Modular instrument for testing microfluidic cartridges useful for point-of-care medical diagnostics and other applications

Abstract

Disclosed herein are embodiments of devices designed to receive microfluidic cartridges, including features used to align internal components of the device, which are also used to align components of the device with a microfluidic cartridge inserted into the device.

Description

[Technical Field]

[0001] The present invention relates to a modular, portable instrument for evaluating a fluid sample (e.g., a bodily fluid sample) contained in a microfluidic cartridge. The present invention further relates to an integrated alignment mechanism for interfacing the microfluidic cartridge to the instrument, as well as for interfacing internal components of the instrument. The instruments described herein are useful, for example, as point-of-care medical diagnostic devices. [Background technology]

[0002] The coagulation system is a delicate balance between hemorrhage and thrombosis. Many disease states and clinical situations (e.g., cancer, autoimmune diseases, infections, trauma, surgery, cardiac disease, drug treatments, etc.) can cause a disruption of this balance, leading to severe, and potentially life-threatening, bleeding or clotting events in patients.

[0003] Several coagulation tests have been developed to diagnose conditions such as hemophilia and monitor the progress of anticoagulant therapy and other medications. Common tests include measuring prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT). Other tests and testing devices have also been developed (see U.S. Patent Application Publication No. 2019 / 0111431, U.S. Patent No. 10,598,675, and U.S. Patent No. 10,534,006). Options for point-of-care testing devices remain limited. Therefore, there is a need in the art for devices suitable for point-of-care analysis of patient blood samples. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] US Patent Application Publication No. 2019 / 0111431 [Patent Document 2] U.S. Patent No. 10,598,675 [Patent Document 3] U.S. Patent No. 10,534,006 Summary of the Invention

[0005] Described herein are embodiments of devices that include alignment features and are configured to receive microfluidic cartridges. The alignment features are used to align internal components of the device. The alignment features are also used to align components of the device with a microfluidic cartridge inserted into the device. Such alignment features may include pins, slots, and / or V-shaped and flat portions, as described herein. Such alignment features are useful in devices designed to test fluid samples contained in microfluidic cartridges; for example, a modular, portable, point-of-care medical diagnostic instrument used to analyze bodily fluid samples (e.g., blood or plasma) contained in a cartridge may include the alignment features and other components described herein.

[0006] In certain embodiments, one or more internal components of the device include slots and / or Vs and flats that interface with pins located on structures within the device (e.g., the base of the device). Interfacing one or more slots and / or one or more Vs and flats on the component with one or more pins on the base of the device provides planar and rotational alignment between the component and the base of the device. Additionally, a microfluidic cartridge inserted into the device may include Vs and flats that interface with the pins, such interfacing providing planar and rotational alignment between the microfluidic cartridge and the device (e.g., with one or more internal components of the device).

[0007] Certain embodiments of the invention relate to devices that include a base, where the base includes pins (e.g., dowel pins). Each pin interfaces with a feature on a component of the device—a slot or a V-shape and a flat feature on the component. For example, in some embodiments, the invention relates to devices that include a base and a gantry, where the base includes three pins (e.g., three dowel pins) and the gantry includes three slots. The arrangement of the pins on the base and the slots in the gantry is such that insertion of the three pins into the three slots provides planar and rotational alignment of the base and the gantry.

[0008] Embodiments of the present invention further relate to a device configured to receive a microfluidic cartridge, the device comprising at least two pins (e.g., at least two dowel pins). For example, the device may comprise a base (e.g., a monolithic base) having two dowel pins. Each of the two pins is oriented on the base such that the pin interfaces with a V-shaped portion and a flat portion on a microfluidic cartridge inserted into the device. The interface between the pins and the V-shaped portion and the flat portion on the microfluidic cartridge provides alignment between the microfluidic cartridge and an internal component of the device, such as a component that also aligns with the two pins (via slots and / or V-shaped portions and flat portions on the component that interface with the pins, as described above). The alignment mechanisms described herein enable alignment of multiple components and microfluidic cartridges to the same reference (e.g., pins described herein).

[0009] Certain embodiments of the present invention relate to a device configured to receive a microfluidic cartridge, the device comprising a kinematic interface for interfacing the microfluidic cartridge with the device, the kinematic interface comprising a V-shaped portion and a flat portion (e.g., a V-shaped portion and a flat portion on the microfluidic cartridge that interface with a pin on the device), a latch that secures the microfluidic cartridge in place after the microfluidic cartridge is inserted into the device, an actuator configured to activate movement of a fluid contained within the microfluidic cartridge, and a user interface. In some embodiments, the user interface comprises an LCD (liquid crystal display) and a touch screen. In additional embodiments, the device may further comprise one or more of a barcode reader, a clicker that generates a sound when the cartridge is inserted, and a heater. In embodiments in which the device does not include a heater, the device may comprise a controller for controlling a heating element included in the microfluidic cartridge.

[0010] The present invention, as described herein, is directed to these and other important aspects. [Brief explanation of the drawings]

[0011] [Figure 1A] 1 shows an isometric view of the front of a device (device 10 according to an embodiment herein). [Figure 1B] 1 shows an isometric view of three modules (Modules 1, 2, and 3) of a device as described in an embodiment herein. Module 1 is a base subassembly 2, module 2 is a gantry subassembly 3, and module 3 is an upper shell subassembly 5. [Figure 1C] 1 shows an isometric view of a fixture (fixture 340) used to align pins (e.g., dowel pins shown as 301A and 301B) to establish key reference features, as described in embodiments herein. [Figure 1D]An isometric view of a cartridge (cartridge 60) is shown aligning with two pins (e.g., dowel pins shown as 301A and 301B in this embodiment). Other features, such as a latch 359, are also depicted in this view. [Figure 1E] An isometric view of the cartridge (cartridge 60) and interface board assembly (interface board 870) is shown. [Figure 2A] FIG. 1 shows an isometric view of the components of Module 1 (Base Subassembly 2). [Figure 2B] A top view of the components of Module 1 (Base Subassembly 2) is shown. [Figure 2C] 1 illustrates components actuated by a linear actuator, as described in embodiments herein. [Figure 2D] A cross-sectional view of the motor mount in the z-plane is shown, including a diagram of the photointerrupt switch function. [Figure 2E] An isometric view of the base and other components is shown with portions of the base removed to show the linear guide rail (linear guide rail 350) and other alignment features. [Figure 2F] 1 shows a rear isometric cross-sectional view in the y-plane with the heater arms in the active configuration. [Figure 2G] 1 shows the alignment surface between the carriage (carriage 351) and the carriage bracket (carriage bracket 352) as described in the embodiments herein. [Figure 3A] 1 shows an isometric view of the components of module 2, a gantry subassembly 3. [Figure 3B] A bottom view of Module 2 (Gantry Subassembly 3) is shown. [Figure 3C] 1 shows an expanded view of the components of a heater (heater 700 as described in embodiments herein). [Figure 3D] FIG. 1 shows a side view of the heater and heater actuator components. [Figure 3E] FIG. 1 shows an isometric view of the heater and heater actuator components. [Figure 3F] FIG. 10 is a cross-sectional side view of the heater mechanism in an undeployed state with components hidden for clarity. [Figure 3G] 1 shows a close-up of the latch, spring, and shoulder bolt that allows the latch to move in the z-direction. [Figure 3H] A detailed view of the latch ball bearing that fits into the latch arm groove is shown. [Figure 3I] FIG. 10 is a close-up perspective view of components on a utility bracket (utility bracket 303 according to an embodiment of the present disclosure). [Figure 4A] An isometric top view of the upper shell subassembly 5, module 3, is shown. [Figure 4B] An isometric bottom view of module 3 (upper shell subassembly 5) is shown. [Figure 4C] The bottom view of the main board (Main PCBA890) is shown. [Figure 4D] An enlarged isometric view of module 3 (upper shell subassembly 5) is shown. [Figure 5A] 1 shows an outline of the structural loop and alignment interdependencies between the cartridge and the device. [Figure 5B] FIG. 10 shows a bottom view of a gantry subassembly with symmetrical kinematic slots. [Figure 5C] FIG. 1 shows an isometric view of a heater, poron, and heater bracket with integrated V-shaped and flat alignment features. [Figure 6] 10 shows an embodiment of the device in which the base of the device tapers towards the bottom, making the device easier to hold in the hand. DETAILED DESCRIPTION OF THE INVENTION

[0012] The drawings and embodiments of the invention described herein are given by way of example, with it being expressly understood that the descriptions and drawings are for illustrative purposes only and that the embodiments are not intended to define the limits of the invention.

[0013] Described herein are modular instruments designed to receive and engage microfluidic cartridges. The instruments may include components, such as heaters, that are useful for performing specific tests on the fluid contained within the cartridge. The instruments described herein may be used as point-of-care medical diagnostic devices.

[0014] As shown in the embodiment depicted in FIGS. 1A and 1B, the device 10 has an inlet 300e for receiving a cartridge 60 containing a fluid sample. In some embodiments, the cartridge has a window 391 above it that is transparent to allow a barcode reader (if present) to read the barcode or label on the cartridge 60 as well as scan, for example, a hospital employee's badge. The bottom of the device may have an elastomeric base 388 to prevent slippage and limit access to the fasteners at the bottom of the base 300. The device's top shell 390 may have an open portion 390a that allows a user to interact with the touchscreen active area 830v using the LCD touchscreen assembly 830. See FIGS. 4A and 4D. The device 10 unit is turned on via a power button 970. The bottom base 300 may be shaped to improve the ergonomics of the device and assist the user in holding the device in their hand, as exemplified in the embodiment depicted in FIG. 6 (see 300Z in FIG. 6). As described in more detail herein, the features of the apparatus 10 allow for precision and efficient manufacturing of the assembly.

[0015] The configuration of device 10 shown in the embodiment depicted in FIG. 1B is divided into three modules: Module 1, the base subassembly 2; Module 2, the gantry subassembly 3; and Module 3, the upper shell subassembly 5. The first module (Module 1) is the base subassembly 2, which uses a base 300 to establish key features for the device and holds many of the mechanical components. Module 2 is the internal gantry subassembly 3, which may include additional hardware such as a heater 700 (see FIG. 3C) for raising the fluid sample in cartridge 60 to the desired testing temperature, as well as other electronic components. Module 3 is the upper shell subassembly 5, which includes a power button 970, an LCD touchscreen assembly 830, and a main circuit board 890.

[0016] Development of the device design began with establishing a single critical reference on the base subassembly 2 for alignment of specific device components and for alignment of the interface or connection between the cartridge 60 and the device 10. Robust, precise alignment can be achieved by maintaining a tight structural loop and referencing or aligning the device's critical components and cartridge to a single critical reference. Such robust alignment minimizes the need for complex tolerance stack-up analysis for critical component alignment. In the illustrated embodiment, the critical reference 30 on the device 10 is two pins, shown as dowel pins 301A and 301B, press-fit into the base (e.g., monolithic base) 300, as shown in FIG. 1C. The two dowel pins 301A and 301B align the cartridge 60, the gantry 302 (module 2) (see FIG. 3A), and the interface board 870 (module 2) (see FIG. 1E).

[0017] In a preferred embodiment, the alignment of the pins (e.g., two dowel pins 301A and 301B) is within 0.5 degrees of perpendicular. In embodiments where the pins are press-fit into the base, a high-precision arbor press may be used as part of the assembly process. An example of an arbor press that may be used includes the Schmidt Precision Manual Toggle Press D78112.

[0018] As shown in FIG. 1C, a fixture 340 can be used to align dowel pins 301A and 301B with reference dowel pin holes 300d on base (e.g., monolithic base) 300. Base 300, when made from commercially available materials, may be made of MIC6 or 6061T651 aluminum. In embodiments where the base is made of aluminum, the aluminum can conduct any operating heat generated by battery 930, stepper motor 310, and other electronic components to the environment. A fixture plate or cast aluminum is preferred to maintain the shape of the base throughout the machining process. Magnesium die-cast aluminum is another option, with post-machining to produce the final shape.

[0019] FIG. 1D shows cartridge 60 having barcode region 600x on cartridge body 600. Cartridge body 600 is aligned with pins 301A and 301B at positions 600a and 600b, respectively (see FIG. 1E). The embodiment of base 300 illustrated in FIG. 1D has latch 359 mounted on base 300. Latch 359 locks cartridge 60 in place while stringer (or push rod) 355 pushes bung 601 inside cartridge cylindrical region 600c (see FIG. 1E). In this example, a fluid sample is inserted into the cartridge through septum 602, as shown in FIG. 1E. Depressing bung 601 activates the fluid within cartridge 60. Cartridge 60 is prevented from moving by latch 359 engaging groove 600y in cartridge body 600. Interface board assembly 870 is aligned with the same two pins 301A and 301B. 1E shows cartridge 60 having a PCB board 800 with a series of contact pads 800a on its front edge. Contact pads 800a make electrical contact with Samtech spring connector 873p. Interface board pcb 871 contains wiring lines to a Tiger Eye connector 872 that ultimately connects to a main PCBA board 890 capable of processing data. Base Sub-Assembly

[0020] In addition to establishing alignment references, the base 300 (which may be a monolithic base) also serves to mount other base subassembly 2 components, such as the battery 930, linear actuator 310, linear guide rail 350, carriage 351, and other related components, as partially shown in Figures 2A and 2B.

[0021] In some embodiments, the base 300 has a window opening 300w below the cartridge fluid region to allow for visual inspection during the assembly process. The window opening 300w is closed by a lid 315 (see FIGS. 2A, 2B, and 2E). A bracket 780 (see FIG. 4B) can be used to engage the Toradex processing chip 891 and direct generated heat into the base 300.

[0022] In certain embodiments, the device (e.g., in the base subassembly) may include a flexible detent engagement mechanism, shown as 300d in FIG. 1C, such as a spring plunger that engages with a detent (detent shown as 600d in FIGS. 1D and 1E) in cartridge 60. Such a flexible detent engagement mechanism can provide tactile feedback to the user that the cartridge is fully engaged. Base Subassembly: Battery

[0023] The device 10 may be designed to be portable, powered from a wall outlet via an AC-to-DC power adapter (similar to a laptop computer) and / or powered by a DC battery 930 enclosed within the device 10. In embodiments where the device may accommodate a battery, the base 300 may have a recessed pocket 300b (as shown in FIG. 1C) for the battery 930. For safety reasons, it may be desirable for all electronic components inside the device to be supplied with DC power. As shown in FIGS. 2A and 4B, the battery 930 has a wire with a connector 943 that mates with the main PCBA 890 at location 890b. The base 300 may secure the battery 930 via an elastic strap 912, which may also be used to pre-load the battery 930 to the base 300. Two brackets 910 may be used to secure the elastic strap 912 to the base 300. Two CAM posts 915 may be used to further restrain the battery 930. There are several other ways to secure and pre-load the battery 930 to the base 300, for example, a rigid bracket with a foam interface may be used to pre-load the battery. Base Subassembly: Linear Actuator

[0024] The device 10 may include at least one actuator whose primary function is to engage the fluid moving mechanism of the cartridge 60 .

[0025] Increasing the number of actuators increases manufacturing costs. The embodiments described herein illustrate how a single actuator can be used for a desired function of the device 10. The embodiment of the base subassembly 2 shown in FIG. 2A illustrates a stepper motor 310 as the actuator. Such an actuator may be used to perform several tasks, including, for example, lowering the heater 700, securing the cartridge 60 in place within the device (e.g., by latching / locking the cartridge 60), and / or depressing a bung in the cartridge 60 to activate the fluid within the cartridge 60. In the embodiment described herein, a cable connects the motor interface 310i (see FIG. 2C) to a connection 890r on the main PCBA 890 (see FIG. 4D).

[0026] In some embodiments, heater 700 may be required to perform a particular test. For example, a coagulation test may require heating the sample to approximately 37°C. A mechanical lever mechanism, such as stepper motor 310 shown in the embodiment depicted in FIG. 2A, may be used to bring heater 700 into contact with cartridge 60. In addition to performing this function of lowering the heater, a mechanical lever mechanism, such as stepper motor 310, may also secure cartridge 60 to device 10. A third task, pressing a bung in cartridge 60 to trigger fluid movement within cartridge 60, may also be actuated by moving push rod (also known as piston rod or stinger) 355 in the negative y-direction via stepper motor 310.

[0027] In the embodiment described above, the latching mechanism (used to secure the cartridge 60 in place within the device) is incorporated into the base subassembly 2. In other embodiments, the latching mechanism may be incorporated into the gantry subassembly 3. Base Subassembly: Linear Guide Rail and Carriage

[0028] Using a single stepper motor 310 to perform the three tasks described above can be achieved by using a linear guide rail 350 and carriage 351 in combination with a multi-function bracket 352 driven by the stepper motor 310, as shown in FIG. 2C. The stepper motor 310 can be mounted to the base 300 using a motor mount 312. The linear guide rail 350 may include a low-profile carriage 351 and be configured to be parallel to the motor's lead screw 310t. As shown in this embodiment, the multi-function bracket 352 mounted to the carriage 351 (via four fasteners 352f, see FIG. 2D) holds the stepper motor nut 311, so that rotation of the lead screw 310t moves the linear carriage 351 in either the positive y-direction or the negative y-direction.

[0029] As shown in FIGS. 2B and 2C, carriage bracket 352 may be used to mount several components, such as heater actuation arm ball bearing 380H, nut 311, latch guide rail 357, and push rod 355. Carriage bracket 352 also has a flag area 352o that engages photointerrupt 320H mounted to motor mount 312 by M3 fastener 320f and lock nut 320n (see FIG. 2D). Photointerrupt 320H serves to ground or guide motor 310 during startup procedures. Photointerrupt wire 320w connects to main carrier PCBA 890 at location 890o using connector 320c (see FIGS. 2C and 4C). As motor lead screw 310t rotates, nut 311 moves along the length of lead screw 310t, moving bracket 352 toward or away from motor mount 312. As shown in Figure 2D, flag 352o on bracket 352 serves to break the beam of photointerrupt 320H, thus "homing" motor 310. A secondary photointerrupt 320 may be mounted on gantry utility bracket 303, where latch actuator 357 may have a flag that triggers the photointerrupt. The purpose of the optional second photointerrupt 320 is as a redundant safety. Base Sub-Assembly: Alignment Mechanism

[0030] As shown in FIG. 2E, the bearing rail 350 can be positioned relative to two protrusions 300k (e.g., dowel pins) or reference edges, while pins 301A and 301B are precisely positioned relative to the base 300. In this way, the cartridge 60 is kinematically aligned by the two pins 301A and 301B contacting the Vs and flats on the cartridge 60, as shown in FIG. 1D, thereby achieving alignment between the axis of motion guiding the push rod 355 and the cartridge cylinder chamber. When the structural loop on the cartridge 60 is locally closed at the entrance to the cylinder bore by the latch arm 357 moving in the negative Y direction, the latch 359 (see FIG. 1D) engages with a mating feature on the cartridge 60, ensuring restraint; the centers of rigidity (the latch) and friction (the sliding seal within the cartridge cylinder bore formed by the push rod 355) are very close to each other, reducing movement that might otherwise cause misalignment. By maintaining alignment of the components, electrical contact between the cartridge 60 and the device 10 is maintained even when high injection forces are generated, for example, by the push rod 355 pushing against the bung 601 in the cartridge 60 to activate fluid movement within the cartridge 60.

[0031] In some embodiments, motor mount 312 is aligned to base 300 via two dowel pins 312D, one located in hole 312p and the other in slot 312s to prevent the components from over-constraining, as shown in FIG. 2F. Carriage bracket 352 can be aligned to carriage 351 by aligning reference surface 352r on carriage bracket 352 with reference flat surface 351r on carriage 351, as shown in FIG. 2G. There are alternative methods for aligning carriage bracket 352 to other device components, including the use of parallel lines and / or fixtures. Gantry Sub-Assembly

[0032] Module 2 of apparatus 10 is gantry subassembly 3, as shown in Figures 3A and 3B. Gantry 302 may hold the instrumentation used to engage cartridge 60. The illustrated embodiment shows several components mounted on gantry 302, including a heating element 700 (see Figure 3C), a latch 359 with associated mechanism for securing the cartridge in place, a barcode reader 850 with associated instrumentation, and a means for generating a click when cartridge 60 is fully inserted.

[0033] FIG. 3B illustrates a bottom view of the gantry subassembly 3, showing the interface board assembly 870, which includes the interface board pcb 871, the tiger eye 872, and the spring connector 873 (see also FIG. 1E). The interface board 870 aligns with the pins 301A and 301B via the V-shapes and flat features on the interface board pcb 871. The interface board 870 is secured to the gantry 302 (after aligning with the two dowel pins 301A and 301B) using two fasteners 870f. The spring connector 873 shown in this embodiment is a 40-pin connector manufactured by Samtech. The connector spring pins 873p engage the cartridge pads 800a, as shown in FIG. 1E. The bottom view also shows three slots 302a, 302b, and 302c, which serve to kinematically align the gantry to dowel pins 301A, 301B, and 301C, respectively (see FIG. 2E). The benefits of kinematic alignment are discussed further herein. The cable connects to a connector 875 at Tiger Eye interface 872. Wire 874 leads to a second connector 875 that connects to main PCBA 890 at location 890c. Gantry Subassembly: Heating Element

[0034] FIG. 3C shows a close-up view of a heater 700 that may contact the cartridge 60.

[0035] The heater 700 may include a heating element 750, as shown in Figure 3C. The heating element 750 may be made of multiple materials, including, but not limited to, polyimide, copper, and / or nickel-copper, and each such material may be a layer bonded to another layer with an adhesive, for example, forming a multi-layer sandwich. A stainless steel laminate 751 may be used to minimize wear on the heating element 750.

[0036] The heater 700 may include a temperature measurement component, such as a thermistor (not shown), which may be mounted on top of the heating element 750 to monitor the temperature of the system.

[0037] The embodiment depicted in FIG. 3C shows a split design, in which the heating element 750 is separated into at least three regions: a heating portion 750h, two flexible arms 750a, and a base region 750b. The heater region 750h serves to heat a portion of the cartridge 60. The base region 750b can be used to mount a connector 701 for observing and actuating the heater 700. The heater 700 is mounted to a heater arm 710 (via two fasteners 700f) at the base region 750b, which has two clearance holes 750c. The two arms 750a can be flexible, isolating the heating portion 750h from the base region 750b. A cable can be used to connect the connector 701 to the PCBA board 890 at connection 890h. The connector 701 can provide a secure engagement and / or include a click connector to pass vibration and drop tests. In some embodiments, the cable is strain relieved to prevent vibration during handling. A second support plate 752 may be included below the connector area to ensure that the bend in the heating element 750 is restrained by the arm 750a. Gantry Subassembly: Heater Mechanism

[0038] As shown in Figures 3D and 3E, the heater mechanism may include several components. The heater 700 may be secured to a disk 709 with a compliant layer 703 (e.g., foam such as Poron foam) between the components. In certain embodiments, the heater disk 709 has a U-shaped bracket 708 that can secure the heater disk 709 to a heater arm 710 using two fasteners 708f (fasteners 708f are shown in the embodiment depicted in Figure 5C). The heater disk 709 can rotate about the x-axis relative to the heater arm 710 via a pin 308 (e.g., with e-clips near both ends) secured via e-clips 371. The heater arm 710 is secured to the gantry 302 via a long pin 370, also secured via e-clips 371. The pin 370 serves as the axis of rotation for the entire heater arm 710. The heater lever 711 can also pivot about the pin 370. The heater lever 711 is rotationally locked to the heater arm 710 by shoulder bolt 702, which transfers force between the two components. A nut 715 fits within a hexagonal pocket 710h in the heater arm 710 (see FIG. 3F), allowing shoulder bolt 702 to fit the heater arm 710 to the heater lever 711. The heater lever 711 has a non-linear groove 711g that serves as a raceway channel for a roller, such as ball bearing 380H (see FIG. 2C) or a sleeve bearing on a post such as a shoulder screw. When ball bearing 380H is in groove entrance region 711e, the heater unit is said to be in its raised configuration, which occurs when carriage bracket 352 is closest to motor mount 312 (home position), see FIG. 3F (some structural components are hidden in FIG. 3F to illustrate the tilt of the heater). As motor 310 rotates in the forward direction, nut 311 moves in the negative y-direction, which in turn moves carriage bracket 352 as three fasteners (311f, 311c as shown in FIG. 2C) secure nut 311 to carriage bracket 352. Ball bearing 380H on carriage bracket 352 rolls in groove 711g.The primary rotation of the heater mechanism occurs as ball bearing 380H moves along groove entrance region 711e. Heater lever 711 has post 711p that fits loosely into slot 312h (see FIG. 2F) to provide some restraint to prevent heater lever 711 from being overstressed during drop testing or vibration.

[0039] Embodiments without a heater are also within the scope of the present invention. For example, in certain embodiments, a microfluidic cartridge may include an internal heating element, and a device configured to receive such a microfluidic cartridge does not include a heater. In some such embodiments, the device may include a controller for activating and controlling the heating element of the microfluidic cartridge. Gantry Subassembly: Latch

[0040] 3G, latch 359 can be mounted to gantry 302 via two shoulder bolts 358P and 358S. Compression spring 365 may be partially retained in a pocket in gantry 302 and partially retained in a pocket in latch 359. In some embodiments, spring 365 is sized to have a preload of less than 2 Newtons and greater than 0.5 Newtons. In other embodiments, latch 359 is mounted to base 300.

[0041] Also shown in Figure 3H is latch 359, a second component actuated by linear actuator 310 (which, as noted above, may be a stepper motor in some embodiments). In certain embodiments, ball bearing 380L is attached to latch 359 using shoulder bolt 360 (shoulder bolt 360 is shown in Figure 3A). The use of ball bearing 380L allows for rolling motion with latch actuation arm 357, resulting in increased product life compared to embodiments employing friction surfaces that are prone to wear and premature failure. The z-motion of the latch occurs as ball bearing 380L moves along latch arm groove 357g. When the cartridge begins to engage, ball bearing 380L rides on top of groove 357t. Gantry Subassembly: Barcode

[0042] In some embodiments, such as in point-of-care settings or other hospital or healthcare provider settings, it may be desirable to have a barcode reader that can read codes on the exterior of the device, as well as read codes on the cartridge. Thus, in some embodiments, barcode reader 850 may be positioned at an oblique angle inside device 10, with transparent window 391 in top shell 390 allowing it to not only scan the barcode on cartridge 60, but also any other barcodes (i.e., for purposes of obtaining or tracking patient information, technician ID, etc.). See FIG. 4A. Window 391 may vary in shape and geometry, as shown by window 391R in the embodiment depicted in FIG. 6.

[0043] In the embodiment depicted in Figure 3I, barcode reader 850 is mounted to gantry utility bracket 303 via three fasteners 850f. In other embodiments, barcode reader 850 is not mounted to the gantry utility bracket; for example, in some embodiments, barcode reader 850 may be mounted to the top shell.

[0044] Several configurations of the barcode reader are possible. In the embodiment illustrated in FIG. 3I, the barcode reader 850 and barcode electronics board 860 are separate components and connected to each other via ribbon cable 855. The barcode electronics board 860 is attached to the utility bracket 303 via fasteners 860f (three of the four fasteners 860f are shown in FIG. 3I). A cable connects the barcode electronics board 860 to the main PCBA 890 at connection 890i. A flat area on the cartridge 60 can be tilted so that the barcode reader 850 reads the barcode on the cartridge when the cartridge is in the engaged position. The configuration shown includes a flat window and a tilted viewing surface; however, in some embodiments, it may be desirable for the window 391 to be parallel to the viewing surface (the flat area on the cartridge).

[0045] The utility bracket 303 in this embodiment also serves to retain (via a recessed hole 303c) a sealed, spring-loaded guide pin 330 (referred to herein as a "clicker") that may serve at least two functions: to produce an audible click when the cartridge is fully inserted, and to provide mechanical feedback to the user that the cartridge 60 is engaged. Depending on the tolerances of some components and mechanisms (such as latches), the clicker 330 may also provide a force that counteracts the force exerted by the rod pushing against the bung in the cartridge 60. There are other means of achieving the same clicking function to provide tactile and / or auditory feedback to the user. Upper Shell Subassembly

[0046] The module 3 of the device 10 is an upper shell subassembly 5, as shown in the embodiment depicted in Figures 4A-4D.

[0047] In some embodiments, the top shell 390 includes an LCD touchscreen assembly 830 that allows a user to input information and interact with the device 10. A power button 970 can turn the device 10 on and off. The power button can be an off-the-shelf component 970P or a custom interface that can turn the main PCBA 890 on and off. The window 391 can be made from a variety of transparent materials, such as cell-cast plastic, optical glass with an anti-reflective coating, etc.

[0048] FIG. 4B shows a bottom view of the upper shell subassembly 5. This bottom view shows the computer main PCBA board 890, processing module 891, structural support brackets 394 and 395, and crossbar 396. The crossbar 396 between the brackets provides crush protection for the shell around the center of the device 10. The two support brackets 394 and 395 have threaded holes (394b and 395b) that secure the upper shell 390 to the base 300 at the midsection via long fasteners 390f. Additionally, the corners of the upper shell 390 have four threaded holes 390C that secure the corners. The PCBA board 890 is aligned to the upper shell 390 using three slots 890s on the PCBA board 890 and dowel pins 392 on the upper shell 390 (see FIG. 4C).

[0049] A main PCBA 890 (see FIG. 4C) with a processing unit 891 functions as a computer system with the following connectors (bold numbers refer to connectors): DC power supply 890d, cartridge 890c, touch screen 890t, heater 890h, barcode 890i, limit switch 890o, actuator 890m, battery 890b, USB-C 890p, USB-A 890a, and LCD screen 890r. Additional sensors and / or ports can be included on main PCBA 890 to enable additional functionality of the device.

[0050] As shown in the embodiment depicted in FIG. 4D , the LCD touchscreen assembly 830 can be secured to the top shell 390 via a bracket 393, which kinematically aligns the touchscreen with three posts on the top shell 390 and applies a preload using two curved sections 393 p. To accommodate the rigidity of the LCD touchscreen assembly 830, the bracket 393 is secured to the top shell 390 with a dozen fasteners 393 f. In addition, the bracket 393 has a threaded hole 393 t that serves to secure brackets 394 and 395. The fasteners 393 f and the threaded hole 393 t are shown in FIG. 4C . The main PCBA 890 is secured to the top shell 390 by fasteners 890 f (see FIG. 4C ), so that forces resulting from use of the touchscreen are not transferred to the electronics board. Instead, loads from pressing on the touchscreen are transferred to the base 300 through the perimeter of the top shell 390 and through brackets 394 and 395. The LCD touchscreen assembly 830 is connected to the main PCBA 890 board via two ribbon cables: the LCD ribbon 830r is connected to the main PCBA 890 at connector 890r, and the touch ribbon 830t is connected to the main PCBA 890 at connector 890t.

[0051] In some embodiments, the device does not include an LCD touchscreen assembly. For example, in certain embodiments, a user may control the device via a computer or other unit (e.g., a smartphone connected to the device via a Bluetooth or wireless connection).

[0052] In the embodiment depicted herein, top shell subassembly 5 mates with base subassembly 2 and is secured with four fasteners that engage threaded holes 390c in the corners of top shell 390 (see FIGS. 1B, 4B, and 4C). The intermediate body of device 10 is further supported by three fasteners: two fasteners that engage threaded portion 394b of bracket 394 and one fastener that engages threaded portion 395b of bracket 395 (see FIG. 4B). In certain embodiments, elastomeric base element 388 can be glued to base 300 (see FIG. 1A) to prevent tampering and disassembly.

[0053] During the concept development phase, the design began by kinematically aligning the cartridge 60 to the components of the device 10 by creating primary datums 30 to maintain tight structural loops, as illustrated schematically in FIG. 5A. In FIG. 5A, primary alignment features are represented by solid lines, while secondary alignment dependencies are represented by dashed lines. The direction of each arrow indicates the direction of constraint. For example, the cartridge 60S derives its position from the dowel pins, not vice versa. As described above, the base 300 holds three dowel pins 301A, 301B, and 301C (see, for example, the embodiment depicted in FIGS. 2B and 2E). In the schematic diagram of FIG. 5A, the base is a monolithic base 300S. The interface between the monolithic base 300S and the datum dowel pins 301A, 301B, and 301C (interface 31 in FIG. 5A) may be achieved by a press fit, allowing for precise positioning. Dowel pins 301A, 301B, and 301C may be further secured using RC2 or RC3 fits using (for example) Loctite 648. In embodiments in which monolithic base 300S is a casting, the cast block is preferably post-machined to help prevent the press fit from cracking the material. The engagement depth of dowel pins 301A, 301B, and 301C can be determined using Saint-Venant characteristic dimension guidance. The engagement depth of each pin 301A, 301B, and 301C is preferably at least 1.6 times the pin diameter, and in some embodiments, the engagement depth of each pin 301A, 301B, and 301C is 3 times the pin diameter. Tolerance stack-up analysis places the tightest tolerances on the placement of these three press fits because they serve to align critical components throughout apparatus 10. Tolerance stack-up analysis can be performed in conjunction with error allocation analysis.

[0054] Gantry 302S has an alignment mechanism with three slots 302a, 302b, 302c oriented for alignment with three dowel pins 301A, 301B, 301C (see, for example, the embodiment depicted in FIG. 3B). Thus, in the schematic diagram of FIG. 5A, interface 32 includes kinematic alignment of the three slots 302a, 302b, 302c with the three dowel pins 301A, 301B, 301C, the tolerances of which allow precise planar and precise alignment of gantry 302S with base 300S (in X, Y, and rotation about the surface normal), and more importantly, provide precise kinematic constraints. The centers of the three slots lie on an imaginary triangle, the angle bisectors of the triangle intersect at a point in the area of ​​maximum alignment accuracy desired between the mating elements, and the centers of the slots lie at the vertices of the triangle with their longitudinal axes aligned with the corresponding angle bisectors at the vertices of the triangle.

[0055] Depending on the component layout and / or the functional requirements of the device, the kinematic alignment slots may be asymmetric, for example, as shown in Figure 3B. In other embodiments, these kinematic alignment slots may be symmetric, for example, as shown in Figure 5B.

[0056] As another example of an alignment mechanism, the main PCBA substrate 890 is aligned to the top shell 390 via three dowel pins 392 that engage with three slots 890s on the PCBA 890. See Figure 4C.

[0057] The interface substrate 871S is aligned to two dowel pins 301A and 301B using a V-shape and a flat shape, establishing the primary alignment mechanism illustrated as interface 33 in FIG. 5A. The three-point contact does not fully constrain the six degrees of freedom of the interface substrate 871S (see, Precise Constraints: Mechanical Design with Kinematics, by Douglas Blanding (ISBN-10:0791800857)). That is, the gantry 302S provides a planar z-reference (represented as a secondary alignment dependency), as shown schematically by interface 34 in FIG. 5A. In the embodiment described herein, a 40-pin connector 873 (shown as 873S in the schematic diagram of FIG. 5A) contacts the cartridge PCB 800 (see, e.g., FIG. 1E). The connector 873S is aligned to the interface substrate 871S via two posts (on the connector's packaging) on ​​the connector's exterior, illustrated as interface 44.

[0058] To enhance the robustness of the design, the cartridge 60S is also aligned with two dowel pins 301A and 301B using V-shaped and flat shapes, illustrated in FIG. 5A as the primary alignment feature, interface 35. The cartridge 60S is further constrained by secondary contact with the gantry 302S (illustrated as interface 41) and the monolithic base 300S (illustrated as interface 43). The clearances and tolerances between the cartridge 60S, gantry 302S, and monolithic base 300S prealign the cartridge 60S as it enters the device 10, and such prealignment can constrain the cartridge 60S to less than 3 degrees after 30 mm (approximately 50%) of engagement. This analysis of cartridge constraint as it enters the device can be performed geometrically or using CAD software. To optimize manufacturing costs and user feedback, a plot of cartridge pitch angle as a function of cartridge engagement percentage can be generated for a particular set of dimensions and manufacturing tolerances.

[0059] The tight structural loops and kinematic alignment of the Vs and flats (interface 35, and interface 33) and the gantry slots and pins (interface 32) ensure that the contact between the cartridge 60S and the interface board connector 873S (interface 42) is consistent and accurate.

[0060] The kinematic alignment of the slots and pins can be asymmetrical for gantry 302, as shown in FIG. 3B, or with some design modifications, can be configured to be symmetrical, as shown in FIG. 5B. Slot 302c can be moved to the midline between 301A and 301B so that new slot 302w is centered. Slots 302a and 302b can be replaced with new, symmetrical slot 302z. Dowel pin 301C can be replaced with dowel pin 301D, which engages with slot 302z on gantry 302.

[0061] The V-shaped portions and flats can also be used to efficiently align other components during assembly. For example, if precise alignment of the heater 700 to the foam (e.g., Poron®) 703 and heater disk 709 is required, features can be added to each of the three components so that each component aligns with the assembly fixture with two dowel pins. Figure 5C shows a modified heater plate 709M with flat areas 709t and v-grooves 709v, a modified Poron 703M with flat areas 703t and grooves 703v, and a modified heater 750M with flat areas 750t and v-grooves 750v, which can be used to efficiently align the components.

[0062] The alignment between components is explained with reference to "Kinematic Coupling: A Review of Design Principles and Applications," by Slocum, A., International Journal of Machining and Manufacturing (2009), doi:10.1016 / j.ijmachtools.2009.10.006.

[0063] It will be understood that the above-described apparatus and methods have been described by way of example, and that the examples do not limit the scope of the invention. Additionally, the order or presentation of method or assembly steps in the above description is not intended to require this order of performing the described steps, unless a particular order is expressly required or apparent from the context. Thus, while the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will recognize in light of this disclosure that various changes in form and detail may be made therein without departing from the scope of the invention, as encompassed, for example, by the appended claims.

Claims

1. 1. An apparatus configured to receive a microfluidic cartridge, the apparatus comprising: (a) a kinematic interface for interfacing the microfluidic cartridge with the device, the kinematic interface comprising a V-section and a flat section; (b) a latch that secures the microfluidic cartridge in place after the microfluidic cartridge is inserted into the device; (c) an actuator configured to activate the movement of a fluid contained within the microfluidic cartridge; (d) a user interface; and An apparatus comprising:

2. The user interface comprises an LCD (liquid crystal display) and a touch screen.

10. The apparatus of claim 1.

3. the apparatus further comprises a barcode reader; 3. An apparatus according to claim 1 or 2.

4. The device further comprises a clicker that produces a sound when the cartridge is inserted.

4. An apparatus according to any one of claims 1 to 3.

5. the apparatus further comprising a heater; 5. An apparatus according to any one of claims 1 to 4.

6. The apparatus further comprises a controller for controlling a heating element of the microfluidic cartridge.

5. An apparatus according to any one of claims 1 to 4.

7. 1. An apparatus configured to receive a microfluidic cartridge, the apparatus comprising: a base having two pins, each of the two pins oriented on the base such that each pin interfaces with a V-shape and a flat shape on the microfluidic cartridge.

8. 1. An apparatus comprising: a base having three pins; a gantry with three slots; Equipped with the alignment of the three slots with the three pins provides planar and rotational alignment of the base with the gantry; Device.

9. the three slots of the gantry are arranged on the gantry such that their centers are located on an imaginary triangle, the center of each slot is located at one of the vertices of the imaginary triangle, the longitudinal axis of each slot is aligned with one of the angle bisectors of the corners included in the imaginary triangle, and the angle bisectors of the corners included in the imaginary triangle intersect at a first point within the imaginary triangle; 9. The apparatus of claim 8.

10. the device is configured to receive a microfluidic cartridge having a V-shaped portion and a flat portion that interfaces with two of the three pins; 9. The apparatus of claim 8.

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