic difference between the measured and actual ceramic temperatures.

[0272] In some implementations, the thermal control unit may include a custom-designed Peltier, fully integrated into the heating / cooling module using semiconductor mass production technologies (“pick-and-place” machines and reflow soldering). This gap-filling copper substrate can replace the Bergquist thermal interface PC board (a 1 mm thick copper substrate) which allows for precise control of copper thickness and pad size. The Bergquist substrate will also provide pad leads for the back-side thermistor and all electrical connections to and from the module. The back-side Peltier will remain similar to currently used devices. Finally, the entire TEC assembly can be encapsulated in silicone for water resistance. In some implementations, the aluminum mounting bracket may also double as a heat sink.

[0273] IX. Diagnostic Platform

[0274] Figure 38 This is a simplified block diagram illustrating an architectural overview of a diagnostic testing system according to some embodiments of the present invention. As with all the figures shown herein, various embodiments may differ from the examples illustrated. For example, some embodiments may be combined, separated, added, and / or omitted. Figure 38 The components are shown in the figure. Furthermore, the function of each component may be provided by one or more devices (e.g., computing devices) located in one or more geographical locations.

[0275] While the accompanying drawings may relate to an "Epsilon instrument," an "Epsilon handheld platform," and specific remote services, various embodiments falling within the scope of this invention are not limited thereto. The techniques described herein are described more generally and can be used by any type of medical device, mobile or other computing device, and remote server. Furthermore, the specific software components and functions described herein can be replaced by various software with similar functions. Those skilled in the art will recognize some variations of the embodiments shown and described below.

[0276] like Figure 38As shown, a diagnostic testing system typically includes three types of components: diagnostic devices (“Epsilon instrument hardware,” referred to herein and in the accompanying drawings as “instruments,” “diagnostic device modules,” or “diagnostic devices”), mobile devices (“Epsilon handheld platforms”), and remote services (collectively referred to as “remote Xpert systems” and “remote Xpert+ systems”). A more detailed description of these components is provided below. Diagnostic devices and mobile devices may coexist at a point of care, such as a health clinic, hospital, or other facility, while remote services may be located at one or more remote locations. Depending on the desired functionality, and as described above, implementations may employ multiple diagnostic devices, mobile devices, and / or remote services.

[0277] Figure 38 The diagnostic device shown includes the Epsilon instrument hardware and various software components shown therein, including the Epsilon instrument core software, Epsilon Xpert Reporter software, Epsilon instrument interface software, and Assay Distributable. As shown, these components can communicate with each other using various interfaces and application programming interfaces (APIs). As previously described, the diagnostic device may include a diagnostic testing system with a combination of testing and computational components, configured to perform diagnostic tests and provide result data to a remote service via a mobile device. In some embodiments, the diagnostic device may additionally process and / or store test data from one or more test results. Components may be implemented at least partially using a combination of software and hardware, which may be incorporated into a computer system (such as regarding...). Figure 53 (as described).

[0278] In some implementations, the diagnostic device can perform non-invasive processing of patient samples (test specimens) and provide summary and detailed test result data to a remote service. Interface software (displayed as "Epsilon Instrument Interface Software") enables the diagnostic device to communicate with mobile device software (displayed as "Epsilon Handheld Software") running on a mobile device. Communication can be accomplished wirelessly using any of a variety of wireless technologies, such as Near Field Communication (NFC) or Bluetooth. TM , Wi-Fi, etc.

[0279] By establishing this communication with the mobile device, the interface software enables the user of the mobile device to control various features of the diagnostic device. For example, using a graphical user interface (GUI) provided on the mobile device's display, the user may be able to manage the device settings; start, pause, or cancel tests performed by the diagnostic device; specify a remote service to which the diagnostic device will send data; and specify the type, content, and / or format of the data. According to some implementations, the mobile device may additionally enable the user to access medical and / or other data stored on the diagnostic device. However, in some implementations, the accessed data may not be stored on the mobile device, thus helping to ensure that data security is not compromised if the mobile device is lost or stolen. This feature facilitates system compliance with various privacy laws, regulations, and other standards.

[0280] The level of control provided to the user by the interface software via the mobile device may depend on the level of authorization provided by the user and / or the mobile device. For example, a user with a higher level of authorization may have access to diagnostic device functions that a user with a lower level of authorization cannot access. The interface software may help ensure system security by requesting authorization and / or authentication of the user and / or mobile device before and / or during communication by requiring unique data such as login information or similar data.

[0281] The diagnostic device can communicate with multiple mobile devices, and can do so simultaneously (or substantially simultaneously). This allows multiple users to control the diagnostic device. For this purpose, the interface software can provide authorization and / or authentication for each of the multiple mobile devices. In some embodiments, when the diagnostic device is effectively communicating with multiple mobile devices, one of the mobile devices can be designated as the master mobile device, through which all data is sent to the remote service. In other words, in some embodiments, while the diagnostic device can be controlled by multiple mobile devices, it can also connect to a single master mobile device, through which the diagnostic device routes data to the remote service.

[0282] Mobile devices can include mobile electronic devices such as smartphones, tablets, laptops, etc. Mobile device software can execute as an application on the mobile device and can also diagnose the mobile device's operating system (OS). Thus, once the mobile device software is installed on the mobile device and properly certified, any of the various mobile devices can be used as the mobile device described in the embodiments herein. Figure 38 As shown, the mobile device can also be connected to printing equipment (such as an off-the-shelf thermal printer).

[0283] In some implementations, the mobile device software can enable authorization and / or authentication of a mobile device with multiple diagnostic devices, allowing a user to control multiple diagnostic devices simultaneously using a single mobile device. In addition to providing control over the diagnostic devices via the mobile device software, the mobile device can also enable the diagnostic devices to communicate with remote services (e.g., provide data to a remote service) via network sharing features. These network sharing features enable data to be transmitted from the diagnostic devices (e.g., via NFC, Bluetooth, Wi-Fi, etc.) to the mobile device and relayed to the remote service from a wide area network (WAN) using connectivity to the mobile device. The WAN can utilize cellular (e.g., 3G, LTE, etc.), satellite, and / or other wireless technologies.

[0284] More generally, the techniques described herein can provide a diagnostic testing system in which one or more diagnostic tests can be controlled using a mobile device with LAN-based functionality on a peer-to-peer base. The same protocol can be used for WAN communications for discrete remote services on mobile devices. Therefore, for the latter functionality, the mobile device can act as a standalone router. Although the embodiments described herein use mobile or “handheld” devices, other embodiments can utilize computing systems that may not be considered mobile or handheld, such as personal computers. References below... Figure 53 The features of the mobile devices and other computing devices described herein will be described in more detail.

[0285] According to some implementations, network sharing features can provide connectivity between diagnostic devices and remote services without storing any permanent data on the mobile device. In other words, the mobile device may be unaware of the data being transmitted. In some implementations, for example, the mobile device can receive sensitive encrypted data (such as patient data) from the diagnostic device, which is then simply passed to the remote reporting system without being stored or decrypted by the mobile device. In such implementations, if the mobile device is lost or stolen, the security of the data will not be compromised, thereby adding another layer of privacy protection to the system, which can help the system comply with privacy laws, regulations, or other standards. Furthermore, the functionality of the diagnostic testing system can be restored in a relatively simple manner by replacing the lost or stolen mobile device. Utilizing such capabilities, the techniques described herein can be used not only in laboratories but also in locations where mobile devices may be more easily lost or stolen (e.g., Ebola clinics in remote parts of Africa).

[0286] Refer again Figure 38Remote services can be executed in the “cloud” by one or more servers located at one or more locations remote from mobile devices and / or diagnostic devices. Remote services can collect data from one or more diagnostic devices, synthesize the data, and store the data in a database. Remote services can collect data not only from one or more diagnostic devices at a single location (e.g., communicating via a specific mobile device), but also more broadly from diagnostic devices in various facilities across diverse geographical locations, enabling the provision of large-scale epidemiological data and the identification of additional valuable health and disease information in one or more populations.

[0287] Alternatively or concurrently, a remote service may aggregate and process data and provide a secure entry point (e.g., via the internet) to viewing entities, through which the processed data can be accessed in various ways (e.g., lists, charts, geographic maps, etc.). The form of viewing the processed data is consistent with the authorization level of the viewing entity. Similarly, data sent to and processed by the remote service may be encrypted (or otherwise securely transmitted) and / or manipulated in accordance with laws, regulations, standards, and / or other applicable regulatory requirements.

[0288] It should be understood that, Figure 38 The components shown can communicate with each other directly or as part of one or more larger data communication networks (such as the LAN and / or WAN described in the above embodiments) using the wireless technologies mentioned above. The data communication network can include any combination of various data communication systems (e.g., cable, satellite, wireless / cellular, or Internet systems) utilizing various technologies and / or protocols (such as radio frequency (RF), optical, satellite, coaxial cable, Ethernet, cellular, twisted pair, other wired and wireless technologies, etc.). The data communication network can include packet and / or circuit type switching and can include one or more open, closed, public, and / or private networks (including the Internet), depending on desired functionality, cost, security, and other factors.

[0289] The remaining descriptions and figures show Figure 38The embodiments of the diagnostic testing system shown herein represent various aspects. Although specific hardware and software components are described with reference to the disclosed embodiments, those skilled in the art will recognize that, in some embodiments, some such components may be replaced, substituted, omitted, and / or otherwise changed compared to other embodiments. For example, a programmable system-on-a-chip (PSoC) may be replaced by multiple components to provide substantially the same functionality. Those skilled in the art will be familiar with various mixed-signal and / or analog microcontrollers suitable for the present invention. The representative state transition (REST) ​​interface may be replaced and / or used with other software structures and / or protocols where appropriate, such as: Create, Read, Update, and Delete (CRUD); Domain Application Protocol (DAP); Hypermedia as Application State Engine (HATEOAS); Open Data Protocol (OData); RESTful API Modeling Language (RAML); RESTful Service Description Language (RSDL), etc.

[0290] 9. BEpsilon instrument core software

[0291] like Figure 38 As shown, in some embodiments, the Epsilon instrument core software (also known as diagnostic assay system software) may include various software modules. Suitable modules that may be included in the instrument core software may include the Cellcore operating system module, the Hardware State Machine (HSM) module, the iCORE software module, the valve software module, the syringe / gate software module, and / or the ultrasonic horn software module. In some embodiments, the Cellcore operating system module is a version of Linux and its support services running on the Cellcore processor. In some embodiments, the HSM module may include all diagnostic device-specific software running on the Cellcore processor and outside of the Java Virtual Machine (JVM). In some embodiments, the iCore software module includes all software running on the iCore PSoC. In some embodiments, the valve software module includes all software running on the valve PSoC. In some embodiments, the syringe / gate software module includes all software running on the syringe / gate PSoC. In some embodiments, the horn software module includes all software running on the horn PSoC.

[0292] In some implementations, the Epsilon instrument interface software may include the Epsilon instrument REST interface module and the Epsilon assay runner software module.

[0293] In some implementations, the Epsilon Xpert Reporter software runs as a client of the Remote Xpert software and runs on the Cellcore processor of the Epsilon instrument hardware within the same JVM as the Epsilon instrument interface software.

[0294] Epsilon instrument hardware can be a physical subsystem that performs the assays. In some implementations, this subsystem may consist only of the instrument's hardware, while the software runs on the instrument as a separate subsystem.

[0295] 9.C Mobile Device

[0296] like Figure 38 As shown, in some embodiments, the mobile device may include various software modules. For example, an embodiment of the illustrated Epsilon handheld software may include an Android application executed by the mobile device, specifically designed to support [the application's functionality] when deployed in a field environment. Figure 38 The system is shown in the diagram. In some implementations, an application from another operating system may be utilized. In some implementations, the software may include all the necessary features to support on-site patient testing using diagnostic devices and / or features to facilitate remote support of these instruments by Cepheid service providers (or service providers of another provider).

[0297] In some implementations, the mobile device may include an off-the-shelf Android handheld target platform selected to support the field environment.

[0298] 9.D Remote Xpert+ System

[0299] In some implementations... Figure 38 The remote Xpert+ system illustrated may include a suite of web applications as services used by both the remote Xpert system and the Epsilon handheld software. REST and / or similar services (as previously described) may be available for internal communication within the remote Xpert+. In some implementations, a limited number of services of the remote Xpert+ system may be available for external systems (e.g., the remote Xpert and Epsilon handheld software). According to some implementations, the primary role of the remote Xpert+ may be centralized management of users, organizations, commands, and suites.

[0300] 9.E Remote Xpert System

[0301] In some implementations... Figure 38The remote Xpert system illustrated may include a collection of web applications used by an organization to manage its instruments and clinical data. Such organizations may include, for example, national or international organizations (e.g., the World Health Organization), emergency response organizations, universities, hospitals, etc. In some implementations, the remote Xpert software may also include parsing software to parse the input and / or output data.

[0302] 9. F test can be allocated

[0303] In some implementations... Figure 38 Components of the illustrated diagnostic device's assay-assignable implementation may include assay titles (summary information for managing assays), assay definitions (which may be, for example, received files), and / or assay UI clippings (which define assay-specific UIs, such as specific sample preparation instructions). These clippings may be limited to areas defined by the UI design, such as sample preparation steps and / or assay-specific help screens. In some implementations, assay assignability may optionally include assay-specific software that can allow the incorporation of new algorithms as needed for future assays. This may require the software performing the assays to support this type of expansion. Additionally, in some implementations, assay assignability may include local handheld assay resources as needed. This may include various resources for implementing the UI of a specific assay. Examples include localized strings for supporting languages, new graphical resources (such as icons, if present), and / or any required help files (e.g., package inserts or portable document format (PDF) of training videos). It may also be noted that in some implementations, due to size constraints (e.g., localized training videos) and regional variations, it may be necessary to divide localized resources into "assignment language packs" or suites.

[0304] 9.G External Interface - Diagnostic Device

[0305] In some implementations... Figure 38 The diagnostic device shown may include one or more external interfaces. For example, the Epsilon Handheld App GUI may be a user interface on a mobile device or may act as a user interface for the diagnostic device. The Remote Xpert GUI may be a web-based user interface provided by Remote Xpert. The Remote Xpert+ GUI may be a web-based user interface provided by Remote Xpert+. In some implementations, the GUI may be accessible only to the entity that provides and / or maintains Remote Xpert+. Alternatively or additionally, the external interface may include SMS messaging, which may be used to report results to an agency clearinghouse and may be provided by the operator through the mobile device's operating system. The diagnostic device may include a data streaming interface that enables a personal computer (PC) or other computing device to provide visualization of the data. Figure 38The GX streaming data interface shown in the diagram can aid in development and debugging. Therefore, in some implementations, this interface may not be used during field deployment.

[0306] 9.H Internal Interface - Diagnostic Device

[0307] In some implementations... Figure 38 The diagnostic device shown may include one or more internal interfaces. For example, the Epsilon instrument hardware / software interface may include an interface between the instrument hardware and the Epsilon instrument core software. The GXIP+ interface may include an interface provided by the Epsilon instrument core software and used by specific software in both clinical setup and field use environments. The assay runner interface may be provided by the Epsilon instrument interface software and used by the Epsilon assay runner software or similar assay software. The instrument persistence API may include an interface provided by the Epsilon instrument interface software and used by the Epsilon Xpert Reporter software.

[0308] 9.1 Mobile Device Interface

[0309] In some implementations, the mobile device may include various interfaces. For example, the Epsilon instrument service interface may include a main interface provided by the Epsilon instrument interface software. For field use environments, this could be the interface used by the Epsilon handheld software to perform tests, obtain instrument status updates, and perform other normal operations.

[0310] The thermal printer interface may include an interface provided by an optional thermal printer, which may be an off-the-shelf model with Wi-Fi network connectivity. This allows the Epsilon handheld software to automatically or upon user request print test results on the printer once they are available. In some implementations, printers utilizing other technologies (e.g., inkjet, etc.) may be used.

[0311] The Android platform API can include interfaces provided by the Android operating system for accessing mobile device hardware and networks. As previously mentioned, alternative implementations may include equivalent or similar components that replace the operating system.

[0312] exist Figure 38The coordination interface shown in the embodiments provides coordination between mobile devices when multiple mobile devices are simultaneously active at a specific location, which can occur at busy sites when more than one user is working or when there are active backup mobile devices. The coordination interface can be implemented to cross-connect all modules to the user interface function control layer on the mobile devices. The purpose and function are to allow multiple instruments to be controlled and monitored as autonomous units via mobile devices and to provide workflow coordination between devices so that operators use the correct instruments to perform a given diagnosis. Point-to-point Wi-Fi management of instruments allows for guaranteed specific control of each device and maintains the chain of custody and key patient identification parameters. The resulting functionality enables an X:Y ratio of mobile devices to diagnostic devices, where X is any number of mobile devices and Y is any number of diagnostic devices. In some embodiments, X and Y can be the same number.

[0313] 9.J Remote Service Interface

[0314] like Figure 38 As shown, in some implementations, remote services may include various interfaces. For example, the EpsilonXpert Reporter Interface may contain a set of REST services that provide functionality such as clinical data uploading and / or instrument synchronization. The Remote Xpert+ Service Interface may contain a set of REST services that provide functionality such as kit management, user management, institution and site management, remote service commands, and / or instrument synchronization.

[0315] 9. K Application for exemption from Clinical Laboratory Improvement Amendments (CLIA)

[0316] In some implementations... Figure 38 The core software interface of the diagnostic device is available for Clinical Laboratory Improvement Amendments (CLIA) exemption applications. Here, the diagnostic device can provide information to proprietary software running on a personal computer via an Ethernet connection. Alternative implementations may employ other computing hardware, software, and / or physical or wireless connections. Further details regarding the GXIP+ interface are provided below.

[0317] 9.L Diagnostic Device - Software Components

[0318] Figure 39A logical view of the software executed by the diagnostic device according to an implementation is provided. As shown, the software may include low-level drivers, including a Universal Serial Bus (USB) driver stack, SM bus I / F and Wi-Fi, Bluetooth and USB dongle drivers. The application layer includes the operating system and other applications. These applications may include a JVM with Xpert Reporter and Epsilon Rest Interface components, a JVM with Epsilon Assay Runner components, a gateway application with DX gateway components, and / or an Epsilon instrument core application with GxIp+, GxStream, PSoC USB, HSM layer and battery I / F and power management components.

[0319] Figure 40 This is a block diagram of the Epsilon instrument core architecture according to some implementations. The diagram illustrates the interactions between the various sub-components of the Epsilon instrument core architecture, as described herein, including the NFC interface, GxIp+ interface, HSM.PSoCI / F, Gx Stream interface, Xpert Reporter / Epsilon REST interface, Epsilon Assay Runner, Dx Gateway, and NB USB.

[0320] In some implementations, the GxIp+ interface can be a main component supporting the GxIp protocol and can implement the required Dx business logic. Business logic can be ported from the 683xx legacy code as the basis for the "northbound" instrument interface to ensure consistency in assay and command execution methods. In some implementations, the GxIp+ interface may also include an adaptive layer connecting the "northbound" Legacy GxIp command and "southbound" Epsilon PSoC command interfaces. For HBDC environments, this can be the Dx equivalent interface used by the Epsilon instrument interface software to run and monitor assays.

[0321] In some implementations, the gateway interface may be a component that supports the GxIp "discovery" protocol. Once discovery is complete, this component can act as a router based on a remote GxIp component and a GxIp+ interface. In some implementations, the gateway interface may be the discovery interface on an Epsilon instrument.

[0322] In some implementations, the GxStreaming interface can be a master component that supports streaming Epsilon core state vectors to remote clients. During development, this interface can be used to support engineering visualization tools (VT) for monitoring and adjusting PSoC performance, ultrasonic and fluorometric equivalence monitoring related to Legacy systems. In some implementations, the GxStreaming interface allows state exchange data to be streamed to mobile devices.

[0323] Figure 41 is a diagram illustrating various states of an HSM component according to some embodiments. As used in this disclosure, the HSM may include a master component that manages the core instrument state and legacy DX-compatible sub-states. Furthermore, the HSM may interact with a GxIp component to enable or disable GxIp commands based on the current instrument core state. In some embodiments, advanced states may include POST-Power On Self Test, RECOVERY, IDLE, WAITING_FOR_CART, LOADING_CART, CARTRIDGE_LOADED, RUNNING_ASSAY, ABORTING, and CARTRIDGE_PROOAD. Those skilled in the art will understand that the names of these states are provided as non-limiting examples, and that the names and functions of these states may vary depending on desired functionality.

[0324] Figure 42 This diagram illustrates the internal components and interfaces of the instrument core according to some implementations. For example, the PSoC USB is an internal interface that serves as the main component for the "southbound" interface supporting PSoC components (speakers, doors, syringes, valves, and ICOREs). This component can use USB 2.0 to create a "data backplane" between the Cell Core and each PSoC. In some implementations, during boot, the PSoC can be enumerated as a bootable endpoint, allowing new firmware to be programmed on each PSoC. In some implementations, during normal operation, the PSoC can be enumerated as a command endpoint and a State Swap endpoint. Here, the State Swap can undertake high-speed PSoC data virtualization on the Cell Core, allowing monitoring and / or analysis of high-speed PSoC data on the Cell Core, and / or supporting Gx Streaming components on the Cell Core.

[0325] In some implementations, the instrument PSoC external interface may include Comms_Task, which may be the master PSoC component supporting the "southbound" interface between the PSoC and the Cell Core. It may also be the master component Pn of the PSoC to create a "data backplane" between the Cell Core and each PSoC. Alternatively, Comms_Task may be a generic interface that allows all PSoCs to create and manage command and status exchange USB endpoint interfaces.

[0326] In some implementations, the analysis task may include another PSoC external interface, which may be the main PSoC component that supports PSoC command processing. In some implementations, the analysis task may include common processing of common commands shared by all PSoCs.

[0327] According to some embodiments of the present invention, the instrument PSoC external interface may further include an ISR. The ISR may allow for co-processing of time and / or specific priority processing of background trajectories on the PSoC.

[0328] 9.M Mobile Devices - Software Components

[0329] Figure 43 This is a block diagram illustrating software components executed on a mobile device according to some embodiments of the present invention. Here, the user interface may follow common Android (or other OS) design patterns. Activities may be components that control the flow through the user interface and views that are always visible. A view may be a set of components that present information to the user. In some embodiments, most of the business logic may be contained within... Figure 43 The service components shown.

[0330] In some implementations, the user interface may present the specific workflows required to run kit-based diagnostics on separate modules, ensuring the accuracy and granularity of patient data associated with specific diagnostic results. This includes an automated chain of custody from sample collection to the kit and instrument database.

[0331] According to some implementations, the data layer may include a data manager that provides persistence for all databases within the application. In some implementations, the mobile database may be SQLite and may be encrypted using SQLCipher. The mobile database may include authorized users, certificates, and / or logging information. Since the mobile device can act as a standalone mobile router for diagnostic data transmission, the data in the database can provide credentials and authentication to initiate and terminate transmission connections. More information on establishing these connections is provided below. In some implementations, the data layer may also provide two APIs to the rest of the system: a data API for general database objects and a logging API for logging critical events. These APIs allow the mobile diagnostic device to connect to a remote database and transparently move diagnostic data and other descriptive data from the diagnostic device to a remote, properly configured internet instance of Xpert.

[0332] like Figure 43 As shown, the implementation may include a site administrator who manages the site's status and can maintain a list of known users, known diagnostic devices, known mobile devices, known labs, and / or known printers. When a mobile device is connected to the internet, the site administrator can coordinate with a remote Xpert+ to manage remote service commands for the site. The site administrator can also interact with peer mobile devices as needed to manage site status and / or handle user authentication.

[0333] Some implementations may also include a configuration manager that can provide cloud communication access to remote Xpert+ services and / or manage the current configuration of the mobile device. In other words, the cloud communication component can establish and manage communication with one or more remote services (e.g., such as...). Figure 38 The diagram shows a bidirectional communication link for a remote Xpert+. Communication can be established through one or more APIs that can parse, interpret, and transmit data (e.g., in proprietary formats) in a standard readable format.

[0334] like Figure 43 As further illustrated, implementations may include an instrument manager that manages a current list of instruments (medical diagnostic devices) and monitors the status of all instruments at the site. The instrument manager may also provide the ability to perform operations on the diagnostic devices. For example, these operations may include performing tests using laboratory tests, installing tests, installing software upgrades, performing diagnostics, and / or synchronizing time references. The instrument manager may further select instruments and / or handle errors reported by instruments when a test is requested. According to some implementations, instrument communication may be encapsulated with communication via the medical diagnostic device's REST API.

[0335] Some implementations may also include a test manager that can manage a list of active tests, manage the workflow for executing tests, report test results upon completion, and / or "archive" tests when no longer needed. In some implementations, SMS communication can encapsulate result reports via SMS to the agency's accounting office. In some implementations, printer communication can encapsulate the ability to print reports on a local thermal printer.

[0336] Generally, the functionality of a mobile device can depend on the available software development kits (SDKs) and APIs for various platforms. For example, with the Android SDK and APIs, application functionality is limited by the public APIs of the Android SDK. Even so, the Android SDK and APIs can be used to provide access to NFC, camera, GPS, SMS messages, and / or the network.

[0337] Some implementations can use SQLite and SQLCipher, which are standard databases on Android. For example, the Open Web Application Security Project (OWASP) cites SQLCipher as the preferred method for protecting data on mobile devices. Nevertheless, alternative implementations can utilize other platforms such as iOS, Windows Mobile, etc. Additionally or alternatively, other data structures and / or query languages ​​such as SQL, HTSQL, 100Q, etc., can be used.

[0338] Some implementations may provide a third-party remote support application that allows for remote display and (if available) remote control of the mobile device provided by the third-party application. In some implementations, the version of the mobile device software may use an associated SDK to provide remote control of the application.

[0339] Furthermore, this invention provides a consolidation of control and management of diagnostic devices, as well as LAN and WAN connectivity on mobile devices (such as the previously described LAN-WAN routing), which is not used in traditional medical diagnostic industrial control and communication. Local control segments of the device (LAN layer) and communication with each diagnostic instrument can be accomplished at a peer-to-peer level (e.g., via Wi-Fi) and data flow management for each instrument can be implemented in both the UI control interface and the remote Xpert data path interface in the cloud.

[0340] Using NFC on mobile devices Figure 43The NFC adapter shown can be used to control the chain of custody for patient samples. Intermediate data provided to the rights holder enables the traceability of these functions, which can be stored in a central cloud repository. NFC can simultaneously connect a test kit containing a patient sample to a separate NFC signal from the diagnostic device to ensure regulatory compliance and reporting accuracy requirements.

[0341] Figure 43 An instrument communication component is also shown, which can establish a peer-to-peer Wi-Fi connection between mobile devices and diagnostic devices. The instrument communication component enables multiple mobile devices to communicate with each other. In some embodiments, a handheld coordinator can provide coordination among multiple mobile devices via Wi-Fi.

[0342] 9.N Remote Diagnostic Reporting Service - Software Component

[0343] Figure 44 This is a block diagram illustrating software components executed by a remote diagnostic reporting service for medical diagnosis and epidemiology, according to some embodiments of the present invention. The remote diagnostic reporting service includes a web server, application server, database server, and file storage, etc.

[0344] According to some implementation methods Figure 44 The logical components of the remote diagnostic reporting service shown can be described as follows: The remote Xpert+ service may include mobile devices and REST web services used by Xpert. The GUI application may include a web application used by entities providing services and support to the diagnostic testing system. Dedicated services may include REST web services used by the GUI application. The core business logic service may include a REST web service containing all business logic. The auditing and logging service may include a REST web service with all logging and auditing functions. Finally, the file transfer service may include a REST web service to retrieve file storage solutions.

[0345] In addition to other benefits, Figure 44 The diagnostic reporting service shown can also enable automated remote diagnostics from Class 2 or 3 medical diagnostic devices to remote databases and presentation layers. Furthermore, hierarchical authentication allows for real-time remote control of the commissioning and diagnostics of remote Class 2 or 3 medical diagnostic devices via WAN connectivity. This can be a service integration of discrete functions, including real-time diagnostics and time-series data specifically designed for applications in PCR-based diagnostic environments.

[0346] 9.0 Establishing a Diagnostic Testing System - Workflow

[0347] Used to establish molecular diagnostic testing systems (e.g.) Figure 38The exemplary workflow of the system shown may include the following stages. It should be understood that although specific wireless technologies (e.g., GSM, CDMA, Wi-Fi, etc.) are mentioned in the exemplary embodiments provided below, additional or alternative technologies may be used depending on the desired functionality.

[0348] First, mobile devices can be delegated to work in the diagnostic testing system. Here, the mobile device utilizes an internet connection (e.g., cellular, Wi-Fi, etc.). For cellular connections (e.g., GSM, CDMA, etc.), the mobile device may need to be provided by the operator. Furthermore, the mobile device can be configured remotely via Xpert+, which may require downloading an initial set of users, determining a set of authorized tests, and assigning them to the site.

[0349] Secondly, a Wi-Fi network can be configured. Here, a mobile device can be selected to act as a Wi-Fi hotspot (e.g., a bridge between a LAN and a WAN network), and other mobile devices can connect to the Wi-Fi hotspot. In some implementations, all diagnostic devices can use a single mobile device acting as a Wi-Fi hotspot to directly access the remote Xpert. Alternatively or additionally, one or more other mobile devices can connect to the mobile device acting as the hotspot via Wi-Fi. If the mobile device acting as the hotspot malfunctions, runs out of power, or is lost, a second mobile device can be used at its location.

[0350] Third, diagnostic devices can be configured. In some implementations, this process may involve sharing Wi-Fi information (e.g., SSID and passphrase) and / or other information with the mobile device. The mobile device can also obtain identification information, such as MAC address, serial number, etc., from the diagnostic device. This information sharing can be done using peer-to-peer NFC. Additional diagnostic devices can be added in the manner described above. If physical sorting is important, the mobile device's user interface can allow the user to specify the placement location of new instruments.

[0351] 9. Data Flow of the P Diagnostic Testing System

[0352] Figures 45 to 46 This is a data flow diagram illustrating different aspects of a diagnostic testing system according to some embodiments of the present invention. As with the other figures provided herein, [the following are also provided]. Figures 45 to 46 As a non-limiting example, alternative implementations may include the additional functions shown in the figures, and / or the functions shown in the figures may be omitted, combined, separated, and / or performed simultaneously. The means for performing the functions of the block may include one or more hardware and / or software components, such as... Figure 38 and 53 Those shown are examples. Those skilled in the art will recognize some variations.

[0353] 9. Q Diagnostic Testing System Top-Level Data Stream

[0354] Figure 45 It shows a diagnostic testing system (such as...) Figure 38 The diagram shows the top-level data flow in a diagnostic testing system. Here, the components of the diagnostic testing system—remote services, mobile devices, and diagnostic devices—are depicted as circles, and the data flow is represented by arrows.

[0355] Data flow can be initiated when the mobile device sends a location configuration request (1) to a remote service. The request can be made when the mobile device is located at a new site where the diagnostic device is located. For example... Figure 45 As shown, the request may only need to be executed once at each location.

[0356] The remote service then responds using the location configuration (2), and the remote service and the mobile device exchange configuration descriptions (3). As previously mentioned, this involves downloading an initial set of users from the remote service to the mobile device, determining a set of authorized tests, etc. The remote service may also provide operational updates to the mobile device (4).

[0357] The mobile device can then participate in the configuration process of the diagnostic device. During this process, the mobile device provides the diagnostic device with diagnostic device registration (5) and operation updates (6).

[0358] Once configured, the diagnostic device can receive operating instructions from the mobile device. The mobile device can then provide device commands (7) to the diagnostic device, which can be based on user input. As previously described, such commands may include, for example, running tests using a laboratory, installing a laboratory, installing software upgrades, performing diagnostics, and / or synchronizing time references. The diagnostic device can provide command responses (8), such as confirmations, status updates, etc.

[0359] When a device command (7) causes a medical diagnosis to be performed, the diagnostic device can then provide an encrypted medical diagnosis result (9) to a remote service. As previously mentioned, the mobile device can provide a hotspot through which the diagnostic device can send the encrypted medical diagnosis result (9). However, the mobile device may not decrypt or store the data. Thus, according to some embodiments, the mobile device merely acts as a conduit through which the encrypted medical diagnosis result (9) can be reported to the remote service. In some embodiments, the encrypted medical diagnosis result (10) can be sent to the mobile device and stored. (As previously mentioned, in some embodiments, the data may not be stored on the mobile device. In such embodiments, the mobile device can send the data to another device—e.g., a storage device on a LAN, a computer, etc.—for storage.) Depending on the required functionality, the encrypted medical diagnosis result (10) sent to the mobile device may be the same as or different from the result sent to the remote service.

[0360] IX. R, Detailed Data Stream of Mobile Devices

[0361] Figure 46 This is a data flow diagram showing a more detailed depiction of the data flow of the components of the mobile device—the WAN interface component, the medical diagnostic logic, and the LAN interface component.

[0362] Similar to Figure 45 The process, Figure 46 The illustrated process can begin with the configuration procedure between the mobile device and the remote service. Here, the medical diagnostic logic sends a request for location configuration to the WAN interface component (1.1), which then sends the request to the remote service (1.2). The remote service responds by providing the location configuration to the WAN interface component (2.1), which in turn provides the location configuration to the medical diagnostic logic (2.2). Configuration descriptions are then exchanged between the remote service and the WAN interface component (3.1), between the WAN interface component and the medical diagnostic logic (3.2), between the medical diagnostic logic and the LAN interface component (3.3), and between the LAN interface component and the medical diagnostic device (3.4). Operation updates are then passed from the remote service to the WAN interface component (4.1) and from the WAN interface component to the medical diagnostic logic (4.2).

[0363] Diagnostic device configuration may include medical diagnostic device registration (5.1), (5.2) using medical diagnostic logic, LAN interface components, and devices. These components will also pass operational updates (6.1), (6.2) from the medical diagnostic logic to the diagnostic device.

[0364] Then the device commands (7.1) and (7.2) can be sent from the medical diagnostic logic to the diagnostic device, and the command responses (8.1) and (8.2) can be sent from the diagnostic device back to the medical diagnostic logic.

[0365] Encrypted diagnostic results (9.1), (9.2) can be sent from the diagnostic device to the LAN interface component, and then directly to the WAN interface component, without passing through the medical diagnostic logic. The encrypted diagnostic results (9.3) can then be sent to a remote service. As previously mentioned, the encrypted diagnostic results (10.1), (10.2) can be sent separately to the medical diagnostic logic, and then they can be sent to an encrypted diagnostic results repository (10.3). Depending on the required functionality, this repository may be separate from the mobile device. The encrypted diagnostic results (11.1), (11.2) can also be sent from the medical diagnostic logic and the remote service via the WAN interface component.

[0366] In some implementations, the remote service may request diagnostics. As shown, the remote service requests diagnostics relayed to the diagnostic device (12.1), (12.2), (12.3), (12.4). This may prompt a diagnostic response relayed back to the remote service (13.1), (13.2), (13.3), (13.4).

[0367] 9.S Diagnostic Testing System Workflow

[0368] Figures 47 to 52 This illustrates a diagnostic testing system (e.g., according to some embodiments of the present invention) Figure 38 The flowchart illustrates the functions of different aspects of the diagnostic testing system shown. As with other figures provided herein, [further details are provided]. Figures 47 to 52 As a non-limiting example, alternative implementations may include the additional functions shown in the drawings, and / or the functions shown in the drawings may be omitted, combined, separated, and / or performed simultaneously. The means for performing the functions of the block may include one or more hardware and / or software components, such as... Figure 38 and 53 Those shown are examples. Those skilled in the art will recognize some variations.

[0369] 9.T Location Configuration Network Workflow

[0370] Figure 47 This is a data flow diagram illustrating the location configuration process for a diagnostic testing system according to an embodiment. (For execution...) Figure 47 The apparatus of one or more blocks shown may include the remote services described herein.

[0371] This process can begin when the mobile device requests location configuration. As previously explained, an exemplary data stream for such a request is... Figure 45 and Figure 46 As shown in the diagram. If the location configuration is available, it is provided by the remote service. If it is not available, the remote service returns an error.

[0372] 9. U-Operation Update Network Workflow - Mobile Devices

[0373] Figure 48 This is a data flow diagram illustrating a process for providing operational updates to a mobile device in a diagnostic testing system according to some embodiments of the present invention. For execution Figure 48 The apparatus of one or more blocks shown may include the remote services and / or mobile devices described herein.

[0374] The process can begin when a locally configured mobile device connects to a remote service. The remote service then obtains a description of the mobile device's operation. If the description matches the required mobile device configuration, the process can end. Otherwise, the remote service sends an operation configuration update to the mobile device.

[0375] 9.V Operation Update Network Workflow - Diagnostic Device

[0376] Figure 49 This is a data flow diagram illustrating, according to some embodiments, the process of providing operational updates to a diagnostic device in a diagnostic testing system. (For execution) Figure 49 The apparatus of one or more blocks shown may include the mobile device and / or diagnostic device described herein.

[0377] This process can begin when the mobile device obtains the diagnostic device configuration description from the diagnostic device. If the diagnostic device is configured correctly, the process can end. Otherwise, the mobile device can send an operation configuration update to the diagnostic device.

[0378] 9.W Remote Diagnostic Network Workflow

[0379] As mentioned above Figure 46 The remote service discussed can remotely request diagnostic information. Figure 50 This is a data flow diagram of such a process in a diagnostic testing system according to an implementation method. Used for execution Figure 50 The apparatus of one or more blocks shown may include the remote services, mobile devices and / or diagnostic devices described herein.

[0380] The process can begin when a remote service requests diagnostic information. The mobile device receives the diagnostic information request. If the diagnostic request is specific to the mobile device, the mobile device performs the requested mobile device diagnostics and sends the mobile device diagnostic information to the remote service. Otherwise, the diagnostic request is sent by the mobile device to a designated diagnostic device (which may be one of several located at a site and / or linked to the mobile device). The diagnostic device then performs the requested diagnostics and sends the diagnostic information to the mobile device. Finally, the mobile device sends the diagnostic device diagnostic information to the remote service.

[0381] 9.X Medical Diagnostic Device Command Network Workflow

[0382] Figure 51 This is a data flow diagram illustrating a process for providing diagnostic device commands in a diagnostic testing system according to some embodiments of the present invention. For execution Figure 51 The apparatus of one or more blocks shown may include the mobile device and / or diagnostic device described herein.

[0383] The process can begin with the mobile device sending a command to the diagnostic device. The diagnostic device then processes the received command. Finally, the diagnostic device sends a response to the mobile device.

[0384] 9. Y-Diagnostic Device Registration Network Workflow

[0385] Figure 52 This is a data flow diagram illustrating a process for providing diagnostic device registration on a network of a diagnostic testing system according to some embodiments of the present invention. [The process is used to execute...] Figure 52 The apparatus of one or more blocks shown may include the mobile device and / or diagnostic device described herein.

[0386] The process can begin when the mobile device queries the diagnostic device for its physical network identifier (e.g., MAC address). As previously described, the mobile device then provides network access information to the diagnostic device. This information may include SSID, username, etc. In some implementations, as previously described, communication between the mobile device and the diagnostic device at this point can be performed via NFC and / or other wireless technologies. The diagnostic device then connects to the network, and the mobile device assigns a local identifier to the diagnostic device.

[0387] 9.Z Computer System

[0388] Figure 53 This is an exemplary illustration of computer system 5300, which may be at least partially incorporated into... Figure 38 The diagnostic testing system shown includes diagnostic devices (Epsilon instruments), mobile devices (Epsilon handheld platforms), and / or remote services (remote Xpert systems and pre-molded Xpert+ systems). Figure 53 A schematic diagram of a computer system 5300 capable of performing methods provided by various embodiments of the present invention is provided. It should be noted that... Figure 53 This is intended only to provide a general description of the various components, in which any or all of the components may be used appropriately.

[0389] The illustrated computer system 5300 includes hardware elements that can be electrically connected (or otherwise communicated where appropriate) via a bus 5306. The hardware elements may include: processing units (such as processor 5310), which may include, but are not limited to, one or more general-purpose processors, one or more special-purpose processors (such as digital signal processing chips, graphics accelerators, etc.), and / or other processing devices; one or more input devices 5315, which may include, but are not limited to, a mouse, keyboard, camera, microphone, touchscreen, medical testing hardware, and / or diagnostic components; and one or more output devices 5320, which may include, but are not limited to, display devices, printers, etc.

[0390] The computer system 5300 may also include (and / or communicate with) one or more non-transitory storage devices 5325, which may include, but are not limited to, local and / or network-accessible memory, and / or may include, but are not limited to, disk drives, drive arrays, optical storage devices, solid-state storage devices such as random access memory (“RAM”) and / or read-only memory (“ROM”), which may be programmable, flash-updatable, etc. Such storage devices can be configured to implement any suitable data storage, including but not limited to various file systems, database structures, etc.

[0391] In some embodiments, computer system 5300 may include a communication subsystem 5330, which may include, but is not limited to, a modem, a network interface card (NIC) (wireless or wired), an infrared communication device, a wireless communication device, and / or a chipset (such as an NFC transceiver, a Bluetooth device, an 802.11 device, a Wi-Fi device, a WiMax device, a cellular transceiver, etc.). Communication subsystem 5330 may include one or more input and / or output communication interfaces to allow data exchange with networks, other computer systems, and / or any other electrical devices described herein (e.g., using peer-to-peer communication as described herein). In some embodiments, as described above, computer system 5300 will include working memory 5335, which may include RAM or ROM devices.

[0392] Computer system 5300 may include software elements shown as currently residing in working memory 5335, including operating system 5340, device drivers, executable libraries and / or other code, such as one or more application programs 5345, which may include computer programs provided by various implementations (e.g., mobile device software, interface software, etc.), and / or may be designed to implement the methods and / or software architectures described herein. The methods and / or architectures provided in the other accompanying figures, by way of example only, may be implemented as code and / or instructions executable by a computer (and / or processing units within a computer); then, in one aspect, such code and / or instructions may then be used to configure and / or adjust a general-purpose computer (or other device) to perform one or more operations according to the described methods.

[0393] This collection of instructions and / or code may be stored on a non-transitory computer-readable storage medium such as the storage device 5325 described above. In some embodiments, the storage medium may be incorporated into a computer system such as computer system 5300. In some embodiments, the storage medium may be separate from the computer system (e.g., a removable medium, such as an optical disc) and / or provided in an installation package, such that the storage medium can be used to program, configure, and / or adjust a general-purpose computer using the stored instructions / code. These instructions may take the form of executable code executable by computer system 5300 and / or may take the form of source code and / or installable code, which, when compiled and / or installed on computer system 5300 (e.g., using any of commonly available compilers, installers, compression / decompression utilities, etc.), then take the form of executable code.

[0394] It will be apparent to those skilled in the art that substantial variations can be made to suit specific requirements. For example, custom hardware may be used, and / or specific elements may be implemented using hardware, software (including portable software such as applets), or both. Connections to other computing devices (e.g., network input / output devices) may be used.

[0395] Some implementations may use a computer system (such as computer system 5300) to perform methods according to some embodiments of the invention. In some implementations, some or all of the processes of these methods are performed by computer system 5300 in response to processor 5310 executing one or more sequences of one or more instructions contained in working memory 5335 (these instructions may be incorporated into operating system 5340 and / or other code, such as application program 5345). Such instructions may be read into working memory 5335 from another computer-readable medium (e.g., one or more storage devices 5325). By way of example only, execution of the sequence of instructions contained in working memory 5335 may cause processor 5310 to perform one or more processes of the methods described herein. Alternatively or additionally, certain portions of the methods described herein may be performed by dedicated hardware.

[0396] As used herein, the terms "machine-readable storage medium" and "computer-readable storage medium" refer to any storage medium that participates in providing data that enables a machine to operate in a particular manner. In some embodiments implemented using computer system 5300, various computer-readable media may relate to providing instructions / code to processor 5310 for execution and / or being used to store and / or carry such instructions / code. In some embodiments, the computer-readable storage medium is a physical and / or tangible storage medium. Such a medium may take the form of a non-volatile medium or a volatile medium. Non-limiting examples of non-volatile media may include optical discs and / or magnetic disks (such as storage device 5325). Non-limiting examples of volatile media may include, but are not limited to, dynamic memory (such as working memory 5335).

[0397] Non-limiting common forms of physical and / or tangible computer-readable media may include, for example, floppy disks, flexible disks, hard disks, magnetic tapes or any other magnetic media, CD-ROMs, any other optical media, RAM, PROMs, EPROMs, FLASH-EPROMs, any other memory chips or cassettes, or any other media from which a computer may read instructions and / or code.

[0398] Various forms of computer-readable media may involve carrying one or more sequences of one or more instructions to processor 5310 for execution. By way of example only, the instructions may initially be carried on a disk and / or optical disk of a remote computer. The remote computer may load the instructions into its dynamic memory and transmit the instructions as signals via a transmission medium for reception and / or execution by computer system 5300.

[0399] The communication subsystem 5330 (and / or its components) typically receives signals, and then the bus 5306 can transmit the signals (and / or the data, instructions, etc. carried by the signals) to the working memory 5335, from which the processor 110 retrieves and executes the instructions. The instructions received by the working memory 5335 may optionally be stored on a non-transitory storage device 5325 before or after execution by the processor 5310.

[0400] 9. Process flow of the AA management diagnostic testing system

[0401] Figure 54 This is a flowchart 5400 of a method for managing a diagnostic testing system with a mobile device according to some embodiments of the present invention. As with other figures provided herein, [the following is also provided]. Figure 54As a non-limiting example, some implementations may include the additional functions shown in the figures, and / or the functions shown in one or more blocks in the figures may be omitted, combined, separated, and / or performed simultaneously (or in close proximity in time). The means for performing the functions of said blocks may include the mobile device described herein, which may implement one or more hardware and / or software components, such as... Figure 53 Those shown are examples. Those skilled in the art will recognize some variations applicable to the invention disclosed herein.

[0402] At box 5410, the mobile device receives user input for controlling the functions of the diagnostic device. As previously described, the mobile device may execute a software application with a GUI that provides the user with various functions of the diagnostic device (e.g., management settings for the diagnostic device); initiate, pause, or cancel medical tests performed by the diagnostic device; specify remote services from which the diagnostic device will send data; specify the type, content, and / or format of the data, etc. At box 5420, in response to receiving user input, the mobile device sends control information to the diagnostic device. If the mobile device is communicatively linked to multiple diagnostic devices, the mobile device may first need to select or identify a diagnostic device from among the multiple diagnostic devices.

[0403] At box 5430, the mobile device receives data from the diagnostic device. The received data may correspond to the type, content, and / or format of the data specified at box 5410 (if these characteristics are specified). However, as indicated, the mobile device may simply be used as a pass-through device where the diagnostic device can communicate with a remote server (e.g., one or more remote services). In other words, the mobile device may act as a transparent bridge to connect a LAN (which may be a peer-to-peer connection as described herein) to a WAN. However, as specified at box 5440, the received data may be relayed to the server without storing or decrypting the data, thereby helping to ensure that sensitive patient data is not misused by the mobile device.

[0404] The methods, systems, and apparatus discussed above are examples. Various configurations can omit, replace, or add various procedures or components as needed. For example, in alternative configurations, methods can be performed in a different order than those described, and / or stages can be added, omitted, and / or combined. Furthermore, features described with respect to certain configurations can be combined in various other configurations. Different aspects and elements of the configurations can be combined in a similar manner. Moreover, technological evolution and some elements as described above are provided as non-limiting examples and therefore do not limit the scope of this disclosure or the claims.

[0405] Specific details are provided in the description to offer a comprehensive understanding of the exemplary configuration, including its implementation. However, the configuration may be implemented without these specific details. For example, well-known circuits, processes, algorithms, structures, and techniques do not show unnecessary details to avoid obscuring the configuration. This description provides exemplary configurations that do not limit the scope, applicability, or configuration of the claims. Rather, the prior description of the configuration will provide those skilled in the art with an enabling description for implementing the described techniques. Various changes may be made to the function and arrangement of the elements without departing from the spirit or scope of this disclosure.

[0406] Furthermore, the configuration can be described as a process depicted as a flowchart or block diagram. While each process can be described as a sequential sequence of operations, some operations can be executed in parallel or simultaneously. Moreover, examples of these methods can be implemented using hardware, software, firmware, middleware, microcode, hardware description languages, or any combination thereof. When implemented in software, firmware, middleware, or microcode, the program code or code segments that perform the necessary tasks can be stored in a non-transitory computer-readable medium, such as a storage medium. The processor can execute the described tasks.

[0407] As used herein, the terms “and” and “or” can include a variety of meanings that are expected to depend at least in part on the context in which these terms are used. Generally, if “or” is used to relate a list (e.g., A, B, or C), it is intended to mean A, B, and C (used herein in an inclusive sense) and A, B, or C (used herein in an exclusive sense). Additionally, the term “one or more” as used herein can be used to describe any feature, structure, or property in its singular form, or can be used to describe some combination of features, structures, or properties. However, it should be noted that this is merely an illustrative example, and the subject matter claimed is not limited to this example. Furthermore, if the term “at least one” is used to relate a list such as A, B, or C, it can be interpreted as referring to any combination of A, B, and / or C, such as A, AB, AA, AAB, AABBCCC, etc.

[0408] Several exemplary configurations have been described, and various modifications, alternative constructions, and equivalents may be used without departing from the spirit of this disclosure. For example, the above elements may be components of a larger system, where other rules may take precedence over or otherwise modify the application of the invention. Furthermore, multiple steps may be performed before, during, or after considering the above elements. Therefore, the above description does not limit the scope of the claims. All patents, patent applications, and other publications referenced in this application are incorporated herein by reference in their entirety for all purposes.

Claims

1. A system for operating a syringe driver of a diagnostic assay system, comprising: a chassis of a diagnostic assay system; a brushless direct current (BLDC) motor coupled to the chassis of the diagnostic assay system; a reversibly drivable lead screw operable by the brushless direct current motor; a plunger rod operable by the lead screw to engage a removable assay cartridge, wherein the brushless direct current motor is configured to operate the lead screw based on monitoring a current draw of the brushless direct current motor, the current associated with a change in pressure within the removable assay cartridge, and wherein the lead screw is not associated with any position sensor and the brushless direct current motor does not include any encoder hardware.

2. The system of claim 1, wherein, the plunger rod is coupled to the lead screw by a cross arm.

3. The system of claim 2, wherein, the plunger rod is operable to engage a plunger head of a removable assay cartridge.

4. The system of claim 1, wherein, the brushless direct current motor is configured to change operation based on detecting a change in the current to change pressure within the removable assay cartridge.

5. The system of claim 4, wherein, changing operation of the brushless direct current motor includes raising the plunger rod to decrease pressure within the removable assay cartridge.

6. The system of claim 4, wherein, changing operation of the brushless direct current motor includes lowering the plunger rod to increase pressure within the removable assay cartridge.

7. The system of claim 4, wherein, changing operation of the brushless direct current motor includes slowing the plunger rod to decrease a rate of pressure change within the removable assay cartridge.

8. The system of claim 4, wherein, changing operation of the brushless direct current motor includes speeding the plunger rod to increase a rate of pressure change within the removable assay cartridge.

9. A method for operating a syringe driver of a diagnostic assay system, the method comprising: receiving a command to power a brushless direct current (BLDC) motor, the brushless direct current motor operable to turn a reversibly drivable lead screw, a plunger rod coupled to the lead screw and movable by the lead screw; applying power to the brushless direct current motor to move the plunger rod to engage a plunger head within a syringe channel of a removable assay cartridge; monitoring movement of the plunger rod within the syringe channel by monitoring at least one current associated with operation of the brushless direct current motor; detecting a change in the current of the brushless direct current motor; and based on detecting the change in the current of the brushless direct current motor, changing operation of the brushless direct current motor to effect a change in movement of the plunger rod within the removable assay cartridge, wherein the lead screw is not associated with any position sensor and the brushless direct current motor does not include any encoder hardware. monitoring the at least one current of the brushless direct current motor occurs as the plunger rod moves.

10. The method of claim 9, wherein, changing operation of the brushless direct current motor includes raising the plunger rod to decrease pressure within the removable assay cartridge.

11. The method of claim 10, wherein, changing operation of the brushless direct current motor includes lowering the plunger rod to increase pressure within the removable assay cartridge.

12. The method of claim 10, wherein, changing operation of the brushless direct current motor includes slowing the plunger rod to decrease a rate of pressure change within the removable assay cartridge.

13. The method of claim 10, wherein, changing operation of the brushless direct current motor includes speeding the plunger rod to increase a rate of pressure change within the removable assay cartridge.

14. The method of claim 10, wherein, ​

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